Effects of a brief interpersonal conflict cognitive reappraisal intervention on improvements in access to emotion regulation strategies and depressive symptoms in college students.
Objective: Research has demonstrated relative success with brief interventions that utilize social psychological theory to target the root cause of unwanted behaviours. Given the intersections among anxious attachment, depression, and emotion dysregulation, the current research utilises an interpersonal conflict cognitive reappraisal intervention to evaluate improvements in depressive symptoms. We also evaluated mediation via improvements in emotion regulation and moderation by attachment anxiety. Design: Undergraduates (N = 260) completed a baseline assessment and were randomised to one of four writing conditions: An interpersonal conflict from (a) their own perspective; (b) the other party's perspective; or (c) a neutral, third-party perspective (primary experimental condition) or about their day (control condition). They also completed a follow-up survey online two weeks later. Main outcome measures included limited access to emotion regulation strategies and depressive symptoms. Results: Consistent with hypotheses, compared to control, participants who adopted the perspective of neutral third party reported improvements in access to emotion regulation strategies. There was also a significant indirect effect on depressive symptoms through changes in strategies. Finally, improving strategies led to a reduction in depressive symptoms, especially for those higher in attachment anxiety. Conclusion: We present promising emerging results for a single-session, conflict-focused, brief cognitive reappraisal intervention on changes in emotion regulation and depressive symptoms.


Identification of urinary metabolites that correlate with clinical improvements in children with autism treated with sulforaphane from broccoli.
Children with autism spectrum disorder (ASD) have urinary metabolites suggesting impairments in several pathways, including oxidative stress, inflammation, mitochondrial dysfunction, and gut microbiome alterations. Sulforaphane, a supplement with indirect antioxidant effects that are derived from broccoli sprouts and seeds, was recently shown to lead to improvements in behavior and social responsiveness in children with ASD. We conducted the current open-label study to determine if we could identify changes in urinary metabolites that were associated with clinical improvements with the goal of identifying a potential mechanism of action. Children and young adults enrolled in a school for children with ASD and related neurodevelopmental disorders were recruited to participate in a 12-week, open-label study of sulforaphane. Fasting urinary metabolites and measures of behavior (Aberrant Behavior Checklist-ABC) and social responsiveness (Social Responsiveness Scale-SRS) were measured at baseline and at the end of the study. Pearson's correlation coefficient was calculated for the pre- to post-intervention change in each of the two clinical scales (ABS and SRS) versus the change in each metabolite. Fifteen children completed the 12-week study. Mean scores on both symptom measures showed improvements (decreases) over the study period, but only the change in the SRS was significant. The ABC improved - 7.1 points (95% CI - 17.4 to 3.2), and the SRS improved - 9.7 points (95% CI - 18.7 to - 0.8). We identified 77 urinary metabolites that were correlated with changes in symptoms, and they clustered into pathways of oxidative stress, amino acid/gut microbiome, neurotransmitters, hormones, and sphingomyelin metabolism. Urinary metabolomics analysis is a useful tool to identify pathways that may be involved in the mechanism of action of treatments targeting abnormal physiology in ASD. This study was prospectively registered at clinicaltrials.gov (NCT02654743) on January 11, 2016.


Chlorination of Schistosoma mansoni cercariae.
Schistosomiasis is a water-based disease acquired through contact with cercaria-infested water. Communities living in endemic regions often rely on parasite-contaminated freshwater bodies for their daily water contact activities, resulting in recurring schistosomiasis infection. In such instances, water treatment can provide safe water on a household or community scale. However, to-date there are no water treatment guidelines that provide information on how to treat water containing schistosome cercariae. Here, we rigorously test the effectiveness of chlorine against Schistosoma mansoni cercariae. S. mansoni cercariae were chlorinated using sodium hypochlorite under lab and field condition. The water pH was controlled at 6.5, 7.0 or 7.5, the water temperature at 20°C or 27°C, and the chlorine dose at 1, 2 or 3 mg/l. Experiments were conducted up to contact times of 45 minutes. 100 cercariae were used per experiment, thereby achieving up to 2-log10 inactivations of cercariae. Experiments were replicated under field conditions at Lake Victoria, Tanzania. A CT (residual chlorine concentration x chlorine contact time) value of 26±4 mg·min/l is required to achieve a 2-log10 inactivation of S. mansoni cercariae under the most conservative condition tested (pH 7.5, 20°C). Field and lab-cultivated cercariae show similar chlorine sensitivities. A CT value of 30 mg·min/l is therefore recommended to disinfect cercaria-infested water, though safety factors may be required, depending on water quality and operating conditions. This CT value can be achieved with a chlorine residual of 1 mg/l after a contact time of 30 minutes, for example. This recommendation can be used to provide safe water for household and recreational water activities in communities that lack safe alternative water sources.


[The Whitaker perfusion test in the diagnosis of organic obstruction of the upper urinary tract].
The X-ray and radioisotopic tools currently used in the diagnosis of upper urinary obstruction fail to take into account the dynamics of the ureter and largely depend on preserved renal function. Therefore Whitaker's test was proposed for this, which involves fluid perfusion along the nephrostomic drain and measurement of intrapelvic pressure. The test was employed in 40 patients and confirmed antegrade pyeloureterographic evidence in 32 (80%) patients, but failed in 8 (20%) patients who were suspected for upper urinary obstruction as shown by anterograde pyeloureterographic findings, whereas the perfusion test excluded the obstruction. The test provided evidence for the obstruction in 6 out of 26 cases, though antegrade pyeloureterography indicated as if the patency of the upper urinary tract were good. The results of Whitaker's test were supported by further clinical examinations and treatment of the patients. Two clinical cases are presented in the paper. It is concluded that Whitaker's perfusion test yields more accurate and objective data on the presence of organic obstruction of the upper urinary tract than do radioisotopic and X-ray tools. So the authors consider it advisable to apply it especially when it is questioned whether the obstruction is present or absent, as well as in patients undergone upper urinary plastic operations.


Computer-assisted analysis of envelope protein sequences of seven human immunodeficiency virus isolates: prediction of antigenic epitopes in conserved and variable regions.
Independent isolates of human immunodeficiency virus (HIV) exhibit a striking genomic diversity, most of which is located in the viral envelope gene. Since this property of the HIV group of viruses may play an important role in the pathobiology of the virus, we analyzed the predicted amino acid sequences of the envelope proteins of seven different HIV strains, three of which represent sequential isolates from a single patient. By using a computer program that predicts the secondary protein structure and superimposes values for hydrophilicity, surface probability, and flexibility, we identified several potential antigenic epitopes in the envelope proteins of the seven different viruses. Interestingly, the majority of the predicted epitopes in the exterior envelope protein (gp120) were found in regions of high sequence variability which are interspersed with highly conserved regions among the independent viral isolates. A comparison of the sequential viral isolates revealed that changes concerning the secondary structure of the protein occurred only in regions which were predicted to be antigenic, predominantly in highly variable regions. The membrane-associated protein gp41 contains no highly variable regions; about 80% of the amino acids were found to be conserved, and only one hydrophilic area was identified as likely to be accessible to antibody recognition. These findings give insight into the secondary and possible tertiary structure of variant HIV envelope proteins and should facilitate experimental approaches directed toward the identification and fine mapping of HIV envelope proteins.


Genetically Predicted Sleep Traits and Functional Outcome After Ischemic Stroke: A Mendelian Randomization Study.
Sleep traits can have implications for ischemic stroke recovery in observational studies. The purpose of our present study was to explore the relationship between genetically predicted sleep traits and poststroke functional outcomes with Mendelian randomization (MR) method. Instrumental variables for insomnia and sleep duration were adopted from genome-wide association studies data of European ancestry individuals. Summary data for functional outcome after ischemic stroke were retrieved from the Genetics of Ischemic Stroke Functional Outcome network. Inverse-variance weighted approach was adopted as the main analyses. Alternative MR approaches were used in sensitivity analyses. I2 and Q value statistics were used to appraise the heterogeneity among genetic variants. In univariable analysis, genetic liability to insomnia was significantly associated with worse functional outcome (modified Rankin Scale ≥3) after ischemic stroke (odds ratio [OR] = 1.30; 95% CI: 1.10-1.54, p = 0.002). Genetic liability to short sleep, long sleep, and continuous sleep duration were not associated with poststroke functional outcome (all p > 0.05). Sensitivity analyses without adjustment for stroke severity also supported that insomnia was causally associated with poor functional outcome (OR = 1.25; 95% CI: 1.08-1.44, p = 0.003). In the multivariable MR analysis adjusting for potentially confounding traits including body mass index, depression, type 2 diabetes, smoking, and alcohol consumption, the overall patterns between genetic liability to insomnia and poststroke outcome remained (all p < 0.05). This MR study supports potential adverse effects of liability to insomnia on functional outcome after ischemic stroke. Interventions that address insomnia may offer a therapeutic target to improve recovery after ischemic stroke and warrant exploration in a clinical context.


Biotic homogenization destabilizes ecosystem functioning by decreasing spatial asynchrony.
Our planet is facing significant changes of biodiversity across spatial scales. Although the negative effects of local biodiversity (α diversity) loss on ecosystem stability are well documented, the consequences of biodiversity changes at larger spatial scales, in particular biotic homogenization, that is, reduced species turnover across space (β diversity), remain poorly known. Using data from 39 grassland biodiversity experiments, we examine the effects of β diversity on the stability of simulated landscapes while controlling for potentially confounding biotic and abiotic factors. Our results show that higher β diversity generates more asynchronous dynamics among local communities and thereby contributes to the stability of ecosystem productivity at larger spatial scales. We further quantify the relative contributions of α and β diversity to ecosystem stability and find a relatively stronger effect of α diversity, possibly due to the limited spatial scale of our experiments. The stabilizing effects of both α and β diversity lead to a positive diversity-stability relationship at the landscape scale. Our findings demonstrate the destabilizing effect of biotic homogenization and suggest that biodiversity should be conserved at multiple spatial scales to maintain the stability of ecosystem functions and services.


Randomized controlled trial comparing pudendal nerve block under ultrasound and fluoroscopic guidance.
Although fluoroscopy is an established imaging modality for pudendal nerve block, ultrasound (US) technique allows physicians better visualization of anatomic structures. This study aimed to compare the effectiveness and safety between the US- and fluoroscopy-guided techniques. A randomized, single-blind, split-plot design was used to conduct the study. Twenty-three patients undergoing bilateral pudendal nerve blocks received US-guided injections to either the left or right side, whereas the contralateral side received a fluoroscopic-guided injection in randomized sequence. Injections consisted of 4 mL of 0.5% bupivacaine and 40 mg methylprednisone. The primary outcome was the success of the block in the distribution of the pudendal nerve along the perineum, rated as either absent, moderate, or strong. Secondary outcomes were the time to administer the blocks, quality of visualization of anatomic structures using US and fluoroscopy, distance of the final US-guided needle position from the ischial spine, and incidence of adverse effects. No differences in the degree of neural blockade were noted between US- or fluoroscopic-guided techniques for either temperature or pinprick blockade. Time to complete the procedure was significantly longer using US compared with fluoroscopy (219 [SD, 65] and 428 [SD, 151] secs, P < 0.0001). No significant differences were noted regarding the occurrence of adverse effects between the 2 techniques. Ultrasound-guided pudendal nerve blockade is as accurate as fluoroscopically guided injections when performed by an experienced clinician. However, the former took a longer time to perform.


[From present day aviation medicine to aviation anthropologic ecology of the future].
Rationale is given to the proposition that aviation medicine including psychophysiology and ergonomics is a peculiar kind of aviation anthropoecology as a variety of the present-day integrative science of human. This is grounded, firstly, on analysis of any scientific finding of aviation medicine in the light of two principles of the contemporary occupational medicine, i.e. human health and reasonable risk (which is an equivalent of safety) and, secondly, systemic study from this angle of all, from molecular to social, levels of the biological integration man of flying.


Sustained production of the labile pheromone component, (Z,Z)-6,9-heneicosadien-11-one, from a stable precursor for monitoring the whitemarked tussock moth.
The principal sex pheromone component of the whitemarked tussock moth (WMTM), Orgyia leucostigma, was recently identified as (Z,Z)-6,9-heneicosadien-11-one (Z6Z9-11-one-21Hy). However, it is thermally unstable and quickly degrades under field conditions so that baited traps are effective for only one night. We have developed a solution to this problem that combines two techniques: (1) the use of a stable pheromone precursor, (Z,Z)-6,9-heneicosadien-11-one ethylene ketal, which is hydrolyzed to the dienone by an acidic aqueous solution (2% p-toluenesulfonic acid in 35% aqueous sorbitol), and (2) use of a small, off-the-shelf, autonomous pump (the Med-e-Cell Infu-disktrade mark) to deliver the precursor continuously to a suitable substrate where it is converted rapidly into the attractive dienone pheromone component. The pump and hydrolysis substrate fit inside sticky traps and because generation and release of pheromone is continuous, the instability of the pheromone is not an issue. In electroantennogram bioassays, dose-dependent responses were obtained with 1 to 1000 ng of hydrolyzed ketal on filter paper, but no response was obtained to 1000 ng of the ketal itself. In wind tunnel bioassays, males were attracted to lures emitting the dienone pheromone component generated from 0.1 to 100 ng of the hydrolyzed ketal. Field tests in 2004 and 2005 showed that sticky traps fitted with the pump delivering the ketal (0.1-1 microg/microL in heptane) at 10 microL/hr to a cotton pad soaked with the hydrolyzing solution were attractive to male WMTM. No moths were caught in controls or traps baited with (Z)-6-heneicosen-11-one. An average of 0.51 moths per trap night was caught over an 18-night period in 2005. The results represent a first step toward developing a sensitive and practical monitoring tool for the WMTM by using a ketal precursor of its unstable dienone pheromone component.


Fecal Excretion of Orally Administered Collagen-Like Peptides in Rats: Contribution of the Triple-Helical Conformation to Their Stability.
Orally ingested peptides are generally digested in the gastrointestinal (GI) tract and absorbed in the form of oligopeptides. We previously reported that intravenously administered collagen-like triple-helical peptides circulated in the bloodstream and were excreted in their intact forms in urine nearly quantitatively. In the present study, we investigated the fates of orally administered collagen-like peptides in rats. (Pro-Hyp-Gly)10 (Hyp: 4-hydroxyproline), which formed a stable triple-helical structure, was stable in the GI tract, and 72.3±13.0% of the peptide was excreted in the feces. Its recovery ratio was similar to that of all-D-(Pro-Pro-Gly)10 (75.1±15.7%), the indigestible control. In contrast, (Pro-Hyp-Gly)5 and (Pro-Pro-Gly)10, the random coil conformations of which were dominant at body temperature, were not detected in fecal samples, indicating that they were digested by proteases. The high stability of the triple-helical conformation in mammalian bodies suggests the potential use of collagen-like peptides as novel scaffolds of peptide drugs.


Fatty acid desaturation and microsomal lipid fatty acid composition in experimental hypothyroidism.
We have studied the influence of experimental hypothyroidism in the rat on the synthesis of unsaturated fatty acids and on liver microsomal lipid fatty acid composition. Hypothyroid rats demonstrated an 80% decrease in delta 9 (stearate) desaturation and a 43% decrease in delta 6 (linoleate) desaturation. Liver microsomal fatty acid composition was altered in the hypothyroid animals with a significantly decreased proportion of arachidonate and increased proportions of linoleate, eicosa-8,11,14-trienoate, eicosapentaenoate and docosahexaenoate. The bulk of these changes occurred in both of the two major phospholipid components, phosphatidylcholine and phosphatidylethanolamine. All of the changes were corrected by treatment of the hypothyroid rat with 25 micrograms of tri-iodothyronine/100 g body wt. twice daily. The diminished delta 9 desaturation did not lead to any changes in fatty acid composition. The increased linoleate and decreased arachidonate levels may be due to the diminished delta 6 desaturase activity, the rate-controlling step in the conversion of linoleate into arachidonate. The increases in the proportions of the other polyunsaturated fatty acid components cannot be explained by changes in the synthesis of unsaturated fatty acids, but are probably due to diminished utilization of these fatty acids.


Cell migration through three-dimensional confining pores: speed accelerations by deformation and recoil of the nucleus.
Directional cell migration in dense three-dimensional (3D) environments critically depends upon shape adaptation and is impeded depending on the size and rigidity of the nucleus. Accordingly, the nucleus is primarily understood as a physical obstacle; however, its pro-migratory functions by stepwise deformation and reshaping remain unclear. Using atomic force spectroscopy, time-lapse fluorescence microscopy and shape change analysis tools, we determined the nuclear size, deformability, morphology and shape change of HT1080 fibrosarcoma cells expressing the Fucci cell cycle indicator or being pre-treated with chromatin-decondensating agent TSA. We show oscillating peak accelerations during migration through 3D collagen matrices and microdevices that occur during shape reversion of deformed nuclei (recoil), and increase with confinement. During G1 cell-cycle phase, nucleus stiffness was increased and yielded further increased speed fluctuations together with sustained cell migration rates in confinement when compared to interphase populations or to periods of intrinsic nuclear softening in the S/G2 cell-cycle phase. Likewise, nuclear softening by pharmacological chromatin decondensation or after lamin A/C depletion reduced peak oscillations in confinement. In conclusion, deformation and recoil of the stiff nucleus contributes to saltatory locomotion in dense tissues. This article is part of a discussion meeting issue 'Forces in cancer: interdisciplinary approaches in tumour mechanobiology'.


Extended longevity of reproductives appears to be common in Fukomys mole-rats (Rodentia, Bathyergidae).
African mole-rats (Bathyergidae, Rodentia) contain several social, cooperatively breeding species with low extrinsic mortality and unusually high longevity. All social bathyergids live in multigenerational families where reproduction is skewed towards a few breeding individuals. Most of their offspring remain as reproductively inactive "helpers" in their natal families, often for several years. This "reproductive subdivision" of mole-rat societies might be of interest for ageing research, as in at least one social bathyergid (Ansell's mole-rats Fukomys anselli), breeders have been shown to age significantly slower than non-breeders. These animals thus provide excellent conditions for studying the epigenetics of senescence by comparing divergent longevities within the same genotypes without the inescapable short-comings of inter-species comparisons. It has been claimed that many if not all social mole-rat species may have evolved similar ageing patterns, too. However, this remains unclear on account of the scarcity of reliable datasets on the subject. We therefore analyzed a 20-year breeding record of Giant mole-rats Fukomys mechowii, another social bathyergid species. We found that breeders indeed lived significantly longer than helpers (ca. 1.5-2.2fold depending on the sex), irrespective of social rank or other potentially confounding factors. Considering the phylogenetic positions of F. mechowii and F. anselli and unpublished data on a third Fukomys-species (F. damarensis) showing essentially the same pattern, it seems probable that the reversal of the classic trade-off between somatic maintenance and sexual reproduction is characteristic of the whole genus and hence of the vast majority of social mole-rats.


Cerebrovascular pathology and amyloid plaque formation in Alzheimer's disease.
Accumulation, aggregation and deposition of the amyloid-β (Aβ) peptides in the brain are widely accepted as the central events in the pathogenesis of Alzheimer's disease (AD). Any factor that is capable of causing these events is potentially a risk factor for AD. In the last decade, evidence has accumulated to support the association between cerebral vascular diseases (CVD) and AD. CVD is known to induce amyloid deposition and affects the age of onset for sporadic AD; whereas, amyloid deposition has been shown to cause cerebrovascular degeneration. In this review, we propose a positive feedback loop between CVD and amyloid deposition. The disease cycle could be triggered by aging and/or other environmental factor-associated CVD, as in late-onset sporadic AD patients, or by over production of Aβ, as in the familial AD patients and amyloid precursor protein transgenic animals.


Fabrication of Nanofiber Reinforced Protein Structures For Tissue Engineering.
Extracellular matrices and degradable nanofibers are two very promising materials in the field of tissue engineering; however both of these structures face limitations as tissue engineering scaffolds. Extracellular matrices, such as collagen, gelatin, laminin, have excellent biocompatibility and allow cell in growth and survival, but structural weakness makes them difficult to handle and greatly limits their uses. Degradable nanofibers support cell attachment and can provide structural support and directional guidance, but individual degradable nanofibers are fragile and have a tendency to form dense fiber bundles which limited the cell penetration into the spaces between the nanofibers, especially in the case of aligned nanofibers. To overcome these difficulties, degradable loose nanofibers were embedded in protein matrix in an attempt to fabricate a hybrid scaffold with improved properties, such as improved strength, guidance, spacing among nanofibers, etc.. Polycaprolactone (PCL) was used as a model material for degradable nanofibers. Gelatin was employed as a model protein for matrix structure formation. Thin hybrid films (average thickness = 2.78 um) were fabricated by wetting the loose aligned undirectional nanofiber arrays or loose aligned bidirectional nanofiber grids with a gelatin aqueous solution, which also allows for live cell loading into the nanofiber-protein composite if cell are premixed with protein solution or on the surface of the films. Gelatin film alone without nanofiber reinforcement cannot be handled due to the weakness of the thin membrane. Gelatin films with a fiber density as low as 3% v/v were structurally robust enough for handling, and manipulation into complex shapes. Mechanical testing confirmed that the addition of nanofibers enhanced the strength of gelatin films, in both dry and hydrated state. In vitro testing confirmed that nanofiber reinforced films were biocompatible and provided cells with directional guidance. Results demonstrate the promise of gelatin/PCL nanofiber composites as a tissue scaffolding material.


Incidence of percutaneous injuries and non-reporting rates among first-aid responders in Taiwan.
We determined the incidence of percutaneous (needlestick and sharps) injuries among emergency medical technicians (EMTs) in one county in Taiwan, compared this with the official reporting rate, and sought reasons for non-reporting. An anonymous questionnaire was distributed to all EMTs in that county, eliciting percutaneous injuries occurrences, reasons why, and reporting data. Data were analyzed by logistic regression. A total of 329 out of 353 EMTs completed the questionnaire, giving a response rate of 93.2%. Thirty-nine EMTs (11.9%) experienced at least one percutaneous injury in the preceding 12 months. Older, less experienced EMTs were at greater risk of percutaneous injuries. None of the EMTs officially reported their percutaneous injuries primarily because they thought reporting was not mandatory and that the reporting process was too complicated. About one in eight EMTs had experienced at least one percutaneous injury in the preceding year. None of these injuries was officially reported to their organization. Ways to make reporting more user friendly are required, along with resources to minimize percutaneous injuries among EMTs in Taiwan.


Acute inflammation reveals GABAA receptor-mediated nociception in mouse dorsal root ganglion neurons via PGE2 receptor 4 signaling.
Gamma-aminobutyric acid (GABA) depolarizes dorsal root ganglia (DRG) primary afferent neurons through activation of Cl- permeable GABAA receptors but the physiologic role of GABAA receptors in the peripheral terminals of DRG neurons remains unclear. In this study, we investigated the role of peripheral GABAA receptors in nociception using a mouse model of acute inflammation. In vivo, peripheral administration of the selective GABAA receptor agonist muscimol evoked spontaneous licking behavior, as well as spinal wide dynamic range (WDR) neuron firing, after pre-conditioning with formalin but had no effect in saline-treated mice. GABAA receptor-mediated pain behavior after acute formalin treatment was abolished by the GABAA receptor blocker picrotoxin and cyclooxygenase inhibitor indomethacin. In addition, treatment with prostaglandin E2 (PGE2) was sufficient to reveal muscimol-induced licking behavior. In vitro, GABA induced sub-threshold depolarization in DRG neurons through GABAA receptor activation. Both formalin and PGE2 potentiated GABA-induced Ca2+ transients and membrane depolarization in capsaicin-sensitive nociceptive DRG neurons; these effects were blocked by the prostaglandin E2 receptor 4 (EP4) antagonist AH23848 (10 μmol/L). Furthermore, potentiation of GABA responses by PGE2 was prevented by the selective Nav1.8 antagonist A887826 (100 nmol/L). Although the function of the Na+-K+-2Cl- co-transporter NKCC1 was required to maintain the Cl- ion gradient in isolated DRG neurons, NKCC1 was not required for GABAA receptor-mediated nociceptive behavior after acute inflammation. Taken together, these results demonstrate that GABAA receptors may contribute to the excitation of peripheral sensory neurons in inflammation through a combined effect involving PGE2-EP4 signaling and Na+ channel sensitization.


Shiba Bound States across the Mobility Edge in Doped InAs Nanowires.
We present a study of Andreev quantum dots fabricated with small-diameter (30 nm) Si-doped InAs nanowires where the Fermi level can be tuned across a mobility edge separating localized states from delocalized states. The transition to the insulating phase is identified by a drop in the amplitude and width of the excited levels and is found to have remarkable consequences on the spectrum of superconducting subgap resonances. While at deeply localized levels only quasiparticle cotunneling is observed, for slightly delocalized levels Shiba bound states form and a parity-changing quantum phase transition is identified by a crossing of the bound states at zero energy. Finally, in the metallic regime, single Andreev resonances are observed.


Semisupervised least squares support vector machine.
The least squares support vector machine (LS-SVM), like the SVM, is based on the margin-maximization performing structural risk and has excellent power of generalization. In this paper, we consider its use in semisupervised learning. We propose two algorithms to perform this task deduced from the transductive SVM idea. Algorithm 1 is based on combinatorial search guided by certain heuristics while Algorithm 2 iteratively builds the decision function by adding one unlabeled sample at the time. In term of complexity, Algorithm 1 is faster but Algorithm 2 yields a classifier with a better generalization capacity with only a few labeled data available. Our proposed algorithms are tested in several benchmarks and give encouraging results, confirming our approach.


Motorcycle injuries in North-Central Nigeria.
The increasing use of commercial motorcycle as mode of transportation in urban cities in Nigeria has become important source of morbidity and mortality. This is coupled with poor helmet use, narrow roads, increasing traffic, and poor licensing of the motorcycle riders. The objectives of this study are to determine the pattern of injuries following accident involving motorcycles, the mortality rate, and the immediate causes of mortality. This is a combined retrospective and prospective study spanning over 2 years (1 year each). Patient's records were retrieved to collate data for the retrospective study while all the patients presenting to the casualty unit of Jos University Teaching Hospital following involvement in motorcycle accidents between April 2006 and March 2007 were selected for the study. Out of 485 motorcycle injured patients, 295 and 190 were recruited from the retrospective and prospective study respectively. The male: female (M: F) ratio was 4.8:1. The ages ranged from 2.5 to 84 years with a peak at 21-30 years. The total number of injuries was 559 with 443 patients singly injured and 42 patients multiply traumatized. Head injury (40.1%) was the most frequently occurring injury followed closely by extremity injuries (38.1%). None of the patients wore protective helmet. Thirty-six (36) mortalities (7.4%) were recorded and all dead patients had head injuries. All deaths occurred within 24 h. Head injury represents a common cause of morbidity and mortality following motorcycle injuries in our environment. Therefore, strict enforcement of helmet laws from May 10, 2010 may reduce morbidity and mortality.


Potentiating role of IGFBP-2 on IGF-II-stimulated alkaline phosphatase activity in differentiating osteoblasts.
The insulin-like growth factor (IGF) system plays an important role in the autocrine and paracrine regulation of bone formation and remodeling. The aim of this study was to evaluate the role of the autocrine IGF system during osteogenic differentiation in rat tibial osteoblasts (ROB) in culture. In this in vitro model, the stages of osteogenesis studied were S1, corresponding to the onset of alkaline phosphatase (AP) expression (days 0-3); S2, coincident with the peak of AP expression in differentiation culture conditions (days 4-6), and S3, corresponding to the onset of mineral deposition in the extracellular matrix (days 7-9). The results showed that conditioned medium of ROB contains greater amounts of IGF-II than IGF-I at all differentiation stages. Both peptides showed the highest concentrations on day 3 of differentiation (end of S1). All IGF-binding proteins (IGFBPs), except IGFBP-1 and -6, were detected, and IGFBP-2 was the most abundant IGFBP present in the conditioned media, and its degradation increased from S1 to S3. By semiquantitative RT-PCR, IGF-I and IGF-II were highly expressed on days 3 and 6, whereas IGFBP-2 was constantly expressed. We focused our study on the role of IGF-II and IGFBP-2 on the synthesis of AP, an early marker of osteoblast maturation. The results showed that a significant increase in AP expression was induced by IGF-II added to the differentiating osteoblasts continuously or in S1 but not in S2 or S3. IGFBP-2 was able to potentiate endogenous and exogenous IGF-II-dependent stimulation of AP activity, and its proteolytic degradation in late stages of osteogenesis (S2 and S3) was highly correlated with the increase of active matrix metalloproteinase-2 in the CM and with the decreased efficacy of IGF-II action. These data suggest that IGFBP-2, at nearly equimolar concentration with IGF-II, plays a potentiating role in IGF-II action on ROB differentiation in vitro.


Illusions and cloaks for surface waves.
Ever since the inception of Transformation Optics (TO), new and exciting ideas have been proposed in the field of electromagnetics and the theory has been modified to work in such fields as acoustics and thermodynamics. The most well-known application of this theory is to cloaking, but another equally intriguing application of TO is the idea of an illusion device. Here, we propose a general method to transform electromagnetic waves between two arbitrary surfaces. This allows a flat surface to reproduce the scattering behaviour of a curved surface and vice versa, thereby giving rise to perfect optical illusion and cloaking devices, respectively. The performance of the proposed devices is simulated using thin effective media with engineered material properties. The scattering of the curved surface is shown to be reproduced by its flat analogue (for illusions) and vice versa for cloaks.


The impact of tocilizumab on anxiety and depression in patients with rheumatoid arthritis.
Mood disorders, such as anxiety and depression, are extremely prevalent among patients with rheumatoid arthritis (RA). In this study, we assessed the impact of treatment with tocilizumab (TCZ), an IL-6 antagonist, upon anxiety and depressive symptoms in a cohort of RA patients. Study participants were adults diagnosed with RA who received a weekly subcutaneous injection of tocilizumab for 24 weeks. We used the Hamilton Depression (HDRS) and Anxiety (HAMA) scores in order to assess the severity of depression and anxiety, respectively. RA disease activity indices and depression and anxiety levels were assessed at baseline, 4 weeks and study completion. Ultimately, 91 patients were included in the study. The mean age was 54 years, and the majority were female (79%). The mean score in all disease activity indices as well as depression and anxiety levels decreased dramatically from baseline to study completion. Sixty patients (66%) demonstrated a significant decrease in anxiety and/or depression levels. When logistic regression was performed, an HDRS score indicative of depression at study baseline demonstrated an independent association with a significant psychiatric response whilst older age and increased baseline weight were negatively associated. HAMA and HDRA scores correlated with the following RA disease activity parameters, respectively; HAQ-DI (r = .4, .42), DAS28 (r = .29, .32) and CDAI (0.28 and 0.33), all of them were statistically significant (P < .01). This study has demonstrated a favourable impact of TCZ therapy on parameters reflecting depression and anxiety severity in patients with RA.


Reinfection after two-stage revision for periprosthetic infection of total knee arthroplasty.
Limited data exist regarding the long-term results or risk factors for failure after two-stage reimplantation for periprosthetic knee infection. The purpose of this retrospective review was to investigate infection-free implant survival and identify variables associated with reinfection after this procedure. Furthermore, a staging system was evaluated as a possible prognostic tool for patients undergoing two-stage reimplantation of infected total knee arthroplasty (TKA). In this level II, retrospective prognostic study, 368 patients with infected TKA treated with a two-stage revision protocol at our institution between 1998 and 2006 were reviewed. Patients who developed recurrent infection and an equal number of patients randomly selected for the control group were analysed for risk factors associated with treatment failure. At the most recent follow-up, 58 (15.8%) patients had developed reinfection after the two-stage reimplantation. The median time to reinfection was 1,303 days (3.6 years), with follow-up time ranging from six to 2,853 days (7.8 years). The strongest positive predictors of treatment failure included chronic lymphoedema [hazard ratio (HR) = 2.28, 95% confidence interval (CI) 1.16-4.48; p = 0.02),and revision between resection and definitive reimplantation (HR = 2.13, 95% CI 1.20-3.79; p = 0.01, whereas patients treated with intravenously administered Cefazolin had a significant reduction in recurrent infection rate (HR = 0.48, 95% CI 0.25-0.90; p = 0.02). Our findings should be of help in counselling patients regarding their prognosis when faced with two-stage exchange for infected TKA and provide a basis for future comparisons.


Categorical perception along the happy-angry and happy-sad continua in the first year of life.
The current study investigated 6-, 9- and 12-month old infants' ability to categorically perceive facial emotional expressions depicting faces from two continua: happy-sad and happy-angry. In a between-subject design, infants were tested on their ability to discriminate faces that were between-category (across the category boundary) or within-category (within emotion category). Results suggest that 9- and 12 month-olds can discriminate between but not within categories, for the happy-angry continuum. Infants could not discriminate between cross-boundary facial expressions in the happy-sad continuum at any age. We suggest a functional account; categorical perception may develop in conjunction with the emotion's relevance to the infant.


Correlations between the structural and functional characteristics of neurons in the superficial laminae and the hamster's superior colliculus.
Intracellular recording, receptive field mapping, and horseradish peroxidase (HRP) injection techniques were used to determine the structural and functional characteristics of neurons in the superficial laminae (stratum griseum superficiale and stratum opticum) of the hamster's superior colliculus (SC). Fifty-nine neurons (from 38 different hamsters) were successfully characterized, injected with HRP, and recovered. Of these, 8 were marginal cells, 14 had stellate morphology, 10 had narrow, vertically oriented dendritic trees, 12 had wide, vertically oriented dendritic arbors, and 8 were horizontal cells. Seven neurons had somatodendritic morphologies which did not fall into any of these groups. Overall, the distribution of receptive field properties for these cells matched that obtained in previous extracellular recordings from the superficial SC laminae in this species (Chalupa, L.M., and R.W. Rhoades (1977) J. Physiol. (Lond.) 270: 595-626; Chalupa, L.M. and R.W. Rhoades (1978) J. Physiol. (Lond.) 274: 571-592). There were significant correlations between receptive field properties and morphology. Sixty-four percent of the stellate cells and 75% of the marginal cells were directionally selective. Only 17% of the other cell types exhibited this response property. In addition, only 36% of the stellate cells and 25% of the marginal neurons were discharged by stationary, flashed spots. Eighty-one percent of the other recovered cells gave reliable responses to such stimuli. Stellate and marginal cells could also be differentiated from the other cell types on the basis of speed selectivity. Only 29% of the stellate and 13% of the marginal cells responded to stimulus speeds in excess of 20 degrees/sec.(ABSTRACT TRUNCATED AT 250 WORDS)


[Chronic recording of scapular movements in quadruped animal (dog)].
The simple and relatively non-traumatic method of attaching the sensor to the scapular for chronic recording the scapula movements with magnetic tracking device is presented. During experiment the sensor fixed to the skin with the nylon thread passing through the m. deltoideus in the middle part of the scapula. This method provided stable recording of the scapular movements, shown in four dogs with previously learned coordination of head and forelimb movements.


Multiple dendritic cell (DC) subpopulations in human gingiva and association of mature DCs with CD4+ T-cells in situ.
Gingival epithelium is a site of active trafficking of Langerhans cells (LCs), while the lamina propria in chronic periodontitis (CP) contains CD83+ mature dendritic cells (mDCs) and CD4+ T-cells. The immune cells that contribute to the mDCs, and whether mDCs engage with T-cells in situ, are unclear. Using several immunohistochemical approaches, combined with fluorescence-, light-, and scanning laser confocal-microscopy, we show that, in addition to LCs, the gingiva contains dermal DCs (DDCs) in the lamina propria; moreover, DDCs increase in number during CP. Furthermore, DDCs, LCs, and B-cells co-express CD83 in CP and contribute to the mDC pool. Double-staining for CD83 and CD4 revealed that mDCs associate with clusters of CD4+ T-cells in the lamina propria. Analysis of these data suggests that multiple DC subsets mature in the gingiva and that mature DCs engage in antigen presentation with T-cells in chronic periodontitis.


Understanding the Effectiveness of Genomic Prediction in Tetraploid Potato.
Use of genomic prediction (GP) in tetraploid is becoming more common. Therefore, we think it is the right time for a comparison of GP models for tetraploid potato. GP models were compared that contrasted shrinkage with variable selection, parametric vs. non-parametric models and different ways of accounting for non-additive genetic effects. As a complement to GP, association studies were carried out in an attempt to understand the differences in prediction accuracy. We compared our GP models on a data set consisting of 147 cultivars, representing worldwide diversity, with over 39 k GBS markers and measurements on four tuber traits collected in six trials at three locations during 2 years. GP accuracies ranged from 0.32 for tuber count to 0.77 for dry matter content. For all traits, differences between GP models that utilised shrinkage penalties and those that performed variable selection were negligible. This was surprising for dry matter, as only a few additive markers explained over 50% of phenotypic variation. Accuracy for tuber count increased from 0.35 to 0.41, when dominance was included in the model. This result is supported by Genome Wide Association Study (GWAS) that found additive and dominance effects accounted for 37% of phenotypic variation, while significant additive effects alone accounted for 14%. For tuber weight, the Reproducing Kernel Hilbert Space (RKHS) model gave a larger improvement in prediction accuracy than explicitly modelling epistatic effects. This is an indication that capturing the between locus epistatic effects of tuber weight can be done more effectively using the semi-parametric RKHS model. Our results show good opportunities for GP in 4x potato.


Venous leakage treatment revisited: pelvic venoablation using aethoxysclerol under air block technique and Valsalva maneuver.
We evaluated the effectiveness of pelvic vein embolization with aethoxysclerol in aero-block technique for the treatment of impotence due to venous leakage in men using sildenafil for intercourse. The aim of the procedure was to reduce the use of sildenafil. A total of 96 patients with veno-occlusive dysfunction, severe enough for the need of PDE5 inhibitors for vaginal penetration, underwent pelvic venoablation with aethoxysclerol. The mean patient age was 53.5 years. Venous leaks were identified by Color Doppler Ultrasound after intracavernous alprostadil injection. Under local anesthesia a 20-gauge needle was inserted into the deep dorsal penile vein. The pelvic venogram was obtained through deep dorsal venography. Aethoxysclerol 3% as sclerosing agent was injected after air-block under Valsalva manoeuver. Success was defined as the ability to achieve vaginal insertion without the aid of any drugs, vasoactive injections, penile prosthesis, or vacuum device. Additionally, a pre- and post- therapy IIEF score and a digital overnight spontaneous erections protocol (OSEP) with the NEVA™-system was performed. At 3 month follow-up 77 out of 96 patients (80.21%) reported to have erections sufficient for vaginal insertion without the use of any drug or additional device. Four (4.17%) patients did not report any improvement. Follow up with color Doppler ultrasound revealed a new or persistent venous leakage in 8 (8.33%) of the patients. No serious complications occurred. Our new pelvic venoablation technique using aethoxysclerol in air-block technique was effective, minimally invasive, and cost-effective. All patients were able to perform sexual intercourse without the previously used dosage of PDE5 inhibitor. This new method may help in patients with contra-indications against PDE5 inhibitors, in patients who cannot afford the frequent usage of expensive oral medication or those who do not fully respond to PDE5-inhibitors.


Hip osteoarthritis: patients with complex comorbidities can make exceptional improvements following intensive exercise and education.
A 71-year-old man presenting with hip osteoarthritis, with a complex range of comorbidities was referred by his general practitioner to CHAIN (Cycling against Hip PAIN), a 6 week programme developed to aid self-management of hip osteoarthritis through exercise, education and advice, as defined by the National Institute for Health and Care Excellence (NICE) guidelines. Significant improvements were seen in Oxford hip score, the Hip disability and Osteoarthritis Outcome Score (HOOS) - function score, sit-to-stand test, timed up and go test, pain scores and hip flexion. There was also a weight loss of 2.1 kg. The man reported 'an amazing difference' in his affected hip and leg, and improved fitness. Many clinicians would have questioned the man's suitability for the programme due to his coexisting medical conditions. This case study shows that patients may be much more able than we think to achieve significant improvement with exercise.


Insulin glargine use during pregnancy.
To review the literature regarding the use of insulin glargine during pregnancy, specifically addressing the issues and concerns surrounding mitogenicity, placental transfer, and maternal and fetal safety. We performed a systematic literature search using MEDLINE and BIOSIS Previews up to March 2011. Additional studies were identified by hand-searching reference lists from original articles. Inclusion was limited to studies and abstracts in the English language. A total of 23 reports with 1001 pregnancies managed with insulin glargine contained relevant information regarding the maternal and fetal safety of its use during pregnancy. Insulin glargine does not appear to have enhanced mitogenic activity when compared with the mitogenic activity of native human insulin. The transplacental transfer of insulin glargine appears to be negligible, although it is possible that antibody-bound insulin glargine may gain access to the fetal compartment. The available data suggest that there are no identifiable, consistent adverse maternal or fetal outcomes with the use of insulin glargine during pregnancy, including during the first trimester. Use of insulin glargine during pregnancy should be seriously considered in uncontrolled diabetes during pregnancy and in those patients taking insulin glargine before conception, because the benefits from improved glycemic control would be expected to outweigh any, as yet, unproven risks of insulin glargine exposure.


Risk of congenital anomalies near the Byker waste combustion plant.
The aim of this study was to determine whether the risk of congenital anomalies in a population resident close to a waste combustion plant located at Byker in the city of Newcastle upon Tyne, United Kingdom, was higher than in a population resident further away. A geographical study was carried out on the prevalence of congenital anomalies in residents living within 3 km (inner zone) of the Byker combustion plant compared with those living 3-7 km (outer zone) from the plant. There were 81255 live births (1985-1999) and 1508 cases with chromosomal and non-chromosomal congenital anomalies. The cases were identified from the Northern Region Congenital Abnormality Survey. After the site commenced operation the estimated rate ratio (inner versus outer zone) was 1.11 (95 per cent confidence interval (CI) 0.96-1.28) adjusted for socio-economic deprivation. There was significant heterogeneity across years and an increasing trend, of marginal significance (p = 0.07), in the rate ratio. The inner zone rate approached or became significantly higher than that in the outer zone in some of the later years. No significant overall association between the number of congenital anomalies and proximity of residence to the Byker waste combustion plant has been found in this study. Significantly increased rates near the site during the later years may suggest a possible risk but are difficult to interpret. More comprehensive, multi-site investigations around other waste combustion plants are indicated.


Apoptosis in different gastric lesions and gastric cancer: relationship with Helicobacter pylori, overexpression of p53 and aneuploidy.
Apoptosis has an essential function in maintaining the integrity of the gastrointestinal mucosa. Its deregulation is associated with the occurrence of lesions such as in atrophic gastritis, peptic ulcers, intestinal metaplasia, and stomach tumorigenesis. Thus, the aim of the present study was to investigate the frequency of apoptotic cells (apoptotic index, AI) by using two different immunohistochemical techniques, TUNEL and anti-activated caspase-3 antibody (CPP32), in gastric dyspepsia [chronic gastritis (CG, N = 34), chronic atrophic gastritis (CAG, N = 11), gastric ulcer (GU, N = 17), and intestinal metaplasia (IM, N = 15)], normal gastric mucosae (NM, N = 8), and gastric adenocarcinoma (GC, N = 12). The relationship was investigated between the AI and Helicobacter pylori infection, diagnosed by PCR, overexpression of p53 protein determined by immunohistochemistry, and aneuploidy by fluorescence in situ hybridization, as performed by our laboratory in previous studies. No significant differences were observed in AI between the different groups, whether by the TUNEL technique (F = 1.60; p = 0.1670) or by CPP32 antibody (F = 1.70; p = 0.1420). Nonetheless, CAG and CG groups had AI statistically higher than those of normal mucosae. These two groups (CAG and CG) also showed a higher frequency of apoptosis-positive cases (TUNEL+ or CPP32+). Generally, there was no correlation between the AI detected by the TUNEL and CPP32 techniques in the groups studied, except in the GC group (r = 0.70). Moreover, there was no significant association between apoptosis and H. pylori infection, overexpression of p53 protein and aneuploidy, but the H. pylori-positive cases only of GU (p = 0.0233) and IM (p = 0.0253) groups displayed a statistically higher AI compared to H. pylori-negative NM, when the CPP32 antibody technique was used. Thus, CG and CAG have increased apoptosis, which may occur independent of an association with H. pylori infection, aneuploidy and overexpression of p53 protein.


Weak habitat specificity in ectomycorrhizal communities associated with Salix herbacea and Salix polaris in alpine tundra.
This study explores mid-alpine ectomycorrhizal communities on Salix herbacea and Salix polaris in plant communities differing in nutrient status and snow conditions. Plant species were identified by tracking roots back to above ground structures while fungal species were identified using molecular methods. The fungi were identified to 34 molecular operational taxonomic units (MOTUs)/species but species accumulation curves indicated that the communities were only partially sampled. The estimated total species richness was 49 (±9 SD) MOTUs/species. No significant ectomycorrhizal community specificity was found between the two plant species and only weak specificity between different plant communities. Furthermore, no difference in proportion of colonized root tips could be demonstrated between plant communities. However, some fungal taxa showed tendencies to associate with specific environmental conditions. Sebacinaceae, Inocybe egenula, Russula cf. emetica, and a Tomentella sp. were found in meadow communities but not in the heath communities. Sistotrema cf. alboluteum and Tomentella cf. terrestris were only found in the dry and mesic heath communities. Classifications into exploration types showed that the contact type is more abundant in the dry heath community than the other communities. Cenococcum geophilum was the most common species but Cortinarius spp., Russula spp., Tomentella spp., and Lactarius spp. were also common. This study confirms that alpine communities are rich in ectomycorrhizal fungi including species from a wide variety of fungal lineages and also show that many dominant species have wide ecological amplitude.


Pharmacological modulation of two melanocortin-5 receptors by MRAP2 proteins in zebrafish.
Melanocortin receptor accessory protein 2 (MRAP2) plays an important role in regulating melanocortin receptors. In zebrafish, MRAP2a and MRAP2b show distinct pharmacological effects on MC4R activity, but how MRAP2 protein regulates other zebrafish melanocortin receptors is barely studied. Zebrafish have two mc5r genes: mc5ra and mc5rb, it is still vague which one is the homologous isoform to the mammalian paralog. Here we utilize synteny and phylogenetic analysis to demonstrate the evolutionary conservation of zebrafish MC5Ra and MC5Rb among different species. We also show that MRAP2a and MRAP2b could interact and regulate surface expression of two MC5R receptors. Bimolecular fluorescence complementation (BiFC) studies suggest that zebrafish MC5Rs could form homo- and hetero- dimers, which are suppressed by co-expression with MRAP2 proteins. In comparison with mammalian MC5R-MRAP2 system and different pharmacological effects of zMRAP2 protein on MC5Rs, zmc5ra is identified as the evolutionary homologous paralog to the mammals and it is regulated by metabolic state in zebrafish brain region.


E2 enzyme inhibition by stabilization of a low-affinity interface with ubiquitin.
Weak protein interactions between ubiquitin and the ubiquitin-proteasome system (UPS) enzymes that mediate its covalent attachment to substrates serve to position ubiquitin for optimal catalytic transfer. We show that a small-molecule inhibitor of the E2 ubiquitin-conjugating enzyme Cdc34A, called CC0651, acts by trapping a weak interaction between ubiquitin and the E2 donor ubiquitin-binding site. A structure of the ternary CC0651-Cdc34A-ubiquitin complex reveals that the inhibitor engages a composite binding pocket formed from Cdc34A and ubiquitin. CC0651 also suppresses the spontaneous hydrolysis rate of the Cdc34A-ubiquitin thioester without decreasing the interaction between Cdc34A and the RING domain subunit of the E3 enzyme. Stabilization of the numerous other weak interactions between ubiquitin and UPS enzymes by small molecules may be a feasible strategy to selectively inhibit different UPS activities.


Galectin-3 and PTEN expression in pancreatic ductal adenocarcinoma, pancreatic neuroendocrine neoplasms and gastrointestinal tumors on fine-needle aspiration cytology.
Galectin-3 has been implicated in the carcinogenesis of pancreatic ductal adenocarcinoma (PDAC). Its applicability in pancreatic fine-needle aspiration (FNA) in separating malignant from benign lesions has never been addressed. In addition, a correlation between Galectin-3 and tumor suppressor phosphatase and tensin homolog (PTEN) and their potential diagnostic value has never been tested. This study analyzed Galectin-3 immunohistochemical expression in FNA cell blocks of PDAC, pancreatic neuroendocrine neoplasms (PNEN), gastrointestinal stromal tumors (GIST) and non-tumor pancreatic tissue. In parallel, Galectin-3 and PTEN levels were evaluated in a tumor tissue microarray (TMA). Forty-four of 46 PDAC FNA and 32 of 33 PDAC TMA demonstrated tumor-specific Galectin-3 positivity. In contrast, Galectin-3 was not detected in PNEN and GIST. Total loss of PTEN was displayed by 26 of 33 PDAC, while non-neoplastic tissues all retained PTEN expression. Galectin-3 could be a valuable marker to help diagnose PDAC and rule out PNEN and GIST. In addition, PTEN positivity strongly argues against a diagnosis of PDAC. These data also advocate their potential diagnostic roles in the work up of challenging cytologic cases requiring ancillary test confirmation.


Insulin-like growth factor-I protects granule neurons from apoptosis and improves ataxia in weaver mice.
Most cerebellar granule neurons in weaver mice undergo premature apoptosis during the first 3 postnatal weeks, subsequently leading to severe ataxia. The death of these granule neurons appears to result from a point mutation in the GIRK2 gene, which encodes a G protein-activated, inwardly rectifying K+ channel protein. Although the genetic defect was identified, the molecular mechanism by which the mutant K+ channel selectively attacks granule neurons in weaver mice is unclear. Before their demise, weaver granule neurons express abnormally high levels of insulin-like growth factor (IGF) binding protein 5 (IGFBP5). IGF-I is essential for the survival of cerebellar neurons during their differentiation. Because IGFBP5 has the capacity to block IGF-I activity, we hypothesized that reduced IGF-I availability resulting from excess IGFBP5 accelerates the apoptosis of weaver granule neurons. We found that, consistently with this hypothesis, exogenous IGF-I partially protected cultured weaver granule neurons from apoptosis by activating Akt and decreasing caspase-3 activity. To determine whether IGF-I protects granule neurons in vivo, we cross-bred weaver mice with transgenic mice that overexpress IGF-I in the cerebellum. The cerebellar volume was increased in weaver mice carrying the IGF-I transgene, predominantly because of an increased number of surviving granule neurons. The presence of the IGF-I transgene resulted in improved muscle strength and a reduction in ataxia, indicating that the surviving granule neurons are functionally integrated into the cerebellar neuronal circuitry. These results confirm our previous suggestion that a lack of IGF-I activity contributes to apoptosis of weaver granule neurons in vivo and supports IGF-I's potential therapeutic use in neurodegenerative disease.


Patient clusters identified by machine learning from a pooled analysis of the clinical development programme of secukinumab in psoriatic arthritis, ankylosing spondylitis and psoriatic arthritis with axial manifestations.
To identify patient clusters based on baseline demographics and clinical indicators. Pooled baseline demographics and clinical data of secukinumab-treated patients from ten Phase III studies in psoriatic arthritis (PsA; FUTURE 1-5 and MAXIMISE), ankylosing spondylitis (AS; MEASURE 1-4), were analysed by machine learning (ML) algorithms. The longitudinal responses of secukinumab 300 mg versus 150 mg were investigated across the clusters and three clinical indicators of tender joints, swollen joints and enthesitis. 3907 patients were grouped into eight distinct clusters based on patient demographics and baseline clinical characteristics. Patients with PsA and axial manifestations (MAXIMISE) were overrepresented in clusters 6-8. Patients in cluster 6 (mean age 48 years; 46% male) were overweight with pronounced psoriasis, higher articular burden in knees, shoulders, elbows and wrists. Patients in cluster 7 (mean age 47 years; 53% male) were less overweight with lower polyarticular joint counts and tenderness of the joints of the feet, wrists and hands. Patients in cluster 8 were predominantly with AS (mean age 43 years; 64% male) with a mean body mass index of 27.3 kg/m2, oligoarthritis and high prevalence of spinal pain. Patients with PsA (FUTURE) were overrepresented in clusters 1-5. Longitudinal analysis showed improvements with secukinumab 300 mg versus 150 mg in clusters 6 and 8 for tender joint counts, and cluster 7 for swollen joint counts. PsA clusters obtained by ML in pooled dataset indicate phenotypical heterogeneity of patients with PsA and axial manifestations and overlapping features across the spondyloarthritis spectrum.


[The carotid sinus syndrome: problems and outlook].
Electrocardiostimulator was implanted in 108 patients for the carotid sinus syndrome. In 38 observations ventricular stimulation was applied, in 19--the two-chamber one and in 51--the atrial. The syncope disappearance was observed while the DDD and AAI modes of stimulation. If the atrioventricular conduction disorder do not occur while doing transoesophageal stimulation of left atrium during the provocation tests the atrial stimulation is indicated.


Use of complementary medicine amongst hypertensive patients in a public primary care clinic in Ipoh.
The use and reasons for use of Complementary Medicine (CM) amongst hypertensive patients attending the Hypertension/ Diabetes/ Asthma Clinic in Greentown Health Clinic, Ipoh was assessed. One hundred and twenty patients were selected by systematic random sampling (1:5) over a 2-week period commencing 26/04/04. Data was obtained from interviews, questionnaires and medical records. Twenty seven percent were on CM. Most commonly used CM was herbal medicine. Majority of those using CM for BP control were Malays. The Chinese and Indians were using CM mainly for other health problems. Ninety six percent were using both CM and conventional therapy concurrently. Therefore doctors should enquire about CM usage during patient assessment to prevent possible drug interactions.


Counting fluorescent dye molecules on DNA origami by means of photon statistics.
Obtaining quantitative information about molecular assemblies with high spatial and temporal resolution is a challenging task in fluorescence microscopy. Single-molecule techniques build on the ability to count molecules one by one. Here, a method is presented that extends recent approaches to analyze the statistics of coincidently emitted photons to enable reliable counting of molecules in the range of 1-20. This method does not require photochemistry such as blinking or bleaching. DNA origami structures are labeled with up to 36 dye molecules as a new evaluation tool to characterize this counting by a photon statistics approach. Labeled DNA origami has a well-defined labeling stoichiometry and ensures equal brightness for all dyes incorporated. Bias and precision of the estimating algorithm are determined, along with the minimal acquisition time required for robust estimation. Complexes containing up to 18 molecules can be investigated non-invasively within 150 ms. The method might become a quantifying add-on for confocal microscopes and could be especially powerful in combination with STED/RESOLFT-type microscopy.


Experimental and theoretical study of rotationally inelastic diffraction of H2(D2) from methyl-terminated Si(111).
Fundamental details concerning the interaction between H2 and CH3-Si(111) have been elucidated by the combination of diffractive scattering experiments and electronic structure and scattering calculations. Rotationally inelastic diffraction (RID) of H2 and D2 from this model hydrocarbon-decorated semiconductor interface has been confirmed for the first time via both time-of-flight and diffraction measurements, with modest j = 0 → 2 RID intensities for H2 compared to the strong RID features observed for D2 over a large range of kinematic scattering conditions along two high-symmetry azimuthal directions. The Debye-Waller model was applied to the thermal attenuation of diffraction peaks, allowing for precise determination of the RID probabilities by accounting for incoherent motion of the CH3-Si(111) surface atoms. The probabilities of rotationally inelastic diffraction of H2 and D2 have been quantitatively evaluated as a function of beam energy and scattering angle, and have been compared with complementary electronic structure and scattering calculations to provide insight into the interaction potential between H2 (D2) and hence the surface charge density distribution. Specifically, a six-dimensional potential energy surface (PES), describing the electronic structure of the H2(D2)/CH3-Si(111) system, has been computed based on interpolation of density functional theory energies. Quantum and classical dynamics simulations have allowed for an assessment of the accuracy of the PES, and subsequently for identification of the features of the PES that serve as classical turning points. A close scrutiny of the PES reveals the highly anisotropic character of the interaction potential at these turning points. This combination of experiment and theory provides new and important details about the interaction of H2 with a hybrid organic-semiconductor interface, which can be used to further investigate energy flow in technologically relevant systems.


Distinct microbial and immune niches of the human colon.
Gastrointestinal microbiota and immune cells interact closely and display regional specificity; however, little is known about how these communities differ with location. Here, we simultaneously assess microbiota and single immune cells across the healthy, adult human colon, with paired characterization of immune cells in the mesenteric lymph nodes, to delineate colonic immune niches at steady state. We describe distinct helper T cell activation and migration profiles along the colon and characterize the transcriptional adaptation trajectory of regulatory T cells between lymphoid tissue and colon. Finally, we show increasing B cell accumulation, clonal expansion and mutational frequency from the cecum to the sigmoid colon and link this to the increasing number of reactive bacterial species.


[Critical periods in the development of mutants in scute Drosophila melanogaster].
Thermosensitive periods of the development of germs of separate pairs of macrochaetae were studied in two lines of mutation of scute Drosophila melanogaster (y/sc4B and cs7). The experiments have revealed the following three features which had not been observed earlier in similar investigations in other mutants of drosophila: 1) change of thermosensitivity in mutants sc7 in different periods of ontogenesis; 2) different sensitivity in mutants of both lines in different critical periods of the same pair of macrochaetae; 3) discrete sensitivity of separate macrochaetae in mutants of both lines at different stages of oogenesis when there are no germs of these organs yet. The change of penetrability of the mutation of scute for scuttellar macrochaetae in mutants y/sc4B caused by the 90-minute-long heating of larvae on the 4th day of their life (critical period of development) is inherited in 15 observed generations of the maternal line. One may consider these periods of the increased thermosensitivity to be tje periods of stepwise determination of germs of separate pairs of macrochaetae.


Comparative rates of androgen production and metabolism in Caucasian and Chinese subjects.
Clinically apparent prostate cancer occurs more commonly among Caucasians living in Western countries than in Chinese in the Far East. Prior studies demonstrated diminished facial and body hair and lower levels of plasma 3 alpha-androstanediol glucuronide and androsterone glucuronide in Chinese than in Caucasian men. Based upon these findings, investigators postulated that Chinese men could have diminished 5 alpha-reductase activity with a resultant decrease in prostate tissue dihydrotestosterone levels and clinically apparent prostate cancer. An alternative hypothesis suggests that decreased 3 alpha-androstanediol glucuronide and androsterone glucuronide levels might reflect reduced production of androgenic ketosteroid precursors as a result of genetic or environmental factors. The present study examined 5 alpha-reductase activity, androgenic ketosteroid precursors, and the influence of genetic and environmental/dietary factors in groups of Chinese and Caucasian men. We found no significant differences in the ratios of 5 beta-:5 alpha-reduced urinary steroids (a marker of 5 alpha-reductase activity) between Chinese subjects living in Beijing, China, and Caucasians living in Pennsylvania. To enhance the sensitivity of detection, we used an isotopic kinetic method to directly measure 5 alpha-reductase activity and found no difference in testosterone to dihydrotestosterone conversion ratios between groups. Then, addressing the alternative hypothesis, we found that the Caucasian subjects excreted significantly higher levels of individual and total androgenic ketosteroids than did their Chinese counterparts. To distinguish genetic from environmental/dietary factors as a cause of these differences, we compared Chinese men living in Pennsylvania and a similar group living in Beijing, China. We detected a reduction in testosterone production rates and total plasma testosterone and sex hormone-binding levels, but not in testosterone MCRs in Beijing Chinese as a opposed to those living in Pennsylvania. Comparing Pennsylvania Chinese with their Caucasian counterparts, we detected no significant differences in total testosterone, free and weakly bound testosterone, sex hormone-binding globulin levels, and testosterone production rates. Taken together, these studies suggest that environmental/dietary, but not genetic, factors influence androgen production and explain the differences between Caucasian and Chinese men.


Comparison of Vildagliptin and Pioglitazone in Korean Patients with Type 2 Diabetes Inadequately Controlled with Metformin.
We compared the efficacies of vildagliptin (50 mg twice daily) relative to pioglitazone (15 mg once daily) as an add-on treatment to metformin for reducing glycosylated hemoglobin (HbA1c) levels in Korean patients with type 2 diabetes. The present study was a multicenter, randomized, active-controlled investigation comparing the effects of vildagliptin and pioglitazone in Korean patients receiving a stable dose of metformin but exhibiting inadequate glycemic control. Each patient underwent a 16-week treatment period with either vildagliptin or pioglitazone as an add-on treatment to metformin. The mean changes in HbA1c levels from baseline were -0.94% in the vildagliptin group and -0.6% in the pioglitazone group and the difference between the treatments was below the non-inferiority margin of 0.3%. The mean changes in postprandial plasma glucose (PPG) levels were -60.2 mg/dL in the vildagliptin group and -38.2 mg/dL in the pioglitazone group and these values significantly differed (P=0.040). There were significant decreases in the levels of total, low density lipoprotein, high density lipoprotein (HDL), and non-HDL cholesterol in the vildagliptin group but increases in the pioglitazone group. The mean change in body weight was -0.07 kg in the vildagliptin group and 0.69 kg in the pioglitazone group, which were also significantly different (P=0.002). As an add-on to metformin, the efficacy of vildagliptin for the improvement of glycemic control is not inferior to that of pioglitazone in Korean patients with type 2 diabetes. In addition, add-on treatment with vildagliptin had beneficial effects on PPG levels, lipid profiles, and body weight compared to pioglitazone.


Physiologic Effects of Microneedle-Mediated Intracochlear Dexamethasone Injection in the Guinea Pig.
Oral or intratympanic corticosteroids are commonly used to treat sudden sensorineural hearing loss (SSHL), tinnitus, and Meniere disease. Direct intracochlear delivery has been proposed to overcome the variability in bioavailability and efficacy of systemic or middle ear delivery. In this study, we aim to characterize the physiologic consequences of microneedle-mediated direct intracochlear injection of dexamethasone through the round window membrane (RWM). In Hartley guinea pigs (n = 5), a post-auricular incision followed by bullostomy was made to access the round window membrane. Using 100 μm diameter hollow microneedles, 1.0 μl of 10 mg/ml dexamethasone was injected through the RWM over 1 min. Compound action potential (CAP) and distortion product otoacoustic action emissions (DPOAE) were measured before perforation, at 1 h, and at 5 h following injection. CAP hearing thresholds were measured from 0.5 to 40 kHz, and DPOAE f2 frequencies ranged from 1.0 and 32 kHz. Repeated measures ANOVA followed by pairwise t-tests were used for statistical analysis. ANOVA identified significant CAP threshold shifts at four frequencies (4, 16, 36, and 40 kHz) and differences in DPOAE at 1 frequency (6 kHz). Paired t-tests revealed differences between the pre-perforation and 1 h time point. By 5 h post injection, both CAP hearing thresholds and DPOAE recover and are not significantly different from baseline thresholds. Direct intracochlear delivery of dexamethasone via microneedles results in temporary shifts in hearing thresholds that resolve by 5 hours, thus supporting microneedle technology for the treatment of inner ear disorders. N/a Laryngoscope, 2023.


Increased coronary sinus lactate concentration during pacing induced angina pectoris after clinical improvement by glyceryl trinitrate.
Ten patients with stable angina pectoris and obstructed coronary arteries (greater than 75% reduction in diameter) were studied before and during two periods of pacing, the second of which was preceded by sublingual administration of glyceryl trinitrate (mean dose 0.78 mg). Coronary sinus blood flow measurements and aortocoronary sinus blood sampling for metabolite determinations were carried out. Although the rate of pacing was increased by 10 beats/minute after glyceryl trinitrate administration, the onset of angina was delayed in eight patients during pacing. Drug administration decreased coronary sinus blood flow by 42% and myocardial oxygen uptake by 41% during pacing and induced a shift in mean lactate extraction towards a net release (from 3.1% to -12.6%). It increased the number of patients producing lactate from three to five. Glyceryl trinitrate administration decreased myocardial glucose uptake throughout the study, decreased lactate extraction during recovery, and increased the aortocoronary sinus citrate gradient at rest and during recovery, while the exchange of free fatty acids remained unchanged. A decrease in aortocoronary sinus lactate difference during pacing after glyceryl trinitrate administration correlated positively with the fall in coronary sinus blood flow. The metabolic data do not indicate an augmented myocardial lactate production after glyceryl trinitrate administration. A decrease in coronary sinus blood flow seems, therefore, to be of primary importance in explaining the elevated coronary sinus lactate concentration. Our finding that coronary sinus lactate concentration increased during pacing after glyceryl trinitrate administration despite clinical improvement questions the validity of its use as a quantitative index of ischaemia.


Overlap in HMO physician networks.
Health maintenance organizations' (HMOs') restrictions on the size of their physician networks may facilitate cost containment and quality improvement activities but may also impede access to care and impose barriers to those wishing to switch health plans or jobs. We examine the extent, variation, and predictors of overlap in HMO physician networks. We predict that people who switch HMOs have a reasonable likelihood (50 percent) of being able to retain their physician. Overlap ranges from an upper quartile of 69 percent to a lower quartile of 34 percent. Group/staff-model HMOs have little overlap, while younger plans, for-profit plans, and plans in small markets have greater overlap.


Lifelog Data-Based Prediction Model of Digital Health Care App Customer Churn: Retrospective Observational Study.
Customer churn is the rate at which customers stop doing business with an entity. In the field of digital health care, user churn prediction is important not only in terms of company revenue but also for improving the health of users. Churn prediction has been previously studied, but most studies applied time-invariant model structures and used structured data. However, additional unstructured data have become available; therefore, it has become essential to process daily time-series log data for churn predictions. We aimed to apply a recurrent neural network structure to accept time-series patterns using lifelog data and text message data to predict the churn of digital health care users. This study was based on the use data of a digital health care app that provides interactive messages with human coaches regarding food, exercise, and weight logs. Among the users in Korea who enrolled between January 1, 2017 and January 1, 2019, we defined churn users according to the following criteria: users who received a refund before the paid program ended and users who received a refund 7 days after the trial period. We used long short-term memory with a masking layer to receive sequence data with different lengths. We also performed topic modeling to vectorize text messages. To interpret the contributions of each variable to model predictions, we used integrated gradients, which is an attribution method. A total of 1868 eligible users were included in this study. The final performance of churn prediction was an F1 score of 0.89; that score decreased by 0.12 when the data of the final week were excluded (F1 score 0.77). Additionally, when text data were included, the mean predicted performance increased by approximately 0.085 at every time point. Steps per day had the largest contribution (0.1085). Among the topic variables, poor habits (eg, drinking alcohol, overeating, and late-night eating) showed the largest contribution (0.0875). The model with a recurrent neural network architecture that used log data and message data demonstrated high performance for churn classification. Additionally, the analysis of the contribution of the variables is expected to help identify signs of user churn in advance and improve the adherence in digital health care.


Niche partitioning shaped herbivore macroevolution through the early Mesozoic.
The Triassic (252-201 Ma) marks a major punctuation in Earth history, when ecosystems rebuilt themselves following the devastating Permian-Triassic mass extinction. Herbivory evolved independently several times as ecosystems comprising diverse assemblages of therapsids, parareptiles and archosauromorphs rose and fell, leading to a world dominated by dinosaurs. It was assumed that dinosaurs prevailed either through long-term competitive replacement of the incumbent clades or rapidly and opportunistically following one or more extinction events. Here we use functional morphology and ecology to explore herbivore morphospace through the Triassic and Early Jurassic. We identify five main herbivore guilds (ingestion generalists, prehension specialists, durophagous specialists, shearing pulpers, and heavy oral processors), and find that herbivore clades generally avoided competition by almost exclusively occupying different guilds. Major ecosystem remodelling was triggered multiple times by external environmental challenges, and previously dominant herbivores were marginalised by newly emerging forms. Dinosaur dominance was a mix of opportunity following disaster, combined with competitive advantage in their new world.


Protocol for the HAPPY Hearts study: cardiovascular screening for the early detection of future adverse cardiovascular outcomes in middle-aged and older women: a prospective, observational cohort study.
Efforts to identify individuals at a higher risk for adverse cardiovascular outcomes focus on traditional risk factors, such as age, sex, smoking status, blood pressure and and cholesterol; however, this approach does not directly assess cardiovascular function and may underestimate the risk of experiencing adverse cardiovascular outcomes in women. This prospective, observational cohort study will examine the ability of the Heart Attack Prevention Program for You (HAPPY) Hearts screening protocol, a series of non-invasive procedures to identify middle-aged and older women who are at an elevated risk for experiencing an adverse cardiovascular event in the 5-year period after screening. The predictive value of the HAPPY Hearts protocol will also be compared with the Framingham Risk Score to determine the sensitivity for estimating risk for an adverse cardiovascular outcome. One thousand women 55 years of age or older will be recruited to be screened by the HAPPY Hearts protocol. This involves the cardiovascular assessment of resting blood pressure, blood pressure response to 3 min of moderate intensity exercise and large and small arterial elasticity. The participants will be classified into risk categories based on these measures. The incidence of the following adverse cardiovascular outcomes will be assessed in the 5-year period after screening in both groups: ischaemic heart disease, acute myocardial infarction, stroke, percutaneous coronary intervention, coronary bypass surgery, congestive heart failure and new hypertension. Information gathered in this research will be published in peer-reviewed journals and presented in a programme evaluation report to inform Manitoba Health and key stakeholders about the outcomes of the study. The University of Manitoba Health Research Ethics Board has approved the study protocol V.2.0, dated 29 September 2014 (H2014:224). NCT02863211.


Preparation and evaluation of smart food packaging films with anthocyanin Sardasht black grape based on Astragalus gummifer and chitosan nanoparticles.
A new and green development in the field of food packaging is the use of colorimetric films containing anthocyanins, which not only can respond to food spoilage but also have no environmental risk and help the environment full of unacceptable and polluted substances created by humans. In this research, a completely natural film (GCNG) was made using natural materials including tragacanth gummifer (G), chitosan nanoparticles (C), and an extract containing anthocyanins of a type of wild grape called Sardasht black (G) with Alumina nanoparticles (N) for use in food packaging. This biodegradable film (GCNG) presented relatively wide color differences from red to blue in different buffer solutions (pH 2-12), which was clearly observed by the naked eye. Sardasht black grape extract contains large amounts of anthocyanins and antioxidants that can be extracted and used in the preparation of packaging films. The properties of prepared films, including mechanical properties, permeability to water vapor, solubility, swelling, as well as antimicrobial properties were checked by measuring the diameter of the diffusion area by agar disk test. GCNG films showed strong antioxidant activity and good antibacterial activity against E. coli and S. aureus. The results suggested this film has promising potential as an active and smart packaging material for applications in the food industry.


Diabetic and nondiabetic lumbosacral radiculoplexus neuropathies: new insights into pathophysiology and treatment.
Diabetic lumbosacral radiculoplexus neuropathy (DLRPN) (also called diabetic amyotrophy) is a well-recognized subacute, painful, asymmetric lower-limb neuropathy that is associated with weight loss and type II diabetes mellitus. Nondiabetic lumbosacral radiculoplexus neuropathy (LRPN) has received less attention. Comparison of large cohorts with DLRPN and LRPN demonstrated that age at onset, course, type and distribution of symptoms and impairments, laboratory findings, and outcomes are similar. Both conditions are lumbosacral radiculoplexus neuropathies that are associated with weight loss and begin focally with pain but that evolve into widespread, bilateral paralytic disorders. Although both are monophasic illnesses, patients have prolonged morbidity from pain and weakness, and many patients become wheelchair-dependent. Although motor-predominant, there is unequivocal evidence that autonomic and sensory nerves are also involved. Cutaneous nerves from patients with DLRPN and LRPN show pathological evidence of ischemic injury (multifocal fiber loss, perineurial thickening and degeneration, neovascularization, microfasciculation, and swollen axons with accumulated organelles) and microvasculitis (mural and perivascular inflammation, separation and fragmentation of mural smooth muscle layers of microvessels and hemosiderin-laden macrophages). Controlled trials with immune-modulating therapies in DLRPN are in progress, and preliminary data suggest that such therapy may be beneficial in LRPN. It is likely that DLRPN and LRPN are immune-mediated neuropathies that should be separated from chronic inflammatory demyelinating polyneuropathy and from systemic necrotizing vasculitis.


Effects of subthalamic nucleus stimulation on emotional prosody comprehension in Parkinson's disease.
Although impaired decoding of emotional prosody has frequently been associated with Parkinson's disease (PD), to date only few reports have sought to explore the effect of Parkinson's treatment on disturbances of prosody decoding. In particular, little is known about how surgical treatment approaches such as high frequency deep brain stimulation (DBS) affect emotional speech perception in patients with PD. Accordingly, the objective of this study was to evaluate the effect of subthalamic nucleus (STN) stimulation on prosody processing. To this end the performance of 13 PD patients on three tasks requiring the decoding of emotional speech was assessed and subsequently compared to the performance of healthy control individuals. To delineate the effect of STN-DBS, all patients were tested with stimulators turned on as well as with stimulators turned off. Results revealed that irrespective of whether assessments were made "on" or "off" stimulation, patients' performance was less accurate as compared to healthy control participants on all tasks employed in this study. However, while accuracy appeared to be unaffected by stimulator status, a facilitation of reactions specific to highly conflicting emotional stimulus material (i.e. stimulus material presenting contradicting emotional messages on a verbal and non-verbal prosodic level) was observed during "on" stimulation assessments. In sum, presented results suggest that the processing of emotional speech is indeed modulated by STN-DBS. Observed alterations might, on the one hand, reflect a more efficient processing of highly conflicting stimulus material following DBS. However, on the other hand, given the lack of an improvement in accuracy, increased impulsivity associated with STN stimulation needs to be taken into consideration.


Autonomic nervous function assessment using thermal reactivity of microcirculation.
There are only a few reliable objective methods of diagnosing peripheral neuronal damage suitable for routine use; the most important is based on measurement of nerve conduction velocity, which only shows changes when severe disturbances are already present. However, it is precisely at this stage that the possibilities of therapy are no longer satisfactory. As small fibres are affected earlier in the course of most forms of PNP than the large ones, assessment of afferent as well as efferent C-fibre function gains importance in the management of this widespread disease. In assessment of autonomic dysfunction, variability of the heartbeat with deep breathing or the Valsalva manoeuvre is a good and generally accepted test, although not strongly associated with other PNP test abnormalities. However, axonal degeneration starts in the most distal parts of the axon due to impaired axonal transport. Therefore, the longest C-fibres, i.e. in the lower extremities, are affected first, and incipient changes are most prominent there. For this reason HLDF, a reflex response of the skin blood flow stimulated by heat, has advantages in assessment of early C-fibre dysfunction. Considering the fact that the afferent and efferent sympathetic C-fibres are involved in regulation of microcirculation, the skin blood flow regulation is investigated by means of laser Doppler flowmetry. The microcirculation is stimulated by heat and the reaction of microcirculation is assessed as a value for the function of afferent and efferent (sympathetic) C-fibres. The results of this method are in close correlation with electrophysiologic tests, which is not achieved with sudomotor function.


Patient-tailored ovarian stimulation for in vitro fertilization.
At present, much attention in medicine is being directed toward individualized or patient-tailored care with the use of novel tools such as biomarkers or genomics. Research tools different from randomized controlled trials, focusing on the heterogeneity of patients rather than the intervention per se, are required to develop this concept further. In infertility care, few examples of individualized approaches with the use of multivariate prediction models can be found, such as the prediction of spontaneous conception chances in infertile patients or regarding the medical treatment of anovulatory infertility. Few prospective studies have been published in recent years concerning individualized dosing based on response prediction for ovarian stimulation in IVF. Potentially much may be gained by such methods because at present ovarian response to stimulation varies greatly, with distinct implications for both efficacy and safety of IVF treatment.


Dual-Reporting Transcriptionally Linked Genetically Encoded Fluorescent Indicators Resolve the Spatiotemporal Coordination of Cytosolic Abscisic Acid and Second Messenger Dynamics in Arabidopsis.
Deciphering signal transduction processes is crucial for understanding how plants sense and respond to environmental changes. Various chemical compounds function as central messengers within deeply intertwined signaling networks. How such compounds act in concert remains to be elucidated. We have developed dual-reporting transcriptionally linked genetically encoded fluorescent indicators (2-in-1-GEFIs) for multiparametric in vivo analyses of the phytohormone abscisic acid (ABA), Ca2+, protons (H+), chloride (anions), the glutathione redox potential, and H2O2 Simultaneous analyses of two signaling compounds in Arabidopsis (Arabidopsis thaliana) roots revealed that ABA treatment and uptake did not trigger rapid cytosolic Ca2+ or H+ dynamics. Glutamate, ATP, Arabidopsis PLANT ELICITOR PEPTIDE, and glutathione disulfide (GSSG) treatments induced rapid spatiotemporally overlapping cytosolic Ca2+, H+, and anion dynamics, but except for GSSG, only weakly affected the cytosolic redox state. Overall, 2-in-1-GEFIs enable complementary, high-resolution in vivo analyses of signaling compound dynamics and facilitate an advanced understanding of the spatiotemporal coordination of signal transduction processes in Arabidopsis.


Management of gastric schwannoma: A retrospective analysis of clinical characteristics, treatments, and outcomes.
This study aimed to investigate the clinical characteristics, treatment options, and prognosis of patients with gastric schwannoma (GS). Patients who were pathologically diagnosed with GS between April 2011 and October 2022 were enrolled. The data of clinical characteristics, pathological features, treatment options, and clinical outcomes were collected and compared between GS patients who underwent endoscopic resection (ER) and surgical resection (SR). Of the 32 cases, 23 underwent SR and nine underwent ER. The median tumor size was significantly smaller in ER group than in SR group (12.0 vs. 40.0 mm, P < 0.001), while patients in SR group were older than those in ER group (54.5 ± 10.6 vs. 45.3 ± 10.9 years, P = 0.036). Moreover, tumors in ER group were more likely to exhibit an intraluminal pattern (100% vs. 26.1%, P < 0.001). Patients in ER group had significantly lower hospitalization cost (25859.2 ± 8623.9 vs. 44953.0 ± 13083.8 RMB, P = 0.011) than those in SR group. No differences were found between the two groups in terms of R0 resection rate, operative time, estimated blood loss, adverse events, and recurrence rate. All patients were followed up for 4-96 months (mean: 35 months; median: 23 months), during which no evidence of recurrence or metastasis was observed. Both ER and SR are safe and effective treatment modalities for the management of GS, with ER being associated with lower medical costs compared to SR. The majority of GS are benign and do not recur, with little possibility of malignant transformation.


Medical Error and Moral Luck.
Medical error is the third-leading cause of death in the United States, but there has been little work done on the associated conceptual and normative questions. What is medical error? Is all medical error bad? The first section of this paper surveys the dominant conception of medical error-promulgated by the Institute of Medicine-and tries to understand whether error necessarily eventuates in adverse events. The second section challenges an asymmetry in the way that we think about error: For example, the received view would allow that undertesting could comprise medical error, whereas overtesting cannot. The third section considers the concept of moral luck and how it bears on our ascriptions of medical error.


Determinants of remaining in the community after discharge: results from New Jersey's Nursing Home Transition Program.
To inform states with nursing home transition programs, we determine what risk factors are associated with participants' long-term readmission to nursing homes within 1 year after discharge. We obtained administrative data for all 1,354 nursing home residents who were discharged, and we interviewed 628 transitioning through New Jersey's nursing home transition program in 2000. We used the Andersen behavioral model to select predictors of long-term nursing home readmission, and we used Cox proportional hazards regressions to examine the relative risk of experiencing such readmissions. Overall, 72.6% of the 1,354 individuals remained in the community, with 8.6% readmitted to a nursing home for long stays (>90 days) and 18.8% dying during the study year. Cox proportional hazards regression analysis showed that being male, single, and dissatisfied with one's living situation; living with others; and falling within 8 to 10 weeks after discharge were significant predictors of long-term nursing home readmission during the first year after discharge. Most of the factors predicting long-term readmission were predisposing, not need, factors. This fact points to the limits of formulaic approaches to assessing candidates for discharge and the importance of working with clients to understand and address their particular vulnerabilities. Consumers, state policy makers, nursing home transition staff, discharge planners, and caregivers can use these findings to understand and help clients understand their particular risks and options, and to identify those individuals needing the greatest attention during the transition period as well as risk-specific services such as fall-prevention programs that should be made available to them.


An experimental study for the compact hydrogen maser with a TE111 septum cavity.
We have made experiments on our compact active hydrogen maser with the cylindrical TE111-mode septum cavity, which is almost one-half the conventional TE011-mode cavity in size. An inductive radiation signal was observed, but the maser did not produce self-oscillation. The system supports oscillation when the cavity is placed in an external feedback loop.