Preferences for Mobile-Supported e-Cigarette Cessation Interventions Among Young Adults: Qualitative Descriptive Study.
Despite the steady rise in electronic cigarette (e-cigarette) uptake among young adults, increasingly more young people want to quit. Given the popularity of smartphones among young adults, mobile-based e-cigarette cessation interventions hold significant promise. Smartphone apps are particularly promising due to their varied and complex capabilities to engage end users. However, evidence around young adults' preferences and expectations from an e-cigarette cessation smartphone app remains unexplored. The purpose of this study was to take an initial step toward understanding young adults' preferences and perceptions on app-based e-cigarette cessation interventions. Using a qualitative descriptive approach, we interviewed 12 young adults who used e-cigarettes and wanted to quit. We inductively derived themes using the framework analysis approach and NVivo 12 qualitative data analysis software. All participants agreed that a smartphone app for supporting cessation was desirable. In addition, we found 4 key themes related to their preferences for app components: (1) flexible personalization (being able to enter and modify goals); (2) e-cigarette behavior tracking (progress and benefits of quitting); (3) safely managed social support (moderated and anonymous); and (4) positively framed notifications (encouraging and motivational messages). Some gender-based differences indicate that women were more likely to use e-cigarettes to cope with stress, preferred more aesthetic tailoring in the app, and were less likely to quit cold turkey compared with men. The findings provide direction for the development and testing of app-based e-cigarette cessation interventions for young adults.


Effects of methylprednisolone on bone mineral density and microarchitecture of trabecular bones in rats with administration time and assessed by micro-computed tomography.
Little research exists on the dynamic effects of glucocorticoids on bone mineral density (BMD) and microarchitecture of trabecular bones of rats assessed by micro-computed tomography (micro-CT). To investigate time-related changes in the BMD and microarchitecture of trabeculae in rats exposed to glucocorticoid. Female Sprague-Dawley rats were recruited into a baseline group, glucocorticoid-treated groups, or control groups. Glucocorticoid-treated rats were given daily subcutaneous injections of methylprednisolone at a dosage of 3.5 mg/kg for 1 or 9 weeks. A high-resolution micro-CT was used to identify the densitometric and microarchitectural properties of trabeculae in both the proximal metaphysis of tibiae and the sixth lumbar vertebrae (L6). Compared with baseline rats, volumetric BMD, tissue BMD, bone volume fraction, trabecular number, and degree of anisotropy of trabeculae from tibiae or L6 increased in control rats and glucocorticoid-treated rats with time; however, changes in the latter group were smaller. Compared with control rats at each time point, a decrease occurred in volumetric BMD, tissue BMD, bone volume fraction, trabecular number, degree of anisotropy, and trabecular connectivity density in trabecular bones from tibiae or L6 in glucocorticoid-treated rats. The decrease was greater in week 9 compared to week 1. Contrarily, an increase was noted in trabecular thickness, trabecular separation, and structure model index in glucocorticoid-treated rats. A time-related analysis within glucocorticoid-treated groups in both skeletal regions showed a decline in bone volume fraction, trabecular connectivity density, trabecular number, and degree of anisotropy with time, but trabecular thickness and trabecular separation were elevated. Methylprednisolone can inhibit bone mineralization and bone mass gain with growth in rats. It can also deteriorate microarchitecture of trabeculae in a time-dependent or an accumulative dose-dependent manner. Further, the remaining trabeculae appear to thicken in order to adapt to altered stress.


[Identification of a protein with properties of tenascin in the matrix of embryonal cartilage tissue and in a culture of human embryonal fibroblasts].
A protein with properties of tenascine has been discovered in extracellular matrix of human embryonic cartilage tissue. Its Mr, as determined by electrophoresis in PAAG with SDS, is 205 and 195 kDa. Immunoblotting with monoclonal antibodies raised against tenascine, revealed 2 precipitation bands, which permitted to identify the discovered protein as tenascine. This is the first report of detection of tenascine in rib cartilage matrix of human embryos. A protein identified as tenascine, has been also detected in a culture of human embryonic fibroblasts.


Emerging drugs for the management of cancer treatment induced bone loss.
We focus our attention on data on the efficacy of currently available and emerging drugs for the management of cancer treatment induced bone loss (CTIBL) found in a PubMed research from 1997 till today. One of the most common and severe safety issues of the antihormonal therapy in both sexes is the CTIBL and the related fragility fractures. In postmenopausal women with estrogenic receptor positive breast cancer, the third-generation aromatase inhibitors (AIs) are the standard therapy. Observational retrospective studies have found that AIs treated patients had a high rate of bone loss and fracture risk (RR 1.3). Also in men with prostate cancer receiving androgen deprivation therapy, the increase in bone turnover and the consequent bone loss are very rapid and sustained significantly increasing the fracture risk. The aim of our review is to provide the current evidences for the management of bone loss and fracture risk in this subpopulation. The very high rate of bone loss and the high incidence of fractures indicate that cancer patients at risk of CTIBL need to be carefully monitored and stratified for fracture risk. Although there is a strong evidence of efficacy in prevention of bone loss and reduction of fracture risk for many drugs approved for postmenopausal osteoporosis (PMO) and male osteoporosis, for CTIBL there are actually no drugs approved for this indication.


Biocompatible smart micro/nanorobots for active gastrointestinal tract drug delivery.
Oral delivery is the most commonly used route of drug administration owing to good patient compliance. However, the gastrointestinal (GI) tract contains multiple physiological barriers that limit the absorption efficiency of conventional passive delivery systems resulting in a low drug concentration reaching the diseased sites. Micro/nanorobots can convert energy to self-propulsive force, providing a novel platform to actively overcome GI tract barriers for noninvasive drug delivery and treatment. In this review, we first describe the microenvironments and barriers in the different compartments of the GI tract. Afterward, the applications of micro/nanorobots to overcome GI tract barriers for active drug delivery are highlighted and discussed. Finally, we summarize and discuss the challenges and future prospects of micro/nanorobots for further clinical applications. Micro/nanorobots with the ability to autonomously propel themselves and to load, transport, and release payloads on demand are ideal carriers for active oral drug delivery. Although there are many challenges to be addressed, micro/nanorobots have great potential to introduce a new era of drug delivery for precision therapy.


The effects of lipid-regulating therapy on haemostatic parameters.
There is growing evidence that the components of the haemostatic system play a significant role in the development and progression of atherosclerosis and its complications. Lipid-lowering interventions have been associated with a significant reduction of morbidity and mortality. However, the improvement in cardiovascular risk seen in several clinical trials is incompletely explained by cholesterol reduction. Therefore, the benefit from lipid lowering drugs may involve non-lipid mechanisms. These include beneficial effects on the arterial wall, improved endothelial function and a favourable influence on blood rheology and thrombogenesis. In this review, we consider the influence of lipid-lowering interventions on rheological and haemostatic parameters as well as the potential clinical relevance of these effects.


Insulin-regulated aminopeptidase inhibitors do not alter glucose handling in normal and diabetic rats.
Insulin-regulated aminopeptidase (IRAP) co-localizes with the glucose transporter 4 (GLUT4) in GLUT4 storage vesicles (GSV) in insulin-responsive cells. In response to insulin, IRAP is the only transmembrane enzyme known to translocate together with GLUT4 to the plasma membrane in adipocytes and muscle cells. Although the intracellular region of IRAP is associated with GLUT4 vesicle trafficking, the role of the aminopeptidase activity in insulin-responsive cells has not been elucidated. The aim of this study was to investigate whether the inhibition of the aminopeptidase activity of IRAP facilitates glucose uptake in insulin-responsive cells. In both in vitro and in vivo studies, inhibition of IRAP aminopeptidase activity with the specific inhibitor, HFI-419, did not modulate glucose uptake. IRAP inhibition in the L6GLUT4myc cell line did not alter glucose uptake in both basal and insulin-stimulated state. In keeping with these results, HFI419 did not affect peripheral, whole-body glucose handling after an oral glucose challenge, neither in normal rats nor in the streptozotocin (STZ)-induced experimental rat model of diabetes mellitus (DM). Therefore, acute inhibition of IRAP aminopeptidase activity does not affect glucose homeostasis.


Use of an Autologous Heterogenous Skin Construct in the Treatment of Intractable Late-Effect Radiation Wounds: Case Series.
Late-effect radiation-induced wounds represent a particularly difficult category of wounds to manage and treat. Fibrosis, impaired cellular activity, ischemia, and wound chronicity all work to impair healing, and this becomes more pronounced when defects are large or when avascular structures such as bone are exposed. Effective treatment options for this type of wound are limited. Thorough excision of irradiated tissue followed by distal pedicled or free flap closure is the most successful; however, this often requires multiple-stage surgeries and prolonged hospitalization and is associated with significant donor site morbidity. This is complicated further when wounds are large or in difficult locations, when surgery is not appropriate, or when there is limited access to surgeons with the appropriate experience/skill to perform such procedures. This case series describes the use of an autologous heterogenous skin construct (AHSC) made from a small full-thickness sample of the patient's healthy skin. Three patients with intractable late-effect radiation wounds were treated with AHSC. Case 1 describes an abdominal wound with tunneling of 7.5 cm to the pubic symphysis, which had been treated for known osteomyelitis, and a shallower full-thickness groin wound. Case 2 describes a right scapular wound with exposed bone, which had failed flap closure. Case 3 describes a right thigh wound in a patient who had been treated for sarcoma with extensive radiation therapy. This eventually resulted in an above-the-knee amputation, which failed to heal, and full exposure of the distal end of the resected femur. All wounds had been present for greater than 10 months. Mean percent volume reduction was 83% (±2.7) at 3 weeks and 92.9% (±4.7) at 4 weeks. The tunneled abdominal wound decreased in depth from 7.5 cm to 1.2 cm in 3 weeks. Complete closure was achieved at 11 weeks for the abdominal and groin wounds (patient 1) and at 16 weeks for the thigh wound (patient 3). The scapular wound volume of patient 2 had decreased by 91.8% at week 4 but was not fully restored until week 21. Mean time to closure was 16.1 (±4.7) weeks. AHSC was effective in covering exposed bone, improving wound bed vascularity, filling in significant wound depth, and achieving complete wound closure with one application in patients with intractable late-effect radiation wounds.


Anti-C1q antibodies and their association with complement components in Indian systemic lupus erythematosus patients.
Systemic lupus erythematosus (SLE) is a prototype autoimmune disease, characterized by immune complex formation and systemic inflammation. Complement components such as C1q and mannose-binding lectin (MBL) play an important role in the clearance of immune complexes. Anti-C1q antibodies are associated with lupus nephritis and reduced levels of the complement components. The objective of this study was to detect anti-C1q antibodies in SLE patients and to evaluate their association with the complement components. Sixty SLE patients were included, of whom 75% had lupus nephritis (LN) and 25% were without renal manifestations (non-LN). The disease activity was assessed at the time of evaluation by the systemic lupus erythematosus disease activity index (SLEDAI). Anti-C1q antibodies, circulating immune complexes, and serum MBL levels were detected by enzyme-linked immunosorbent assay. The anti-C1q antibody prevalence was 58.3%. The LN patients showed 60% anti-C1q positivity with a higher percentage in membranoproliferative glomerulonephritis patients (51.9%). Anti-dsDNA positivity was slightly higher among the anti-C1q positives than in the anti-C1q negatives (65.7% vs. 60%). A higher percentage of reduced C3 and C4 levels was noted among the anti-C1q positives. The LN patients showed a higher percentage of low MBL levels among anti-C1q negatives than in the anti-C1q positives (61.1% vs. 55.6%). Non-LN patients showed a higher percentage of low MBL levels among anti-C1q positives than among anti-C1q negatives (87.5% vs. 57.1%). Anti-C1q antibodies were found in both LN and non-LN patients, but there was no correlation with the clinical severity of the disease.


Blood flow, volume, and transit time in the pulmonary microvasculature using laser-Doppler.
Capillary transit time is determined by the ratio of capillary volume to flow rate. Exercise-induced hypoxemia is thought to occur because of the short transit time of erythrocytes in capillaries. The effect of flow rate on capillary volume (recruitment vs. distension) is controversial. In a perfused left lower lobe preparation in canine lungs, we used laser-Doppler flowmetry (model ALF21R) to monitor changes in blood flow, volume, and transit time in the microvasculature near the subpleural surface. Changes in total flow, blood volume, and total transit time (tt) were also measured. The results showed that microvascular volume approached maximum when flow rate was at resting value (0.4 l/min) and pressure in the pulmonary artery was > 6 mmHg relative to the level of the capillaries. In contrast, the total blood volume increased gradually over a wide range of flow rates. When flow increased 4.2 times (from 155 to 650 ml/min), tt decreased from 7.32 to 3.53 s; meanwhile, microvascular flow increased from 6.0 to 12.7 units and microvascular transit time decreased from 3.14 to 1.81 units. The changes in microvascular volume and transit time were essentially independent of whether the venous pressure was higher or lower than alveolar pressure. At very high flow (6-10 times resting value), tt fell gradually to approximately 1 s. Direct monitoring of transit time with the laser-Doppler also revealed a gradual decline in microvascular transit time as flow rate increased from 2 to 10 times the normal flow. (ABSTRACT TRUNCATED AT 250 WORDS)


Risk of cardiovascular disease in patients with alcohol use disorder: A population-based retrospective cohort study.
The complex effects of alcohol consumption on the cardiovascular system vary with mean daily consumption and duration of intake. This population-based retrospective cohort study aimed to explore the risk of cardiovascular disease (CVD) in patients with alcohol use disorder (AUD). Data was collected from the Taiwan National Health Insurance Research Database from 2000 to 2013. A total of 7,420 patients with AUD were included in our study group, and 29,680 age- and sex-matched controls without AUD in the control group. Cox proportional hazard regression analysis was used to investigate the effects of AUD on the risk of CVD. Most patients were men aged 25-44 years. At the end of the follow-up period, the AUD group had a significantly higher incidence of CVD (27.39% vs. 19.97%, P<0.001) and more comorbidities than the control group. The AUD group also exhibited a significantly higher incidence of CVD than the control group based on the Cox regression analysis and Fine and Gray's competing risk model (adjusted hazard ratio [AHR] = 1.447, 95% confidence interval [CI] = 1.372-1.52 5, P<0.001). Furthermore, male sex, diabetes mellitus, hypertension, hyperlipidemia, chronic kidney disease, chronic obstructive pulmonary disease, anxiety, depression, and a high Charlson Comorbidity Index were also associated with an increased risk of CVD. Patients with AUD in different CVD subgroups, such as those with CVD, ischemic heart disease (IHD), and stroke, were at a significantly higher risk of disease than those without AUD; CVD (AHR = 1.447, 95% CI = 1.372-1.525, P<0.001), IHD (AHR = 1.304, 95% CI = 1.214-1.401, P<0.001), and stroke (AHR = 1.640, 95% CI = 1.519-1.770, P<0.001). The risk also significantly differed among patients in the different CVD subgroups. We observed an association between AUD and development of CVD even after adjusting for several comorbidities and medications in our nationwide population cohort.


Pollution by Nonylphenol in river, tap water, and aquatic in an acid rain-plagued city in southwest China.
Nonylphenol (NP) has provoked much environmental concern because of their weak estrogenic activities; however, few data are available on the environmental levels of the chemical in China. Environmental or river samples were assayed for NP by high-performance liquid chromatography (HPLC) technique. The concentration for NP measured in Xiangjiang River, ranging from 0.174 to 3.411 μg/L with a mean value of 1.73 μg/L, was lower than the Water Quality Criteria for NP of the US (6.6 μg/L); however, the NP concentration was maintained at a higher level compare to the developed countries and other civil cities. NP concentration in downstream water was markedly higher than that both in midstream and upstream water. Tissue accumulation of NP was observed in aquatics. A ratio of mean concentration of NP in aquatic (chlamys farreri and hemiculter leucisculus) to that in river water was 241 and 1087, respectively. The presence of NP in tap water in two urban districts of Zunyi was common with a detectable rate reached 100.0%. Mean NP concentration in terminal tap water in Huichuan district was six times as high as Honghuagang district, which was above Standards for the Drinking Water Quality for Phenols of China (2 μg/L). The pollution of NP in Xiangjiang River, tap water, and aquatic in Zunyi belongs to moderate or severe level in the world.


Deguelin Attenuates Allergic Airway Inflammation via Inhibition of NF-κb Pathway in Mice.
Asthma is a chronic respiratory disease characterized by airway inflammation and remodeling, resulting in a substantial economic burden on both patients and society. Deguelin, a constituent of the Leguminosae family, exhibits anti-proliferative and anti-inflammatory activities in cancer mice models via inhibiting phosphatidylinositol 3-kinases and the NF-κB pathway. We demonstrated that deguelin effectively reduced OVA-induced inflammatory cell recruitment, decreased lung tissue inflammation and mucus production, suppressed airway hyperresponsiveness, and inhibited serum immunoglobulin and Th2 cytokine levels in a dose-dependent manner in asthmatic mice. In addition, we found that deguelin reduced inflammatory gene expressions both in vivo and in vitro, which were closely associated with activation of the NF-κB signaling pathway. Thus, we further explored the underlying mechanisms of deguelin in normal human bronchial epithelial cells (BEAS-2B). Our results suggested that deguelin inhibited NF-κB binding activity by enhancing the ability of IκBα to maintain NF-κB in an inactive form in the cytoplasm and preventing the TNF-α induced translocation of p65 to the nucleus. In conclusion, our research indicates that deguelin attenuates allergic airway inflammation via inhibition of NF-κB pathway in mice model and may act as a potential therapeutic agent for patients with allergic airway inflammation.


Trona and sodium bicarbonate in beef cattle diets: effects on pH and volatile fatty acid concentrations.
A study was conducted to evaluate the effectiveness of NaHCO3 and trona in beef cattle diets. Trace element (n = 28) analysis revealed no toxicological or safety concerns with the use of trona. Trona was more (P less than .05) soluble in ruminal fluid than Na2CO3, and NaHCO3 and had greater (P less than .05) buffering capacity (9.6 meq/g) than NaHCO3 (6.1 meq/g) but less (P less than .05) than Na2CO3 (11.1 meq/g). Calcium carbonate was insoluble and did not buffer ruminal fluid. Six yearling (avg 272 kg) Hereford X Angus steers, each with ruminal, duodenal and ileal cannulas, were fed 50:50 (cracked corn-based concentrate:cottonseed hulls) or 90:10 concentrate diets with no buffer, 1% NaHCO3 or with 1% trona. Intake, across all treatments, averaged 2.4% of body weight. Propionate (mmol/liter) increased (17.6 vs 13.5; P less than .05) and butyrate decreased (3.5 vs 5.2; P less than .05) with trona in the 90:10 diet as compared with no buffer. Propionate (16.8) increased (P less than .05) with NaHCO3 in the 90:10 diet. Average ruminal pH was greater (P less than .05) in 90:10 diets with trona or NaHCO3 than with no buffer (5.61, 5.61 vs 5.55); duodenal pH was greater (P less than .01) with trona than with no buffer (2.66 vs 2.55). Trona reduced ruminal pH-hours (P less than .05) and pH-area (P less than .12; time and area below mean pH of control) below control for both concentrate levels.(ABSTRACT TRUNCATED AT 250 WORDS)


Targeted delivery of oral vaccine antigens to aminopeptidase N protects pigs against pathogenic E. coli challenge infection.
Oral subunit vaccines are an interesting alternative strategy to traditional live-attenuated or inactivated vaccines for conferring protection against gut pathogens. Despite being safer and more cost-effective, the development of oral subunit vaccines remains challenging due to barriers imposed by the gastrointestinal tract, such as digestive enzymes, a tolerogenic immune environment and the inability of larger proteins to cross the epithelial barrier. Recent advances have focused on overcoming these barriers by using potent mucosal adjuvants or pH-responsive delivery vehicles to protect antigens from degradation and promote their release in the intestinal lumen. A promising approach to allow vaccine antigens to pass the epithelial barrier is by their targeting towards aminopeptidase N (APN; CD13), an abundant membrane protein present on small intestinal enterocytes. APN is a peptidase involved in digestion, but also a receptor for several enteric pathogens. In addition, upon antibody-mediated crosslinking, APN facilitated the transport of antibody-antigen fusion constructs across the gut epithelium. This epithelial transport resulted in antigen-specific immune responses. Here, we present evidence that oral administration of APN-specific antibody-antigen fusion constructs comprising the porcine IgA Fc-domain and the FedF tipadhesin of F18-fimbriated E. coli elicited both mucosal and systemic immune responses and provided at least partial protection to piglets against a subsequent challenge infection with an F18-fimbriated STEC strain. Altogether, these findings will contribute to the further development of new oral subunit vaccines and provide a first proof-of-concept for the protective efficacy of APN-targeted vaccine antigens.


Quality of Clinician-Reported Cancer History When Ordering Genetic Testing.
Clinical history data reported on test requisition forms (TRFs) for hereditary cancer multigene panel testing (MGPT) are routinely used by genetic testing laboratories. More recently, publications have incorporated TRF-based clinical data into studies exploring yield of testing by phenotype and estimating cancer risks for mutation carriers. We aimed to assess the quality of TRF data for patients undergoing MGPT. Ten percent of patients who underwent hereditary cancer MGPT between January and June 2015 at a clinical laboratory were randomly selected. TRF-reported cancer diagnoses were evaluated for completeness and accuracy for probands and relatives using clinical documents such as pedigrees and chart notes as the comparison standard in cases where these documents were submitted after the time of test order. TRF-reported cancer sites and ages at diagnosis were complete for > 90.0% of proband cancer diagnoses overall, and the completion rate was even higher (> 96.0%) for breast, ovarian, colorectal, and uterine cancers. When reported, these data were accurate on TRFs for > 99.5% of proband cancer sites and > 97.5% of proband ages at diagnosis. Cancer site and age at diagnosis data were also complete on the TRF for the majority of cancers among first- and second-degree relatives. Completeness decreased as relation to the proband became more distant, whereas accuracy remained high across all degrees of relation. Data collected as part of cancer genetic risk assessment is completely and accurately reported on TRFs for the majority of probands and their close relatives and is comparable to information directly obtained from clinic notes, particularly for breast and other cancers commonly associated with hereditary cancer syndromes.


Performance characterization of fiber Bragg grating thermal response in space vacuum thermal environment.
We investigated the fiber Bragg grating (FBG) thermal response in space vacuum thermal environment. The FBGs were packaged with 6061-T6 aluminum. The liquid nitrogen immersion experiment results show that its wavelength shift standard deviation is 0.76 pm for 217 h. The combination effect of vacuum and cryogenic temperature was studied by thermal cycling process in space environment simulator. The FBG sensors show accuracy better than 2% full scale, and the hysteresis errors are below 1%. It proves that these metal packaged FBG sensors can survive and meet the requirement of space measurement.


Addressing HPV vaccine myths: practical information for healthcare providers.
Human papillomavirus (HPV) vaccine uptake consistently lags behind that of other adolescent vaccines. In 2017, uptake of a single HPV vaccine dose and HPV vaccine series completion was 66% and 49%, respectively, compared to uptake of tetanus, diphtheria, and acellular pertussis vaccine (89%) and quadrivalent meningococcal conjugate vaccine (85%). Reasons for not vaccinating adolescents again HPV are varied, and in many cases, are rooted in commonly spread myths and misperceptions about the vaccine. In this review, we address five key myths - HPV vaccination is not effective at preventing cancer; Pap smears are sufficient to prevent cervical cancer; HPV vaccination is not safe; HPV vaccination is not needed since most infections are naturally cleared by the immune system; 11-12 years of age is too young to vaccinate. For each myth, we summarize the scientific evidence refuting the myth and provide speaking prompts for healthcare professionals to communicate about HPV vaccination.


Human platelets respond differentially to lysophosphatidic acids having a highly unsaturated fatty acyl group and alkyl ether-linked lysophosphatidic acids.
Lysophosphatidic acid (LPA) is a physiological agonist that is produced by lysophospholipase D, phospholipase A(1) and phospholipase A(2) in the blood of animals. It exerts diverse biological actions on a broad range of animal cells. Specific receptors for this important agonist have been characterized. In this investigation, for the first time we prepared LPAs having a highly unsaturated fatty acyl group, such as the eicosapentaenoyl or docosahexaenoyl residue, and their acetylated derivatives. Human platelets aggregated more potently in response to the highly unsaturated acyl-LPAs than to LPAs with a C(18) fatty acyl group, such as an oleoyl group, while alkyl ether-linked LPAs (alkyl-LPA) had much stronger aggregating activity. Two positional isomers of LPAs with an arachidonoyl, eicosapentaenoyl or docosahexaenoyl group had equipotent aggregatory activity as well as the positional isomers of their acetylated analogues, indicating that putative LPA receptors could not distinguish the difference between the positional isomers. We found that platelet preparations from two individuals showed no aggregatory response to alkyl-LPAs, although they contained mRNAs for known LPA receptors in the following order of expression level: endothelial differentiation gene (Edg)-4>Edg-7>Edg-2. We also obtained evidence that 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (ONO-RS-082), a phospholipase A(2) inhibitor, potentiated alkyl-LPA-induced platelet aggregation, but inhibited highly unsaturated acyl-LPA-induced platelet aggregation. These results indicated that human platelets express acyl-LPA-selective and alkyl-LPA-selective receptors on their plasma membrane.


Morphological background detection and illumination normalization of text image with poor lighting.
In this paper, some morphological transformations are used to detect the unevenly illuminated background of text images characterized by poor lighting, and to acquire illumination normalized result. Based on morphologic Top-Hat transform, the uneven illumination normalization algorithm has been carried out, and typically verified by three procedures. The first procedure employs the information from opening based Top-Hat operator, which is a classical method. In order to optimize and perfect the classical Top-Hat transform, the second procedure, featuring the definition of multi direction illumination notion, utilizes opening by reconstruction and closing by reconstruction based on multi direction structuring elements. Finally, multi direction images are merged to the final even illumination image. The performance of the proposed algorithm is illustrated and verified through the processing of different ideal synthetic and camera collected images, with backgrounds characterized by poor lighting conditions.


The immunogenicity and safety of GSK's recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience.
Engerix B (GSK HepB, GSK, Belgium) was the first recombinant hepatitis B virus vaccine to be licensed, and marked its 30th anniversary in 2016. Vaccination of adult populations against HBV is usually implemented on a risk-based approach with varying degrees of success. Confirmation of ongoing vaccine effectiveness requires monitoring the performance of HBV immunization as reported in individual studies, using systematic methods. Areas covered: We conducted a systematic review of the literature to summarize 30 years of immunogenicity and safety data for GSK HepB in adult populations. Expert commentary: Primary 3-dose vaccination of healthy individuals is generally associated with seroprotection rates of 90% or more, although seroprotection decreases with older age. Accelerated 0, 1, 2-month or 0, 7 and 21-day schedules require the recommended booster dose to achieve similar rates of seroprotection. Lower rates of seroprotection were also observed in adults with underlying chronic disease and with a weakened immune system. GSK HepB had a clinically acceptable safety profile in all of the populations studied, including individuals with underlying co-morbidities and immunosuppression. GSK HepB will continue to contribute to global HBV control for the foreseeable future. Further investigation is needed into how to optimize seroprotection in less immune-competent groups.


A monograph proposing the use of canine mammary tumours as a model for the study of hereditary breast cancer susceptibility genes in humans.
Canines are excellent models for cancer studies due to their similar physiology and genomic sequence to humans, companion status and limited intra-breed heterogeneity. Due to their affliction to mammary cancers, canines can serve as powerful genetic models of hereditary breast cancers. Variants within known human breast cancer susceptibility genes only explain a fraction of familial cases. Thus, further discovery is necessary but such efforts have been thwarted by genetic heterogeneity. Reducing heterogeneity is key, and studying isolated human populations have helped in the endeavour. An alternative is to study dog pedigrees, since artificial selection has resulted in extreme homogeneity. Identifying the genetic predisposition to canine mammary tumours can translate to human discoveries - a strategy currently underutilized. To explore this potential, we reviewed published canine mammary tumour genetic studies and proposed benefits of next generation sequencing canine cohorts to facilitate moving beyond incremental advances.


Topical xylitol administration by parents for the promotion of oral health in infants: a caries prevention experiment at a Finnish Public Health Centre.
This demonstration programme tested topical use of xylitol as a possible oral health promoting regimen in infants at a Finnish Public Health Centre in 2002-2011. Parents (usually mothers) began once- or twice-daily administration of a 45% solution of xylitol (2.96 m) onto all available deciduous teeth of their children at the age of approximately 6-8 months. The treatment (xylitol swabbing), which continued till the age of approximately 36 months (total duration 26-28 months), was carried out using cotton swabs or a children's toothbrush; the approximate daily xylitol usage was 13.5 mg per each deciduous tooth. At the age of 7 years, caries data on the deciduous dentition of 80 children were compared with those obtained from similar, untreated children (n = 90). Xylitol swabbing resulted in a significant (P < 0.001) reduction in the incidence of enamel and dentine caries compared with the comparison subjects (relative risk 2.1 and 4.0, respectively; 95% confidence intervals 1.42-3.09 and 2.01-7.98, respectively). Similar findings were obtained when the children were 5 or 6 years old. The treatment reduced the need of tooth filling relative risk and 95% confidence intervals at 7 years: 11.86 and 6.36-22.10, respectively; P < 0.001). Compared with untreated subjects, the oral counts of mutans streptococci were reduced significantly (P < 0.001). Considerable improvement in dental health was accomplished in infants participating in a topical at-home xylitol administration experiment, which was offered to families in the area by the Public Health Centre as a supplement to standard oral health care. Caregiver assessment of the programme was mostly rated as high or satisfactory.


One-Pot Synthesis of Silver Nanoparticles from Garcinia gummi-gutta: Characterisation, Antimicrobial, Antioxidant, Anti-Cancerous and Photocatalytic Applications.
Methods like the bio-synthesis of silver nanoparticles (Ag NPs) using plant extracts have become promising due to their eco-friendly approach. The study aimed to examine the utilization of Garcinia gummi-gutta fruit phytochemicals as agents in the biosynthesis of Ag NPs, evaluation of the antimicrobial, antioxidant, and anti-cancerous properties, as well as the photocatalytic ability of bio-synthesized Ag NPs against Crystal Violet (CV), a triphenylmethane dye. The characterization of the physical properties of the Ag NPs synthesized via the green route was done using UV-Vis spectrophotometry (UV-Vis), X-ray Diffraction (XRD), Fourier Transform Infrared Spectrophotometry (FTIR), Scanning Electron Microscopy (SEM), Zeta potential analysis, and Transmission Electron Microscopy (TEM). The dye degradation efficiency of CV was determined using synthesized Ag NPs under UV light by analyzing the absorption maximum at 579 nm. The antimicrobial efficacy of Ag NPs against E. coli, S. aureus, Candida tropicalis, and Candida albicans was examined using the broth dilution method. The antioxidant and anti-cancer properties of the synthesized Ag NPs were assessed using the DPPH and MTT assays. The UV analysis revealed that the peak of synthesized Ag NPs was 442 nm. Data from FTIR, XRD, Zeta potential, SEM, and TEM analysis confirmed the formation of nanoparticles. The SEM and TEM analysis identified the presence of spherical nanoparticles with an average size of 29.12 nm and 24.18 nm, respectively. Maximum dye degradation efficiency of CV was observed at 90.08% after 320 min without any silver leaching, confirming the photocatalytic activity of Ag NPs. The bio-efficiency of the treatment was assessed using the Allium cepa root growth inhibition test, toxicity analysis on Vigna radiata, and Brine shrimp lethality assay. The findings revealed the environmentally friendly nature of green Ag NPs over physical/chemically synthesized Ag NPs. The synthesized Ag NPs can effectively be used in biomedical and photocatalytic applications.


Computational fluid dynamics modeling of ventilation of confined-space manure storage facilities: applications.
Fatalities associated with entry into on-farm confined-space manure storage tanks occur each year The fatalities are due to asphyxiation or poisoning by exposure to high concentrations of hydrogen sulfide, methane, and carbon dioxide. Forced ventilation has been shown to be an effective way to reduce concentrations of these noxious gases to levels that are safe for human entry into these storage tanks. Hydrogen sulfide (H2S) was used as an indicator gas to investigate the effectiveness of forced ventilation strategies for eliminating the toxic and oxygen-deficient atmospheres in confined-space manure tanks. Validated computational fluid dynamics (CFD) modeling protocols were used to simulate H2S evacuation from fan-ventilated manure tanks. The simulation studies were conducted for rectangular and circular manure tanks, and the effects of pollutant source, inter-contamination (process by which a portion of exhausted contaminant gas enters a ventilated confined airspace through the fresh air intake), storage size (i.e., length, diameter), and air exchange rate on H2S removalfrom fan-ventilated manure tanks were investigated. For the same air exchange rate, as the size (i.e., length, diameter) of the tank increased, the rate of evacuation of the H2S from the confined space decreased. For rectangular and circular manure tanks, the higher the air exchange rate, the higher the rate of evacuation of the H2S from the confined space. For the rectangular tank geometries and ventilation system layouts simulated, evacuation times decreased exponentially with air exchange rate. Evacuation times for the circular tanks simulated decreased linearly with air exchange rate.


Molecular genetics of obsessive-compulsive disorder: a comprehensive meta-analysis of genetic association studies.
Twin studies indicate that obsessive-compulsive disorder (OCD) is strongly influenced by additive genetic factors. Yet, molecular genetic association studies have yielded inconsistent results, possibly because of differences across studies in statistical power. Meta-analysis can yield greater power. This study reports the first comprehensive meta-analysis of the relationship between OCD and all previously examined polymorphisms for which there was sufficient information in the source studies to compute odds ratios (ORs). A total of 230 polymorphisms from 113 genetic association studies were identified. A full meta-analysis was conducted for 20 polymorphisms that were examined in 5 or more data sets, and a secondary meta-analysis (limited to the computation of mean effect sizes) was conducted for 210 polymorphisms that were examined in fewer than 5 data sets. In the main meta-analysis, OCD was associated with serotonin-related polymorphisms (5-HTTLPR and HTR2A) and, in males only, with polymorphisms involved in catecholamine modulation (COMT and MAOA). Nonsignificant trends were identified for two dopamine-related polymorphisms (DAT1 and DRD3) and a glutamate-related polymorphism (rs3087879). The secondary meta-analysis identified another 18 polymorphisms with significant ORs that merit further investigation. This study demonstrates that OCD is associated with multiple genes, with most having a modest association with OCD. This suggests a polygenic model of OCD, consistent with twin studies, in which multiple genes make small, incremental contributions to the risk of developing the disorder. Future studies, with sufficient power to detect small effects, are needed to investigate the genetic basis of OCD subtypes, such as early vs late onset OCD.


Associations between simultaneous alcohol and cannabis use and next-day negative affect among young adults: The role of sex and trait anxiety.
The simultaneous use of alcohol and cannabis ("simultaneous alcohol and marijuana [SAM] use") is common among young adults and associated with negative substance-related consequences. SAM use may be tied to fluctuating mood states such as negative affect and individual characteristics including trait level of anxiety and sex. However, little is understood about their collective role. In this study, we sought to understand the daily link between SAM use and negative affect and whether this link might differ by both trait anxiety and sex. Participants were 154 young adults (57.8% female, 72.7% White, M age = 20.2) who completed baseline surveys on trait anxiety symptoms and up to 14 consecutive daily surveys on their substance use and affective states. Multilevel models tested for associations of type of substance use day (i.e., alcohol-only days, cannabis-only days, and no use days relative to SAM use days) with next-day negative affect. Three-way and lower order interactions were tested for substance use day type, anxiety, and sex. Two three-way interactions between cannabis-only days, anxiety, and sex and between alcohol-only days, anxiety, and sex emerged such that SAM use was associated with greater next-day negative affect relative to single substance use days particularly among female participants with elevated anxiety. Anxiety and sex are salient factors in the link between SAM use relative to single-substance use and daily negative affect. Study findings reinforce the need to account for all of these factors in order to develop maximally efficacious substance use interventions.


Identification of Meloidogyne species on traditional Chinese medicine plants in the Qinling mountain area of China and their aggressiveness to different medicinal herbs.
Root-knot nematodes (Meloidogyne spp.) are plant-parasitic nematodes that cause serious damage on a worldwide basis. There are many species of traditional Chinese medicine (TCM) plants, but only a few have been reported to be infected by Meloidogyne species. From 2020 to 2022, a survey was conducted in the Qinling mountain area, which is the main producing region of TCM plants in China. Obvious galling symptoms were observed on the root systems of fifteen species of TCM plants. Females were collected from diverse diseased TCM plants and subsequently identified at morphological and molecular level. Among the twenty diseased root samples collected, Meloidogyne hapla populations were identified in twelve samples (60%) and Meloidogyne incognita populations were identified in eight samples (40%). Among the fifteen species of diseased TCM plants, eight of them, namely Scutellaria baicalensis, Leonurus japonicus, Dioscorea zingiberensis, Cornus officinalis, Viola philippica, Achyranthes bidentata, Senecio scandens, and Plantago depressa were reported to be infected by Meloidogyne species for the first time. The host status of five species of TCM plants for two M. hapla isolates and one M. incognita isolate from TCM plants in this study was then evaluated. Differences in TCM plants' response to nematode infection were apparent when susceptibility was evaluated by the egg counts per gram fresh weight of root and the reproduction factor of the nematodes. Among the five species of TCM plants tested, Salvia miltiorrhiza and Gynostemma pentaphyllum were the most susceptible, while S. baicalensis and V. philippica were not considered suitable hosts for M. hapla or M. incognita.


Magnetic nanoparticles for drug delivery applications.
In recent past magnetic nanoparticles have been explored for a number of biomedical applications due to their superparamagnetic moment with high magnetic saturation value. For these biomedical applications, magnetic nanoparticles require being monodispersed so that the individual nanoparticle has almost identical physico-chemical properties for biodistribution, bioelimination and contrast imaging potential. Further, the surface functionalization/modification of magnetic nanoparticles ultimately facilitate the protein or DNA separation, detection and magnetic resonance imaging contrast, drug delivery and hyperthermia applications. The essential goal of this review is to evaluate the recent advances of magnetic nanoparticles for tumor, brain targeting and hyperthermia applications.


Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.
There are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children. IRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months. There were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 μg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups. Treatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children. ClinicalTrials.gov NCT01322009.


Targeting histone deacetylases for the treatment of cancer and inflammatory diseases.
Histone deacetylases (HDACs) are involved in chromatin remodeling and modification of nonhistone transcription regulatory proteins, thus modulating the expression of genes important for complex biological events. Dysregulation of HDACs and aberrant chromatin acetylation and deacetylation may be implicated in the pathogenesis of various diseases, including cancer and inflammatory diseases. A significant number of HDAC inhibitors (HDIs) have been developed in the past decade. These inhibitors demonstrate strong anti-neoplastic effects in vitro and in vivo by inducing growth arrest, differentiation, and programmed cell death, inhibiting cell migration, invasion, and metastasis, and suppressing angiogenesis. More than a dozen HDIs are currently being evaluated in phase I-II clinical trials in patients with solid and hematological malignancies, and some have already shown promising activity with low toxicity. HDIs also exhibit strong anti-inflammatory effects in vitro and in animal models for various inflammatory diseases, thus representing a new class of promising agents for treating inflammatory diseases. This review provides an overview of HDACs in gene regulation, HDIs for cancer therapy and for potential treatment of inflammatory diseases, and future perspectives.


Alteration of frequency range for binaural beats in acute low-tone hearing loss.
The effect of acute low-tone sensorineural hearing loss (ALHL) on the interaural frequency difference (IFD) required for perception of binaural beats (BBs) was investigated in 12 patients with unilateral ALHL and 7 patients in whom ALHL had lessened. A continuous pure tone of 30 dB sensation level at 250 Hz was presented to the contralateral, normal-hearing ear. The presence of BBs was determined by a subjective yes-no procedure as the frequency of a loudness-balanced test tone was gradually adjusted around 250 Hz in the affected ear. The frequency range in which no BBs were perceived (FRNB) was significantly wider in the patients with ALHL than in the controls, and FRNBs became narrower in the recovered ALHL group. Specifically, detection of slow BBs with a small IFD was impaired in this limited (10 s) observation period. The significant correlation between the hearing level at 250 Hz and FRNBs suggests that FRNBs represent the degree of cochlear damage caused by ALHL.


"With a little help from my friends" social predictors of clinical recovery in first-episode psychosis.
Social functioning is a conglomerate of factors central to clinical recovery after a first-episode psychosis. There is a lack of studies investigating the relative impact of factors related to social interaction. Disentangling these could facilitate improvement of psychosocial interventions. This study aims to investigate the impact of social interactions on two-year clinical recovery in first-episode psychosis, by examining frequency and satisfaction of relationships with family and friends. A baseline sample of 178 first-episode psychosis individuals were followed up over two years regarding social functioning and clinical status. We longitudinally compared those who were to those who were not recovered using generalized estimating equations analyses. Our results showed that frequency of social interactions with friends was a significant positive predictor of clinical recovery over a two-year period. Perceived satisfaction with relationships, and frequency of family interaction did not show significant effects. We conclude that interaction with friends is a malleable factor that could be targeted for early intervention. This would facilitate protective factors through the preservation of existing social networks and thus reduce the risk of disability associated with long-term psychosis. Findings indicate that even individuals with an inclination towards social withdrawal and isolation could benefit from this type of intervention.


Caution advised with dapagliflozin in the setting of male urinary tract outlet obstruction.
We describe an adverse outcome in a 70-year-old man with type 2 diabetes mellitus treated with sodium-glucose cotransporter type 2 (SGLT2) inhibitor dapagliflozin. SGLT2 inhibitors act in the proximal tubules to prevent glucose reabsorption and induce urinary glucose excretion, they have been associated with increased risk of urinary tract infection (UTI). Our patient presented to hospital with Escherichia coli septicaemia with positive urine and blood cultures on the background of two previous UTIs occurring post commencement of dapagliflozin in the community. Renal tract ultrasound in hospital revealed incomplete bladder emptying with evidence of urinary stasis, and a postvoid residual volume of 180 mL. His dapagliflozin was ceased, and he has had no further episodes of UTI. This case suggests there may be an increased risk of UTI in patients prescribed SGLT2 inhibitors who also have evidence of bladder outlet obstruction-caution is advised in the prescribing of SGLT2 inhibitors in this setting.


Host-Bacterium Interaction Mechanisms in Staphylococcus aureus Endocarditis: A Systematic Review.
Staphylococci sp. are the most commonly associated pathogens in infective endocarditis, especially within high-income nations. This along with the increasing burden of healthcare, aging populations, and the protracted infection courses, contribute to a significant challenge for healthcare systems. A systematic review was conducted using relevant search criteria from PubMed, Ovid's version of MEDLINE, and EMBASE, and data were tabulated from randomized controlled trials (RCT), observational cohort studies, meta-analysis, and basic research articles. The review was registered with the OSF register of systematic reviews and followed the PRISMA reporting guidelines. Thirty-five studies met the inclusion criteria and were included in the final systematic review. The role of Staphylococcus aureus and its interaction with the protective shield and host protection functions was identified and highlighted in several studies. The interaction between infective endocarditis pathogens, vascular endothelium, and blood constituents was also explored, giving rise to the potential use of antiplatelets as preventative and/or curative agents. Several factors allow Staphylococcus aureus infections to proliferate within the host with numerous promoting and perpetuating agents. The complex interaction with the hosts' innate immunity also potentiates its virulence. The goal of this study is to attain a better understanding on the molecular pathways involved in infective endocarditis supported by S. aureus and whether therapeutic avenues for the prevention and treatment of IE can be obtained. The use of antibiotic-treated allogeneic tissues have marked antibacterial action, thereby becoming the ideal substitute in native and prosthetic valvular infections. However, the development of effective vaccines against S. aureus still requires in-depth studies.


Discrimination of Mentha species grown in different geographical areas of Algeria using 1H-NMR-based metabolomics.
1H-NMR-based metabolomics have been applied to identify potential NMR-markers and biomarkers capable of distinguishing, qualifying and classifying three Mentha species:- Mentha pulegium L., Mentha × rotundifolia (L.) Huds., Mentha spicata L., and their ecotypes. Samples of the 3 species were collected in seven different locations in Algeria, with the aim to establish a quality control protocol based on the use of NMR fingerprint profiles of polar extracts. NMR data indicate that the identification of the Mentha genus can be confirmed by the presence of the doublet proton signals with identical coupling constants at δ 7.49 (d, 15.9 Hz) and δ 6.29 (d, 15.9 Hz); these correspond to the protons of the double-bond conjugated to the ester group of rosmarinic acid, a bioactive compound found in all three species. Differences in NMR proton chemical shifts and/or signal intensities were clearly demonstrated on the orthogonal projections to latent structures discriminating analysis (OPLS-DA). Several potential biomarkers discriminating the three Mentha species were originated using S-plots, loading score plots, NMR data analysis and literature search. These discriminating signals point to glycosylated flavonols, oxygenated terpenoids and hydrocarbon terpenoids to distinguish M. pulegium, M. × rotundifolia and M. spicata, respectively. Within the same species, Principal Component Analysis (PCA) scores clearly discriminated the metabolite content according to regions in which the plants were grown. The 6 zones in which Mentha pulegium samples were harvested were clearly separated along either or both PC1 and PC2; by contrast, the harvesting locations were divided into two groups along PC1 for both M. × rotundifolia and M. spicata. The total antioxidant activity of the Mentha species was impacted by the abiotic factors of the different regions.


Monoclonal antibody OKT3-induced T cell proliferation: differential role of HLA class II determinants expressed by T cells and monocytes.
Monoclonal antibodies (MAb) to monomorphic determinants of HLA Class II antigens inhibit monocyte-dependent T cell proliferation induced by MAb OKT3 to a different extent, suggesting a differential regulatory role of the corresponding determinants in T cell proliferation. To elucidate the mechanism(s) underlying this pattern, the MAb CR10-343 and Q5/6 with high inhibitory effect and MAb CR11-462 and CR12-356 with low inhibitory effect were characterized. Cross-inhibition studies showed that the four MAb recognize distinct determinants. The determinants recognized by MAb CR10-343 and CR12-462 are spatially close. The determinants recognized by the four MAb appear to be functionally independent in MAb OKT3-induced T cell proliferation, since the inhibitory effect of the combination of MAb CR10-343 and Q5/6 and of the MAb CR11-462 and CR12-356 was additional but not synergistic. To compare the functional activity of HLA Class II determinants expressed by monocytes and by activated T cells in MAb OKT3-induced T cell proliferation, the effect of the four MAb on MAb OKT3-induced T cell proliferation in a monocyte-dependent and in a monocyte-free system was studied. Dose-response and proliferation kinetics studies showed that the four MAb display a similar inhibitory effect on MAb OKT3-induced T cell proliferation in a monocyte-free system. These results suggest fine differences in the role played by monocyte- and T cell-bound HLA Class II determinants in the regulation of MAb OKT3-induced T cell proliferation. This functional heterogeneity may enhance the flexibility of HLA Class II antigens to mediate cell-cell interactions involved in the proliferative response to a variety of mitogenic stimuli.


Deep Learning and Artificial Intelligence Applied to Model Speech and Language in Parkinson's Disease.
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in the world, and it is characterized by the production of different motor and non-motor symptoms which negatively affect speech and language production. For decades, the research community has been working on methodologies to automatically model these biomarkers to detect and monitor the disease; however, although speech impairments have been widely explored, language remains underexplored despite being a valuable source of information, especially to assess cognitive impairments associated with non-motor symptoms. This study proposes the automatic assessment of PD patients using different methodologies to model speech and language biomarkers. One-dimensional and two-dimensional convolutional neural networks (CNNs), along with pre-trained models such as Wav2Vec 2.0, BERT, and BETO, were considered to classify PD patients vs. Healthy Control (HC) subjects. The first approach consisted of modeling speech and language independently. Then, the best representations from each modality were combined following early, joint, and late fusion strategies. The results show that the speech modality yielded an accuracy of up to 88%, thus outperforming all language representations, including the multi-modal approach. These results suggest that speech representations better discriminate PD patients and HC subjects than language representations. When analyzing the fusion strategies, we observed that changes in the time span of the multi-modal representation could produce a significant loss of information in the speech modality, which was likely linked to a decrease in accuracy in the multi-modal experiments. Further experiments are necessary to validate this claim with other fusion methods using different time spans.


Simultaneous analysis of kynurenine and tryptophan in human plasma by capillary electrophoresis with UV detection.
Plasma kynurenine (Kyn)/tryptophan ratio has been proposed as a useful marker for the monitoring activation of the cellular immune system. Here, we describe an easy capillary electrophoresis method with UV detection for the separation and detection of Kyn and tryptophan in human plasma using methltryptophan as internal standard. The plasma samples were simply treated with acentonitrile for the elimination of proteins, the supernatant was evaporated, and the dried sample was resuspended with water and directly injected on the capillary without sample derivatization procedures. The use of a run buffer composed by 100 mmol/L Bis-Tris propane at pH 2.15 allowed to baseline resolve the analytes within 9 min. Precision tests indicated a good repeatability of our method both for times (CV< 0.53%) and areas (CV< 2.8%). Moreover, a good reproducibility of intra-assay and interassay tests was obtained (CV < 3.9% and CV < 7.6%, respectively). The obtained limit of detections for Kyn and tryptophane, evaluated at 226 nm, were 0.15 and 0.40 μmol/L, respectively. The method suitability was tested by measuring analyte levels both in healthy volunteers, acute myocardial infarction and chronic kidney disease patients.


Gas chromatography-mass spectrometry of sapucainha oil (Carpotroche brasiliensis) triacylglycerols comprising straight chain and cyclic fatty acids.
Sapucainha oil, which may be used to treat leprosy, comprises straight chain and cyclic fatty acids (FA), and triacylglycerols (TAG). The FA and TAG content of the oil sample was analysed using gas chromatography-electron ionisation mass spectrometry (GC-EIMS). FA analysis was performed after derivatisation to fatty acid methyl esters (FAME). For free FA and TAG analysis, the oil sample was dissolved in hexane and injected into a short, high-temperature column, for GC with MS analysis. Free FA and FAME were tentatively identified based on mass spectrum information of their molecular and fragment ions, as well as library matching. Overlapping TAG peaks were deconvoluted based on mass fingerprint data. The FA composition was utilised to predict possible TAG identities. FA residues of TAG were identified based on characteristic fragment ions, such as [M-RCO2]+, [RCO+128]+, [RCO+74]+ and RCO+ where R is the aliphatic hydrocarbon chain. FAME analysis showed that the cyclic FA hydnocarpic (36.1%), chaulmoogric (26.5%) and gorlic (23.6%) acids were the major components. In addition, straight chain FA such as palmitic, palmitoleic, stearic, oleic and linoleic acids were detected. Palmitic, oleic, hydnocarpic, chaulmoogric and gorlic acids were also detected as free FA in the oil sample. Six groups of TAG peaks were eluted from GC at temperatures ≥330 °C. After deconvolution and mass spectrum analysis, each TAG peak group was revealed to comprise 2 to 5 co-eluted TAG molecules; >18 TAG were identified. These TAG consisted of a mix of both cyclic and straight chain FA, but were mostly derived from cyclic FA.


A permanent hole burning study of the FMO antenna complex of the green sulfur bacterium Prosthecochloris aestuarii.
A permanent hole burning study on the Fenna-Matthews-Olson, or FMO, antenna complex of the green sulfur bacterium Prosthecochloris aestuarii was carried out at 6 K. Excitation resulted not only in relatively sharp features resonant with the burn wavelength but also in broad absorbance changes in the wavelength region of 800-820 nm. The shape of the latter changes was almost independent of the wavelength of excitation. Evidence is given that they are induced by a different mechanism than that which causes the resonant holes and that they may be due to a conformational change of the protein. The original spectrum was restored upon warming to 60 K. The effective dephasing times T2, as obtained from the homogeneous line widths, increased from about 0.5 ps at 803 nm to >/=20 ps at 830 nm and are in good agreement with recent measurements of accumulated photon-echo and time-resolved absorbance changes.


Infrared Diffusion-Ordered Spectroscopy Reveals Molecular Size and Structure.
Inspired by ideas from NMR, we have developed Infrared Diffusion-Ordered Spectroscopy (IR-DOSY), which simultaneously characterizes molecular structure and size. We rely on the fact that the diffusion coefficient of a molecule is determined by its size through the Stokes-Einstein relation, and achieve sensitivity to the diffusion coefficient by creating a concentration gradient and tracking its equilibration in an IR-frequency resolved manner. Analogous to NMR-DOSY, a two-dimensional IR-DOSY spectrum has IR frequency along one axis and diffusion coefficient (or equivalently, size) along the other, so the chemical structure and the size of a compound are characterized simultaneously. In an IR-DOSY spectrum of a mixture, molecules with different sizes are nicely separated into distinct sets of IR peaks. Extending this idea to higher dimensions, we also perform 3D-IR-DOSY, in which we combine the conformation sensitivity of femtosecond multi-dimensional IR spectroscopy with size sensitivity.


Acoustic analysis of the voiced-voiceless distinction in Dutch tracheoesophageal speech.
Confusions between voiced and voiceless plosives and voiced and voiceless fricatives are common in Dutch tracheoesophageal (TE) speech. This study investigates (a) which acoustic measures are found to convey a correct voicing contrast in TE speech and (b) whether different measures are found in TE speech than in normal laryngeal (NL) speech. The main focus was on plosives. Nine TE and 5 NL speakers were included in this study. Fourteen acoustic measures were selected and analyzed. Comparisons were made between voiced and voiceless for the groups separately and between TE and NL speakers. Conditional inference trees were used to establish the most important distinguishing cue. TE speakers do not differ significantly from NL speakers, except for pitch-related measures. For plosives, all measures distinguished between voiced and voiceless for both speaker groups. The main distinguishing measure for the plosives was relative phonation time in the closure. TE and NL speakers differ less in the way the voiced-voiceless distinction is conveyed than expected. Further research is needed to show whether the main acoustic cue is also perceptually most relevant.


The thiopyran route to polypropionates: enantioselective synthesis of membrenone B from racemic fragments.
(6S,7S,8S,9R,10S)-(--)-Membrenone B was synthesized in nine steps (9.4% overall yield) beginning with two-directional aldol coupling of tetrahydro-4H-thiopyran-4-one with racemic 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde. The first aldol reaction occurs with dynamic kinetic resolution to give a single adduct (>98% ee). The second aldol reaction is highly diastereoselective (three of eight possible adducts), and both major products are converted to membrenone B. The route also constitutes a formal synthesis of membrenone A.


The immunomodulatory effect of lithium as a mechanism of action in bipolar disorder.
Bipolar disorder (BD) is a chronic mental disorder characterized by recurrent episodes of mania and depression alternating with periods of euthymia. Although environmental and genetic factors have been described, their pathogenesis is not fully understood. Much evidence suggests a role for inflammatory mediators and immune dysregulation in the development of BD. The first-line treatment in BD are mood-stabilizing agents, one of which is lithium (Li) salts. The Li mechanism of action is not fully understood, but it has been proposed that its robust immunomodulatory properties might be one of the mechanisms responsible for its effectiveness. In this article, the authors present the current knowledge about immune system changes accompanying BD, as well as the immunomodulatory effect of lithium. The results of studies describing connections between immune system changes and lithium effectiveness are often incoherent. Further research is needed to understand the connection between immune system modulation and the therapeutic action of lithium in BD.


Breaking a cycle of hospitalization through the psychiatric house call.
The authors discuss a case in which family therapy administered in a home setting helped to break a cycle of psychiatric hospitalization that had continued for ten years. Their patient had adopted a persistent behavioral pattern involving protective magic rituals and consultations with spirits as a defense against other problems in her family relationships. With regular visits from the therapists and cooperation from each member of the family, the patient's symptoms were ameliorated and the family situation greatly improved after eight months. The authors believe that because they worked with the entire family as a system, were able to recognize sociocultural factors that had not been dealt with in the patient's hospitalizations, and were able to stimulate communication among family members in a home setting, they were able to see more immediate results and thus were able to break the costly cycle of repeated hospitalizations.


Improved biochemical disease-free survival of men younger than 60 years with prostate cancer treated with high dose conformal external beam radiotherapy.
We report the long-term prostate specific antigen relapse-free survival rates and predictors of biochemical outcome for patients 60 years or younger with prostate cancer treated with high dose conformal external beam radiotherapy. We retrospectively reviewed the records of 740 patients with prostate cancer treated with 3-dimensional conformal radiotherapy or intensity modulated external beam radiotherapy. Patients who also received androgen deprivation therapy were excluded from this analysis. Median radiation dose was 75.6 Gy and median followup was 88 months with a minimum followup of 24 months. Median followup for patients 60 years or younger in this report was 54 months (range 24 to 132). Biochemical failure was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. Biochemical failure developed in 20 (21%) of the 96 men 60 years or younger, which was similar to the 22% failure rate observed in 644 patients older than 60. The 5 and 7-year biochemical disease-free survival rates were 82% and 79% in younger men, and 79% and 78% in older men, respectively (p = 0.48). For younger patients who received 81 Gy or greater, the 7-year prostate specific antigen relapse-free survival rates for favorable, intermediate and unfavorable risk patients were 96%, 87% and 50%, respectively. Multivariate analysis revealed that among patients 60 years or younger the most important predictor of biochemical relapse was radiation doses less than 75.6 Gy followed by Gleason score greater than 7. Men with prostate cancer 60 years or younger treated with high dose radiotherapy have an excellent biochemical outcome and fare as well as older patients. The use of conventional dose levels in patients 60 years or younger was associated with an 8-fold increase in the biochemical relapse rate and these doses should not be considered appropriate for the treatment of localized prostate cancer.


Thoracoscopic findings of a small posterior mediastinal parathyroid adenoma.
We report herein the rare case of a posterior mediastinal parathyroid adenoma 8 mm in diameter, that was identified by both 99m-technetium-methoxyisobutylisonitrile scintigraphy (Tc-MIBI) and high-resolution chest computed tomography (HRCT). Thoracoscopy clearly showed a mediastinal parathyroid adenoma which was successfully removed.


Construction of SH-EP1-alpha4beta2-hAPP695 cell line and effects of nicotinic agonists on beta-amyloid in the cells.
(1) Nicotinic acetylcholine receptors in central nervous system are thought to be new targets for Alzheimer's disease. However, the most involved nicotinic receptor subtype in Alzheimer's disease is unclear. alpha4beta2 receptor is the most widely spread subtype in brain, involving in several important aspects of cognitive and other functions. We constructed cell line by transfecting human amyloid precursor protein (695) gene into SH-EP1 cells which have been transfected with human nicotinic receptor alpha4 subunit and beta2 subunit gene, to observe effects of alpha4beta2 receptors activation on beta-amyloid, expecting to provide a new cell line for drug screening and research purpose. (2) Liposome transfection was used to express human amyloid precursor protein (695) gene in SH-EP1-alpha4beta2 cells. Function of the transfected alpha4beta2 receptors was tested by patch clamp. Effects of nicotine and epibatidine (selective alpha4beta2 nicotinic receptor agonist) on beta-amyloid were detected by Western blot and ELISA. Effects of nicotine and epibatidine on amyloid precursor protein (695) mRNA level were measured using real-time PCR. (3) Human amyloid precursor protein (695) gene was stably expressed in SH-EP1-alpha4beta2 cells; Nicotine (1 muM) and epibatidine (0.1 muM) decreased intracellular and secreted beta-amyloid in the cells; and activation of alpha4beta2 receptors did not affect amyloid precursor protein (695) mRNA level. (4) These results suggest that the constructed cell line, expressing both amyloid precursor protein (695) gene and human nicotinic receptor alpha4 subunit and beta2 subunit gene, might be useful for screening specific nicotinic receptor agonists against Alzheimer's disease. Alteration of Abeta level induced by activation of alpha4beta2 nAChR in our study might occur at a post-translational level.


Effect of immunosuppressive therapy for renal allografts on the number of circulating sheep red blood cells rosetting cells.
Patients receiving renal allografts from relatively incompatible donors were randomly assigned to one of two immunosuppressive regimens: azathioprine and prednisone with or without a 2-week course of horse antihuman thymocyte globulin (ATG). The number of circulating lymphocytes fell to about one-third of pretreatment values in both groups of patients. In patients given ATG, the proportion of sheep red blood cell-rosetting lymphocytes (SRBC-R) fell promptly to less than 10% of pretreatment values. In contrast, the percentage of SRBC-R remained at about 70% in patients receiving only prednisone and azathioprine. The addition of ATG reduced the number of SRBC-R/mm3 to one-tenth to one-thirtieth the number seen in non-ATG-treated patients. Plasma of patients undergoing therapy did not inhibit rosetting in vitro. It is proposed that the monitoring of circulating rosetting cells may be a useful clinical guide to the degree of T cell immunosuppression. It is also suggested that the regimen of azathioprine, prednisone, and ATG results in a more effective suppression of circulating T cells than that produced by azathioprine and prednisone alone.


Risk of lung cancer from residential heating and cooking fuels in Montreal, Canada.
Among the major sources of indoor air pollution are combustion by-products from heating and cooking. Concern is increasing that use of polluting heating and cooking sources can increase cancer risk. In Canada, most cooking and heating currently relies on electricity or natural gas, but, in the past, and still in some areas, coal and wood stoves were used for heating and gas and wood for cooking. In the course of a case-control study of lung cancer carried out in Montreal in 1996-2001, the authors collected information on subjects' lifetime exposure to such sources of domestic pollution by means of a personal interview with the subject or a next-of-kin proxy. Questionnaires were completed for 739 male cases, 925 male controls, 466 female cases, and 616 female controls. Odds ratios were computed in relation to a few indices of exposure to traditional heating and cooking sources, adjusting for a number of covariates, including smoking. Among men, there was no indication of excess risks. Among women, the odds ratio for those exposed to both traditional heating and cooking sources was 2.5 (95% confidence interval: 1.5, 3.6; n = 253). The findings for women suggest the need for research dedicated to exploring this association, with particular emphasis on improved exposure assessment.


Utilization of matrix-assisted laser desorption and ionization time-of-flight mass spectrometry for identification of infantile seborrheic dermatitis-causing Malassezia and incidence of culture-based cutaneous Malassezia microbiota of 1-month-old infants.
Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has been utilized for identification of various microorganisms. Malassezia species, including Malassezia restricta, which is associated with seborrheic dermatitis, has been difficult to identify by traditional means. This study was performed to develop a system for identification of Malassezia species with MALDI-TOF-MS and to investigate the incidence and variety of cutaneous Malassezia microbiota of 1-month-old infants using this technique. A Malassezia species-specific MALDI-TOF-MS database was developed from eight standard strains, and the availability of this system was assessed using 54 clinical strains isolated from the skin of 1-month-old infants. Clinical isolates were cultured initially on CHROMagar Malassezia growth medium, and the 28S ribosomal DNA (D1/D2) sequence was analyzed for confirmatory identification. Using this database, we detected and analyzed Malassezia species in 68% and 44% of infants with and without infantile seborrheic dermatitis, respectively. The results of MALDI-TOF-MS analysis were consistent with those of rDNA sequencing identification (100% accuracy rate). To our knowledge, this is the first report of a MALDI-TOF-MS database for major skin pathogenic Malassezia species. This system is an easy, rapid and reliable method for identification of Malassezia.


Malignant pleural mesothelioma: adjuvant therapy with radiation therapy.
It is a challenge to treat malignant pleural mesothelioma with radiation therapy (RT). For many years, conventional RT was delivered after extrapleural pneumonectomy (EPP) with acceptable results. However, the benefit of RT has never been definitively proven. Intensity modulated radiation therapy (IMRT) has been used, but some of the early experiences revealed fatal toxicity. As experience has increased, it now appears that RT, particularly with IMRT, is both feasible and effective.


Secretion of matrix metalloproteinase-2 and -9 after mechanical trauma injury in rat cortical cultures and involvement of MAP kinase.
Matrix metalloproteinases (MMP) are involved in the pathophysiology of brain injury. We recently showed that knockout mice deficient in MMP-9 expression were protected against traumatic brain injury. However, the cellular sources of MMP activity after trauma remain to be fully defined. In this study, we investigated the hypothesis that resident brain cells secrete MMP after mechanical trauma injury in vitro, and mitogen-activated protein (MAP) kinase signal transduction pathways are involved in this response. Rat primary cortical neurons, astrocytes, and co-cultures were subjected to needle scratch mechanical injury, and levels of MMP-2 and MMP-9 in conditioned media were assayed by zymography. MMP-2 and MMP-9 were increased in cortical astrocytes and co-cultures, whereas only MMP-2 was increased in neurons. Western blots showed that phosphorylated extracellular signal regulated kinase (ERK1/2) and p38 were rapidly upregulated in co-cultures after mechanical injury. No change in phosphorylated c-jun N-terminal kinase (JNK) was observed. In-gel kinase assays confirmed this lack of response in the JNK pathway. Treatment with either 10 microM of U0126 (a MAP kinase/ERK1/2 kinase inhibitor) or 10 microM of SB203580 (a p38 inhibitor) had no detectable effect on MMP-2 and MMP-9 levels after mechanical injury. However, combination treatment with both inhibitors significantly reduced secretion of MMP-9. Herein, we demonstrate that (1) resident brain cells secrete MMP after mechanical injury, (2) astrocytes are the main source of MMP-9 activity, and (3) ERK and p38 MAP kinases are upregulated after mechanical injury, and mediate the secretion of MMP-9.


[Treatment outcomes of colon cancer surgery combined with radical lymphadenectomy].
The authors analyzed a group of 1281 subjects with colorectal cancer operated and followed up in a single institution from I/1992 to VIII/2007. Colon carcinoma patients were assessed separately (C18). Patients with rectal and rectosigmoid tumors are not included in the presentation. A total of 846 patients were operated for colon carcinomas. In 546 subjects, radical R0 resections were achieved. In the R0 group, the male/female ratio is 315/231, age 29-94 years, the mean age of 69 years. The R0 group stratification by TNM classification was: I 17.8%, II 49.6%, III 24.0%, IV 8.1%, TNMx 0.5%. Irrespective of the TNM staging, three-year, five-year and ten-year survival rates were 80%, 71%, and 51%, resp. The median survival time was 9.85 years. Postoperative morality was 5.5%, morbidity 29.8%, anastomic leak occured in 5.7%. Systematic lymph node dissection up to the apical level, had been gradually introduced as an integral part of the R0 surgery. The aim of the study is to analyze outcomes of the colon carcinoma surgical management, combined with radical lymphadenectomy. Furthermore, effects of the extensive procedure on the postoperative morbidity and moratility rates are analyzed as well.


Cocaine enhances figural, but impairs verbal 'flexible' divergent thinking.
Anecdotal evidence suggests that cocaine use will help overcome creative 'blocks' by enhancing flexible thinking. Given that cocaine is likely to enhance dopamine (DA) levels, which in turn are positively associated with divergent thinking (DT); is a possibility that is tested in the present study. Furthermore, the impact of cocaine is tested on convergent thinking (CT), another aspect of creative thinking, which has been reported to be impaired with high DA levels. It was hypothesized that cocaine would enhance DT and impair CT. A placebo-controlled within-subjects study including 24 healthy poly-drug users was set up to test the influence of oral cocaine (300 mg) on creativity. Verbal CT was assessed with the Remote Associates Task (RAT); figural CT was assessed with the Picture Concepts Task (PCT) and the Tower of London (TOL). Verbal DT was assessed with the Alternative Uses Task (AUT); figural DT was assessed with the Pattern/Line Meanings Task (PLMT). Findings showed that, compared to placebo, cocaine impaired figural CT (TOL) and flexible DT of verbal stimuli (AUT), while it enhanced figural DT (PLMT). No significant effects of cocaine were observed regarding the PCT and RAT. It was demonstrated that cocaine-induced effects on creativity in poly-drug users are stimulus-dependent. Cocaine enhanced performance on figural DT but impaired performance on verbal (flexible) DT. Cocaine impaired CT on only one figural task and but not on the other tasks. As creativity is an important aspect in cognitive therapies, it is important to further understand these discrepancies in creativity task performance.


Congenic interval mapping of RNO10 reveals a complex cluster of closely-linked genetic determinants of blood pressure.
Genetic dissection of the rat genome for identifying alleles that cause abnormalities in blood pressure (BP) resulted in the mapping of a significant number of BP quantitative trait loci (QTLs). In this study we mapped at least one such BP QTL on rat chromosome 10 (RNO10) as being within the introgressed segment of a S.LEW congenic strain S.LEWx12x2x3x8 spanning 1.34 Mb from 70,725,437 bp to 72,063,232 bp. BP of 3 congenic strains that span shorter segments of this region was additionally examined. Results obtained indicate that LEW alleles that comprise a 375-kb introgressed segment of the congenic strain S.LEWx12x2x3x5 (70,725,437 bp to 71,100,513 bp) increase BP. The magnitude of change in BP exhibited by the 2 strains, S.LEWx12x2x3x8 and S.LEWx12x2x3x5, is the net phenotypic effect of the underlying genetic determinants of BP. In this respect, the current data are superior to previous QTL localization of BP QTL1, which was hypothesized based on differential congenic segments. Genetic dissection using these 2 congenic strains as tools is expected to facilitate further dissection of the regions. Meanwhile, differential congenic segments were used to predict and thereby prioritize regions for candidate gene analysis. Using this approach, 2 distinct regions of 401 kb and 409 kb within S.LEWx12x2x3x8 and a 104 kb region within S.LEWx12x2x3x5 were prioritized for further consideration. Because all of these genetic elements are located within a 1.06-Mb region of RNO10, our study has revealed a remarkable insight into a genomic module comprising very closely-linked, opposing genetic determinants of BP.


The hamster (Mesocricetus auratus) as an experimental model of toxocariasis: histopathological, immunohistochemical, and immunoelectron microscopic findings.
Toxocariasis is a globally distributed parasitic infection caused by the larval stage of Toxocara spp. The typical natural hosts of the parasite are dogs and cats, but humans can be infected by the larval stage of the parasite after ingesting embryonated eggs in soil or from contaminated hands or fomites. The migrating larvae are not adapted to complete their life cycle within accidental or paratenic hosts like humans and laboratory animals, respectively, but they are capable of invading viscera or other tissues where they may survive and induce disease. In order to characterize hamsters (Mesocricetus auratus) as a model for Toxocara canis infection, histopathological and immunohistochemistry procedures were used to detect pathological lesions and the distribution of toxocaral antigens in the liver, lungs, and kidneys of experimentally infected animals. We also attempted to characterize the immunological parameters of the inflammatory response and correlate them with the histopathological findings. In the kidney, a correlation between glomerular changes and antigen deposits was evaluated using immunoelectron microscopy. The hamster is an adequate model of experimental toxocariasis for short-term investigations and has a good immunological and pathological response to the infection. Lung and liver manifestations of toxocariasis in hamsters approximated those in humans and other experimental animal models. A mixed Th2 immunological response to T. canis infection was predominant. The hamster model displayed a progressive rise of anti-toxocaral antibodies with the formation of immune complexes. Circulating antigens, immunoglobulin, and complement deposits were detected in the kidney without the development of a definite immune complex nephropathy.


A new anthraquinone from Gladiolus gandavensis.
A new anthraquinone, 1,6,7-trihydroxy-3-methoxyanthraquinone, along with three known compounds methyl trans-p-hydroxycinnamate, eugenin and 1,3,6-trihydroxy-8-methylanthraquinone, were isolated from the subterranean rhizomes of Gladiolus gandavensis Van Houtt. Their structures were established on the basis of spectroscopic data including 2D NMR techniques and chemical methods.


Frey syndrome in neurofibromatosis 1.
A healthy 18-month-old girl presented with a history of intermittent hemifacial flushing when eating. Her symptom seemed to be exclusively triggered by chewing. Examination revealed cutaneous features of neurofibromatosis type 1 (NF1) and mild facial asymmetry. Imaging confirmed cerebral vacuolisation changes seen in NF1 and a left facial plexiform neurofibroma involving the parotid gland. This is the first reported case of Frey syndrome complicating NF1.


Analysis of plasma free amino acid profiles in canine brain tumors.
Canine brain tumors are best diagnosed using magnetic resonance imaging (MRI). However, opportunities of MRI examination are restricted due to its limited availability in veterinary facilities; thus, numerous canine brain tumors are diagnosed at an advanced stage. Therefore, development of a noninvasive diagnostic biomarker is required for the early detection of brain tumors. In the present study, plasma free amino acid (PFAA) profiles between dogs with and without brain tumors were compared. A total of 12 dogs with brain tumors, diagnosed based on clinical signs, and on the results of intracranial MRI and/or pathological examination were evaluated. In addition, eight dogs diagnosed with idiopathic epilepsy and 16 healthy dogs were also included. A liquid chromatography system with automated pre-column derivatization functionality was used to measure the levels of 20 amino acids. As a result, the levels of three amino acids (alanine, proline and isoleucine) were increased significantly (1.6-, 1.5- and 1.6-fold, respectively) in the plasma of dogs with brain tumors as compared with the levels in control dogs (all P<0.05). Thus, the PFAA levels of dogs with brain tumors differed from those of healthy dogs. The present study demonstrated that analysis of PFAA levels of dogs with brain tumors may serve as a useful biomarker for the early detection of canine brain tumors.


A narrative review of neuromonitoring modalities in critically ill children.
Acute neurologic injury is common in critically ill children. Some conditions - such as traumatic brain injury, meningitis, and hypoxic-ischemic injury following cardiac arrest - require careful consideration of cerebral physiology. Specialized neuromonitoring techniques provide insight regarding patient-specific and disease-specific insight that can improve diagnostic accuracy, aid in targeting therapeutic interventions, and provide prognostic information. In this review, we will discuss recent innovations in invasive (e.g., intracranial pressure monitoring and related computed indices) and noninvasive (e.g., transcranial doppler, near-infrared spectroscopy) neuromonitoring techniques used in traumatic brain injury, central nervous system infections, and after cardiac arrest. We will discuss the pertinent physiological mechanisms interrogated by each technique and discuss available evidence for potential clinical application. We will also discuss the use of innovative neuromonitoring techniques to detect and manage neurologic complications in critically ill children with systemic illness, focusing on sepsis and cardiorespiratory failure requiring extracorporeal membrane oxygenation.


[New Implementation Technique of USED Phase Matching for CARS].
Phase matching is one of the key techniques in temperature measuring by coherent anti-Stokes Raman scattering (CARS). In order to overcome the disadvantages of large background radiation, inconvenient adjusting and low-usage of Stokes laser energy in traditional unstable-resonator spatially enhanced detection (USED) phase matching, new implementation technique of USED CARS phase matching is researched. A piece of oblique reflector, which is as big as the Stokes spot and with an angle of 45 degrees, was used to replace the annular reflector in traditional USED to reflect the Stokes fully. Then, pump laser shines from the back of the oblique reflector to satisfy USED phase matching with reflected Stokes. In the new USED CARS phase matching, background radiation caused by reflecting was weakened for the area of oblique reflector is smaller than that of annular reflector; Furthermore, oblique reflector can be used as an adjusting component in experiments which can make beam path adjusting more easier; Finally, Stokes laser was in high-usage for it was fully reflected by the oblique reflector. Temperature measuring results on laminar flame suggest that new USED CARS phase matching has lower standard deviation and it is a more effective phase matching method.


Stromal changes following removal of epithelium in rat cornea.
Morphologic and metabolic changes were studied in the corneal stroma of the rat eye following denudation of the epithelium. By touching the cornea with a glass slide coated with 10% gelatin the epithelium was removed with minimal trauma to the underlying stroma. The underlying superficial keratocytes degenerated promptly leaving an anterior acellular zone within 12 hours. At 24 hours wandering cells invaded this damaged stroma, coincident with reepithelialization of the surface. This suggests not only an interaction of epithelium and keratocytes but also of epithelium and wandering cells. Repair of the acellular zone began about 24 hours after the denudation. At 48 hours mitotic figures were abundant with vigorous incorporation of the 3H-thymidine in the remaining keratocytes. The acellular zone became repopulated with new stromal cells advancing from the posterior stroma toward the anterior stroma.


Rifampicin, a keystone inducer of drug metabolism: from Herbert Remmer's pioneering ideas to modern concepts.
In 1972, Herbert Remmer's group at the University of Tübingen had developed a micro method to assess cytochrome P450 contents and activities of drug metabolising enzymes in needle biopsies from human liver. Upon application of this method to patients receiving different kinds of drug therapy, Herbert Remmer was the first to describe that total human hepatic cytochrome P450 was markedly elevated by the new anti-tuberculosis drug rifampicin. Similar observations were made for the antimycotic clotrimazol. In 1975, Herbert Remmer's group described the unique species difference that induction of cytochrome P450 by rifampicin did not occur in the rat. After the first clinical reports of impaired effectiveness of oral contraception in persons treated with rifampicin, studies at Herbert Remmer's Institute showed a 4-fold increase, after repetitive rifampicin administration to humans, in the ability of hepatic microsomes to ortho-hydroxylate the contraceptive estrogen ethinylestradiol, compared to microsomes from untreated normal subjects. Subsequent pharmacokinetic investigations were compatible with this induction of the estrogen-2-hydroxylase by rifampicin and provided a rational explanation for the classical drug interaction between rifampicin and oral contraceptives. These early studies, in the 1970s in Tübingen, were followed by further developments. It was realized that the cytochrome P450 isoenzyme 3A4 (CYP3A4) is the major CYP isozyme in the human liver metabolizing a variety of xenobiotics and endobiotics, being also responsible for the 2-hydroxylation of ethinylestradiol. The inducibility of CYP3A4 by barbiturates and rifampicin explains the effects of inducers to enhance the clearance of ethynylestradiol and thereby to reduce the effectiveness of oral contraceptives, rifampicin being one of the most potent inducers of human CYP3A4 gene expression. Since 1998, novel "orphan" members of the nuclear hormone receptor superfamily were cloned from mouse, rat, rabbit, and human origin. These so-called pregnane X receptors (PXR), across species, are activated by inducers of CYP3A4 expression. It now appears that PXR is a key mediator of complex induction processes of xenobiotic processing enzymes, which are triggered by rifampicin and other inducers. Studies of the structure and substrate affinities of PXR have provided the rational explanation of the unique species difference of rifampicin induction between humans and rats that was first described by Herbert Remmer.


International consensus on histologic diagnosis of early hepatocellular neoplasia.
1. The precursor lesions for the development of hepatocellular carcinoma are believed to be high-grade dysplastic nodules. These lesions have atypical and proliferative features that distinguish them from normal or cirrhotic liver but are not sufficient for the diagnosis of carcinoma. 2. Individual HGDN are often heterogeneous and complete sampling may reveal regions of carcinoma within these otherwise benign lesions. 3. Invasion of stroma is considered a definitive feature of HCC. However, this feature is not always present in early HCC and is seldom found in needle biopsies. 4. Accurate diagnosis of dysplastic nodules and well-differentiated HCC requires skill and experience. However, accurate diagnosis with needle biopsies may be impossible if the highest grade of atypia is not sampled. Fine needle aspiration is not appropriate for small lesions that are expected to be early hepatic neoplasia. This technique should be reserved for suspected moderate- or poorly differentiated HCC.


Sounds in the ocean at 1-100 Hz.
Very-low-frequency sounds between 1 and 100 Hz propagate large distances in the ocean sound channel. Weather conditions, earthquakes, marine mammals, and anthropogenic activities influence sound levels in this band. Weather-related sounds result from interactions between waves, bubbles entrained by breaking waves, and the deformation of sea ice. Earthquakes generate sound in geologically active regions, and earthquake T waves propagate throughout the oceans. Blue and fin whales generate long bouts of sounds near 20 Hz that can dominate regional ambient noise levels seasonally. Anthropogenic sound sources include ship propellers, energy extraction, and seismic air guns and have been growing steadily. The increasing availability of long-term records of ocean sound will provide new opportunities for a deeper understanding of natural and anthropogenic sound sources and potential interactions between them.


[Assessment of the prognosis in patients who remain comatose after resuscitation from cardiac arrest].
In Denmark there are around 3,500 unexpected cardiac arrests (CA) out of hospital each year. There is an unknown number of CA in hospitals. The survival rate after CA outside a hospital in Denmark is 10% after 30 days. There are varying data for the neurological outcome in this group of patients. The purpose of this work is to disseminate new knowledge and to help standardizing the treatment in the group of patients who remain comatose after being resuscitated from CA. Assessment of the prognosis for a patient in this group can be made after 72 hours and a multi-modal approach to the patient is required.