See before you jump: full recognition of parafoveal words precedes skips during reading.
Serial attention models of eye-movement control during reading were evaluated in an eye-tracking experiment that examined how lexical activation combines with visual information in the parafovea to affect word skipping (where a word is not fixated during first-pass reading). Lexical activation was manipulated by repetition priming created through prime-target pairs embedded within a sentence. The boundary technique (Rayner, 1975) was used to determine whether the target word was fully available during parafoveal preview or whether it was available with transposed letters (e.g., Herman changed to Hreman). With full parafoveal preview, the target word was skipped more frequently when it matched the earlier prime word (i.e., was repeated) than when it did not match the earlier prime word (i.e., was new). With transposed-letter (TL) preview, repetition had no effect on skipping rates despite the great similarity of the TL preview string to the target word and substantial evidence that TL strings activate the words from which they are derived (Perea & Lupker, 2003). These results show that lexically based skipping is based on full recognition of the letter string in parafoveal preview and does not involve using the contextual constraint to compensate for the reduced information available from the parafovea. These results are consistent with models of eye-movement control during reading in which successive words in a text are processed 1 at a time (serially) and in which word recognition strongly influences eye movements.


Potential human pathogenic bacteria in five hot springs in Eritrea revealed by next generation sequencing.
Human pathogens can survive and grow in hot springs. For water quality assessment, Escherichia coli or Enterococci are the main thermotolerant enteric bacteria commonly used to estimate the load of pathogenic bacteria in water. However, most of the environmental bacteria are unculturable thus culture methods may cause bias in detection of most pathogens. Illumina sequencing can provide a more comprehensive and accurate insight into environmental bacterial pathogens, which can be used to develop better risk assessment methods and promote public health awareness. In this study, high-throughput Illumina sequencing was used to identify bacterial pathogens from five hot springs; Maiwooi, Akwar, Garbanabra, Elegedi and Gelti, in Eritrea. Water samples were collected from the five hot springs. Total community DNA was extracted from samples using the phenol-chloroform method. The 16S rRNA gene variable region (V4-V7) of the extracted DNA was amplified and library construction done according to Illumina sequencing protocol. The sequence reads (length >200 bp) from Illumina sequencing libraries ranged from 22,091 sequences in the wet sediment sample from Garbanabra to 155,789 sequences in the mat sample from Elegedi. Taxonomy was assigned to each OTU using BLASTn against a curated database derived from GreenGenes, RDPII, SILVA SSU Reference 119 and NCBI. The proportion of potential pathogens from the water samples was highest in Maiwooi (17.8%), followed by Gelti (16.7%), Akwar (13.6%) and Garbanabra (10.9%). Although the numbers of DNA sequence reads from Illumina sequencing were very high for the Elegedi (104,328), corresponding proportion of potential pathogens very low (3.6%). Most of the potential pathogenic bacterial sequences identified were from Proteobacteria and Firmicutes. Legionella and Clostridium were the most common detected genera with different species. Most of the potential pathogens were detected from the water samples. However, sequences belonging to Clostridium were observed more abundantly from the mat samples. This study employed high-throughput sequencing technologies to determine the presence of pathogenic bacteria in the five hot springs in Eritrea.


Toxicity-dependent feasibility bounds for the escalation with overdose control approach in phase I cancer trials.
Phase I trials of anti-cancer therapies aim to identify a maximum tolerated dose (MTD), defined as the dose that causes unacceptable toxicity in a target proportion of patients. Both rule-based and model-based methods have been proposed for MTD recommendation. The escalation with overdose control (EWOC) approach is a model-based design where the dose assigned to the next patient is one that, given all available data, has a posterior probability of exceeding the MTD equal to a pre-specified value known as the feasibility bound. The aim is to conservatively dose-escalate and approach the MTD, avoiding severe overdosing early on in a trial. The EWOC approach has been applied in practice with the feasibility bound either fixed or varying throughout a trial, yet some of the methods may recommend incoherent dose-escalation, that is, an increase in dose after observing severe toxicity at the current dose. We present examples where varying feasibility bounds have been used in practice, and propose a toxicity-dependent feasibility bound approach that guarantees coherent dose-escalation and incorporates the desirable features of other EWOC approaches. We show via detailed simulation studies that the toxicity-dependent feasibility bound approach provides improved MTD recommendation properties to the original EWOC approach for both discrete and continuous doses across most dose-toxicity scenarios, with comparable performance to other approaches without recommending incoherent dose escalation. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.


Effectiveness of different solid-phase microextraction fibres for differentiation of selected Madeira island fruits based on their volatile metabolite profile--identification of novel compounds.
A headspace solid-phase microextraction (HS-SPME) procedure based on five commercialised fibres (85 μm polyacrylate - PA, 100 μm polydimethylsiloxane - PDMS, 65 μm polydimethylsiloxane/divinylbenzene - PDMS/DVB, 70 μm carbowax/divinylbenzene - CW/DVB and 85 μm carboxen/polydimethylsiloxane - CAR/PDMS) is presented for the characterization of the volatile metabolite profile of four selected Madeira island fruit species, lemon (Citrus limon), kiwi (Actinidia deliciosa), papaya (Carica papaya L.) and Chickasaw plum (Prunus angustifolia). The isolation of metabolites was followed by thermal desorption gas chromatography-quadrupole mass spectrometry (GC-qMS) methodology. The performance of the target fibres was evaluated and compared. The SPME fibre coated with CW/DVB afforded the highest extraction efficiency in kiwi and papaya pulps, while in lemon and plum the same was achieved with PMDS/DVB fibre. This procedure allowed for the identification of 80 compounds, 41 in kiwi, 24 in plums, 23 in papaya and 20 in lemon. Considering the best extraction conditions, the most abundant volatiles identified in kiwi were the intense aldehydes and ethyl esters such as (E)-2-hexenal and ethyl butyrate, while in Chicasaw plum predominate 2-hexenal, 2-methyl-4-pentenal, hexanal, (Z)-3-hexenol and cyclohexylene oxide. The major compounds identified in the papaya pulp were benzyl isothiocyanate, linalool oxide, furfural, hydroxypropanone, linalool and acetic acid. Finally, lemon was shown to be the most divergent of the four fruits, being its aroma profile composed almost exclusively by terpens, namely limonene, γ-terpinene, o-cymene and α-terpinolene. Thirty two volatiles were identified for the first time in the fruit or close related species analysed and 14 volatiles are reported as novel volatile metabolites in fruits. This includes 5 new compounds in kiwi (2-cyclohexene-1,4-dione, furyl hydroxymethyl ketone, 4-hydroxydihydro-2(3H)-furanone, 5-acetoxymethyl-2-furaldehyde and ethanedioic acid), 4 in plum (4-hydroxydihydro-2(3H)-furanone, 5-methyl-2-pyrazinylmethanol, cyclohexylene oxide and 1-methylcyclohexene), 4 in papaya (octaethyleneglycol, 1,2-cyclopentanedione, 3-methyl-1,2-cyclopentanedione and 2-furyl methyl ketone) and 2 in lemon (geranyl farnesate and safranal). It is noteworthy that among the 15 volatile metabolites identified in papaya, 3-methyl-1,2-cyclopentanedione was previously described as a novel PPARγ (peroxisome proliferator-activated receptor γ) agonist, having a potential to minimize inflammation.


Tumor Lysis Syndrome: A Rare Complication of Metastatic Gastric Cancer and a Possible Indicator of Disease Progression.
Tumor lysis syndrome (TLS) is an oncologic emergency that is usually associated with hematologic malignancies either spontaneously or following early chemotherapy and is caused by massive tumor cell lysis. However, it has been rarely reported in solid tumors. We report a case of 25-year-old lady recently diagnosed with metastatic gastric adenocarcinoma who developed TLS after the fourth cycle of chemoimmunotherapy (FOLFOX plus Nivolumab). She presented with abdominal pain, decrease in oral intake and decreased urine output. Laboratory studies showed acute kidney injury with electrolyte disturbances and was diagnosed initially with autoimmune nephritis secondary to Nivolumab but was later found to have TLS and recovered after appropriate treatment. Soon after this complication, our patient was found to have disease progression on imaging which makes the incidence of TLS an indicator of disease progression.


Practical imaging in acute pancreatitis.
Pancreatitis may be acute or chronic, mild or severe. In patients with acute pancreatitis the optimal imaging test is dynamic intravenous and oral contrast enhanced computed tomography (CECT). Serial CECTs are useful to monitor disease progression and to assess intraabdominal complications in patients with severe acute pancreatitis. CECT is helpful in planning the approach (endoscopic transmural versus percutaneous) for pancreatic drainage. Computed tomography or ultrasound-guided aspiration of pancreatic collections is safe, sensitive, and specific and has become a routine procedure used to screen for infected necrosis. When pancreatic drainage is contemplated, magnetic resonance imaging is useful for identifying residual necrotic debris within the collection. Patients with mild acute pancreatitis usually require no cross-sectional imaging study other than ultrasound screening for gallstones, if gallstone pancreatitis is suspected clinically. In patients with chronic pancreatitis, screening for complications such as superimposed acute pancreatitis or development of pancreatic pseudocysts may be performed with CECT or ultrasound.


Intracranial hemorrhage detection over time using susceptibility-weighted magnetic resonance imaging.
The reliable detection of intracranial hemorrhages is important, but just 1 year after the hemorrhage onset it might be missed using T2-weighted spin-echo and gradient-echo sequences. Susceptibility-weighted imaging (SWI) is a new magnetic resonance imaging sequence that is extremely sensitive in hemorrhage detection and that might improve the detection of hemorrhages over time. To investigate whether the detectability of intracranial blood and its degradation products is independent of the time span after intracranial hemorrhage using SWI. Sixty-six consecutive patients (28 men, 38 women) with definitely known time point of intracranial hemorrhage and available SWI sequence (1.5 or 3 T) were analyzed retrospectively. Twenty-one patients had a SWI follow-up. All SWI images were assessed by two radiologists in consensus regarding hemorrhage visibility using a 5-point scale. Statistical analysis was performed using Spearman's correlation test. Median time interval between hemorrhage and first available SWI measurement was 819 days (range, 0 days to 13.2 years). Nine of 66 patients had an isolated subarachnoid hemorrhage (iSAH) and were therefore analyzed separately. In eight of these nine patients the hemorrhage could clearly be detected, the remaining one had minor iSAH. Spearman analysis showed no significant correlation between time span and visibility (P = 0.660). In the remaining 57 patients (no iSAH) the hemorrhage was always visible achieving at least 3/5 points on the 5-point scale, and Spearman's analysis revealed only a weak correlation between time span and visibility (r = 0.493, P < 0.001). The detectability of blood and its degradation products using SWI is reliably possible over a long period after intracranial hemorrhage.


Transepithelial potential measurements in the isolated, perfused head of a marine teleost.
The transepithelial potential (TEP) across the gills of a seawater teleost, the long-horned sculpin (Myoxocephalus octodecimspinosus), was measured both in vivo and utilizing an isolated, perfused head preparation (IPHP). The TEP of the IPHP was compared to that of the whole animal while in normal seawater and Na- or Cl-free seawater. The TEP or the IPHP in seawater was similar to that measured in vivo (+7.7 versus +7.2 mV, respectively). Na-free seawater induced a depolarization of both the IPHP and the intact fish, while Cl-free seawater hyperpolarized the TEP in vivo. The positive TEP of the sculpin, measured both in vivo and in vitro, is indicative of a transbranchial Na+ to Cl- permeability ratio greater than unity. The IPHP of the sculpin exhibits differential ion permeabilities similar to that of the whole animal. TEP comparisons described here should be applied to other IPHP systems now in use.


Cholinergic interneurons in the rat striatum modulate substitution of habits.
Behavioural flexibility is crucial for adaptive behaviour, and recent evidence suggests that cholinergic interneurons of the striatum play a distinct role. Previous studies of cholinergic function have focused on strategy switching by the dorsomedial or ventral striatum. We here investigated whether cholinergic interneurons in the dorsolateral striatum play a similar role at the level of switching of habitual responses. Because the dorsolateral striatum is particularly involved in habitual responding, we developed a habit substitution task that involved switching habitual lever-press responses to one side to another. We first measured the effect of cholinergic activation in the dorsolateral striatum on this task. Chemogenetic activation of cholinergic interneurons caused an increase in the response rate for the substituted response that was significantly greater than the increase normally seen in control animals. The increase was due to burst-like responses with shorter inter-press intervals. However, there was no effect on inhibiting the old habit, or on habitual responding that did not require a switch. There was also no effect on lever-press performance and its reversal before lever-press responses became habitual. Conversely, neurochemically specific ablation of cholinergic interneurons did not significantly change habitual responding or response substitution. Thus, activation -but not ablation -of cholinergic interneurons in the dorsolateral striatum modulates expression of a new habit when an old habit is replaced by a new one. Together with previous work, this suggests that striatal cholinergic interneurons facilitate behavioural flexibility in both dorsolateral striatum in addition to dorsomedial and ventral striatum.


[Determination of needs of terminally ill patients in the hospice care].
The aim of palliative care is the solution of bio-psycho-social and spiritual problems of patients and achievement of the highest possible quality of life. This is related to a need of understanding the patient and his needs. The aim of our research was to determine bio-psychosocial-spiritual needs of patients in hospice care in conjunction with the quality of life and rate of their saturation. Further then to determine, whether the needs vary depending on length of stay in hospice, gender, age and religion. The sample consisted of 36 patients from the hospice of St. Luke in Ostrava. For data collection we used modified questionnaire for the identification of needs PNPC and questionnaire for assessing the quality of life EORTC QOL-C30. As the most important need patients considered the privacy (4,80), the opportunity to make their own decisions (4,77), treatment with respect and dignity (4,75) and pain relieve (4,72). The most frequently reported problem was fatigue, sleep and fear of addiction. Patients have positively rated pain prevention. In repeated measurements were reported significant improvements of assessment of saturation needs in 10 items (p < 0.05). The patients evaluated overall quality of life rather positively. A relationship between quality of life and saturation of needs in the area of autonomy and physical needs (p < 0.05) was found. During the stay in hospice patients' satisfaction with saturation of some needs and overall assessment of quality of life increased.


Evaluation of extended release brimonidine intravitreal device in normotensive rabbit eyes.
To evaluate the safety profile of a brimonidine extended release intravitreal implant, in normotensive rabbit eyes. Devices were made from hollow poly-l-lactic acid (PLA) tubes and contained hundred micrograms of brimonidine pamoate. Device was injected intravitreally in one eye of 12 New Zealand pigmented rabbits, whereas other eye was injected with a sham implant in masked fashion. Ocular examination was conducted at baseline and months 1, 3 and 6 including dilated fundus examination and electro-retinogram (ERG). Four rabbits were sacrificed at each time-point for retinal histology. ERG data were compared between groups and time-points using anova. No complications were reported from either eye of any rabbits over a 6-month period. Photopic A wave was reduced in the control eye at 1 month compared with baseline (p < 0.01). There was no significant difference in other ERG parameters between the groups at different time-points. Gross retinal histology was normal at all time-points. Extended release intravitreal brimonidine device was found to be safe and in normotensive rabbit eyes.


Integrated Computational Protocol for the Analysis of Quadrupolar Splittings from Natural-Abundance Deuterium NMR Spectra in (Chiral) Oriented Media.
Despite its low natural abundance, deuterium NMR spectroscopy in weakly oriented (chiral) solvents gives easy access to deuterium residual quadrupolar couplings (2 H-RQCs). These are formally equivalent to one-bond residual dipolar couplings ((13 C-1 H)-RDCs) for calculation of the Saupe tensor, and provide similar information for the study of molecular structure and orientational behavior. Because the quadrupolar interaction is one order of magnitude larger than the dipolar one, 2 H-RQC analysis is a much more sensitive tool for the detection of subtle structural differences and also tiny differences in molecular alignment, such as those observed for different enantiomers in chirally aligned media. To promote the analytical advantages of anisotropic, natural-abundance deuterium NMR (NAD NMR) spectroscopy in the organic chemistry community, we describe a 2 H-RQC/DFT-based integrated computational protocol for the evaluation of the order parameters of aligned solutes by using singular-value decomposition. Several examples of 2 H-RQC-assisted analysis of chiral and prochiral molecules dissolved in various polypeptide lyotropic chiral liquid crystals are reported. The role of the molecular shape in the ordering mechanism was investigated through the determination of intertensor angles between alignment tensors and inertia tensors by using the proposed protocol.


Selective sorption of lead, cadmium and zinc ions by a polymeric cation exchanger containing nano-Zr(HPO3S)2.
A novel polymeric hybrid sorbent, namely ZrPS-001, was fabricated for enhanced sorption of heavy metal ions by impregnating Zr(HPO3S)2 (i.e., ZrPS) nanoparticles within a porous polymeric cation exchanger D-001. The immobilized negatively charged groups bound to the polymeric matrix D-001 would result in preconcentration and permeation enhancement of target metal ions prior to sequestration, and ZrPS nanoparticles are expected to sequester heavy metals selectively through an ion-exchange process. Highly effective sequestration of lead, cadmium, and zinc ions from aqueous solution can be achieved by ZrPS-001 even in the presence of competing calcium ion at concentration several orders of magnitude greater than the target species. The exhausted ZrPS-001 beads are amenable to regeneration with 6 M HCI solution for repeated use without any significant capacity loss. Fixed-bed column treatment of simulated waters containing heavy metals at high or trace levels was also performed. The content of heavy metals in treated effluent approached or met the WHO drinking water standard.


A model for the synthesis of chemical compounds in red blood cells, with an application to diabetes.
The amount of a substance produced and stored in red blood cells is modelled as the solution to a first-order differential equation involving the stochastic rate of production of the substance within each cell, the lifespans of the cells, and the birth and death rates of the cells. Estimation of the parameters of the model is outlined for a special case, and the model is fitted to a set of real data taken from clinically diabetic dogs.


Infants tested for hearing loss--United States, 1999-2001.
Hearing loss (HL) occurs in one to three of 1,000 live births annually and, when left undetected, can result in developmental delays. To promote communication from birth, Early Hearing Detection and Intervention (EHDI) programs support early identification of infants with HL. Without EHDI programs, the average age of identification for HL is age 1.5-3.0 years, which is past the start of the critical period for optimal language acquisition. In 2001, a total of 48 states/areas with EHDI tracking and surveillance systems (30 funded by CDC) reported the percentage of newborns screened for HL. This report summarizes the results of an analysis of surveillance data for 1999-2001, which indicate that more infants were screened for HL, received diagnostic audiologic evaluations, and were enrolled in early intervention services in 2001 than in 1999 and 2000. Continued development of EHDI surveillance systems should assist states/areas in providing needed services to children with HL.


An office guide to whole-gut transit time. Patients' recollection of their stool form.
Forty-seven patients (ages 17-74 years, 33 women) who had irritable bowel syndrome and who attended a gastroenterology clinic had their whole-gut transit time (WGTT) assessed by an abdominal radiograph after ingesting 20 radioopaque markers on 4 consecutive days. Immediately afterward, the patients completed a questionnaire that asked about their stool form on the Bristol Scale, their bowel frequency, and whether they thought they had been experiencing diarrhea or constipation during the previous 5 days. WGTT varied from 7 to 96 h. Stool form correlated significantly with WGTT (r = -0.57, p < 0.001), whereas stool frequency did not (r = 0.31, NS). The regression equation relating WGTT to stool form was WGTT (h) = 75-10 (stool form). WGTT, stool form, and frequency were significantly different in patients reporting constipation compared with those who reported diarrhea, diarrhea and constipation, or neither, but in the last three groups these parameters were not significantly different from each other. Patients' recollection of stool form is a reasonable guide to their transit time and can be used in the office to identify pseudodiarrhea and true constipation.


Left ventricular contractility after hypothermic preservation: predictive value of phosphorus 31-nuclear magnetic resonance spectroscopy.
Early graft failure accounts for a substantial portion of the mortality after heart transplantation. This factor underscores the need for the development of reliable methods for predicting graft performance and thus ensuring optimal clinical outcome. The aim of this study was to describe the link between myocardial metabolism evaluated throughout preservation with the use of phosphorus 31-nuclear magnetic resonance spectroscopy and ventricular contractility after reperfusion. Thirteen pig hearts were excised and preserved from 3 to 12 hours with clinical techniques. During preservation the hearts underwent phosphorus 31-nuclear magnetic resonance spectroscopy. After reperfusion, left ventricular contractility was evaluated with an isolated heart model undergoing isovolumetric contraction. Throughout storage, beta-adenosine triphosphate remained stable and intracellular pH and phosphocreatine decreased exponentially, whereas inorganic phosphate increased exponentially. Intracellular pH, phosphocreatine, inorganic phosphates measured at the onset of preservation, and intracellular pH and phosphocreatine measured at the end of preservation correlated significantly with the left ventricular contractility after reperfusion. We conclude that the metabolic state of myocardium at excision is especially important and that phosphorus 31-nuclear magnetic resonance evaluation of the heart during preservation appears to provide reliable indexes for predicting subsequent ventricular contractility after reperfusion.


Simvastatin reduces platelet thromboxane formation and restores normal platelet sensitivity against prostacyclin in type IIa hypercholesterolemia.
The effect of lowering total serum cholesterol and low-density lipoprotein (LDL) cholesterol on platelet function, thromboxane formation and platelet sensitivity against PGI2 was studied in platelet-rich plasma ex vivo. Additionally, PGI2 receptors were determined in membrane preparations of these platelets. Twelve patients suffering from familial hyperlipoproteinemia type IIa (FH) were treated for 8 months with simvastatin (20-40 mg/day) and compared with 10 untreated FH patients and 10 untreated normocholesterolemic subjects. Compared with those of healthy controls, platelets of untreated FH patients were hyperreactive, as shown by an enhanced aggregation response and release of ATP and thromboxane after stimulation by collagen (0.3-5 micrograms/ml) and ADP (0.3-10 micrograms/ml). Simvastatin reduced the total and LDL serum cholesterol towards control levels while HDL cholesterol remained unchanged. This was accompanied by a significant decrease of platelet aggregation, thromboxane formation and ATP secretion being no more different from normocholesterolemic controls. In addition, the reduced platelet sensitivity against prostacyclin (aggregation, stimulation of cAMP formation) in untreated FH patients was improved to normal values by simvastatin. This was associated with a significant elevation of the reduced prostacyclin binding sites and might be explained by an improved access of prostacyclin to its receptors at platelet membranes. These data demonstrate that the reduction of total and LDL serum cholesterol by simvastatin results in a normalization of platelet function by (i) reduction of platelet hyperreactivity and (ii) improvement of the sensitivity against prostacyclin towards normal via enhanced PGI2-binding sites.


[Beta-blockers usage in cardio-vascular diseases co-existing with COPD].
Chronic obstructive pulmonary disease (COPD) is one of the most frequent chronic diseases. Slightly reversable and progressive decrease in airflow through the airways is characteristic for the disease. It has been brought up last years that COPD course influences not only pulmonary system status but also many co-existing diseases in the eldery, especially cardio-vascular diseases, such as: ischaemic heart disease, hypertension, heart arrythmias, heart infarction. Wide usage and established position in the treatment of cardio-vascular diseases have the antagonists of beta-adrenergic receptors (beta-blockers). The aim of this work was the combination of the studies results quoted in the literature about the usage of beta-blockers in cardiovascular diseases co-existing with COPD. Conclusions. Nowadays there are no unambiguous recommendations for the usage of beta-blocker in patients with COPD and the decision about including them into treatment depends on the individually estimated risk of complications.


Prenatal maternal mood is associated with altered diurnal cortisol in adolescence.
Experimental animal work shows that prenatal stress has a persisting effect on the hypothalamic-pituitary-adrenal (HPA) axis of offspring. The implications of these findings for human health and development are not yet clear. The data are based on the ALSPAC cohort, a prospective longitudinal study of a community sample that has followed mothers and children from pregnancy. When the children were aged 15 years, diurnal cortisol samples were collected at wake-up, 30 min post-awakening and at afternoon and evening times on up to three consecutive days on n=889 adolescents. Diurnal cortisol was predicted from prenatal anxiety and depression, obstetric, life-style, socio-demographic, and postnatal covariates. Multilevel model analysis indicated that maternal prenatal anxiety was associated with a modest alteration of diurnal cortisol, indexed by a reduced cortisol awakening response and flatter diurnal slope. The effects were independent of psychosocial and obstetric covariates and measures of maternal postnatal anxiety; effects were similar for prenatal maternal depression. There was no association between adolescent cortisol and paternal prenatal anxiety. There are small but persisting associations between maternal prenatal mood and diurnal cortisol in the child that persist into adolescence and may constitute a programming effect.


Osteoporosis-related kyphosis and impairments in pulmonary function: a systematic review.
We conducted a systematic review to examine the relationship between osteoporotic vertebral fractures, kyphosis, and pulmonary function. Findings suggest modest but predictable declines in vital capacity related to the degree of kyphosis. However, there were only four studies, and all had significant methodologic limitations. Further high-quality research is needed. Our objective was to systematically review the extent to which osteoporosis-related vertebral fractures and kyphosis affect pulmonary function. We used a literature search from 1966 to 2006 (using Medline, EMBASE, and hand searches of references) for studies examining pulmonary function in patients without known lung disease who had vertebral fractures or kyphosis secondary to osteoporosis. Two reviewers independently abstracted data. Heterogeneity precluded formal meta-analysis. Initial searches yielded 453 articles. After applying eligibility criteria, only four case-control studies of limited quality (e.g., only one study was blinded) remained. Since 1966, only 109 patients (6 men) have been studied. All four studies reported reductions in vital capacity (VC), with values ranging from 68% to 94% of predicted values. This was quantified as a 9% reduction in predicted VC per vertebral fracture in one study. The degree of kyphosis clinically (one study) or radiographically (three studies) correlated with declines in VC; impairments were most notable at kyphotic angles>55 degrees. Statistically significant differences in percent predicted VC were obtained only when arm span or recalled height, rather than measured height, was used (two studies). Despite conventional teaching, the evidence relating osteoporotic vertebral fractures or kyphosis to pulmonary function is limited. On the basis of available studies, declines in VC secondary to kyphosis seem modest and directly related to the number of vertebral fractures or degree of kyphosis. Future studies need longitudinal follow-up of larger numbers of men and women, appropriate proxies for height, standardized measures for pulmonary function and kyphosis, and efforts to blind outcomes ascertainment.


[Clinicopathological analysis of 3 cases in which pulmonary metastasis from the urothelial carcinoma was resected].
We describe 3 cases in which the pulmonary metastasis from the urothelial carcinoma of the bladder and upper urinary tract was resected. The duration from the operation of the primary lesion to the occurrence of the pulmonary metastasis was 19, 11, and 4 years in each of the 3 cases. Repeated treatment of the local recurrence was performed in all the 3 cases. Local recurrence in the bladder membrane was observed in 1 case. In 2 cases, computed tomography( CT) scans revealed that the cavitation had penetrated the tumor. Histological findings of the surgical specimen obtained from the 3 cases revealed severe tumor necrosis. Immunostaining of the surgical specimen resulted in a definitive diagnosis of pulmonary metastasis from the urothelial carcinoma in 2 cases in which a differential diagnosis could not identify the primary lung cancer from the pulmonary metastasis. The prognoses in terms of survival in each of the 3 cases were shorter than 32, 19, and 6 months from the operation of the pulmonary metastasis. However, the prognoses could be improved by multidisciplinary treatment, including the resection of the pulmonary metastasis.


Recent Advances on Transition Metal Dichalcogenides for Electrochemical Energy Conversion.
Transition metal dichalcogenides (TMDCs) hold great promise for electrochemical energy conversion technologies in view of their unique structural features associated with the layered structure and ultrathin thickness. Because the inert basal plane accounts for the majority of a TMDC's bulk, activation of the basal plane sites is necessary to fully exploit the intrinsic potential of TMDCs. Here, recent advances on TMDCs-based hybrids/composites with greatly enhanced electrochemical activity are reviewed. After a summary of the synthesis of TMDCs with different sizes and morphologies, comprehensive in-plane activation strategies are described in detail, mainly including in-plane-modification-induced phase transformation, surface-layer modulation, and interlayer modification/coupling. Simultaneously, the underlying mechanisms for improved electrochemical activities are highlighted. Finally, the strategic evaluation on further research directions of TMDCs in-plane activation is featured. This work would shed some light on future design trends of TMDCs-based functional materials for electrochemical energy-related applications.


Serotonin initiation of delayed-type hypersensitivity: mediation by a primitive Thy-1+ antigen-specific clone or by specific monoclonal IgE antibody.
Elicitation of delayed-type hypersensitivity (DTH) responses is due to the required sequential action of two different antigen (Ag)-specific Thy-1+ cells: early acting, DTH-initiating cells and locally recruited CD4+, alpha beta-TCR+, DTH effector T cells. DTH-initiating cells have an unusual phenotype for Ag-specific cells (Thy-1+, CD5+, CD4-, CD8-, CD3-, sIg-, B220+ (CD45RA+), Mac 1+, IL-2R- and IL-3R+) and act by producing Ag-specific non-IgE factors that sensitize mast cells for release of the vasoactive amine serotonin (5HT) at the local site of elicitation of DTH by challenge. Another mechanism of DTH initiation involves Ag-specific IgE antibodies that also can sensitize mast cells for local serotonin release. Serotonin initiates DTH by activating the local endothelial cells to allow recruitment of DTH effector T cells, and also by activating 5HT-2 receptors on these recruited T cells.


Docked secretory vesicles undergo Ca2+-activated exocytosis in a cell-free system.
The Ca2+-activated fusion of secretory vesicles with the plasma membrane responsible for regulated neurotransmitter and hormone secretion has previously been studied in permeable neuroendocrine cells, where requirements for ATP and cytosolic proteins were identified. As reported here, Ca2+-activated fusion mechanisms are also preserved following cell homogenization. The release of norepinephrine (NE) and other vesicle constituents from a PC12 cell membrane fraction was activated by micromolar Ca2+ (EC50 approximately 3 microM) and exhibited a dependence upon MgATP and cytosol. Ca2+-dependent NE release was inhibited by botulinum neurotoxins and by CAPS (Ca2+-dependent activator protein for secretion) antibody implying that syntaxin, synaptobrevin, SNAP-25 (synaptosomal-associated protein of 25 kDa), and CAPS are required for regulated exocytosis in this system. The exocytosis-competent membrane fraction consisted of rapidly sedimenting dense core vesicles associated with plasma membrane fragments. Free vesicles did not release NE either in the absence or presence of plasma membranes, indicating that only docked vesicles were competent for exocytosis under the reconstitution conditions used. A cell-free system for Ca2+-activated fusion will facilitate studies on the roles of essential proteins such as syntaxin, synaptobrevin, SNAP-25, and CAPS that act at post-docking steps in the regulated exocytotic pathway.


Integration of non-communicable diseases in health care: tackling the double burden of disease in African settings.
Sub-Saharan African countries now face the double burden of Non Communicable and Communicable Diseases. This situation represents a major threat to fragile health systems and emphasises the need for innovative integrative approaches to health care delivery. Health services need to be reorganised to address populations' needs holistically and effectively leverage resources in already resource-limited settings. Access and delivery of quality health care should be reinforced and implemented at primary health care level within the framework of health system strengthening. Competencies need to be developed around services provided rather than specific diseases. New models of integration within the health sector and other sectors should be explored and further evidence generated to inform policy and practice to combat the double burden.


Efficacy of N-acetylcysteine on idiopathic or postinfective non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis protocol.
Non-cystic fibrosis (non-CF) bronchiectasis is a chronic pulmonary disorder that causes destruction and permanent dilatation of the airways, resulting in excessive sputum production, repeated infection and inflammation. A need for high-quality and specialised care has been highlighted in recent years. N-acetylcysteine (NAC) is a widely used mucolytic agent in respiratory diseases that not only possesses a property to enhance secretion clearance, but also exhibits antioxidant and anti-inflammatory effects. However, the efficacy and safety of NAC are not well described in idiopathic or postinfective non-CF bronchiectasis. This study aims to evaluate the efficacy and safety of NAC in patients with idiopathic or postinfective non-CF bronchiectasis. PubMed/Medline, Embase, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials will be searched from inception to 1 March 2022 for eligible randomised controlled trials that investigating the effects of NAC on exacerbations, health-related quality of life, lung functions, sputum volume and colour, inflammation markers, exercise capacity and adverse events in patients with idiopathic or postinfective non-CF bronchiectasis, with ongoing trials being identified by searches on the websites of Chinese Clinical Trial Registry and ClinicalTrials.gov. Two independent reviewers will identify eligible studies, two will fulfil the data extraction and three will perform the quality appraisal. To generate more accurate analyses, the Grading of Recommendations Assessment, Development and Evaluation will be used to grade the evidence. χ2 test and I2 statistic will be used to assess heterogeneity. Subgroup analyses and meta-regression will be used to explore potential sources of heterogeneity. The potential publication bias will be examined using funnel plots. No research ethics approval is required in this study because it is a systematic review. The results of this study are expected to be disseminated through peer-reviewed journals and conferences. CRD42021239438.


Angiographic features of the coronary arteries during intracoronary thrombolysis.
The angiographic appearance of the coronary arteries during successful thrombolysis with urokinase was determined in 35 patients with acute myocardial infarction. The lysing process passed through several phases: (a) total coronary occlusion with a convex or irregular distal margin (phase 0); (b) increasing patency of the lumen (phase 1); (c) re-establishment of flow but with intraluminal filling defects and delayed distal flow possibly due to microemboli (phase 2); (d) partial or complete disappearance of the filling defects (phase 3); and (e) further widening of the lumen which eventually attains a smooth regular outline (phase 4). The angiographic features which indicate the presence of coronary thrombosis are occlusion with an irregular or scalloped margin, staining with contrast medium, and progressive patency of the occluded vessel showing intraluminal filling defects.


Internal fixation of open unstable pelvic fractures.
From 1980 through 1990 14 patients with severely complicated unstable fractures of the pelvis were treated. There were 13 men and one women (mean age, 28 years). Eight fractures also involved the acetabulum. The injuries were accompanied by anorectal (nine), urogenital (eight), vascular (three), and nerve (three) injuries. After resuscitation, fractures were stabilized immediately, preferably using internal fixation, notwithstanding fecal contamination in certain cases. Anorectal ruptures were treated with lavage of the distal colon and a divergent stoma. The urogenital lesions also were treated primarily. Two patients died early after treatment of accompanying injuries. Infectious complications were seen seven times. In one patient internal fixation broke down. All fractures healed with good functional results. At last follow-up examination all patients were continent for feces. It is concluded that early internal stabilization of these complex injuries achieves a low mortality rate and good functional results. Immediate repair of urogenital and sphincter lesions, with concomitant divergent stoma and lavage of the distal colon, gives good results notwithstanding the risk of infectious complications.


Gestational Age at Term and Educational Outcomes at Age Nine.
To estimate associations between gestational age (GA) and teacher-reported academic outcomes at age 9 years among children born at term (37-41 weeks). A secondary data analysis of 1405 children participating in a national US birth cohort study was conducted. At age 9 years, students were evaluated by their teachers in the areas of mathematics, science and social studies, and language and literacy. Unadjusted and adjusted logistic regression models of associations between GA and teacher-reported academic outcomes were estimated and neonatal morbidities were explored as potential pathways. A continuous measure of GA in weeks was significantly associated with above-average rankings in all areas. The associations were similar across outcomes (eg, mathematics [odds ratio (OR): 1.13; confidence interval (CI): 1.02-1.25], science and social studies [OR: 1.13; CI: 1.01-1.26], and language and literacy [OR: 1.16; CI: 1.05-1.28]) in a model that adjusted for child sex, maternal characteristics, and obstetric risk factors and delivery complications. Other specifications indicate a positive association between late term (41 weeks) and mathematics and a negative association between early term (37-38 weeks) and language and literacy, compared with term (39-40). The associations did not appear to operate through neonatal morbidity. The findings highlight the importance of GA, even at term. Whereas current guidelines suggest waiting until at least 39 weeks to deliver when possible, our findings add to a small group of studies suggesting that GA through 41 weeks is associated with improvements in some educational outcomes.


[Cerebral hemangiopericytoma. Ultrastructural study of one case].
The authors report electron-microscopic observations upon a primitive cerebral haemangiopericytoma. The vascular appearance of the tumour is due to the presence of abundant extracellular material which has a structure like that of vascular basement membranes. The fact that the tumour cells are pericytes is confirmed by the existence of intracytoplasmic microfilaments of 60-80 A in diameter, sometimes gathered into osmiophilic aggregations and forming simple cellular junctions (zonulae adherentes). Stress is laid upon the importance of differentiating this rare tumour from an angioblastic meningioma; the haemangiopericytoma is more rapidly growing and carries a more serious prognosis.


[Expression of hypoxia-inducible factor 1α in osteosarcoma and its value in predicting chemosensitivity].
To investigate the prognostic values of HIF-1α, APE1, VEGF, and COX-2 protein expressions and their predictive value of tumor necrosis rate and prognosis in osteosarcoma, as well as their interrelationships. Formalin-fixed paraffin-embedded tissue samples were obtained from patients with osteosarcoma. Immunohistochemical assay was performed in pre-chemotherapy samples to determine the HIF-1α, VEGF, APE1, and COX-2 protein expression levels. Hematoxylin-eosin staining was used in post-operative samples to determine the tumor necrosis rate. Univariate and multivariate analyses were used to assess the impact of protein expression on prognosis. Tumor tissues were obtained from 49 patients. Their median follow up was 29 months. HIF-1α was significantly correlated to every protein we tested: VEGF (P = 0.032), APE1 (P < 0.001), and COX-2 (P < 0.001). HIF-1α protein expression had a significant impact on disease free survival (P = 0.006). Expression of HIF-1α had a sensitivity of 64.7% and a specificity of 71.9% for poor pathological response (< 90% of tumor necrosis) versus good pathological response to chemotherapy (≥ 90% necrosis). Expression of HIF-1α is a predictor of tumor response to neoadjuvant chemotherapy and outcome in osteosarcoma and is correlated with VEGF, APE1, and COX-2 expression.


Changing the bonding force of impression tray to edentulous maxillary jaw simulator with impression valve system: in vitro study.
The aim of this study was to evaluate the effect of an impression valve system (IVS) on the bonding force between an impression tray and an edentulous maxillary jaw. In this in vitro study, a polyether-coated maxillary jaw simulator (PM) was used to model an edentulous maxillary jaw. The IVS was placed into individual impression trays. An irreversible hydrocolloid impression was taken of the PM when the IVS was open and closed. The impression tray bonding force was measured using a digital dynamometer. Student's t-test was used to determine the significance of the difference between these two groups. The impression tray was more easily separated from the PM when the IVS was open (108 ± 3.9 N). The separation was more difficult when the IVS was closed (153.7 ± 14.2 N). The difference between these two findings (P = 0.000) was significant. The use of an IVS facilitates the removal of the impression tray from the mouth when taking impressions from an edentulous maxillary jaw.


Intrapelvic protrusion of the acetabular component following total hip replacement.
Protrusion of the acetabular component into the true pelvis following total hip replacement has occurred in 5 patients, 4 with severe rheumatoid arthritis and 1 with a destructive type of degenerative hip disease. Preoperatively all hips had severe protrusio acetabuli, a markedly thin acetabular medial wall and advanced osteoporosis. Four had a McKee-Farrar prosthesis, a metal-to-metal device with high frictional torque, particularly when the contact is equatorial, and no damping capacity against marginal impingement in the extreme range of motion. In order to reduce the incidence of intrapelvic protrusion, extreme care should be given to preserve the medial bone stock of the acetabulum, more so when it is already damaged or defective. If anchoring holes are used they should be restricted to the superior ilium, pubis and ischium and should not perforate the medial wall. Once loosening is present, reoperation is indicated to avoid progressive bone reabsorption by the abrasive motion of the loosened prosthesis, that might lead to irreparable bone loss. To reduce the stress transmitted to an already weakened acetabulum, select a total prosthetic device with low friction; fix it with acrylic cement in order to distribute the stress over a large surface; carefully orient both components to avoid marginal impingement; be certain to preserve the medial wall as much as possible and if it is already defective reinforce it by bone grafting and/or wire mesh.


Income and employment of people living with combined HIV/AIDS, chronic mental illness, and substance abuse disorders.
This paper examines the labor market outcomes of HIV triply-diagnosed adults having a combination of HIV, mental illness and substance abuse problems. We sought to determine the sources of money income for HIV triply diagnosed adults (public or private), receipt of transfer income (e.g., welfare) and financial support from others. We further sought to ascertain their employment status and analyze the characteristics associated with full- and part-time employment. We use self-reported money income during the past 30 days and self-reported employment status. We calculate earnings losses due to illness by subtracting self-reported earnings from average earnings for all U.S. workers based on 5-year age and gender categories. We provide descriptive statistics to show how income and employment vary by patient characteristics and logistic regression analysis to examine correlates of income and employment. Average income is below the poverty level for single individuals, with more than two-thirds coming from public income sources. The likelihood of receiving disability/retirement income was lower among those with the worst mental health (RR=0.80; 95% CI=0.64, 0.97). Blacks were more likely than others to rely on public assistance (RR=1.24; 95% CI=1.02, 1.55) and married individuals were less likely (RR=0.60; 95% CI=0.41, 0.79). While most private income comes from employment, less than 15 percent of this population is employed full- or part-time. On a monthly basis, the average individual in our sample lost $2,726 in income when compared to the earnings of individuals of the same age and sex in the general population. The relative probability of current full-time/part-time employment was lower among females (RR=0.56; 95% CI=0.34, 0.83); such employment also was lower among those in the worst physical health (RR=0.39; 95% CI=0.26, 0.65) and those in moderate physical health (RR=0.55; 95% CI=0.34, 0.81) relative to those in the best physical health. This population represents an important opportunity for better health and labor market outcomes through prevention and improved treatment adherence. Despite its relatively small size (at least 100,000), this population merits closer attention due to a combination of their high medical and companion social costs (e.g., income transfers) and the large potential for improving their ability to earn income. Future research should determine the marginal contribution of mental health conditions or substance abuse on income or labor market outcomes relative to individuals having only HIV/AIDS. This would allow policymakers to better understand how much of income and employment can be attributed to HIV/AIDS, mental health or substance abuse. Future work also should examine the impact of integrated treatment services on income and employment for this population.


[Bilateral rupture of the quadriceps tendon--case report and review of the literature].
We report a very rare case of bilateral simultaneous rupture of the quadriceps tendons in a 64-year-old patient following a minor trauma. The reconstruction of the ruptured tendons was achieved by intertwined PDS-sutures which were supportively fixed in the patellae. After wound healing, the patient was mobilized in his two casts which were applied for 6 weeks. After the period of one year, a satisfactory result could be seen. We report the etiology, pathogenesis, diagnosis, therapy and postoperative treatment which are described in the literature.


Cellular synthesis and axonal transport of gamma-aminobutyric acid in a photoreceptor cell of the barnacle.
1. [3H]glutamate or [3H]gamma-aminobutyric acid (GABA) was injected into the photoreceptor cell of the lateral ocellus of Balanus eburneus, in order to study the transmitter substance of the cell. 2. The photoreceptor cell synthesized [3H]GABA from injected [3H]glutamate. 3. The newly formed [3H]GABA moved inside the photoreceptor axon towards the axon terminal with a velocity of about 0.9 mm/hr. Injected [3H]GABA moved at 0.9 mm/hr and also at 0.4 mm/hr. 4. Axonally transported [3H]GABA reached the axon terminal within several hours following the injection. It did not accumulate at the terminal, but gradually disappeared. 5. Light-microscope and electron-microscope autoradiography following the injection of [3H]GABA revealed that [3H]-reacted silver grains were present in a certain type of axon terminal. The terminal thus identified as that of a photoreceptor cell contains many clear, polymorphic synaptic vesicles about 300-500 A in diameter, some dense-cored vesicles 700-1300 A in diameter, and glycogen granules. The terminal forms many synapses, and each synapse has a synaptic dense body. The terminal always faces two post-synaptic elements at the synapse, forming a triad with a gap distance of about 160-200 A. 6. A GABA analogue, [3H]di-aminobutyric acid, was selectively taken up into the terminals previously identified as those of photoreceptors. 7. These results support the notion that the transmitter substance of the photoreceptor cell of the barnacle is GABA.


[The cardiovagal, cardiosympathetic and vasosympathetic arterial baroreflexes and the neural control of short-term blood pressure].
The factors that control the blood pressure are punctually regulated to keep it in reference values. These are maintained through autoregulatory mechanisms, humoral, nervous and endothelial-related. The humoral mechanisms are complex and modify the long-term blood pressure, in the other hand, the neurogenic mechanisms, are reflexive and can be observed in beat-to-beat changes of blood pressure. The nervous cardiovascular reflexes are mediated by high-pressure and low-pressure baroreceptors, as cardiovagal, cardiosympathetic and vasosympathetic. The arterial baroreceptor are stimulated when the blood volume-ejected by the ventricle distend the arterial walls. The neural discharge travels to the autonomic centers in the brain stem and the result is the modification of the heart rate and the vascular smooth muscle tone. This sudden modification is the responsible of the beat-to-beat (short-term) blood pressure variability. A review was made on the history of the physiology and experiments of the cardiovagal, cardiosympathetic and vasosympathetic baroreflexes and its influence in the short-term blood pressure variability.


Role for the ubiquitin-proteasome system in Parkinson's disease and other neurodegenerative brain amyloidoses.
Many neurodegenerative brain amyloidoses, including Alzheimer's and Parkinson's disease, are characterized by selective neuronal loss together with the appearance of intraneuronal ubiquitin-positive proteinaceous aggregates or inclusion bodies. These features usually result from the abnormal accumulation and processing of mutant, misfolded, or damaged intracellular proteins. It has recently become clear that both genetic factors and aberrant proteolytic degradation may therefore play a major role in neuronal degeneration. Indeed, the linkage of two genes directly involved in the ubiquitin-proteasome system (UPS) in familial Parkinson's disease clearly indicates a central role for the UPS in neurodegeneration, and thus Parkinson's disease is considered the prototypical disorder associated with UPS dysfunction. In this review, we provide an overview of the key genes/proteins implicated in the abnormal UPS-mediated proteolytic processing of unwanted proteins observed in neurodegenerative brain amyloidoses. We also provide an outline of the various components and pathways involved in the normal cellular functioning of the UPS and discuss the mechanisms by which UPS dysfunction can compromise neuronal integrity. A more complete understanding of the UPS and its relationship to the neurodegenerative process will undoubtedly provide tremendous insight into the molecular pathogenesis of amyloidogenic neurodegenerative disorders and will allow the development of novel rational therapies for treating these disorders.


Imaging structural and functional connectivity: towards a unified definition of human brain organization?
Diffusion tractography and functional/effective connectivity MRI provide a better understanding of the structural and functional human brain connectivity. This review will underline the major recent methodological developments and their exceptional respective contributions to physiological and pathophysiological studies in vivo. We will also emphasize the benefits provided by computational models of complex networks such as graph theory. Imaging structural and functional brain connectivity has revealed the complex brain organization into large-scale networks. Such an organization not only permits the complex information segregation and integration during high cognitive processes but also determines the clinical consequences of alterations encountered in development, ageing, or neurological diseases. Recently, it has also been demonstrated that human brain networks shared topological properties with the so-called 'small-world' mathematical model, allowing a maximal efficiency with a minimal energy and wiring cost. Separately, magnetic resonance tractography and functional MRI connectivity have both brought new insights into brain organization and the impact of injuries. The small-world topology of structural and functional human brain networks offers a common framework to merge structural and functional imaging as well as dynamical data from electrophysiology that might allow a comprehensive definition of the brain organization and plasticity.


Rare earth elements distribution in grapevine varieties grown on volcanic soils: an example from Mount Etna (Sicily, Italy).
A geochemical and statistical approach has allowed identifying in rare earth elements (REEs) absorption a good fingerprinting mark for determining the territoriality and the provenance of Vitis vinifera L. in the district of Mount Etna (southern Italy). Our aim is to define the REEs distribution in different parts of the plants which grow in the same volcanic soil and under the same climate conditions, and therefore to assess whether REEs distribution may reflect the composition of the provenance soil or if plants can selectively absorb REEs in order to recognize the fingerprint in the Etna Volcano soils as well as the REEs pattern characteristic of each cultivar of V. vinifera L. The characteristic pattern of REEs has been determined by ICP-MS analyses in the soils and in the selected grapevine varieties for all the following parts: leaves, seeds, juice, skin, and berries. These geochemical criteria, together with the multivariate statistical analysis of the principal component analysis (PCA) and of the linear discriminant analysis (LDA) that can be summarized with the box plot, suggest that leaves mostly absorb REEs than the other parts of the plant. This work investigates the various parts of the plant in order to verify if each grape variety presents a characteristic geochemical pattern in the absorption of REEs in relationship with the geochemical features of the soil so to highlight the individual compositional fingerprint. Based on REE patterns, our study is a useful tool that allows characterizing the differences among the grape varieties and lays the foundation for the use of REEs in the geographic origin of the Mount Etna wine district.


[Lipid composition of human malignant brain tumors].
Malignant transformation is characterized by the uncontrolled proliferation of cells. And changes in the composition of glycolipids, cell surface component which may be involved in regulation of cell growth, were often observed in the malignant transformation. In this study, cholesterol, lipid-bound phosphorus, cerebroside, sulfatide and ganglioside were quantitated in the tissue of 20 human malignant brain tumors (malignant glioma, 8; low grade glioma, 4; metastatic tumor, 7; malignant meningioma, 1). As compared with normal brain, all tumor tissue contained lower cholesterol, sialic acid, cerebroside and sulfatide. Metastatic brain tumor or glioma showed characteristic patterns in the content of ganglioside, cerebroside and sulfatide respectively. The ganglioside patterns of metastatic tumor or glioma contained a greater proportion of structurally simpler gangliosides than normal brain. And in metastatic tumor, GM3 was a major ganglioside. On the contrary, glioma had increased proportion of GM3 and GD3 gangliosides. High grade glioma such as Grade 3-4 contained higher proportion of GM3 and GD3, whereas low grade glioma (Grade 1-2) contained less proportion of GM3 and GD3.


Effects of recombinant interleukin-2 and revaccination for hepatitis B in previously vaccinated, non-responder, chronic uraemic patients. Collaborative Group of Girona.
Growing evidence suggests that it is possible to seroconvert chronic renal failure patients who are absolute non-responders to hepatitis B vaccine by means of either additional booster vaccine doses or associated IL-2 administration or both. We have studied the possibilities of hepatitis B seroconversion by revaccination and its dependence on vaccine dose, and the effects of a concurrent low-dose rHuIL-2 regime. Forty known absolute non-responders with chronic renal failure were entered into a complete revaccination protocol. Patients were randomly assigned to two dosage groups of either 20 or 40 micrograms hepatitis B vaccine administered at 0, 1, 2 and 6 months. Further randomly selected patients from each dosage group were given 500,000 U of rHuIL-2 in the same deltoid area 4 h after vaccine administration. Sixty-seven per cent of patients revaccinated with 40 micrograms attained antibody protecting levels compared to only 20% of those receiving doses of 20 micrograms (P < 0.025). When compared with initial values, the ThCD4/CD25 cell count was significantly reduced immediately after HuR-IL2 administration (P < 0.003) and significantly increased 1 month after the last dose was given (P < 0.0003). A definite rHuIL-2 effect on HBV antibody synthesis could not be demonstrated, nor was erythropoietin found to enhance seroconversion. From these results we suggest that more intense and frequent antigenic stimulation as obtained by revaccination using four doses of 40 micrograms may effectively reduce the pool of hepatitis B vaccine nonresponders in chronic renal failure patients.


Support provider's appraisal detection bias and the efficacy of received support in medical students preparing for an exam.
Matching social support to the recipient's needs requires diagnostic sensitivity on the part of the provider. In particular, support needs to be responsive to the recipient's stress-related appraisals to be maximally effective. To assess the impact of bias in interpersonal stress assessment, medical students in 43 dyads reported on their own and each other's stress appraisals, social support, affect and performance during a 5-day preparation period culminating in a multiple choice examination. Less biased perceptions of loss appraisals by support providers within dyads were followed by support transactions associated with lower negative affect and better exam performance among recipients. More biased perceptions of threat appraisals were followed by increases in the recipients' negative affect. Results therefore suggest that support is more effective when the provider understands the recipient's concerns.


Method for simulating dose reduction in digital mammography using the Anscombe transformation.
This work proposes an accurate method for simulating dose reduction in digital mammography starting from a clinical image acquired with a standard dose. The method developed in this work consists of scaling a mammogram acquired at the standard radiation dose and adding signal-dependent noise. The algorithm accounts for specific issues relevant in digital mammography images, such as anisotropic noise, spatial variations in pixel gain, and the effect of dose reduction on the detective quantum efficiency. The scaling process takes into account the linearity of the system and the offset of the detector elements. The inserted noise is obtained by acquiring images of a flat-field phantom at the standard radiation dose and at the simulated dose. Using the Anscombe transformation, a relationship is created between the calculated noise mask and the scaled image, resulting in a clinical mammogram with the same noise and gray level characteristics as an image acquired at the lower-radiation dose. The performance of the proposed algorithm was validated using real images acquired with an anthropomorphic breast phantom at four different doses, with five exposures for each dose and 256 nonoverlapping ROIs extracted from each image and with uniform images. The authors simulated lower-dose images and compared these with the real images. The authors evaluated the similarity between the normalized noise power spectrum (NNPS) and power spectrum (PS) of simulated images and real images acquired with the same dose. The maximum relative error was less than 2.5% for every ROI. The added noise was also evaluated by measuring the local variance in the real and simulated images. The relative average error for the local variance was smaller than 1%. A new method is proposed for simulating dose reduction in clinical mammograms. In this method, the dependency between image noise and image signal is addressed using a novel application of the Anscombe transformation. NNPS, PS, and local noise metrics confirm that this method is capable of precisely simulating various dose reductions.


The Cold Shock Response.
This review focuses on the cold shock response of Escherichia coli. Change in temperature is one of the most common stresses that an organism encounters in nature. Temperature downshift affects the cell on various levels: (i) decrease in the membrane fluidity; (ii) stabilization of the secondary structures of RNA and DNA; (iii) slow or inefficient protein folding; (iv) reduced ribosome function, affecting translation of non-cold shock proteins; (v) increased negative supercoiling of DNA; and (vi) accumulation of various sugars. Cold shock proteins and certain sugars play a key role in dealing with the initial detrimental effect of cold shock and maintaining the continued growth of the organism at low temperature. CspA is the major cold shock protein of E. coli, and its homologues are found to be widespread among bacteria, including psychrophilic, psychrotrophic, mesophilic, and thermophilic bacteria, but are not found in archaea or cyanobacteria. Significant, albeit transient, stabilization of the cspA mRNA immediately following temperature downshift is mainly responsible for its cold shock induction. Various approaches were used in studies to detect cold shock induction of cspA mRNA. Sugars are shown to confer protection to cells undergoing cold shock. The study of the cold shock response has implications in basic and health-related research as well as in commercial applications. The cold shock response is elicited by all types of bacteria and affects these bacteria at various levels, such as cell membrane, transcription, translation, and metabolism.


The potential role of the glycoprotein osteoactivin/glycoprotein nonmetastatic melanoma protein B in pancreatic cancer.
Pancreatic ductal adenocarcinoma is still one of the deadliest solid cancers so the finding of new therapeutic approaches and novel targets are of utmost importance. Glycoprotein nonmetastatic melanoma protein B (GPNMB), initially termed glycoprotein nonmetastatic gene B and also named osteoactivin (OA), is a type 1 transmembrane protein that has been recently found to play a role in cancer cell proliferation, angiogenesis, and invasion. Due to its potential responsibility in cancer aggressiveness, the main objective of this work was to assess the role of GPNMB/OA in human pancreatic cancer. Using the human pancreatic cancer cell line Panc-1 in vitro, the effects of GPNMB on growth, proliferation, and invasion were tested by BrdU uptake, cell cycle and Annexin V-FITC analysis, RT-PCR, protein expression, and invasion chamber assays. Our results showed that GPNMB/OA protein expression prevents cells from apoptosis-enhancing proliferation and represents a novel modulator of the invasion and metastasis in pancreatic cancer cells. Due to its main membrane localization in cancer cells and its role in the aggressiveness of pancreatic cancer, GPNMB/OA could represent a novel targeted therapy for pancreatic cancer being attractive for antibody-based therapies.


Lung Transplant From Donor With Tracheal Bronchus: Case Report and Literature Review.
Donor lung abnormalities are quite rare; one of them is the presence of bronchial anomalies, whose incidence range is from 0.1% to 0.5%. The upper right tracheal bronchus is one of the most frequent anatomic variations. We present a case of successful double lung transplant in a young female patient affected by cystic fibrosis from a donor with upper right tracheal bronchus, emerging 2 rings before the tracheal carina. During implantation of the left lung, we performed a double apical segmentectomy on back table; therefore, the right lung was implanted with the standard technique. Four cases of graft transplant characterized by the presence of tracheal bronchus are reported in the scientific literature; the authors report 4 different technical solutions to tackle the problem of anatomic anomaly. We report the first case of graft segmentectomy at back table suggesting a simple, safe, and time-sparing procedure. In conclusion, provided that the team has sufficient skill in reductive surgery at the back table and the anthropometric data are permissive, we stress the opportunity to downsize the graft in order to minimize anastomotic risks and save time.


MethylPCA: a toolkit to control for confounders in methylome-wide association studies.
In methylome-wide association studies (MWAS) there are many possible differences between cases and controls (e.g. related to life style, diet, and medication use) that may affect the methylome and produce false positive findings. An effective approach to control for these confounders is to first capture the major sources of variation in the methylation data and then regress out these components in the association analyses. This approach is, however, computationally very challenging due to the extremely large number of methylation sites in the human genome. We introduce MethylPCA that is specifically designed to control for potential confounders in studies where the number of methylation sites is extremely large. MethylPCA offers a complete and flexible data analysis including 1) an adaptive method that performs data reduction prior to PCA by empirically combining methylation data of neighboring sites, 2) an efficient algorithm that performs a principal component analysis (PCA) on the ultra high-dimensional data matrix, and 3) association tests. To accomplish this MethylPCA allows for parallel execution of tasks, uses C++ for CPU and I/O intensive calculations, and stores intermediate results to avoid computing the same statistics multiple times or keeping results in memory. Through simulations and an analysis of a real whole methylome MBD-seq study of 1,500 subjects we show that MethylPCA effectively controls for potential confounders. MethylPCA provides users a convenient tool to perform MWAS. The software effectively handles the challenge in memory and speed to perform tasks that would be impossible to accomplish using existing software when millions of sites are interrogated with the sample sizes required for MWAS.


Liver holidays? A meta-analysis of drinking the same amount of alcohol daily or non-daily and the risk for cirrhosis.
Several alcohol drinking guidelines indicate that daily alcohol consumption should be avoided because of its negative impact on the liver and to avoid the development of alcohol use disorders. Evidence that supports this recommendation is scarce. Our aim was to compare daily versus non-daily drinking and its association with liver cirrhosis. We conducted a review using PubMed/Medline and Embase as databases, selecting longitudinal or case control studies. A random effects meta-analysis was conducted. Five mainly large-scale studies were retrieved. Daily drinking was associated with a significant increase in risk of liver cirrhosis compared to non-daily drinking, with a pooled relative risks of 1.71 (95% confidence interval 1.23-2.23) for men and 1.56 (95% confidence interval 1.39-1.74) for women. The consistent exposure to acetaldehyde and other toxins for daily drinkers may explain our findings. There should be days of abstinence to allow the liver to recover, especially for heavier drinkers.


Treatment of severe secondary hyperparathyroidism with administration of calcium carbonate, intermittent high oral doses of 1,25-dihydroxyvitamin D3 and dialysate with 3 mEq/1 calcium concentration.
In this study, we evaluated the effect of long-term administration of daily calcium carbonate (2-4 g/day) and intermittent high oral doses of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3, 3-4 micrograms, given twice a week] in conjunction with a 3-mEq/1 calcium concentration in the dialysate for the treatment of severe secondary hyperparathyroidism in 6 hemodialysis patients. All patients had reduced serum levels of 1,25-(OH)2D3, which increased significantly (p < 0.005) reaching the maximum level in the 4th month. Serum total and ionized calcium levels significantly increased also, in relation to those before treatment. No patients developed hypercalcemia. Serum phosphorus did not significantly change during the study. Initial serum intact parathyroid hormone (PTH) (1,241 +/- 233 pg/ml, mean +/- SEM) markedly decreased after starting treatment with 1,25-(OH)2D3, being 542 +/- 174 pg/ml in the 5th month and 477 +/- 174 pg/ml in the 8th month. These changes are statistically significant (p < 0.05 and < 0.007, respectively). Alkaline phosphatase behavior was similar to that of intact PTH. A constant direct correlation between intact PTH and alkaline phosphatase and an inverse significant correlation between intact PTH and 1,25-(OH)2D3 was evidenced by us. We conclude that oral 1,25-(OH)2D3 pulse therapy is very effective in suppressing PTH secretion. The administration of calcium carbonate and the use of dialysate with a reduced calcium concentration would allow to prevent hyperphosphatemia and the administration of high oral doses of 1,25-(OH)2D3 without concomitant hypercalcemia.


Galectins in Intestinal Inflammation: Galectin-1 Expression Delineates Response to Treatment in Celiac Disease Patients.
Galectins, a family of animal lectins characterized by their affinity for N-acetyllactosamine-enriched glycoconjugates, modulate several immune cell processes shaping the course of innate and adaptive immune responses. Through interaction with a wide range of glycosylated receptors bearing complex branched N-glycans and core 2-O-glycans, these endogenous lectins trigger distinct signaling programs thereby controling immune cell activation, differentiation, recruitment and survival. Given the unique features of mucosal inflammation and the differential expression of galectins throughout the gastrointestinal tract, we discuss here key findings on the role of galectins in intestinal inflammation, particularly Crohn's disease, ulcerative colitis, and celiac disease (CeD) patients, as well as in murine models resembling these inflammatory conditions. In addition, we present new data highlighting the regulated expression of galectin-1 (Gal-1), a proto-type member of the galectin family, during intestinal inflammation in untreated and treated CeD patients. Our results unveil a substantial upregulation of Gal-1 accompanying the anti-inflammatory and tolerogenic response associated with gluten-free diet in CeD patients, suggesting a major role of this lectin in favoring resolution of inflammation and restoration of mucosal homeostasis. Thus, a coordinated network of galectins and their glycosylated ligands, exerting either anti-inflammatory or proinflammatory responses, may influence the interplay between intestinal epithelial cells and the highly specialized gut immune system in physiologic and pathologic settings.


What is the function of hippocampal theta rhythm?--Linking behavioral data to phasic properties of field potential and unit recording data.
The extensive physiological data on hippocampal theta rhythm provide an opportunity to evaluate hypotheses about the role of theta rhythm for hippocampal network function. Computational models based on these hypotheses help to link behavioral data with physiological measurements of different variables during theta rhythm. This paper reviews work on network models in which theta rhythm contributes to the following functions: (1) separating the dynamics of encoding and retrieval, (2) enhancing the context-dependent retrieval of sequences, (3) buffering of novel information in entorhinal cortex (EC) for episodic encoding, and (4) timing interactions between prefrontal cortex and hippocampus for memory-guided action selection. Modeling shows how these functional mechanisms are related to physiological data from the hippocampal formation, including (1) the phase relationships of synaptic currents during theta rhythm measured by current source density analysis of electroencephalographic data from region CA1 and dentate gyrus, (2) the timing of action potentials, including the theta phase precession of single place cells during running on a linear track, the context-dependent changes in theta phase precession across trials on each day, and the context-dependent firing properties of hippocampal neurons in spatial alternation (e.g., "splitter cells"), (3) the cholinergic regulation of sustained activity in entorhinal cortical neurons, and (4) the phasic timing of prefrontal cortical neurons relative to hippocampal theta rhythm.


Clinical research: a globalized network.
Clinical research has become increasingly globalized, but the extent of globalization has not been assessed. To describe the globalization of clinical research, we used all (n = 13,208) multinational trials registered at ClinicalTrials.gov to analyzed geographic connections among individual countries. Our findings indicate that 95% (n = 185) of all countries worldwide have participated in multinational clinical research. Growth in the globalization of clinical research peaked in 2009, suggesting that the global infrastructure that supports clinical research might have reached its maximum capacity. Growth in the globalization of clinical research is attributable to increased involvement of non-traditional markets, particularly in South America and Asia. Nevertheless, Europe is the most highly interconnected geographic region (60.64% of global connections), and collectively, Europe, North America, and Asia comprise more than 85% of all global connections. Therefore, while the expansion of clinical trials into non-traditional markets has increased over the last 20 years and connects countries across the globe, traditional markets still dominate multinational clinical research, which appears to have reached a maximum global capacity.


Carbapenemase-producing Enterobacteriaceae and Aeromonas spp. present in wastewater treatment plant effluent and nearby surface waters in the US.
Carbapenemase-producing bacteria (CPB) are rare, multidrug resistant organisms most commonly associated with hospitalized patients. Metropolitan wastewater treatment plants (WWTP) treat wastewater from large geographic areas which include hospitals and may serve as epidemiologic reservoirs for the maintenance or expansion of CPB that originate from hospitals and are ultimately discharged in treated effluent. However, little is known about the potential impact of these WWTP CPB on the local surface water and their risk to the public health. In addition, CPB that are present in surface water may ultimately disseminate to intensively-managed animal agriculture facilities where there is potential for amplification by extended-spectrum cephalosporins. To better understand the role of WWTPs in the dissemination of CPB in surface waters, we obtained samples of treated effluent, and both upstream and downstream nearby surface water from 50 WWTPs throughout the US. A total of 30 CPB with clinically-relevant genotypes were recovered from 15 WWTPs (30%) of which 13 (50%) serviced large metropolitan areas and 2 (8.3%) represented small rural populations (P < 0.05). Recovery of CPB was lowest among WWTPs that utilized ultraviolet radiation for primary disinfection (12%), and higher (P = 0.11) for WWTPs that used chlorination (42%) or that did not utilize disinfection (50%). We did not detect a difference in CPB recovery by sampling site, although fewer CPB were detected in upstream (8%) compared to effluent (20%) and downstream (18%) samples. Our results indicate that WWTP effluent and nearby surface waters in the US are routinely contaminated with CPB with clinically important genotypes including those producing Klebsiella pneumoniae carbapenemase (KPC) and New Delhi metallo-beta-lactamase (NDM). This is a concern for both public health and animal agriculture because introduction of CPB into intensively managed livestock populations could lead to their amplification and foodborne dissemination.


Exploiting drug delivery systems for oral route in the peptic ulcer disease treatment.
Peptic ulcer disease (PUD) is a common condition that is induced by acid and pepsin causing lesions in the mucosa of the duodenum and stomach. The pathogenesis of PUD is a many-sided scenario, which involves an imbalance between protective factors, such as prostaglandins, blood flow, and cell renewal, and aggressive ones, like alcohol abuse, smoking, Helicobacter pylori colonisation, and the use of non-steroidal anti-inflammatory drugs. The standard oral treatment is well established; however, several problems can decrease the success of this therapy, such as drug degradation in the gastric environment, low oral bioavailability, and lack of vectorisation to the target site. In this way, the use of strategies to improve the effectiveness of these conventional drugs becomes interesting. Currently, the use of drug delivery systems is being explored as an option to improve the drug therapy limitations, such as antimicrobial resistance, low bioavailability, molecule degradation in an acid environment, and low concentration of the drug at the site of action. This article provides a review of oral drug delivery systems looking for improving the treatment of PUD.


Effects of coinfection with Pomphorhynchus bulbocolli on development of leptorhynchoides thecatus (Acanthocephala) in amphipods (Hyalella azteca).
The effect of the presence of Pomphorhynchus bulbocolli on the development of Leptorhynchoides thecatus (Acanthocephala) in amphipod intermediate hosts (Hyalella azteca) was examined. Two groups of amphipods were exposed either to eggs of both species (experimental) or only to L. thecatus eggs (control). Amphipods of both groups were dissected 39 days postexposure. The percentage of L. thecatus at the cystacanth stage and mean abundance of cystacanths and precystacanths per amphipod were determined. Contingency table analysis and Fisher's exact tests demonstrated that a significantly smaller proportion of L. thecatus reached the cystacanth stage in coinfected amphipods of the experimental group than either worms in the control group or worms in L. thecatus-only infections of the experimental group. Interspecific interaction between acanthocephalans in intermediate hosts has not been reported previously. Coinfection reduces the number of L. thecatus in amphipods available for transmission to definitive hosts. Habitat separation by eggs of L. thecatus and P. bulbocolli might reduce this effect if amphipods are less likely to become coinfected when eggs are in different microhabitats than when they are not.


The interplay between evolution, regulation and tissue specificity in the Human Hereditary Diseasome.
Human disease genes can be distinguished from essential (embryonically lethal) and non-disease genes using gene attributes. Such attributes include gene age, tissue specificity of expression, regulatory capacity, sequence length, rate of sequence variation and capacity for interaction. The resulting information has been used to inform data mining approaches seeking to identify novel disease genes. Given the dynamic nature of this field and the rapid rise in relevant information, we have chosen to perform a single integrated mining approach to explore relationships among gene attributes and thereby characterise evolutionary trends associated with disease genes. All against all cross comparison of 2,522 disease gene attributes revealed significant relationships existed between the age, disease-association and expression pattern of genes and the tissues within which they are expressed. We found that the over-representation of disease genes among old genes holds for tissue-specific genes, but the correlation between age and disease association vanished when conditioning on tissue-specificity. Of the 32 tissues studied, the genes expressed in pancreas are on average older than the genes expressed in any other tissue, while the testis expressed the lowest proportion of old genes. Following a focussed analysis on the impact of regulatory apparatus on evolution of disease genes, we show that regulators, comprising transcription factors and post-translation modified proteins, are over-represented among ancient disease genes. In addition, we show that the proportion of regulator genes is affected by gene age among disease genes and by tissue-specificity among non-disease genes. Finally, using 55,606 true positive gene interaction data, we find that old disease genes interacts with other old disease genes and interacting new genes interacts with genes originating from higher phylostrata. This study supports the non-random nature of the human diseasome. We have identified a variety of distinct features and correlations to other molecular attributes that can be used to distinguish the set of disease causing genes. This was achieved by harnessing the power of mining large scale datasets from OMIM and other databases. Ultimately such knowledge may contribute to the identification of novel human disease genes and an enhanced understanding of human biology.


Use of gesture development in profiling children's prelinguistic communication skills.
Comparing children's skills across and within domains of development has become a standard in providing early intervention services. Profiling a child's strengths and challenges can help in making decisions regarding eligibility, diagnosis, and intervention. Profiling is particularly important for children who are not yet talking, due to the variability in production skills and the lack of guidelines as to which children are "at risk" for communication deficits versus those who are "late talkers." One area underutilized in profiling is gesture development, despite the fact that research has indicated that the amount and type of gesture use can help in early identification and is predictive of later language. To guide practicing professionals and researchers in using gesture development to profile children's communication skills, this article provides an overview of the types of gestures and their development, describes assessment methods and tools to document gesture development, pinpoints behaviors and factors important in identifying children with disabilities, and ends with brief examples of using profiling in assessment and intervention planning. Gesture use should be an important component in profiling children's communication skills, and this type of profiling can enhance both the assessment and intervention process.


Constitutive relations in dense granular flows.
We use simulations to investigate constitutive relations in dry granular flow. Our system is comprised of polydisperse sets of spherical grains falling down a vertical chute under the influence of gravity. Three phases or states of granular matter are observed: a free-fall dilute granular gas region at the top of the chute, a granular fluid in the middle and then a glassy region at the bottom. We examine a complete closed set of constitutive relations capable of describing the local stresses, heat flow, and dissipation in the different regions. While the pressure can be reasonably described by hard sphere gas models, the transport coefficients cannot. Transport coefficients such as viscosity and heat conductivity increase with decreasing temperature in the fluid and glassy phases. The glass exhibits signs of a finite yield stress and we show that the static sand pile is a limit of our glassy state.


Resting State Functional Connectivity of the Lateral and Medial Hypothalamus in Cocaine Dependence: An Exploratory Study.
The role of dopamine in cocaine misuse has been extensively documented for the mesocorticolimbic circuit. Preclinical work from earlier lesion studies to recent multidisciplinary investigations has suggested that the hypothalamus is critically involved in motivated behavior, with the lateral and medial hypothalamus each involved in waking/feeding and resting/satiety. However, little is known of hypothalamus function and dysfunction in cocaine misuse. Here, we examined resting state functional connectivity of the lateral and medial hypothalamus in 70 individuals with cocaine dependence (CD) and 70 age as well as gender matched healthy controls (HC). Image pre-processing and analyses followed published work. Compared to HC, CD showed increased lateral hypothalamic connectivity with dorsolateral prefrontal cortex and decreased functional connectivity with the ventral precuneus. CD showed increased medial hypothalamic connectivity with the inferior parietal lobule and decreased connectivity with the ventromedial prefrontal cortex, temporal gyrus, fusiform gyrus, and ventral striatum. Further, at trend level significance, the connectivity strength between lateral hypothalamus and dorsolateral prefrontal cortex was positively correlated with total amount of cocaine use in the past month (p = 0.004, r = 0.35) and the connectivity strength between medial hypothalamus and ventral striatum was negatively correlated with cocaine craving as assessed by the Tiffany Cocaine Craving Questionnaire (p = 0.008, r = -0.33). Together, the findings demonstrated altered resting state functional connectivity of the hypothalamus and may provide new insight on circuit level deficits in cocaine dependence.


Degree of Conversion and Oxygen-Inhibited Layer Effect of Three Dental Adhesives.
This study investigated the effect of the oxygen-inhibited layer on the degree of conversion (DC) of three dental adhesives, comparing two different protocols. Quartz-tungsten-halogen (QTH) light curing and light-emitting diode (LED) were used to cure three adhesives: OptiBond All in One (OAIO), Adper Easy Bond (AEB) and ExciteF (EXF). The DC was calculated utilizing Fourier Transform infrared spectroscopy (FTIR) (n = 12). The two protocols used were as follows: (i) prevent the oxygen-inhibited layer using a Mylar plastic strip pushed onto each bonding adhesive; and (ii) polymerize samples without a plastic strip. The data was analyzed statistically by a three-way ANOVA, and Tukey Test (a = 0.05). The presence of an oxygen-inhibited layer reduced the DC of the adhesives by 64% for EXF, 46% for AEB and 32% for OAIO. This study suggests that there are differences among the oxygen-inhibited layers present for the adhesives tested.


Intravascular ultrasound imaging in the assessment of atherosclerotic plaques in rabbit abdominal aorta: comparison with histologic findings.
To examine the correlation between the echogenicity and the components of atherosclerotic plaques in rabbit. The atherosclerotic plaque formation in the abdominal aortas of hyperlipidemic or normolipidemic rabbits was stimulated by inserting polyethylene tubing. Intravascular ultrasound (30-MHz, 4.5 F catheter) investigation was performed at locations in the vessel. The intravascular ultrasound images of the plaques were evaluated and compared with the histologic findings. Ultrasound images delineated areas showing hyperechoic or hypoechoic ultrasound beams in the plaques. Histologic studies revealed that the hyperechoic areas were closely associated with a dense fibrous extracellular matrix, whereas the hypoechoic areas corresponded to lesions showing a marked accumulation of foamy macrophages or proteoglycan-rich loose myxoid extracellular matrix with smooth muscle cell proliferation. A good correlation between ultrasound images and histologic features was observed. These results suggest that intravascular ultrasound imaging could provide useful information for assessing the tissue characteristics of atherosclerotic lesions.


Semilunar Flap for Minimizing the Scar Length in Nipple Reconstruction.
Nipple reconstruction is an essential procedure to change an amorphous breast mound to a distinct breast. Various skin flaps have been proposed for nipple reconstruction. In the C-V flap technique, which is one of the most commonly used flaps for nipple reconstruction, the scar that is developed after closure of the donor site of the V-flap frequently extends beyond a new areola area. To reduce the length of the donor site scar, various modifications of the C-V flap have been proposed. We adopted the semilunar flap instead of the V flap of C-V flap by changing the angle of V flap for nipple reconstruction. The semilunar flap design allowed generation of a donor flap with sufficient width and length of the skin flap for a nipple barrel without increasing the length of the donor site scar. In most cases, the semilunar flaps showed stable outcomes and resulted in angled donor-site scars that were usually located within the boundary of a new areola. We think the semilunar flap represents a good alternative method in nipple reconstruction by changing the angle of the donor-site scar and leaving the scar length within the new areolar area.


Electrofriction and dynamic stern layers at planar charged surfaces.
Using dynamic simulations, the electrophoretic mobility of counterions at a substrate with fixed or mobile surface charges under the action of a lateral electric field is studied. The lateral charge inhomogeneity and corrugation of the substrate is taken into account. Because of the pronounced electrofriction between counterions and surface ions, a large fraction of counterions is practically immobilized for highly charged substrates. This explains the experimentally observed saturation of the electrophoretic mobility of charged particles in the limit of high surface charge density.


The risk of serious infection in rheumatoid arthritis patients receiving tocilizumab compared with tumor necrosis factor inhibitors in Korea.
To examine the risk of serious infections (SIs) among patients with rheumatoid arthritis (RA) treated with tocilizumab compared with tumor necrosis factor inhibitor (TNFi) in Korea. We conducted a retrospective cohort study using the Korean National Health Insurance data. The study cohort included patients ≥18 years with RA who were initiated with tocilizumab or TNFi between January 2013 and June 2018. The primary outcome was a composite endpoint of SIs, defined as an infection resulting in intravenous antimicrobial therapy or hospitalization. Secondary outcomes were organ-specific SIs. To control for confounders, we used inverse probability of treatment weighting (IPTW) using propensity score. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using a multivariable Cox regression model. A total of 8794 patients were identified: 1395 and 7399 patients initiated with tocilizumab and TNFi, respectively. The mean follow-up durations were 1.2 years for tocilizumab initiators and 1.0 year for TNFi initiators. After IPTW and adjustment, no increased risk of SIs was observed in tocilizumab versus TNFi (HR, 1.00; 95%CI, 0.90-1.11). In the secondary analysis, tocilizumab was associated with a higher risk of skin and subcutaneous tissue infections (HR, 1.26; 95%CI, 1.02-1.54) and a lower risk of urological and gynecological infections (HR, 0.65; 95%CI, 0.49-0.87) compared to TNFi. In this population-based cohort of RA patients in Korea, tocilizumab was not associated with a higher risk of SI compared to TNFi. However, tocilizumab should be carefully used for patients at high risk for skin-related infections.


Electroporation of Mycobacteria.
The introduction of DNA into bacterial cells is one of the foundational methods of bacterial genetics. Transformation of mycobacterial species is complicated due to the structure of the cell wall, which has a complex outer layer with low permeability. Electroporation has become a routine procedure in genetic studies. In this process, cells are subjected to a brief high-voltage electrical impulse which allows the entry of DNA. It can be used to introduce plasmid DNA, phage DNA, or oligonucleotides. This chapter presents methods for introducing DNA into a representative slow-growing species, M. tuberculosis, and a representative fast-growing species, M. smegmatis. Other mycobacteria can be transformed using variations of these methods, although the efficiency of transformation will vary.