Dimensionality Reduction in Surrogate Modeling: A Review of Combined Methods.
Surrogate modeling has been popularized as an alternative to full-scale models in complex engineering processes such as manufacturing and computer-assisted engineering. The modeling demand exponentially increases with complexity and number of system parameters, which consequently requires higher-dimensional engineering solving techniques. This is known as the curse of dimensionality. Surrogate models are commonly used to replace costly computational simulations and modeling of complex geometries. However, an ongoing challenge is to reduce execution and memory consumption of high-complexity processes, which often exhibit nonlinear phenomena. Dimensionality reduction algorithms have been employed for feature extraction, selection, and elimination for simplifying surrogate models of high-dimensional problems. By applying dimensionality reduction to surrogate models, less computation is required to generate surrogate model parts while retaining sufficient representation accuracy of the full process. This paper aims to review the current literature on dimensionality reduction integrated with surrogate modeling methods. A review of the current state-of-the-art dimensionality reduction and surrogate modeling methods is introduced with a discussion of their mathematical implications, applications, and limitations. Finally, current studies that combine the two topics are discussed and avenues of further research are presented.


Trends in segmentectomy for the treatment of stage 1A non-small cell lung cancers: Does the robot have an impact?
Lobectomy may unnecessarily resect healthy lung parenchyma in Stage 1A non-small cell lung cancers (NSCLC). Segmentectomies may provide a lung-sparing option. VATS segmentectomies can be technically challenging; robotics may have features that provide advantages in performing segmentectomies. We describe the association of the robot on national trends in segmentectomies. The National Cancer Database (2010-2017) was queried for patients with Stage 1A NSCLC who underwent lobectomies and segmentectomies. The proportion of segmentectomies vs. lobectomies and the proportion of robotic vs. VATS segmentectomies was calculated annually. The proportion of segmentectomies increased compared to lobectomies for all surgical approaches but remained constant for minimally-invasive approaches. The proportion of robotic segmentectomies increased over the years compared to VATS segmentectomies. Descriptive statistics are reported as numbers and proportions. Trends in the proportions of lobectomies and segmentectomies were compared using Chi-squared test for categorical variables and unpaired t-test for independent means. A p-value of <0.05 was considered statistically significant. Statistical analysis was performed using SPSS Statistics Software version 24 (IBM Corp, Armonk, NY). We demonstrate an increasing trend and proportion of robotic segmentectomies being performed in comparison to VATS segmentectomies. The robotic platform may facilitate the performance of more segmentectomies for early-stage NSCLC.


Structure-property relation and relevance of beam theories for microtubules: a coupled molecular and continuum mechanics study.
Quasi-one-dimensional microtubules (MTs) in cells enjoy high axial rigidity but large transverse flexibility due to the inter-protofilament (PF) sliding. This study aims to explore the structure-property relation for MTs and examine the relevance of the beam theories to their unique features. A molecular structural mechanics (MSM) model was used to identify the origin of the inter-PF sliding and its role in bending and vibration of MTs. The beam models were then fitted to the MSM to reveal how they cope with the distinct mechanical responses induced by the inter-PF sliding. Clear evidence showed that the inter-PF sliding is due to the soft inter-PF bonds and leads to the length-dependent bending stiffness. The Euler beam theory is found to adequately describe MT deformation when the inter-PF sliding is largely prohibited. Nevertheless, neither shear deformation nor the nonlocal effect considered in the 'more accurate' beam theories can fully capture the effect of the inter-PF sliding. This reflects the distinct deformation mechanisms between an MT and its equivalent continuous body.


High concentrations of neutral amino acids activate NMDA receptor currents in rat hippocampal neurons.
High concentrations (30 microM-5 mM) of the neutral amino acids L-serine, L-cysteine, L-alanine, L-proline and glycine elicited inward current responses when applied to hippocampal neurons patch clamped at -60 mV in the presence of 1-10 microM glycine and 1 microM strychnine. The amplitude of the response to L-serine increased in a concentration-dependent fashion within the range 0.1-10 mM (EC50, 2.6 mM). L-Serine (1 mM) currents were attenuated by Mg2+ (100 microM) and completely blocked by the competitive N-methyl-D-aspartate (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1- phosphonic acid (CPP) (30 microM). The CPP block could be overcome by raising the concentration of L-serine. We conclude that high concentrations of some neutral amino acids activate NMDA receptor-coupled ion channels by acting as agonists at the NMDA recognition site.


Thermodynamic analysis of the binding of component enzymes in the assembly of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus.
The peripheral subunit-binding domain (PSBD) of the dihydrolipoyl acetyltransferase (E2, EC 126.96.36.199) binds tightly but mutually exclusively to dihydrolipoyl dehydrogenase (E3, EC 18.104.22.168) and pyruvate decarboxylase (E1, EC 188.8.131.52) in the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus. Isothermal titration calorimetry (ITC) experiments demonstrated that the enthalpies of binding (DeltaH degrees ) of both E3 and E1 with the PSBD varied with salt concentration, temperature, pH, and buffer composition. There is little significant difference in the free energies of binding (DeltaG degrees = -12.6 kcal/mol for E3 and = -12.9 kcal/mol for E1 at pH 7.4 and 25 degrees C). However, the association with E3 was characterized by a small, unfavorable enthalpy change (DeltaH degrees = +2.2 kcal/mol) and a large, positive entropy change (TDeltaS degrees = +14.8 kcal/mol), whereas that with E1 was accompanied by a favorable enthalpy change (DeltaH degrees = -8.4 kcal/mol) and a less positive entropy change (TDeltaS degrees = +4.5 kcal/mol). Values of DeltaC(p) of -316 cal/molK and -470 cal/molK were obtained for the binding of E3 and E1, respectively. The value for E3 was not compatible with the DeltaC(p) calculated from the nonpolar surface area buried in the crystal structure of the E3-PSBD complex. In this instance, a large negative DeltaC(p) is not indicative of a classical hydrophobic interaction. In differential scanning calorimetry experiments, the midpoint melting temperature (T(m)) of E3 increased from 91 degrees C to 97.1 degrees C when it was bound to PSBD, and that of E1 increased from 65.2 degrees C to 70.0 degrees C. These high T(m) values eliminate unfolding as a major source of the anomalous DeltaC(p) effects at the temperatures (10-37 degrees C) used for the ITC experiments.


Visualization of basilar artery atherosclerotic plaques by conventional T2-weighted magnetic resonance imaging: A case-control study.
In vivo visualization of intracranial atherosclerotic plaque has been performed only with high-resolution magnetic resonance imaging (HRMR). We investigated whether atherosclerotic plaque of the basilar artery (BA) can be identified in conventional magnetic resonance imaging (MRI). Patients with acute ischemic stroke who had BA stenosis ("symptomatic BAA") were retrospectively recruited using the prospective stroke registry. In the HRMR databank, subjects without BA stenosis were recruited and classified as those with silent plaque ("silent BAA") and without any plaque ("normal controls"). Outer diameter of the BA and T2 plaque sign (an eccentric or complete obscuration of normal flow-void) within the BA were assessed by two blinded raters using conventional T2 MRI. Seventy-five patients with symptomatic BAA, 40 with asymptomatic BAA, and 36 normal controls were included in the study. Maximal BA diameter was significantly larger in symptomatic BAA patients with <30%, 30-50%, 50-70%, and >70% stenosis (all p<0.01 in each subgroup) and silent BAA subjects (p = 0.018) than controls. T2 plaque signs were present in 46 (61.3%) patients with symptomatic BAA and 6 (14.6%) subjects with asymptomatic BAA, while none in normal controls (p <0.001 and 0.057, respectively). Detection rates were increased with an increase in stenosis degree (25.0% in <30% stenosis, 57.9% in 30-50% stenosis, 38.5% in 50-70% stenosis, 92.3% in 70-99% stenosis, and 100.0% in occlusion). Our data suggest that BA atherosclerosis can be detected by conventional MRI. When the use of HRMR is limited, conventional MR imaging may give additive information to clinicians.


Effect of platelet-rich plasma (PRP) concentration on the viability and proliferation of alveolar bone cells: an in vitro study.
Previous studies have shown that a combination of platelet-rich plasma (PRP) and autogenous bone graft can increase the rate of osteogenesis and enhance bone formation qualitatively. However, contradictory results were reported in a recent animal study. In order to clarify this inconsistency, this study examined the influence of the PRP concentrations on the viability and proliferation of alveolar bone cells in vitro. Bone cells obtained from the alveolar bone chips were exposed to various PRP concentrations. After a culture period of 7 days, cellular viability and proliferation were evaluated by counting the number of cells and a MTT assay. The results showed that the viability and proliferation of alveolar bone cells were suppressed by high PRP concentrations, but were stimulated by low PRP concentrations (1-5%). These in vitro results support the view that variations in the PRP concentrations might influence the bone formation within the PRP-treated bone grafts.


Factors associated with labor market participation of persons with traumatic SCI in Switzerland: analyzing the predictive power of social background, health, functional independence, and the environment.
Cross-sectional study using data from the 2012 community survey of the Swiss Spinal Cord Injury Cohort Study. To identify associations between selected factors related to the social background, health, functional independence, and the environment of persons with spinal cord injury (SCI) and their labor market participation. Community-based, Switzerland. Labor market participation (i.e., involvement in paid work or not) was determined for a sample of 966 persons with traumatic SCI who were of employable age at the time of the survey. Applying an exploratory approach, potential predictors of labor market participation were selected based on the literature and using a bidirectional stepwise variable selection approach. Descriptive statistics were calculated and weighted bootstrapped multiple logistic regressions were applied to describe the associations between the selected predictor variables and labor market participation, controlling for sociodemographic and SCI-related characteristics. A total of 568 (58.8%) of the participants were involved in paid work at the time of the survey. From the 17 selected predictor variables, general functional independence and Swiss citizenship showed a significant positive association, and chronic pain a negative association with involvement in paid work. Beyond previously established sociodemographic and injury-related risk factors such as female gender, low education, and high lesion severity, functional independence, chronic pain, and nationality proved crucial for labor market participation. These factors should receive particular attention in medical and vocational strategies striving for a sustainable work integration of persons with SCI.


Finite-time stability analysis and control of stochastic SIR epidemic model: A study of COVID-19.
Finite-time stability analysis is a powerful tool for understanding the long-term behavior of epidemiological models and has been widely used to study the spread of infectious diseases such as COVID-19. In this paper, we present a finite-time stability analysis of a stochastic susceptible-infected-recovered (SIR) epidemic compartmental model with switching signals. The model includes a linear parameter variation (LPV) and switching system that represents the impact of external factors, such as changes in public health policies or seasonal variations, on the transmission rate of the disease. We use the Lyapunov stability theory to examine the long-term behavior of the model and determine conditions under which the disease is likely to die out or persist in the population. By taking advantage of the average dwell time method and Lyapunov functional (LF) method, and using novel inequality techniques the finite-time stability (FTS) criterion in linear matrix inequalities (LMIs) is developed. The finite-time stability of the resultant closed-loop system, with interval and linear parameter variation (LPV), is then guaranteed by state feedback controllers. By analyzing the modified SIR model with these interventions, we are able to examine the efficiency of different control measures and determine the most appropriate response to the COVID-19 pandemic and demonstrate the efficacy of the suggested strategy through simulation results.


A brevifoliol analogue from the Himalyan yew Taxus wallichiana.
The needles of Taxus wallichiana gave a new brevifoliol derivative whose structure was established by spectral data.


Diagnostic trajectories in child and adolescent mental health services: exploring the prevalence and patterns of diagnostic adjustments in an electronic mental health case register.
Community-based epidemiological studies show transitions between psychiatric disorders are common during child development. However, little research has explored the prevalence or patterns of the diagnostic adjustments that occur in child and adolescent mental health services (CAMHS). Understanding diagnostic trajectories is necessary to inform theory development in developmental psychopathology and clinical judgements regarding risk and prognosis. In this study, data from CAMHS clinical records were extracted from a British mental health case register (N = 12,543). Analysis calculated the proportion of children whose clinical records showed a longitudinal diagnostic adjustment (i.e. addition of a subsequent diagnosis of a different diagnostic class, at > 30 days' distance from their first diagnosis). Regression analyses investigated typical diagnostic sequences and their relationships with socio-demographic variables, service use and standardised measures of mental health. Analysis found that 19.3% of CAMHS attendees had undergone a longitudinal diagnostic adjustment. Ethnicity, diagnostic class and symptom profiles significantly influenced the likelihood of a diagnostic adjustment. Affective and anxiety/stress-related disorders longitudinally predicted each other, as did hyperkinetic and conduct disorders, and hyperkinetic and pervasive developmental disorders. Results suggest that approximately one in five young service users have their original psychiatric diagnosis revised or supplemented during their time in CAMHS. By revealing the most common diagnostic sequences, this study enables policy makers to anticipate future service needs and clinicians to make informed projections about their patients' likely trajectories. Further research is required to understand how young people experience diagnostic adjustments and their psychological and pragmatic implications.


Promoting infant mental health in the neonatal intensive care unit (NICU): A review of nurturing factors and interventions for NICU infant-parent relationships.
Premature and medically vulnerable infants experience early and sometimes prolonged separation from their parents, intrusive and unnatural environments, painful and distressing procedures, difficulties with physiological regulation, increased biological and neurological vulnerabilities, and grow up to have higher rates of neurocognitive and psychosocial difficulties. Parents of infants born prematurely or with medical vulnerabilities, in turn, experience significant distress and are a psychiatrically vulnerable population, with very high rates of depression, anxiety, and posttraumatic stress disorder. The combination of these factors cause significant challenges for some of these infants and parents in developing an early optimal relationship and connection. Given the critical importance of early relationships with main caregivers for infant mental health and long-term developmental outcomes, we review various targets of intervention to promote healthy infant and parent mental health and bonding thereby facilitating an optimal infant-parent relationship in the NICU population.


Expression of FasL and its interaction with Fas are mediated by c-Jun N-terminal kinase (JNK) pathway in 6-OHDA-induced rat model of Parkinson disease.
Our previous studies and those of others have strongly suggested that c-Jun N-terminal kinase (JNK) signaling pathway plays a critical role in 6-hydroxydopamine (6-OHDA)-induced dopaminergic neuron injury in the substantia nigra. However, the downstream mechanism that accounts for the proapoptotic actions of JNK in 6-OHDA lesion remains to be investigated in detail. Fas, a member of the tumor necrosis factor receptor family with proapoptotic functions, was reported to be elevated within the striatum and substantia nigra pars compacta (SNc) of Parkinson's disease (PD) patients. In the present study, we examined the changes in the protein level of Fas ligand (FasL) and its interaction with Fas in a rat model of PD. We demonstrate that the expression of FasL and not Fas was increased after 6-OHDA lesion; additionally, the interaction of FasL and Fas was increased due to 6-OHDA lesion. This indicates that the 6-OHDA-induced activation of Fas signaling pathway is mediated by JNK and that FasL may be a promising target in the therapeutic approach for PD patients.


Cutaneous temperature and pressure pain threshold in individuals with knee osteoarthritis.
Osteoarthritis is a common disease in which skin temperature may be included among the pathophysiological factors. Thermography allows the mapping of cutaneous temperature and may be employed in the investigation of osteoarthritis. To evaluate cutaneous temperature of the lower limbs, as well as to verify its association with pressure pain thresholds in individuals with knee osteoarthritis. This case series study was conducted with individuals of both genders aged 48-77 years with unilateral knee osteoarthritis. Volunteers underwent thermographic evaluation by an infrared sensor (FLIR T650SC). The anterior region of the thigh and leg and the knee area were evaluated. Pressure pain thresholds (PPT) were evaluated by algometry (Pain Diagnostics, Great Neck, USA) at the vastus medialis, vastus lateralis, rectus femoris, and patellar tendon. Data analysis was conducted with the statistical package SPSS v.24 for Windows. Comparisons between affected and unaffected sides were made by paired Student's t-test or the Mann-Whitney U test, and associations between variables were assessed by Pearson or Spearman's correlation coefficient. In all cases, the significance level was set at p ≤ 0.05. Eleven volunteers (63.1 ±9.5 years) participated in this study. When comparing cutaneous temperature, only the region of the knee showed a significant difference between sides (p = 0.02). There were no differences between affected and unaffected knees regarding pain tolerance (PPT) at all sites evaluated. There were also no significant associations between the study variables. Individuals with knee osteoarthritis presented a higher temperature of the affected knee, but this was not associated with pressure pain thresholds.


Disturbance of peripheral microcirculation by LHRH-agonists. II.
It could be demonstrated with the aid of a cheek pouch model of the hamster that the LHRH-agonist lutrelin (Wyeth, WY 40972) caused disturbances of microcirculation within minutes, for example constriction of the arterioles and venules, reduction in capillary density and increased permeability, effects which were not reversible within the observation period (1 h) and could not be antagonized by the cyclooxygenase inhibitor indomethacin. Likewise, the lutrelin-induced accumulation of leucocytes in the capillaries of the testes of the rat could not be prevented within 6 hours after administration of indomethacin, whereas the harmful effect of lutrelin on the germinal epithelium could be antagonized by indomethacin within 24 hours. A biphasal course is assumed, characterised by an acute non-prostaglandin-dependent phase and a second prostaglandin-dependent phase, which causes the definitive damage to the testis of the rat.


Role of hTERT in apoptosis of cervical cancer induced by histone deacetylase inhibitor.
Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase holoenzyme as well as the rate-limiting component of the telomerase enzyme complex. However, the role of the hTERT in apoptosis induced by histone deacetylase inhibitor has only been marginally addressed. For the first time, our study demonstrated that trichostatin A (TSA) briefly activated the proliferation of cervical cancer cell lines, HeLa and SiHa, within 12 h, but then inhibited cell growth after that time point. In response to TSA, hTERT expression, telomerase activity, and telomere length also underwent similar changes during the same time frame. Furthermore, the data in our study showed that cells transfected with dominant negative hTERT were more likely to undergo apoptosis induced by TSA than cells transfected with wild-type hTERT. The cyclin/cdk inhibitor p21waf1 was down-regulated by hTERT without changing the expression of p53. Results from this study suggest that the hTERT might be a primary target of TSA and the anti-apoptosis effect of hTERT might be carried out through a p21waf1-dependent and p53-independent pathway.


Dietary fat modifies the in vivo mutagenicity of some food-borne carcinogens.
Female BALB/c mice were fed a low fat diet (1% safflower oil, by weight) or one supplemented with 25% (by weight) of beef fat or olive oil. The abilities of these diets to modify the in vitro and in vivo hepatic conversion of the dietary carcinogens aflatoxin B1, 2-amino-3, 4-dimethylimidazo[4,5-f]quinoline (MeIQ) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) to bacterial mutagens was evaluated. Dietary olive oil appeared to increase the metabolism of both MeIQ and Trp-P-2 to bacterial mutagens in vivo using the intrasanguineous host-mediated assay. Feeding mice either of the high-fat diets increased hepatic conversion of these two compounds to bacterial mutagens in vitro. Dietary fat had no effect on the metabolism of aflatoxin B1. Subsequent experiments suggested that the in vivo effects of dietary olive oil on MeIQ and Trp-P-2 mutagenesis were due to the induction of hepatic enzyme activities rather than to increased rates of uptake of the carcinogen from the gut-lumen.


Distribution of neuropeptides in the limbic system of the rat: the hippocampus.
The distribution of several neuropeptides (vasoactive intestinal polypeptide, cholecystokinin octapeptide, substance P, neurotensin, methionine-enkephalin and somatostatin) in the hippocampal formation has been studied with immunocytochemical techniques. Numerous vasoactive intestinal polypeptide, cholecystokinin-octapeptide and somatostatin-positive cell bodies were found within the hippocampus and subiculum. Neurotensin-positive cell bodies were found within the subiculum, but no substance P or methionine-enkephalin-containing cell bodies were seen in either hippocampus proper or subiculum. Vasoactive intestinal polypeptide and cholecystokinin-octapeptide-positive cell bodies were predominantly located in the stratum moleculare and stratum radiatum of CA 1-2 regions and dentate gyrus, whilst somatostatin-containing cell bodies were found mainly in the stratum oriens. Nerve fibres containing each of the six peptides were found within the hippocampus. Large numbers of vasoactive intestinal polypeptide, cholecystokinin-octapeptide and somatostatin fibres innervated the pyramidal and granule cell layers, with smaller numbers in the stratum radiatum and fewer still in the stratum moleculare and stratum oriens. Other than a moderately dense neurotensin-positive fibre plexus in the dorsal subiculum, fewer neurotensin, substance P and methionine-enkephalin fibres were present. However, when present, these three peptides had a distribution restricted to a region close to the pyramidal layer in the CA 2/3 region and to the stratum moleculare of the CA 1 region. Peptide-containing fibres were identified entering or leaving the hippocampus in three ways, via (i) the fornix (all six peptides), (ii) the dorsal subiculum (neurotensin-positive fibres projecting to the cingulate cortex: somatostatin, vasoactive intestinal polypeptide, and cholecystokinin-octapeptide present in fibres running between the dorsal subiculum and occipito-parietal cortex) and (iii) the ventral subiculum (vasoactive intestinal polypeptide, cholecystokinin-octapeptide and somatostatin in fibres running between entorhinal cortex and hippocampus, and all six peptides in fibres crossing the amygdalo-hippocampal border). These findings indicate a major distinction between those peptides (vasoactive intestinal polypeptide, cholecystokinin-octapeptide, somatostatin, neurotensin) which are found in cell bodies intrinsic to the hippocampal formation and those peptides (substance P, methionine-enkephalin) which are found only in hippocampal afferents.(ABSTRACT TRUNCATED AT 400 WORDS)


What motivates German consumers to reduce their meat consumption? Identifying relevant beliefs.
High levels of meat consumption cause problems related to public health, the environment, and animal welfare. Therefore, it is crucial to improve our understanding of the drivers and barriers involved in reducing meat consumption. Using the Theory of Planned Behavior (TPB), we examined to what extent attitude, subjective norm, and perceived behavioral control (PBC) affect intention and willingness to reduce meat consumption. In line with the TPB and going beyond existing literature, we also explored which specific beliefs determine these three constructs. In 2021, we conducted an online survey with a sample representative of the German population (N = 1093). Hierarchical regression models revealed that after controlling for sociodemographic characteristics, the TPB constructs explained 55% of the variance in intention and 61% of the variance in willingness. Importantly, each of the three TPB constructs affected intention and willingness to reduce meat consumption, with attitude having the largest impact. Habit strength and past behavior in addition to the TPB constructs did not improve prediction. Multiple linear regression models showed that attitude was determined by the beliefs that reducing meat consumption leads to a healthier diet, a reduced risk of developing certain diseases, a more natural diet, and the feeling of missing meat. In contrast, environmental and animal welfare concerns showed no significant effect on attitude. Both family and friends contributed to the perceived social pressure. The beliefs of being able to prepare meat-free meals, having enough time to spend on one's diet, and being able to easily purchase meat substitutes led to higher PBC. Based on these findings, we provide recommendations for intervention strategies and derive implications for future research.


In vitro analysis of lymphocytes: markers and functions.
Current dermatologic literature is becoming replete with articles elucidating current concepts in the pathophysiology of lymphocytic diseases. Much of this knowledge emanates from the increasingly sophisticated and complex methods of identifying lymphocytes. No longer does it suffice to know that B lymphocytes or T lymphocytes are present, but rather the key information involves knowing what subsets of these cells are present and/or their functional status. The reader attempting to assimilate all this information is thus confronted with an overwhelming, as well as frequently changing, array of analytic methods. This paper is presented as a review of thinking, principles, and methods employed in research on lymphocytic disease.


Highly stretchable, fast self-healing nanocellulose hydrogel combining borate ester bonds and acylhydrazone bonds.
Self-healing hydrogels have received considerable attention as a promising material for flexible electronic devices given their mechanical durability and structurally tunable properties. In this study, a highly stretchable self-healing hydrogel with dual cross-linking network was developed via borate ester bonds generated by polyvinyl alcohol and borax, and acylhydrazone bonds formed by aldehyde nanocellulose with adipic acid dihydrazide-modified alginate. Compared with the single network hydrogel composed of polyvinyl alcohol and borax, the introduction of dynamic acylhydrazone bonds greatly increases the flexibility of the hydrogel. The elongation rate increased from 480 % to approximately 1440 %, and the self-healing efficiency increased from 84.6 % to 92.7 % after healing for 60 min at ambient temperature without any stimulus. Moreover, the longer the self-healing time, the more evident the self-healing effect of the acylhydrazone bonds. In addition, electrical measurements confirmed a wide working strain range (ca.1000 %), durability, and reliability. Once assembled as a strain sensor, the hydrogel is able to monitor both large and subtle human motions. Besides, this hydrogel exhibited desirable biocompatibility, as demonstrated by in vitro cytotoxicity towards NIH 3T3 cells. These integrated properties make this nanocomposite hydrogel a promising candidate for future applications as green, flexible, and smart sensors.


Two-dimensional gel analysis of cyclic AMP effects in cultured S49 mouse lymphoma cells: protein modifications, inductions and repressions.
In this study, we used two-dimensional gel electrophoresis to analyze the responses of cultured S49 mouse lymphoma cells to incubation with analogs or inducers of cyclic AMP (cAMP). Putative phosphorylations were detected by charge alterations in proteins labeled with 35S--methionine and, in some cases, confirmed by labeling with 32P--phosphate. We assessed the relative stabilities of proteins affected by cAMP, the periods of susceptibility of proteins to cAMP-dependent modification and any cAMP-mediated changes in protein synthesis or stability. Five proteins (of about 650 resolved) behave as expected for "orthodox" substrates of a cAMP-activated protein kinase: both newly synthesized and prelabeled forms of these proteins are subject to modification; this modification involves an acidic charge shift of about one unit; and cAMP-mediated conversion of these proteins to their modified forms is virtually complete. The acidic forms of at least three of these proteins also exhibit cAMP-mediated increases in 32P--phosphate incorporation. Each protein comprised less than approximately 0.005% of cellular protein. Under basal conditions they appear to be phosphorylated to an extent about 20--30% of that found in fully stimulated cells. Nine proteins show cAMP-dependent changes in rates of synthesis with six inductions and three repressions. Most of these changes are of a magnitude of about 3 to 5 fold, and reach their maximal extents after about 4--5 hr of exposure to dibutyryl cAMP. In addition to the phosphorylations, inductions and repressions mentioned above, approximately 12 other reproducible cAMP-dependent changes in protein patterns are observed. Mutant cell lines deficient in catalytic activity of cAMP-dependent protein kinase show none of the changes in protein pattern attributable to cAMP.


The Genus Thionia Stål, 1859 (Hemiptera: Auchenorrhyncha: Issidae) in Colombia: Highlighting the Value of Entomological Collections.
Entomological collections represent a key source of information about the biological heritage of a country. However, the taxonomy and knowledge of many arthropods from megadiverse countries are underrepresented in these natural history collections as is the case with several planthoppers of the suborder Auchenorrhyncha. Issidae are fulgoromorphs distributed worldwide, except the poles and Greenland. Despite this ubiquity, Colombian planthoppers remain very poorly known and studied. Our objective was to provide the first consolidated records and distributional data for Colombian Issidae. We used reports of the representative genus Thionia deposited in biological collections in Colombia. In addition, we linked voucher specimen information and Olson's life zones showing an inter-Andean valley and Eastern Andean Cordillera distribution within Colombia. Our survey of Colombian biological collections revealed 55 individuals of the genus Thionia Stål, 1859 (53 adults, 2 immatures [nymphs]), which were collected by different methods; however, many of those records may be opportunistic. This genus (and its species) needs further study, with systematic and ecological revision, as is the case with other terrestrial Colombian hemipterans. Our consolidated records represent an advance to the knowledge of Issidae (and Thionia specifically) for the Neotropics and Colombia in particular, and a baseline for further study of distributional and biogeographic patterns of the suborder Auchenorrhyncha.


Symptomatic cavernous malformations of the brainstem: functional outcome after microsurgical resection.
Brainstem cavernous malformations are associated with a considerable risk of hemorrhage and subsequent morbidity. This study provides a detailed work-up of clinical and radiological outcome as well as identification of prognostic factors in patients who had suffered from symptomatic hemorrhages. Patients who had undergone surgery of symptomatic BSCMs were evaluated pre- and postoperatively both neurologically and neuroradiologically supplemented by telephone interviews. Additionally, patients were scored according to the Scandinavian Stroke Scale. Multiple uni- and multivariate analyses of possible clinical and radiological prognostic factors were conducted. The study population comprised 35 patients. Mean age at operation was 39.3 ± 13.0 years with microsurgical resection of a total of 37 different BSCMs between 2002 and 2011. Median clinical follow-up was 44.0 months (range 8-116 months). Postoperative MRI showed eventually complete resection of all BSCMs. Postoperative overall outcome revealed complete resolution of neurological symptoms for 5/35 patients, 14/35 improved and 9/35 remained unchanged. 7/35 suffered from a postoperative new and permanent neurological deficit, mostly affecting the facial nerve or hemipareses with mild impairment. Pre- and postoperative Scandinavian Stroke Scale scores were 11.0 ± 2.4 and 11.4 ± 2.2 (p = 0.55). None of the analyzed factors were found to significantly correlate with patients' clinical outcome. Complete resection of brainstem cavernous malformations can be achieved with an acceptable risk for long-term morbidity and surgery-related new deficits (~20 %). Neurological outcome is mainly determined within the first 6 months after surgery. Surgical treatment of brainstem cavernous malformations is recommended in symptomatic patients, in whom the lesion is accessible for surgery.


Prenatal wellbeing of mothers, their partners, and couples: a cross-sectional descriptive study.
Prenatal posttraumatic stress symptoms (PTSS), fear of childbirth (FOC), and depressive symptoms have been related to various negative effects during pregnancy, childbirth, and in the postnatal period. This study evaluates the prevalence of PTSS, FOC, depressive symptoms, and health-related quality of life (HRQoL) among pregnant women, their partners, and as couples. In a cohort of 3853 volunteered, unselected women at the mean of 17th weeks of pregnancy with 3020 partners, PTSS was evaluated by Impact of Event Scale (IES), FOC by Wijma Delivery Expectancy Questionnaire (W-DEQ-A), depressive symptoms by Edinburgh Postnatal Depression Scale (EPDS), and HRQoL by 15D instrument. PTSS (IES score ≥ 33) was identified among 20.2% of the women, 13.4% of the partners, and 3.4% of the couples. Altogether, 5.9% of the women, but only 0.3% of the partners, and 0.04% of the couples experienced symptoms suggestive of phobic FOC (W-DEQ A ≥ 100). Respectively, 7.6% of the women, 1.8% of the partners, and 0.4% of the couples reported depressive symptoms (EPDS ≥ 13). Nulliparous women and partners without previous children experienced FOC more often than those with previous children, but there was no difference in PTSS, depressive symptoms, or HRQoL. Women's mean 15D score was lower than partners' and that of age- and gender-standardized general population, while partners' mean 15D score was higher than that of age- and gender-standardized general population. Women whose partners reported PTSS, phobic FOC, or depressive symptoms, often had the same symptoms (22.3%, 14.3%, and 20.4%, respectively). PTSS were common in both women and partners, as well as in couples. FOC and depressive symptoms were common in women but uncommon in partners, thus they rarely occurred simultaneously in couples. However, special attention should be paid to a pregnant woman whose partner experiences any of these symptoms.


Associations between single nucleotide polymorphisms in thyroid hormone transporter genes (MCT8, MCT10 and OATP1C1) and circulating thyroid hormones.
Thyroid hormone (TH) action takes place intracellularly; therefore, transport across the plasma membrane by specific TH transporters, such as MCT8, MCT10 and OATP1C1, is necessary. Several single nucleotide polymorphisms (SNPs) in these genes were reported to be associated with TH concentrations; however, results have been inconsistent. Six SNPs in TH transporter genes (rs5937843-G/T and rs6647476-T/C in MCT8, rs14399-C/A in MCT10, rs10444412-C/T, rs10770704-C/T and rs36010656-C/A in OATP1C1) were genotyped in 2 cohorts; one consisting of 2416 men and women aged 35-55 yrs (Asklepios), and the other of 941 men aged 25-45 yrs (Siblos), using KASPar technology. TSH, FT3, FT4 and total T3 were determined by immuno-electrochemiluminescence in both cohorts; in the second cohort additional determination of total T4 by electrochemiluminescence and of reverse T3 (rT3) and thyroid binding globulin (TBG) by radioimmunoassays was performed. The first SNP in MCT8 (rs5937843-G/T) was inversely associated with FT4 concentrations in men but not in women. In Siblos, this SNP showed also negative associations with TT4 and rT3; in men from Asklepios a trend for positive association with TSH was observed. The second SNP in MCT8 (rs6647476-T/C) was negatively associated with FT3 levels in men from the Siblos and the Asklepios cohort. In addition, an inverse association with TT3 levels in men from the Siblos was observed. Rs36010656 (C/A) in OATP1C1 was not in Hardy-Weinberg equilibrium and therefore excluded from further analyses. The other 2 SNPs in OATP1C1 (rs10444412-C/T and rs10770704-C/T) and the SNP in MCT10 (rs14399-C/A) were not related to TH levels in either cohort. Two SNPs in MCT8 were related to circulating thyroid hormone levels in men but not in women: the rs5937843 polymorphism (G/T) was inversely associated with FT4 levels and the rs6647476 (T/C) polymorphism related negatively to circulating FT3.


A record of Anzyginabilli Fletcher & Larivière, 2009 (Hemiptera: Cicadellidae) from New Zealand.
The presence in New Zealand of the typhlocybine cicadellid Anzyginabilli Fletcher & Larivière, 2009 is confirmed, based on new material from Auckland. Rubus sp. is confirmed as a host plant.


Development and validation of a modified performance-oriented mobility assessment tool for assessing mobility in children with hypophosphatasia.
To modify the Performance-Oriented Mobility Assessment-Gait (POMA-G) subtest and validate this modified POMA-G (mPOMA-G) in children with hypophosphatasia (HPP), a rare metabolic disorder that can manifest with musculoskeletal symptoms that impair mobility and ambulation. Based on feedback from an expert panel, the POMA-G was modified by removing gait initiation/path assessments and expanding the rating scale for step length/continuity to capture aspects of observational gait analysis relevant to children with HPP. Three trained physical therapists used the mPOMA-G for video-based assessments of gait in 14 children with childhood HPP who participated in a clinical study of asfotase alfa or in a natural history study. Intraclass correlation coefficients (ICCs) were calculated to determine interrater and intrarater agreement. Concurrent validity was evaluated by correlations with other validated assessment tools. Across 192 observations from available videos, interrater and intrarater agreement of mPOMA-G scores was significant (ICCs: 0.76 for both; P< 0.001). mPOMA-G scores had strong concurrent validity with the Childhood Health Assessment Questionnaire, Pediatric Outcomes Data Collection Instrument Transfer and Mobility Scale, Sports and Physical Function subscale, and 6-Minute Walk Test (all P⩽ 0.0002). The mPOMA-G is a reliable and valid measure for detecting clinically significant impairments in children with HPP.


Overcoming the monster! Perceptions of physiotherapy students regarding the use of stroke master plots for building therapeutic relationships; a vignette study.
Narrative master plots identify illness stories which are recognisable within clinical settings. Responses to different master plots by physiotherapy students can lack empathy and need to be understood further. One narrative master plot for people with stroke that has not been well studied is called 'overcoming the monster'. Research is needed to understand physiotherapy students' reactions to this master plot. To examine the responses of physiotherapy students to three variations of the master plot called 'overcoming the monster' generated from patients who have had a stroke. A qualitative narrative vignette study was undertaken. A university in the West Midlands (England) was used to access physiotherapy students on the pre-registration programs. A purposive sample of students volunteered to complete a single vignette questionnaire at one time point. The vignette provided three unique examples of the master plot overcoming the monster as told by people with stroke. Students responded to each by asking specific questions that captured demographic information and questions that captured reactions to the different versions of the master plot. Categorical-content narrative analysis was undertaken. Thirty-two first year (BSc) students, thirty-nine first year (pre-registration) MSc students and nineteen third year (BSc) students participated in this study. Neither first year groups had undertaken any clinical placement hours. All third-year students had finished the required clinical placement hours for the physiotherapy course. Students consistently demonstrated empathy towards this master plot. Students often valued the variant of the story which illustrated how difficulties following stroke could be experienced as an 'adventure'. Students also valued and were motivated by the story variant that considered a family member as a source of motivation and encouragement. The story variant which focused on the shortcomings of the health care system was more often related to by the final year BSc students and MSc students. However, first year students, particularly BSc students, reported being more emotionally affected by the vignette. All variants of the master plot overcoming the monster appeared to generate empathetic responses. This is important because it highlights the value of students' understanding the patients' story and challenges or 'monsters' faced. Therapeutic relationships will benefit from training physiotherapy students on the importance of listening and exploring challenges people with stroke face.


HIV as an independent risk factor for incident lung cancer.
It is unclear whether the elevated rate of lung cancer among HIV-infected persons is due to biological effects of HIV, surveillance bias, or excess smoking. We compared the incidence of lung cancer between HIV-infected and demographically similar HIV-uninfected patients, accounting for smoking and stage of lung cancer at diagnosis. Data from the Veterans Aging Cohort Study Virtual Cohort were linked to data from the Veterans Affairs Central Cancer Registry, resulting in an analytic cohort of 37,294 HIV-infected patients and 75,750 uninfected patients. We calculated incidence rates of pathologically confirmed lung cancer by dividing numbers of cases by numbers of person-years at risk. We used Poisson regression to determine incidence rate ratios (IRRs), adjusting for age, sex, race/ethnicity, smoking prevalence, previous bacterial pneumonia, and chronic obstructive pulmonary disease. The incidence rate of lung cancer in HIV-infected patients was 204 cases per 100,000 person-years [95% confidence interval (CI) 167-249] and among uninfected patients was 119 cases per 100,000 person-years (95% CI 110-129). The IRR of lung cancer associated with HIV infection remained significant after multivariable adjustment (IRR 1.7; 95% CI 1.5-1.9). Lung cancer stage at presentation did not differ between HIV-infected and uninfected patients. In our cohort of demographically similar HIV-infected and uninfected patients, HIV infection was an independent risk factor for lung cancer after controlling for potential confounders including smoking. The similar stage distribution between the two groups indicated that surveillance bias was an unlikely explanation for this finding.


Surface trueness and precision of interim restorations fabricated by digital light processing and CAD-CAM milling systems.
The development of digital dental technologies has enabled clinicians to use additive and subtractive manufacturing techniques to fabricate interim restorations. However, knowledge of the trueness and precision of such restorations fabricated using digital light processing (DLP) and computer-aided design and computer-aided manufacturing (CAD-CAM) methods is limited. The purpose of this in vitro study was to assess and compare the accuracy of interim crowns fabricated using DLP and CAD-CAM methods. A typodont mandibular first molar was prepared for a ceramic crown, and a digital scan (Medit T500) was obtained to design interim crowns by using the CAD software program. The CAD data were designated as the reference data. A total of 20 crowns were fabricated by DLP and CAD-CAM technology. The fabricated interim crowns were further scanned using a laboratory scanner and were superimposed with the CAD data by using a 3-dimensional (3D) point cloud assessing software program (CloudCompare) for the evaluation of trueness and precision. Root mean square values (RMS) were obtained for the evaluation of discrepancies. The Student t test was used to compare data as the Shapiro-Wilk test confirmed the normal distribution. RMS values for the trueness values of the external and intaglio surfaces of the 3D printed and milled interim crown displayed no statistically significant differences (P>.05). Precision for the external surface reported significance (P<.05), whereas that for the intaglio surface reported no significance (P>.05). The accuracy of interim crowns fabricated by using DLP was comparable with that of milled crowns. Both manufacturing systems produced a true reproduction of the CAD. As for precision, the external surface of the DLP interim crown was statistically different from that of the milled group as it relates to the CAD.


Epileptic prodromes: are they nonconvulsive status epilepticus?
The aim of this study was to assess how frequently prodromes occur in an adult patient group from a tertiary referral epilepsy centre and to investigate the EEG changes during the prodromes. 578 consecutive patients were interviewed on subjective phenomena, experiences heralding the seizures, for at least 30min before the start of the seizure. EEGs were recorded during the prodromes. Ten out of 490 included patients had prodromes (2%). We were able to record EEG during prodromes in 6 patients. Three patients had EEG changes corresponding to nonconvulsive status epilepticus. Three patients had unrevealing EEG recordings during prodromes. Our results suggest that at least in a part of the patients, the prodromes are actually ictal phenomena, and should be treated as nonconvulsive status epilepticus.


Optimal pacemaker sensing with respect to amplitude and slew rate of intracardiac electrograms: theoretical analysis by computer simulation.
The optimal amplitude and slew rate of intracardiac electrograms for pacemaker sensing were examined on a theoretical basis by computer simulation. The simulation was based on the concept that it is the voltage at the position of the pacing electrode in an electrical field of a moving electrical dipole. By changing the distance between the electrode and the myocardium and the moving velocity of the electrical dipole, simulated ECGs with arbitrary amplitudes and slew rates were generated by the computer and fed to a bandpass filter. This filter was equivalent to those assembled in some models of permanent pacemakers and had a center pass-band frequency of 50 Hz and a Q of 1.0. The outputs of the filter were measured. The results showed that, for pacemakers sensing, simulated intracardiac electrograms with high amplitude should have high slew rates and those with low amplitudes should have low slew rates, although the absolute values depend on the characteristics of the bandpass filter and the sensing threshold of the pacemaker.


Perceptual learning in visual search: fast, enduring, but non-specific.
Visual search has been suggested as a tool for isolating visual primitives. Elementary "features" were proposed to involve parallel search, while serial search is necessary for items without a "feature" status, or, in some cases, for conjunctions of "features". In this study, we investigated the role of practice in visual search tasks. We found that, under some circumstances, initially serial tasks can become parallel after a few hundred trials. Learning in visual search is far less specific than learning of visual discriminations and hyperacuity, suggesting that it takes place at another level in the central visual pathway, involving different neural circuits.


Review on Deep Learning Methodologies in Medical Image Restoration and Segmentation.
This paper comprehensively reviews two major image processing tasks, such as restoration and segmentation in the medical field, from a deep learning perspective. These processes are essential because restoration removes noise and segmentation extracts the specific region of interest of an image, both of which are necessary for accurate diagnosis and therapy. This paper mainly focuses on deep learning techniques. It plays a prominent role over other conventional techniques in handling a large number of datasets in the medical field and provides accurate results. This paper reviewed the application of different convolutional neural network architectures in the restoration and segmentation processes. Based on the results in the case of image restoration, TLR-CNN and Stat-CNN are promising in achieving better PSNR, noise suppression, artifact suppression and improving the overall image quality. For the segmentation process, LCP net achieves the Dice score of 98.12% and sensitivity of 98.95% in the cell contour segmentation; the 3D FCNN model is found to be the best method for the segmentation of brain tumors. This review shows that deep learning methodologies can be a better alternative for medical image restoration and segmentation tasks, as data size is an important concern today.


Single and Dual Vector Gene Therapy with AAV9-PHP.B Rescues Hearing in Tmc1 Mutant Mice.
AAV-mediated gene therapy is a promising approach for treating genetic hearing loss. Replacement or editing of the Tmc1 gene, encoding hair cell mechanosensory ion channels, is effective for hearing restoration in mice with some limitations. Efficient rescue of outer hair cell function and lack of hearing recovery with later-stage treatment remain issues to be solved. Exogenous genes delivered with the adeno-associated virus (AAV)9-PHP.B capsid via the utricle transduce both inner and outer hair cells of the mouse cochlea with high efficacy. Here, we demonstrate that AAV9-PHP.B gene therapy can promote hair cell survival and successfully rescues hearing in three distinct mouse models of hearing loss. Tmc1 replacement with AAV9-PHP.B in a Tmc1 knockout mouse rescues hearing and promotes hair cell survival with equal efficacy in inner and outer hair cells. The same treatment in a recessive Tmc1 hearing-loss model, Baringo, partially recovers hearing even with later-stage treatment. Finally, dual delivery of Streptococcus pyogenes Cas9 (SpCas9) and guide RNA (gRNA) in separate AAV9-PHP.B vectors selectively disrupts a dominant Tmc1 allele and preserves hearing in Beethoven mice, a model of dominant, progressive hearing loss. Tmc1-targeted gene therapies using single or dual AAV9-PHP.B vectors offer potent and versatile approaches for treating dominant and recessive deafness.


Complete nucleotide sequences of seven eubacterial genes coding for the elongation factor Tu: functional, structural and phylogenetic evaluations.
The nucleotide sequences of cloned genes coding for the elongation factor Tu of seven eubacteria have been determined. These genes were from Anacystis nidulans, Bacillus subtilis, Bacteroides fragilis, "Deinonema" spec., Pseudomonas cepacia, Shewanella putrefaciens and Streptococcus oralis. The primary structures of the genes were compared to the available sequences of prokaryotic elongation factors Tu and eukaryotic elongation factors 1 alpha. A conservation profile was determined for homologous amino acid residues. Sites of known or putative functions are usually located at highly conserved positions or within highly conserved sequence stretches. The aligned 24 amino acid sequences were used as basis for a phylogenetic analysis. The phylogenetic tree corroborates the kingdom as well as phylum concept deduced from 16S rRNA data.


Non-adherent culture induces paclitaxel resistance in H460 lung cancer cells via ERK-mediated up-regulation of βIVa-tubulin.
Circulating tumor cells (CTCs) are metastasizing epithelial cancer cells that adapt to survive when floating in bloodstream during metastasis. This condition can be mimicked in vitro by using non-adherent cell culture. The chemosensitivity of CTCs appears to correlate with the response of metastatic cancer patients to therapy, but chemoresistance is also frequently observed in advanced stage cancer patients, who have never previously received chemotherapy. We hypothesize that adaptation of epithelial cancer cells to become floating CTCs could lead to development of chemoresistance. Here, we explore whether chemoresistance is induced in epithelial cancer cells when cultured under non-adherent conditions. Increased paclitaxel-specific resistance was observed in floating cells compared to attached cells in H460, MCF-7, and HepG2 human cancer cell lines, by 15.6-, 3.9-, and 2.6-fold increases in IC50 values, respectively. qRT-PCR analysis showed that a paclitaxel-resistant β-tubulin isotype, βIVa-tubulin, was the most up-regulated gene compared with other β-tubulin isotypes in H460 floating cells, concomitant with elevated ERK activation. ERK inhibitor treatment could attenuate the up-regulation of βIVa-tubulin, and decreased the paclitaxel resistance of H460 floating cells, even though other β-tubulin isotypes were up-regulated when the ERK activation was blocked. In conclusion, we show induction of paclitaxel resistance in epithelial cancer cells, when floating in non-adherent culture, and this might occur with CTCs of cancer patients.


Factor VIII inhibitor bypassing activity (FEIBA) - addressing safety issues.
Bypassing therapy is usually necessary to control or prevent bleeding episodes in patients with haemophilia A or B and high-titre inhibitors. Factor VIII inhibitor bypassing activity (FEIBA) has a long history of successful use in the acute, surgical and prophylactic treatment settings, but safety concerns have made some reluctant to administer this bypassing agent. A review of the literature and clinical trial data show that FEIBA has a low prevalence of thrombosis, a low prevalence of anamnesis that does not impact haemostatic efficacy and an excellent record of pathogen safety and clinical tolerability.


Molecular cloning of cDNA for rat and human carbamyl phosphate synthetase I.
Recombinant plasmids with inserts complementary to the mRNA for carbamyl phosphate synthetase I were identified from a rat liver cDNA library by hybrid-selected mRNA translation. Four clones, the largest being 3100 base pairs, were identified for the rat liver enzyme. Using the rat liver cDNA as a probe, two homologous recombinant plasmids of approximately 1200 base pairs in length were isolated from a human liver cDNA library. Northern blot analysis of rat liver mRNA and baboon liver mRNA revealed the presence of a 5000-base mRNA homologous to both rat and human cDNA probes. No homologous mRNA was observed in mRNA from rat heart or rat kidney as is consistent with the known tissue distribution of this enzyme. The induction of carbamyl phosphate synthetase and argininosuccinate synthetase mRNA during the fetal and postnatal development of the rat was studied by dot blot analysis of isolated mRNA. The mRNA for both enzymes appeared between 17 and 19 days of fetal life and reached approximately 40% of adult levels during this period. This initial increase was followed by a rapid decline just prior to birth. The mRNA levels slowly increased during postnatal life, not reaching adult levels until after the 20th day of neonatal life. Using the human cDNA clones, the human carbamyl phosphate synthetase gene was mapped to chromosome 2 utilizing a panel of Chinese hamster X human somatic cell hybrids. Analysis of one hybrid with a human-Chinese hamster translocation provided a provisional assignment to the short arm of chromosome 2.


Clinical and molecular diagnosis of Bardet-Biedl syndrome (BBS).
Bardet-Biedl syndrome (BBS) is a rare genetic disease of the group of ciliopathies, a group of pathologies characterized mainly by defects in the structure and/or function of primary cilia. The main features of this ciliopathy are retinal dystrophy, obesity, polydactyly, urogenital and renal abnormalities, and cognitive impairment, commonly accompanied by various secondary features, making clear the extensive clinical heterogeneity associated with this syndrome, which, together with the frequent overlapping phenotype with other ciliopathies, greatly complicates its diagnosis. Patients are mainly detected by their pediatrician at quite early ages, usually between 2 and 6years. The pediatrician, given the main symptoms they present, usually refers patients to a specialist. Personalized medicine brought diagnosis closer to many patients who lacked it. It usually presents an autosomal recessive mode of inheritance, but in recent years several authors have proposed more complex inheritance models to explain the frequent inter- and intra-familial clinical variability. The main molecular techniques used for diagnosis are gene panels, the clinical exome and, in certain cases, the patient's complete genome. Although numerous studies have contributed to defining the role of the different BBS genes and designing various strategies for the molecular diagnosis of BBS, as well as delving into the functions performed by these proteins, these advances have not been sufficient to develop a complete treatment for this syndrome. and to be able to offer patients some therapeutic options.


Treatment of pigmented villonodular synovitis with yttrium-90: changes in immunologic features, Tc-99m uptake measurements, and MR imaging of one case.
Pigmented villonodular synovitis (PVNS) is an uncommon proliferative disease of synovium. We report a 35-year-old male with diffuse form of PVNS of left knee, treated with intraarticular injection of 5 mCi of yttrium-90 (Y-90) silicate colloid consisting of two doses with a 3-month interval between them. During follow-up, the affected knee showed clinical improvement and was accompanied by a decrease of the levels of soluble interleukin-2 receptor in sera and synovial fluids (SF). When compared to osteoarthritis subjects, SF lymphocyte subsets of this case before Y-90 therapy showed a lower CD4:CD8 cell ratio and absence of suppressor inducer cells (CD4+ 2H4+). The Tc-99m pertechnetate knee uptake indexes correlated well with clinical improvement. Serial magnetic resonance imaging revealed significant change one year after Y-90 therapy. The findings of immunological assessment suggested that immunoregulatory dysfunction may be related to the pathogenesis of PVNS.


Improving the screening of potato breeding lines for specific nutritional traits using portable mid-infrared spectroscopy and multivariate analysis.
Efficient selection of potato varieties with enhanced nutritional quality requires simple, accurate and cost effective assays to obtain tuber chemical composition information. In this study, 75 Andean native potato samples from 7 Solanum species with different colors were characterized and quantified for their anthocyanin, phenolics and sugar content using traditional reference methods. IR (infrared) spectra of potato extracts were collected using a portable infrared system and partial least squares regression (PLSR) calibration models were developed. These models were validated using both full cross-validation and an independent sample set giving strong linear correlation coefficients of prediction (rPred)>0.91 and standard error of prediction (SEP) of 24mg/100g phenolics, 7mg/100g monomeric anthocyanins, 0.1g/100g reducing sugars and 0.12g/100g sucrose. Overall, portable infrared system with PLSR showed great potential to facilitate potato breeding and certain aspects of crop management, material selection for potato processing and related research by providing alternative prediction models.


Mediation of synergistic chemotherapy and gene therapy via nanoparticles based on chitosan and ionic polysaccharides.
Nanoparticles (NPs)-based on various ionic polysaccharides, including chitosan, hyaluronic acid, and alginate have been frequently summarized for controlled release applications, however, most of the published reviews, to our knowledge, focused on the delivery of a single therapeutic agent. A comprehensive summarization of the co-delivery of multiple therapeutic agents by the ionic polysaccharides-based NPs, especially on the optimization of the polysaccharide structure for overcoming various extracellular and intracellular barriers toward maximized synergistic effects, to our knowledge, has been rarely explored so far. For this purpose, the strategies used for overcoming various extracellular and intracellular barriers in vivo were introduced first to provide guidance for the rational design of ionic polysaccharides-based NPs with desired features, including long-term circulation, enhanced cellular internalization, controllable drug/gene release, endosomal escape and improved nucleus localization. Next, four preparation strategies were summarized including three physical methods of polyelectrolyte complexation, ionic crosslinking, and self-assembly and a chemical conjugation approach. The challenges and future trends of this rapidly developing field were finally discussed in the concluding remarks. The important guidelines on the rational design of ionic polysaccharides-based NPs for maximized synergistic efficiency drawn in this review will promote the future generation and clinical translation of polysaccharides-based NPs for cancer therapy.


Cyclosporin A promotes translational silencing of autocrine interleukin-3 via ribosome-associated deadenylation.
Translation is regulated predominantly by an interplay between cis elements at the 3' and 5' ends of mRNAs and trans-acting proteins. Cyclosporin A (CsA), a calcineurin antagonist and blocker of interleukin-2 (IL-2) transcription in T cells, was found to inhibit translation of IL-3 mRNA in autocrine mast cell tumor lines. The mechanism involved ribosome-associated poly(A) shortening and required an intact AU-rich element in the 3' untranslated region. FK506, another calcineurin inhibitor, shared the effect. The translational inhibition by CsA was specific to oncogenically induced lymphokines IL-3 and IL-4 but not to IL-6, c-jun, and c-myc, which are expressed in the nonmalignant precursor cells. Furthermore, no translational down-regulation of the mRNA was observed in IL-3-transfected precursor cells. These data suggest that translational silencing is associated with the tumor phenotype.


Carbohydrate transition state mimics: synthesis of imidazolo-pyrrolidinoses as potential nectrisine surrogates.
The syntheses of four glyco-imidazoles, which are pentose-derivatives belonging to the D-series, as well as the syntheses of their L-enantiomers, are reported. Starting from the known linear xylo, lyxo, arabino, and ribo imidazolo-pentoses in both the L- and the D-series, intramolecular Walden inversion led to the corresponding arabino, ribo, xylo, and lyxo pyrrolidinopentoses in the D- and the L-series, respectively, protection and deprotection steps being unavoidable prerequisites. The structures and configurations of all eight pyrrolidinopentoses were determined unambiguously, by a combination of 1H/13C NMR spectroscopy, circular dichroism and [alpha](D) values, in conjunction with single-crystal X-ray diffraction analysis of the L-xylo stereoisomer. Examination of the inhibitory properties of these imidazolo-pyrrolidinoses against six commonly encountered glycosidases led to the conclusion that by and large the L-stereoisomers are inactive, whereas three out the four D-stereoisomers proved to be poor to moderate inhibitors. It appears therefore that the most basic N(1) atom is not located in an optimal topology to be protonated easily inside the enzyme's active site.


Petroleum Coke Combustion in Fixed Fluidized Bed Mode in the Presence of Metal Catalysts.
Petroleum coke is one of the waste products generated in the oil refining industry that can be used as fuel in energetics. However, the low volatile matter content and graphite-like structure of petroleum coke are the reasons for its high ignition temperature and combustion complexity. In this research, petroleum coke combustion and oxidation kinetics in the presence of metal catalysts were investigated. To evaluate the effect of the catalyst on the ignition temperature and the apparent activation energy, a new approach of a "fixed fluidized bed" was proposed. In this mode, petroleum coke particles spaced from each other by inert quartz powder kind of "freeze" in the porous layer. This regime allows us to determine the ignition temperature of petroleum coke particles in the static mode by differential thermography and calculate the activation energy by gas analysis. Organic and inorganic salts of copper, iron, and cerium are used as catalysts for petroleum coke combustion. A series of experiments were carried out in the porous media thermo-effect cell (PMTEC) and on a thermogravimetric (TG) analyzer. The kinetics of the combustion processes was calculated by Kissinger-Akahira-Sunose and Ozawa-Flynn-Wall methods. The results obtained in the "fixed bed" mode showed that the ignition temperature and the average apparent activation energy significantly decreased in the presence of CuCl2 and FeCl3. The results obtained by the new approach were compared with the results of the thermogravimetric analysis.


Subcutaneous immunoglobulin 16.5% for the treatment of pediatric patients with primary antibody immunodeficiency.
Human immunoglobulin (IG) administered intravenously (IVIG) or subcutaneously (SCIG) is used to prevent infections in patients with primary immunodeficiency diseases (PIDDs) such as primary antibody immunodeficiencies. This review provides an overview of PIDD with a focus on SCIG treatment, including the properties and clinical trial results of a new SCIG 16.5% (Cutaquig, Octapharma) in pediatric patients. We also discuss the various benefits of SCIG including stable serum immunoglobulin G levels, high tolerability with fewer systemic side effects, and the flexibility of self-administration. Individualized treatment for PIDD in children is necessary given the different factors that affect administration of SCIG. Variables such as the dose, dosing interval, administration sites, and ancillary equipment can be adjusted to impact the long-term satisfaction with SCIG administration in pediatric patients. The successful work that has been conducted by both professional and patient organizations to increase awareness of PIDD, especially in pediatric patients, is substantial and ongoing. The importance of early diagnosis and treatment in the pediatric patient population cannot be overstated. The safety, efficacy, and tolerability of SCIG 16.5% have been demonstrated in pediatric patients with PIDDs providing an additional therapeutic option in this vulnerable population.


AML1B transcriptional repressor function is impaired by the Flt3-internal tandem duplication.
Fms-like tyrosine kinase 3 (Flt3) is a type III receptor tyrosine kinase. The internal tandem duplication (ITD) of the juxtamembrane region of this receptor is the most prevalent mutation in acute myeloid leukaemia (AML). The silencing mediator of retinoic and thyroid hormone receptors (SMRT) co-repressor recruits histone deacetylases (HDAC) and mediates transcriptional repression by interacting with various transcription factors. We recently reported that Flt3-ITD interferes with the transcriptional and biological action of promyelocytic leukaemia zinc finger transcriptional repressor by dissociating it from SMRT. In this study, we aimed to clarify whether the repressional activity of other well-known oncoproteins, such as AML1/Runx1 (AML1), is also affected by Flt3-ITD. We verified that the repression activity of AML1B, the isoform of AML1, is dependent on HDAC activity by using HDAC inbitor trichostatin A in GAL4 reporter assays. Mammalian two-hybrid assays demonstrated that this protein interacts with SMRT. Furthermore, this AML1B-SMRT interaction was disrupted by the overexpression of Flt3-ITD, leading to the reduction of AML1B repression activity. Additionally, we showed AML1B repression target, p21 (WAF1/CIP1), was aberrantly expressed in Flt3-ITD stably expressed BaF3 cells. Taken together, Flt3-ITD disrupts transcriptional repressor functions resulting in aberrant gene regulation in leukaemic cells.


Poisoning by abnormally high blood phenobarbital concentration treated with extracorporeal therapy.
Phenobarbital poisoning, which may cause circulatory collapse as well as respiratory arrest in severe cases, has one of the highest mortality rates among acute drug poisonings. A 58-year-old man arrived at the emergency room in a deep coma (Glasgow Coma Scale E1V1M1) after taking an unknown dose of phenobarbital which had been prescribed for his cat's seizures. Venous blood gas analysis revealed hypercapnia (PvCO2: 113.0 mmHg) and a blood phenobarbital concentration of 197.3 μg/mL. Shortly after his arrival, respiratory arrest and circulatory collapse occurred. Mechanical ventilation after intubation, intravenous noradrenaline infusion, and multiple-dose activated charcoal through a nasogastric tube was started. Six hours after arrival, blood phenobarbital concentration was abnormally elevated to 356.8 μg/mL with circulatory collapse requiring an increased dose of intravenous noradrenaline infusion (up to 0.13 μg/kg/min). Continuous renal replacement therapy including high flow continuous hemodialysis was performed until hospital day 5, during which blood phenobarbital concentration decreased to 96.2 μg/mL on hospital day 4, resulting in a sufficient resumption of spontaneous breathing and full improvement of circulatory collapse. A search of the literature revealed that the peak phenobarbital concentration in the present case exceeded those of fatal cases, as well as those of survivors of acute phenobarbital poisoning. However, the patient was successfully treated with continuous renal replacement therapy. Among modalities of extracorporeal treatment, continuous renal replacement therapy could be considered if a patient's circulation is unstable.


Responsive robotic prey reveal how predators adapt to predictability in escape tactics.
To increase their chances of survival, prey often behave unpredictably when escaping from predators. However, the response of predators to, and hence the effectiveness of, such tactics is unknown. We programmed interactive prey to flee from an approaching fish predator (the blue acara, Andinoacara pulcher) using real-time computer vision and two-wheeled robots that controlled the prey's movements via magnets. This allowed us to manipulate the prey's initial escape direction and how predictable it was between successive trials with the same individual predator. When repeatedly exposed to predictable prey, the predators adjusted their behavior before the prey even began to escape: prey programmed to escape directly away were approached more rapidly than prey escaping at an acute angle. These faster approach speeds compensated for a longer time needed to capture such prey during the subsequent pursuit phase. By contrast, when attacking unpredictable prey, the predators adopted intermediate approach speeds and were not sensitive to the prey's escape angle but instead showed greater acceleration during the pursuit. Collectively, these behavioral responses resulted in the prey's predictability having no net effect on the time taken to capture prey, suggesting that unpredictable escape behavior may be advantageous to prey in fewer circumstances than originally thought. Rather than minimizing capture times, the predators in our study appear to instead adjust their behavior to maintain an adequate level of performance during prey capture.


Incidental findings on cone beam computed tomography scans in cleft lip and palate patients.
Cone beam computed tomography (CBCT) is frequently used in treatment planning for alveolar bone grafting (ABG) and orthognathic surgery in patients with cleft lip and palate (CLP). CBCT images may depict coincident findings. The aim of this study was to assess the prevalence of incidental findings on CBCT scans in CLP patients. Initial CBCTs taken from consecutive patients (n = 187; mean age 11.7 years, range 6.9-45) with a non-syndromic orofacial cleft from January 2006 until June 2012 were systematically evaluated. Twenty-eight patients (mean age 19.3 years, range 13.2-30.9) had been subjected to ABG before their first CBCT was taken; 61 patients had a CBCT before and after ABG. Sinuses, nasopharynx, oropharynx, throat, skull, vertebrae, temporomandibular joint (TMJ), maxilla and mandible were checked for incidental findings. On 95.1 % of the CBCTs, incidental findings were found. The most prevalent were airway/sinus findings (56.1 %), followed by dental problems, e.g. missing teeth (52 %), nasal septum deviation (34 %), middle ear and mastoid opacification, suggestive for otitis media (10 %) and (chronic) mastoiditis (9 %), abnormal TMJ anatomy (4.9 %) and abnormal vertebral anatomy (1.6 %). In the 28 patients whose first CBCT was taken at least 2 years after ABG, bone was still present in the reconstructed cleft area except in 2 out of 12 patients with a bilateral CLP. The ABG donor site (all bone grafts were taken from the chin area) was still recognizable in over 50 % of the patients. Based on the CBCT findings, 10 % of the patients were referred for further diagnosis and 9 % for further treatment related to dental problems. Incidental findings are common on CBCTs. Compared with the literature, CLP patients have more dental, nasal and ear problems. Thus, whenever a CBCT is available, this scan should be reviewed by all specialists in the CLP team focusing on their specific background knowledge concerning symptoms and treatment of these patients. The high number of findings indicates that CBCT imaging is a helpful tool in the treatment of CLP patients not only related to alveolar bone grafting and orthognathic surgery but it also provides diagnostic information for almost all specialties involved in CLP treatment.


Damage of Trypanosoma cruzi deoxyribonucleic acid by nitroheterocyclic drugs.
Kinetoplast DNA (kDNA) from Trypanosoma cruzi epimastigotes pretreated with the trypanocidal drugs nifurtimox (10 or 100 microM) or benznidazole (38 or 380 microM) showed an increased number of strand-breaks, as revealed by (a) trapping of alkali-denatured kDNA by nitrocellulose filters and (b) electrophoresis in an alkaline 2% agarose gel. Similar damage was observed in nuclear DNA (nDNA), as detected by centrifugation in an alkaline-sucrose gradient. DNA damage was reversible since reincubation in fresh medium for 24 hr restored filtration and electrophoretic and sedimentation patterns to normal.


The myoglobin of an echidna (Tachyglossus aculeatus aculeatus).
The skeletal myoglobin of the echidna was composed of 153 residues. Its primary amino acid sequence has been determined and compared with that of platypus. Nine differences were found. The number of differences from known marsupial and eutherian myoglobin is about twice as much.


Hyperglycemia Aggravates the Cerebral Ischemia Injury via Protein O-GlcNAcylation.
At least one-third of Alzheimer's disease (AD) patients have cerebrovascular abnormalities, micro- and macro-infarctions, and ischemic white matter alterations. Stroke prognosis impacts AD development due to vascular disease. Hyperglycemia can readily produce vascular lesions and atherosclerosis, increasing the risk of cerebral ischemia. Our previous research has demonstrated that protein O-GlcNAcylation, a dynamic and reversible post-translational modification, provides protection against ischemic stroke. However, the role of O-GlcNAcylation in the exacerbation of cerebral ischemia injury due to hyperglycemia remains to be elucidated. In this study, we explored the role and underlying mechanism of protein O-GlcNAcylation in the exacerbation of cerebral ischemia injury caused by hyperglycemia. High glucose-cultured brain microvascular endothelial (bEnd3) cells were injured by oxygen-glucose deprivation. Cell viability was used as the assay result. Stroke outcomes and hemorrhagic transformation incidence were assessed in mice after middle cerebral artery occlusion under high glucose and streptozotocin-induced hyperglycemic conditions. Western blot estimated that O-GlcNAcylation influenced apoptosis levels in vitro and in vivo. In in vitro analyses showed that Thiamet-G induces upregulation of protein O-GlcNAcylation, which attenuates oxygen-glucose deprivation/R-induce injury in bEnd3 cells cultured under normal glucose conditions, while aggravated it under high glucose conditions. In in vivo analyses, Thiamet-G exacerbated cerebral ischemic injury and induced hemorrhagic transformation, accompanied by increased apoptosis. While blocking protein O-GlcNAcylation with 6-diazo-5-oxo-L-norleucine alleviated cerebral injury of ischemic stroke in different hyperglycemic mice. Overall, our study highlights the crucial role of O-GlcNAcylation in exacerbating cerebral ischemia injury under conditions of hyperglycemia. O-GlcNAcylation could potentially serve as a therapeutic target for ischemic stroke associated with AD.


Vaginal descent and pelvic floor symptoms in postmenopausal women: a longitudinal study.
To determine whether vaginal descent changes are associated with pelvic floor symptoms in postmenopausal women. This 4-year prospective study included 260 postmenopausal women with an intact uterus enrolled at one Women's Health Initiative (WHI) clinical trial site. All completed at least two annual pelvic organ prolapse quantification (POP-Q) examinations and symptom questionnaires (30 bladder, bowel, and prolapse symptom items, modified from the Pelvic Floor Distress Inventory). Symptoms were grouped, and group scores categorized into two or three evenly distributed levels. Year 4 data collection was incomplete because the overall WHI study halted. Generalized logistic linear models and generalized estimating equation methods were used to measure associations between vaginal descent and a symptom or symptom score, controlling for time, age, and body mass index (BMI). Mean age was 68+/-5 years, BMI 30+/-6 kg/m(2), and median parity 4. Ninety-five percent of women had POP-Q stages I-II prolapse. Increasing maximal vaginal descent was associated with "see/feel a bulge" and "sensation of protrusion or bulging," and with obstructive bladder, prolapse, and obstructive bowel scores. Increasing apical descent (POP-Q point C) was associated with "see/feel a bulge," increasing anterior descent (POP-Q point Ba) with bladder pain and obstructive bladder scores, and increasing posterior descent (POP-Q point Bp) with the bowel incontinence score. Although previous work showed that most pelvic floor symptoms correlated poorly with levels of early prolapse, longitudinal analysis suggests that vaginal descent progression over time is positively associated with various bladder, bowel, and prolapse symptoms in postmenopausal women with stages I-II prolapse. II.


Equinus contracture following Bryant's traction.
A case of a 14-year-old girl with both foot and hip sequelae secondary to the use of Bryant's traction at the age of 2 years, 8 months, is presented. It serves as a reminder of the dangers of Bryant's traction, which should be used with discretion, if at all.


Use of the Radiation Therapy Oncology Group recursive partitioning analysis classification system and predictors of survival in 19 women with brain metastases from ovarian carcinoma.
Brain metastases are an uncommon complication in women with primary ovarian carcinoma; thus, little is known about whether the Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) prognostic classification system is valid in this patient population. From September 1985 to June 2002, 19 patients with brain metastases resulting from primary ovarian carcinoma underwent treatment at the Cleveland Clinic Foundation. The medical records of these patients were retrospectively reviewed. At the time of data analysis, all 19 women had died. The median age at diagnosis of primary ovarian carcinoma and brain metastasis was 51 and 54 years of age, respectively. Fifteen patients presented with a Karnofsky performance status (KPS) of 70 or higher. Seven patients had a single brain lesion and 12 had multiple lesions. All RTOG RPA prognostic classes were represented, with median survivals of 24.7, 8.9, and 2.6 months for Classes I, II, and III, respectively (P = 0.31). Patients who underwent surgical resection survived longer than those who did not (33.7 vs. 7.4 mos). The presence of multiple lesions was adversely related to survival on multivariate analysis (P = 0.03). Primary control was an important predictor of survival on multivariate analysis as well (P = 0.01) and was achieved in 15 of the 19 women. This is the first study to support the prognostic usefulness of the RTOG RPA classification for ovarian carcinoma patients with metastasis to the brain. The number of metastatic intracranial lesions should be included when determining the prognosis.


Assessing the guest-accessible volume in MOFs using two-photon fluorescence microscopy.
The assessment of guest-accessible volume in MOFs can be reliably done by using two-photon confocal fluorescence microscopy (TPM) with a tool-box of dyes with a wide range of sizes. It would be applicable to any porous materials, whose single-crystal structures are not available, or non-crystalline materials.


Recent Growth and Expansion of Birch Shrubs Across a Low Arctic Landscape in Continental Canada: Are These Responses More a Consequence of the Severely Declining Caribou Herd than of Climate Warming?
The recent widespread expansion of deciduous shrubs across much of the Arctic has been largely attributed to climate warming. This study investigated decadal growth rates of dwarf birch (Betula glandulosa) across a low Arctic landscape in the continental interior of Canada. Detailed birch cover (100 m2 replicate plots) and individual shrub stature measurement datasets for five representative habitat-types were compared between 2006 and 2016, and evaluated in relation to environmental characteristics. Furthermore, dendrochronologically-based annual growth rates were assessed in relation to the 20-year climate record. Birch height, lateral dimensions, and patch groundcover all increased 20-25% relative to 2006 values, but these increases were similar among the habitat-types. Together, the limited evidence of recent warming at this site, the absence of significant habitat-type growth rate differences, and the lack of correlation between annual climate and stem secondary growth strongly suggest that climate change was not the principal cause. Instead, we propose that release from caribou impacts following the recent severe herd decline may explain the net shrub growth. Individual shrub growth rates were correlated with soil nutrient availability, but the latter was highly variable, suggesting that growth rates are primarily determined by fine-scale rather than habitat-scale spatial heterogeneity in nutrient supply. Together, our results demonstrate that birch growth has been enhanced across a variety of habitat-types in the Daring Lake landscape over the decade since 2006, and suggest that the recent severe caribou herd declines may be at least as significant as climate warming in driving birch shrub expansion in the Canadian central low Arctic.


Role for nanomaterial-autophagy interaction in neurodegenerative disease.
Nanotechnology is the control and manipulation of materials in the size range of 1-100 nm. Due to increasing research into the potential beneficial applications of nanotechnology, there is an urgent need for the study of possible health risks. Several researchers, including those in our laboratory, have demonstrated elevated levels of autophagic vacuoles upon exposure of cells to certain nanomaterials, including carbon- and metal-based nanoparticles. While this apparent increase in autophagic activity may be an appropriate cellular response toward nanomaterial clearance, often the interaction between nanomaterials and the autophagy pathway is disruptive, resulting in severe morphological changes and coincident cell death. Interestingly, epidemiological studies have identified an association between exposure to combustion-derived ambient particles (which are predominantly nanoscale) and neurological conditions with Alzheimer's and Parkinson's disease-like pathologies. Becuse impaired autophagy may play an important role in the pathogenesis of these and other diseases, it is intriguing to speculate about the plausible involvement of nanoscale particulates in this process. The interaction of nanomaterials with the autophagy pathway, and the potential negative consequences of resulting autophagy dysfunction, should be explored further.


Cognitive features and surgical outcome of patients with long-term epilepsy-associated tumors (LEATs) within the temporal lobe.
The objective of the study was to evaluate cognitive and epilepsy-related features in 166 surgically treated patients with epilepsy with long-term epilepsy-associated tumors (LEATs) located in the temporal lobe. Pre- and postsurgical cognitive as well as the one-year seizure outcome of adult patients with histopathologically confirmed LEATs (28 grade-I dysembryoplastic neuroepithelial tumors (DNET), 95 grade-I gangliogliomas (GG), 24 grade-I pilocytic astrocytomas (PA), 9 grade-II pleomorphic xanthoastrocytoma (PXA), 10 grade-II diffuse astrocytoma (DA)) who underwent epilepsy surgery in Bonn/Germany between 1988 and 2012 were evaluated. At baseline, tumor groups differed in regard to age at epilepsy onset and location within the temporal lobe. Postoperative seizure freedom was achieved most frequently (>77.8%) in DNET, GG, and DA, less often in PXA (62.5%) and the least in PA (56.5%). Preoperative memory was impaired in 67.1% of all patients, executive functions in 44.7%, and language in 45.5%. Patients with PA displayed the poorest cognitive performance. Individual significant memory decline that was observed in 27.1% of all patients was predicted by left-sided surgery, a mesial pathology, and extended hippocampal resection. Executive functions depended on antiepileptic drug (AED) load and remained stable (72.0%) or even improved (21.6%) after surgery. Language functions were unchanged in 89.5% of patients. Patients with LEATs in the temporal lobe frequently show cognitive impairments. Predictors for pre- and postoperative cognition mostly correspond to what is known for temporal lobe epilepsy and resections in general. However, different tumor types appear to be associated with different cognitive and seizure outcomes with astrocytoma as the least benefitted group.


The role of IL-7 in renal proximal tubule epithelial cells fibrosis.
Hyperglycemia is the most important risk factor in the progression of renal fibrosis in diabetic kidney. Based on previous studies, interleukin-7 (IL-7) may exert antifibrotic activities in pulmonary fibrosis model. However, the role of IL-7 in the pathogenesis of renal tubulointerstitial fibrosis remains unclear. Thus, we hereby elucidate the effects of IL-7 in cultured renal proximal tubular epithelial cells (designated as HK-2) treated under hyperglycemic condition. Cells were cultured in high glucose (27.5mM) for 2 days. Different concentration of IL-7 (10, 50, 100 or 200ng/ml) was added in the last 24h of culture. ELISA was used to evaluate the secreted protein such as fibronectin and TGF-β(1). Western blot was used to examine the EMT marker (including α-smooth muscle actin (α-SMA) and E-cadherin), signal transducer (including Smad Smad2/3 and Smad7) and EMT initiator (e.g. Snail). Immunofluorescence staining was used to assay the in situ expression of proteins (e.g. fibronectin and Snail). We found that IL-7 significantly attenuated high glucose-inhibited cellular growth and high glucose-induced fibrosis. More importantly, high glucose-induced up-regulation of fibronectin, TGF-β, TGF-β RII and pSmad2/3 was markedly inhibited by IL-7. On the contrary, high glucose-induced down-regulation of Smad7 was significantly reversed by IL-7 instead. IL-7 markedly inhibited high glucose-induced increase in α-SMA and Snail and decrease in E-cadherin. We demonstrate that IL-7 has the potential to inhibit high glucose-induced renal proximal tubular fibrosis partly by modulating Smads and EMT pathway.


Plasmid-mediated AmpC in Klebsiella pneumoniae and Escherichia coli from septicaemic neonates: diversity, transmission and phenotypic detection.
Presence and dissemination of plasmid-mediated AmpC genes (pAmpCs) have made bacteria cephalosporin-resistant and assessment of their prevalence and diversity is essential. Coexistence of pAmpCs with New Delhi metallo-β-lactamase (blaNDM) has facilitated their spread and NDM interferes with correct pAmpC phenotypic identification. Assessment of pAmpCs in different species and sequence types (STs), co-transmission with blaNDM and phenotypic detection were analysed among Klebsiella pneumoniae (n = 256) and Escherichia coli (n = 92) isolated from septicaemic neonates over 13 years. pAmpCs were present in 9% (30/348) of strains, 5% in K. pneumoniae and 18% in E. coli. pAmpC genes (blaCMY and blaDHA) were detected, blaCMY-42 and blaDHA-1 variants being predominant. Strains were resistant to most antimicrobials tested. blaCMY and blaDHA were dominant among E. coli (14/17) and K. pneumoniae (9/13), respectively. pAmpC-bearing strains belonged to diverse STs, including epidemic K. pneumoniae ST11 and ST147. Some strains co-harboured carbapenemase genes, blaNDM (17/30) and blaOXA-48 (5/30). In 40% (12/30) of strains, pAmpC genes were transferred by conjugation, of which 8/12 exhibited co-transfer with blaNDM. pAmpCs were frequently found in replicons as follows: blaDHA-1 with IncHIB-M, blaCMY-4 with IncA/C, blaCMY-6 with IncA/C, and blaCMY-42 with IncFII. The combination disk-diffusion test correctly detected pAmpC in 77% (23/30) of pAmpC-bearing strains. However, correct detection of pAmpC was higher in strains that did not harbour blaNDM vs. those with blaNDM (85% vs. 71%). Presence of pAmpCs along with carbapenemases, linkage with multiple STs, and replicon types indicated their potential for spread. pAmpCs can go undetected in the presence of blaNDM; hence, regular surveillance is required.


Cross-cultural adaptation, validity and reliability of the Arabic version of the Forgotten Joint Score for knee arthroplasty.
To evaluate the validity and reliability of the Arabic version of this questionnaire in Arabic patients who underwent total knee arthroplasty (TKA). The Arabic version of the English FJS (Ar-FJS) was modified according to cross-cultural adaptation best practices. The study included 111 patients who underwent TKA 1-5 years ago and completed the Ar-FJS. The reduced Western Ontario and McMaster Universities Osteoarthritis Index (rWOMAC) and 36-Item Short Form (SF-36) were used to assess the construct validity of the study. Fifty-two individuals took the Ar-FJS test twice to evaluate the test-retest reliability. The reliability of the Ar-FJS demonstrated a Cronbach's α value of 0.940 and an intraclass correlation coefficient of 0.951. The ceiling effect of the Ar-FJS was 5.4% (n = 6), whereas the floor effect was 1.8% (n = 2). Additionally, the Ar-FJS showed correlation coefficients of 0.753 and 0.992 for the rWOMAC and SF-36, respectively. The Ar-FJS-12 demonstrated excellent internal consistency, repeatability, construct validity, and content validity and can be recommended for patients in Arabic-speaking communities who have undergone knee arthroplasty.


Efferent connections of the dorsal cortex of the lizard Gekko gecko studied with Phaseolus vulgaris-leucoagglutinin.
The efferent connections from the dorsal cortex of the lizard Gekko gecko have been studied with the anterograde tracer Phaseolus vulgaris-leucoagglutinin. It appeared that the dorsal cortex is not a homogeneous structure as far as the efferent connections are concerned. All parts of the dorsal cortex project to the septum. All parts except the most medial project to the dorsal ventricular ridge, amygdala, nucleus periventricularis hypothalami, area lateralis hypothalami, and the anterior olfactory nucleus. The most medial part, in addition to the septal projections, is connected with the medial cortex and the contralateral medial and dorsal cortices. From the rostral part additional projections could be traced to the nucleus dorsolateralis hypothalami, nucleus ventromedialis thalami, nucleus dorsolateralis thalami, striatum, pallial thickening, medial cortex, nucleus olfactorius anterior, and the main and accessory olfactory bulbs. From the caudal part additional projections exist to the nucleus dorsomedialis thalami, nucleus accumbens, and the contralateral dorsal cortex. A system of intrinsic connections exists that can be subdivided into four subsystems, each of which subserves the interconnections within four subdivisions of the cortex: 1) the superficial medial part, 2) the deep medial part, 3) the caudal lateral and caudal intermediate parts, and 4) the rostral lateral and rostral intermediate parts. Connections between these four areas are scarce. From the present results the conclusion is drawn that the dorsal cortex of the lizard Gekko gecko has many hodological aspects in common with the ventral subiculum of mammals. The present results do not support the hypothesis that the dorsal cortex is the reptilian equivalent of the mammalian neocortex.


Magnetic Resonance of Small Bowel Tumors.
Tumors of the small intestine represent less than 5% of all gastrointestinal tract neoplasms. Magnetic resonance (MR) imaging is rapidly increasing clinical acceptance to evaluate the small bowel and can be the initial imaging method to investigate small bowel diseases. MR examinations may provide the first opportunity to detect and characterize tumors of the small bowel. Intraluminal and extraluminal MR findings, combined with contrast enhancement and functional information, allow accurate diagnoses and consequently characterization of small bowel neoplasms. This article describes the MR findings of primary small bowel neoplasms and the MR findings for the differential diagnosis are discussed.


Inactivation of de novo DNA methyltransferase activity by high concentrations of double-stranded DNA.
The activity of eukaryotic DNA methyltransferase diminishes with time when the enzyme is incubated with high concentrations (200-300 micrograms/ml) of unmethylated double-stranded Micrococcus luteus DNA. Under similar conditions, single-stranded DNA induces only a limited decrease of enzyme activity. The inactivation process is apparently due to a slowly progressive interaction of the enzyme with double-stranded DNA that is independent of the presence of S-adenosyl-L-methionine. The inhibited enzyme cannot be reactivated either by high salt dissociation of the DNA-enzyme complex or by extensive digestion of the DNA. Among synthetic polydeoxyribonucleotides both poly(dG-dC).poly(dG-dC) and poly(dA-dT).poly(dA-dT), but not poly(dI-dC).poly(dI-dC), cause inactivation of DNA methyltransferase. This inactivation process may be of interest in regulating the 'de novo' activity of the enzyme.