Instrumentation for laparoscopic renal surgery--Padron Endoscopic Exposing Retractor (PEER) and Endoholder: point of technique.
During laparoscopic surgery, as in open surgery, exposure is critical. However, this can be difficult during laparoscopy due to limited haptic feedback and the loss of 3-dimensional visualization. Excessive force may be inadvertently applied by assistants when anatomic structures are retracted; similarly, the retractors may be unknowingly moved because the limited field of view with the laparoscope precludes constant visualization of the retracting instrument. To overcome these problems, we have been using a 5- or 10-mm PEER retractor in combination with an articulating arm instrument holder (Endoholder) to aid laparoscopic renal surgery. The adjustable spring-loaded articulating instrument holder (Endoholder) consists of 4 components, including table attachment, a base rod, flexible extension arm, and precision clamp. The clamp accommodates variously sized instruments, and the flexible extension arm rotates 360 degrees to aid in positioning. The instrument holder is clamped to the table via the base rod over a sterile drape. A PEER Retractor, Roto-lok ratchet (5- or 10-mm diameter and 32-cm length) is placed intracorporeally to retract and position the kidney for hilar, upper, and lower pole dissection. The PEER retractor's handle is secured in place using the precision clamp of the instrument holder. The articulating instrument holder and PEER retractor are used for our renal, adrenal, and ureteral laparoscopic procedures. Placement of the retractor through a 5- or 10-mm port and deployment can be done quickly. Adequate and stable positioning of the retractor provides excellent and secure visualization of the operative field. These instruments have been used in more than 200 cases without any complication except 1 minor liver laceration. The articulating instrument holder with the PEER retractor is a very useful aid during laparoscopic renal surgery. This instrument reduces the chances of inadvertent injury to viscera by the assistant while maintaining an excellent anatomic view throughout the procedure. This will have a significant impact on the advancement of laparoscopy and its acceptance by every urologist.


Giant Mechanocaloric Effects in Fluorite-Structured Superionic Materials.
Mechanocaloric materials experience a change in temperature when a mechanical stress is applied on them adiabatically. Thus, far, only ferroelectrics and superelastic metallic alloys have been considered as potential mechanocaloric compounds to be exploited in solid-state cooling applications. Here we show that giant mechanocaloric effects occur in hitherto overlooked fast ion conductors (FIC), a class of multicomponent materials in which above a critical temperature, Ts, a constituent ionic species undergoes a sudden increase in mobility. Using first-principles and molecular dynamics simulations, we found that the superionic transition in fluorite-structured FIC, which is characterized by a large entropy increase of the order of 10(2) JK(-1) kg(-1), can be externally tuned with hydrostatic, biaxial, or uniaxial stresses. In particular, Ts can be reduced several hundreds of degrees through the application of moderate tensile stresses due to the concomitant drop in the formation energy of Frenkel pair defects. We predict that the adiabatic temperature change in CaF2 and PbF2, two archetypal fluorite-structured FIC, close to their critical points are of the order of 10(2) and 10(1) K, respectively. This work advocates that FIC constitute a new family of mechanocaloric materials showing great promise for prospective solid-state refrigeration applications.


Primes and Consequences: A Systematic Review of Meritocracy in Intergroup Relations.
Psychological interest in Meritocracy as an important social norm regulating most of the western democratic societies has significantly increased over the years. However, the way Meritocracy has been conceptualized and operationalized in experimental studies has advanced in significant ways. As a result, a variety of paradigms arose to understand the social consequences of Meritocracy for intergroup relations; in particular, to understand the adverse consequences of Meritocracy for disadvantaged group members. The present research seeks to understand whether there is strong support for the idea that (manipulated) Meritocracy disproportionally affects members of low status groups, and also to understand which specific components of this norm have been successfully manipulated and to what consequences. And this is particularly important given the recent call for greater transparency in how the success of experimental manipulations is reported. Thus, we carried out a systematic review examining the content of different prime tasks, summarizing prime manipulation checks' effectiveness, and analyzing whether priming Meritocracy leads to less favorable orientations toward low status groups. Results across 33 studies revealed that despite the existing differences in the components highlighted, the salience of any of the Meritocracy dimensions facilitates the use of internal causal attributions, negative evaluations and stereotyping toward low status groups, affecting negatively decisions involving low-status group members, particularly in specific domains, as organizational contexts. These results carry both practical and theoretical implications for future research on the role of Meritocracy in intergroup settings.


A phase II multicenter study of troxacitabine in relapsed or refractory lymphoproliferative neoplasms or multiple myeloma.
Options for patients with relapsed/refractory lymphoproliferative disorders and multiple myeloma are currently limited. Troxacitabine has shown promise in preclinical studies in a variety of malignancies; hence, the current study was conducted to evaluate the activity of troxacitabine in relapsed or refractory lymphoid malignancies. This was a phase II, open-label, multinational, multicenter study of patients with relapsed or refractory lymphoproliferative disorders or multiple myeloma. Thirty-four adults were enrolled in the study and received the study drug at either 5.4 mg/m2 (n = 16) or 4.3 mg/m2 (n = 18). The dose was decided in a phase I study, during which dose escalation was carried to reach a maximum tolerated dose with an acceptable toxicity profile. Two separate phase I studies were performed in Europe and the US. Troxacitabine was administered by intravenous infusion over 30 min daily for days 1 - 5 every 4 weeks. Treatment was continued to disease progression or until the subjects met criteria for withdrawal or unacceptable toxicities were evident as outlined in the protocol. Two patients had a partial response (PR) to treatment with troxacitabine to yield an overall response rate of 13%. There were no complete responses seen with the drug. Stable disease was achieved in 15 patients (44%). All patients had at least one treatment related adverse event, which led to six withdrawals from the study. Hematologic toxicity constituted the most common adverse events. Serious adverse effects were seen in 62% of patients. None of the 13 deaths were attributed directly to troxacitabine. As a single agent, troxacitabine has limited benefit in patients with advanced lymphoproliferative disorders or multiple myeloma. Future studies will be needed to address modified dosing according to emerging pharmacokinetic and pharmacodynamic data and combination therapy which may lead to improved clinical benefit for troxacitabine in hematologic malignancies.


Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.
Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.


Risk Assessment of Industrial Microbes Using a Terrestrial Mesocosm Platform.
Industrial microbes and bio-derived products have emerged as an integral component of the bioeconomy, with an array of agricultural, bioenergy, and biomedical applications. However, the rapid development of microbial biotechnology raises concerns related to environmental escape of laboratory microbes, detection and tracking thereof, and resultant impact upon native ecosystems. Indeed, though wild-type and genetically modified microbes are actively deployed in industrial bioprocesses, an understanding of microbial interactivity and impact upon the environment is severely lacking. In particular, the persistence and sustained ecosystem impact of industrial microbes following laboratory release or unintentional laboratory escape remains largely unexplored. Herein, we investigate the applicability of soil-sorghum mesocosms for the ecological risk assessment of the industrial microbe, Saccharomyces cerevisiae. We developed and applied a suite of diagnostic and bioinformatic analyses, including digital droplet PCR, microscopy, and phylogenomic analyses to assess the impacts of a terrestrial ecosystem perturbation event over a 30-day time course. The platform enables reproducible, high-sensitivity tracking of S. cerevisiae in a complex soil microbiome and analysis of the impact upon abiotic soil characteristics and soil microbiome population dynamics and diversity. The resultant data indicate that even though S. cerevisiae is relatively short-lived in the soil, a single perturbation event can have sustained impact upon mesocosm soil composition and underlying microbial populations in our system, underscoring the necessity for more comprehensive risk assessment and development of mitigation and biocontainment strategies in industrial bioprocesses.


The use of a dorsal double-wing flap without skin grafts for congenital syndactyly treatment: A STROBE compliant study.
Numerous techniques have been developed that use various flaps to treat syndactyly. Skin grafts have often been used to cover remaining surgical defects. The long-term aim of surgery is to find new methods of separating the digits without using skin grafts. This paper describes a new surgical technique for the correction of simple, incomplete, and complete syndactyly. The technique consists of a dorsal double-wing flap to cover the newly created web space and zigzag incisions in the fingers, thus avoiding the use of skin grafts in this space. Overall, 35 web spaces in 24 patients were treated using this technique. Patient follow-up ranged from 6 months to nearly 5 years. There were no complications such as hematoma, infection or flap necrosis, and no fingers needed skin grafts after separation. The average operative time for each web space was approximately 45 minutes. Ninety-seven percent of patients treated with the dorsal double-wing flap procedure achieved good function, and superior cosmetic results following a single surgery. The technique is simple, rapid, safe, and easily performed and does not require the use of skin grafts.


Before the deluge: The 1932 International Congress of Psychology in Copenhagen.
The Tenth International Congress of Psychology, held in Copenhagen in late August of 1932, was the last International Congress held before events leading up to World War II came to interfere with the course of the congresses. Despite the difficult times, primarily because of the Great Depression and the fragile political situation, the congress nevertheless managed to bring together participants from many countries, thus emphasizing the international profile of psychology. The 1932 congress was characterized by the wide range of topics presented and discussed. A book of proceedings, containing all the papers delivered, was planned but never appeared, as the organizers of the congress were unable to obtain funds required for the publication. Therefore, relatively little has been written about the congress. The congress, however, aroused great interest in the Danish newspapers. Many participants took part in interviews, casting an interesting light on their approaches to psychology. The newspaper reports, along with archival sources, make it possible to describe the course of the conference. It clearly emerges that psychology had, by this time, shed the narrow experimental focus of its earliest decades. The gathering clouds of international unrest had some effects on the course of the congress. Shortly after the congress, the careers and even the lives of many of the participants faced serious challenges. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Agreement of the Resting Distal to Aortic Coronary Pressure With the Instantaneous Wave-Free Ratio.
Recently, 2 randomized controlled trials showed that the instantaneous wave-free ratio (iFR), a resting coronary physiological index, is noninferior to fractional flow reserve for guiding revascularization. The resting distal to aortic coronary pressure (Pd/Pa) measured at rest is another adenosine-free index widely available in the cardiac catheterization laboratory; however, little is known about the agreement of Pd/Pa using iFR as a reference standard. The goal of this study was to investigate the agreement of Pd/Pa with iFR. A total of 763 patients were prospectively enrolled from 12 institutions. iFR and Pd/Pa were measured under resting conditions. Using iFR ≤0.89 as a reference standard, the agreement of Pd/Pa and its best cutoff value were assessed. According to the independent core laboratory analysis, iFR and Pd/Pa were analyzable in 627 and 733 patients (82.2% vs. 96.1%; p < 0.001), respectively. The median iFR and Pd/Pa were 0.90 (interquartile range: 0.85 to 0.94) and 0.92 (interquartile range: 0.88 to 0.95), and the 2 indices were highly correlated (R2 = 0.93; p < 0.001; iFR = 1.31 * Pd/Pa -0.31). According to the receiver-operating characteristic curve analysis, Pd/Pa showed excellent agreement (area under the curve: 0.98; 95% confidence interval: 0.97 to 0.99; p < 0.001) with a best cutoff value of Pd/Pa ≤0.91. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 93.0%, 91.4%, 94.4%, 93.3%, and 92.7%, respectively. These results were similar in patients with acute coronary syndrome and stable angina. Pd/Pa was analyzable in a significantly higher number of patients than iFR. Pd/Pa showed excellent agreement with iFR, suggesting that it could be applied clinically in a similar fashion. (Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology? [CONTRAST]; NCT02184117).


Sever's injury; treat it with a heel cup: a randomized, crossover study with two insole alternatives.
Sever's injury (apophysitis calcanei) is considered to be the dominant cause of heel pain among children. Common advice is to reduce physical activity. However, our previous study showed that application of insoles reduced pain in Sever's injury without having to reduce physical activity. The purpose of this study was to test which of the two insoles, the heel wedge or the heel cup, provided best pain relief during sport activity in boys with Sever's injury (n=51). There was a crossover design in the first randomized part of the study. In the second part, the boys, 9-14 years, chose which insole they preferred. There was a reduction in odds score for pain to a fifth (a reduction of 80%) for the cup compared with the wedge (P<0.001). When an active choice was made, the heel cup was preferred by >75% of the boys. All boys maintained their high level of physical activity throughout. At 1-year follow-up, 22 boys still used an insole and 19 of them reported its effect on pain as excellent or good (n=41).


Lysis by activated lymphocytes of melanoma and small cell lung cancer cells surviving in vitro treatment with mafosfamide.
Six short term-cultured melanoma cell lines and one small cell lung cancer cell line were treated in vitro with the alkylating agent mafosfamide. The sensitivity of the surviving cells to in vitro lysis by recombinant interleukin 2-activated autologous and allogeneic lymphocytes was then investigated. In no case did chemo-surviving tumor cells appear less sensitive to lymphocyte-mediated lysis than untreated counterparts. In three of seven cases (two of which were derived from the same patient), chemo-selected cells were even more sensitive to cytotoxic lymphocytes, a difference not explained by a different distribution of neoplastic cells in the various cell cycle phases. We also studied the inhibitory activity of activated lymphocytes on the clonogenic potential of chemo-surviving tumor cells by the human tumor clonogenic assay. Inhibitions of tumor cell growth in the two patients tested were 100 and 94%, respectively; the activity of lymphocytes was dependent on the coculture time and the effector/target cell ratio. These data indicate that in vitro treatment with mafosfamide does not select cells resistant to the action of activated lymphocytes and that, given the right experimental conditions, these immune effectors can completely lyse tumor cells.


The Application of Iodine Quantitative Information Obtained by Dual-Source Dual-Energy Computed Tomography on Chemoradiotherapy Effect Monitoring for Cervical Cancer: A Preliminary Study.
The aim of the study is to investigate the potential contribution of the iodine quantitative parameters of dual-phase dual-energy computed tomography (DECT) scanning for chemoradiotherapy (CRT) response monitoring for cervical cancer. Patients who were pathologically certified having cervical cancer and intended for concurrent radiotherapy and chemotherapy were prospectively included in our study. Contrast-enhanced DECT scanning was performed before CRT, which was repeated after 1 month of therapy, using a dual-source CT scanner onset. Changes in tumor size were assessed according to RECIST 1.0. Quantification of volume-normalized iodine uptake (mg/mL) was measured in dual phases and was standardized using the iodine uptake in the iliac artery. The decreased ratio of the standard iodine uptake was calculated and compared with the tumor size for the evaluation of the CRT effect. Data were analyzed using the statistics software SPSS version 19.0. Twenty women who performed normal pelvic contrast-enhanced CT scanning were randomly chosen as the control group for the radiation dose comparison with the dual-energy group. A total of 21 patients who completed therapeutic courses and performed the contrast-enhanced CT scanning were subsequently evaluated. According to RECIST 1.0, 15 cases were classified into the regression (R, including 5 completed regression cases and 10 partial regression cases) group. The remaining 6 cases were classified into the nonregression (NR, including 6 stable disease cases) group. The iodine value decreased ratio in the arterial phase (standardized iodine in arterial phase [SAI]) of the partial regression group was significantly higher than that of the stable disease group (P < 0.01), and there was no significant difference in the venous phase (P > 0.05). In a general quantitative comparison between the R group and the NR group before CRT, we controlled for the maximum diameter, age, iodine uptake in the arterial phase before CRT (pre-SAI), iodine uptake in the venous phase before CRT, and cell differentiated level, and we ultimately found no significant statistical differences except for the pre-SAI. In other words, the iodine value in the arterial phase of the R group before CRT was significantly higher than that of the NR group (P < 0.01). When the pre-SAI was 0.345, the area under the curve was 0.875 for therapeutic effect prediction. The mean effective dose was 5.63 ± 1.68 mSv for the DECT group and 5.37 ± 1.82 mSv for the control group (t = -1.137, P = 0.262), which showed no statistical difference in the radiation dose between the 2 scanning methods. The iodine mapping can be used to help evaluate the radiochemotherapy response effectively on the basis of tumor size change and can also be helpful in predicting the radiochemotherapy outcome for cervical cancer. The dual-phase DECT scanning did not increase the radiation dose and provided more valuable information, and thus, it was suitable for promotion in clinical application.


Cloning of the cDNA and gene encoding mouse lysosomal sialidase and correction of sialidase deficiency in human sialidosis and mouse SM/J fibroblasts.
Lysosomal sialidase occurs in a multienzyme complex that also contains beta-galactosidase and cathepsin A. We previously cloned the human lysosomal sialidase cDNA and characterized mutations in human sialidosis patients. Here, we report the cloning and expression of the mouse lysosomal sialidase cDNA and gene. The 1.77 kb cDNA encodes an open reading frame of 408 amino acids which shows high homology to the human lysosomal sialidase (80%), the rat cytosolic sialidase (65%) and viral and bacterial sialidases (50-55%). The sialidase gene is approximately 4 kb long and contains six exons. The five introns range in size from 96 to 1200 bp. Northern blot analysis revealed high expression of multiple sialidase transcripts in kidney and epididymis, moderate levels in brain and spinal cord, and low levels in adrenal, heart, liver, lung and spleen. Transient expression of the cDNA clone in sialidase-deficient SM/J mouse fibroblasts and human sialidosis fibroblasts restored normal levels of sialidase activities in both cell types. Immunocytochemically expressed sialidase co-localized with a lysosomal marker, LAMP2, confirming its lysosomal nature. Since sialidase activity requires its association with beta-galactosidase and cathepsin A, the expression of mouse sialidase within human sialidosis cells underlines the structural similarity between mouse and human enzymes and suggests that the mechanism for complex formation and function is highly conserved.


[Relationship between hippocampal arachidonic acid content and induction of LTP in aged rats].
There are several lines of evidence indicating that membrane AA correlates with the ability of aged rats to sustain LTP. The age-related decrease in membrane AA seems to be triggered by increased lipid peroxidation, which is involved with the decline of LTP. The chronic treatment of DHA could decrease membrane AA without an increase in lipid peroxidation. We have thus investigated the effect of chronic treatment of DHA on hippocampal LTP to assess whether the decrease in membrane AA could directly affect the induction of LTP. The effects of daily supplementation of DHA for 3 months on membrane AA, LTP, and Ca2+ response were evaluated using hippocampal slices from 26-month-old Wistar rats. Chronic treatment of DHA reduced the hippocampal AA significantly, but did not change the amplitude of LTP. Neither 30 mM K+ nor 500 microM NMDA-induced Ca2+ response was affected by chronic treatment of DHA, while the 500 microM carbachol-induced Ca2+ response was reduced. From these results, the reduction of membrane AA might suppress the carbachol-induced Ca2+ response by inhibiting the muscarinic receptor function, IP3 formation and/or Ca2+ release from Ca2+ stores by IP3. However, the reduction of membrane AA is not likely to be a main causal factor of the decline of LTP.


Hydroxychloroquine, QTc prolongation and risk of torsades de pointes.
Hydroxychloroquine (HCQ) is a common medication used for the treatment of rheumatic diseases. As a result of its widespread use during COVID-19, there are increasing concerns about its cardiotoxicity. HCQ is known to cause QTc prolongation, and its long-term use has been associated with cardiomyopathy and conduction abnormalities. Despite reports of ventricular arrhythmia in COVID-19 patients taking HCQ, there have been reassuring data in approved indications. HCQ has been in use for several decades with a good safety profile. In addition to better disease control and prevention of flares, it is associated with decreased risk of cardiovascular diseases. But given its small risk of cardiotoxicity, clinicians should be aware of this effect and monitor patients for developing cardiac symptoms.


[Prediction of complications of I trimester of pregnancy in women with distressed reproductive history by detection of transcervical trophoblastic cells].
The present study investigated the possibility of using trophoblastic (fetal) cells in cervical mucus of pregnant women with complicated reproductive history to predict the course of early I trimester of pregnancy. We examined 86 women at 5-6 weeks of gestation, 56 of them with normal pregnancy, 12 with missed abortion, 18 with tubal pregnancy. As a control we used 21 non-pregnant womеn with primary infertility. Trophoblastic cells we detected by immunohistochemical method and then counted. It was revealed that in the normal course of early I trimester transcervical trophoblastic cells were detected in 4 times more likely than in missed abortion and 5 times more often than in women with tubal pregnancy. In women of the control group, who never had pregnancies, trophoblastic cells were not detected. Thus, the determination of the number of transcervical trophoblastic cells can be used in the complex diagnosis of pathological course of I trimester of pregnancy in women with complicated reproductive history.


Chromatin interaction of TATA-binding protein is dynamically regulated in human cells.
Gene transcription in mammalian cells is a dynamic process involving regulated assembly of transcription complexes on chromatin in which the TATA-binding protein (TBP) plays a central role. Here, we investigate the dynamic behaviour of TBP by a combination of fluorescence recovery after photobleaching (FRAP) and biochemical assays using human cell lines of different origin. The majority of nucleoplasmic TBP and other TFIID subunits associate with chromatin in a highly dynamic manner. TBP dynamics are regulated by the joint action of the SNF2-related BTAF1 protein and the NC2 complex. Strikingly, both BTAF1 and NC2 predominantly affect TBP dissociation rates, leaving the association rate unchanged. Chromatin immunoprecipitation shows that BTAF1 negatively regulates TBP and NC2 binding to active promoters. Our results support a model for a BTAF1-mediated release of TBP-NC2 complexes from chromatin.


Ca2+-activated K+ channels in cultured medullary thick ascending limb cells.
The conductive properties of a clone of medullary thick ascending limb (MTAL) cells (GRB-MAL1) were assessed using conventional microelectrodes and the patch clamp technique. The apical cell membrane potential (Va) of MTAL cells was -46 +/- 3 mV. Addition of Ba2+ (1 mM) to the apical solution induced a 22 +/- 2 mV depolarization of Va, whereas furosemide hyperpolarized Va by -5 +/- 1 mV. In the cell-attached patch configuration, the most frequently occurring channel had a single channel conductance of 121 +/- 5 pS and carried outward current. In excised patches, current movement was down the electrochemical K+ gradient. Fluctuations were activated by depolarization of Va and by increasing Ca2+ concentration on the intracellular face. Micromolar amounts of Ba2+ on the intracellular face of the membrane inhibited channel activity. We conclude that cultures of MTAL cells GRB-MAL1 retain at least two of the properties of the mature phenotype, namely, an apical K+ conductance and a sensitivity to loop diuretics; the most frequently occurring channel in the apical cell membrane is a Ca2+-activated, maxi-K+ channel; and, finally Ca2+-activated K+ channels may play a role in generating the apical K+ conductance in cultured MTAL cells.


SecYEG proteoliposomes catalyze the Deltaphi-dependent membrane insertion of FtsQ.
In Escherichia coli, the insertion of most inner membrane proteins is mediated by the Sec translocase. Ribosome-bound nascent chains of Sec-dependent inner membrane proteins are targeted to the SecYEG complex via the signal recognition particle pathway. We now demonstrate that the signal recognition particle-dependent co-translational membrane targeting and membrane insertion of FtsQ can be reconstituted with proteoliposomes containing purified SecYEG. SecA and a transmembrane electrical potential are essential for the translocation of the large periplasmic domain of FtsQ, whereas co-reconstituted YidC has an inhibitory effect. These data demonstrate that membrane protein insertion can be reconstituted with a minimal set of purified Sec components.


Transethnic replication of association of CTG18.1 repeat expansion of TCF4 gene with Fuchs' corneal dystrophy in Chinese implies common causal variant.
To test the association between the CTG18.1 trinucleotide repeat expansion of TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Chinese population. The trinucleotide repeat polymorphism CTG18.1 was genotyped using short tandem repeat and triplet repeat primed polymerase chain reaction assays in 57 Chinese subjects with FECD and 121 controls. Statistical association of the expanded CTG18.1 allele and 18 single nucleotide polymorphisms (SNPs) across TCF4 with FECD was evaluated. To investigate the linkage disequilibrium structure of the TCF4 region, haplotype analysis was performed on our study subjects and compared with genotyping data of 97 Han Chinese and 85 Caucasians in the 1000 Genomes Project. The expanded CTG18.1 allele was associated with FECD (P = 4.7 × 10(-14)), with the odds ratio of each copy of the expanded allele estimated to be 66.5 (95% confidence interval: 12.6-350.1). Five TCF4 SNPs showed association with FECD at a nominal level (P < 5.0 × 10(-2)); however, conditional on the expanded CTG18.1 polymorphism, none of the SNPs showed association with FECD. The only haplotype associated with the disease was the one with the expansion at the CTG18.1 locus. Transethnic replication of the association between the CTG18.1 repeat expansion in the TCF4 gene and FECD suggests it is a common, causal variant shared in Eurasian populations conferring significant risk for the development of FECD. Our data suggest that the expanded CTG18.1 allele is the main, if not sole, causal variant at this gene locus in the Chinese population.


Computational (DFT) and Experimental (EXAFS) Study of the Interaction of [Ir(IMes)(H)2 (L)3 ] with Substrates and Co-substrates Relevant for SABRE in Dilute Systems.
Signal amplification by reversible exchange (SABRE) is an emerging hyperpolarization method in NMR spectroscopy, in which hyperpolarization is transferred through the scalar coupling network of para-hydrogen derived hydrides in a metal complex to a reversibly bound substrate. Substrates can even be hyperpolarized at concentrations below that of the metal complex by addition of a suitable co-substrate. Here we investigate the catalytic system used for trace detection in NMR spectroscopy with [Ir(IMes)(H)2 (L)3 ](+) (IMes=1,3-dimesitylimidazol-2-ylidene) as catalyst, pyridine as a substrate and 1-methyl-1,2,3-triazole as co-substrate in great detail. With density functional theory (DFT), validated by extended X-ray absorption fine structure (EXAFS) experiments, we provide explanations for the relative abundance of the observed metal complexes, as well as their contribution to SABRE. We have established that the interaction between iridium and ligands cis to IMes is weaker than that with the trans ligand, and that in mixed complexes with pyridine and triazole, the latter preferentially takes up the trans position.


Relative sensitivity of fetal and newborn mice to induction of hapten-specific B cell tolerance.
Mice were rendered tolerant to the hapten fluorescein (FLU) by a single injection of FLU-human gamma globulin (FLU5HGG) 2-3 d after birth or via the maternal circulation at 14.5 d of fetal life. After 7-9 d, the degree of functional nonresponsiveness induced in vivo among splenic FLU-specific B cells of tolerized mice was assessed by limiting-dilution analysis in vitro, and the serum levels of trace-labeled tolerogen were determined. When tolerogen was introduced before the appearance of any B cells, and was thus present during the pre-B to B cell transition stage, a concentration of 5.4 x 10(-13) M effectively silenced 50% of the clonable anti-FLU PFC precursors; but a similar reduction on newborns required a minimal tolerogen concentration of 1.3 x 10(-10) M, > 300-fold less than has previously been shown to equally affect adult B cells, but at least 240-fold more than in the in utero situation. Neonatally induced tolerance using a relatively high tolerogen dose lasted approximately 12 wk.


Validity and reliability of the Structured Clinical Interview for Mood Spectrum: Brazilian version (SCIMOODS-VB).
The aim of this study was to translate the Structured Clinical Interview for Mood Spectrum into Brazilian Portuguese, measuring its reliability, validity, and defining scores for bipolar disorders. Questionnaire was translated (into Brazilian Portuguese) and back-translated into English. Sample consisted of 47 subjects with bipolar disorder, 47 with major depressive disorder, 18 with schizophrenia and 22 controls. Inter-rater reliability was tested in 20 subjects with bipolar disorder and MDD. Internal consistency was measured using the Kuder Richardson formula. Forward stepwise discriminant analysis was performed. Scores were compared between groups; manic (M), depressive (D) and total (T) threshold scores were calculated through receiver operating characteristic (ROC) curves. Kuder Richardson coefficients were between 0.86 and 0.94. Intraclass correlation coefficient was 0.96 (CI 95 % 0.93-0.97). Subjects with bipolar disorder had higher M and T, and similar D scores, when compared to major depressive disorder (ANOVA, p < 0.001). The sub-domains that best discriminated unipolar and bipolar subjects were manic energy and manic mood. M had the best area under the curve (0.909), and values of M equal to or greater than 30 yielded 91.5% sensitivity and 74.5% specificity. Structured Clinical Interview for Mood Spectrum has good reliability and validity. Cut-off of 30 best differentiates subjects with bipolar disorder vs. unipolar depression. A cutoff score of 30 or higher in the mania sub-domain is appropriate to help make a distinction between subjects with bipolar disorder and those with unipolar depression.


Autologous cultured fibroblast injection for facial contour deformities: a prospective, placebo-controlled, Phase III clinical trial.
Previous data indicate that injections of autologous fibroblasts increase collagen formation, accompanied by a concomitant increase in thickness and density of dermal collagen. The purpose of this study was to determine efficacy and side effects of autologous living fibroblast injections versus placebo in a randomized Phase III trial for the treatment of various facial contour defects. This was a double-blind, randomized comparison of injectable living autologous fibroblast cells and placebo for the treatment of facial contour defects (N=215). Live fibroblasts (20 million/mL) or placebo (the transport medium without living cells) were given as three doses administered at 1- to 2-week intervals. Efficacy evaluations were performed 1, 2, 4, 6, 9, and 12 months after the first injection. Living fibroblasts produced statistically significantly greater improvements in dermal deformities and acne scars than did placebo. The difference between live fibroblast injections and placebo achieved statistical significance at 6 months (p<.0001). At 9- and 12-month follow-up, live fibroblast-treated patients continued to demonstrate benefit from treatment with response rates of 75.0 and 81.6%, respectively. No serious treatment-related adverse events were reported. Our results indicate that autologous fibroblast injections can safely and effectively produce improvements in rhytids, acne scars, and other dermal defects continuing for at least 12 months after injection.


A qualitative study of design stakeholders' views of developing and implementing a registry-based learning health system.
New opportunities to record, collate, and analyze routine patient data have prompted optimism about the potential of learning health systems. However, real-life examples of such systems remain rare and few have been exposed to study. We aimed to examine the views of design stakeholders on designing and implementing a US-based registry-enabled care and learning system for cystic fibrosis (RCLS-CF). We conducted a two-phase qualitative study with stakeholders involved in designing, implementing, and using the RCLS-CF. First, we conducted semi-structured interviews with 19 program personnels involved in design and delivery of the program. We then undertook 11 follow-up interviews. Analysis of interviews was based on the constant comparative method, supported by NVivo software. The organizing principle for the RCLS-CF was a shift to more partnership-based relationships between patients and clinicians, founded in values of co-production, and facilitated by technology-enabled data sharing. Participants proposed that, for the system to be successful, the data it collects must be both clinically useful and meaningful to patients and clinicians. They suggested that the prerequisites included a technological infrastructure capable of supporting data entry and joint decision-making in an accessible way, and a set of social conditions, including willingness from patients and clinicians alike to work together in new ways that build on the expertise of both parties. Follow-up interviews highlighted some of the obstacles, including technical challenges and practical constraints on refiguring relationships between clinicians and patients. The values and vision underlying the RCLS-CF were shared and clearly and consistently articulated by design stakeholders. The challenges to realization were often not at the level of principle, but were both practical and social in character. Lessons from this study may be useful to other systems looking to harness the power of "big data" registries, including patient-reported data, for care, research, and quality improvement.


Effect of pre- and post-weaning high-fat dietary manipulation on intestinal microflora and alkaline phosphatase activity in male rats.
We investigated the impact of a high-fat (HF) diet during pre- and post-weaning periods on the intestinal microbiota and alkaline phosphatase (AP) activity in male rats. Nutrition from birth was influenced by feeding rat dams with either a standard or HF diet. After weaning male pups nursed by control dams continued on a standard diet (CC) or HF diet (C->HF), while offspring nursed by HF dams continued on HF diet (HF) or standard diet (HF->C). The numbers of Bacteroides/Prevotella (BAC) and Lactobacillus/Enterococcus (LAB) in the gut were determined by FISH technique. HF pups displayed enhanced adiposity and increased AP activity (19 %), as well as higher LAB (P<0.001) and lower numbers of BAC (P<0.001) in the jejunum and colon than controls. In HF->C rats, post-weaning lower fat intake resulted in decreased fat deposition accompanied by reduced AP activity (20 %) compared to HF rats. Composition of the intestinal microbiota in these rats was not influenced. In contrast, in comparison with controls, C->HF rats displayed higher LAB (P<0.001) and lower BAC (P<0.001) together with increased adiposity and AP activity (14 %). These results indicate that consumption of diet with different fat content could modulate gut microbial/functional conditions depending on the period when the nutritional manipulation occurs.


CCR7 and CXCR4 expression predicts lymph node status including micrometastasis in gastric cancer.
The chemokine receptors CCR7 and CXCR4 play a major role in the mechanism of lymph node metastasis from primary tumor cells. We postulated that their expression in gastric tumor cells could predict lymph node status including lymph node micrometastasis (LNMM). We assessed CCR7 and CXCR4 expression in 93 resected gastric tumor specimens by immunohistochemistry. Dissected lymph nodes were examined by reverse transcription-polymerase chain reaction and immunohistochemistry using cytokeratin monoclonal antibody to detect LNMM in addition to hematoxylin-eosin (H&E) staining. Levels of CCR7 and CXCR4 expression were high in 26.9% (25/93) and in 32.3% (30/93), respectively of tumor cells and the levels significantly correlated with lymph node metastasis according to H&E staining (P=0.0212 and P=0.0115, respectively). We identified LNMM in 25 of 83 (30.1%) node-negative patients. Both CCR7 and CXCR4 expression significantly correlated with lymph node status including LNMM (P=0.0092 and P=0.0075, respectively). Furthermore, levels of combined CCR7 and CXCR4 expression significantly correlated with lymph node metastatic status (P=0.0021). Assessment of CCR7 and CXCR4 expression in gastric cancer is a useful tool for predicting lymph node metastatic status including LNMM.


New bioactive glass-ceramic: synthesis and application in PMMA bone cement composites.
In present study, a new composition of glass-ceramic was synthesized based on the Na2O-CaO-SiO2-P2O5 glass system. Heat treatment of glass powder was carried out in 2 stages: 600 °C as the nucleation temperature and different temperature on crystallization at 850, 950 and 1000 °C. The glass-ceramic heat-treated at 950 °C was selected as bioactive filler in commercial PMMA bone cement; (PALACOS® LV) due to its ability to form 2 high crystallization phases in comparison with 850 and 1000 °C. The results of this newly glass-ceramic filled PMMA bone cement at 0-16 wt% of filler loading were compared with those of hydroxyapatite (HA). The effect of different filler loading on the setting properties was evaluated. The peak temperature during the polymerization of bone cement decreased when the liquid to powder (L/P) ratio was reduced. The setting time, however, did not show any trend when filler loading was increased. In contrast, dough time was observed to decrease with increased filler loading. Apatite morphology was observed on the surface of the glass-ceramic and selected cement after bioactivity test.


Atrial fibrillation--future directions.
AF has finally been reviewed with an importance compatible with its huge burden on the health care system. Careful evaluation of the knowledge to date reveals many areas that require further research. Many hurdles remain to be overcome in order to make a significant impact on this arrhythmia that is both troublesome and carries significant morbidity and mortality.


Effects of caffeine on sleep and cognition.
Caffeine can be used effectively to manipulate our mental state. It is beneficial in restoring low levels of wakefulness and in counteracting degraded cognitive task performance due to sleep deprivation. However, caffeine may produce detrimental effects on subsequent sleep, resulting in daytime sleepiness. This justifies a careful consideration of risks related to sleep deprivation in combination with caffeine consumption, especially in adolescents. The efficacy of caffeine to restore detrimental effects of sleep deprivation seems to be partly due to caffeine expectancy and to placebo effects. The claim that stimulant effects of caffeine are related to withdrawal or withdrawal reversal seems to be untenable.


Accuracy of creatinine results reported by participants in the CAP Chemistry Survey Program.
This report summarizes the creatinine data reported by over 6,000 participants in the 1982 to 1983 College of American Pathologists Chemistry Survey Program. Participants analyzed lyophilized serum samples on a quarterly basis. The most widely used methods employed the kinetic alkaline picrate reaction. Selected samples also were analyzed at the National Bureau of Standards using an isotope dilution-mass spectrometry definitive method. The participant mean results of each method principle group showed positive biases to the definitive values. The kinetic alkaline picrate and enzymatic method groups had the least biases to the definitive values. Excellent correlations between these two method groups and the definitive values were demonstrated. The consensus mean values of these two method groups would provide reliable target values for creatinine in survey samples. Interlaboratory precision improved significantly in each method group as the creatinine concentration increased.


Improving neonatal mortality in an Ethiopian referral hospital.
Ethiopia has one of the world's poorest neonatal mortality rates (1). As a British paediatrician working for one year, the main aim was to improve neonatal care in a referral hospital's neonatal unit. An initial project looking at all admissions to the unit over the month of October 2012, revealed the death rate within the unit was 21% of all admissions. Of the 55 admissions only 43 (75%) had a temperature recorded at admission. 29 (67%) of these were hypothermic, and of these 29 initially hypothermic babies, 19 (65%) remained hypothermic or did not have another temperature documented during their stay. Only 33 (56%) had a heart rate and respiratory rate recorded on admission and only 11 (19%) had any further vital signs recorded during their stay. 19 of the admitted infants had a diagnosis of low birth weight and 10 (53%) of these either died or left against medical advice. With this information regular basic neonatal care teaching sessions for doctors and nursing staff were initiated. Vital signs charts were introduced and unit specific protocols were written. Continuous Positive Airway Pressure (CPAP) was trialled and found to be effective, and CPAP training was given to all nurses and doctors on the unit. A room was set aside to be used solely as Kangaroo Mother Care (KMC). The nurses were taken to a very effective neonatal unit as an 'experience sharing' trip to help with motivation and a grant was also obtained for basic equipment. After 6 months the project was repeated for all the admissions during February 2013. The death rate had progressively fallen and was 10% in February. 54 patients (98%) had a temperature taken on admission and of these, 27 (49%) were hypothermic. 25 (93%) of these hypothermic infants had subsequent temperatures documented which were normal. 54 (98%) had heart rate and respiratory rate recorded on admission and 50 (90%) had them recorded at least daily during their stay. Of the 22 babies with low birth weight (40%), only 4 (18%) died/left against medical advice. 4 received CPAP and 6 were treated with KMC.


Functional MRI of postnatal visual development in normal rat superior colliculi.
This study employed blood oxygenation level-dependent functional MRI (BOLD-fMRI) to evaluate the visual responses in the superior colliculus of the developing rat brain from the time of eyelid opening to adulthood. Upon flash illumination to the contralateral eye, the regional BOLD response underwent a systematic increase in amplitude with age especially after the third postnatal week. However, no significant difference in BOLD signal increase was found between postnatal days 14 and 21. Our results constitute the first fMRI report in demonstrating the critical period of visual functions in the rat brain during maturation. This can be potentially useful in establishing the links between changes in relation to visual sensory development.


Calpain 3 is activated through autolysis within the active site and lyses sarcomeric and sarcolemmal components.
Calpain 3 (Capn3) is known as the skeletal muscle-specific member of the calpains, a family of intracellular nonlysosomal cysteine proteases. This enigmatic protease has many unique features among the calpain family and, importantly, mutations in Capn3 have been shown to be responsible for limb girdle muscular dystrophy type 2A. Here we demonstrate that the Capn3 activation mechanism is similar to the universal activation of caspases and corresponds to an autolysis within the active site of the protease. We undertook a search for substrates in immature muscle cells, as several lines of evidence suggest that Capn3 is mostly in an inactive state in muscle and needs a signal to be activated. In this model, Capn3 proteolytic activity leads to disruption of the actin cytoskeleton and disorganization of focal adhesions through cleavage of several endogenous proteins. In addition, we show that titin, a previously identified Capn3 partner, and filamin C are further substrates of Capn3. Finally, we report that Capn3 colocalizes in vivo with its substrates at various sites along cytoskeletal structures. We propose that Capn3-mediated cleavage produces an adaptive response of muscle cells to external and/or internal stimuli, establishing Capn3 as a muscle cytoskeleton regulator.


Insights from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) cohort study.
The dramatic emergence of noncommunicable diseases (NCD) in Asia, albeit with ethnic variation, has coincided with the rapid socioeconomic and nutritional transition taking place in the region, with the prevalence of diabetes rising 5-fold in Singapore in less than 4 decades. The Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study recruited 1,247 expectant mothers of Chinese, Malay, or Indian ethnicity in their first trimester, with detailed longitudinal tracking--through the antenatal period, birth, and the child's first 4 years of life--to examine the potential roles of fetal, developmental, and epigenetic factors in early pathways to metabolic and neurodevelopmental outcomes. A number of findings with a translational and clinical focus have already emerged. In the mothers, we found that changes and differences in food consumption varied across ethnic groups, with persistence of traditional beliefs, during pregnancy and the postpartum period. During pregnancy, higher maternal glucose levels, even in the absence of gestational diabetes mellitus, had graded relations with infant adiposity. Relations between maternal emotional health and birth outcomes and neurodevelopment have been identified. Genotype (25%) and in particular gene × environment interactions (75%) shape interindividual variations in the DNA methylome at birth. The complex effects of fixed genetic variations and different in utero environments can influence the epigenetic status at birth and the later-life phenotype. The richness of the clinical data in 3 ethnicities, the extent of the biospecimen collection, and the extensive infancy and preschool follow-up have allowed us to study the biological pathways that link fetal development to health outcomes. In the coming years, more sophisticated analyses of epigenotype-phenotype relationships will become possible as the children grow and develop. Our studies will lead to the development of clinical and population-based interventions to reduce the burden of NCD.


Modeling the Economic Feasibility of Large-Scale Net-Zero Water Management: A Case Study.
While municipal direct potable water reuse (DPR) has been recommended for consideration by the U.S. National Research Council, it is unclear how to size new closed-loop DPR plants, termed "net-zero water (NZW) plants", to minimize cost and energy demand assuming upgradient water distribution. Based on a recent model optimizing the economics of plant scale for generalized conditions, the authors evaluated the feasibility and optimal scale of NZW plants for treatment capacity expansion in Miami-Dade County, Florida. Local data on population distribution and topography were input to compare projected costs for NZW vs the current plan. Total cost was minimized at a scale of 49 NZW plants for the service population of 671,823. Total unit cost for NZW systems, which mineralize chemical oxygen demand to below normal detection limits, is projected at ~$10.83 / 1000 gal, approximately 13% above the current plan and less than rates reported for several significant U.S. cities.


TIQS: Targeted Iterative Question Selection for Health Interventions.
While healthcare has traditionally existed within the confines of formal clinical environments, the emergence of population health initiatives has given rise to a new and diverse set of community interventions. As the number of interventions continues to grow, the ability to quickly and accurately identify those most relevant to an individual's specific need has become essential in the care process. However, due to the diverse nature of the interventions, the determination need often requires non-clinical social and behavioral information that must be collected from the individuals themselves. Although survey tools have demonstrated success in the collection of this data, time restrictions and diminishing respondent interest have presented barriers to obtaining up-to-date information on a regular basis. In response, researchers have turned to analytical approaches to optimize surveys and quantify the importance of each question. To date, the majority of these works have approached the task from a univariate standpoint, identifying the next most important question to ask. However, such an approach fails to address the interconnected nature of the health conditions inherently captured by the broader set of survey questions. Utilizing data mining and machine learning methodology, this work demonstrates the value of capturing these relations. We present a novel framework that identifies a variable-length subset of survey questions most relevant in determining the need for a particular health intervention for a given individual. We evaluate the framework using a large national longitudinal dataset centered on aging, demonstrating the ability to identify the questions with the highest impact across a variety of interventions.


[Epidemiology of diseases of the veins of the lower extremities in various climato-geographic conditions].
An epidemiological study performed in different contrast climatic and geographic zones of the country has shown higher incidence of diseases of veins in regions of Siberia as compared to regions of Middle Asia. Risk factors of diseases of lower extremity veins occur 1.5-2 times more often in Siberia than in Middle Asia. Rural population have diseases of the lower extremity veins 1.5-2 times more often that the urban population in the both regions. Such diseases are found 3-5 times more often in people with the presence of risk factors than in the population without them.


IL-22 Paucity in APECED Is Associated With Mucosal and Microbial Alterations in Oral Cavity.
Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is caused by recessive mutations in the AIRE gene. The hallmark of the disease is the production of highly neutralizing autoantibodies against type I interferons and IL-22. Considering the importance of IL-22 in maintaining mucosal barrier integrity and shaping its microbial community, we sought to study potential changes in the oral cavity in this model of human IL-22 paucity. We found that besides known Th22 cell deficiency, APECED patients have significantly fewer circulating MAIT cells with potential IL-22 secreting capacity. Saliva samples from APECED patients revealed local inflammation, the presence of autoantibodies against IFN-α and IL-22, and alterations in the oral microbiota. Moreover, gene expression data of buccal biopsy samples suggested impaired antimicrobial response and cell proliferation, both of which are processes regulated by IL-22. Our data complement the knowledge gained from mouse models and support the concept of IL-22 being a critical homeostatic cytokine in human mucosal sites.


Living and Training at 825 m for 8 Weeks Supplemented With Intermittent Hypoxic Training at 3,000 m Improves Blood Parameters and Running Performance.
Wonnabussapawich, P, Hamlin, MJ, Lizamore, CA, Manimmanakorn, N, Leelayuwat, N, Tunkamnerdthai, O, Thuwakum, W, and Manimmanakorn, A. Living and training at 825 m for 8 weeks supplemented with intermittent hypoxic training at 3,000 m improves blood parameters and running performance. J Strength Cond Res 31(12): 3287-3294, 2017-We aimed to investigate the effect of an 8-week low-altitude training block supplemented with intermittent hypoxic training, on blood and performance parameters in soccer players. Forty university-level male soccer players were separated into altitude (n = 20, 825 m) or sea-level (n = 20, 125 m) groups. Before (1-2 days ago) and after (1 and 14 days later) training, players were asked to give a resting venous blood sample and complete a series of performance tests. Compared with sea level, the altitude group increased erythropoietin, red blood cell (RBC) count, and hematocrit 1 day after training (42.6 ± 24.0%, 1.8 ± 1.3%, 1.4 ± 1.1%, mean ± 95% confidence limits (CL), respectively). By 14 days after training, only RBC count and hemoglobin were substantially higher in the altitude compared with the sea-level group (3.2 ± 1.8%, 2.9 ± 2.1% respectively). Compared with sea level, the altitude group 1-2 days after training improved their 50-m (-2.9 ± 1.4%) and 2,800-m (-2.9 ± 4.4%) run times and demonstrated a higher maximal aerobic speed (4.7 ± 7.4%). These performance changes remained at 14 days after training with the addition of a likely higher estimated V[Combining Dot Above]O2max in the altitude compared with the sea-level group (3.2 ± 3.0%). Eight weeks of low-altitude training, supplemented with regular bouts of intermittent hypoxic training at higher altitude, produced beneficial performance improvements in team-sport athletes, which may increase the viability of such training to coaches and players that cannot access more traditional high altitude venues.


The invasive spider mite Tetranychus evansi (Acari: Tetranychidae) alters community composition and host-plant use of native relatives.
The tomato spider mite Tetranychus evansi Baker and Pritchard (Acari: Tetranychidae), is a worldwide pest of solanaceous crops that has recently invaded many parts of the world. In the present study we examined the ecological impact of its arrival in the Mediterranean region. The spider mite and phytoseiid mite assemblages in various crop and non-crop plants in three areas of Valencia (Spain) were studied a few months before and 10 years after the invasion of T. evansi. According to rarefaction analyses, the invasion of T. evansi did not affect neither the total number of species in the mite community examined (spider mite and phytoseiid species) nor the number of species when the two communities were examined separately. However, after the invasion, the absolute and relative abundance of the native Tetranychus species was significantly reduced. Before the invasion, T. urticae and T. turkestani were the most abundant spider mites, accounting for 62.9 and 22.8 % of the specimens. After the invasion, T. evansi became the most abundant species, representing 60 % of the total spider mites recorded, whereas the abundance of T. urticae was significantly reduced (23 %). This reduction took place principally on non-crop plants, where native species were replaced by the invader. Null model analyses provided evidence for competition structuring the spider mite community on non-crop plants after the invasion of T. evansi. Resistance to acaricides, the absence of efficient native natural enemies, manipulation of the plant defenses and the web type produced by T. evansi are discussed as possible causes for the competitive displacement.


Comparative transcriptomics of maturity-associated color change in Hawaiian spiders.
Discontinuous variation within individuals is increasingly recognized as playing a role in diversification and ecological speciation. This study is part of an effort to investigate the molecular genetic underpinnings of adaptive radiation in Hawaiian spiders (genus Tetragnatha). This radiation is found throughout the Hawaiian Islands, showing a common pattern of evolutionary progression from older to younger islands. Moreover, the species are characterized by repeated evolution of similar ecomorphs that can be recognized on the basis of color--Green, Maroon, Large Brown, and Small Brown. However, 2 species (including T. kauaiensis from Kauai) are polyphenic, changing from 1 ecomorph (Green) to another (Maroon) at a specific developmental period. The current study focuses on the age-associated color change in the early stages of the radiation to determine whether this ancestral flexibility in phenotype may have translated into diversification of more derived taxa. We conducted a comparative analysis of transcriptome data (expressed genes) from the Maroon morph of T. kauaiensis and T. perreirai (Oahu), which exhibits a single fixed ecomorph (Maroon). Over 70 million sequence reads were generated using Illumina sequencing of messenger RNA. Using reciprocal best hit BLAST searches, 9027 orthologous genes were identified, of which 32 showed signatures of positive selection between the 2 taxa and may be involved in the loss of the ancestral developmental polyphenism and associated switch to separate monophenic ecomorphs. These results provide critical groundwork that will allow us to advance our understanding of the genomic elements associated with adaptive radiations.


Mechanisms of renal tubular defects in old age.
The mechanisms of renal tubular dysfunction in old age have been examined in twenty-eight clinically healthy elderly subjects without infection, and in fourteen subjects of similar age with laboratory evidence of intrarenal infection. The data were compared with those from thirteen clinically healthy young subjects. Studied were: proximal tubular (Tm(PAH)) and distal tubular (CH2O) activity, minimal and maximal osmolal U/P ratios, maximal osmolal excretion in hydropenia, and GFR levels under standard hydration and under water-loading. The reduction of GFR in old age is evident particularly in men under conditions of standard hydration: it is accentuated in the presence of renal infection. Proximal tubular activity is also significantly lower in elderly men, especially if they have chronic bacteriuria. The reduction is closely related to GFR levels, with identical Tm(PAH):C(in) ratios in all groups. This supports the intact nephron hypothesis for this part of the nephron. Distal tubular activity is depressed in old age in both sexes proportionately more than proximal tubular activity or the GFR. The lower CH2O: GFR ratios imply a selective distal tubular damage. Maximal osmolal U/P ratios in hydropenia are significantly higher in the young (mean 367) than in either the elderly non-infected (mean 279) or the elderly infected subjects (mean 212). Conversely, minimal U/P ratios in water-loading are lower in the young (mean 0.247) than in either elderly group (means 0.418 and 0.668). Osmolal excretion in hydropenia is not different between the groups, but urine flows in water-loading clearly separate them. The data indicate that simple functions of the distal-collecting tubule (e.g. the CH2O), are less affected in old age than are functions involving several medullary structures (as is the maximal U(osm) or U/P ratio). They suggest that the main impairment of the distal tubular cell involves the failure to achieve a proper osmotic gradient between tubular fluid and blood, rather than an inability to excrete or re-absorb an adequate amount of solute. Finally, it appears that renal infection aggravates the larger glomerular and proximal tubular deficits observed in non-infected men: it depresses distal tubular function equally in both sexes.


Experimental Study of Surface Roughness of Dental Ceramics After Polishing with Three Types of Polishing Systems.
This study evaluated the surface roughness of three dental ceramics after polishing with three types of extraoral ceramic polishing sets. One hundred and twenty specimens were fabricated from feldspathic porcelain, lithium disilicate, and zirconia ceramics. The specimens were randomly allocated into four subgroups (n = 10). Group one was glazed (control) and the other three groups were ground using fine diamond burs and then sequentially polished by two rubber wheels from three polishing sets: feldspathic porcelain, lithium disilicate, and zirconia sets. The surface roughness measurement was performed with a profilometer and the surfaces were analyzed using scanning electron microscopy. Elemental compositions of three polishing sets were examined using x-ray powder diffraction. The surface roughness values of three polishing systems were compared by one-way analysis of variance with Dunnett's T3 post hoc test. The significance level was set at p < 0.05. There was no significant difference in surface roughness when polishing ceramics with the lithium disilicate and zirconia polishing sets. In addition, those two sets provided lower roughness compared with the feldspathic porcelain polishing set and glazing. The main component of all polishing wheels was carbon, and only zirconia polishing wheel had more additional trace elements, which were titanium and silica. Lithium disilicate and zirconia extraoral polishing sets achieved superior results compared to feldspathic polishing set and glazing.


The Kinesin-related protein Costal2 associates with membranes in a Hedgehog-sensitive, Smoothened-independent manner.
In Drosophila, Hedgehog (Hh) signal transduction has been shown to require a multiprotein complex (Hedgehog signaling complex (HSC)), which includes the Kinesin-related protein Costal2 (Cos2), the serine/threonine protein kinase Fused (Fu), and the transcription factor Cubitus interruptus (Ci). We present evidence that a biologically relevant fraction of the HSC is found in association with cellular membranes. We demonstrate that Cos2 is capable of tethering an exogenous protein to vesicular membranes and that Cos2 association with membranes is Hh-sensitive. In addition, we demonstrate that Cos2 associates with membranes in cells that lack the transmembrane protein Smoothened (Smo) through a domain of Cos2 distinct from its recently characterized Smo binding domain. We suggest that an Hh-regulated membrane binding activity of Cos2 is part of the mechanism by which Cos2 contributes to Hh signaling. We propose a model in which there are two distinct HSCs with discrete subcellular localizations and activities: one is endosome-associated and facilitates production of a repressor form of Ci (HSC-R), and one is Smo-associated and promotes Ci activation (HSC-A). In response to Hh and through interaction with Cos2, Smo mediates both inhibition of the endosome-associated HSC-R and activation of HSC-A at the plasma membrane.


Black-White variation in the relationship between early educational experiences and trajectories of cognitive function among US-born older adults.
Black adults face a substantially higher risk for dementia in later life compared to their White peers. Given the critical role of educational attainment and cognitive function in later life dementia risk, this paper aims to determine if early educational experiences and educational attainment are differentially related to trajectories of cognitive status across race and if this further varies by education cohort. We use data from the Life History Mail Survey (LHMS) and prospective data on cognition from the Health and Retirement Study (HRS). We restrict our sample to Black and White US-born adults who provided at least one measure of cognitive status from 1995/6-2016. We find evidence of Black-White differences in the association between educational experiences and level of cognitive function, episodic memory, and working memory, but little evidence of Black-White differences in these associations with decline. Having a learning problem was associated with lower levels of cognitive function, episodic memory, and working memory for White and Black older adults, but was more strongly related to these outcomes among Black older adults. Further, the Black-White difference in this association was generally found in older cohorts that completed schooling after enactment of federal policies that improved educational resources for children with learning disabilities. Attending racially discordant schools was positively associated with level of these cognitive outcomes for Black older adults but not for White older adults. We also find that the educational gradient in level of cognitive function was larger for Black compared to White older adults in older cohorts not benefiting from the Brown v Board of Education decision but was similar for Black and White older adults attending school in the post-Brown era.


Organizational culture in a terminally ill hospital.
This study analyzed an organizational culture in a community hospital in Texas to measure organizational culture change and its impact on Patient Satisfaction (PS). The study employed primary and secondary data, combining quantitative and qualitative methods for a case study. Participant observation was used and archival data were collected to provide a better understanding of the organizational culture and the context in which change was taking place. This study also applied a "Shared Vision" of the organization as the central process in bringing forth the knowledge shared by members of the community hospital who were both subjects and research participants. The results from the study suggest an increase in PS due to the shared vision of one subculture within the hospital. There were powerful subcultures in this organization based on occupation and specialization, and their interests and functional orientations were not conducive to a systems approach. Hospital management was conducted in "silos" and there was lack of feedback between organizational levels of the hospital, especially in financial management, with organizational dysfunctionality in reacting and adapting to the health care market.


A c-Jun NH2-terminal kinase inhibitor SP600125 (anthra[1,9-cd]pyrazole-6 (2H)-one) blocks activation of pancreatic stellate cells.
In response to pancreatic injury and in cell culture, pancreatic stellate cells (PSCs) are transformed ("activated") into highly proliferative myofibroblast-like cells that express alpha-smooth muscle actin and produce extracellular matrix components. Activated PSCs are implicated in the pathogenesis of pancreatic fibrosis and inflammation. We here evaluated the effects of SP600125 (anthra[1,9-cd]pyrazole-6 (2H)-one), an inhibitor of c-Jun NH(2)-terminal kinase (JNK), on the activation of PSCs. PSCs were isolated from rat pancreas tissue and used in their culture-activated, myofibroblast-like phenotype unless otherwise stated. Activation of JNK was determined by Western blotting using anti-phosphospecific JNK and c-Jun antibodies. Activation of transcription factors was determined by electrophoretic mobility shift assay. The effects of SP600125 on the key parameters of activation (chemokine production, collagen production, and proliferation) were examined. The effect of SP600125 on the activation of freshly isolated PSCs in culture also was examined. Interleukin-1beta activated both 46- and 54-kDa JNK, whereas platelet-derived growth factor-BB activated only 46-kDa JNK. SP600125 inhibited interleukin-1beta-induced JNK activity and activator protein-1 activation, but it did not affect the activation of extracellular-regulated kinase, p38 mitogen-activated protein kinase, and nuclear factor-kappaB. SP600125 inhibited platelet-derived growth factor-induced proliferation, inducible monocyte chemoattractant protein-1 production, and serum-induced type I collagen production. Although SP600125 did not inhibit the transformation, it attenuated the proliferation of freshly isolated PSCs in culture. Collectively, our results suggest a role of JNK in the activation of PSCs, and a potential application of JNK inhibitors for the treatment of pancreatic fibrosis and inflammation.


Non-inferiority of fragmented care for high-risk pediatric neuroblastoma patients: a single institution analysis.
Pediatric neuroblastoma (NB) patients receive multi-modal therapy and may experience care fragmented among multiple institutions with a significant travel burden, which has been associated with poor outcomes for some adult cancers. We hypothesized that fragmented care for pediatric NB patients is associated with inferior outcomes compared to treatment consolidated at one location. We reviewed paper and electronic records for pediatric NB patients who received ≥1 hematopoietic stem cell transplant (HSCT) at Duke from 1990-2017. Fragmented care was defined by treatment at >1 institution and grouped by 2 institutions vs. 3+ institutions. Distances were calculated using Google Maps. To compare all care groups, we used Fisher's Exact and Kruskal-Wallis tests for demographic and treatment characteristics, Kaplan-Meier for unadjusted overall survival (OS), and Cox proportional hazards for factors associated with OS. Of 127 eligible patients, 102 (80.3%) patients experienced fragmented care, with 17 treated at 3+ facilities. Kaplan-Meier analysis did not associate fragmented care with increased mortality (log-rank p = 0.13). With multivariate analysis, only earlier diagnostic decade and greater distance to HSCT remained significantly associated with worsened OS. In this single institutional study, we found fragmented care did not impact overall survival. Worsened overall survival was associated with increased travel distance for HSCT and further research should aim to improve supportive processes for patients undergoing HSCT for high-risk neuroblastoma.


Alcohol Protective Behavioral Strategies in Young Spanish Adults in the Community: A Prospective Study of Perceived Efficacy and Social Norms.
Protective behavioral strategies (PBS) have been shown to be useful for reducing excessive alcohol use and alcohol-related problems. However, research on the explanatory factors of PBS is limited. This paper prospectively examines the contribution of perceived efficacy of PBS in reducing alcohol-related consequences and perceived descriptive norms of close peers´ PBS use in young adults. The mediating role of perceived efficacy of PBS between descriptive norms of PBS use and personal PBS use is also examined. Targeted sampling was used to recruit a community-based sample of 339 young Spanish adults aged 18-25 years, who completed baseline and two-month follow-up questionnaires. Three types of PBS (serious harm reduction-SHR, manner of drinking-MOD, and stopping/limiting drinking-SLD) were measured. Both perceived efficacy and descriptive norms at baseline were positively associated with personal PBS use (SHR, MOD and SLD) at follow-up. A partial mediation effect of perceived efficacy between descriptive norms and personal PBS use was found for the three PBS subscales. Our findings support the usefulness of correcting misperceptions of PBS use by peers in interventions aimed at reducing excessive drinking and alcohol-related consequences in young adults in the community. Moreover, PBS perceived efficacy should be included as a component of these interventions.


Effects of birth season, breed, sex, and sire family on cardiac morphology determined in pigs (Sus scrofa domestica) by use of echocardiography.
Echocardiography played an important role in the screening and diagnosis of hypertrophic cardiomyopathy. In the study reported here, we attempted to evaluate the effects of birth season, breed, sex, and sire family on cardiac morphology determined in pigs by use of echocardiography. A total of 411 pigs (mean body weight and age of 105.7 +/- 10.6 kg and 214.4 +/- 25.5 days, respectively) with different genetic backgrounds (Landrace, Yorkshire, and their two-way crossbred) were studied. Cardiac morphologic measurements included thickness of left ventricle and interventricular septum at end-systolic and end-diastolic phases. Meanwhile, the statistical model included the following effects: birth season, breed, sex, interaction between breed and sex, sire family, body weight, and age. Mean cardiac morphologic measurements were as follows: thickness of the interventricular septum at end-systolic and end-diastolic phases was 1.74 and 1.14 cm, respectively; and thickness of the left ventricular free wall at end-systolic and end-diastolic phases was 1.81 and 0.98 cm, respectively. Medium positive correlations existed among the cardiac morphologic measurements r = 0.31 to 0.53; P < 0.001). Pigs born in spring had significantly (P < 0.05) lower cardiac thickness at the end systolic phase than did pigs born in other seasons, and Landrace pigs had higher cardiac morphologic measurements than did Yorkshire and two-way crossbred pigs. Additionally, thickness of interventricular septum at the end-diastolic phase in male pigs was significantly higher than that in female pigs (P < 0.05). Cardiac morphologic measurements for the sire family were significantly (P < 0.05) different, and contributed 77.2 to 87.9% of the total variation, suggesting that genetic variation in cardiac morphology might exist in pigs. Cardiac morphology of pigs might be influenced by genetic background. The effects of birth season, breed, sire family, and sex should be adjusted when using pigs as an animal model for comparative cardiovascular studies.


[Relationship between Helicobacter pylori infection other factors and diffuse-and intestinal type stomach carcinomas].
To investigate the role of Helicobacter Pylori (HP) infection and other factors in the development of stomach carcinoma, a matched case-control study was conducted in Dalian, China. A total number of 95 paired cases and controls were involved in the study. The cases were divided into two histological types: diffuse- and intestinal-type. IgG antibody of HP in the subjects was tested with ELISA method. The results revealed that the prevalences of HP infection in cases and in controls were 77.5% and 50.0%, respectively, and that the matched OR was 5.0 (2.08-12.01). The stratified analysis showed that the risk effect of HP in intestinal-type was more significant (OR = 5.75, 1.99-16.63) than it in defuse-type (OR = 3.5, 0.73-16.89). Cancer history within family and blood group A were associated with diffuse-type while the environmental factors such as low economic status, irregular eating and fast-eating habits were mainly associated with intestinal-type. We conclude from our findings that HP infection may play a role in the development of stomach cancer, especially for intestinal-type gastric cancer. The two Lauren's histological types of stomach cancer might be different in terms of pathogenesis and characteristics.


The antioxidant Glycitin protects against intervertebral disc degeneration through antagonizing inflammation and oxidative stress in nucleus pulposus cells.
Intervertebral disc degeneration (IVDD) is a kind of typical degenerative disorder of the skeletal muscle system caused by many factors including aging, abnormal mechanical stress and inflammatory responses. Glycitin is a natural isoflavone extracted from legumes. Previous studies have found that it is anti-inflammatory and promotes wound repair. However, the role of Glycitin in IVDD has not been elucidated. In the present research, we were surprised that Glycitin antagonized the NF-κB pathway activity. In addition, we also found that Glycitin alleviated TNF-α-induced metabolic disorders, extracellular matrix degradation, oxidative stress, inflammation responses, and mitochondrial damage. Furthermore, in in vivo experimental study, we discovered Glycitin attenuated IVDD. The results revealed that Glycitin alleviated the degenerative phenotype of IVDD. According to this research, Glycitin has anti-inflammatory properties that might exert a protective function in IVDD, suggesting a prospective therapeutic approach for IVDD.


Pyrosequencing-based comparative genome analysis of Vibrio vulnificus environmental isolates.
Between 1996 and 2006, the US Centers for Disease Control reported that the only category of food-borne infections increasing in frequency were those caused by members of the genus Vibrio. The gram-negative bacterium Vibrio vulnificus is a ubiquitous inhabitant of estuarine waters, and is the number one cause of seafood-related deaths in the US. Many V. vulnificus isolates have been studied, and it has been shown that two genetically distinct subtypes, distinguished by 16S rDNA and other gene polymorphisms, are associated predominantly with either environmental or clinical isolation. While local genetic differences between the subtypes have been probed, only the genomes of clinical isolates have so far been completely sequenced. In order to better understand V. vulnificus as an agent of disease and to identify the molecular components of its virulence mechanisms, we have completed whole genome shotgun sequencing of three diverse environmental genotypes using a pyrosequencing approach. V. vulnificus strain JY1305 was sequenced to a depth of 33×, and strains E64MW and JY1701 were sequenced to lesser depth, covering approximately 99.9% of each genome. We have performed a comparative analysis of these sequences against the previously published sequences of three V. vulnificus clinical isolates. We find that the genome of V. vulnificus is dynamic, with 1.27% of genes in the C-genotype genomes not found in the E- genotype genomes. We identified key genes that differentiate between the genomes of the clinical and environmental genotypes. 167 genes were found to be specifically associated with environmental genotypes and 278 genes with clinical genotypes. Genes specific to the clinical strains include components of sialic acid catabolism, mannitol fermentation, and a component of a Type IV secretory pathway VirB4, as well as several other genes with potential significance for human virulence. Genes specific to environmental strains included several that may have implications for the balance between self-preservation under stress and nutritional competence.


[Multiple mutants of Saccharomyces cerevisiae. III. The identification of the mutational changes that occur].
Localization and molecular nature of mutations in multiple mutants of yeast Sacchromyces cerevisiae were studied. It was found that simultaneous changes in several genes located in more than five linkage groups took place during the arise of multiple mutants after a single UV-irradiation (at a dose of 300 erg/nm2). It was shown that reversions of original nonsense-mutations were due to mutational changes in the same genes and the arise of the forward nonsense-mutations in the other genes took place as a result of base changes in DNA.


Ca2+ and voltage inactivate Ca2+ channels in guinea-pig ventricular myocytes through independent mechanisms.
1. L-type Ca2+ currents and Ca2+ channel gating currents were studied in isolated guinea-pig ventricular heart cells using the whole-cell patch-clamp technique, in order to investigate the mechanism of Ca(2+)-dependent inactivation. The effect of altering the intracellular Ca2+ concentration ([Ca2+]i) on these currents was studied through photorelease of intracellular Ca2+ ions using the photolabile Ca2+ chelators DM-nitrophen and nitr-5. 2. We found that step increases in [Ca2+]i produced by photorelease could either increase or decrease the L-type Ca2+ current. Specifically, Ca2+ photorelease from DM-nitrophen almost exclusively caused inactivation of the Ca2+ current. In contrast, Ca2+ photorelease from nitr-5 had a biphasic effect: a small, rapid inactivation of the Ca2+ current was followed by a slow potentiation. These two Ca(2+)-dependent processes seemed to differ in their Ca2+ dependence, as small Ca2+ photoreleases elicited potentiation without a preceding inactivation, whereas larger photoreleases elicited both inactivation and potentiation. 3. The mechanism of the Ca(2+)-dependent inactivation of Ca2+ channels was explored by comparing the effects of voltage and photoreleased Ca2+ on the Ca2+ current and the Ca2+ channel gating current. Voltage was found to reduce both the Ca2+ current and the gating current proportionally. However, Ca2+ photorelease from intracellular DM-nitrophen inactivated the Ca2+ current without having any effect on the gating current. 4. The dephosphorylation hypothesis for Ca(2+)-dependent inactivation was tested by applying isoprenaline to the cells before eliciting a maximal rise of [Ca2+]i (maximal flash intensity, zero external [Na+]i). Isoprenaline could completely prevent Ca(2+)-dependent inactivation under these conditions, even when [Ca2+]i rose so high as to cause an irreversible contracture of the cell. 5. We concluded from these experiments that voltage and Ca2+ ions inactivate the L-type Ca2+ channel through separate, independent mechanisms. In addition, we found that Ca(2+)-dependent inactivation does not result in the immobilization of gating charge, and apparently closes the Ca2+ permeation pathway through a mechanism that does not involve the voltage-sensing region of the channel. Furthermore, we found that Ca(2+)-dependent inactivation is entirely sensitive to beta-adrenergic stimulation. These facts suggest that either Ca(2+)-dependent inactivation results from Ca(2+)-dependent dephosphorylation of the Ca2+ channel, or that Ca(2+)-dependent inactivation is modulated by protein kinase A.


Evaluation of feedback given to trainees in medical specialties.
The aim of this study was to evaluate the quality of feedback provided to specialty trainees (ST3 or higher) in medical specialties during their workplace-based assessments (WBAs). The feedback given in WBAs was examined in detail in a group of 50 ST3 or higher trainees randomly selected from those taking part in a pilot study of changes to the WBA system conducted by the Joint Royal Colleges of Physicians Training Board. They were based in Health Education Northeast (Northern Deanery) and Health Education East of England (Eastern Deanery). Thematic analysis was used to identify commonly occurring themes. Feedback was mainly positive but there were differences in quality between specialties. Problems with feedback included insufficient detail, such that it was not possible to map the progression of the trainee, insufficient action plans made and the timing of feedback not being contemporaneous (feedback not being given at the time of assessment). Recommendations included feedback should be more specific; there need to be more options in the feedback forms for the supervisor to compare the trainee's performance to what is expected and action plans need to be made.


How long range is contour integration in human color vision?
We quantified and compared the effect of element spacing on contour integration between the achromatic (Ach), red-green (RG), and blue-yellow (BY) mechanisms. The task requires the linking of orientation across space to detect a contour in a stimulus composed of randomly oriented Gabor elements (1.5 cpd, sigma = 0.17 deg), measured using a temporal 2AFC method. A contour of ten elements was pasted into a 10 x 10 cells array, a ndbackground elements were randomly positioned within the available cells. The effect of element spacing was investigated by varying the mean interelement distance between two and six times the period of the Gabor elements (lambda = 0.66 deg) while the total number of elements was fixed. Contour detection was measured as a function of its curvature for jagged contours and for closed contours. At all curvatures, we found that performance for chromatic mechanisms declines more steeply with the increase in element separation than does performance for the achromatic mechanism. Averaged critical element separations were 4.6 +/- 0.7, 3.6 +/- 0.4, and 2.9 +/- 0.2 deg for Ach, BY, and RG mechanisms, respectively. These results suggest that contour integration by the chromatic mechanisms relies more on short-range interactions in comparison to the achromatic mechanism. In a further experiment, we looked at the combined effect of element size and element separation in contour integration for the Ach mechanism. We found that the critical separation decreases linearly with the spatial frequency, from about 5 deg at low spatial frequency (larger elements) to about 1 deg at high spatial frequency (smaller elements) suggesting a scale invariance in contour integration. In both experiments we also found no differences between closed and open jagged contours detection in terms of element separation. The neuroanatomical implications of these findings relatively to area V1 are discussed.


Clinical Application of Antioxidants to Improve Human Oocyte Mitochondrial Function: A Review.
Mitochondria produce adenosine triphosphate (ATP) while also generating high amounts of reactive oxygen species (ROS) derived from oxygen metabolism. ROS are small but highly reactive molecules that can be detrimental if unregulated. While normally functioning mitochondria produce molecules that counteract ROS production, an imbalance between the amount of ROS produced in the mitochondria and the capacity of the cell to counteract them leads to oxidative stress and ultimately to mitochondrial dysfunction. This dysfunction impairs cellular functions through reduced ATP output and/or increased oxidative stress. Mitochondrial dysfunction may also lead to poor oocyte quality and embryo development, ultimately affecting pregnancy outcomes. Improving mitochondrial function through antioxidant supplementation may enhance reproductive performance. Recent studies suggest that antioxidants may treat infertility by restoring mitochondrial function and promoting mitochondrial biogenesis. However, further randomized, controlled trials are needed to determine their clinical efficacy. In this review, we discuss the use of resveratrol, coenzyme-Q10, melatonin, folic acid, and several vitamins as antioxidant treatments to improve human oocyte and embryo quality, focusing on the mitochondria as their main hypothetical target. However, this mechanism of action has not yet been demonstrated in the human oocyte, which highlights the need for further studies in this field.


Outcome of Neuromuscular Electrodiagnostic Testing in Children.
This study aimed to describe the spectrum of the results of neuromuscular electrodiagnostic investigations performed by age and pathology in paediatric patients. This retrospective observational study took place from January 2019 to December 2021. Electrodiagnostic records of paediatric patients (birth to 15 years) were referred to the electromyography (EMG) laboratory for EMG and nerve conduction study (NCS). Electrodiagnostic and demographic data were collected. Among these, 151 (56%) were males and 118 (44%) were females. Forty-four percent tests came out to be normal and 151(56%) tests revealed electrophysiological abnormality. Peripheral nerve neuropathy (n = 39, 14.5%), polyneuropathy (n = 35, 13%) and myopathy (n = 28, 10%) were the most common electrophysiological diagnoses. The electrodiagnostic test helps in differentiating the aetiologies, thus guiding the subsequent work-up logically in the paediatric population. Key Words: Brachial plexus neuropathies, Electromyography, Duchene muscular dystrophy, Neuromuscular junction disorders, Nerve conduction studies, Acute inflammatory demyelinating polyneuropathy, Rehabilitation, Electromyography, Hereditary sensory motor polyneuropathy.


Elimination of Senescent Osteocytes by Bone-Targeting Delivery of Β-Galactose-Modified Maytansinoid Prevents Age-Related Bone Loss.
The accumulation of senescent cells in bone during agbling contributes to senile osteoporosis and clearance senescent cells by senolytics could effectively alleviate bone loss. However, the applications of senolytics are limited due to their potential toxicities. Herein, we have modified small extracellular vesicles (sEVs) by incorporating bone-targeting peptide, specifically (AspSerSer)6 , to encapsulate galactose-modified Maytansinoids (DM1). These modified vesicles are referred to as (AspSerSer)6 -sEVs /DM1-Gal, and they have been designed to specifically clear the senescent osteocytes in bone tissue. In addition, the elevated activity of lysosomal β-galactosidase (β-gal) in senescent osteocytes but not normal cell in bone tissue could break down DM1-Gal to release free DM1 for selective elimination of senescent osteocytes. Mechanically, DM1 could disrupt tubulin polymerization, subsequently induce senescent osteocytes apoptosis. Further, administration of bone-targeting senolytics to aged mice could alleviate aged-related bone loss without non-obvious toxicity. Overall, this bone-targeting senolytics could act as a novel candidate for specific clearance of senescent osteocytes, ameliorating age-related bone loss, with a promising therapeutic potential for senile osteoporosis. This article is protected by copyright. All rights reserved.


Outward current and repolarization in hypoxic rat myocardium.
We studied the effects of brief periods (20-30 min) of hypoxia in the presence of 5 and 50 mM glucose and of glycolytic blockade (10(-4) M iodoacetic acid, IAA) on action potentials, membrane currents, and mechanical activity in rat ventricular papillary muscles using a single sucrose gap voltage-clamp technique. Steady-state outward current (iss) was determined at the end of a 500-ms clamp to the test potential following a 600-ms clamp to a holding potential of -50 mV. In the presence of 5 mM glucose, hypoxia resulted in a decrease in action potential duration (APD) and an increase in iss (on the order of 60% at 0 mV) over the potential range studied. The increase in iss did not appear to be due to an increase in leakage current or to a change in the cable properties of the preparation. Addition of 50 mM glucose prevented the change in both APD and iss with hypoxia. In addition, glycolytic blockade with IAA did not alter iss in the presence of oxygen. We conclude that an increase in iss appears to be a major factor in the abbreviation of rat ventricular action potential seen with hypoxia. Glycolysis appears to be a sufficient (with 50 mM glucose) but not necessary source of energy for the maintenance of normal iss.


Cognitive performance effects of subcutaneous nicotine in smokers and never-smokers.
In a double-blind placebo-controlled crossover study the effects of two doses of subcutaneous nicotine and saline were compared on a range of performance measures in 18 abstaining smokers and 18 never-smokers. Each subject received two injections (40 min apart) of saline, 0.3 mg nicotine, or 0.6 mg nicotine in a balanced order over three sessions. Performance was assessed before and after the injections on nine tests [news recall, Sternberg memory task, finger tapping, logical reasoning, rapid visual information processing (RVIP), long-term word recognition, digit recall, Stroop test, and critical flicker fusion threshold]. In the abstinent smokers, nicotine produced significantly faster correct responses on the logical reasoning test, more target hits, faster reaction times and improved sensitivity on the RVIP task, and more correct responses on word recognition. In never-smokers, nicotine produced faster reaction times on the RVIP and digit-recall tasks, although in the latter case this was at the expense of fewer correct responses. There were no significant differences between the two groups' responses to nicotine but smokers performed worse than never-smokers prior to injections, even controlling for background characteristics. These results are consistent with other recent research suggesting a primary effect of nicotine in enhancing cognitive performance.


Ocean color spectra measured off the Oregon coast: characteristic vectors.
The ocean color spectrum is defined as the ratio of the spectrum of light upwelled from the sea to the spectrum of light incident on the sea surface. Ocean color spectra, observed from an airplane flown over waters off Oregon, are analyzed. The original spectra are resolved into fifty-five wavelength bands, each 5 nm wide. The shapes of these spectra are parametrized by, and shown to be accurately recoverable from, their first four principal components Y(i)(i = 1, 2, 3, 4). These Y(i) are the scalar projections of each spectrum on the first four characteristic vectors of the sample covariance matrix. Empirically determined characteristic vectors like these, but derived from a much larger and more globally representative sample of color spectra, may someday provide an efficient, standard basis for parameterizing ocean color spectra. Regression equations are found with which phytoplankton pigment concentration and water transparency may be estimated as linear functions of the parameters Y(i). Pigment concentration estimates thus obtained are imprecise. The poor fit is at least partly due to the inappropriateness of the linear regression model and the neglect of other optically important substances typically present in sea water.