The serotonin transporter polymorphisms and major depression following traumatic brain injury.
The purpose of this study was to examine the role of the serotonin transporter gene polymorphisms on the risk of major depression following traumatic brain injury (TBI). Seventy-five patients who had sustained a TBI and who met the Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV) criteria for mood disorder due to TBI were compared to 99 controls with TBI but no mood disorder. The severity of depression was rated using the Hamilton Depression Rating Scale (HAMD) for the depressed patients. All patients were genotyped for the serotonin transporter gene-linked polymorphic region (5-HTTLPR) with the assay for the rs25531 allelic variant. The distribution of genotype frequencies was not different between the depressed and control groups (chi(2) = 1.43, df = 2, p = 0.488) and for the depressed patients there was no association between HAMD scores and the polymorphisms (t-test = 1.71, df = 68, p = 0.092). There was no evidence of association between the serotonin transporter gene polymorphisms and depression post-TBI. Future research is indicated into the possible role of other candidate genes as risk factors for depression in this population.


Effect of informal employment on the relationship between psychosocial work risk factors and musculoskeletal pain in Central American workers.
The constant increase on the psychosocial demands experienced at work seems to contribute to the increase in health problems such as musculoskeletal pain (MSP). This association may be especially important in low-income and middle-income countries, where there is a large proportion of informal workers among whom there is little research. We analysed the association between psychosocial work risk factors and MSP among formal and informal workers using the First Central American Survey of Working Conditions and Health. This is a representative sample (n=12 024) of the economically active population of the six Spanish-speaking countries of Central America. Prevalence ratios (PR) and corresponding 95% CIs from Poisson regression models were used to estimate the association between psychosocial work risk factors and the MSP. Compared with formal workers, informal workers reported higher prevalence of MPS in the body regions analysed (ie, cervicodorsal, lumbosacral, upper extremities) and higher exposure to psychosocial work risk factors. However, on the whole, the associations between the exposure to psychosocial work risk factors and the prevalence of MSP were similar for both formal and informal workers. Only the association between exposure to high demands and MSP in the upper extremities was higher (p=0.012) among formal (PR=1.69, 95% CI 1.46 to 1.96) than among informal workers (PR=1.40; 95% CI 1.30 to 1.51). Exposure to adverse levels of psychosocial work risk factors is associated with higher prevalence of MPS among both formal and informal workers. However, the role of employment informality in this association is complex and requires further examination.


Independent effects of palatability and within-meal pauses on intake and appetite ratings in human volunteers.
The effects of the introduction of timed pauses within meals and palatability on food intake and changes in rated appetite during a meal were assessed in three experiments in which volunteers ate a lunch of pasta with a tomato sauce. Eating was monitored using a disguised electronic balance attached to a micro-computer, which also allowed the introduction of timed pauses within meals. In the first experiment, 16 subjects were tested with both a bland and palatable food (with 0.27% oregano), with eating uninterrupted or with pauses after every 50 g consumed during which appetite ratings were completed. Both the addition of oregano and the introduction of regular within-meal pauses enhanced overall intake. Rated hunger increased in the early stages of eating the palatable food in the interrupted condition, and then declined, whereas hunger declined throughout with the bland food. Similarly, the linear function relating intake to time in the uninterrupted condition was greater with the palatable food. In the second experiment, nine subjects ate the palatable food with no pauses within meals, with 30-second pauses with appetite ratings or with 30-second pauses in a non-appetite task. Intake was greater in both pause conditions than when eating was uninterrupted. In Experiment 3, the effect of pause duration was investigated in a further 16 subjects, with either no pause or a pause of 5, 30 or 60 seconds. Subjects ate more in all pause conditions than with no pauses, while ratings of hunger and fullness suggested that subjects were less satisfied at the end of the meal with longer pauses. These data confirm previous work which suggests that palatability exerts its effect by stimulating appetite and eating rate, but also suggest that the introduction of pauses within meals enhances intake as well, contradicting the idea that pausing within meals should reduce intake by allowing more time for post-ingestive satiety to develop.


Bibliometric analysis of the effects of ginseng on skin.
Ginseng is widely used in cosmetics and skin care. The progress of research on the effect of ginseng on the skin was explored through a summary and analysis of skin-related studies on ginseng conducted over in the past 20 years, and this exploration aimed to elucidate new research opportunities with regard to the development and application of ginseng treatments for the skin. Keywords were used to retrieve human studies related to the use of ginseng to treat skin conditions from the Web of Science. Scientometric analyses were performed in R to analyze the studies on the human skin-related effects of ginseng conducted from 2000 to 2019. The main active ingredient in ginseng is ginsenoside, and its effects on the skin are mostly anti-aging and whitening. Ginseng extract regulates the levels of matrix metalloproteinases in human fibroblast type I collagen to improve the elasticity and water content of skin. In addition, ginseng inhibits the transcription factors or signaling pathways involved in the formation of melanin, it exerts a whitening effect. The authors of the retrieved studies are mostly located in Asia, mainly South Korea and China. Wang Y, Kim JH, and Kim YJ are relatively influential scholars, these ginseng-related articles published in the Journal of Ginseng Research, Molecules and other journals are very important in this field. This study shows the development of trends in research on ginseng as a raw cosmetic material used on the skin and thus enables researchers to rapidly understand the key information in the field of ginseng research, comprehend the research directions, and improve their research efficiency.


Molecular genetic and chemical assessment of radix Angelica (Danggui) in China.
The roots of Angelica sinensis (Danggui), a traditional Chinese medicine, have been used for invigorating blood circulation for over 2000 years in China. Three common species of Angelica roots are found in Asia: A. sinensis from China, A. acutiloba from Japan, and A. gigas from Korea. By using a molecular genetic approach, the 5S-rRNA spacer domains of the three species of Angelica were amplified, and their nucleotide sequences were determined. Diversity in DNA sequences among various species was found in their 5S-rRNA spacer domains, which could serve as markers for authentic identification of Angelica roots. In chemical analyses, the main constituents of Angelica roots including ferulic acid and Z-ligustilide were determined by HPLC; roots of A. sinensis were clearly distinct in that they contained approximately 10-fold higher levels of ferulic acid and Z-ligustilide as compared to roots of A. acutiloba and A. gigas. In addition, the amounts of main constituents in roots of A. sinensis varied according to different regions of cultivation and different methods of preservation. The chemical profile determined by HPLC therefore could serve as a fingerprint for quality control of Angelica roots.


Factors affecting the production of candicidin.
Factors affecting candicidin synthesis and mycelial growth of Streptomyces griseus IMRU 3570 were studied. Inorganic phosphate was found to inhibit candicidin synthesis but to stimulate mycelial growth. Zinc, iron, and magnesium ions stimulated candicidin synthesis at relatively high concentrations in a complex medium but not in a synthetic medium. No other factors studied, such as temperature, oxygen absorption rate, and sugar concentration, were found to differentially affect antibiotic synthesis and mycelial growth. Optimum concentration of inorganic phosphate for candicidin synthesis in a chemically defined medium was found to be between 5 x 10(-5) and 5 x 10(-4) M. The culture in idiophase stage can be reverted to typical trophophase growth by the addition of inorganic phosphate, suggesting the controlling role of inorganic phosphate in repression and derepression of secondary metabolic and primary metabolic activity of the culture. With a soya peptone-glucose medium, the maximum rate of candicidin production could be maintained and extended for a considerable length of time by controlling the culture pH at 8.0, using glucose to adjust the pH during the later stages of a batch fermentation. Carrying out fermentations in this way has given candicidin yields up to 4 g/liter.


Effect of brain death and non-heart-beating kidney donation on renal function and injury: an assessment in the isolated perfused rat kidney.
Ischemic injury to the renal allograft prior to implantation is considered as the major cause of primary non and never-function (PNF) and delayed graft function (DGF). Evidence has been put forward that brain dead and non-heart-beating (NHB) donor organs are of marginal quality compared to living donors. The purpose of this study was to evaluate renal function and injury of brain dead and NHB donor kidneys using the isolated perfused rat kidney. Fisher F344 rats were either maintained brain death for 4 hr or subjected to cardiac arrest for 45 min (NHB). Living rats served as controls. To omit additional effects of cold ischemia, kidneys were immediately reperfused. Renal function and injury were assessed by monitoring urine production, glomerular filtration rate (GFR), Na+ and K+ reabsorption, glucose metabolism and reabsorption, as well as release of brush border, lysosomal, and intracellular enzymes. Renal dysfunction and injury were most pronounced in NHB donor kidneys reflected by a highly reduced urine production, anaerobic glucose metabolism resulting in lactate formation, and significant higher luminal release of intracellular and lysosomal enzymes. Brain dead kidneys showed an increased urine production and were functionally abnormal in K+ reabsorption showing a net excretion of K+, probably as a result of ATP depletion. Loss of brush border occurred during brain death and cardiac arrest. Both, brain death and cardiac arrest have deleterious effects on renal function and renal injury. The ischemically injured NHB donor kidney was functionally inferior compared to the brain dead donor kidney and living donor kidneys. However, both brain dead and NHB kidneys showed considerable renal damage compared to kidneys from living donors.


Failure to detect the presence of Chlamydia pneumoniae in sarcoid pathology specimens.
The pathogenesis of sarcoidosis is not yet known. On the basis of seroepidemiological data, an association between Chlamydia pneumoniae infection and sarcoidosis has been suggested, but so far no study has addressed the direct detection of this agent in the affected tissues. The aim of the present study was to detect C. pneumoniae deoxyribonucleic acid (DNA) within sarcoid tissue specimens by means of a two-step polymerase chain reaction. Lung biopsy specimens of 33 patients with histologically confirmed pulmonary sarcoidosis and 21 control lung biopsies or pathology specimens of patients with pulmonary carcinoma or emphysema were retrospectively analysed. A nested polymerase chain reaction was applied using two sets of primers designed to detect a fragment of the 16 strand ribosomal ribonucleic acid (rRNA) gene of C. pneumoniae. The results of the study failed to demonstrate the presence of C. pneumoniae in biopsy specimens of sarcoid tissue and in the control lung biopsies or pathology specimens. Our results, therefore, tend to rule out the possibility of a direct involvement of Chlamydia pneumoniae in the pathogenesis of sarcoidosis.


Interleukin 28B gene variation at rs12979860 determines early viral kinetics during treatment in patients carrying genotypes 2 or 3 of hepatitis C virus.
Single-nucleotide polymorphisms upstream of the interleukin 28B (interferon λ3) gene (IL28B) strongly influence treatment efficacy in patients carrying hepatitis C virus (HCV) of genotype 1. In patients receiving 12 or 24 weeks of interferon-ribavirin therapy for infection with genotype 2 or 3 (n = 341), we found that rs12979860 strikingly determined the first phase of viral elimination (P < .001). In patients treated for 24 weeks, rs12979860 also predicted the rate of sustained virologic response (P = .02), especially among those with high baseline HCV RNA levels (P = .002) or older than 45 years (P = .01). Patients carrying CC(rs12979860) had higher baseline HCV RNA levels (P < .001) and did not, when treated for 12 weeks, achieve sustained virologic response more often than those carrying CT(rs1297986) or TT(rs1297986). The results indicate that IL28B gene testing may identify patients carrying genotype 2 or 3 who could benefit from extended treatment.


Culture Independent Genomic Comparisons Reveal Environmental Adaptations for Altiarchaeales.
The recently proposed candidatus order Altiarchaeales remains an uncultured archaeal lineage composed of genetically diverse, globally widespread organisms frequently observed in anoxic subsurface environments. In spite of 15 years of studies on the psychrophilic biofilm-producing Candidatus Altiarchaeum hamiconexum and its close relatives, very little is known about the phylogenetic and functional diversity of the widespread free-living marine members of this taxon. From methanogenic sediments in the White Oak River Estuary, NC, USA, we sequenced a single cell amplified genome (SAG), WOR_SM1_SCG, and used it to identify and refine two high-quality genomes from metagenomes, WOR_SM1_79 and WOR_SM1_86-2, from the same site. These three genomic reconstructions form a monophyletic group, which also includes three previously published genomes from metagenomes from terrestrial springs and a SAG from Sakinaw Lake in a group previously designated as pMC2A384. A synapomorphic mutation in the Altiarchaeales tRNA synthetase β subunit, pheT, caused the protein to be encoded as two subunits at non-adjacent loci. Consistent with the terrestrial spring clades, our estuarine genomes contained a near-complete autotrophic metabolism, H2 or CO as potential electron donors, a reductive acetyl-CoA pathway for carbon fixation, and methylotroph-like NADP(H)-dependent dehydrogenase. Phylogenies based on 16S rRNA genes and concatenated conserved proteins identified two distinct sub-clades of Altiarchaeales, Alti-1 populated by organisms from actively flowing springs, and Alti-2 which was more widespread, diverse, and not associated with visible mats. The core Alti-1 genome suggested Alti-1 is adapted for the stream environment with lipopolysaccharide production capacity and extracellular hami structures. The core Alti-2 genome suggested members of this clade are free-living with distinct mechanisms for energy maintenance, motility, osmoregulation, and sulfur redox reactions. These data suggested that the hamus structures found in Candidatus Altiarchaeum hamiconexum are not present outside of stream-adapted Altiarchaeales. Homologs to a Na(+) transporter and membrane bound coenzyme A disulfide reductase that were unique to the brackish sediment Alti-2 genomes, could indicate adaptations to the estuarine, sulfur-rich environment.


The impact of volunteer mentoring schemes on carers of people with dementia and volunteer mentors: a systematic review.
This systematic review aims to examine the differences and similarities between the various types of volunteer mentoring (befriending, mentoring and peer support) and to identify the benefits for carers and volunteers. Literature searching was performed using 8 electronic databases, gray literature, and reference list searching of relevant systematic reviews. Searches were carried out in January 2013. Four studies fitted the inclusion criteria, with 3 investigating peer support and 1 befriending for carers. Quantitative findings highlighted a weak but statistically significant (P =.04) reduction in depression after 6 months of befriending. Qualitative findings highlighted the value carers placed on the volunteer mentors' experiential similarity. Matching was not essential for the development of successful volunteer mentoring relationships. In conclusion, the lack of need for matching and the importance of experiential similarity deserve further investigation. However, this review highlights a lack of demonstrated efficacy of volunteer mentoring for carers of people with dementia.


A review of telemedicine in vascular surgery.
Telemedicine refers to the delivery of medical care through telecommunications and has been utilized by many medical specialists. In its basic form, telemedicine can involve the use of a telephone or fax. More advanced forms are the transmission of still images, often referred to as "store-and-forward" technology, or real-time two-way interactive video. The former is possible over existing phone lines or the Internet and has enjoyed success in visually oriented disciplines such as radiology and dermatology. The latter requires high bandwidth communication lines and is therefore considerably more expensive. This article reviews the use of telemedicine as applied specifically to vascular surgery. Initial studies indicate that store-and-forward technology can be used to adequately assess and treat wounds in vascular patients. A recent study reported the use of two-way interactive video for remote assessment of a wide variety of vascular patients. Diagnosis and treatment recommendations by the remote physician were found to be comparable to conventional on-site examinations. Patient satisfaction with the telemedicine examination was noted to be extremely high. In conclusion, telemedicine, although not commonly used in vascular surgery, has the potential of increasing patient access to specialty care, while decreasing patient or physician travel. The use of telemedicine in vascular surgery will likely continue to expand as technology improves and costs decrease.


Accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) compared with standard CEF in metastatic breast cancer patients: results of a multicenter, randomized phase III study of the Italian Gruppo Oncologico Nord-Ouest-Mammella Inter Gruppo Group.
To evaluate whether an accelerated-intensified cyclophosphamide, epirubicin, and fluorouracil (CEF) chemotherapy regimen with the support of granulocyte colony-stimulating factor (G-CSF) induces a higher activity and efficacy compared with standard CEF in metastatic breast cancer patients. Stage IV breast cancer patients were randomized to receive as first-line chemotherapy either standard CEF (cyclophosphamide 600 mg/m(2), epirubicin 60 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 21 days (CEF21) or accelerated-intensified CEF (cyclophosphamide 1,000 mg/m(2), epirubicin 80 mg/m(2), and fluorouracil 600 mg/m(2)) administered every 14 days (HD-CEF14) with the support of G-CSF. Treatment was administered for eight cycles. A total of 151 patients were randomized (74 patients on the CEF21 arm and 77 on the HD-CEF14 arm). In both arms, the median number of administered cycles was eight. The dose-intensity actually administered was 93% and 86% of that planned, in CEF21- and HD-CEF14-treated patients, respectively. Compared with the CEF21 arm, the dose-intensity increase in the HD-CEF14 arm was 80%. Both nonhematologic and hematologic toxicities were higher in the HD-CEF14 arm than in the CEF21 arm. During chemotherapy, four deaths occurred in the HD-CEF14 arm. No difference in overall response rate (complete plus partial responses) was observed: 49% and 51% in the CEF21 and HD-CEF14 arms, respectively (P =.94). A slightly non-statistically significant higher percentage of complete response was observed in the HD-CEF14 arm (20% v 15%). No difference in efficacy was observed. The median time to progression was 14.3 and 12.8 months in the CEF21 and HD-CEF14 arms, respectively (P =.69). Median overall survival was 32.7 and 27.2 months in the CEF21 and HD-CEF14 arms, respectively (P =.16). In metastatic breast cancer patients, an 80% increase in dose-intensity of the CEF regimen, obtained by both acceleration and dose intensification, does not improve the activity and the efficacy compared with a standard dose-intensity CEF regimen.


Compared behavioral responses of maleDrosophila melanogaster (Canton S) to natural and synthetic aphrodisiacs.
Cuticular aphrodisiacs fromD. melanogaster females were further characterized and the male response specificity towards such natural and synthetic unsaturated hydrocarbons was investigated. The behavioral activity seems to be correlated with some chain-length requirement and double-bond position; at least one double bond in position 7 seems necessary. This position is more abundant among natural monoenes, and among dienes which also bear a second double bond in position 11, whatever the chain length. Bioassays of the synthetic (Z,Z)-7,11-heptacosadiene yielded a dose-response curve close to that of the natural mixture of heptacosadienes in which the 7-11 isomer is predominant. This female specific 7,11 heptacosadiene appears to be the most potent aphrodisiac for males of the species. Its threshold is lower than that of both 7,11-nonacosadiene and 7-pentacosene which might also play a role in sex and species recognition.


Regulation of pulmonary resistance during cardiopulmonary preservation.
To characterize the neural and vasoactive mediators of pulmonary vasoconstriction and determine whether the beneficial effect of isoproterenol could be mimicked by other agents that increase cyclic adenosine monophosphate, heart and lung organ blocks were harvested from calves and studied in a normothermic autoperfusion circuit. In the experimental protocol, measurements were obtained (A) after sternotomy but before autoperfusion (in vivo); (B) during stimulation of in vivo control with tert-butyl hydroperoxide (t-BuOOH), a lipid peroxide; (C) after cannulation and institution of in situ autoperfusion (innervated preparation); (D) following denervation and explanation (ex vivo); (E) during stimulation of ex vivo preparation with t-BuOOH; and (F,G) after administration of isoproterenol, aminophylline and prostaglandin E1 to the ex vivo preparation with (time G) and without (time F) stimulation using t-BuOOH. Plots of transpulmonary pressure gradient versus cardiac output were generated for each animal, and an index of pulmonary vascular resistance was obtained from the slope of the linear relationship. Blood samples were collected for measurement of thromboxane-B2, 6-keto-prostaglandin-F1 alpha, and complement activation products C3a and C5a. Pulmonary vasoconstriction occurred during in situ autoperfusion prior to denervation and increased further following denervation and ex vivo autoperfusion; vasoconstriction correlated with increased levels of circulating vasoactive mediators. The pulmonary vasoconstrictor response was greater in the denervated vascular bed compared with the innervated state. All agents reduced postexplant pulmonary vasoconstriction. We conclude that agents that increase cyclic AMP modulate the pulmonary vasoconstrictor response and thus may enhance lung preservation in the autoperfusion model as well as with other current preservation methods.


Cognitive and sociodemographic risk factors for mortality in the Seattle Longitudinal Study.
The relationship between cognitive function and survivorship was examined in a community-dwelling sample. Survival analysis was used to examine how level and change in intellectual functioning, verbal memory, perceptual speed, and psychomotor speed were related to mortality in a sample of 601 individuals who subsequently died (decedents; n = 342 men; n = 259 women; M = 73.81 years of age) and a control group of 609 survivors (n = 296 men; n = 313 women; M = 71.96). The sample of survivors was selected to be of similar age and to have a similar level of education as the decedents. Individuals in the lowest 25th percentile of performance (crystallized abilities, visualization abilities, verbal memory, and perceptual and psychomotor speed) had a significant risk for subsequent mortality compared to individuals in the highest 25th percentile. However, after adjusting for demographic variables and psychomotor speed, only perceptual speed remained a significant risk factor for mortality. Significant 7-year declines (lowest 25th percentile) in measurements of Verbal Meaning, Spatial Ability, Reasoning Ability, and Psychomotor Speed were risk factors for subsequent mortality relative to those who had the least amount of decline. The relationship between mortality and cognitive function tended to be a specific rather than a pervasive phenomenon, even after adjusting for sociodemographic factors and psychomotor speed. Decrease in cognitive performance tended to be a better predictor of subsequent mortality than was the level of cognitive performance.


Chloroplast DNA variation and postglacial recolonization of common ash (Fraxinus excelsior L.) in Europe.
We used chloroplast polymerase chain reaction-restriction-fragment length polymorphism (PCR-RFLP) and chloroplast microsatellites to assess the structure of genetic variation and postglacial history across the entire natural range of the common ash (Fraxinus excelsior L.), a broad-leaved wind-pollinated and wind-dispersed European forest tree. A low level of polymorphism was observed, with only 12 haplotypes at four polymorphic microsatellites in 201 populations, and two PCR-RFLP haplotypes in a subset of 62 populations. The clear geographical pattern displayed by the five most common haplotypes was in agreement with glacial refugia for ash being located in Iberia, Italy, the eastern Alps and the Balkan Peninsula, as had been suggested from fossil pollen data. A low chloroplast DNA mutation rate, a low effective population size in glacial refugia related to ash's life history traits, as well as features of postglacial expansion were put forward to explain the low level of polymorphism. Differentiation among populations was high (GST= 0.89), reflecting poor mixing among recolonizing lineages. Therefore, the responsible factor for the highly homogeneous genetic pattern previously identified at nuclear microsatellites throughout western and central Europe (Heuertz et al. 2004) must have been efficient postglacial pollen flow. Further comparison of variation patterns at both marker systems revealed that nuclear microsatellites identified complex differentiation patterns in south-eastern Europe which remained undetected with chloroplast microsatellites. The results suggest that data from different markers should be combined in order to capture the most important genetic patterns in a species.


Immune checkpoint inhibitors in hepatocellular carcinoma: A review of current clinical trials.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer with a poor prognosis due to advanced disease presentation or recurrence despite curative-intent resection. Since the approval of sorafenib in 2007, few systemic therapies offered a significant improvement in treatment outcomes. Over the last 3 years, however, rapid advancements in the field of immunotherapy have led to approval of checkpoint inhibitors in 2020 for use in advanced HCC. Since then, a few other clinical trials have shown promising results in the adjuvant and neoadjuvant setting. The objective of this review is to summarize data from existing clinical trials evaluating the use of systemic immune checkpoint inhibitors in HCC and to follow the natural evolution of this development across the metastatic, adjuvant, and neoadjuvant landscapes.


Rationale for the application of exposure and response prevention to the treatment of anorexia nervosa.
Anorexia nervosa (AN) is a life threatening and difficult to treat illness with a high relapse rate. Current treatments are inadequate and new approaches to treatment are needed. We review the data on anxiety in AN, the relationship between anxiety disorders and AN, and the use of Exposure and Response Prevention in treatment. The overlap between AN and anxiety disorders suggest a model of AN in which baseline anxiety features yield eating related fears, avoidance behaviors, and ritualized safety behaviors that promote the underweight state and the perpetuation of the disorder. We propose an Exposure and Response Prevention treatment to prevent relapse in AN. Overlap between AN and anxiety disorders suggests that Exposure and Response Prevention may be a new and beneficial approach to preventing relapse in individuals with AN.


Optimization of eight-element multi-detector row helical CT technology for evaluation of the abdomen.
To evaluate protocols for abdominal imaging with an eight-element multi-detector row computed tomographic (CT) scanner. An eight-element helical CT scanner was used to acquire data in two phantoms with four-element (pitch, 0.75 and 1.5; section thickness, 1.25, 2.5, and 5.0 mm) and eight-element (pitch, 0.625, 0.875, 1.35 and 1.675; section thickness, 1.25 and 2.5 mm) protocols. One phantom was used for low-contrast detectability and streak artifact; the other, for high-contrast performance. Protocols included near constant radiation dose (140 kV and varied tube current, confirmed by using the above protocols to scan a dedicated radiation dose phantom). Data were analyzed by three blinded readers for streak artifacts, contrast-to-noise ratio, and z-axis resolution (contrast-transfer function). Statistical analysis included studentized range tests. Contrast-to-noise ratios for four and eight elements were not consistently different. Qualitative evaluation for streak artifacts revealed fewer artifacts for all eight-element 1.25-mm-thick section protocols, as compared with eight-element 2.5-mm protocols. All eight-element 2.5-mm protocols except that with 27.0 mm per rotation had fewer streak artifacts than did four-element protocols (P =.02-.04). Contrast-transfer functions along the z axis for eight-element protocols were better than those for four-element protocols, demonstrating improved z-axis resolution (P <.05). Images acquired at eight sections per rotation demonstrated no sacrifice of contrast-to-noise ratio, improved z-axis resolution, and fewer streak artifacts, even when radiation dose was similar to that for four-element CT.


[Serious mushroom poisoning by Cortinarius and Amanita virosa].
Following a characteristic long latent period (3-17 days), the nephrotoxins of Cortinarius rubellus and Cortinarius orellanus can cause the orellanus syndrome, due to severe damage of the proximal tubular epithelium. Amanita virosa is known to produce serious toxic effects in the liver and the kidneys after an initial asymptomatic latent phase. We discuss the toxicity, clinical features and treatment of the orellanus and the phalloides syndromes and present six case histories. Ingestion of Cortinarius rubellus and Cortinarius orellanus resulted in permanent renal failure in four out of five patients, following a latent period of about ten days. One patient who ingested Amanita virosa, developed hepatotoxicity. He was given silibinin and symptomatic treatment and recovered. After ingestion of Cortinarius rubellus and Cortinarius orellanus, no specific treatment is available. The therapy is directed toward the renal failure, including dialysis and possible transplantation. Poisoning by Amanita virosa is treated with the nonspecific antidote silibinin.


The allure and peril of hematopoietic stem cell transplantation: overcoming immune challenges to improve success.
Since its inception in the mid-twentieth century, the complication limiting the application and utility of allogeneic hematopoietic stem cell transplantation (allo-HSCT) to treat patients with hematopoietic cancer is the development of graft-versus-host disease (GVHD). Ironically, GVHD is induced by the cells (T lymphocytes) transplanted for the purpose of eliminating the malignancy. Damage ensuing to multiple tissues, e.g., skin, GI, liver, and others including the eye, provides the challenge of regulating systemic and organ-specific GVH responses. Because the immune system is also targeted by GVHD, this both: (a) impairs reconstitution of immunity post-transplant resulting in patient susceptibility to lethal infection and (b) markedly diminishes the individual's capacity to generate anti-cancer immunity--the raison d'etre for undergoing allo-HSCT. We hypothesize that deleting alloreactive T cells ex vivo using a new strategy involving antigen stimulation and alkylation will prevent systemic GVHD thereby providing a platform for the generation of anti-tumor immunity. Relapse also remains the major complication following autologous HSCT (auto-HSCT). While GVHD does not complicate auto-HSCT, its absence removes significant grant anti-tumor responses (GVL) and raises the challenge of generating rapid and effective anti-tumor immunity early post-transplant prior to immune reconstitution. We hypothesize that effective vaccine usage to stimulate tumor-specific T cells followed by their amplification using targeted IL-2 can be effective in both the autologous and allogeneic HSCT setting. Lastly, our findings support the notion that the ocular compartment can be locally targeted to regulate visual complications of GVHD which may involve both alloreactive and self-reactive (i.e., autoimmune) responses.


ILB® Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis.
Oxidative/nitrosative stress and mitochondrial dysfunction is a hallmark of amyotrophic lateral sclerosis (ALS), an invariably fatal progressive neurodegenerative disease. Here, as an exploratory arm of a phase II clinical trial (EudraCT Number 2017-005065-47), we used high performance liquid chromatography(HPLC) to investigate changes in the metabolic profiles of serum from ALS patients treated weekly for 4 weeks with a repeated sub-cutaneous dose of 1 mg/kg of a proprietary low molecular weight dextran sulphate, called ILB®. A significant normalization of the serum levels of several key metabolites was observed over the treatment period, including N-acetylaspartate (NAA), oxypurines, biomarkers of oxidative/nitrosative stress and antioxidants. An improved serum metabolic profile was accompanied by significant amelioration of the patients' clinical conditions, indicating a response to ILB® treatment that appears to be mediated by improvement of tissue bioenergetics, decrease of oxidative/nitrosative stress and attenuation of (neuro)inflammatory processes.


Weaning-induced cardiac dysfunction: where are we today?
The concept of weaning-induced cardiac dysfunction emerged 26 years ago with the publication of a clinical study conducted by François Lemaire and collaborators. One objective of this article is to remember the results and the historical context under which our pivotal study was conducted. Another objective is to review some of the subsequent studies that aimed to analyze the underlying mechanisms, to noninvasively detect the cardiac origin of weaning failure, and to propose specific therapies enabling weaning success. Weaning-induced cardiac dysfunction has become an established cause of weaning failure. Underlying mechanisms may differ from one patient to another. Important progress has already been made in its diagnosis thanks to relevant clinical research studies. Ongoing and future technological advances in ultrasonography and in biomarker research should certainly help in diagnosing weaning induced-pulmonary edema and in identifying the main mechanisms responsible for its development. Progress on appropriate therapeutic options on an individual basis is still expected.


Partial characterization of murine and monkey helper factor to a streptococcal antigen.
Helper factors specifically stimulating cooperative antibody responses by normal mouse spleen cells to a dinitrophenylated protein antigen from Streptococcus mutans (DNP-SA) were produced in vitro from monkey peripheral blood leucocytes and mouse spleen cells. The factors were partially characterized by gel filtration on Sephadex G-75, isoelectric focusing, treatment with heat and degradative enzymes and binding to specific immunoadsorbents. Gel filtration of both the monkey and mouse factors showed coelution with human serum albumin, suggesting a molecular weight of approximately 70,000. The isoelectric points fell within the range of 4.9-5.2 for monkey and 6.4-6.7 for the mouse helper factors. The glycoprotein nature of both factors was suggested by their lability to heat and sensitivity to pronase and neuraminidase. The factors carried a small fragment of the stimulating antigen and showed specific binding to SA but not to keyhole limpet haemocyanin (KLH). Monkey factor bound to rabbit antisera directed against the Fc portion of monkey IgM, but not to the IgG or IgA isotypes. The mouse factor contained determinants coded for by the I-Ak but not I-Jk subregion of the MHC. Both factors were absorbed by an antiserum to helper factor raised in rabbits against a KLH-specific mouse helper factor as immunogen. A corresponding antiserum to suppressor factor failed to adsorb either factor. This emphasizes the specific identities of helper and suppressor factors and suggests an evolutionary relationship between those derived from monkey and mouse leucocytes.


Robust approach to combining multiple markers to improve surrogacy.
Identifying effective and valid surrogate markers to make inference about a treatment effect on long-term outcomes is an important step in improving the efficiency of clinical trials. Replacing a long-term outcome with short-term and/or cheaper surrogate markers can potentially shorten study duration and reduce trial costs. There is sizable statistical literature on methods to quantify the effectiveness of a single surrogate marker. Both parametric and nonparametric approaches have been well developed for different outcome types. However, when there are multiple markers available, methods for combining markers to construct a composite marker with improved surrogacy remain limited. In this paper, building on top of the optimal transformation framework of Wang et al. (2020), we propose a novel calibrated model fusion approach to optimally combine multiple markers to improve surrogacy. Specifically, we obtain two initial estimates of optimal composite scores of the markers based on two sets of models with one set approximating the underlying data distribution and the other directly approximating the optimal transformation function. We then estimate an optimal calibrated combination of the two estimated scores which ensures both validity of the final combined score and optimality with respect to the proportion of treatment effect explained by the final combined score. This approach is unique in that it identifies an optimal combination of the multiple surrogates without strictly relying on parametric assumptions while borrowing modeling strategies to avoid fully nonparametric estimation which is subject to the curse of dimensionality. Our identified optimal transformation can also be used to directly quantify the surrogacy of this identified combined score. Theoretical properties of the proposed estimators are derived, and the finite sample performance of the proposed method is evaluated through simulation studies. We further illustrate the proposed method using data from the Diabetes Prevention Program study.


Genome-wide association and genome partitioning reveal novel genomic regions underlying variation in gastrointestinal nematode burden in a wild bird.
Identifying the genetic architecture underlying complex phenotypes is a notoriously difficult problem that often impedes progress in understanding adaptive eco-evolutionary processes in natural populations. Host-parasite interactions are fundamentally important drivers of evolutionary processes, but a lack of understanding of the genes involved in the host's response to chronic parasite insult makes it particularly difficult to understand the mechanisms of host life history trade-offs and the adaptive dynamics involved. Here, we examine the genetic basis of gastrointestinal nematode (Trichostrongylus tenuis) burden in 695 red grouse (Lagopus lagopus scotica) individuals genotyped at 384 genome-wide SNPs. We first use genome-wide association to identify individual SNPs associated with nematode burden. We then partition genome-wide heritability to identify chromosomes with greater heritability than expected from gene content, due to harbouring a multitude of additive SNPs with individually undetectable effects. We identified five SNPs on five chromosomes that accounted for differences of up to 556 worms per bird, but together explained at best 4.9% of the phenotypic variance. These SNPs were closely linked to genes representing a range of physiological processes including the immune system, protein degradation and energy metabolism. Genome partitioning indicated genome-wide heritability of up to 29% and three chromosomes with excess heritability of up to 4.3% (total 8.9%). These results implicate SNPs and novel genomic regions underlying nematode burden in this system and suggest that this phenotype is somewhere between being based on few large-effect genes (oligogenic) and based on a large number of genes with small individual but large combined effects (polygenic).


The talk of the town: kit manufacturers negotiate the building industry, 1905-1929.
Urban historical scholars have neglected smaller urban centers, including their residential environments and the forces that shaped them. For a time, one of these forces was the mail-order kit home. Kit manufacturers sold houses to families throughout the United States and Canada but enjoyed their greatest success in small towns where detached single-family homes were the norm. They worked to insert themselves into local building industries: They challenged lumber dealers and ignored architects but strove to mollify the contractors on whom they and their customers depended. They attracted considerable attention and met with initial success: Emerging rapidly after 1905, they had hit their stride by 1914 and enjoyed a heyday in the 1920s. They were stricken by, and failed to recover from, the Depression in large part because lumber dealers had learned how to compete with them.


[Perioperative and perinatal morbidity and mortality. Pilot study by a working team of Swiss gynecological hospitals].
The article presents joint annual statistics for 1982 as a perioperative and perinatal morbidity and mortality analysis representing a pilot study by the working team of 41 Swiss gynaecological hospitals. This serves as a model for a meaningful quality control programme. The data of 50,770 patients (including 24,656 births) have been stored. The evaluation programmes which can be read off directly supply for every index word on the patient record the median and quartile ranges of the entire data bank and hence the basis of internal control within the hospital.


Drosophila pachea asymmetric lobes are part of a grasping device and stabilize one-sided mating.
Multiple animal species exhibit morphological asymmetries in male genitalia. In insects, left-right genital asymmetries evolved many times independently and have been proposed to appear in response to changes in mating position. However, little is known about the relationship between mating position and the interaction of male and female genitalia during mating, and functional analyses of asymmetric morphologies in genitalia are virtually non-existent. We investigated the relationship between mating position, asymmetric genital morphology and genital coupling in the fruit fly Drosophila pachea, in which males possess an asymmetric pair of external genital lobes and mate in an unusual right-sided position on top of the female. We examined D. pachea copulation by video recording and by scanning electron microscopy of genital complexes. We observed that the interlocking of male and female genital organs in D. pachea is remarkably different from genital coupling in the well-studied D. melanogaster. In D. pachea, the female oviscapt valves are asymmetrically twisted during copulation. The male's asymmetric lobes tightly grasp the female's abdomen in an asymmetric 'locking' position, with the left and right lobes contacting different female structures. The male anal plates, which grasp the female genitalia in D. melanogaster, do not contact the female in D. pachea. Experimental lobe amputation by micro-surgery and laser-ablation of lobe bristles led to aberrant coupling of genitalia and variable mating positions, in which the male was tilted towards the right side of the female. We describe, for the first time, how the mating position depends on coupling of male and female genitalia in a species with asymmetric genitalia and one-sided mating position. Our results show that D. pachea asymmetric epandrial lobes do not act as a compensatory mechanism for the change from symmetric to one-sided mating position that occurred during evolution of D. pachea's ancestors, but as holding devices with distinct specialized functions on the left and right sides.


Rasch analysis of the Edmonton Symptom Assessment System and research implications.
Reliable and valid assessment of the disease burden across all forms of cancer is critical to the evaluation of treatment effectiveness and patient progress. The Edmonton Symptom Assessment System (esas) is used for routine evaluation of people attending for cancer care. In the present study, we used Rasch analysis to explore the measurement properties of the esas and to determine the effect of using Rasch-proposed interval-level esas scoring compared with traditional scoring when evaluating the effects of an exercise program for cancer survivors. Polytomous Rasch analysis (Andrich's rating-scale model) was applied to data from 26,645 esas questionnaires completed at the Juravinski Cancer Centre. The fit of the esas to the polytomous Rasch model was investigated, including evaluations of differential item functioning for sex, age, and disease group. The research implication was investigated by comparing the results of an observational research study previously analysed using a traditional approach with the results obtained by Rasch-proposed interval-level esas scoring. The Rasch reliability index was 0.73, falling short of the desired 0.80-0.90 level. However, the esas was found to fit the Rasch model, including the criteria for uni-dimensional data. The analysis suggests that the current esas scoring system of 0-10 could be collapsed to a 6-point scale. Use of the Rasch-proposed interval-level scoring yielded results that were different from those calculated using summarized ordinal-level esas scores. Differential item functioning was not found for sex, age, or diagnosis groups. The esas is a moderately reliable uni-dimensional measure of cancer disease burden and can provide interval-level scaling with Rasch-based scoring. Further, our study indicates that, compared with the traditional scoring metric, Rasch-based scoring could result in substantive changes to conclusions.


The Impact of COVID-19 on the Response to Hypoxia.
Louis, Alexandre, Charlotte Pröpper, Yann Savina, Corentin Tanne, Guy Duperrex, Paul Robach, Pascal Zellner, Stéphane Doutreleau, Jean-Michel Boulet, Alain Frey, Fabien Pillard, Cristina Pistea, Mathias Poussel, Thomas Thuet, Jean-Paul Richalet, and François Lecoq-Jammes. The impact of COVID-19 on the response to hypoxia. High Alt Med Biol. 00:000-000, 2023. Introduction: Severe high-altitude illness (SHAI) and coronavirus disease 2019 (COVID-19), while differing in most aspects of pathophysiology, both involve respiratory capacity. We examined the long-term impact of COVID-19 on response to hypoxia in individuals free of symptoms but having tested positive during the pandemic. The need for recommendations for such individuals planning a stay at high altitude are discussed. Methods: This multicenter study recruited participants from the multiSHAI cohort, all of whom had previously undergone a hypoxic exercise test. These participants were classified into two groups depending on whether they had since suffered mild-to-moderate COVID-19 (COVID+) or not (Control) and then asked to retake the test. Primary outcomes were: desaturation induced by hypoxia at exercise (ΔSpE), hypoxic cardiac response at exercise, hypoxic ventilatory response at exercise, and SHAI risk score. Results: A total of 68 participants retook the test, 36 classified in the COVID+ group. Analyses of primary outcomes showed no significant differences between groups. However, the COVID+ group showed significantly increased ventilation (VE) parameters during both hypoxic (p = 0.003) and normoxic exercise (p = 0.007). However, only the VE/oxygen consumption relationship during hypoxic exercise was significantly different. Conclusion: This study demonstrates no negative impact of COVID-19 on response to hypoxia as evaluated by the Richalet test. Clinical Trial Registration: NTC number: NCT05167357.


The associations among GNB3 C825T polymorphism, erectile dysfunction, and related risk factors.
Vascular etiologies are the most common risk factors for erectile dysfunction (ED). Published studies have reported the associations of GNB3 C825T polymorphism with many vascular diseases. However, there are few reports about the association between this gene polymorphism and ED. To investigate the associations among GNB3 C825T polymorphism, ED, and related risk factors in Taiwanese subjects. A total of 155 patients with ED and 81 healthy controls were enrolled. All men had complete clinical histories taken. The 5-item International Index of Erectile Function (IIEF-5) was used to assess erectile conditions. The GNB3 C825T polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism method. Patients with ED were defined as those having an IIEF-5 of <21. Two hundred thirty-six men were enrolled with a mean (standard deviation) age of 59.0 (10.2) years. Diabetes mellitus (DM), hypertension, and age were the three most significant independent risk factors for ED in a multiple logistic regression analysis (P = 0.008, 0.003, and 0.007, respectively). The prevalence of DM, hypertension, and body mass index (BMI) was significantly higher in GNB3 825T allele (CT/TT) carriers (P = 0.023, 0.049, and 0.035, respectively). There was no significant difference of ED prevalence between T and C allele carriers (69.1% vs. 56.2%, P = 0.07). However, the T allele carriers had significantly lower IIEF-5 scores (P = 0.02) associated with an increment of the T allele number (16.4[CC] vs. 14.4[CT] vs. 13.2[TT], P = 0.04). In the present study, DM, hypertension, and BMI had significant associations with GNB3 825T allele carriers. Our results failed to show a significant association of the GNB3 C825T polymorphisms with ED prevalence. However, we cannot exclude that the presence of the T allele might influence the risk for ED severity indirectly through an increased risk for some vascular diseases.


Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.
The ESCRT pathway is evolutionarily conserved across eukaryotes and plays key roles in a variety of membrane remodeling processes. A new Drosophila mutant recovered in our forward genetic screens for synaptic transmission mutants mapped to the vps24 gene encoding a subunit of the ESCRT-III complex. Molecular characterization indicated a loss of VPS24 function, however the mutant is viable and thus loss of VPS24 may be studied in a developed multicellular organism. The mutant exhibits deficits in locomotion and lifespan and, notably, these phenotypes are rescued by neuronal expression of wild-type VPS24. At the cellular level, neuronal and muscle cells exhibit marked expansion of a ubiquitin-positive lysosomal compartment, as well as accumulation of autophagic intermediates, and these phenotypes are rescued cell-autonomously. Moreover, VPS24 expression in glia suppressed the mutant phenotype in muscle, indicating a cell-nonautonomous function for VPS24 in protective intercellular signaling. Ultrastructural analysis of neurons and muscle indicated marked accumulation of the lysosomal compartment in the vps24 mutant. In the neuronal cell body, this included characteristic lysosomal structures associated with an expansive membrane compartment with a striking tubular network morphology. These findings further define the in vivo roles of VPS24 and the ESCRT pathway in lysosome homeostasis and their potential contributions to neurodegenerative diseases characterized by defective ESCRT or lysosome function.


Satellite glial cells in the trigeminal ganglion as a determinant of orofacial neuropathic pain.
Satellite glial cells (SGCs) tightly envelop the perikarya of primary sensory neurons in peripheral ganglion and are identified by their morphology and the presence of proteins not found in ganglion neurons. These SGC-unique proteins include the inwardly rectifying K(+) channel Kir4.1, the connexin-43 (Cx43) subunit of gap junctions, the purinergic receptor P2Y4 and soluble guanylate cyclase. We also present evidence that the small-conductance Ca(2+)-activated K(+) channel SK3 is present only in SGCs and that SGCs divide following nerve injury. All the above proteins are involved, either directly or indirectly, in potassium ion (K(+)) buffering and, thus, can influence the level of neuronal excitability, which, in turn, has been associated with neuropathic pain conditions. We used in vivo RNA interference to reduce the expression of Cx43 (present only in SGCs) in the rat trigeminal ganglion and show that this results in the development of spontaneous pain behavior. The pain behavior is present only when Cx43 is reduced and returns to normal when Cx43 concentrations are restored. This finding shows that perturbation of a single SGC-specific protein is sufficient to induce pain responses and demonstrates the importance of PNS glial cell activity in the pathophysiology of neuropathic pain.


Micellar catalysis-enabled sustainable ppm Au-catalyzed reactions in water at room temperature.
Several ppm level gold-catalyzed reactions enabled by the ligand HandaPhos can be performed at room temperature in aqueous nanoreactors composed of the surfactant Nok. Variously substituted allenes undergo cycloisomerization leading to heterocyclic products in good yields. Likewise, cyclodehydration is also illustrated under similar conditions, as is an intermolecular variant, hydration of terminal alkynes. Recycling of the catalyst and reaction medium is also illustrated. A low E factor associated with limited solvent use and therefore, waste generation, documents the greenness of this process.


The natural order of events: how speakers of different languages represent events nonverbally.
To test whether the language we speak influences our behavior even when we are not speaking, we asked speakers of four languages differing in their predominant word orders (English, Turkish, Spanish, and Chinese) to perform two nonverbal tasks: a communicative task (describing an event by using gesture without speech) and a noncommunicative task (reconstructing an event with pictures). We found that the word orders speakers used in their everyday speech did not influence their nonverbal behavior. Surprisingly, speakers of all four languages used the same order and on both nonverbal tasks. This order, actor-patient-act, is analogous to the subject-object-verb pattern found in many languages of the world and, importantly, in newly developing gestural languages. The findings provide evidence for a natural order that we impose on events when describing and reconstructing them nonverbally and exploit when constructing language anew.


Current Status of Cellulosic and Nanocellulosic Materials for Oil Spill Cleanup.
Recent developments in the application of lignocellulosic materials for oil spill removal are discussed in this review article. The types of lignocellulosic substrate material and their different chemical and physical modification strategies and basic preparation techniques are presented. The morphological features and the related separation mechanisms of the materials are summarized. The material types were classified into 3D-materials such as hydrophobic and oleophobic sponges and aerogels, or 2D-materials such as membranes, fabrics, films, and meshes. It was found that, particularly for 3D-materials, there is a clear correlation between the material properties, mainly porosity and density, and their absorption performance. Furthermore, it was shown that nanocellulosic precursors are not exclusively suitable to achieve competitive porosity and therefore absorption performance, but also bulk cellulose materials. This finding could lead to developments in cost- and energy-efficient production processes of future lignocellulosic oil spillage removal materials.


BRG1 and BRM chromatin-remodeling complexes regulate the hypoxia response by acting as coactivators for a subset of hypoxia-inducible transcription factor target genes.
Chromatin remodeling is an active process, which represses or enables the access of transcription machinery to genes in response to external stimuli, including hypoxia. However, in hypoxia, the specific requirement, as well as the molecular mechanism by which the chromatin-remodeling complexes regulate gene expression, remains unclear. In this study, we report that the Brahma (BRM) and Brahma-related gene 1 (BRG1) ATPase-containing SWI/SNF chromatin-remodeling complexes promote the expression of the hypoxia-inducible transcription factor 1α (HIF1α) and HIF2α genes and also promote hypoxic induction of a subset of HIF1 and HIF2 target genes. We show that BRG1 or BRM knockdown in Hep3B and RCC4T cells reduces hypoxic induction of HIF target genes, while reexpression of BRG1 or BRM in BRG1/BRM-deficient SW13 cells increases HIF target gene activation. Mechanistically, HIF1 and HIF2 increase the hypoxic induction of HIF target genes by recruiting BRG1 complexes to HIF target gene promoters, which promotes nucleosome remodeling of HIF target gene promoters in a BRG1 ATPase-dependent manner. Importantly, we found that the function of BRG1 complexes in hypoxic SW13 and RCC4T cells is dictated by the HIF-mediated hypoxia response and could be opposite from their function in normoxic SW13 and RCC4T cells.


A vision for cancer incidence surveillance in the United States.
A comprehensive framework for cancer surveillance should span the entire lifespan and be capable of providing information on risk, burden, disparity, cost, cancer care, survival, and death. Cancer incidence, the point in the continuum when an individual is diagnosed with cancer, has a strong, well-developed system to produce information about newly diagnosed cancer cases. However, in the future, this system must be enhanced and integrated with other cancer surveillance networks and other systems to provide timely information on the burden of newly diagnosed patients with respect to various cross-cutting population characteristics (e.g., social, economic, race/ethnic, urbanicity, or access to care) to define, monitor, and reduce incidence and various disparities noted among population groups. Collaboration in data collection, standard setting, surveillance activities, research, education and training, data use, and advocacy among all registries and national programs will be important to the continued success of the cancer incidence surveillance system. The cancer registry is an integral part of the infrastructure to reduce the burden of cancer, including the numbers of newly diagnosed cases.


Long-term prognosis after myocardial infarction in men with diabetes.
Men (1306) who survived a first myocardial infarction (MI) were studied. The mean follow-up time was 6.5 yr, and at the end of the follow-up period survival status was known for all patients. By the time of the MI the prevalence of diabetes was 5.6%. Patients with and without diabetes were compared. There were no differences in the estimated primary or secondary risk. The cumulative survival rate 1, 2, and 5 yr after the MI was 82, 78, and 58% among the diabetic subjects compared with 94, 92, and 82% among the nondiabetic subjects (P less than 0.001). The difference remained even after allowance for age and estimated secondary risk in a multivariate regression analysis. There were no differences in mortality rates among patients with type I diabetes compared with type II diabetes, nor among patients treated with diet alone, sulfonylurea, or insulin, but the numbers were small. The cumulative rate of reinfarctions after 1, 2, and 5 yr was 18, 28, and 46% in diabetic subjects and 12, 17, and 27% in nondiabetic subjects (P = 0.004). A history of diabetes was an independent secondary risk factor among male survivors of a first MI with respect to deaths and reinfarctions.


Postdeployment Behavioral Health Screens and Linkage to the Veterans Health Administration for Army Reserve Component Members.
Approximately three to six months after returning from deployment, military service members complete the Post-Deployment Health Reassessment (PDHRA), which includes screens for alcohol misuse, depression, and posttraumatic stress disorder (PTSD). To determine whether Army Reserve Component (RC) members (Army National Guard and Army Reserve) with positive screening scores on the PDHRA receive needed care, the investigators examined the association between positive scores and enrollment and utilization of care ("linkage") in the Veterans Health Administration (VHA), as well as rescreening scores, diagnosis, and behavioral treatment in VHA. Mixed-effects regression models were used to predict linkage to VHA within six months after RC members (N=73,164) completed the PDHRA, with alcohol misuse, depression, and PTSD screen scores as key independent variables. Regression models were stratified by gender and National Guard versus Reserve status. Among those who linked to VHA (N=25,168), screening scores and subsequent diagnosis and treatment in VHA were also examined. Army RC members with positive PTSD and depression screening scores were more likely than those with negative screens to link to VHA, and most (54%-84%) received VHA treatment once diagnosed. Positive screens for alcohol misuse were associated with linkage to VHA for men but not for women, and treatment rates for alcohol use disorders were relatively low (0%-25%) for both men and women diagnosed as having an alcohol use disorder. The finding that Army RC members with greater indications of behavioral health problems linked to VHA is encouraging. However, more outreach and treatment engagement strategies could be directed to those with alcohol use disorder, particularly women.


The relationship between the quantity and type of macronutrients in diet and frailty in older outpatients.
The aim of this study is to determine the relationship between the quantity and type of macronutrients in the diet and frailty. A total of 106 patients were included in the study. Exclusion criteria included patients with pacemakers, edema, advanced dementia, acute infectious and inflammatory disease, and those using oral or enteral nutritional supplements. Frailty was assessed using the Fried Frailty Phenotype. Three-day dietary records were taken, 2 days on weekdays and 1 day on weekends. The Nutrition Information System (BeBis) 8.2 full version program was used to analyze the average energy and nutrient values of the consumed foods. Insufficient protein and energy intake were defined as taking less than 1 or 1.2 g/kg/day for protein and less than 30 kcal/kg/day for energy, respectively. The mean age of the participants was 74.3 (± 6.75), and 68.9% (n = 73) of them were women. 26.4% (n = 28) of the patients were classified as frail. There was no difference between the energy consumption of < 30 kcal/kg/day in the frail and non-frail groups. Protein consumption of less than 1.2 g/kg/day had a significant relationship with frailty. There was no significant difference between the consumed plant/animal protein ratio and frailty, but plant protein, polyunsaturated fatty acids, and fiber intake were significantly lower in frail patients. Decreased consumption of polyunsaturated fatty acids (PUFAs), advanced age, and increased number of medications were identified as independently associated factors with frailty. This study found that frailty was associated with less than 1.2 g/kg/day protein consumption, lower fiber, and PUFA consumption.


Protein profile typing--a new method of typing Morganella morganii strains.
A new, simple and stable method for typing Morganella morganii strains is described. The 150 strains examined, principally from faeces, contained haemolytic and non-haemolytic representatives of diverse O serogroup, bacteriocin type and biotype. Among the biotypes were some trehalose-fermenting, tetracycline-resistant strains and some non-motile, tetracycline-sensitive, glycerol fermenters. After analysis of cell lysates by sodium dodecyl sulphate-discontinuous polyacrylamide gel electrophoresis, strains could be differentiated into 21 types on the basis of outer membrane proteins (OMP) of 35-40 Kda. The OMP profile was not altered by culture on various common media and was unrelated to either O antigen or morganocin p-type. The finest strain recognition in M. morganii can be achieved by application of all three distinct typing methods.


Solution-processed indium oxide electron transporting layers for high-performance and photo-stable perovskite and organic solar cells.
Interface engineering is considered the key to improving the device performance and stability of solar cells. In particular, TiO2 nanostructures, when used as electron transporting layers (ETLs) in metal halide perovskite solar cells (PSCs), led to excellent power conversion efficiencies (PCEs) of over 20%. They effectively transferred charge carriers from the perovskite and suppressed charge recombination at the interfaces. However, the photocatalytic effect of TiO2 on the perovskite can significantly degrade the device performance under ultraviolet illumination. Therefore, other classes of n-type metal oxides with a wide band gap should be developed to improve their photo-stability. Herein, we demonstrate the development of In2O3 thin films by a solution process and their application as ETLs in PSCs and organic solar cells (OSCs). Pin hole-free In2O3 ETLs obtained by the thermal decomposition of an In precursor thin film exhibit high conductivity (2.49 × 10-4 S cm-1) and low surface roughness (7.33 nm). This leads to impressive PCEs of 14.63% and 3.03% for the PSC and the inverted OSC, respectively. Furthermore, the In2O3-PSC shows better photo-stability than the TiO2-PSC by virtue of the wider band gap of In2O3, which leads to a PCE retention of 74% and 46%, relative to the initial PCE values of the PSC and the inverted OSC, respectively.


Antiplasmodial and Antileishmanial Activities of a New Limonoid and Other Constituents from the Stem Bark of Khaya senegalensis.
Plasmodium falciparum and Leishmania sp. resistance to antiparasitic drugs has become a major concern in malaria and leishmaniasis control. These diseases are public health problems with significant socioeconomic impacts, and mostly affect disadvantaged populations living in remote tropical areas. This challenge emphasizes the need to search for new chemical scaffolds that preferably possess novel modes of action to contribute to antimalarial and antileishmanial research programs. This study aimed to investigate the antimalarial and antileishmanial properties of a methanol extract (KS-MeOH) of the stem bark of the Cameroonian medicinal plant Khaya senegalensis and its isolated compounds. The purification of KS-MeOH led to the isolation of a new ordered limonoid derivative, 21β-hydroxybourjotinolone A (1a), together with 15 known compounds (1bc-14) using a repeated column chromatography. Compound 1a was obtained in an epimeric mixture of 21α-melianodiol (1b) and 21β-melianodiol (1c). Structural characterization of the isolated compounds was achieved with HRMS, and 1D- and 2D-NMR analyses. The extracts and compounds were screened using pre-established in vitro methods against synchronized ring stage cultures of the multidrug-resistant Dd2 and chloroquine-sensitive/sulfadoxine-resistant 3D7 strains of Plasmodium falciparum and the promastigote form of Leishmania donovani (1S(MHOM/SD/62/1S). In addition, the samples were tested for cytotoxicity against RAW 264.7 macrophages. Positive controls consisted of artemisinin and chloroquine for P. falciparum, amphotericin B for L. donovani, and podophyllotoxin for cytotoxicity against RAW 264.7 cells. The extract and fractions exhibited moderate to potent antileishmanial activity with 50% inhibitory concentrations (IC50) ranging from 5.99 ± 0.77 to 2.68 ± 0.42 μg/mL, while compounds displayed IC50 values ranging from 81.73 ± 0.12 to 6.43 ± 0.06 μg/mL. They were weakly active against the chloroquine-sensitive/sulfadoxine-resistant Pf3D7 strain but highly potent toward the multidrug-resistant PfDd2 (extracts, IC50 2.50 ± 0.12 to 4.78 ± 0.36 μg/mL; compounds IC50 2.93 ± 0.02 to 50.97 ± 0.37 μg/mL) with selectivity indices greater than 10 (SIDd2 > 10) for the extract and fractions and most of the derived compounds. Of note, the limonoid mixture [21β-hydroxylbourjotinolone A (1a) + 21α-melianodiol (1b) + 21β-melianodiol (1c)] exhibited moderate activity against P. falciparum and L. donovani. This novel antiplasmodial and antileishmanial chemical scaffold qualifies as a promising starting point for further medicinal chemistry-driven development of a dually active agent against two major infectious diseases affecting humans in Africa.


Human fibronectin contains distinct adhesion- and motility-promoting domains for metastatic melanoma cells.
The active migration of tumor cells through extracellular matrices has been proposed to play a role in certain aspects of metastasis. Metastatic tumor cells migrate in vitro in response to substratum-bound adhesive glycoproteins such as fibronectin. The present studies use affinity-purified proteolytic fragments of fibronectin to determine the nature of adhesion- and/or motility-promoting domains within the protein. Two distinct fragments were identified with cell adhesion-promoting activities. By a number of criteria, the adhesive activity promoted by these two fragments was distinct. One fragment, a 75-kD tryptic fragment purified by monoclonal antibody chromatography, promoted the adhesion, spreading, and haptotactic motility of melanoma cells. Experiments using a synthetic cell attachment peptide in solution indicated that at least part of the attachment activity exhibited by the 75-kD fragment is mediated by the sequence arg-gly-asp-ser. It was not possible to demonstrate migration-stimulating activity using a small (11.5 kD) peptic fragment containing this sequence (Pierschbacher, M.D., E. G. Hayman, and E. Ruoslahti, 1981, Cell, 26:259-267) suggesting that another cell-binding activity within the 75 kD fragment distinct from arg-gly-asp-ser might be required for motility. The second fragment that stimulated melanoma adhesion was a 33-kD tryptic/catheptic carboxyl-terminal heparin-binding fragment, which is localized to the A chain of fibronectin. This fragment promotes adhesion and spreading but not the motility of these cells. Melanoma adhesion to this heparin-binding fragment was sensitive to the effects of cycloheximide, which contrasted adhesion to the haptotaxis-promoting fragment. Importantly, these studies illustrate that haptotaxis in response to fibronectin is not due to simple adhesion gradients of this protein. The results are discussed in light of a model for multiple distinct cell surface constituents mediating cell adhesion and motility on fibronectin.


Recognition of protein structure: determining the relative energetic contributions of beta-strands, alpha-helices and loops.
We examine the role of residues of secondary structure in recognition of the native structure of proteins. The accuracy of recognition was estimated by computing the Z-score values for fragments of protein chains in threading tests. By testing different combinations of secondary structure fragments of 240 non-homologous proteins we show that the overwhelming majority of proteins can be successfully recognized by the energies of interaction between residues of secondary structure. We also found that beta-structures contribute more significantly to fold recognition than alpha-helices or loops. To validate the Z-score calculations in measuring the accuracy of recognition we evaluated the deviation of the energy distribution from the normal law. The normal law satisfactory approximates the shape of the energy distribution for the majority of proteins and chain fragments; however, deviations are often observed for short fragments and for fragments with relatively high Z-score values. The results of the study justify recognition of remote homologs by threading methods based on a backbone of secondary structure rather than of a whole chain because loops of homologs differ more significantly than strands and helices, and the contribution of loops in structure recognition is relatively small.


Immunologic approaches to the study of cyclic nucleotide phosphodiesterases.
The cyclic nucleotide PDE activity in crude tissue extracts is due to the composite activity of several distinct isozymes, each having different kinetic and functional characteristics. Most of these isozymes will hydrolyze the same substrates, that is, cyclic AMP and cyclic GMP. Therefore, it is difficult to conclusively identify and quantitate any given isozyme in crude systems. Since the cyclic nucleotide PDE are present in low concentrations in cells, it is also difficult to isolate these proteins without having specific solid phase affinity probes. This chapter described the use of monoclonal antibodies as probes to specifically identify, measure, characterize, and isolate the PDE isozymes in impure preparations. Monoclonal antibodies have been produced to the cyclic-GMP-stimulated PDE, ROS PDE, and a calcium-calmodulin-dependent PDE of bovine tissues. A polyclonal antiserum has also been produced to the cyclic-GMP-stimulated PDE. Sensitive immunoprecipitation assays for the measurement of PDE activity and cyclic GMP binding have been developed that have allowed the detection of femtomole amounts of each specific PDE isozyme. None of the antibodies appear to recognize antigenic determinants on other isozymes, suggesting that the PDE are antigenically distinct and therefore different proteins. Most of the monoclonal antibodies do not appear to affect kinetic parameters of the enzymes and have been used to specifically identify, measure, and characterize each isozyme in crude systems. A monoclonal antibody to the calcium-calmodulin-dependent PDE requires calcium and calmodulin for high-affinity binding to the enzyme. This apparent conformational requirement has been used to purify the isozyme from both bovine brain and heart. These two tissues contain enzymes with differing subunit MW on SDS-polyacrylamide gel electrophoresis, although no other biochemical differences were observed.


Formulation, development and characterization of mucoadhesive film for treatment of vaginal candidiasis.
The objective of the present investigation was formulation, optimization and characterization of mucoadhesive film of clotrimazole (CT) which is patient-convenient and provides an effective alternative for the treatment of vaginal candidiasis. CT is an antimycotic drug applied locally for the treatment of vaginal candidiasis. Mucoadhesive vaginal films were prepared by solvent casting technique using hydroxyl propylcellulose and sodium alginate as polymers. Propylene glycol and polyethylene glycol-400 were evaluated as plasticizers. The mucoadhesive vaginal films were evaluated for percentage elongation, tensile strength, folding endurance, drug content, in vitro disintegration time, in vitro dissolution study, swelling index, bioadhesive strength, and diffusion study. Among various permeation enhancers used, isopropyl myristate was found to be suitable. To evaluate the role of the concentration of permeation enhancer and concentration of polymers in the optimization of mucoadhesive vaginal film, 3(2) full factorial design was employed. Optimized batch showed in vitro disintegration time, 18 min; drug content, 99.83%; and tensile strength, 502.1 g/mm(2). In vitro diffusion study showed that 77% drug diffusion occurred in 6 h. This batch was further evaluated by scanning electron microscopy indicating uniformity of the film. In vitro Lactobacillus inhibition and in vitro antifungal activity of optimized batch showed an inhibitory effect against Candida albicans and no effect on Lactobacillus, which is a normal component of vaginal flora. Mucoadhesive vaginal film of CT is an effective dosage form for the treatment of vaginal candidiasis.


Regulatory T-cell therapy approaches.
Regulatory T cells (Tregs) have enormous therapeutic potential to treat a variety of immunopathologies characterized by aberrant immune activation. Adoptive transfer of ex vivo expanded autologous Tregs continues to progress through mid- to late-phase clinical trials in several disease spaces and has generated promising preliminary safety and efficacy signals to date. However, the practicalities of this strategy outside of the clinical trial setting remain challenging. Here, we review the current landscape of regulatory T-cell therapy, considering emergent approaches and technologies presenting novel ways to engage Tregs, and reflect on the progress necessary to deliver their therapeutic potential to patients.


Global review of delay time in seeking medical care for chest pain: An integrative literature review.
The aim of this review is to summarise research from a range of countries describing the differences in time taken to seek medical care for chest pain and factors which contribute to delay times. An integrative literature review was undertaken using the Medline, CINAHL and Scopus databases for publications between 1994 and 2014. Articles dealing with delay time, and the factors associated with delay time, were extracted from the literature. The search yielded 395 articles of which 205 full-text articles were assessed for eligibility. Finally, twenty-three articles met the inclusion criteria for the review. It was found that time to seeking treatment (delay times) varied between countries, ranging from 1.6 to 12.9h, with a mean of 3.4h. The mean delay times reported in all the selected studies were greater than the recommended time-frame for seeking treatment. As well, time to decision to seek treatment (decision time) was reported as a major component of delay time. Meanwhile, the utilisation rates of ambulance services ranged from 3.1% in Brazil to 61.0% in Australia. A majority of the reviewed studies reported on the factors associated with longer delay times, including old age, female gender, ethnicity, low education level, history of chronic disease, lack of knowledge of the symptoms, and underutilisation of ambulance services. Only three studies included a sub-analysis by ethnicity, reporting that ethnic groups had longer delay times than Caucasians. Variability in delay times occurred across countries and within continents. The mean time taken to seek care for chest pain in the countries reviewed did not meet the recommended times according to international guidelines. Demographic and social factors, as well as cognitive and emotional factors, influenced delay times. Further research on these influencing factors is recommended, including the impact of ethnicity on patient's care-seeking behaviours for chest pain.


Risk of gastrointestinal bleeding with direct oral anticoagulants: a systematic review and network meta-analysis.
Direct oral anticoagulants are increasingly used for a wide range of indications. However, data are conflicting about the risk of major gastrointestinal bleeding with these drugs. We compared the risk of gastrointestinal bleeding with direct oral anticoagulants, warfarin, and low-molecular-weight heparin. For this systematic review and meta-analysis, we searched MEDLINE and Embase from database inception to April 1, 2016, for prospective and retrospective studies that reported the risk of gastrointestinal bleeding with use of a direct oral anticoagulant compared with warfarin or low-molecular-weight heparin for all indications. We also searched the Cochrane Library for systematic reviews and assessment evaluations, the National Health Service (UK) Economic Evaluation Database, and ISI Web of Science for conference abstracts and proceedings (up to April 1, 2016). The primary outcome was the incidence of major gastrointestinal bleeding, with all gastrointestinal bleeding as a secondary outcome. We did a Bayesian network meta-analysis to produce incidence rate ratios (IRRs) with 95% credible intervals (CrIs). We identified 38 eligible articles, of which 31 were included in the primary analysis, including 287 692 patients exposed to 230 090 years of anticoagulant drugs. The risk of major gastrointestinal bleeding with direct oral anticoagulants did not differ from that with warfarin or low-molecular-weight heparin (factor Xa vs warfarin IRR 0·78 [95% CrI 0·47-1·08]; warfarin vs dabigatran 0·88 [0·59-1·36]; factor Xa vs low-molecular-weight heparin 1·02 [0·42-2·70]; and low-molecular-weight heparin vs dabigatran 0·67 [0·20-1·82]). In the secondary analysis, factor Xa inhibitors were associated with a reduced risk of all severities of gastrointestinal bleeding compared with warfarin (0·25 [0.07-0.76]) or dabigatran (0.24 [0.07-0.77]). Our findings show no increase in risk of major gastrointestinal bleeding with direct oral anticoagulants compared with warfarin or low-molecular-weight heparin. These findings support the continued use of direct oral anticoagulants. Leeds Teaching Hospitals Charitable Foundation.


Social inequality in perceived oral health among adults in Australia.
To establish population estimates of self-assessed tooth loss and subjective oral health and describe the social distribution of these measures among dentate adults in Australia. Self-report data were obtained from a nationally representative sample of 3,678 adults aged 18-91 years who participated in the 1999 National Dental Telephone Interview Survey and completed a subsequent mail survey. Oral health was evaluated using (1) self-assessed tooth loss, (2) the 14-item Oral Health Impact Profile, and (3) a global six-point rating of oral health. While the absolute difference in tooth loss across household income levels increased at each successive age group (18-44 years, 45-64 years, 65+ years) from 0.7 teeth to 6.1 teeth, the magnitude of the difference was approximately twofold at each age group. For subjective oral health measures, the magnitude of difference across income groups was most pronounced in the 18-44 years age group. In multivariate analysis, low household income, blue-collar occupation, and high residential area disadvantage were positively associated with social impact from oral conditions and pathological tooth loss. Speaking other than English at home (relative to English), low household income (relative to high income), and vocational relative to tertiary education were each associated with more than twice the odds of poor self-rated oral health. Significant social differentials in perceived oral health exist among dentate adults. Inequalities span the socio-economic hierarchy. In addition to improving overall levels of oral health in the adult community, goals and targets should aim to reduce social inequalities in the distribution of outcomes.


Comparison of the maternal and neonatal effects of halothane, enflurane, and isoflurane for cesarean delivery.
The maternal and neonatal effects of 50% O2-50% N2O alone and 50% O2-50% N2O combined with 0.5% halothane, 1.0% enflurane, or 0.75% isoflurane were studied in 42 healthy parturients undergoing general anesthesia for elective primary or repeat cesarean delivery at term. All patients received thiopental and succinylcholine for induction and were intubated and ventilated with a tidal volume of 10 ml/kg at a rate of 10 breaths/min. Two of 12 (17%) patients given O2-N2O alone had recall; none who received a potent inhalation agent had any recall. Blood loss was similar in all four groups. There were no significant differences between groups in induction-to-delivery and uterine incision-to-delivery intervals, the frequency of Apgar scores less than 7 at 1 and 5 min, maternal and fetal blood-gas tensions, acid-base balance, lactate values, and early neonatal neurobehavioral scores at 2-4 h. It is concluded that analgesic concentrations of halothane, enflurane, and isoflurane can be safely added to 50% O2-50% N2O to prevent maternal awareness during general anesthesia for cesarean delivery while maintaining normal maternal and neonatal conditions.


Human pancreatic icosapeptide: isolation, sequence, and immunocytochemical localization of the COOH-terminal fragment of the pancreatic polypeptide precursor.
In dogs, the COOH-terminal part of the pancreatic polypeptide precursor gives rise to a stable icosapeptide product against which an antiserum has been raised. By immunohistochemistry, icosapeptide immunoreactivity was localized in human pancrease exclusively to cells that also stored pancreatic polypeptide. Analytical peptide chemistry demonstrated that a peptide corresponding to the canine icosapeptide could be extracted from the pancreatic polypeptide-rich duodenal part of the human pancreas. The human pancreatic icosapeptide was isolated by acid ethanol extraction, gel filtration, anion-exchange chromatography, and reverse-phase high-performance liquid chromatography. The COOH-terminal sequence of the human icosapeptide is very similar to that of the canine icosapeptide, whereas none of the first nine amino acid residues are identical. When the primary structure of peptides from three different species are compared, it is apparent that the pancreatic polypeptide part of the common precursor is a well-conserved sequence as compared to the icosapeptide part, although 8 out of 11 residues in the COOH-terminal sequence of the icosapeptide are identical in all three species.


P-cresol Alters Brain Dopamine Metabolism and Exacerbates Autism-Like Behaviors in the BTBR Mouse.
Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction/communication, stereotypic behaviors, restricted interests, and abnormal sensory-processing. Several studies have reported significantly elevated urinary and foecal levels of p-cresol in ASD children, an aromatic compound either of environmental origin or produced by specific gut bacterial strains. Methods: Since p-cresol is a known uremic toxin, able to negatively affect multiple brain functions, the present study was undertaken to assess the effects of a single acute injection of low- or high-dose (1 or 10 mg/kg i.v. respectively) of p-cresol in behavioral and neurochemical phenotypes of BTBR mice, a reliable animal model of human ASD. Results: P-cresol significantly increased anxiety-like behaviors and hyperactivity in the open field, in addition to producing stereotypic behaviors and loss of social preference in BTBR mice. Tissue levels of monoaminergic neurotransmitters and their metabolites unveiled significantly activated dopamine turnover in amygdala as well as in dorsal and ventral striatum after p-cresol administration; no effect was recorded in medial-prefrontal cortex and hippocampus. Conclusion: Our study supports a gene x environment interaction model, whereby p-cresol, acting upon a susceptible genetic background, can acutely induce autism-like behaviors and produce abnormal dopamine metabolism in the reward circuitry.


Reactive Hyperemia Index Associated With Atherosclerotic Cardiovascular Disease Under Treatment for Lifestyle Diseases.
Endothelial dysfunction is an early phase of atherosclerosis and causes atherosclerotic cardiovascular disease (ASCVD), but the cutoff reactive hyperemia index (RHI) for identifying ASCVD patients under treatment for lifestyle diseases is unknown. Patients who visited Cardiology Section, Izumi General Medical Center, Kagoshima, Japan and were measured RHI using Endo-PAT 2000 during May 2014 and March 2016 were enrolled. We divided them into ASCVD and non-ASCVD groups and investigated the association with RHI between the groups. ASCVD group included 195 patients and non-ASCVD group included 288 patients. Age, body mass index and the rate of male, hypertension, diabetes, dyslipidemia and chronic kidney disease in the ASCVD group were significantly higher than those in non-ASCVD group. RHI in the ASCVD group (1.65 (1.40 - 1.92)) was significantly lower than that in the non-ASCVD group (1.73 (1.45 - 2.24)) (P < 0.05). In multi-regression analysis, RHI (odds ratio: 0.67, 95% confidence interval: 0.45 - 0.99, P = 0.04) was independently associated with ASCVD after adjusted by age, sex, body mass index, smoking, hypertension, diabetes, dyslipidemia and chronic kidney disease. The cutoff RHI value between the groups was 1.80. RHI was significantly associated with ASCVD under treatment for lifestyle diseases and the cutoff value was 1.80.


Natural Type II Collagen Hydrogel, Fibrin Sealant, and Adipose-Derived Stem Cells as a Promising Combination for Articular Cartilage Repair.
Objective Articular cartilage is an avascular tissue with limited ability of self-regeneration and the current clinical treatments have restricted capacity to restore damages induced by trauma or diseases. Therefore, new techniques are being tested for cartilage repair, using scaffolds and/or stem cells. Although type II collagen hydrogel, fibrin sealant, and adipose-derived stem cells (ASCs) represent suitable alternatives for cartilage formation, their combination has not yet been investigated in vivo for focal articular cartilage defects. We performed a simple experimental procedure using the combination of these 3 compounds on cartilage lesions of rabbit knees. Design The hydrogel was developed in house and was first tested in vitro for chondrogenic differentiation. Next, implants were performed in chondral defects with or without ASCs and the degree of regeneration was macroscopically and microscopically evaluated. Results Production of proteoglycans and the increased expression of collagen type II (COL2α1), aggrecan (ACAN), and sex-determining region Y-box 9 (SOX9) confirmed the chondrogenic character of ASCs in the hydrogel in vitro. Importantly, the addition of ASC induced a higher overall repair of the chondral lesions and a better cellular organization and collagen fiber alignment compared with the same treatment without ASCs. This regenerating tissue also presented the expression of cartilage glycosaminoglycan and type II collagen. Conclusions Our results indicate that the combination of the 3 compounds is effective for articular cartilage repair and may be of future clinical interest.


Substrate-specificities of acid and alkaline ceramidases in fibroblasts from patients with Farber disease and controls.
The specific activity of acid ceramidase (N-acylsphingosine deacylase, EC 220.127.116.11) was measured at pH4.5 in normal fibroblasts and in fibroblasts from patients with Farber disease and obligate heterozygotes. Greater activity was found when the synthetically made ceramide substrates contained shorter-chain fatty acids or higher content of double bonds. Acid ceramidase activities towards N-lauroyl- (C(12:0)), N-myristoyl- (C(14:0)) and N-palmitoyl- (C(16:0)) sphingosine (C(18:1)) were respectively about 38, 26 and 6 times higher than the activity towards the N-stearoyl (C(18:0)) substrate. The activity towards N-linolenoylsphingosine (C(18:3)/C(18:1)), N-linoleoylsphingosine (C(18:2)/C(18:1)) and N-oleoylsphingosine (C(18:1)/C(18:1)) were respectively about 5, 4 and 3 times higher than the activity towards N-stearoylsphingosine (C(18:0)/C(18:1)). The activity towards N-stearoyldihydrosphingosine (C(18:0)/C(18:0)) was about 40% of that towards N-stearoylsphingosine. Fibroblast alkaline ceramidase possessed significant activity only towards ceramides of unsaturated fatty acids, with a pH optimum of about 9.0. Deficiency of acid ceramidase activity in fibroblasts from patients with Farber disease and intermediate activities in obligate heterozygotes were demonstrated with all ceramides examined except for N-hexanoylsphingosine (C(6:0)/C(18:1)), whereas alkaline ceramidase activity was unaffected. Comparative kinetic studies of acid ceramidase activity with N-lauroylsphingosine and N-oleoylsphingosine demonstrated about 5 (2-12)-fold and 7 (4-17)-fold higher K(m) values in fibroblasts from patients with Farber disease as compared with normal controls. N-Lauroylsphingosine, towards which acid ceramidase activity in control fibroblasts was about 10 times higher than that towards N-oleoylsphingosine, may serve as a better substrate for enzymic diagnosis of Farber disease as well as for further characterization of the catalytically defective acid ceramidase.


The brain response to personally familiar faces in autism: findings of fusiform activity and beyond.
Past functional MRI (FMRI) studies of autism have reported reduced activation in response to the faces of strangers primarily in the 'fusiform face area' (FFA). An alternative and potentially stronger test of FFA function in autism is one that attempts to affect levels of FFA activity using factors believed to modulate function in this brain region, such as face familiarity and the perception of face identity. The current study presented personally meaningful faces, such as mother and co-worker, as well as stranger faces in a rapid event-related FMRI design. Seven autistic and nine normal control adults participated and pressed a button in response to all female faces. A deconvolution analysis revealed significant FFA activity in response to familiar and stranger faces in both autism and normal control groups. Individuals with autism also showed greater fusiform activity in response to familiar faces than stranger faces, as well as the prototypical right hemisphere dominance in response to both types of faces. Normal subjects showed additional activation to familiar faces in the posterior cingulate, amygdala and medial frontal lobes, including the anterior cingulate. Subjects with autism showed a similar, but more limited, network in response to familiar faces. This network included the amygdala and implies that this structure, involved in multiple socio-emotional functions, can be responsive in autism in the presence of stimuli that represent high reward value, such as mother's face. Furthermore, the presence of a distinct network to process familiar faces in autism, one that included limbic structures and was not found in response to the faces of strangers, suggests socio-emotional processing in autism. A potentially noteworthy trend, however, was evidence for a reduction in medial frontal lobe function in the autism group. The main finding of FFA activity in autism stands in contrast to most past FMRI studies of face processing in this disorder. This positive result may reflect the use of personally significant faces that enhanced attention and motivation in the autistic participants. Furthermore, given the proposed role of the FFA in establishing person identity, the use of almost a dozen different personally familiar faces for each participant (totalling 32 non-repeating faces) may have additionally maximized FFA involvement. Therefore, dysfunction in the FFA found in other studies of autism may reflect defects in systems that modulate the FFA, rather than the FFA itself.


Effective bandwidth of terahertz antiresonant reflecting pipe waveguide.
We numerically investigate the transmission of the antiresonant-reflection-based terahertz (THz) pipe waveguide in which the cladding layer is very thin or the cladding index is close to one. It is found that robustness of the waveguide confinement is maintained when the cladding thickness is small, while the guiding ability deteriorates when the cladding index approaches to one. Hence, to increase the effective bandwidth of the pipe waveguide, reducing the cladding thickness is more desirable. Moreover, we also examine the effective bandwidth under the condition that the pipe waveguide is subject to a fixed ratio of core diameter to cladding thickness. Numerical result indicates that, as the ratio increases, the effective bandwidth increases as well.