Functional Metagenomics Reveals an Overlooked Diversity and Novel Features of Soil-Derived Bacterial Phosphatases and Phytases.
Phosphatases, including phytases, play a major role in cell metabolism, phosphorus cycle, biotechnology, and pathogenic processes. Nevertheless, their discovery by functional metagenomics is challenging. Here, soil metagenomic libraries were successfully screened for genes encoding phosphatase activity. In this context, we report the largest number and diversity of phosphatase genes derived from functional metagenome analysis. Two of the detected gene products carry domains which have never been associated with phosphatase activity before. One of these domains, the SNARE-associated domain DedA, harbors a so-far-overlooked motif present in numerous bacterial SNARE-associated proteins. Our analysis revealed a previously unreported phytase activity of the alkaline phosphatase and sulfatase superfamily (cl23718) and of purple acid phosphatases from nonvegetal origin. This suggests that the classical concept comprising four classes of phytases should be modified and indicates high performance of our screening method for retrieving novel types of phosphatases/phytases hidden in metagenomes of complex environments.IMPORTANCE Phosphorus (P) is a key element involved in numerous cellular processes and essential to meet global food demand. Phosphatases play a major role in cell metabolism and contribute to control the release of P from phosphorylated organic compounds, including phytate. Apart from the relationship with pathogenesis and the enormous economic relevance, phosphatases/phytases are also important for reduction of phosphorus pollution. Almost all known functional phosphatases/phytases are derived from cultured individual microorganisms. We demonstrate here for the first time the potential of functional metagenomics to exploit the phosphatase/phytase pools hidden in environmental soil samples. The recovered diversity of phosphatases/phytases comprises new types and proteins exhibiting largely unknown characteristics, demonstrating the potential of the screening method for retrieving novel target enzymes. The insights gained into the unknown diversity of genes involved in the P cycle highlight the power of function-based metagenomic screening strategies to study Earth's phosphatase pools.


Spatiotemporal elements in a poisoned bait strategy against the long-tailed silverfish (Lepismatidae: Zygentoma).
The long-tailed silverfish Ctenolepisma longicaudatum (Lepismatidae: Zygentoma) is a nuisance problem in buildings and a major concern in museums, libraries and archives where it cause damage to historical and priceless items. We used laboratory bioassays and two field studies of infested buildings to evaluate spatial and temporal elements of a poisoned bait strategy. In both laboratory experiments and field studies, the efficiency of poisoned bait with indoxacarb as the active ingredient was significantly improved by placing many small bait droplets evenly distributed along all edges of the treated area compared to more clustered distributions. Extended duration of bait presence and removal of competing food sources improved the control effect significantly in the laboratory bioassays. Bait-treated populations also showed a significant decline in the number of eggs deposited and emergence of new nymphs. The study supports poisoned bait as an efficient and low risk approach against the long-tailed silverfish in which extended duration of bait presence, wide distribution of bait droplets in combination with sanitation was crucial for control in the infested premises.


Cardiorenal outcomes in eligible patients referred for bariatric surgery.
Bariatric surgery is associated with reduced atherosclerotic cardiovascular disease (CVD) and heart failure hospitalization in people with type 2 diabetes (T2D) and those with prior CVD. Most patients undergoing bariatric surgery do not have T2D or CVD. Many otherwise eligible patients do not have surgery because of self-exclusion. Clinical outcomes in these groups are less established. This study retrospectively assessed cardiorenal outcomes in 8,568 patients after acceptance of referral for surgery. A total of 63.8% patients did not undergo surgery. After multivariate adjustment for sex, age, BMI, income quintile, distance from hospital, hypertension, T2D, and CVD, hazard ratios (HR) for the primary (incident myocardial infarction, stroke, heart failure hospitalization, and death; HR = 0.52, 95% CI: 0.4-0.66) and secondary CVD outcomes (primary outcomes and coronary/carotid revascularization; HR = 0.53, 95% CI: 0.42-0.67) were lower in the surgery cohort. This reduction was seen in those with (primary: HR = 0.45, 95% CI: 0.32-0.63, secondary: HR = 0.47, 95% CI: 0.34-0.65) and without T2D (primary: HR = 0.61, 95% CI: 0.42-0.88, secondary: HR = 0.53, 95% CI: 0.42-0.67). Reduced kidney disease (HR = 0.46, 95% CI: 0.22-0.92) but increased liver disease hospitalization (HR = 2.5, 95% CI: 1.45-4.27) was observed with surgery. Non-progression to surgery associates with increased CVD despite low baseline prevalence of CVD. The cardiorenal benefits of bariatric surgery warrant confirmation in a well-powered randomized clinical trial.


First Report of the Morphology and rDNA Sequences of Two Pseudopolydora Species (Annelida: Spionidae) from Japan.
The morphology of two Pseudopolydora species, P. cf. reticulata Radashevsky and Hsieh, 2000 and P. achaeta Radashevsky and Hsieh, 2000 are reported from Japan for the first time. Pseudopolydora cf. reticulata was collected from Japanese tidal flats, and individuals possess the characteristic netlike pigmentation on the dorsum of anterior chaetigers and the longitudinal black band along midline of caruncle. Pseudopolydora achaeta was collected from subtidal bottom mud of Onagawa Bay, and individuals have distinctive characteristics, such as intensive black pigmentation on dorsal and ventral sides of the anterior body and nearly straight vertical rows of major spines on the fifth chaetiger. The morphology of P. cf. reticulata is very similar to that of P. cf. kempi, with which it had been confused in Japan. We analyzed the 18S and 28S rRNA gene sequences of all five Pseudopolydora species recorded from Japan and found strong evidence that they are genetically distinct. Our analysis also suggests that boring polydorids have evolved among non-boring ones; the genus Pseudopolydora, which mostly shows the non-boring form, appears to have remained in a more ancestral condition.


Metabolism of acetylcholine in the nervous system of Aplysia californica. II. Reginal localization and characterization of choline uptake.
The choline required for synthesis of acetylcholine is derived exogenously by Aplysia ganglia. Under physiological conditions choline was taken up primarlily by neuropile and nerves and not by cholinergic cell bodies. In addition, compared with their contents of choline acetyltransferase, those components of nervous tissue which contain nerve terminals and axons synthesized acetylcholine far more efficiently. Choline was accumulated by high and low affinity uptake processes; the high affinity process appeared to be characteristic of cholinergic nuerons (Swartz, J. H., M. L. Eisenstadt, and H. Cedar.1975. J. Gen. Physiol. 65:255). The two uptake processes were similarly affected by temperature with a Q10 of 2.8. Both were dependent on a variety of ions in a complicated manner. High affinity uptake seemed to be more dependent on Na+, showed greater inhibition by ouabain, and was selectively inhibited by oxotremorine. We found that the functional state of neurons did not alter uptake of radioactive choline by either process, nor did it change the conversion to radioactive acetylcholine.


Blood oxygen transport and metabolism of the confined lugworm Arenicola marina (L.).
Oxygen consumption (MO2), haemoglobin oxygen saturation level (SVO2) and pH (pHv) in prebranchial blood were measured in lugworms experimentally confined in sea water at 15 degrees C. Total blood flow through the gills (Vb) was estimated. For sea water oxygen partial pressure (PwO2) between 120 and 150 Torr MO2, SVO2 and Vb were high and nearly constant. For PwO2 less than 120 Torr, Vb fell quickly, MO2 progressively dropped, and metabolism remained aerobic at the expense of the prebrancial blood oxygen store. For PwO2 less than 50 Torr, Vb and SvO2 values were extremely low, and the low pHv and the modified buffer power of the surrounding sea water showed that anaerobic metabolism was occurring. Changes in respiratory gas exchanges and metabolism during the tidal cycle are deduced from the comparison of these results with data obtained in the field.


Modulation of aggrecan and link-protein synthesis in articular cartilage.
The addition of serum or insulin-like growth factor-I (IGF-I) to the medium of explant cultures of bovine articular cartilage is known to stimulate the synthesis of aggrecan in a dose-dependent manner. The half-life of the pool of proteoglycan core protein was measured in adult articular cartilage cultured for 6 days in the presence and absence of 20 ng of IGF-I/ml and shown to be 24 min under both sets of conditions. The half-life of the mRNA pool coding for aggrecan was also determined and shown to be approx. 4 h in cartilage maintained in culture with or without IGF-I. The pool size of mRNA coding for aggrecan core protein increased 5-6-fold in cartilage explants maintained in culture in medium containing 20% (v/v) fetal-calf serum; however, in tissue maintained with medium containing IGF-I there was no increase in the cellular levels of this mRNA. This suggests that aggrecan synthesis is stimulated by IGF-I at the level of translation of mRNA coding for the core protein of this proteoglycan and that other growth factors are present in serum that stimulate aggrecan synthesis at the level of transcription of the core-protein gene. Inclusion of serum or IGF-I in the medium of cartilage explant cultures induced increases in the amounts of mRNA coding for type II collagen and link protein, whereas only serum enhanced the amount of mRNA for the core protein of decorin.


Compensatory Cognitive Training for Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans With Mild Traumatic Brain Injury.
The purpose of the study was to evaluate the efficacy of group-based compensatory cognitive training (CCT) for Operation Enduring Freedom (OEF)/Operation Iraqi Freedom(OIF)/Operation New Dawn (OND) Veterans with a history of mild traumatic brain injury. One hundred nineteen OEF/OIF/OND Veterans with history of mild traumatic brain injury participated at 3 sites, and 50 of the Veterans were randomized to CCT group, while 69 Veterans were randomized to the usual care control group. The CCT group participated in 10 weeks of CCT. Both CCT and usual care groups were assessed at baseline, 5 weeks (midway through CCT), 10 weeks (immediately following CCT), and 15 weeks (5-week follow-up) on measures of subjective cognitive complaints, use of cognitive strategies, psychological functioning, and objective cognitive performance. Veterans who participated in CCT reported significantly fewer cognitive and memory difficulties and greater use of cognitive strategies. They also demonstrated significant improvements on neurocognitive tests of attention, learning, and executive functioning, which were 3 of the cognitive domains targeted in CCT. Findings indicate that training in compensatory cognitive strategies facilitates behavioral change (ie, use of cognitive strategies) as well as both subjective and objective improvements in targeted cognitive domains.


Integrins are not essential for entry of coxsackievirus A9 into SW480 human colon adenocarcinoma cells.
Coxsackievirus A9 (CV-A9) is a pathogenic enterovirus type within the family Picornaviridae. CV-A9 infects A549 human epithelial lung carcinoma cells by attaching to the αVβ6 integrin receptor through a highly conserved Arg-Gly-Asp (RGD) motif, which is located at the exposed carboxy-terminus of the capsid protein VP1 detected in all studied clinical isolates. However, genetically-modified CV-A9 that lacks the RGD motif (CV-A9-RGDdel) has been shown to be infectious in some cell lines but not in A549, suggesting that RGD-mediated integrin binding is not always essential for efficient entry of CV-A9. Two cell lines, A549 and SW480, were used in the study. SW480 was the study object for the integrin-independent entry and A549 was used as the control for integrin-dependent entry. Receptor levels were quantitated by cell sorting and quantitative PCR. Antibody blocking assay and siRNA silencing of receptor-encoding genes were used to block virus infection. Peptide phage display library was used to identify peptide binders to CV-A9. Immunofluorescence and confocal microscopy were used to visualize the virus infection in the cells. We investigated the receptor use and early stages of CV-A9 internalization to SW480 human epithelial colon adenocarcinoma cells. Contrary to A549 infection, we showed that both CV-A9 and CV-A9-RGDdel internalized into SW480 cells and that function-blocking anti-αV integrin antibodies had no effect on the binding and entry of CV-A9. Whereas siRNA silencing of β6 integrin subunit had no influence on virus infection in SW480, silencing of β2-microglobulin (β2M) inhibited the virus infection in both cell lines. By using a peptide phage display screening, the virus-binding peptide identical to the N-terminal sequence of HSPA5 protein was identified and shown to block the virus infection in both A549 and SW480 cell lines. HSPA5 was also found to co-localize with CV-A9 at the SW480 cell periphery during the early stages of infection by confocal microscopy. The data suggest that while αVβ6 integrin is essential for CV-A9 in A549 cell line, it is not required in SW480 cell line in which β2M and HSPA5 alone are sufficient for CV-A9 infection. This suggests that the choice of CV-A9 receptor(s) is dependent on the tissue/cellular environment.


Effects of hypercalcemia and ouabain on plasma atrial natriuretic polypeptide in anesthetized dogs.
For the purpose of examining the role of calcium ion in the secretory process of atrial natriuretic polypeptide (ANP), we studied the effects of hypercalcemia and ouabain on plasma concentration of immunoreactive ANP (irANP). Pentobarbital sodium-anesthetized dogs were treated with calcium chloride infusion (0.136 mmol.kg-1.min-1, 10 min) or ouabain injection (30 micrograms/kg), and plasma irANP concentration, right atrial pressure, mean arterial pressure, heart rate, and serum calcium concentration were measured. To evaluate the effect of rising arterial pressure, plasma irANP concentration was also measured in dogs treated with phenylephrine hydrochloride (10 micrograms/kg). With calcium chloride infusion, serum calcium concentration and plasma irANP concentration, respectively, increased to about three times and about four times their basal levels. This increase of plasma irANP concentration was not attenuated by pretreatment with adrenoceptor blockers. Ouabain increased plasma irANP concentration to approximately 2.5 times the initial level. Neither calcium chloride nor ouabain produced any effect on right atrial pressure and heart rate, but both significantly increased mean atrial pressure. Phenylephrine caused a greater increase in mean arterial pressure than both calcium chloride and ouabain. However, there was no significant increase in plasma irANP concentration. These results suggest that the calcium ion may play a key role in the secretory process of ANP.


Chemokine transport across human vascular endothelial cells.
Leukocyte migration across vascular endothelium is mediated by chemokines that are either synthesized by the endothelium or transferred across the endothelium from the tissue. The mechanism of transfer of two chemokines, CXCL10 (interferon gamma-inducible protein [IP]-10) and CCL2 (macrophage chemotactic protein [MCP]-1), was compared across dermal and lung microvessel endothelium and saphenous vein endothelium. The rate of transfer depended on both the type of endothelium and the chemokine. The permeability coefficient (Pe) for CCL2 movement across saphenous vein was twice the value for dermal endothelium and four times that for lung endothelium. In contrast, the Pe value for CXCL10 was lower for saphenous vein endothelium than the other endothelia. The differences in transfer rate between endothelia was not related to variation in paracellular permeability using a paracellular tracer, inulin, and immunoelectron microscopy showed that CXCL10 was transferred from the basal membrane in a vesicular compartment, before distribution to the apical membrane. Although all three endothelia expressed high levels of the receptor for CXCL10 (CXCR3), the transfer was not readily saturable and did not appear to be receptor dependent. After 30 min, the chemokine started to be reinternalized from the apical membrane in clathrin-coated vesicles. The data suggest a model for chemokine transcytosis, with a separate pathway for clearance of the apical surface.


3D collagen microchamber arrays for combined chemotherapy effect evaluation on cancer cell numbers and migration.
Breast cancer metastasis involves complex mechanisms, particularly when patients are undergoing chemotherapy. In tissues, tumor cells encounter cell-cell interactions, cell-microenvironment interactions, complex nutrient, and drug gradients. Currently, two-dimensional cell culture systems and animal models are challenging to observe and analyze cell responses to microenvironments with various physical and bio-chemical conditions, and microfluidic technology has been systematically developed to address this dilemma. In this study, we have constructed a combined chemotherapy evaluation chip (CCEC) based on microfluidic technology. The chip possesses 192 diamond-shaped microchambers containing MDA-MB-231-RFP cells, and each microchamber is composed of collagen to mimic breast cancer and its surrounding microenvironment. In addition, by adding medium containing different drugs to the medium channels of CCEC, composite drug (paclitaxel+gemcitabine+7rh and paclitaxel+fluorouracil+PP2) concentration gradients, and single drug (paclitaxel, gemcitabine, 7rh, fluorouracil, PP2) concentration gradients have been established in the five collagen regions, respectively, so that each localized microchamber in the regions has a unique drug microenvironment. In this way, we evaluated the composite and single chemotherapy efficacy on the same chip by statistically analyzing their effects on the numbers and migration of the cell. The quantitative results in CCECs reveal that the inhibition effects on the numbers and migration of MDA-MB-231-RFP cell under the composite drug gradients are more optimal than those of the single drugs. Besides, the cancer cell inhibition effect between the groups composed of two drugs has also been compared, that is the paclitaxel+gemcitabine, paclitaxel+fluorouracil, and paclitaxel+PP2 have better cell numbers and migration inhibition effects than paclitaxel+7rh. The results indicate that the bio-mimetic and high-throughput combined chemotherapy evaluation platform can serve as a more efficient and accurate tool for preclinical drug development and screening.


Age- and sex-dependent variation in relatedness corresponds to reproductive skew, territory inheritance, and workload in cooperatively breeding cichlids.
Kin selection plays a major role in the evolution of cooperative systems. However, many social species exhibit complex within-group relatedness structures, where kin selection alone cannot explain the occurrence of cooperative behavior. Understanding such social structures is crucial to elucidate the evolution and maintenance of multi-layered cooperative societies. In lamprologine cichlids, intragroup relatedness seems to correlate positively with reproductive skew, suggesting that in this clade dominants tend to provide reproductive concessions to unrelated subordinates to secure their participation in brood care. We investigate how patterns of within-group relatedness covary with direct and indirect fitness benefits of cooperation in a highly social vertebrate, the cooperatively breeding, polygynous lamprologine cichlid Neolamprologus savoryi. Behavioral and genetic data from 43 groups containing 578 individuals show that groups are socially and genetically structured into subgroups. About 17% of group members were unrelated immigrants, and average relatedness between breeders and brood care helpers declined with helper age due to group membership dynamics. Hence the relative importance of direct and indirect fitness benefits of cooperation depends on helper age. Our findings highlight how both direct and indirect fitness benefits of cooperation and group membership can select for cooperative behavior in societies comprising complex social and relatedness structures.


Rapid purification of recombinant betaB2-crystallin using hydrophobic interaction chromatography.
BetaB2-crystallin, the major subunit of beta-crystallins, is difficult to purify either from lens homogenate or from betaH-or betaL-crystallins. It has been prepared by heterologous expression in Escherichia coli. Most often, the methods used for purifying a recombinant globular protein employ the combination of ion-exchange with gel filtration chromatography. In the case of betaB2-crystallin too, different approaches have been used to obtain the purified protein, majority of which use a combination of ion-exchange and gel filtration chromatography. We present a new approach to purify betaB2-crystallin using hydrophobic interaction chromatography. In this method, the protein is bound to the hydrophobic matrix in the presence of high concentration of a non-chaotropic salt and eluted by decreasing the salt concentration. The method that we have used for the purification of this globular protein has definite advantages over the earlier methods in its simplicity and efficiency. The most noted advantage of this procedure is the rapid purification with a relatively purified product and a comparatively high yield (>20 mg/L of culture). Over all, the present protocol provides a rapid, efficient and simplified procedure for the preparation of betaB2-crystallin in large yield, sufficient for structural and functional studies.


Single-Plant Selection at Ultra-Low Density Enhances Buffering Capacity of Barley Varieties and Landraces to Unpredictable Environments and Improves Their Agronomic Performance.
Rainfall and temperature are unpredictable factors in Mediterranean environments that result in irregular environmental conditions for crop growth, thus being a critical source of uncertainty for farmers. This study applied divergent single-plant selection for high and low yield within five barley varieties and two Tunisian landraces under semi-arid conditions at an ultra-low density of 1.2 plants/m2 for two consecutive years. Progeny evaluation under dense stands following farmers' practices was conducted in two semi-arid locations in Tunisia during one cropping season and in one location during a second season, totalling three environments. The results revealed significant genotypic effects for all recorded agronomic and physiological traits. No genotype × environment interaction was shown for biological yield, implying a biomass buffering capacity for selected lines under different environmental conditions. However, genotype × environment interaction was present in terms of grain yield since plasticity for biomass production under drought stress conditions was not translated directly to yield compensation for some of the lines. Nevertheless, several lines selected for high yield were identified to surpass their source material and best checks in each environment, while one line (IH4-4) outperformed consistently by 62.99% on average, in terms of grain yield, the best check across all environments. In addition, improved agronomic performance under drought conditions induced an indirect effect on some grain quality traits. Most of the lines selected for high yield maintained or even improved their grain protein content in comparison to their source material (average increase by 2.33%). On the other hand, most of the lines selected for low yield indicated a poor agronomic performance, further confirming the coherence between selection under ultra-low density and performance under dense stand.


Fuhrman grading is not appropriate for chromophobe renal cell carcinoma.
This study was undertaken to assess the prognostic effectiveness of Fuhrman nuclear grading and the individual components of this grading system, in a series of chromophobe renal cell carcinomas. Eighty-seven cases of chromophobe renal cell carcinoma were investigated. There were 47 males and 40 females, 28 to 78 years of age. The carcinomas ranged from 25 to 180 mm in size and on TNM staging there were 38 stage I, 25 stage II, 22 stage III, and 2 stage IV tumors. Whole tumor Fuhrman grading was grade 1, 6 cases; grade 2, 72 cases; grade 3, 8 cases; and grade 4, 1 case, whereas focal (single high power field) grading was grade 1, 1 case; grade 2, 62 cases; grade 3, 21 cases; and grade 4, 3 cases. On assignment of nucleolar grading using Fuhrman criteria there were 37 grade 1, 44 grade 2, and 4 grade 3 tumors on whole tumor assessment and 3 grade 1, 63 grade 2, and 21 grade 3 tumors on assessment of the high power field showing the greatest degree of nuclear pleomorphism. Measurements of nuclear size showed nuclear area to range from 26.14 to 100.74 microm2, nuclear perimeter from 19.73 to 39.28 microm, and nuclear major axis from 6.49 to 13.21 microm, whereas the ranges of measures of nuclear shape were; shape factor 0.798 to 0.890, compactness 14.260 to 15.843, and feret diameter 5.694 to 11.242. Follow-up ranged from 1 to 150 months and 8 patients died of tumor-related causes 5 to 53 months from diagnosis. On log rank testing against survival, only patient age (P=0.016) and tumor maximum diameter (P=0.0055) were significant, whereas patient sex and TNM stage were not significant. Whole tumor and focal Fuhrman grading, as well as all measures of nucleolar prominence, nuclear size, and nuclear shape showed no significant association with outcome. It is concluded that neither Fuhrman grading, nor any of the components of the Fuhrman grading system, is useful as prognostic indicators for this tumor type.


Anterior herniation of lumbar disc induces persistent visceral pain: discogenic visceral pain: discogenic visceral pain.
Visceral pain is a common cause for seeking medical attention. Afferent fibers innervating viscera project to the central nervous system via sympathetic nerves. The lumbar sympathetic nerve trunk lies in front of the lumbar spine. Thus, it is possible for patients to suffer visceral pain originating from sympathetic nerve irritation induced by anterior herniation of the lumbar disc. This study aimed to evaluate lumbar discogenic visceral pain and its treatment. Twelve consecutive patients with a median age of 56.4 years were enrolled for investigation between June 2012 and December 2012. These patients suffered from long-term abdominal pain unresponsive to current treatment options. Apart from obvious anterior herniation of the lumbar discs and high signal intensity anterior to the herniated disc on magnetic resonance imaging, no significant pathology was noted on gastroscopy, vascular ultrasound, or abdominal computed tomography (CT). To prove that their visceral pain originated from the anteriorly protruding disc, we evaluated whether pain was relieved by sympathetic block at the level of the anteriorly protruding disc. If the block was effective, CT-guided continuous lumbar sympathetic nerve block was finally performed. All patients were positive for pain relief by sympathetic block. Furthermore, the average Visual Analog Scale of visceral pain significantly improved after treatment in all patients (P < 0.05). Up to 11/12 patients had satisfactory pain relief at 1 week after discharge, 8/12 at 4 weeks, 7/12 at 8 weeks, 6/12 at 12 weeks, and 5/12 at 24 weeks. It is important to consider the possibility of discogenic visceral pain secondary to anterior herniation of the lumbar disc when forming a differential diagnosis for seemingly idiopathic abdominal pain. Continuous lumbar sympathetic nerve block is an effective and safe therapy for patients with discogenic visceral pain.


The patient experience of Raynaud's phenomenon in systemic sclerosis.
RP is the most common manifestation of SSc and a major cause of disease-related morbidity. This review provides a detailed appraisal of the patient experience of SSc-RP and potential implications for disease classification, patient-reported outcome instrument development and SSc-RP clinical trial design. The review explores the clinical features of SSc-RP, the severity and burden of SSc-RP symptoms and the impact of SSc-RP on function, work and social participation, body image dissatisfaction and health-related quality of life in SSc. Where management of SSc-RP is concerned, the review focuses on the 'patient experience' of interventions for SSc-RP, examining geographic variation in clinical practice and potential barriers to the adoption of treatment recommendations concerning best-practice management of SSc-RP. Knowledge gaps are highlighted that could form the focus of future research. A more thorough understanding of the patient experience could support the development of novel reported outcome instruments for assessing SSc-RP.


Good visibility of TITAN-2 coronary stents demonstrable on cardiac computer tomographic angiography: a report of 2 cases.
Numerous studies have sought to assess stent patency by cardiac computer tomographic angiography (CCTA) in comparison with invasive coronary angiography in patients who had undergone percutaneous coronary stenting. Even with newer generation scanners, CCTA has been of limited value in the assessment of the revascularized patient. The main reason being blooming artifact from metallic stents often obscures stent luminal dimension, making the stented segment unassessable. We report on a novel finding of good visibility of TITAN-2 coronary stents demonstrable on CCTA for 2 patients and discuss the possible mechanism and potential implications of this observation.


A Bio-economic Study of the Trophic Structure of the Omani Fish Catch.
The present study was conducted to obtain estimates of certain biological and economic indices of the trophic structure of the Omani landed fish catch, namely, the mean trophic level (MTL), the fishing-in-balance (FiB) index and the relative price index (RPI). The MTL generally decreased from 1995 to 2010, indicating a fishing-down of the marine trophic web. The FiB index increased, indicating an imbalance in the fisheries. An economic index, the RPI, decreased from 1994 to 2007, indicating that the values of lower trophic level (TL) species increased relative to those of higher TL species.


Use of the mitochondria toxicity assay for quantifying the viable cell density of microencapsulated jurkat cells.
The mitochondria toxicity assay (MTT assay) is an established method for monitoring cell viability based on mitochondrial activity. Here the MTT assay is proposed for the in situ quantification of the living cell density of microencapsulated Jurkat cells. Three systems were used to encapsulate the cells, namely a membrane consisting of an interpenetrating polyelectrolyte network of sodium cellulose sulphate/poly(diallyldimethylammonium chloride) (NaCS/PDADMAC), a calcium alginate hydrogel covered with poly(L-lysine) (Ca-alg-PLL), and a novel calcium alginate-poly(ethylene glycol) hybrid material (Ca-alg-PEG). MTT results were correlated to data obtained by the trypan blue exclusion assay after release of the cells from the NaCS/PDADMAC and Ca-alg-PLL capsules, while a resazurin-based assay was used for comparison in case of the Ca-alg-PEG material. Analysis by MTT assay allows quick and reliable determination of viable cell densities of encapsulated cells independent of the capsule material. The assay is highly reproducible with inter-assay relative standard deviations below 10%.


Spiralyde A, an Antikinetoplastid Dolabellane from the Brown Alga Dictyota spiralis.
Bioassay-guided fractionation of the antikinetoplastid extract of the brown alga Dictyota spiralis has led to the isolation of spiralyde A (1), a new dolabellane aldehyde, along with other five known related diterpenes (2⁻6). Their structures were determined by HRESIMS, 1D and 2D NMR spectroscopy, and comparison with data reported in the literature. The antiparasitic activity of all compounds was evaluated. Spiralyde A (1) and the known compound 3,4-epoxy-7,18-dolabelladiene (2) were the most active compounds against Leishmania amazonensis and Trypanosoma cruzi. Spiralyde A (1) was the most potent compound, comparable to benznidazole, the reference drug for trypanocidal activity.


Safety and efficacy of depatuxizumab mafodotin in Japanese patients with malignant glioma: A nonrandomized, phase 1/2 trial.
INTELLANCE-J was a phase 1/2 study of a potent antibody-drug conjugate targeting epidermal growth factor receptor (EGFR), depatuxizumab mafodotin (Depatux-M), as a second- or first-line therapy, alone or combined with chemotherapy or chemoradiotherapy in 53 Japanese patients with World Health Organization (WHO) grade III/IV glioma. In second-line arms, patients with EGFR-amplified recurrent WHO grade III/IV glioma received Depatux-M plus chemotherapy (temozolomide) or Depatux-M alone regardless of EGFR status. In first-line arms, patients with newly diagnosed WHO grade III/IV glioma received Depatux-M plus chemoradiotherapy. The study was halted following lack of survival benefit with first-line Depatux-M in the global trial INTELLANCE-1. The primary endpoint was 6-month progression-free survival (PFS) in patients with EGFR-amplified tumors receiving second-line Depatux-M plus chemotherapy. Common nonocular treatment-emergent adverse events (TEAEs) with both second-line and first-line Depatux-M included lymphopenia (42%, 33%, respectively), thrombocytopenia (39%, 47%), alanine aminotransferase increase (29%, 47%), and aspartate aminotransferase increase (24%, 60%); incidence of grade ≥3 TEAEs was 66% and 53%, respectively. Ocular side effects (OSEs) occurred in 93% of patients receiving second-line Depatux-M plus chemotherapy and all patients receiving second-line Depatux-M alone or first-line Depatux-M plus chemoradiotherapy. Most OSEs were manageable with dose modifications and concomitant medications. The 6-month PFS estimate was 25.6% (95% confidence interval [CI] 11.4-42.6), and median PFS was 2.1 months (95% CI 1.9-3.9) with second-line Depatux-M plus chemotherapy in the EGFR-amplified subgroup. This study showed acceptable safety profile of Depatux-M alone or plus chemotherapy/chemoradiotherapy in Japanese patients with WHO grade III/IV glioma. The study was registered at ClinicalTrials.gov (NCT02590263).


Avoidance Bias to Angry Faces Predicts the Development of Depressive Symptoms among Adolescent Girls.
Interpersonal-motivational models posit that heightened avoidance of aversive social stimuli and diminished approach of appetitive social stimuli increases social withdrawal and reduces positive social interactions, thereby increasing risk for future social anxiety and depression. The current study examined if approach-avoidance biases toward angry and happy faces, measured during the Approach Avoidance Task (AAT), would be associated with the development of adolescent depressive and social anxiety symptoms. At baseline, participants included 129 never-depressed adolescent girls (ages 11-13), two-thirds of whom were at high-risk for internalizing problems due to shy/fearful temperament. Girls reported their depressive and social anxiety symptoms every 6 months for 24 months and completed the AAT at baseline and 24-mo follow-up. Heightened avoidance bias toward angry faces at baseline predicted increases in depressive symptoms across the follow-up, even after accounting for temperament and pubertal status. In contrast, girls with greater depression and social anxiety symptoms at 24-mo follow-up exhibited less avoidance bias for angry faces at the same time point. Findings suggest that avoidance behaviors (i.e., avoiding people or settings associated with angry faces, which are often perceived as hostile, critical, or rejecting) may be a risk factor for depression, above and beyond risk imparted by temperament or advances in puberty. However, with increasing internalizing symptoms, it may become more difficult for adolescents to maintain avoidance for aversive social stimuli, and without the introduction of more adaptive emotion regulation strategies, these biases may continue to increase and maintain risk for internalizing problems.


When leaving your ex, love yourself: observational ratings of self-compassion predict the course of emotional recovery following marital separation.
Divorce is a highly stressful event, and much remains to be learned about the factors that promote psychological resilience when marriages come to an end. In this study, divorcing adults (N = 109) completed a 4-min stream-of-consciousness recording about their marital separation at an initial laboratory visit. Four judges rated the degree to which participants exhibited self-compassion (defined by self-kindness, an awareness of one's place in shared humanity, and emotional equanimity) in their recordings. Judges evidenced considerable agreement in their ratings of participants' self-compassion, and these ratings demonstrated strong predictive utility: Higher levels of self-compassion at the initial visit were associated with less divorce-related emotional intrusion into daily life at the start of the study, and this effect persisted up to 9 months later. These effects held when we accounted for a number of competing predictors. Self-compassion is a modifiable variable, and if our findings can be replicated, they may have implications for improving the lives of divorcing adults.


Musculoskeletal analyses of the forearm in young women with Turner syndrome: a study using peripheral quantitative computed tomography.
Turner syndrome (TS) is associated with multiple skeletal abnormalities. Fracture incidence appears to be increased, but the reasons for this are not entirely clear. In the present study, we used peripheral quantitative computed tomography to evaluate bone mass, density, geometry, and strength of the radial metaphysis and diaphysis as well as maximum forearm muscle cross-sectional area (CSA) in a group of 21 TS patients. These individuals were 19.5 +/- 2.3 yr of age (mean +/- SD; range, 16.2-25.4 yr) and had completed growth after having received GH therapy; all but one were receiving estrogen supplementation. Despite short stature, cross-sectional bone size was normal compared with age-matched healthy controls. However, bone mineral content was decreased, resulting in a low total volumetric bone mineral density. This was due to decreased cortical thickness at both sites of measurement, whereas trabecular volumetric bone mineral density of the metaphysis was normal. Muscular CSA was normal. The relationship between muscle CSA and external bone size was similar between TS patients and healthy young women. However, TS patients had less bone mineral content and cortical CSA relative to muscle CSA than healthy young women, but similar muscle-bone relationships as healthy prepubertal girls. These findings are compatible with a normal adaptation of external bone size to the mechanical loads imposed by the muscle system and a lack of pubertal effect on the endocortical bone surface, despite estrogen supplementation. Bone strength may not be adequate for the relatively high body weight of TS patients (+0.8 SD score), which could contribute to an increased propensity for fractures.


Late appearance of intra-abdominal abscesses after total colectomy for inflammatory bowel disease.
Intra-abdominal abscesses after colon surgery usually appear within eight weeks. Over the past few years, we have observed nine patients who underwent colectomy for inflammatory bowel disease in whom large and relatively asymptomatic abscesses developed, requiring surgical drainage as long as three to five years after the operation. In five patients, there was no report of intraoperative complications such as perforation or fecal spillage. At the time of discharge from the hospital, all patients were afebrile. In three of these patients, abscesses were discovered when they were readmitted to the hospital for elective abdominal procedures; most of the others had localized abdominal pain.


[Effects of a preventive intervention program for improving self-complexity on depression among college students].
The present study developed an intervention program for self-complexity (SC; Linville, 1987), and examined the effects of this program on college students. Participants (N = 40) were randomly assigned to an intervention group or a control group. The intervention group received one session of psycho-education about SC, and kept daily records of self-aspects (social roles, interpersonal relationships, specific events/behaviors, traits, abilities, etc.) for one week. All participants were asked to complete a self-report questionnaire three times (pre, post, and follow-up). The questionnaire was comprised of items evaluating depression (The Center for Epidemiologic Studies Depression Scale), SC, positive self-complexity (P-SC), and negative self-complexity (N-SC). The results indicated that P-SC at the post-test was significantly increased and P-SC at the follow-up test was marginally increased in the intervention group, compared with the control group. Furthermore, structured equation modeling revealed that in the intervention group, high P-SC was related to low level of depressed mood after the program.


Expression of beta-nerve growth factor receptor mRNA in Sertoli cells downregulated by testosterone.
Nerve growth factor (NGF) is synthesized in male germ cells. The NGF receptor (NGFR) mRNA was found in the Sertoli cells of rat testis. Hypophysectomy increased both NGFR mRNA in testis and the number of NGFR hybridizing cells in seminiferous tubules. This was suppressed by treatment with chorionic gonadotropin or testosterone, but not with follicle-stimulating hormone. The NGFR mRNA also increased after destruction of Leydig cells or blocking of the androgen receptor. This suggests that NGF produced by male germ cells regulates testicular function in an androgen-modulated fashion by mediating an interaction germ and Sertoli cells.


Efficacy of reductive ventricular osmotherapy in a swine model of traumatic brain injury.
The presence of osmotic gradients in the development of cerebral edema and the effectiveness of osmotherapy are well recognized. A modification of ventriculostomy catheters described in this article provides a method of osmotherapy that is not currently available. The reductive ventricular osmotherapy (RVOT) catheter removes free water from ventricular cerebrospinal fluid (CSF) by incorporating hollow fibers that remove water vapor, thereby providing osmotherapy without increasing osmotic load. To increase osmolarity in the ventricular CSF through use of RVOT in vivo. Twelve Yorkshire swine with contusional injury were randomized to external ventricular drainage (EVD) or RVOT for 12 hours. MR imaging was obtained. Serum, CSF, and brain ultrafiltrate were analyzed. Histology was compared using Fluor-Jade B and hematoxylin and eosin (H & E) stains. With RVOT, CSF osmolality increased from 292 ± 2.7 to 345 ± 8.0 mOsmol/kg (mean ± SE, P = 0.0006), and the apparent diffusion coefficient (ADC) in the injury region increased from 0.735 ± 0.047 to 1.135 ± .063 (P = 0.004) over 24 hours. With EVD controls, CSF osmolarity and ADC were not significantly changed. Histologically, all RVOT pigs showed no evidence of neuronal degeneration (Grade 1/4) compared to moderate degeneration (Grade 2.6 ± .4/4) seen in EVD treated animals (P = 0.02). The difference in intracranial pressure (ICP) by area under the curve approached significance at P = .065 by Mann Whitney test. RVOT can increase CSF osmolarity in vivo after experimental traumatic brain injury (TBI). In anticipated clinical use, only a slight increase in CSF osmolarity may be required to reduce cerebral edema.


Spatiotemporal Heterogeneity and Intragenus Variability in Rhizobacterial Associations with Brassica rapa Growth.
Microbial communities in the rhizosphere are distinct from those in soils and are influenced by stochastic and deterministic processes during plant development. These communities contain bacteria capable of promoting growth in host plants through various strategies. While some interactions are characterized in mechanistic detail using model systems, others can be inferred from culture-independent methods, such as 16S amplicon sequencing, using machine learning methods that account for this compositional data type. To characterize assembly processes and identify community members associated with plant growth amid the spatiotemporal variability of the rhizosphere, we grew Brassica rapa in a greenhouse time series with amended and reduced microbial treatments. Inoculation with a native soil community increased plant leaf area throughout the time series by up to 28%. Despite identifying spatially and temporally variable amplicon sequence variants (ASVs) in both treatments, inoculated communities were more highly connected and assembled more deterministically overall. Using a generalized linear modeling approach controlling for spatial variability, we identified 43 unique ASVs that were positively or negatively associated with leaf area, biomass, or growth rates across treatments and time stages. ASVs of the genus Flavobacterium dominated rhizosphere communities and showed some of the strongest positive and negative correlations with plant growth. Members of this genus, and growth-associated ASVs more broadly, exhibited variable connectivity in networks independent of growth association (positive or negative). These findings suggest host-rhizobacterial interactions vary temporally at narrow taxonomic scales and present a framework for identifying rhizobacteria that may work independently or in concert to improve agricultural yields. IMPORTANCE The rhizosphere, the zone of soil surrounding plant roots, is a hot spot for microbial activity, hosting bacteria capable of promoting plant growth in ways like increasing nutrient availability or fighting plant pathogens. This microbial system is highly diverse and most bacteria are unculturable, so to identify specific bacteria associated with plant growth, we used culture-independent community DNA sequencing combined with machine learning techniques. We identified 43 specific bacterial sequences associated with the growth of the plant Brassica rapa in different soil microbial treatments and at different stages of plant development. Most associations between bacterial abundances and plant growth were positive, although similar bacterial groups sometimes had different effects on growth. Why this happens will require more research, but overall, this study provides a way to identify native bacteria from plant roots that might be isolated and applied to boost agricultural yields.


Preschool Children's Processing of Events during Verb Learning: Is the Focus on People (Faces) or Their Actions (Hands)?
Verbs are central to the syntactic structure of sentences, and, thus, important for learning one's native language. This study examined how children visually inspect events as they hear, and do not hear, a new verb. Specifically, there is evidence that children may focus on the agent of the action or may prioritize attention to the action being performed; to date, little evidence is available. This study used an eye tracker to track 2-, 3-, and 4-year-olds' looking to the agent (i.e., face) vs. action (i.e., hands) while viewing events linked to a new verb as well as distractor events. A Tobii X30 eye tracker recorded children's fixations to AOIs (head/face and hands) as they watched three target events and two distractor events in different orders during the learning phase, and pointed to one of two events in two test trials. This was repeated for a second novel verb. Pointing results show that children in all age groups were able to learn and extend the new verbs to new events at test. Additionally, across age groups, when viewing target events, children increased their looking to the hands (where the action is taking place) as those trials progressed and decreased their looking to the agents' face, which is less informative for learning a new verb's meaning. In contrast, when viewing distractor events, children decreased their looking to hands over trials and maintained their attention to the face. In summary, children's visual attention to agents' faces and hands differed depending on whether the events cooccurred with the new verb. These results are important as this is the first study to show this pattern of visual attention during verb learning, and, thus, these results help reveal underlying attentional strategies children may use when learning verbs.


On the size of pores arising in erythrocytes under the action of detergents.
The size of pores arising in human erythrocytes under the action of two detergents (Triton X-100 and sodium dodecyl sulfate) and causing the slow component of hemolysis was estimated by the method of osmotic protectors. The pore diameters were found to be about 40 A. The pores responsible for the fast component of hemolysis induced by sodium dodecyl sulfate were shown to be of greater size and even molecules of polyethylene glycol 4000 could pass through them. The unusual decrease. In the rate and percentage of this hemolytic component was caused by the side action of the protectors, i.e., by the acceleration of erythrocyte vesiculation, a process that competed with pore formation. Vesiculation protected erythrocytes against fast and slow detergent-induced hemolysis. It is shown that the method of osmotic protectors can not be used for estimation of pore size in fast hemolysis by sodium dodecyl sulfate. The application of this method for hemolysis by other amphiphilic compounds is discussed.


NiCo2 O4 /Hollow Mesoporous Carbon Nanosphere Hybrids Enabling Super-Hydrophobicity, Thermal Insulation, and Highly Efficient Microwave Absorption.
The combination of 2D magnetic nanosheets and mesoporous carbon with unique interfaces shows considerable prospects for microwave absorption (MA). However, traditional assembly procedures make it impossible to accurately manage the assembly of magnetic nanosheets in carbon matrices. Herein, a reverse strategy for preparing complex magnetic nanosheet cores inside carbon-based yolk-shell structures is developed. This innovative approach focuses on controlling the initial crystallite formation sites in a hydrothermal reaction as well as the inflow and in situ growth behavior of 2D NiCo-layered double hydroxide precursors based on the capillary force induced by hollow mesoporous carbon nanospheres. Accordingly, the as-prepared YS-CNC-2 absorber exhibits remarkable MA performances, with an optimal reflection loss as low as -60.30 dB at 2.5 mm and an effective absorption bandwidth of 5.20 GHz at 2.0 mm. The loss of electromagnetic waves (EMW) depends on natural resonance loss, dipole polarization relaxation, and multiple scattering behavior. On top of that, the functionalized super-hydrophobic MA coating is produced in spraying and curing processes utilizing YS-CNC-2 nanoparticles and fumed silica additives in the polydimethylsiloxane matrix. The excellent thermal insulation, self-cleaning capability, and durability in diverse solutions of the coating promise potential applications for military equipment in moist situations.


Meander wavelength of alluvial rivers.
Data on river channel and sediment characteristics were collected at 36 cross sections of stable alluvial river channels in Australia and western United States. These data demonstrate that the meander wavelength of a river is dependent not only on water discharge, but also on the type of sediment load moved through the channel. The meander wavelength of rivers that are transporting a high proportion of their total sediment load as both sand and gravel will be greater than the meander wavelengths of channels of similar discharge which are transporting mainly fine sediment loads.


Quantitative Assessment for Self-Tracking of Acute Stress Based on Triangulation Principle in a Wearable Sensor System.
Due to the variation in factors surrounding humans, the physiological impact of stress is reported to be different for each individual. Thus, an efficient stress monitoring system needs to assess both the physiological and psychological impact of stress on individual basis and translate these assessments into an accurate quantitative metric that is of value to the individual. Therefore, this study proposed a logistic regression based model that integrates data from psychological Stress Response Inventory, biochemical (salivary cortisol), and physiological (HRV measures) domains via a principle of triangulation for achieving high reliability and consistency during stress assessment. With the proposed model, a mental stress index (MSI) based on the correlation between salivary cortisol and HRV time-/frequency-domain features were established. A total of 30 college students were recruited to verify the feasibility of proposed method by identifying targeted stressful event. The obtained results reveal that MSI values were sensitive to acute stress, and could predict the association level of normal individual to a stress group with approximately 97% accuracy. Findings from this study could provide potential insight on self-tracking and training of individual's stress with adoption of wearable sensor system in a dynamic setting.


A novel ENU-mutation in ankyrin-1 disrupts malaria parasite maturation in red blood cells of mice.
The blood stage of the plasmodium parasite life cycle is responsible for the clinical symptoms of malaria. Epidemiological studies have identified coincidental malarial endemicity and multiple red blood cell (RBC) disorders. Many RBC disorders result from mutations in genes encoding cytoskeletal proteins and these are associated with increased protection against malarial infections. However the mechanisms underpinning these genetic, host responses remain obscure. We have performed an N-ethyl-N-nitrosourea (ENU) mutagenesis screen and have identified a novel dominant (haploinsufficient) mutation in the Ank-1 gene (Ank1(MRI23420)) of mice displaying hereditary spherocytosis (HS). Female mice, heterozygous for the Ank-1 mutation showed increased survival to infection by Plasmodium chabaudi adami DS with a concomitant 30% decrease in parasitemia compared to wild-type, isogenic mice (wt). A comparative in vivo red cell invasion and parasite growth assay showed a RBC-autonomous effect characterised by decreased proportion of infected heterozygous RBCs. Within approximately 6-8 hours post-invasion, TUNEL staining of intraerythrocytic parasites, showed a significant increase in dead parasites in heterozygotes. This was especially notable at the ring and trophozoite stages in the blood of infected heterozygous mutant mice compared to wt (p<0.05). We conclude that increased malaria resistance due to ankyrin-1 deficiency is caused by the intraerythrocytic death of P. chabaudi parasites.


Multifocal haemorrhagic brain damage following hypoxia and blood pressure lability: case report and rat model.
Haemorrhagic brain damage is frequently encountered as a complication of premature birth. Much less frequently, multifocal petechial haemorrhage is identified in asphyxiated term newborns. Our goal was to develop an experimental rat model to reproduce this pattern of brain damage. Neonatal rat pups were exposed to a 24-h period of 10% or 8% hypoxia followed by a single dose of phenylephrine. Acute and subacute changes, as well as long-term outcomes, were investigated by histology, brain magnetic resonance imaging and behavioural assessment. Immunostaining for vascular endothelial growth factor and caveolin-1 was performed in the rat brains as well as in a 17-day human case. Small foci of haemorrhage were identified in almost all regions of the rat brain subjected to hypoxia plus phenylephrine, but not hypoxia alone. Exposure to 8% hypoxia was associated with more haemorrhagic foci than 10% hypoxia. With rare exceptions, the blood deposits were too small to be detected by magnetic resonance imaging. Altered immunohistochemical detection of vascular endothelial growth factor and caveolin-1 in the child and the rat model suggests a role for blood-brain barrier compromise. There were no clear behavioural changes and no residual morphological abnormalities in the 78-day follow-up of the rats. We conclude that transient hypoxia, in a dose-dependent manner, can weaken the vasculature and predispose to brain haemorrhage in the situation of labile blood pressure. Persistent hypoxia is likely to be important in the genesis of permanent severe brain damage.


Epidemiology of hepatitis C in Croatia in the European context.
We analyzed prevalence, risk factors and hepatitis C virus (HCV) genotype distribution in different population groups in Croatia in the context of HCV epidemiology in Europe, with the aim to gather all existing information on HCV infection in Croatia which will be used to advise upon preventive measures. It is estimated that 35000-45000 of the Croatian population is chronically infected with HCV. Like in other European countries, there have been changes in the HCV epidemiology in Croatia over the past few decades. In some risk groups (polytransfused and hemodialysis patients), a significant decrease in the HCV prevalence was observed after the introduction of routine HCV screening of blood/blood products in 1992. Injecting drug users (IDUs) still represent a group with the highest risk for HCV infection with prevalence ranging from 29% to 65%. Compared to the prevalence in the Croatian general population (0.9%), higher prevalence rates were found in prison populations (8.3%-44%), human immunodeficiency virus-infected patients (15%), persons with high-risk sexual behavior (4.6%) and alcohol abusers (2.4%). Low/very low prevalence was reported in children and adolescents (0.3%) as well as in blood donors (0%-0.009%). In addition, distribution of HCV genotypes has changed due to different routes of transmission. In the general population, genotypes 1 and 3 are most widely distributed (60.4%-79.8% and 12.9%-47.9%, respectively). The similar genotype distribution is found in groups with high-risk sexual behavior. Genotype 3 is predominant in Croatian IDUs (60.5%-83.9%) while in the prison population genotypes 3 and 1 are equally distributed (52.4% and 47.6%). Data on HCV prevalence and risk factors for transmission are useful for implementation of preventive measures and HCV screening.


Episodic memory in frontotemporal dementia: a critical review.
This review offers a critical appraisal of the literature on episodic memory performance in frontotemporal dementia. Historically, description of patients diagnosed with what was then known as Pick's disease included the presence of memory deficits and an underlying amnestic syndrome was noted in some of these patients. Over the last 20 years, however, the clinical view has been that episodic memory processing is relatively intact in the frontotemporal dementia syndrome. In particular, patients with the subtypes of behavioural variant frontotemporal dementia and progressive non-fluent aphasia are reported to perform within normal limits on standard memory tests. In the third clinical presentation of frontotemporal dementia, semantic dementia, relatively intact episodic memory against a significantly impaired semantic memory was regarded as the hallmark. This position was instrumental in the development of clinical diagnostic criteria for frontotemporal dementia in which amnesia was explicitly listed as an exclusion criterion for the disease. The relative intactness of episodic memory, therefore, appeared to be a useful diagnostic marker to distinguish early frontotemporal dementia from Alzheimer's disease, in which early episodic memory disturbance remains the most common clinical feature. We argue that recent evidence questions the validity of preserved episodic memory in frontotemporal dementia, particularly in behavioural variant frontotemporal dementia. In semantic dementia, a complex picture emerges with preservation of some components of episodic memory, notably recognition-based visual memory and recall of recent autobiographical events. We propose a critical synthesis of recent neuropsychological evidence on retrograde and anterograde memory in light of neuroimaging and neuropathological findings, demonstrating involvement of medial temporal structures in frontotemporal dementia, structures known to be critical for episodic memory processing. We further argue that the multifactorial nature of most memory tests commonly used clinically fail to capture the memory deficits in frontotemporal dementia and that sensitive assessment tools of memory are needed. Together, recent clinical and experimental findings and the historical evidence represent a strong case for a re-evaluation of the importance of memory disturbance in the clinical diagnosis of frontotemporal dementia.


Reaction of the vesical wall to bacterial penetration: resistance to attachment, desquamation and leukocytic activity.
To determine the contribution of the bladder wall to defense against infection we designed a series of experiments wherein movement of introduced bacteria and inflammatory processes (cystitis) were observed by an autoradiographic technique. As a first defense line the bladder mucosal surface showed strong resistance against bacterial attachment and penetration. Moreover, epithelial cells gripped and penetrated by bacteria were desquamated and eliminated through voiding, thus arresting deeper invasion into the bladder wall. When organisms did penetrate the bladder wall they were phagocytized by polymorphonuclear leukocytes and macrophages in the submucosa and muscularis. In contrast, once leukocytes had migrated into the urine within the bladder they no longer participated in phagocytosis. Organisms also entered the veins, the lymphatics or both and disappeared rapidly from the local site through the action of the reticuloendothelial system. These observations indicate that in addition to mechanical emptying resistance to bacterial attachment, desquamation of invaded cells, activity of leukocytes and macrophages, and disappearance of bacteria from local site are 4 mechanisms whereby the bladder resists and fights infection.


Socio-economic determinants of disease progression among HIV infected adults in Kenya.
Socioeconomic determinants have been shown to have an effect on the progression of HIV disease evidenced by studies carried out largely in developed countries. Knowledge of these factors could inform on prioritization of populations during scale up of highly active antiretroviral therapy (HAART) constrained health systems. The objective of this study was to identify socioeconomic correlates of HIV disease progression in an adult Kenyan population. We analysed data from 312 HIV positive individuals, drawn from a cohort enrolled in a randomized clinical trial investigating the effectiveness of Acyclovir in the prevention of HIV transmission among serodiscordant couples. In this study we included individuals with CD4 counts ≥ 350 cells/mm(3) and World Health Organization (WHO), clinical stage one or two. The exposure variables measured were: - daily household income available for expenditure, age, gender, housing type and level of formal education. We used a composite outcome of disease progression to WHO clinical stage 3 or 4 or a laboratory outcome of CD4 count below 350 cells/mm(3) after two years of follow-up. Logistic regression was used to determine associations of variables that were found to be significant at univariate analysis, and to control for potential confounders. Seventy eight (25 %) individuals reported HIV disease progression. Majority (79.9 %) were female. The median age was 30 year and 93.6 % had attained a primary level of education. Median CD4 at enrolment into the clinical trial was 564 cells/mm(3); those who had disease progression were enrolled with a significantly (p < 0.001) lower CD4 count. Daily household income available for expenditure adjusted for CD4 count at enrolment was associated significantly (p = 0.04) with HIV disease progression. Disease progression was five times more likely to occur in study subjects with daily income available for expenditure of less than US$1 compared to those with more than US$ 5 available for daily expenditure [adjusted Odds Ratio 4.6 (95 % Confidence Interval 1.4-14.4)]. Disease progression was not associated with age, gender, type of housing or level of education attained (p < 0.05). Populations with low household incomes should be considered vulnerable to disease progression and should therefore be prioritized during the scale up of HAART for treatment as prevention.


Identification of a Tumor Cell Associated Type I IFN Resistance Gene Expression Signature of Human Melanoma, the Components of Which Have a Predictive Potential for Immunotherapy.
We developed a human melanoma model using the HT168-M1 cell line to induce IFN-α2 resistance in vitro (HT168-M1res), which was proven to be maintained in vivo in SCID mice. Comparing the mRNA profile of in vitro cultured HT168-M1res cells to its sensitive counterpart, we found 79 differentially expressed genes (DEGs). We found that only a 13-gene core of the DEGs was stable in vitro and only a 4-gene core was stable in vivo. Using an in silico cohort of IFN-treated melanoma tissues, we validated a differentially expressed 9-gene core of the DEGs. Furthermore, using an in silico cohort of immune checkpoint inhibitor (ICI)-treated melanoma tissues, we tested the predictive power of the DEGs for the response rate. Analysis of the top four upregulated and top four downregulated genes of the DEGs identified WFDC1, EFNA3, DDX10, and PTBP1 as predictive genes, and analysis of the "stable" genes of DEGs for predictive potential of ICI response revealed another 13 genes, out of which CDCA4, SOX4, DEK, and HSPA1B were identified as IFN-regulated genes. Interestingly, the IFN treatment associated genes and the ICI-therapy predictive genes overlapped by three genes: WFDC1, BCAN, and MT2A, suggesting a connection between the two biological processes.


[Patients expect antibiotics. Or not? A folie a deux].
Doctors often feel pressured by patients to prescribe antibiotics for a common cold or a sore throat, against their better judgment. Yet do patients really put pressure on their doctor or even expect a prescription for an antibiotic or some other medicine? Several interesting studies shed some light on this issue. Doctors in an emergency department, for example, prescribed an antibiotic much more frequently than their patients expected them to. Only in 25% of cases were the doctors correct in their assumptions about patient expectations. In a Norwegian study, the authors found that parents wanted more time and explanation for their coughing children and fewer prescriptions. So instead of assuming that patients want antibiotics for innocent symptoms, we should put more effort into exploring patients' expectations and providing them with relevant information. That way we can step out of the folie a deux.


Anhydrobiosis in five species of plant associated nematodes.
Five species of nematodes - Hemicriconemoides pseudobrachyurum, Hemicycliophora conida, Macroposthonia ornata, Aphelenchoides ritzemabosi, and Psilenchus hilarulus -were desiccated to study their capacity to survive anhydrobiotically. Results indicate that the ability of the sheath to shrink quickly and its relatively loose attachment with the nematode body allow H. conida to survive longer than H. pseudobrachyurum; the survival of M. ornata was intermediate, A. ritzemabosi and P. hilarulus survived immersion in paraffin oil for 12 and 17 days, respectively. Both of these nematodes possess multiple contraction ability; i.e., coiling coupled with transverse and longitudinal folding of the cuticle. P. hilarulus is a new addition to the list of anhydrobiotic nematodes.


Novel monoclonal antibodies GMab-r1 and LMab-1 specifically recognize IDH1-R132G and IDH1-R132L mutations.
Isocitrate dehydrogenase 1 (IDH1) catalyzes the oxidative carboxylation of isocitrate to α-ketoglutarate in cytosol. IDH1 mutations, which are specific to a single codon in the conserved and functionally important Arginine 132 (R132), result in the ability of the enzyme to catalyze the reduced NADP-dependent reduction of α-ketoglutarate to onco-metabolite R(-)-2-hydroxyglutarate (2-HG). IDH1 mutations, which are early and frequent genetic alterations that occur in gliomas, cartilaginous tumors, and leukemias. We previously established two monoclonal antibodies (MAbs) that are specific for IDH1 mutations: clone HMab-1 against IDH1-R132H and clone SMab-1 against IDH1-R132S. However, specific MAbs against IDH1-R132G or IDH1-R132L have not been reported. To establish IDH1-R132G-specific or IDH1-R132L-specific MAbs, we immunized rats with each mutation-containing IDH1 peptides, and IDH1-R132G-specific or IDH1-R132L-specific MAbs were screened in ELISA. Established MAb GMab-r1 reacted with the IDH1-R132G peptide, but not with IDH1-wild type (WT) in ELISA. In contrast, LMab-1 reacted with the IDH1-R132L peptide, but not with IDH1-WT. Western blot analysis also showed that GMab-r1 and LMab-1 reacted with the IDH1-R132G and IDH1-R132L recombinant proteins, respectively, but not with IDH1-WT or other IDH1 mutants, indicating that GMab-r1 and LMab-1 are IDH1-mutation-specific. Furthermore, GMab-r1 and LMab-1 specifically stained the IDH1-R132G- and IDH1-R132L-expressing cells in immunocytochemistry, respectively. This is the first report to establish anti-IDH1-R132G-specific or IDH1-R132L-specific MAbs, which could be useful in the diagnosis of mutation-bearing tumors.


[Studies on circular dichroism of some reactional intermediates of artemisinine and artemisinine in B].
This paper reports circular dichroism, sector and the olefin octant projection of 6-pair synthetic intermediates of qinghaosu (artemisinine) and qinghaosu B (artemisinine B): gamma-lactone (compounds 1-4, 7-10), delta-lactone (compounds 5-6) and endo-alpha, beta-unsaturated-gamma-lactone (compounds 11-12). The relationship between double bond in the ring A and Cotton effect signs of different lactone chromophore has been studied. By using lactone sector rule, the olefin octant rule, allylic oxygen rule and Beecham rule with C = C-C-O and C = C-C = O chromophore, their absolute configurations were assigned. The results show that the Cotton effect signs of lactone chromophore of compounds 2, 4, 6, and 12 should be inverted while compounds 8 and 10 are independent on the double bond in ring A.


l-Asparaginase from Aspergillus spp.: production based on kinetics, thermal stability and biochemical characterization.
This study describes the production of native l-asparaginases by submerged fermentation from Aspergillus strains and provides the biochemical characterization, kinetic and thermodynamic parameters of the three ones that stood out for high l-asparaginase production. For comparison, the commercial fungal l-asparaginase was also studied. Both commercial and l-asparaginase from Aspergillus oryzae CCT 3940 showed optimum activity and stability in the pH range from 5 to 8 and the asparaginase from Aspergillus niger LBA 02 was stable in a more alkaline pH range. About the kinetic parameters, the denaturation constant increased with the heating temperature for all l-asparaginases, indicating that the l-asparaginase activity decreased at higher temperatures, especially above 60 °C. Moreover, l-asparaginase from A. oryzae CCT 3940 remained stable after 60 min at 50 °C. None of the l-asparaginases were inhibited by high NaCl concentrations, which are highly desirable for food industry application. The catalytic activities of all the l-asparaginases were enhanced by the presence of Mn2+ and inhibited by p-chloromercuribenzoate and iodoacetamide. The l-asparaginase from the Aspergillus strains and the commercial enzyme had similar K m when l-asparagine was used as substrate. None of the l-asparaginases, except the l-asparaginase from A. niger LBA 02, could hydrolyze the substrate l-glutamine, which is of interest for medical proposes, since the glutaminase activity is usually related to adverse reaction during the leukemia treatment. This study showed that these new three non-recombinant l-asparaginases studied have potential application in the food and pharmaceutical industries, especially due to their good thermostability.


Functional genomic analyses of the gut microbiota for CRC screening.
The evidence for a strong correlation between the gut microbiota and colorectal carcinogenesis is quickly gathering pace. This correlation raises important questions, such as whether analysis of the microbiota can be used for screening purposes, and whether targeted intervention can influence the risk of development and progression of neoplasia. The recovery of several pathobionts-such as members of the different bacterial phyla Proteobacteria, Bacteroidetes and Fusobacteria-from the tumour microenvironment of patients with colorectal cancer (CRC) now provides a link between specific microbial colonization and cancer. However, other intestinal bacteria belonging to another major intestinal phylum, Firmicutes, might be effective in the treatment of pathogenic inflammation related to CRC. Future approaches based on the analysis of the gut microbiota of patients with CRC combined with large human cohort studies might open up new possibilities for further prophylactic, screening and treatment strategies.


[Encephalitis associated to novel influenza A virus infection (H1N1) in two young adults].
At today, neurologic desorders associated with novel influenza A (H1N1) virus were reported only in children but not in adult. We report two cases of encephalitis associated to H1N1 virus infection occurred in females of age 28 and 37 years. In both cases disease was less severe without neurologic sequelae. In one case PCR analysis of CSF sample showed a positivity for HSV1. Novel influenza A (H1N1) viral RNA by real time PCR was detected in nasopharyngeal specimens.


Role of the nucleus ambiguus in the regulation of heart rate and arterial pressure.
The present study examined the effect of lesion of cell bodies in the nucleus ambiguus area on the development of neurogenic hypertension and further explored the cardiovascular responses produced by chemical and electrical stimulation of the nucleus ambiguus and the neighboring C1 region. Three days after chemical lesion of the nucleus ambiguus with kainic acid, arterial pressure and heart rate were unchanged; however, subsequent sinoaortic deafferentation produced a significantly greater increase of arterial pressure (157 +/- 7 vs 132 +/- 5 mm Hg) and heart rate (436 +/- 10 vs 374 +/- 10 beats/min) compared with those produced by sham lesion. Glutamate injected into the nucleus ambiguus increased arterial pressure and heart rate at 20 nmol/100 nl and decreased heart rate at 50 nmol/100 nl. Glutamate injected into the C1 area increased arterial pressure and heart rate at both doses. Gamma-Aminobutyric acid at 50 nmol/100 nl produced bradycardia and a fall in arterial pressure when injected into both the nucleus ambiguus and C1 area. The heart rate responses to gamma-aminobutyric acid and glutamate were attenuated in sinoaortic-deafferentated rats. The nucleus ambiguus and the C1 region were mapped using electrical stimulation with microelectrodes. All points stimulated in three anteroposterior sections in the nucleus ambiguus and the C1 area produced increases in arterial pressure, whereas bradycardia was restricted to the middle of three lateral coordinates associated with the center of the nucleus ambiguus and the C1 area ventral to the nucleus ambiguus.(ABSTRACT TRUNCATED AT 250 WORDS)


Host plant defenses of black (Solanum nigrum L.) and red nightshade ( Solanum villosum Mill.) against specialist Solanaceae herbivore Leptinotarsa decemlineata (Say).
Black nightshade (Solanum nigrum, S. nigrum L.) and red nightshade ( Solanum villosum, S. villosum Mill.) are medicinal plants from the Solanaceae family that synthesize glycoalkaloids and other secondary metabolites. To recognize the potential insecticide activity of these compounds, leaf extracts (containing glycoalkaloid and methanol fractions) were tested for enzyme inhibition, antifeedant activity and toxicity. For in-vitro glutathione S-transferase (GST) inhibition activity, we used insecticide-resistant Colorado potato beetle, Leptinotarsa decemlineata ( L. decemlineata; Say) midgut and fat-body homogenate. In-vivo toxicity and the antifeedant activity were performed using larval bioassays. The methanol extracts had greater GST inhibitory activity compared to the glycoalkaloids, as well as greater 2nd instar larvae mortality and antifeedant activity. Furthermore, the green leaf volatile compound, cis-hex-3-enyl acetate, at the concentration of 5 ppm, caused 50% mortality of 2nd instar larvae. Our findings suggest the potential usefulness of S. nigrum and S. villosum extracts to control L. decemlineata.


Effect of alpha-naphthylisothiocyanate on blood clearance of 99mTc-phytate in dogs.
The effect of alpha-naphthylisothiocyanate (ANIT) on blood clearance of 99mTc-phytate (99mTc-P) in dogs was examined, and blood clearance test of 99mTc-P was compared with the cases of serum transaminase test or serum bilirubin test. Serum transaminase and bilirubin levels in dogs increased after ANIT administration, however, the degree of increase in these parameters was much lower than the cases in rats. The disappearance rate of 99mTc-P from blood in dogs decreased with the increase in dose of ANIT and with the passage of time after the ANIT administration. Changes of the blood clearance of 99mTc-P after ANIT treatment in dogs may be influenced by the disorder in the hepatocytes rather than in the bile ductule cells. The blood clearance test of 99mTc-P in dogs showed a sensitive reaction for the acute hepatic dysfunction induced by ANIT equally to the serum transaminase test or the serum bilirubin test.


Injections of nociceptin into nucleus accumbens shell or ventromedial hypothalamic nucleus increase food intake.
The novel opioid receptor ORL1 is widely distributed throughout the CNS of the rat, and is present in high densities in several brain regions known to participate in the control of food intake. We injected a recently identified endogenous agonist of this receptor, nociceptin, into two of these feeding-related areas. Microinjections of nociceptin (2.5-25 nmol) into either the ventromedial hypothalamic nucleus or the nucleus accumbens shell significantly increased food intake in rats. We believe this to be the first report of a specific effect of nociceptin on a motivated behavior.


Electron microscopic observations on the virus particles in Herpes simplex encephalitis.
Cerebral cortex from eight fatal cases of Herpes simplex encephalitis has been studied by electron microscopy. The diagnosis had been based on clinical findings, necropsy evidence of bitemporal necrosis, and histological confirmation of intranuclear inclusions with a lymphocytic inflammatory response, even though virus cultures were unsuccessful. Virus particles were seen predominantly in nuclei in six of these cases, utilizing tissue which had been preserved in formalin for up to four years or had been embedded in paraffin. Although demonstration of these particles is only indicative of the herpes group and not specifically of Herpes simplex, electron microscopy of either biopsy or postmortem material may be a useful adjunct in making the diagnosis and can be accomplished before virological studies have been completed.


All-inorganic perovskite nanocrystal assisted extraction of hot electrons and biexcitons from photoexcited CdTe quantum dots.
Excitation of semiconductor quantum dots (QDs) by photons possessing energy higher than the band-gap creates a hot electron-hole pair, which releases its excess energy as waste heat or under certain conditions (when hν > 2Eg) produces multiple excitons. Extraction of these hot carriers and multiple excitons is one of the key strategies for enhancing the efficiency of QD-based photovoltaic devices. However, this is a difficult task as competing carrier cooling and relaxation of multiple excitons (through Auger recombination) are ultrafast processes. Herein, we study the potential of all-inorganic perovskite nanocrystals (NCs) of CsPbX3 (X = Cl, Br) as harvesters of these short-lived species from photo-excited CdTe QDs. The femtosecond transient absorption measurements show CsPbX3 mediated extraction of both hot and thermalized electrons of the QDs (under a low pump power) and (under a high pump fluence) extraction of multiple excitons prior to their Auger assisted recombination. A faster timescale of thermalized electron transfer (∼2 ps) and a higher extraction efficiency of hot electrons (∼60%) are observed in the presence of CsPbBr3. These observations demonstrate the potential of all-inorganic perovskite NCs in the extraction of these short-lived energy rich species implying that complexes of the QDs and perovskite NCs are better suited for improving the efficiency of QD-sensitized solar cells.


Mitochondrial spongiotic brain disease: astrocytic stress and harmful rapamycin and ketosis effect.
Mitochondrial DNA (mtDNA) depletion syndrome (MDS) is a group of severe, tissue-specific diseases of childhood with unknown pathogenesis. Brain-specific MDS manifests as devastating spongiotic encephalopathy with no curative therapy. Here, we report cell type-specific stress responses and effects of rapamycin treatment and ketogenic diet (KD) in mice with spongiotic encephalopathy mimicking human MDS, as these interventions were reported to improve some mitochondrial disease signs or symptoms. These mice with astrocyte-specific knockout of Twnk gene encoding replicative mtDNA helicase Twinkle (TwKOastro) show wide-spread cell-autonomous astrocyte activation and mitochondrial integrated stress response (ISRmt) induction with major metabolic remodeling of the brain. Mice with neuronal-specific TwKO show no ISRmt Both KD and rapamycin lead to rapid deterioration and weight loss of TwKOastro and premature trial termination. Although rapamycin had no robust effects on TwKOastro brain pathology, KD exacerbated spongiosis, gliosis, and ISRmt Our evidence emphasizes that mitochondrial disease treatments and stress responses are tissue- and disease specific. Furthermore, rapamycin and KD are deleterious in MDS-linked spongiotic encephalopathy, pointing to a crucial role of diet and metabolism for mitochondrial disease progression.


Utilization of Machine Learning to Model Important Features of 30-day Readmissions following Surgery for Metastatic Spinal Column Tumors: The Influence of Frailty.
Retrospective cohort study. The aim of this study was to determine the relative importance and predicative power of the Hospital Frailty Risk Score (HFRS) on unplanned 30-day readmission after surgical intervention for metastatic spinal column tumors. All adult patients undergoing surgery for metastatic spinal column tumor were identified in the Nationwide Readmission Database from the years 2016 to 2018. Patients were categorized into 3 cohorts based on the criteria of the HFRS: Low(<5), Intermediate(5-14.9), and High(≥ 15). Random Forest (RF) classification was used to construct predictive models for 30-day patient readmission. Model performance was examined using the area under the receiver operating curve (AUC), and the Mean Decrease Gini (MDG) metric was used to quantify and rank features by relative importance. There were 4346 patients included. The proportion of patients who required any readmission were higher among the Intermediate and High frailty cohorts when compared to the Low frailty cohort (Low:33.9% vs. Intermediate:39.3% vs. High:39.2%, P < .001). An RF classifier was trained to predict 30-day readmission on all features (AUC = .60) and architecturally equivalent model trained using only ten features with highest MDG (AUC = .59). Both models found frailty to have the highest importance in predicting risk of readmission. On multivariate regression analysis, Intermediate frailty [OR:1.32, CI(1.06,1.64), P = .012] was found to be an independent predictor of unplanned 30-day readmission. Our study utilizes machine learning approaches and predictive modeling to identify frailty as a significant risk-factor that contributes to unplanned 30-day readmission after spine surgery for metastatic spinal column metastases.


COVID-19 vaccine perceptions in New York State's intellectual and developmental disabilities community.
People with intellectual and developmental disabilities (IDD) are at disproportionate risk for severe COVID-19 outcomes, particularly those living in congregate care settings. Yet, there is limited data on vaccine perceptions in the disability community. To explore COVID-19 vaccine perceptions in individuals with IDD, their family members, and those who work with them, to inform a statewide vaccine information and messaging project. A national survey, adapted in five languages for the IDD community, was distributed to a convenience sample of IDD organizations throughout New York State. Constructs included vaccine intention, reasons for vaccine hesitancy, and trusted sources of vaccine information. Zip code data were used to map respondent location and vaccine preferences. Of n = 825 respondents, approximately 75% intended to or had received the vaccine across roles (i.e., people with developmental disabilities, family members, direct care workers) and racial/ethnic groups. Greater vaccine hesitancy was reported in younger individuals and those making decisions on behalf of a person with IDD. Concerns included side effects and the swiftness of vaccine development. Black and Hispanic participants had heightened concerns about being an "experiment" for the vaccine. Trusted sources of information included healthcare providers and family members. Respondents who intended to/received the vaccine were dispersed throughout the state. Vaccine preferences in this New York State disability community sample align with national data. Identified concerns suggest the need for community education that addresses misperceptions. Age and race differences in perspectives highlight the need for tailored education, delivered by trusted messengers.


A physical simulator for endoscopic endonasal drilling techniques: technical note.
In this paper, the authors present a physical model developed to teach surgeons the requisite drilling techniques when using an endoscopic endonasal approach (EEA) to the skull base. EEA is increasingly used for treating pathologies of the ventral and ventrolateral cranial base. Endonasal drilling is a unique skill in terms of the instruments used, the long reach required, and the restricted angulation, and gaining competency requires much practice. Based on the successful experience in creating custom simulators, the authors used 3D printing to build an EEA training model from post-processed thin-cut head CT scans, formulating the materials to provide realistic haptic feedback and endoscope handling. They performed a preliminary assessment at 2 institutions to evaluate content validity of the simulator as the first step of the validation process. Overall results were positive, particularly in terms of bony landmarks and haptic response, though minor refinements were suggested prior to use as a training device.


Fabrication of high quality and low cost microlenses on a glass substrate by direct printing technique.
The fabrication of high quality and low cost microlenses on a glass substrate using a simple, rapid, and precise direct microplotting technique is shown in this paper. The fabrication method is based on the use of a microplotter system, which is significantly different from the existing inkjet, roll-to-roll printing, and reactive ion etching technology and could work with higher viscosity materials. By optimizing the parameters of voltage, dispense time, and concentration of the polymer solution, high quality microlenses with a diameter of 20 μm could be obtained. The geometrical and optical characteristics of the microlenses are analyzed by measurement of the surface profile and the imaging properties in the near-field and far-field zones as well as the diffraction pattern. We think that the fabricated microlenses could be attractive for enhancing the light extraction efficiency of light emitting diodes.


Testicular biopsy and cryopreservation for fertility preservation of prepubertal boys with Klinefelter syndrome: a pro/con debate.
In about one-half of adult Klinefelter syndrome (KS) patients, spermatozoa can be retrieved by means of testicular biopsy (TESE). Given the expected increase in the number of diagnosed KS patients owing to the use of noninvasive prenatal testing, the probable questions of young KS patients and their parents regarding future fertility, and the fact that widespread apoptosis of spermatogonia occurs at onset of puberty, an attempt to increase the retrieval rates at TESE above those found in adult KS men by undertaking preservation techniques peripubertally has been initiated. To date, however, only a limited number of KS adolescents have been examined, demonstrating no increases in the chances of finding sperm. Furthermore, spermatogonial stem cell and testicular tissue freezing techniques, as well as in vitro maturation strategies, require further validation. Given these controversies, banking testicular tissue from prepubertal KS boys should be performed only in a research framework.


Similarity-driven multi-dimensional binning algorithm (SIMBA) for free-running motion-suppressed whole-heart MRA.
Whole-heart MRA techniques typically target predetermined motion states, address cardiac and respiratory dynamics independently, and require either complex planning or computationally demanding reconstructions. In contrast, we developed a fast data-driven reconstruction algorithm with minimal physiological assumptions and compatibility with ungated free-running sequences. We propose a similarity-driven multi-dimensional binning algorithm (SIMBA) that clusters continuously acquired k-space data to find a motion-consistent subset for whole-heart MRA reconstruction. Free-running 3D radial data sets from 12 non-contrast-enhanced scans of healthy volunteers and six ferumoxytol-enhanced scans of pediatric cardiac patients were reconstructed with non-motion-suppressed regridding of all the acquired data ("All Data"), with SIMBA, and with a previously published free-running framework (FRF) that uses cardiac and respiratory self-gating and compressed sensing. Images were compared for blood-myocardium sharpness and contrast ratio, visibility of coronary artery ostia, and right coronary artery sharpness. Both the 20-second SIMBA reconstruction and FRF provided significantly higher blood-myocardium sharpness than All Data in both patients and volunteers (P < .05). The SIMBA reconstruction provided significantly sharper blood-myocardium interfaces than FRF in volunteers (P < .001) and higher blood-myocardium contrast ratio than All Data and FRF, both in volunteers and patients (P < .05). Significantly more ostia could be visualized with both SIMBA (31 of 36) and FRF (34 of 36) than with All Data (4 of 36) (P < .001). Inferior right coronary artery sharpness using SIMBA versus FRF was observed (volunteers: SIMBA 36.1 ± 8.1%, FRF 40.4 ± 8.9%; patients: SIMBA 35.9 ± 7.7%, FRF 40.3 ± 6.1%, P = not significant). The SIMBA technique enabled a fast, data-driven reconstruction of free-running whole-heart MRA with image quality superior to All Data and similar to the more time-consuming FRF reconstruction.


Microbial Community Structures and Methanogenic Functions in Wetland Peat Soils.
Methane metabolism in wetlands involves diverse groups of bacteria and archaea, which are responsible for the biological decomposition of organic matter under certain anoxic conditions. Recent advances in environmental omics revealed the phylogenetic diversity of novel microbial lineages, which have not been previously placed in the traditional tree of life. The present study aimed to verify the key players in methane production, either well-known archaeal members or recently identified lineages, in peat soils collected from wetland areas in Japan. Based on an ana-lysis of microbial communities using 16S rRNA gene sequencing and the mole-cular cloning of the functional gene, mcrA, a marker gene for methanogenesis, methanogenic archaea belonging to Methanomicrobiales, Methanosarcinales, Methanobacteriales, and Methanomassiliicoccales were detected in anoxic peat soils, suggesting the potential of CH4 production in this natural wetland. "Candidatus Bathyarchaeia", archaea with vast metabolic capabilities that is widespread in anoxic environments, was abundant in subsurface peat soils (up to 96% of the archaeal community) based on microbial gene quantification by qPCR. These results emphasize the importance of discovering archaea members outside of traditional methanogenic lineages that may have significant functions in the wetland biogeochemical cycle.


A refined compilation of implementation strategies: results from the Expert Recommendations for Implementing Change (ERIC) project.
Identifying, developing, and testing implementation strategies are important goals of implementation science. However, these efforts have been complicated by the use of inconsistent language and inadequate descriptions of implementation strategies in the literature. The Expert Recommendations for Implementing Change (ERIC) study aimed to refine a published compilation of implementation strategy terms and definitions by systematically gathering input from a wide range of stakeholders with expertise in implementation science and clinical practice. Purposive sampling was used to recruit a panel of experts in implementation and clinical practice who engaged in three rounds of a modified Delphi process to generate consensus on implementation strategies and definitions. The first and second rounds involved Web-based surveys soliciting comments on implementation strategy terms and definitions. After each round, iterative refinements were made based upon participant feedback. The third round involved a live polling and consensus process via a Web-based platform and conference call. Participants identified substantial concerns with 31% of the terms and/or definitions and suggested five additional strategies. Seventy-five percent of definitions from the originally published compilation of strategies were retained after voting. Ultimately, the expert panel reached consensus on a final compilation of 73 implementation strategies. This research advances the field by improving the conceptual clarity, relevance, and comprehensiveness of implementation strategies that can be used in isolation or combination in implementation research and practice. Future phases of ERIC will focus on developing conceptually distinct categories of strategies as well as ratings for each strategy's importance and feasibility. Next, the expert panel will recommend multifaceted strategies for hypothetical yet real-world scenarios that vary by sites' endorsement of evidence-based programs and practices and the strength of contextual supports that surround the effort.


[Prevalence of serologic markers of hepatitis A, B, C, and D viruses in pregnant women].
To determine the seroprevalence of hepatitis A, B, C and D virus infection among pregnant women attending a perinatal care hospital. A prospective study was carried out to determine the seroprevalence of hepatitis A virus IgG antibodies (anti-HAV), hepatitis B virus markers (anti-HBcAg and HBsAg) and hepatitis C virus antibodies (anti-HCV) in pregnant women. In HBsAg positive cases. HBeAg and hepatitis D virus antibodies (anti-HDV) were investigated. All analyses were performed with the ELISA technique. Of the 1500 pregnant women studied. 93.3% were positive for anti-HAV IgG. The HBsAg seroprevalence was 0.26% and anti-HCV seroprevalence was 0.53%. There were no patients with HBeAg or anti-HDV. A higher seroprevalence of HBsAg was found in this study than in other studies of pregnant Mexican women. We propose that HBsAg screening become a routine prenatal test.


Duodenal Diverticular Perforation Treated Conservatively: Reassessing Indications for Treatment.
A 59-year-old woman presented with a chief complaint of melena. She had no abdominal findings, such as tenderness or tapping pain. Laboratory tests revealed a white blood cell count of 5,300 cells/μL and C-reactive protein level of 0.07 mg/dL. Inflammation and anemia (hemoglobin 12.4 g/dL) were denied. Contrast-enhanced computed tomography (CT) revealed multiple duodenal diverticula and air surrounding a descending duodenal diverticulum. Based on these findings, duodenal diverticular perforation (DDP) was suspected. Oral food intake was stopped, and nasogastric tube feeding and conservative treatment with cefmetazole, lansoprazole, and ulinastatin were begun. On day 8 of hospitalization, follow-up CT revealed the disappearance of the air surrounding the duodenum, and the patient was discharged on day 19 after the resumption of oral feeding.