Evaluation of oxidative stress markers in obstructive sleep apnea syndrome and additional antioxidant therapy: a review article.
The hypoxia and reoxygenation cycles in obstructive sleep apnea syndrome (OSAS) cause a change in the oxidative balance, leading to the formation of reactive oxygen species capable of reacting with other organic molecules impairing their functions. This study aimed to determine the best markers of oxidative stress in OSAS and what better antioxidant agent to be used to treat the disease. Searches were conducted in three different databases (PubMed, LILACS, SCIELO), using as descriptors the terms obstructive sleep apnea, oxidative stress, and antioxidant therapy. A total of 120 articles were found but only those considered of interest to the research were selected. Thus, 10 articles were included for further analysis regarding the biomarkers of oxidative stress in OSAS, and 6 articles to evaluate the antioxidant most often used for demonstration of efficacy. The thioredoxin, malondialdehyde, superoxide dysmutase, and reduced iron were the most commonly used biomarkers and showed a more consistent relationship between increased oxidative stress and OSAS. As antioxidant therapy, vitamin C and N-acetylcysteine (NAC) presented interesting results as a reduction of oxidative stress, which may become an alternative to the complementary treatment of OSAS. This review's findings agree mostly to measure that the markers of oxidative stress in OSAS may be a contributing aspect to assessment and monitoring of patient, and the antioxidant therapy appears to be beneficial in the treatment of OSAS.


Localization of substance P, acetylcholinesterase, muscarinic receptors and alpha-bungarotoxin binding sites in the rat interpeduncular nucleus.
On the basis of acetylcholinesterase (AChE) staining, the rat interpeduncular nucleus was subdivided into five distinct zones. Intense AChE staining was observed in the dorsal cap and the lateral zones. Moderate staining was seen in the median zone and the dorsoventral column. The perivascular zones were unlabeled. Adjacent sections were stained for AChE and for substance P immunofluorescence. Substance P like immunoreactivity was found to coincide with the localization of AChE in the dorsal cap and the lateral zones. Both muscarinic receptors and alpha-bungarotoxin binding sites had distributions resembling that of AChE. Neither unilateral nor bilateral lesions of the habenulae changed the number or distribution pattern of the receptors. It was concluded that cholinergic receptors are localized postsynaptically. Our study suggests AChE and substance P containing fibers terminate in well defined zones of the interpeduncular nucleus which also contain muscarinic and nicotinic receptors.


Tobacco company efforts to influence the Food and Drug Administration-commissioned Institute of Medicine report clearing the smoke: an analysis of documents released through litigation.
Spurred by the creation of potential modified risk tobacco products, the US Food and Drug Administration (FDA) commissioned the Institute of Medicine (IOM) to assess the science base for tobacco "harm reduction," leading to the 2001 IOM report Clearing the Smoke. The objective of this study was to determine how the tobacco industry organized to try to influence the IOM committee that prepared the report. We analyzed previously secret tobacco industry documents in the University of California, San Francisco Legacy Tobacco Documents Library, and IOM public access files. (A limitation of this method includes the fact that the tobacco companies have withheld some possibly relevant documents.) Tobacco companies considered the IOM report to have high-stakes regulatory implications. They developed and implemented strategies with consulting and legal firms to access the IOM proceedings. When the IOM study staff invited the companies to provide information on exposure and disease markers, clinical trial design for safety and efficacy, and implications for initiation and cessation, tobacco company lawyers, consultants, and in-house regulatory staff shaped presentations from company scientists. Although the available evidence does not permit drawing cause-and-effect conclusions, and the IOM may have come to the same conclusions without the influence of the tobacco industry, the companies were pleased with the final report, particularly the recommendations for a tiered claims system (with separate tiers for exposure and risk, which they believed would ease the process of qualifying for a claim) and license to sell products comparable to existing conventional cigarettes ("substantial equivalence") without prior regulatory approval. Some principles from the IOM report, including elements of the substantial equivalence recommendation, appear in the 2009 Family Smoking Prevention and Tobacco Control Act. Tobacco companies strategically interacted with the IOM to win several favored scientific and regulatory recommendations.


Super responders to guselkumab treatment in moderate-to-severe psoriasis: a real clinical practice pilot series.
The term super responders defines a subset of patients with moderate-to-severe psoriasis that present a rapid and higher rate of response to biological treatments in comparison to the general population. Little scientific evidence to explain the behavior and clinical characteristics of these psoriatic patients has been published thus far. Its characterization could be important to improve therapeutic optimization and to identify the profile of patients that will respond efficiently to biological treatments. The main objective of this study was to evaluate and characterize the proportion of super-responder patients (who achieved PASI = 0 at week 12 and 24) in a total of 87 patients with moderate-to-severe psoriasis treated with guselkumab. Also, our intent was to analyze and evaluate differences in response to guselkumab in absolute PASI, PASI 75, PASI 90, PASI 100, BSA, VAS pruritus, and DLQI between groups. A total of 14 out of 87 patients treated with guselkumab were characterized as SR. No differences in demographic characteristics were found. The percentage of patients reaching PASI 75, PASI 90, and PASI 100 were numerically greater for SR than N-SR at week 12, 24, 36, and 52. These differences were more pronounced for PASI 100 > PASI 90 > PASI 75. SR performed better and faster to guselkumab treatment as assessed by absolute PASI, BSA, VAS pruritus, and DLQI. Statistically significant differences were found in absolute PASI, BSA, VAS pruritus, and DLQI between groups along the 52 weeks of study. No differences in drug survival were found between groups (P = 0.3326). Our study demonstrated for the first time, in a real clinical practice setting, the presence of a subpopulation of patients that super respond to guselkumab at week 12 and 24 and maintain this efficacy for 52 weeks. Further research must be performed to identify basal specific characteristics of this SR population.


Characterization of "plasma proteins" secreted by cultured rat macroglial cells.
The brain is isolated behind a blood-tissue barrier that restricts the access of circulating proteins to neural cells. There is evidence that some of these proteins are synthesized within the central nervous system. The present study examines the synthesis and secretion of such proteins by cultured macroglial cells. Primary glial cultures were derived from cortical and subcortical regions of neonatal rat brains, and subsequent secondary cultures were enriched in type-1 astrocytes, type-2 astrocytes, or oligodendrocytes. Newly synthesized proteins were immunoprecipitated from the culture media using antisera directed against whole rat serum. All three types of glial cells secreted a range of plasma proteins. In general, type-1 astrocytes secreted more of these proteins than did type-2 astrocytes or oligodendrocytes, although the one-dimensional polyacrylamide gel electrophoresis (PAGE) profiles were specific for each cell type. Anti-sera directed against specific plasma proteins identified three of the most abundant proteins secreted by type-1 astrocytes as transferrin, alpha-2-macroglobulin, and ceruloplasmin. Northern blot analysis of cellular RNA confirmed that type-1 astrocytes contained transferrin mRNA, and that it was more abundant in cultures derived from subcortical regions than from cortical regions. In situ hybridization studies revealed that virtually all type-1 and type-2 astrocytes contained transferrin mRNA. Since the proteins identified in this study have been proposed to have a variety of neurotrophic roles in the central nervous system, these data further extend the range of possible functions that glial cells may serve in the CNS.


High pressure/temperature pasting and gelling of starch related to multilevel structure-analyzed with RVA 4800.
This paper evaluated the relationship between multi-scale structure and high-pressure gelation properties of nine types of starches with different amylose (AM) content and crystalline polymorphic structure by RVA 4800. Higher average chain lengths of long amylopectin (AP) chains (DP > 36) and AM content, and lower relative content of short AP chains (DP ≤ 36) contributed to the higher peak temperature and peak time at 95-140 °C, and lower peak viscosity, through viscosity, and final viscosity at 95-110 °C. Rheological and texture parameters including storage modulus, loss modulus, hardness, and gumminess, had no significant correlation with starch structural parameters at 95-120 °C, but were instead controlled by AM molecular structure at 130-140 °C. AM content was mainly responsible for the rheological behaviors of starch gels at 130-140 °C, and short and intermediate AM chains were mainly associated with the texture of starch gels at the temperature ranges.


Immunohistochemical evaluation of a sarcomatoid hepatocellular carcinoma with osteoclastlike giant cells.
Malignant liver tumors with osteoclast-like giant cells are rare. A literature search showed 17 previously reported cases that included the following: (1) 8 undifferentiated hepatocellular carcinomas, (2) 5 sarcomatous tumors with osteoclast-like giant cells associated with intrahepatic cholangiocarcinoma or liver cystadenocarcinoma, and (3) 4 sarcomatoid tumors with osteoclast-like giant cells associated with areas of a conventional hepatocellular carcinoma. A 68-year-old man presented with a tumor of the right lobe of the liver on ultrasonography and computed tomography. Laparoscopy showed a tumor (diameter, 4 cm) in segments 7 and 8 of the right liver lobe that adhered to the retroperitoneum. The tumor recurred 3 months after liver segmentectomy. Repeat laparoscopy showed diffuse and nodular metastases to the omentum and peritoneum. Light microscopy showed that part of the tumor had features of classic hepatocellular carcinoma. Another part of the tumor had a solid sarcomatous pattern with osteoclast-like giant cells that were irregularly distributed between the smaller undifferentiated tumor cells; cells of this part of the tumor were positive for heppar-1. Light microscopic findings including osteoclast-like giant cells, and the strong reaction of heppar-1 antibody with cells of the sarcomatous part of the tumor, confirmed that this sarcomatous element was a metaplastic or transformed portion of hepatocellular carcinoma. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6000512901462616.


Expression of excision repair genes in non-malignant bone marrow from cancer patients.
The patterns of expression of 3 human DNA-repair genes (ERCC1, ERCC2, ERCC6) were assessed in 52 bone-marrow specimens obtained from cancer patients prepared for autologous bone-marrow transplantation. Marrow was collected prior to the initiation of treatment in patients with sarcoma or testicular cancer; marrow was collected after initial cytoreductive therapy for patients with non-Hodgkin's lymphoma, Hodgkin's disease, and other tumors. Slot-blot analysis of marrow RNA showed a bimodal pattern of ERCC1, ERCC2 and ERCC6 gene expression with relative expression values ranging more than 200-fold. This pattern was seen in all patient groups and appeared to be independent of whether or not patients had received prior chemotherapy. In all patient groups, when expression was low for ERCC1, expression was also low for ERCC2 and ERCC6, suggesting that expression of these genes may be coordinated within an individual although they are located on two different chromosomes. Southern blot analyses of Pst I digests of DNA from 6 bone-marrow samples indicate no differences in ERCC1 gene copy number between high expressors and low expressors. There is absence of restriction fragment length polymorphism for ERCC1 suggesting that the different levels of expression in high and low expressors were not due to major deletions or rearrangements of the ERCC1 gene. We conclude that expression of these ERCC genes may vary widely between individuals, and that within an individual, their expression may be linked and coordinated by a common regulatory mechanism.


Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure: role of glutamine redefined.
Acute liver failure (ALF) is characterized neuropathologically by cytotoxic brain edema and biochemically by increased brain ammonia and its detoxification product, glutamine. The osmotic actions of increased glutamine synthesis in astrocytes are considered to be causally related to brain edema and its complications (intracranial hypertension, brain herniation) in ALF. However studies using multinuclear (1)H- and (13)C-NMR spectroscopy demonstrate that neither brain glutamine concentrations per se nor brain glutamine synthesis rates correlate with encephalopathy grade or the presence of brain edema in ALF. An alternative mechanism is now proposed whereby the newly synthesized glutamine is trapped within the astrocyte as a consequence of down-regulation of its high affinity glutamine transporter SNAT5 in ALF. Restricted transfer out of the cell rather than increased synthesis within the cell could potentially explain the cell swelling/brain edema in ALF. Moreover, the restricted transfer of glutamine from the astrocyte to the adjacent glutamatergic nerve terminal (where glutamine serves as immediate precursor for the releasable/transmitter pool of glutamate) could result in decreased excitatory transmission and excessive neuroinhibition that is characteristic of encephalopathy in ALF. Paradoxically, in spite of renewed interest in arterial ammonia as a predictor of raised intracranial pressure and brain herniation in ALF, ammonia-lowering agents aimed at reduction of ammonia production in the gut have so far been shown to be of limited value in the prevention of these cerebral consequences. Mild hypothermia, shown to prevent brain edema and intracranial hypertension in both experimental and human ALF, does so independent of effects on brain glutamine synthesis; whether or not hypothermia restores expression levels of SNAT5 in ALF awaits further studies. While inhibitors of brain glutamine synthesis such as methionine sulfoximine, have been proposed for the prevention of brain edema in ALF, potential adverse effects have so far limited their applicability.


Improving Facial Fat Graft Survival Using Stromal Vascular Fraction-Enriched Lipotransfer: A Prospective Multicenter, Randomized Controlled Study.
Although previous clinical studies have reported that cell-assisted lipotransfer increases the fat survival rate in facial fat transplants, most were case studies without quantitative evaluation. A multi-center, prospective, randomized, controlled study was performed to evaluate the safety and efficacy of the stromal vascular fraction (SVF) in facial fat grafts. Twenty-three participants were enrolled for autologous fat transfer in the face, and randomly assigned to the experimental ( n =11) and control ( n =12) groups. Fat survival was assessed using magnetic resonance imaging at 6 and 24 weeks postoperatively. Subjective evaluations were performed by the patients and surgeons. To address safety concerns, results of an SVF culture and the postoperative complications were recorded. The overall fat survival rate was significantly higher in the experimental group than in the control group (6 weeks: 74.5±9.99% vs. 66.55±13.77%, p <0.025; 24 weeks: 71.27±10.43% vs. 61.98±13.46%, p <0.012). Specifically, graft survival in the forehead was 12.82% higher in the experimental group when compared with that in the control group at 6 weeks ( p <0.023). Furthermore, graft survival in the forehead ( p <0.021) and cheeks ( p <0.035) was superior in the experimental group at 24 weeks. At 24 weeks, the aesthetic scores given by the surgeons were higher in the experimental group than in the control group ( p <0.03); however, no significant intergroup differences were noted in the patient-evaluated scores. Neither bacterial growth from SVF cultures nor postoperative complications were noted. SVF enrichment for autologous fat grafting can be a safe and effective technique for increasing the fat retention rate.


"Cullin 4 makes its mark on chromatin".
Cullin 4 (Cul4), a member of the evolutionally conserved cullin protein family, serves as a scaffold to assemble multisubunit ubiquitin E3 ligase complexes. Cul4 interacts with the Ring finger-containing protein ROC1 through its C-terminal cullin domain and with substrate recruiting subunit(s) through its N-terminus. Previous studies have demonstrated that Cul4 E3 ligase ubiquitylates key regulators in cell cycle control and mediates their degradation through the proteasomal pathway, thus contributing to genome stability. Recent studies from several groups have revealed that Cul4 E3 ligase can target histones for ubiquitylation, and importantly, ubiquitylation of histones may facilitate the cellular response to DNA damage. Therefore, histone ubiquitylation by Cul4 E3 ligase constitutes a novel mechanism through which Cul4 regulates chromatin function and maintains genomic integrity. We outline these studies and suggest that histone ubiquitylation might play important roles in Cul4-regulated chromatin function including the cellular response to DNA damage and heterochromatin gene silencing.


Modulating reproductive activity in stallions: a review.
Situations in which suppression or stimulation of reproductive activity in stallions has been attempted, or is desired, include resolution of the equine arteritis virus 'shedding' state, induction of testicular descent in inguinal cryptorchids, and the improvement of sperm production capacity and/or semen quality in sub-fertile stallions. However, the most common reason for wanting to modulate reproductive activity in a stallion is to alter the expression of sexual behaviour. In the case of intact stallions used for competitive or recreational purposes, the overt expression of sexual or aggressive behaviour can be distracting for both animal and owner and, in some cases, dangerous to all concerned. By the same token, a breeding stallion that displays little interest in mounting a mare/phantom, or is slow to achieve erection and/or ejaculation, can be extremely frustrating. This paper reviews the major pharmacological agents reported to usefully modify reproductive activity in stallions, and outlines their pros and cons when compared to training, management or surgical alternatives.


Clinical characteristics and natural course of recurrent vestibulopathy: a long-term follow-up study.
To investigate the clinical characteristics and the natural course of recurrent vestibulopathy (RV). Retrospective study. During the period April 2002 to February 2008, we reviewed the clinical records of 98 patients diagnosed with RV. All patients were approached by telephone and using a questionnaire. The analysis included age, sex distribution, natural history, pure-tone audiometry, caloric response, age at onset, and the characteristics of vertigo. Median follow-up was 63.1 months (range, 24-103 months). Patients had a mean age at onset of 39 years and a mean duration of 4.2 years. An obvious female predilection was found, and unilateral caloric paresis (≥ 25%) was seen in 35%. Of the 98 patients, symptoms resolved in 82% but were unchanged in 12%. RV developed to Ménière's disease in four patients and to migraine in two. No patient with RV developed a central nervous system disease or benign paroxysmal positional vertigo during follow-up. The study suggests that in the majority of cases, vertigo spontaneously resolves and that the risks of development to Ménière's disease or migraine are low.


Differences in Motivating Factors for SARS-CoV-2 Vaccination and Perceptions of Infection Risk among Healthcare and EMS Personnel in South Carolina.
Although medical workers were prioritized to receive the coronavirus disease 2019 (COVID-19) vaccination, many have declined. Even though studies have investigated differences in COVID-19-related attitudes and vaccination for workers in hospitals and long-term care facilities, none have included emergency medical services (EMS) personnel. We investigated the association between type of medical worker (EMS vs healthcare worker [HCW]) and COVID-19 vaccination, vaccine beliefs, vaccine motivators, personal protection behaviors, and risk perceptions. The data for self-identified HCWs came from surveys distributed to randomly selected residents of South Carolina and EMS personnel recruited at a targeted surveillance testing event during the South Carolina EMS Symposium. Pearson χ2 and Fisher exact tests analyzed differences in the distribution of demographic characteristics and self-reported COVID-19 vaccination attitudes by medical workers. Multivariable logistic regression assessed the association between COVID-19 vaccination and type of medical worker, adjusting for age, sex, race, and frontline status, and assessed the associations among vaccine beliefs, vaccine motivators, personal protection behaviors, and risk perceptions by type of medical worker, adjusting for age, sex, race, frontline status, and vaccination status. Of the 126 respondents 57.9% were EMS, 42.1% were HCWs, and 73.6% of the cohort were self-reported frontline medical workers. Approximately two-thirds of respondents received a vaccine for COVID-19, with no significant differences between EMS and HCWs; however, EMS workers were significantly less likely to receive the vaccination out of concern about exposures at work/school (adjusted odds ratio [aOR] 0.22, 95% confidence interval [CI] 0.08-0.57), concern about exposures within the community (aOR 0.18, 95% CI 0.07-0.48), or to do their part to control the pandemic (aOR 0.20, 95% CI 0.06-0.69). EMS workers also were significantly less likely to wear a mask all/most of the time when outside the home (aOR 0.04, 95% CI 0.0-0.21) and less concerned about the spread of COVID-19 in their community as compared with HCWs (aOR 0.19, 95% CI 0.06-0.56). EMS personnel were significantly less concerned about the spread of COVID-19 in their community and significantly less likely to wear a mask all/most of the time while outside the home as compared with HCWs. Differences in the COVID-19-related attitudes and personal protection behaviors of EMS personnel should be used to develop targeted interventions to increase vaccine motivation and adherence to personal protection protocols.


Light evoked release of radioactivity from rabbit retinas preloaded with (3H)-GABA.
Light flashes evoke an increased release of radioactivity in vitro from rabbit retinas preloaded with (3H)-GABA in vivo. Constant light does not affect the release. No light evoked release can be demonstrated from the glia. Pentobarbitone and AOAA depress the evoked release. The results are consistent with GABA being a retinal neuro-transmitter, most likely in a class of amacrines.


Effect of size and temperature on the quantity of immunoglobulin in channel catfish, Ictalurus punctatus.
Concentrations of serum immunoglobulin (Ig) were determined for 30 channel catfish from pond water at 10 degrees C. These values were compared to measurements of 15 channel catfish from pond water at 30 degrees C. Channel catfish from 10 degrees C pond water had no significant (P greater than 0.05) different Ig concentrations (mean, 398 mg/dl) than catfish from 30 degrees C pond water (mean, 367 mg/dl). Serum Ig concentrations appear not to be different in cold (10 degrees C) vs warm (30 degrees C) pond water for 37.5-45 cm catfish. Channel catfish, 7.5-15 cm (n = 24) had significantly (P less than 0.05) lower Ig levels (mean, 104 mg/dl) than catfish either 7.5-25.5 cm (n = 57, mean, 232 mg/dl) or 37.5-45 cm (n = 45, mean, 388 mg/dl). Also, catfish 17.5-25.5 cm had a significantly (P less than 0.05) less Ig than catfish 37.5-45 cm. The concentrations of serum Ig increase with size (P = 0.0001) of catfish. The mean Ig concentration for 7.5-45 cm catfish (n = 126) was 263 mg/dl. The Ig concentration range was 44 to 650 mg/dl of serum.


Effects of hypothermia and rewarming on the neonatal circulation.
Thirteen unanesthetized lambs, aged 1-3 days, were cooled from 40 degrees to 30 degrees C and then rewarmed. During cooling, heart rate dropped from 196 +/- 47 to 140 +/- 42 beats per minute, a 29% change; cardiac output, femoral arterial and pulse pressures did not change significantly; but inferior vena cava pressure (IVC) increased from 5 to 9 mm of mercury, and left ventricular end diastolic pressure (LVEDP) increased from 8 to 25 mm/Hg. Mean pulmonary arterial pressure increased from 29 to 40 mm/Hg. Metabolic acidosis and hypoxia developed during the cooling. There were marked changes in the distribution of cardiac output; the proportion of cardiac output increased by 450% to brown fat, 66% to the skeletal muscles, and 30% to the right ventricular myocardium and atria. No significant change in the distribution to the left ventricule and septum was observed. Distribution to the other organs decreased markedly. After rewarming, all the previous parameters returned to normal except CVP and LVEDP, which remained elevated.


Factor validation of an instrument measuring group power.
Few publications have reported empirical findings regarding the measurement of nursing group power. This article reports the confirmatory factor analyses of the Sieloff-King Assessment of Group Power Within Organizations (SKAGPO) for instrument and middle-range theory development. Secondary analyses were conducted using cross-sectional data collected in 1999. The target population of the initial research was the chief nurse executives (CNEs) of all hospitals within the United States (including Alaska and Hawaii). A sample of 600 hospitals from across the United States was selected through a stratified random sampling process. A total of 350 executives comprised the final sample. Second-order confirmatory 8-factor analysis revealed factor loadings ranging from .43 to .89. The overall fit of the proposed model was: X2 = 1,360, df = 586, p < .00, GFI = .82, CFI = .86, and RMSEA = .06, indicating an acceptable fit with the data. Statistical support was found for the proposed model with the subsequent development of an alternate model that better fit the data. The study results indicated that the SKAGPO has acceptable psychometric properties.


MHC-linked susceptibility to a bacterial infection, but no MHC-linked cryptic female choice in whitefish.
Non-random gamete fusion is one of several potential cryptic female choice mechanisms that have been postulated and that may enhance the survival probability of the offspring. Previous studies have found that gamete fusion in mice is influenced by genes of the major histocompatibility complex (MHC) region. Here we test (i) whether there is MHC-dependent gamete fusion in whitefish (Coregonus sp.) and (ii) whether there is a link between the MHC and embryo susceptibility to an infection by the bacterium Pseudomonas fuorescens. We experimentally bred whitefish and reared sibships in several batches that either experienced or did not experience strong selection by P. fluorescens. We then determined the MHC class II B1 genotype of 1016 surviving larvae of several full sibships. We found no evidence for MHC-linked gamete fusion. However, in one of seven sibships we found a strong connection between the MHC class II genotype and embryo susceptibility to P. fluorescens. This connection was still significant after correcting for multiple testing. Hence, the MHC class II genotype can considerably influence embryo survival in whitefish, but gamete fusion seems to be random with respect to the MHC.


Evidence for the existence of inhibitory postsynaptic potentials in dendrites and their functional significance in hippocampal pyramidal cells of adult rabbits.
(1) Hyperpolarizing potentials were studied in hippocampal pyramidal cells of normal, adult rabbits, anesthetized with Nembutal and, in addition, curarized. (2) Single shock stimulation of the fornix produced in these cells long-lasting hyperpolarizing potentials (400-2000 msec). As a rule, the early part of these potentials (about 200 msec from the onset) was influenced by the diffusion of Cl ions into the cell and current injections, whereas their late part was not. The early part exhibited impedance changes whereas the late part did not. From these results it was concluded that the former was the inhibitory postsynaptic potential (IPSP) occurring in the soma while the latter originated in the dendrites. Evidence was obtained suggesting that the latter was also a Cl-mediated IPSP. The hyperpolarization elicited in these cells by mesencephalic stimulation was similar in properties to the latter. (3) Disfacilitation in the dendrites and the functional significance of the dendritic IPSP were discussed.


New light on an age-old issue.
In this issue, Varadhan and colleagues propose a methodologic framework that seeks to quantify impaired resiliency in dynamic systems underlying the frailty syndrome. We view this work, which is based on modeling stimulus-response data, as an exciting expansion of longstanding theories of age-related decline in physiologic reserve across systems. We outline ways in which this methodology might make substantial contributions in frailty research and clinical practice, and we discuss potential obstacles in its operationalization.


Larger phase angle between sleep propensity and melatonin rhythms in sighted humans with non-24-hour sleep-wake syndrome.
This study was aimed to clarify phase angle between sleep propensity and the circadian pacemaker in patients with non-24-hour sleep-wake syndrome (Non-24). A case-control study was underaken. Sighted patient with Non-24 (4 males and 1 female, aged 16 to 39 y), and sex- and age-matched healthy controls (12 males and 3 females, aged 19 to 35 y) participated the study. MEASUREMENT AND INTERVENTION: Following an actigraphic assessment of the sleep-wake cycle in their homes, the participants entered an ultra-short sleep-wake schedule together with simultaneous measurement of dim light melatonin rhythm after 24-hour sleep deprivation. The period of the sleep-wake cycle observed at home was longer in the Non-24 patients (25.12 hours) than in the controls (24.02 hours, p<0.0001). The interval from sleep propensity (SP) onset to the melatonin midpoint (MLmid) was significantly shorter in the Non-24 patients than in the controls. The interval from the MLmid to the SP offset was significantly longer in the Non-24 patients than in the controls. It was postulated that Non-24 sufferers' delayed SP onset relative to the circadian pacemaker may accelerate the light-induced phase-delay, leading to sleep-wake cycle that is longer than 24 hours.


The dosimetric effects of limited elective nodal irradiation in volumetric modulated arc therapy treatment planning for locally advanced non-small cell lung cancer.
Contemporary radiotherapy guidelines for locally advanced non-small cell lung carcinoma (LA-NSCLC) recommend omitting elective nodal irradiation, despite the fact that evidence supporting this came primarily from older reports assessing comprehensive nodal coverage using 3D conformal techniques. Herein, we evaluated the dosimetric implications of the addition of limited elective nodal irradiation (LENI) to standard involved field irradiation (IFI) using volumetric modulated arc therapy (VMAT) planning. Target volumes and organs-at-risk (OARs) were delineated on CT simulation images of 20 patients with LA-NSCLC. Two VMAT plans (IFI and LENI) were generated for each patient. Involved sites were treated to 60 Gy in 30 fractions for both IFI and LENI plans. Adjacent uninvolved nodal regions, considered high risk based on the primary tumor site and extent of nodal involvement, were treated to 51 Gy in 30 fractions in LENI plans using a simultaneous integrated boost approach. All planning objectives for PTVs and OARs were achieved for both IFI and LENI plans. LENI resulted in significantly higher esophagus Dmean (15.3 vs. 22.5 Gy, p < 0.01), spinal cord Dmax (34.9 vs. 42.4 Gy, p = 0.02) and lung Dmean (13.5 vs. 15.9 Gy, p = 0.02), V20 (23.0 vs. 27.9%, p = 0.03), and V5 (52.6 vs. 59.4%, p = 0.02). No differences were observed in heart parameters. On average, only 32.2% of the high-risk nodal volume received an incidental dose of 51 Gy when untargeted in IFI plans. The addition of LENI to VMAT plans for LA-NSCLC is feasible, with only modestly increased doses to OARs and marginal expected increase in associated toxicity.


5-fluorouracil-induced increase of total serum thyroxine and triiodothyronine.
Total serum thyroxine and triiodothyronine levels in a group of 15 patients with advanced mammary carcinoma significantly increased during weekly treatment with 5-fluorouracil, whereas serum free thyroxine levels and serum thyroid stimulating hormone levels were unchanged. No clinical signs of hyperthyroidism in these treated patients have been observed.


Protein kinase C-θ inhibits inducible regulatory T cell differentiation via an AKT-Foxo1/3a-dependent pathway.
Protein kinase C (PKC)-θ has been shown to be a critical TCR signaling molecule that promotes the activation and differentiation of naive T cells into inflammatory effector T cells. In this study, we demonstrate that PKC-θ-mediated signals inhibit inducible regulatory T cell (iTreg) differentiation via an AKT-Foxo1/3A pathway. TGF-β-induced iTreg differentiation was enhanced in PKC-θ(-/-) T cells or wild-type cells treated with a specific PKC-θ inhibitor, but was inhibited by the PKC-θ activator PMA, or by CD28 crosslinking, which enhances PKC-θ activation. PKC-θ(-/-) T cells had reduced activity of the AKT kinase, and the expression of a constitutively active form of AKT in PKC-θ(-/-) T cells restored the ability to inhibit iTreg differentiation. Furthermore, knockdown or overexpression of the AKT downstream targets Foxo1 and Foxo3a was found to inhibit or promote iTreg differentiation in PKC-θ(-/-) T cells accordingly, indicating that the AKT-Foxo1/3A pathway is responsible for the inhibition of iTreg differentiation of iTregs downstream of PKC-θ. We conclude that PKC-θ is able to control T cell-mediated immune responses by shifting the balance between the differentiation of effector T cells and inhibitory Tregs.


Exposure to "Exergames" Increases Older Adults' Perception of the Usefulness of Technology for Improving Health and Physical Activity: A Pilot Study.
High rates of sedentary behaviors in older adults can lead to poor health outcomes. However, new technologies, namely exercise-based videogames ("exergames"), may provide ways of stimulating uptake and ongoing participation in physical activities. Older adults' perceptions of the use of technology to improve health are not known. The study aimed to determine use and perceptions of technology before and after using a 5-week exergame. Focus groups determined habitual use of technology and the participant's perceptions of technology to assist with health and physical activity. Surveys were developed to quantitatively measure these perceptions and were administered before and after a 5-week intervention. The intervention was an exergame that focused on postural balance ("Your Shape Fitness Evolved 2012"). Games scores, rates of game participation, and enjoyment were also recorded. A total of 24 healthy participants aged between 55 and 82 years (mean 70, SD 6 years) indicated that after the intervention there was an increased awareness that technology (in the form of exergames) can assist with maintaining physical activity (P<.001). High levels of enjoyment (Physical Activity Enjoyment Scale [PACES-8] score mean 53.0, SE 0.7) and participation rates over the whole study (83%-100%) were recorded. Older adults' have low perception of the use of technology for improving health outcomes until after exposure to exergames. Technology, in the form of enjoyable exergames, may be useful for improving participation in physical activity that is relevant for older adults.


The involvement of miR-150/β-catenin axis in colorectal cancer progression.
Colorectal cancer remains as a serious global cause of morbidity and mortality. The current therapies for colorectal cancer treatment are still unsatisfactory and thus, identification of novel targets is an urgent requisite. Recent evidence has reported miRNAs are closely correlated with colorectal cancer development. miR-150 has been identified in tumor progression in various cancers. Nevertheless, its roles in colorectal cancer remain poorly known. In our study, a decreased miR-150 expression in colorectal cancer tissues and cells was observed. Meanwhile, we reported a negative correlation between miR-150 and β-catenin in colorectal cancer. β-catenin can participate in the physiological mechanism of many types of cancers. Then, miR-150 was overexpression in SW480 and HT-29 cells and it was show that miR-150 repressed SW480 and HT-29 cell viability, proliferation and colony formation capacity. Moreover, colorectal cancer cell progression was triggered by the inhibition of miR-150 via negatively regulating β-catenin. Subsequently, the direct binding correlation between miR-150 and β-catenin was demonstrated. β-catenin, c-myc and CyclinD1 level was significantly restrained by the up-regulation of miR-150 in SW480 and HT-29 cells. Finally, it was proved that miR-150 depressed colorectal cancer growth through modulating β-catenin in vivo. Overall, it was implied that miR-150 could inhibit colorectal cancer progression and serve as a tumor suppressor via inactivating β-catenin pathway.


Fusion imaging-guided percutaneous biopsy of focal hepatic lesions with poor conspicuity on conventional sonography.
The purpose of this study was to evaluate the effectiveness of real-time fusion imaging (sonography combined with computed tomography or magnetic resonance imaging) for percutaneous sonographically guided biopsy of focal hepatic lesions with poor sonographic conspicuity. This study was conducted as a retrospective analysis of a prospective database and was approved by the Institutional Review Board. Patients who had target lesions with poor conspicuity on B-mode sonography for percutaneous biopsy were enrolled in the study. Lesion conspicuity was assessed by conventional B-mode sonography first and then by fusion imaging later in the same session. We compared lesion conspicuity and detection rates between B-mode sonography and fusion imaging and evaluated how many cases of initially invisible lesions on B-mode sonography became visible on fusion imaging. The technical success rate was evaluated on the basis of the final diagnoses, which were established by pathologic examination of the biopsy specimens as well as follow-up clinical and radiologic examinations. A total of 22 patients were enrolled in the study. On fusion imaging, lesion conspicuity was increased in 63.6% of focal hepatic lesions (14 of 22). Moreover, 66.7% of lesions (6 of 9) that were invisible on B-mode sonography became visible on fusion imaging. The true-positive detection rate was significantly different between B-mode sonography and fusion imaging (9 of 22 versus 19 of 22; P = .0044). Percutaneous biopsy was performed for all lesions, including 3 target lesions that were invisible even on fusion imaging. The technical success rate was 95.5% (21 of 22). Fusion imaging is effective for percutaneous biopsy of focal hepatic lesions with poor sonographic conspicuity.


United we stand: emphasizing commonalities across cognitive-behavioral therapies.
Cognitive behavioral therapy (CBT) has a rich history of alleviating the suffering associated with mental disorders. Recently, there have been exciting new developments, including multicomponent approaches, incorporated alternative therapies (e.g., meditation), targeted and cost-effective technologies, and integrated biological and behavioral frameworks. These field-wide changes have led some to emphasize the differences among variants of CBT. Here, we draw attention to commonalities across cognitive-behavioral therapies, including shared goals, change principles, and therapeutic processes. Specifically, we offer a framework for examining common CBT characteristics that emphasizes behavioral adaptation as a unifying goal and three core change principles, namely (a) context engagement to promote adaptive imagining and enacting of new experiences; (b) attention change to promote adaptive sustaining, shifting, and broadening of attention; and (c) cognitive change to promote adaptive perspective taking on events so as to alter verbal meanings. Further, we argue that specific intervention components, including behavioral exposure/activation, attention training, acceptance/tolerance, decentering/defusion, and cognitive reframing, may be emphasized to a greater or lesser degree by different treatment packages but are still fundamentally common therapeutic processes that are present across approaches and are best understood by their relationships to these core CBT change principles. We conclude by arguing for shared methodological and design frameworks for investigating unique and common characteristics to advance a unified and strong voice for CBT in a widening, increasingly multimodal and interdisciplinary, intervention science.


A mitogen-activated protein (MAP) kinase activating factor in mammalian mitogen-stimulated cells is homologous to Xenopus M phase MAP kinase activator.
The mitogen-activated protein (MAP) kinases, a family of 40-45-kDa kinases whose activation requires both tyrosine and threonine/serine phosphorylations, are suggested to play key roles in various phosphorylation cascades. A previous study of Krebs and co-workers (Ahn, N. G., Seger, R., Bratlien, R. L., Diltz, C. D., Tonks, N. K., and Krebs, E. G. (1991) J. Biol. Chem. 266, 4220-4227) detected an activity in epidermal growth factor (EGF)-stimulated 3T3 cells that can stimulate inactive MAP kinases. We observed this activity in rat 3Y1 cells treated with various mitogenic factors and in PC12 cells treated with nerve growth factor (NGF). Its kinetics of activation and deactivation following EGF or NGF stimulation roughly paralleled that of MAP kinase. The MAP kinase activator required the presence of ATP and a divalent cation such as Mn2+ and Mg2+ and was inactivated by phosphatase 2A treatment in vitro. This activator has been isolated from EGF-stimulated 3Y1 cells by sequential chromatography and identified as a 45-kDa monomeric protein. It was able to activate mammalian and Xenopus MAP kinases in vitro and was very similar to Xenopus M phase MAP kinase activating factor, which was purified previously from mature oocytes (Matsuda, S., Kosako, H., Takenaka, K., Moriyama, K., Sakai, H., Akiyama, T., Gotoh, Y., and Nishida, E. (1992) EMBO J. 11, 973-982), in terms of its functional, immunological, and physicochemical properties. Thus, the same or a similar upstream activating factor may function in mitogen-induced and M phase-promoting factor-induced MAP kinase activation pathways.


A single-blinded comparative study between the use of glycolic acid 70% peel and the use of topical nanosome vitamin C iontophoresis in the treatment of melasma.
Melasma is a common pigmentary disorder. Despite the availability of a wide range of skin-lightening treatments, melasma of skin remains a therapeutic challenge. The aim of this study was to evaluate the efficacy and safety of nanosome vitamin C iontophoresis and to compare the therapeutic effects of nanosome vitamin C iontophoresis vs. glycolic acid peel 70% in the treatment of melasma in Egyptian women. This study included 14 patients of melasma with skin type IV-V taken for a right-left comparison study of six sessions. Glycolic acid 70% peel was applied on the right side, whereas nanosome vitamin C was applied by iontophoresis on the other side. The results are evaluated using the melasma area and severity index score and with photographs at baseline and after six sessions. Also the photographs were evaluated by two single-blinded physicians before and after sessions. Both sides were improved, but the side treated with nanosome vitamin C showed better results. Side effects were few and transient. We concluded that nanosome vitamin C is a new, safe and effective, easy and painless method in the treatment of melasma.


Anticoagulant-active sulfated arabinogalactan from Chaetomorpha linum: Structural characterization and action on coagulation factors.
A sulfated polysaccharide from the green alga Chaetomorpha linum, designated CLS4, was isolated by water extraction, anion-exchange and size-exclusion chromatography. Chemical and spectroscopic analyses demonstrated that CLS4 was a sulfated arabinogalactan, which was constituted by (1→6)-β-d-galactopyranose and (1→5)-α-l-arabinofuranose residues with sulfate groups at C-2/ C-3 of (1→5)-α-l-arabinofuranose and C-2/C-4 of (1→6)-β-d-galactopyranose. CLS4 possessed strong anticoagulant activity in vitro or in vivo as evaluated by activated partial thromboplastin time and thrombin time assays. CLS4 largely inhibited the activities of the coagulation factors XII, XI, IX and VIII. CLS4 was a potent thrombin inhibitor mediated by antithrombin III (ATIII) or heparin cofactor II, and it also effectively stimulated the factor Xa inhibition by potentiating ATIII. Moreover, CLS4 had a high thrombolytic activity in vitro as assessed by clot lytic rate assay. The results suggested that CLS4 could be a promising source of anticoagulant agent.


Digital picture analysis in microphotometry of biological materials.
Automatic evaluation of two-dimensional thin-layer-chromatograms exemplarily demonstrates the applicability of signal processing, image analysis, and pattern recognition to microphotometry by an enlarged dynamic range of the photometer, improved reproducibility by noise reduction, discrimination between objects and background, feature extraction and automatic classification of the results. Emphasis is put on simple procedures which are tested in routine work and can be implemented on minicomputers.


Six-year experience of microvascular free-flap reconstruction of head and neck neoplasms.
Microvascular free-flap reconstruction is one of the treatment options after large resection of head and neck neoplasms. The objectives of this study are to identify short-term outcomes and risk factors for flap complication in patients who underwent neoplasms resection of head and neck with microvascular free-flap reconstruction. Retrospective study of patients who underwent surgery for head and neck neoplasm with microvascular free-flap reconstruction between January 2014-2020. Complications were studied at 30-days follow-up and divided into medical and flap complications. Factors independently associated with flap complication were analyzed. We included 31 patients (15 men). The mean age was 60 years. Reconstruction was performed with radial-forearm flap in 74% (n=23) and with free-fibula flap in 26% (n=8). Mean surgical time was 420 minutes. Median hospital length of stay was 7 days. Medical complications were of 23%. Minor complications were of 35% and major of 32%. There was no mortality in 30-days follow-up. Flap complications were of 35%. Reintervention was of 29%, surgical site infection of 9%, dehiscence of 29% and flap loss of 9.7%. Surgical site infection was independently associated with prolonged surgical time (Odds ratio [OR]=1.03, IC95%=0.98-1.04, p=0.02) and body mass index equal to or greater than 30 (OR=1.38, IC95%=0.84-2.26, p=0.04) while flap loss was associated with prolonged surgical time (OR=1.02, IC95%=0.99-1.04, p=0.01). Microsurgical free-flap reconstruction should be considered in our population in patients with large head and neck neoplasms. Preoperative assessment of the risk of postoperative complications is essential before selecting patients for this surgery.


Fasting Ramadan During COVID-19 Pandemic: Immunomodulatory Effect.
As of April 24, 2020, more than 1. 6 billion Muslims observe the holy fasting month of Ramadan worldwide. The safety of fasting of healthy adult Muslims during the COVID-19 era is debatable. In this perspective, we discuss the available scientific evidence of the advantages of fasting against COVID-19.


Morphophysiological characteristics of connexions between single ventrolateral tract fibres and individual motoneurones in the frog spinal cord.
In experiments on the isolated frog spinal cord, simultaneous intracellular recordings were performed from synaptically connected individual ventrolateral tract fibres and lumbar motoneurones. Statistical parameters of amplitude fluctuations of unitary excitatory postsynaptic potentials evoked by direct activation of presynaptic axons were compared with the number of synaptic contacts at the same connexions revealed by staining both pre- and postsynaptic elements with horseradish peroxidase. Close correspondence between the number of contacting boutons and that of release elements (n) determined from binomial relations was observed.


Changes in the cytoskeletal structure of human platelets following thrombin activation.
The temporal changes in human platelet actin polymerization, cytoskeletal morphology, and protein content that occur during thrombin-induced platelet activation were investigated by analysis of Triton-extracted platelets. Measurement of the DNase inhibitory activity of control platelets immediately after adding an equal volume of 2% Triton X-100, 10 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid, and 0.1 M Tris, pH 7.4, showed that approximately 50% of the actin in unstimulated platelets was filamentous and unable to inhibit DNase-catalyzed hydrolysis of DNA. Activation of platelets with thrombin for 15 s caused the amount of actin in the filamentous form to increase to approximately 65%. Examination of the morphology and protein composition of these filamentous structures showed that the cytoskeletal structures from control platelets consisted of a random array of filaments which contained 14% of the total platelet myosin and 6% of the total actin-binding protein. In contrast, the cytoskeletal structures of thrombin-activated platelets appeared as cytoskeletal structures of individual platelets. The composition of these cytoskeletons varied depending on the time of thrombin activation. Those from platelets activated with thrombin for 15 to 30 s contained 90% of the platelet myosin and 20% of the platelets with thrombin before Triton addition resulted in a decreased association of myosin to 60% with no change in either the actin or actin-binding protein content of the cytoskeletal structures. Since these changes are rapid and precede serotonin secretion, it is suggested that they are involved in the physiological response of the platelet.


Experimental studies of pollen carryover: effects of floral variability in Ipomopsis aggregata.
In the montane herb Ipomopsis aggregata, size and placement of stamens and pistils vary substantially among flowers within plants, among nearby plants, and among groups of plants separated by 50-100 m. We trained captive hummingbirds to feed from flowers of this species in a flight cage, and explored the effects of different degrees of floral variability on carryover of fluorescent dyes that act as pollen mimics. We found that the slopes of linear dye carryover functions generally became more shallow as floral variability increased; this led to substantially longer carryover in the treatment with greatest variability. On the other hand, total amounts of dye transferred did not appear to be sensitive to the degree of variability. Floral variability may have a subtle but important effect on plant fitness by influencing the distance of pollen transfer.


Patterns of care in the management of high-risk COPD in the US (2011-2019): an observational study for the CONQUEST quality improvement program.
In this study, we compare management of patients with high-risk chronic obstructive pulmonary disease (COPD) in the United States to national and international guidelines and quality standards, including the COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST). Patients were identified from the DARTNet Practice Performance Registry and categorized into three high-risk cohorts in each year from 2011 to 2019: newly diagnosed (≤12 months after diagnosis), already diagnosed, and patients with potential undiagnosed COPD. Patients were considered high-risk if they had a history of exacerbations or likely exacerbations (respiratory consult with prescribed medication). Descriptive statistics for 2019 are reported, along with annual trends. In 2019, 10% (n = 16,610/167,197) of patients met high-risk criteria. Evidence of spirometry for diagnosis was low; in 2019, 81% (n = 1228/1523) of patients newly diagnosed at high-risk had no record of spirometry/peak expiratory flow in the 12 months pre- or post-diagnosis and 43% (n = 651/1523) had no record of COPD symptom review. Among those newly and already diagnosed at high-risk, 52% (n = 4830/9350) had no evidence of COPD medication. Findings suggest inconsistent adherence to evidence-based guidelines, and opportunities to improve identification, documentation of services, assessment, therapeutic intervention, and follow-up of patients with COPD. This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global and AstraZeneca Ltd. No funding was received by the Observational & Pragmatic Research Institute Pte Ltd (OPRI) for its contribution.


C-factor: a cell-cell signaling protein required for fruiting body morphogenesis of M. xanthus.
During fruiting body development, the product of the csgA gene is necessary for cellular aggregation, for spore differentiation, and for gene expression that is initiated after 6 hr of starvation. From nascent wild-type fruiting bodies we have purified a polypeptide of 17 kd called C-factor, which, at approximately 1 to 2 nM, restores normal development to csgA mutant cells. C-factor activity is not recovered from extracts of unstarved, growing cells or csgA mutant cells. The amino acid sequence from purified C-factor demonstrates that it is the product of the csgA gene. C-factor is active over a narrow range of concentration and has properties of a morphogenetic paracrine signal.


Autosomal dominant precalcaneal congenital fibrolipomatous hamartoma.
Precalcaneal congenital fibrolipomatous hamartoma is a rare minor malformation previously reported only as sporadic. We report this finding in three family members from two generations, suggesting autosomal dominant inheritance.


Ensuring Maintenance of Oral Hygiene in Persons with Special Needs.
Patients with special needs often must rely on inadequately trained caregivers for oral health maintenance. Consequently, full compliance is often not achieved. It is crucial that dentists carefully consider restorative materials and restoration design to maximize durability and facilitate cleansing in these challenging circumstances. This article discusses materials selection, prosthetic design, and oral hygiene techniques for caregivers to ensure longevity and maintenance of oral health in the special needs population.


Carbonized human hair derived carbon dots for detection of clozapine.
Clozapine (CLZ) is known as the most effective antipsychotic medication for schizophrenia. However, low dosage or over dosage of CLZ is adverse to the treatment of Schizophrenia. Thus, it is necessary to develop effective detection method for CLZ. Recently, due to the advantages such as excellent optical properties, good photobleachability and sensitivity, carbon dots (CDs)-based fluorescent sensors for the detection of target analytes have drawn a great deal of attention. In this work, blue fluorescent CDs (Named as B-CDs) with quantum yield (QY) as high as 38% were obtained by using carbonized human hair as source material through one-step dialysis method for the first time. B-CDs showed obvious graphite-like structure with an average of 1.76 nm, containing abundant functional groups such as -C=O, amino N and C-N on the surface of carbon cores. Optical analysis showed that the B-CDs exhibited excitation-dependent emission property with maximum emission wavelength of 450 nm. Moreover, B-CDs were further applied as a fluorescence sensor to the detection of CLZ. The B-CDs based sensor exhibited a good quenching response by CLZ through the inner filter effect and static quenching mechanism with a limit of detection of 67 ng/mL, which was much lower than the minimal effective concentration in blood (0.35 μg/mL). Finally, to test the practical application value of the developed fluorescence method, the determination of the content of CLZ in tablets and the concentration in blood was carried out. Compared with the results of high-performance liquid chromatography (HPLC) method, it can be found that the constructed fluorescence detection method showed high accuracy and had great application potential in the detection of CLZ. Additionally, the results of cytotoxicity experiment showed that B-CDs had low cytotoxicity, which laid the foundation for the subsequent application of B-CDs in biological systems.


Screening of poplar biomass for bio-active compounds: a simple method to assess antioxidant activity.
Poplar bud resinoids are a potential source of natural antioxidants. As poplar culture today involves many hybrids, a simple screening test to assess antioxidant properties was proposed. This method used the second derivative of the UV spectra at 233 nm of the iron induced peroxidienes resulting from linoleic acid peroxidation. Kinetic data showed a lag period followed by a quadratic increase in peroxidienes. These two phases were more clearly separated using the square root of the data. An acceptable linear fitting of the length of the lag phase with antioxidant concentration was observed. Calibrating the experimental test with BHA therefore allowed an antioxidant assessment as "BHA equivalent". First results clustered well with taxonomic data, with typically 0.5, 0.15 and 0.08 "BHA equivalent" for P. nigra, P. X euramericana and P. X interamericana, respectively.


Glycosaminoglycans reduce oxidative damage induced by copper (Cu+2), iron (Fe+2) and hydrogen peroxide (H2O2) in human fibroblast cultures.
Acid glycosaminoglycans (GAGs) antioxidant activity was assessed in a fibroblast culture system by evaluating reduction of oxidative system-induced damage. Three different methods to induce oxidative stress in human skin fibroblast cultures were used. In the first protocol cells were treated with CuSO4 plus ascorbate. In the second experiment fibroblasts were exposed to FeSO4 plus ascorbate. In the third system H2O2 was utilised. The exposition of fibroblasts to each one of the three oxidant systems caused inhibition of cell growth and cell death, increase of lipid peroxidation evaluated by the analysis of malondialdehyde (MDA), decrease of reduced glutathione (GSH) and superoxide dismutase (SOD) levels, and rise of lactate dehydrogenase activity (LDH). The treatment with commercial GAGs at different doses showed beneficial effects in all oxidative models. Hyaluronic acid (HA) and chondroitin-4-sulphate (C4S) exhibited the highest protection. However, the cells exposed to CuSO4 plus ascorbate and FeSO4 plus ascorbate were better protected by GAGs compared to those exposed to H2O2. These outcomes confirm the antioxidant properties of GAGs and further support the hypothesis that these molecules may function as metal chelators.


Molecular Mechanism of Helicobacter pylori-Induced Gastric Cancer.
Various types of cancers threaten human life. The role of bacteria in causing cancer is controversial, but it has been determined that the Helicobacter pylori infection is one of the identified risk factors for gastric cancer. Helicobacter pylori infection is highly prevalent, and about half of the world,s population is infected with it. The aim of this study was the role of Helicobacter pylori in the development of gastric cancer. We obtained information from previously published articles. The bacterium has various virulence factors, including cytotoxin- associated gene A, vacuolating cytotoxin A, and the different outer membrane proteins that cause cancer by different mechanisms. These virulence factors activate cell signaling pathways such as PI3-kinase/Akt, JAK/STAT and Ras, Raf, and ERK signaling that control cell proliferation. Uncontrolled proliferation can lead to cancer.


Step-down approach to behavioural weight loss treatment: a pilot of a randomised clinical trial.
In a stepped-down approach, patients begin with a more intensive treatment and are stepped down to a less intensive treatment based on achieving treatment goals. This study compared a standard behavioural weight loss programme (BWLP) to a stepped-down approach to treatment. Fifty-two overweight/obese adults (Age: M = 47 years, SD = 13.5; female = 67%) participated in an 18-week BWLP. Half of them were randomly assigned to be stepped down from weekly group meetings based on completion of weight loss goals (3%) every 6 weeks, while the other half remained in their groups regardless of weight loss. There was a significant difference favouring the BWLP in the proportion of participants who met or exceeded their 3% weight loss goal during the first six weeks. While not statistically significant by the end of treatment, the BWLP participants lost nearly 3% more body weight than stepped-down participants (SC = 4.9% vs. BWLP = 7.8%; p = .10). Greater self-monitoring was associated with increased likelihood of stepped-care eligibility and higher percent weight loss at the end of treatment (p < .01). There was little evidence to support the efficacy of the stepped-down approach for behavioural weight loss treatment employed in this investigation.


Glomerular injury induced in mice by intraperitoneal injection of Shiga-like toxins.
Shiga-like toxins I and II (Stx1 and Stx2) play an important role in the pathogenesis of renal disease by causing renal microvascular injury. A murine model was used to study glomerular lesions produced by Stx1 and Stx2. Swiss albino mice of the Rockefeller strain were inoculated intraperitoneally with LD(50) doses of endotoxin-free Stx1 of Stx2 and observed for signs of disease. Samples of renal cortical tissue from mice were examined with the electron microscope. the mice developed systemic and neurological symptoms including hind limb paralysis and generalised convulsions. Renal arteriolar damage and glomerular endothelial cytoplasmic swelling, vacuolation, lysis and intravascular coagulation were present and resembled the microangiopathy seen in renal biopsies from patients. these experiments establish the role of Stx1 and Stx2 in glomerular vascular injury and provide a model for studying the pathogenesis of Shiga-like toxin related microangiopathy.


Early colorectal carcinoma with special reference to its development de novo.
The growth type of early colorectal carcinoma was classified into two types. The first type is intramucosal polypoid growth (PG-Ca) and the second type nonpolypoid growth (NPG-Ca) which shows mainly massive infiltration of tumor cells below the submucosal layer. The incidence of adenoma-carcinoma sequence was 72 of 75 lesions (96.0%) in pedunculated polypoid carcinoma, and 61 of 71 lesions (85.9%) in sessile and broad-based polypoid carcinomas. Their average sizes were 15.0 and 18.7 mm, respectively. Submucosal invasive carcinoma (SM-Ca) showed a low incidence. They were detected as microscopical or scattered lesions with a few lymphatic and venous permeation. The NPG-Ca contained 32 lesions. Intramucosal carcinoma without adenoma showing slight depression consisted of ten lesions of which the average size was 5.1 mm. The other 22 lesions showed massive submucosal invasion with marked lymphatic and venous permeation. The average size was 10.3 mm being smaller than PG-Ca. Histologically, NPG-Ca was not accompanied with adenoma. The NPG-Ca arose from de novo carcinoma less than 10 mm in diameter and invaded into the submucosal layer. In advanced carcinoma, the PG-Ca showed a low incidence (21.8%), and almost all cases were of the NPG type (78.2%). The NPG advanced carcinomas increased in those over the size of 20 mm. It is concluded that nonpolypoid early colorectal carcinomas easily progress to advanced carcinoma, and de novo carcinoma occupied about 80% of colorectal carcinoma.


The microtubular system of crayfish retinula cells and its changes in relation to screening-pigment migration.
The organization of the microtubular system in crayfish retinula cells and its changes in relation to the light-dependent migrations of the screening pigment were studied by electron microscopy. A massive column of microtubules extends longitudinally throughout each retinula cell and its axon. The column is formed by overlapping fascicles of microtubules that originate from the vicinity of the rhabdomeres at multiple levels along the rhabdom. The pigment granules and other organelles are in general aligned with these fascicles and peripheral to the microtubular column. Close associations between microtubules and pigment granules are frequent. The total number of microtubules decreases nucleofugally from an average of about 500 at the middle of the rhabdom, to 390 at the proximal end of the rhabdom, and 240 in the axon below the basement membrane. The longitudinal distribution of microtubules was found similar for cells with the screening pigment in opposite extreme positions. In cells with the pigment in an intermediate position the number of microtubules was found to be nearly doubled in each of the mentioned levels; however, this change was correlated with a parallel increase in the cross-sectional area of the cells during the intermediate state. Thus, the density of microtubules tends to remain fairly constant throughout the light/dark adaptation cycle. These observations suggest that the microtubular system of the crayfish retinula cells constitutes a relatively stationary framework during screening-pigment movements, and could possibly act as a supportive guiding track for pigment transport.


Residency training at the Kansas City Veterans Administration Medical Center: the first 10 years.
Hospital residency training is relatively new to optometry. At the present time, 48 residents are in training at 30 VA Medical Centers and approximately 17 residents are in training elsewhere. This paper reviews the initial 10 years (1975-1985) of the first Council on Optometric Education accredited VA residency program at Kansas City, and describes the program and future plans.


TdT positive B-cell acute lymphoblastic leukaemia (B-ALL) without Burkitt characteristics.
The leukaemic cells in a 23-year-old man were small to medium-sized lymphoblasts with no cytoplasmic vacuoles and negative with PAS as well with peroxidase and acid phosphatase staining. Cytogenetic analysis showed -6, +12, -22, +mar (6p::22q), resulting in a trisomy 12 and monosomy of the long arm of chromosome 6. Immunological marker analysis revealed that the majority of the blasts was positive for terminal deoxynucleotidyl transferase (TdT) as well as surface membrane immunoglobulin (SmIg, mu, lambda), although B-ALL are supposed to be negative for TdT. The blasts were also positive for HLA-DR, CD9 (BA-2), CD10 (VIL-A1) and CD24 (BA-1), but negative for the B-cell markers CD20 (B1) and Y29/55. Double immunofluorescence staining confirmed that almost all TdT+ cells were also positive for Sm mu, Sm lambda, HLA-DR and CD10. We thus made a diagnosis of TdT+ B-ALL without Burkitt characteristics. Since we could not detect SmIg+/TdT+ cells in bone marrow samples from adult healthy volunteers and from 10 children with ALL in complete remission, we conclude that TdT+ B-ALL cells may not have a normal counterpart in bone marrow or represent a malignant counterpart of a very rare cell in an intermediate differentiation stage between the pre-B-cell and the early B lymphocyte.


SCA8 RAN polySer protein preferentially accumulates in white matter regions and is regulated by eIF3F.
Spinocerebellar ataxia type 8 (SCA8) is caused by a bidirectionally transcribed CTG·CAG expansion that results in the in vivo accumulation of CUG RNA foci, an ATG-initiated polyGln and a polyAla protein expressed by repeat-associated non-ATG (RAN) translation. Although RAN proteins have been reported in a growing number of diseases, the mechanisms and role of RAN translation in disease are poorly understood. We report a novel toxic SCA8 polySer protein which accumulates in white matter (WM) regions as aggregates that increase with age and disease severity. WM regions with polySer aggregates show demyelination and axonal degeneration in SCA8 human and mouse brains. Additionally, knockdown of the eukaryotic translation initiation factor eIF3F in cells reduces steady-state levels of SCA8 polySer and other RAN proteins. Taken together, these data show polySer and WM abnormalities contribute to SCA8 and identify eIF3F as a novel modulator of RAN protein accumulation.


Characterization of a spinach photosystem II core preparation isolated by a simplified method.
A photosystem II core complex from spinach exhibiting high rates of electron transport was obtained rapidly and in high yield by treatment of a Tris-extracted, O2-evolving photosystem II preparation with the detergent dodecyl-beta-D-maltoside. The core complex was essentially free of light-harvesting chlorophyll-protein and photosystem I polypeptides, and was highly enriched in the polypeptides associated with the photosystem II reaction center (45 and 49 kDa), cytochrome b559, and three polypeptides in the region 32-34 kDa. The photosystem II core complex contained two chlorophyll-proteins which had a slightly higher apparent molecular mass than CPa-1 and CPa-2. Additionally, a high-molecular-mass chlorophyll-protein complex termed CPa* was observed, which exhibited a low fluorescence yield when illuminated with ultraviolet light. This observation suggests that CPa* contains a functionally efficient quencher of chlorophyll fluorescence, possibly P680.


Bax/Bcl-2 protein expression ratio and leukocyte function are related to reduction of Walker-256 tumor growth after β-hydroxy-β-methylbutyrate (HMB) administration in Wistar rats.
This study investigated the mechanisms by which β-hydroxy-β-methylbutyrate (HMB) administration in rats reduces Walker-256 tumor growth. Male Wistar rats were supplemented with HMB (76 mg/kg/day) (HW), or a placebo (W), during 8 wk by gavage. At the 6th wk, rats were inoculated with a suspension of Walker 256 tumor cells (3 × 10(7)/mL). Fifteen days after inoculation, the HW group showed higher glycemia (109.4 ± 5.53 vs. 89.87 ± 7.02 mg/dL, P < 0.05) and lower spleen (1.35 ± 0.05 vs. 1.65 ± 0.12 g, P < 0.05) and tumor weights (9.64 ± 1.07 vs. 13.55 ± 1.19 g, P < 0.05) compared to the W group. Tumor cells extracted from the HMB-treated rats displayed a 36.9% decrement in rates of proliferation ex vivo and a significant increase in the Bax/Bcl-2 protein expression ratio in comparison to those extracted from the placebo-treated rats (P < 0.05). Both phagocytic capacity and H(2)O(2) production rates were higher in polymorphnuclear cells that were obtained from the blood of the HW rats in comparison to those from the W rats (P < 0.05). Reduction of necrotic regions and an intense infiltration of leukocytes and activated granulocytes in HW were evident by transmission electron microscopy. Our findings suggest that HMB supplementation decreases tumor burden by modifying the inner environment of tumor cells and by interfering with blood leukocyte function.


Taxifolin attenuates inflammation via suppressing MAPK signal pathway in vitro and in silico analysis.
Taxifolin is a natural flavonoid compound that can be isolated from onions, grapes, oranges and grapefruit. It also acts as a medicine food homology with extraordinary antioxidant and anti-inflammatory activity. This study aims to explain the protective effects and potential mechanisms of taxifolin against inflammatory reaction. Levels of interleukin (IL)-6, IL-1β and intracellular reactive oxygen species (ROS) were assessed in different time after the treatment of taxifolin in RAW264.7 cells induced by lipopolysaccharide (LPS). Subsequently, the mRNA and protein levels of inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α and the phosphorylation expression levels of the MAPK signal pathway were also evaluated. A silico analysis was used to explain the binding situation for the investigation of taxifolin and MAPK signal pathway. And then MAPK inhibitors were used to reveal the expression level of iNOS, VEGF, COX-2 and TNF-α in RAW264.7 cells. It was demonstrated that cell inflammatory damage induced by LPS was significantly alleviated after the treatment of taxifolin. Then, the mRNA and protein levels of iNOS, VEGF, COX-2 and TNF-α were reduced and the phosphorylation expression levels of the MAPK signal pathway were down-regulated remarkably as well. In silico analysis, taxifolin could form a relatively stable combination with MAPK signal pathway. MAPK inhibitors showed increasing or decreasing effect in the mRNA levels of iNOS, VEGF, COX-2 and TNF-α, which suggesting that taxifolin down-regulated iNOS, VEGF, COX-2 and TNF-α expressions were not entirely through the MAPK pathway. This finding demonstrated that taxifolin improved the inflammatory responses that partly involved in the phosphorylation expression level of MAPK signal pathway in RAW264.7 cells exposed to acute stress.


The AST petal dedicated bifurcation stent: first-in-human experience.
The aim of this first-in-human study was to evaluate the feasibility and safety of the novel AST petal side-access bifurcation stent. Outcomes following percutaneous coronary intervention for bifurcations remain inferior to those of nonbifurcated lesions. Even with drug-eluting stents, restenosis occurs especially at the side-branch (SB) ostium. The petal stent uniquely deploys strut elements into the SB, supporting the ostium and carina. The primary endpoint of this 13-patient prospective registry was in-hospital major adverse cardiac events (MACE). Secondary end points included acute minimum lumen diameter (MLD) at the SB ostium, lesion success, device success, procedural success, 30-day MACE, and 4-month SB ostial MLD. The study lesion was successfully treated in 13 patients with the study stent being successfully implanted in 12. Target lesions were left anterior descending coronary artery in nine subjects, left circumflex in three, and right coronary artery in one. In-hospital MACE were limited to two non-Q-wave myocardial infarctions. In-stent main branch MLD increased from a mean of 0.63 +/- 0.45 mm to 2.61 +/- 0.47 mm at the index procedure and for this initial bare metal version of the stent, 4-month mean MLD measured 1.02 +/- 0.42 mm and there was target vessel revascularization on two patients. The feasibility of safely deploying this first-generation petal stent was demonstrated in selected patients with challenging coronary bifurcation lesions. It is a promising platform for drug delivery, with unique scaffolding of the side-branch ostium.


New density functional approach for solid-liquid-vapor transitions in pure materials.
A new phase field crystal (PFC) type theory is presented, which accounts for the full spectrum of solid-liquid-vapor phase transitions within the framework of a single density order parameter. Its equilibrium properties show the most quantitative features to date in PFC modeling of pure substances, and full consistency with thermodynamics in pressure-volume-temperature space is demonstrated. A method to control either the volume or the pressure of the system is also introduced. Nonequilibrium simulations show that 2- and 3-phase growth of solid, vapor, and liquid can be achieved, while our formalism also allows for a full range of pressure-induced transformations. This model opens up a new window for the study of pressure driven interactions of condensed phases with vapor, an experimentally relevant paradigm previously missing from phase field crystal theories.


Akt-mediated Ephexin1-Ras interaction promotes oncogenic Ras signaling and colorectal and lung cancer cell proliferation.
Ephexin1 was reported to be highly upregulated by oncogenic Ras, but the functional consequences of this remain poorly understood. Here, we show that Ephexin1 is highly expressed in colorectal cancer (CRC) and lung cancer (LC) patient tissues. Knockdown of Ephexin1 markedly inhibited the cell growth of CRC and LC cells with oncogenic Ras mutations. Ephexin1 contributes to the positive regulation of Ras-mediated downstream target genes and promotes Ras-induced skin tumorigenesis. Mechanically, Akt phosphorylates Ephexin1 at Ser16 and Ser18 (pSer16/18) and pSer16/18 Ephexin1 then interacts with oncogenic K-Ras to promote downstream MAPK signaling, facilitating tumorigenesis. Furthermore, pSer16/18 Ephexin1 is associated with both an increased tumor grade and metastatic cases of CRC and LC, and those that highly express pSer16/18 exhibit poor overall survival rates. These data indicate that Ephexin1 plays a critical role in the Ras-mediated CRC and LC and pSer16/18 Ephexin1 might be an effective therapeutic target for CRC and LC.


Statistical tests for homogeneity of variance for clinical trials and recommendations.
In most clinical trials, the main interest is to test whether there are differences in the mean outcomes among the treatment groups. When the outcome is continuous, a common statistical test is a usual t-test for a two-group comparison. For more than 2 groups, an ANOVA setup is used and the test for equality for all groups is based on the F-distribution. A key assumption for these parametric tests is that data are normally, independently distributed and the response variances are equal. The robustness of these tests to the first two assumptions is quite well investigated, but the issues arising from heteroscedasticity are less studied. This paper reviews different methods for ascertaining homogeneity of variance across groups and investigates the consequences of heteroscedasticity on the tests. Simulations based on normal, heavy-tailed, and skewed normal data demonstrate that some of the less known methods, such as the Jackknife or Cochran's test, are quite effective in detecting differences in the variances.


Effect of arachidonic acid metabolism on the release of histamine and SRS (leukotrienes) from guinea-pig lung.
The effect of arachidonic acid (AA) metabolism on histamine release and SRS (leukotrienes) production has been studied in guinea-pig lung using anaphylactic reaction and Ca2+ ionophore as the triggering agents in vitro. AA and L-cysteine enhanced SRS production without any appreciable effect on histamine release. Two nonsteroid anti-inflammatory agents, indomethacin and ketoprofen, which block prostaglandin production by the cyclooxygenase pathway, stimulated SRS production but had hardly any effect on histamine release, indicating that SRS synthesis is more sensitive to prostaglandin regulation. Enhancement of SRS production was more pronounced for antigen than for Ca2+ ionophore. This might be related to different cellular origin of SRS with the two triggering agents. Using rat peritoneal cells, both mast cells and the other cells were found to produce SRS in response to Ca2+ ionophore, the amount formed by the latter type of cells being higher. Inhibition of lipoxygenase by 5,8,11,14-eicosatetraynoic acid and nordihydroguaiaretic acid depressed SRS production, but had no effect on histamine release. SRS production triggered by Ca2+ ionophore was more sensitive, possibly because of different cellular origin of SRS in response to the two stimuli. The explanation for the discrepancy between the effect on SRS production and histamine release may also have to be sought in their different origins. SRS may mainly stem from cells, which are more sensitive to the inhibitors than the mast cell, which is the source of histamine.


Extended half-life factor IX prophylaxis up to every 21 days in hemophilia B: a longitudinal analysis of the efficacy and safety in selected adult patients.
Extended half-life factor IX (FIX) products have revolutionized prophylactic treatment for patients with hemophilia B as patients maintain protective FIX levels with minimal occurrence of spontaneous bleeding. rIX-FP is an extended half-life FIX product that allows prolonged dosing intervals. To assess individualized and prolonged prophylactic dosing interval up to 21 days in adult patients (≥18 years) with hemophilia B in the rIX-FP clinical trial program. Patients who were included in the PROLONG-9FP phase III study or who received rIX-FP during surgery could continue into an extension study for long-term assessment. Patients began 7-day prophylaxis with rIX-FP, and after 6 months, they could extend dosing intervals to every 14 days. In the extension study, adult patients could switch to a 21-day regimen if well-controlled on a 14-day regimen. Eleven patients transitioned from a 7-day prophylaxis regimen to a 14-day regimen and finally to a 21-day regimen, 5 of whom were treated on demand at enrollment. Patients who switched to the 21-day regimen had a median annualized spontaneous bleeding rate of 0.0 across all regimens. The median observed FIX activity remained >5 IU/dL until day 21 after a single 100-IU/kg dose of rIX-FP. After 6 months on the 21-day regimen, 2 patients switched back to a 14-day regimen. No inhibitors, anaphylactic reactions, or thromboembolic events occurred. Patients who are well controlled on a once-weekly regimen might extend their treatment interval to 14 days, and in adult patients, further extension to up to 21 days (100 IU/kg) may be considered.


Increase in histone poly (ADP-ribosylation) in mitogen-activated lymphoid cells.
Poly (ADP-ribosylated) histones appear to be intermediates in nuclear processes that involve DNA strand breaks. We have studied histone ADP-ribosylation in cellular lysates from activated human lymphoid cells in culture. Modified histones differing in the number of ADP-ribose groups gave separate bands upon two-dimensional gel electrophoresis. Cellular lysates from control cells contained histones modified with 1 to 15 ADP-ribose groups. Stimulation of the cells during culture with phytohemagglutinin (PHA) or a phorbol ester (TPA) as well as combinations of these two reagents led to a significant increase in the upper limit number of ADP-ribose groups attached to histones in the presence of divalent metal ions. Hyper (ADP-ribosylated) H2B carrying at least 32 ADP-ribose groups gave a distinctly characteristic pattern on two-dimensional gels showing that highly ordered enzymatic steps are followed for its synthesis. Moreover, it was found that PHA and/or TPA induces branching of the poly (ADP-ribose) on H2B. The increase in histone poly (ADP-ribosylation) following lymphocyte activation was less dramatic during incubation of cellular lysates in the absence of divalent metal ions. The increased histone modification observed in this study may result from an increase in cell proliferation during activation of lymphoid cells. The finding that the number of ADP-ribose groups on H4 equals or exceeds by one the number of acetyl groups suggests that the two modifications may share common functions.


Capsaicin causes release of a substance P-like peptide in guinea-pig inferior mesenteric ganglia.
The effects of capsaicin (0.5-100 microM) on neurones of the isolated inferior mesenteric ganglia (i.m.g.) of the guinea-pig were investigated by means of intracellular recording techniques. When applied to neurones of the i.m.g. that exhibited a slow non-cholinergic excitatory potential (Dun & Jiang, 1982), capsaicin caused in the large majority of these cells a long lasting depolarization accompanied by intense neuronal discharges. During and immediately following the depolarization, repetitive presynaptic stimulation consistently failed to elicit the non-cholinergic depolarization; a partial recovery was observed in relatively few neurones. The fast (nicotinic) excitatory post-synaptic potentials (e.p.s.p.s) were not suppressed by capsaicin in any of these cells. The membrane potential, input resistance and the amplitude of fast e.p.s.p.s in neurones of the i.m.g. that generated no detectable non-cholinergic depolarizations were not affected by capsaicin. Post-synaptic membrane sensitivity to exogenous application of substance P was not altered following capsaicin superfusion even though the latter effectively abolished the non-cholinergic depolarization in the same neurones. Superfusing the i.m.g. with a Ca-free Krebs solution markedly attenuated or abolished the depolarizing effect of capsaicin whereas tetrodotoxin (1 microM) was without effect. Capsaicin was without effect in a few neurones that generated a non-cholinergic depolarization; the latter was not desensitized by bath application of substance P. Capsaicin caused no appreciable effects in neurones of the bullfrog sympathetic ganglia; thus, the fast and slow post-synaptic potentials including the late slow e.p.s.p. the transmitter of which is the peptide luteinizing hormone-releasing hormone (Jan & Jan, 1982) were not affected. The results suggest that the depolarizing effect of capsaicin in neurones of the guinea-pig i.m.g. is due to a selective release of ganglionic substance P or a substance P-like peptide in a Ca-dependent manner, and that the non-cholinergic potentials elicited in capsaicin-insensitive neurones may be generated by a transmitter(s) other than substance P.


Lecturers and students as stakeholders for education commissioning for learning disability nursing: focus group findings from a multiple method study.
In England, the numbers of learning disability nurses are declining; a need for urgent attention to workforce planning issues has been advocated. This paper considers views of lecturers, students and potential students as legitimate stakeholders for future education commissioning for this field of nursing. This project aimed to undertake a strategic review of learning disability nursing educational commissioning, to provide an 'evidence based' evaluation to inform future strategic commissioning of learning disability nursing for one Health Authority, UK. The project adopted a structured multiple methods approach to generate evidence from a number of data sources, this paper reports on the findings from one method [focus groups] used for two groups of stakeholders. Informants comprised 10 learning disability nursing students studying at a Higher Education Institution, 25 health and social care students studying at a Further Education College, and 6 academic staff from 5 universities; all informants were from the south of England. The method reported on in this paper is focus group methodology. Once completed, transcripts made were read in full, and subjected to content analysis. The process of content analysis led to the development of 11 theoretical categories that describe the multiplicity of views of informants, as to issues of importance for this element of the health workforce. The paper concludes by identifying key messages from these informants. It is suggested that both method and findings have national and international resonance, as stakeholder engagement is a universal issue in health care education commissioning.


Sensory systems: seeing the world in a new light.
Most terminally differentiated sensory neurons express a single sensory receptor molecule. A Drosophila photoreceptor organ breaks this rule by switching to expressing a different type of Rhodopsin as it metamorphoses from larva to adult.


Excitability increase of neurons in olfactory cortex slices of the guinea pig after penicillin administration.
The mechanism underlying the effects of penicillin on slices of the olfactory cortex of the guinea pig was examined. In a previous report it was shown that penicillin increases the amplitude of the presynaptic action potential, the population EPSP and, more strongly, the population responses of the postsynaptic cells. Moreover, the postsynaptic population responses increased in number and suggested strong repetitive firing. These results were confirmed in the present study. Analysis of stimulus-response relationships suggested that the enhancement of the postsynaptic response was due to an increase in excitability of the postsynaptic neurons by penicillin. The amplitude changes of the presynaptic action potential and the EPSP were probably largely, if not completely, due to an increase in resistance of the bathing fluid. It was found that the changes in population responses paralleled to a large extent changes in cell discharge. In addition, penicillin was found to induce spontaneous firing of the postsynaptic cells. The changes in cell discharge were consistent with an increase in excitability of the postsynaptic cells.


Chitosan-carboxymethylcellulose interpolymer complexes for gastric-specific delivery of clarithromycin.
Chitosan (CS) and carboxymethylcellulose (CMC) sodium interpolymer complexes were formed using the novel method "tablets-in-capsule" for stomach drug delivery. The aim of this study was to investigate the influence of the molecular weight (M.wt.) of CS and the proportion CS/CMC on physical properties and clarithromycin (CAM) release. Swelling was dependent on CS M.wt., on medium pH and on proportion polymer/polymer. The higher M.wt., the major presence of protonated amined moieties that can be ionized and modify the swelling/eroding and dissolution medium uptake capacity. Swelling kinetics at pH 1.2, were close to Fickian diffusion, whereas at pH 4.2 were non-Fickian. Furthermore, dissolution medium uptake capacity can be adjusted to an exponential equation at pH 1.2 (r2> or =0.96), and to a linear equation at pH 4.2 (r2> or =0.99), showing that at low pHs the repulsion among ionized chains is higher. CAM release rates have shown to be dependent on pH and on polymer proportion. At pH 1.2, the fastest profile was obtained when using high M.wt. CS. Drug diffusion was Fickian, so the process is governed by swelling/eroding. Whereas at pH 4.2, CAM release followed zero-order kinetics with no influence on M.wt. So, release is controlled by CAM low solubility.


A comparison of the prognostic value of antibody-dependent lymphocyte cytotoxicity and other EBV antibody assays in Chinese patients with nasopharyngeal carcinoma.
Antibody titres to EBV-associated antigens in Chinese NPC patients were analysed according to length of survival after diagnosis and to disease stage. Geometric mean titres of ADLC antibody were highest in the long-term survivors, whereas VCA, EA and EBNA antibody titres showed an inverse relationship to survival. High VCA, EA and EBNA titres were less frequent, and high ADLC titres were more frequent in long-term survivors than in intermediate or short-term survivors. The association of geometric mean titres of EBV antibodies with prognosis could not be entirely explained by stage of disease. A functional role for the ADLC antibody is suggested by the association of a high ADLC antibody titre with a good prognosis regardless of stage of disease.


The relationship of cerebral atrophy and T1 in alcoholics: an MRI study.
There was a significant correlation between two measures of cerebral atrophy (the ventricle to brain ratio and the relative cerebral volume) and T1 in 19 detoxified alcoholics. This provides further evidence that T1 is a marker of structural damage in alcoholics although the partial volume effect of CSF may contribute to this finding. This has implications for studies comparing alcoholics to normal controls and suggests that better ways of excluding CSF need to be found.


Human pluripotent stem cell differentiation into authentic striatal projection neurons.
Here we present the principles and steps of a protocol that we have recently developed for the differentiation of hES/iPS cells into the authentic human striatal projection medium spiny neurons (MSNs) that die in Huntington's Disease (HD). Authenticity is judged by the convergence of multiple features within individual cells. Our procedure lasts 80 days and couples neural induction via BMP/TGF-β inhibition with exposure to the developmental factors sonic hedgehog (SHH) and dickkopf1 (DKK-1) to drive ventral telencephalic specification, followed by terminal differentiation [1]. Authenticity of the resulting neuronal population is monitored by the appearance of FOXG1(+)/GSX2(+) progenitor cells of the lateral ganglionic eminence (LGE) at day 15-25 of differentiation, followed by appearance of CTIP2-, FOXP1- and FOXP2-positive cells at day 45. These precursor cells then mature into MAP2(+)/GABA(+) neurons with 20 % of them ultimately co-expressing the DARPP-32 and CTIP2 diagnostic markers and carrying electrophysiological properties expected for fully functional MSNs.The protocol is characterized by its replicability in at least three human pluripotent cell lines. Altogether this protocol defines a useful platform for in vitro developmental neurobiology studies, drug screening, and regenerative medicine approaches.


Anatomical relationships between the ventral mesencephalic tegmentum--a 10 region and the locus coeruleus as demonstrated by anterograde and retrograde tracing techniques.
We have searched for anatomical connections between the ventral mesencephalic tegmentum (VMT), including the dopaminergic cell group A10 and the locus coeruleus (LC) region. Tritiated leucine (120--220 nl) and horseradish peroxidase delivered by electrophoresis were injected in the VMT-A10 region. We have demonstrated, on the one hand bilateral projections from the VMT-A10 region to LC, and on the other hand a possible contralateral projection from LC to VMT-A10 region. These relationships, reported for the first time may have some important functional significance.


The top risk factors for endodontic flare-up: a Monte Carlo simulation.
The aim of this study was to analyze the strength of risk factors related to endodontic flare-ups and rank them in order of their importance MATERIALS AND METHODS: A systematic literature search of PubMed, Cochrane Central Register of Controlled Trials, Scopus, and ISI Web of Knowledge, and grey literature was conducted up to November 2019. One hundred ninety-eight publications were identified. Twelve records fulfilled the eligibility criteria, and eight significant risk factors for flare-up, namely, "Periapical lesion," "multiple-visit treatment," "preoperative pain," "necrotic teeth," "female gender," "retreatment," "percussion pain," and "analgesics," were selected to construct the simulation model. The final data pool was established by the integration of data of common risk factors in the included articles. Monte Carlo method was used to analyze of combined numerical data, for simulation of the risk factor impacts. Ten thousand iterations were generated in the simulation model. The results of the simulation revealed that the risk estimates of the factors had varying ranges of influence and probability on the flare-up risk. "Periapical lesion" was found to be the most sensitive risk factor, following by "preoperative pain" which was ranked the second place. The third-ranked risk factor was "multiple-visit treatment." The least sensitive risk factors for endodontic flare-up were "retreatment," "female gender," "necrotic teeth," and "analgesics." The present study provides better comprehension on the importance of risk factors for flare-up based on their risk estimates. A Monte Carlo simulation was adopted to identify the most influential risk factors for endodontic flare-up with a ranking, which can be used to provide meaningful predictions and further insights into clinicians' perception of flare-up risk.


Culture of patient-derived multicellular clusters in suspended hydrogel capsules for pre-clinical personalized drug screening.
A personalized medication regimen provides precise treatment for an individual and can be guided by pre-clinical drug screening. The economical and high-efficiency simulation of the liver tumor microenvironment (TME) in a drug-screening model has high value yet challenging to accomplish. Herein, we propose a simulation of the liver TME with suspended alginate-gelatin hydrogel capsules encapsulating patient-derived liver tumor multicellular clusters, and the culture of patient-derived tumor organoids(PDTOs) for personalized pre-clinical drug screening. The hydrogel capsule offers a 3D matrix environment with mechanical and biological properties similar to those of the liver in vivo. As a result, 18 of the 28 patient-derived multicellular clusters were successfully cultured as PDTOs. These PDTOs, along with hepatocyte growth factor (HGF) of non-cellular components, preserve stromal cells, including cancer-associated fibroblasts (CAFs) and vascular endothelial cells (VECs). They also maintain stable expression of molecular markers and tumor heterogeneity similar to those of the original liver tumors. Drugs, including cabazitaxel, oxaliplatin, and sorafenib, were tested in PDTOs. The sensitivity of PDTOs to these drugs differs between individuals. The sensitivity of one PDTO to oxaliplatin was validated using magnetic resonance imaging (MRI) and biochemical tests after oxaliplatin clinical treatment of the corresponding patient. Therefore, this approach is promising for economical, accurate, and high-throughput drug screening for personalized treatment.