Simultaneous analysis of trans- and cis-isomers of 2-glucosyloxycinnamic acids and coumarin derivatives in Dendrobium thyrsiflorum by high-performance liquid chromatography (HPLC)-photodiode array detection (DAD)-electrospray ionization (ESI)-tandem mass spectrometry (MS).
A novel method has been developed for simultaneous analysis for three pairs of trans- and cis-isomers of 2-glucosyloxycinnamic acids, along with their biogenic metabolites (three coumarin derivatives including scopoletin, scoparone and ayapin) in a Chinese medicinal herb Dendrobium thyrsiflorum by using high-performance liquid chromatography (HPLC)-photodiode array detection (DAD)-electrospray ionization (ESI)-tandem mass spectrometry (MS). The method was carried out by using a Polaris C18 column with a gradient solvent system of 0.5% acetic acid aqueous solution-acetonitrile. Seven target analytes including isodensifloside, isothyrsifloside, densifloside, thyrsifloside, scoparone, ayapin and scopoletin were exclusively identified by comparing their retention behaviors, UV and MS spectra with the authentic standards, and their contents in D. thyrsiflorum were simultaneous determined by employing UV detection at 342 nm. In addition, another pair of isomers of 2-glucosyloxycinnamic acids was putatively elucidated mainly based on the MS fragmentation. The method was validated and found to be satisfactorily linear, selective and robust. Recoveries ranged from 95.56 to 97.94% for all compounds at three different spiking levels. The limits of detection (LOD) and quantitation (LOQ) ranged, respectively, from 0.02 to 0.13 microg mL(-1) and 0.07 to 0.39 microg mL(-1) depending on various compounds. The established quality evaluation method was successfully used for evaluating the quality of D. thyrsiflorum samples of different organs and collections.


Tuberculous pericarditis: ten year experience with a prospective protocol for diagnosis and treatment.
Thirteen patients with tuberculous pericarditis (12 men and 1 woman aged 13 to 70 years [mean 41]) were identified in a group of 294 patients consecutively admitted for primary acute pericardial disease. The diagnosis was made by the following studies: sputum culture (n = 4), culture of pericardial fluid obtained by pericardiocentesis (n = 3), histologic study and culture of pericardial biopsy (n = 3), lymph node biopsy (n = 2) and pleural biopsy (n = 1). Clinical presentation was remarkably variable: four patients had an acute, apparently self-limited course, one had relapsing tamponade, four had tamponade effectively treated with pericardiocentesis and four had toxic symptoms with persistent fever. The interval from hospital admission to diagnosis ranged from 1 to 14 weeks (mean 5.2). Constrictive pericarditis developed in six patients and effusive-constrictive pericarditis in one; all seven required pericardiectomy 2 to 3.5 months after admission. No patient died. It is concluded that 1) tuberculous pericarditis has a variable clinical presentation and therefore it should be considered in the evaluation of all instances of pericarditis without a rapidly self-limited course; 2) the diagnosis should be based only on objective data obtained with a systematic study protocol; 3) early definitive diagnosis is still difficult to achieve; and 4) development of subacute constrictive pericarditis requiring pericardiectomy is common.


Quality Improvement Models and Methods for Maternal Health in Lower-Resource Settings.
Optimizing maternal health in lower-resource settings requires a joint focus to simultaneously increase skilled delivery care access and improve the quality of preventive and emergency maternal health care provided. Evidence-based interventions are largely established, yet despite increasing access, poor quality is limiting health gains. Assessing quality and implementing quality improvement approaches across varied health system levels is imperative to address health priorities. Evaluations of maternal care quality improvement suggest the need for enhancing standardized monitoring strategies and identifying optimal implementation strategies for translating findings into practice within different lower-resource settings to increase adoption and sustainability.


Treatment of pleural empyema.
To determine the clinical presentation and treatment strategies for children admitted with pleural empyema. Retrospective review of medical and radiological records of 54 patients admitted with pleural empyema between January 1989 and April 1997. Fever (98%), cough (83%), chest pain (38%), clinical cyanosis (17%) and abdominal pain (16%) were common clinical features. The causative organism was identified in 17 patients (31%). Intravenous antibiotics were given for a mean of 18. 2 +/- 7.5 days. Forty-seven (87%) patients had closed chest tube drainage and 21(39%) patients underwent decortication for unsatisfactory response to medical treatment. The chest tube insertion was more likely to be delayed in patients who required decortication, although the difference was not significant (8.1 +/- 5.4 vs 6.3 +/- 5.2 days of illness, P = 0.67). All patients were discharged well, with almost complete resolution of the chest radiograph at 6 months. Intensive medical management with adequate chest tube drainage and appropriate antibiotics will result in full resolution for most patients. Surgical intervention is important in patients who fail to receive adequate treatment early in the disease.


Influence of acetyl homocysteine thiolactone on erythrocyte superoxide dismutase activity.
The administration of 8 mg of acetylhomocysteinethiolactone/kg body wt determines a significant (P less than 0.001) increase in rat erythrocyte superoxide dismutase activity.


[Diet and body weight at the beginning of the COVID-19 pandemic in Mexico].
Weight changes in adults have strong repercussions on people's health status. During the COVID-19 pandemic, these changes could be more evident due to the mandatory confinement, as well as eating habits and lifestyle. In this study, changes in diet and body weight in Mexican population at the beginning of COVID-19 lockdown period (weeks 4-7) were evaluated using an online survey. To identify the characteristics of the diet and the perceived change in body weight at the beginning of the COVID-19 pandemic in Mexico. Descriptive, cross-sectional study of 1281 people over 18 years of age, electronic survey in weeks 4-7 of confinement with sociodemographic data, food consumption and perception of body weight. The change in food consumption was 53.9%, finding differences according to gender in beverages (carbonated, juices, alcoholic), coffee/tea, fruits, legumes (p < 0.05). The perception of body weight increases by 3.4 (increased) and 2.1 (lowered) times more than the risk of change in diet. The dietary differences refer to a tendency to the type of food consumed, mainly sugary drinks, with the perception of changes in positive body weight in women.


Viral load testing among pregnant women living with HIV in Mutare district of Manicaland province, Zimbabwe.
Viral load (VL) monitoring of pregnant women living with HIV (PWLHIV) and antiretroviral therapy (ART) may contribute to lowering the risk of vertical transmission of HIV. The aims of this study were to assess the uptake of HIV VL testing among PWLHIV at entry to the prevention-of-mother-to-child transmission (PMTCT) services and identify facilitatory factors and barriers to HIV VL access. A retrospective, cross-sectional study was conducted at 15 health facilities in Mutare district, Manicaland Province, Zimbabwe from January to December 2018. This analysis was complemented by prospective interviews with PWLHIV and health care providers between October 2019 and March 2020. Quantitative data were analysed using descriptive and inferential statistical methods. Risk factors were evaluated using multivariate logistic regression. Open-ended questions were analysed and recurring and shared experiences and perceptions of PWLHIV and health care providers identified. Among 383 PWLHIV, enrolled in antenatal care (ANC) and receiving ART, only 121 (31.6%) had a VL sample collected and 106 (88%) received their results. Among these 106 women, 93 (87.7%) had a VL < 1000 copies/mL and 77 (73%) a VL < 50 copies/mL. The overall median duration from ANC booking to VL sample collection was 87 (IQR, 7-215) days. The median time interval for the return of VL results from date of sample collection was 14 days (IQR, 7-30). There was no significant difference when this variable was stratified by time of ART initiation. VL samples were significantly less likely to be collected at local authority compared to government facilities (aOR = 0.28; 95% CI 0.16-0.48). Barriers to VL testing included staff shortages, non-availability of consumables and sub-optimal sample transportation. Turnaround time was prolonged by the manual results feedback system. The low rate of HIV VL testing among PWLHIV in Mutare district is a cause for concern. To reverse this situation, the Ministry of Health should consider interventions such as disseminating antiretroviral guidelines and policies electronically, conducting regular PMTCT mentorship for clinical staff members, and utilising point of care testing and telecommunication devices like mHealth to increase uptake of VL testing and improve results turnaround time.


Long-term durability of valve-sparing root replacement in patients with and without connective tissue disease.
The goal of this study was to evaluate the long-term outcomes of valve-sparing root replacement in patients with connective tissue disease (CTD) and compare them with patients without CTD who underwent valve-sparing root replacement for root aneurysm. Of 487 patients, 380 (78%) did not have CTD and 107 (22%) had CTD; 97 (91%) with Marfan syndrome, 8 (7%) with Loeys-Dietz syndrome, and 2 (2%) with Vascular Ehlers-Danlos syndrome. Operative and long-term outcomes were compared. The CTD group was younger (36 ± 14 years vs 53 ± 12 years; P < .001), had more women (41% vs 10%; P < .001) and had less hypertension (28% vs 78%; P < .001) and bicuspid aortic valve (8% vs 28%; P < .001). Other baseline characteristics did not differ between the groups. Overall operative mortality was nil (P = 1.000); the incidence of major postoperative complications was 1.2% (0.9% vs 1.3%; P = 1.000) and did not differ between groups. Residual mild aortic insufficiency (AI) was more frequent in the CTD group (9.3% vs 1.3%, P < .001) with no difference in moderate or greater AI. Ten-year survival was 97.3% (97.2% vs 97.4%; log-rank P = .801). Of the 15 patients with residual AI, 1 had none, 11 remained mild, 2 had moderate, and 1 had severe AI on follow-up. Ten-year freedom from moderate/severe AI was 89.6% (hazard ratio, 1.05; 95% CI, 0.8-1.37; P = .750) and 10-year freedom from valve reoperation was 94.9% (hazard ratio, 1.21; 95% CI, 0.43-3.39; P = .717). The operative outcomes as well as long-term durability of valve-sparing root replacement is excellent in patients with or without CTD. Valve function and durability are not influenced by CTD.


Subfreezing growth of the sea ice bacterium "Psychromonas ingrahamii".
"Psychromonas ingrahamii," named for John L. Ingraham, was isolated from sea ice from off Point Barrow, Alaska. This large rod-shaped bacterium belongs to the gamma-Proteobacteria. "P. ingrahamii" is a psychrophilic, heterotrophic bacterium that is gas vacuolate and nonmotile. "P. ingrahamii" is notable in that it grows at a temperature of -12 degrees C with a generation time of 240 h. This is the lowest growth temperature of any organism authenticated by a growth curve.


Relation of leisure time, occupational, domestic, and commuting physical activity to health indicators in Europe.
To investigate relationships between physical activities in different domains (leisure time, occupational, domestic, commuting) and health indicators (self-rated health, body mass index). The short version of the International Physical Activity Questionnaire (IPAQ) and additional questions on domain specific physical activity were submitted face-to-face to 29,193 individual's age 15 years and older in the 27 member states of the Europe Union, 2 affiliated nations (Croatia, Turkey), and Cyprus North in 2005 as part of Eurobarometer 64.3. Leisure time physical activity (compared to no leisure time physical activity) was positively associated with self-rated health (males: Odds Ratio (OR)=2.85, 95% Confidence Interval (CI): 2.27, 3.58; females: OR=2.77, 95% C.I. 2.16, 3.56) and inversely with obesity (males: OR=0.65, 95% C.I. 0.50, 0.83; females: OR=0.46, 95% C.I. 0.34, 0.63). Being in the highest quartile of the total volume of physical activity expressed using metabolic equivalents (in MET-min/week) (compared to being in the lowest quartile) was not related to self-rated health (males: OR=0.99, 95% C.I. 0.81, 1.21; females: OR=1.19, 95% C.I 0.98, 1.43) or obesity (males: OR=1.25, 95% C.I., 0.99, 1.59; females: OR=1.26, 95% C.I. 1.02, 1.57). Gender-specific effects were observed for other domains of physical activity. Analysis on national levels showed pronounced relationships of leisure time physical activity to health indicators. Domains of physical activity being related to health indicators, they may pertain to surveillance.


Cultivating resiliency in patients with neurofibromatosis 2 who are deafened or have severe hearing loss: a live‑video randomized control trial.
Patients with NF2 who are deaf or have significant hearing loss face numerous and unique challenges which lead to poor quality of life, and thus may benefit from resiliency programs. We performed secondary data analyses on a single blind, randomized controlled trial of an 8 week mind-body resiliency program (the Relaxation Response and Resiliency program for Deaf NF2; d3RP-NF2) versus a health education control (Health Enhancement Program for Deaf NF2;dHEP-NF2) which showed improvement in quality of life (Funes in JAMA 2019, https://doi.org/10.1007/s11060-019-03182-3). Here we report on improvements in resiliency factors (i.e. optimism, gratitude, perceived social support, mindfulness, and perceived coping abilities) assessed at baseline, post-test and 6-month follow-up. Both programs were delivered via Skype using Communication Access Real-Time Translation. Patients who were randomized to the d3RP-NF2 program exhibited significant improvements from baseline to post-program in gratitude (Mdifference = 4.04, 95% CI 1.58-6.50; p = 0.002), perceived social support (Mdifference = 16.36, 95% CI 9.20-23.51; p < 0.001), mindfulness (Mdifference = 4.02, 95% CI 1.10-6.94; p = 0.008), perceived coping (Mdifference = 15.25, 95% CI 10.21-20.28; p < 0.001), and a non-significant trend of improvement in optimism (Mdifference = 1.15, 95% CI -0.14-12.44; p = 0.079). These improvements were all maintained through the 6-month follow up. Improvements in perceived coping (Mdifference = 12.34, 95% CI 4.75-19.93; p = 0.002), social support (Mdifference = 13.11, 95% CI 2.19-24.03; p = 0.02), and gratitude (Mdifference = 4.59, 95% CI 0.83-8.36; p = 0.018) were over and above the changes observed in those randomized to dHEP-NF2. The d3RP-NF2 sustainably improves multiple dimensions of resiliency. Promoting resiliency may be of utmost importance for this uderserved population.


A numerical model for aggregations formation and magnetic driving of spherical particles based on OpenFOAM®.
This work presents a numerical model for the formation of particle aggregations under the influence of a permanent constant magnetic field and their driving process under a gradient magnetic field, suitably created by a Magnetic Resonance Imaging (MRI) device. The model is developed in the OpenFOAM platform and it is successfully compared to the existing experimental and numerical results in terms of aggregates size and their motion in water solutions. Furthermore, several series of simulations are performed for two common types of particles of different diameter in order to verify their aggregation and flow behaviour, under various constant and gradient magnetic fields in the usual MRI working range. Moreover, the numerical model is used to measure the mean length of aggregations, the total time needed to form and their mean velocity under different permanent and gradient magnetic fields. The present model is found to predict successfully the size, velocity and distribution of aggregates. In addition, our simulations showed that the mean length of aggregations is proportional to the permanent magnetic field magnitude and particle diameter according to the relation : l¯a=7.5B0di3/2. The mean velocity of the aggregations is proportional to the magnetic gradient, according to : u¯a=6.63G˜B0 and seems to reach a steady condition after a certain period of time. The mean time needed for particles to aggregate is proportional to permanent magnetic field magnitude, scaled by the relationship : t¯a∝7B0. A numerical model to predict the motion of magnetic particles for medical application is developed. This model is found suitable to predict the formation of aggregations and their motion under the influence of permanent and gradient magnetic fields, respectively, that are produced by an MRI device. The magnitude of the external constant magnetic field is the most important parameter for the aggregations formation and their driving.


Anatomical variations of cystic artery, cystic duct, and gall bladder and their associated intraoperative and postoperative complications: an observational study.
Anatomical variations in the calots triangle encountered during laparoscopic cholecystectomy are not uncommon. Misidentification and misperception of these structures are the major cause of vasculobiliary injuries. This study was conducted to estimate the prevalence of anatomical variations of the cystic artery, cystic duct (CD), and gall bladder. This is the first study in India to access the rate of intraoperative and postoperative complications in anatomical variants compared to normal individuals. It was a prospective observational study on patients undergoing laparoscopic cholecystectomy in the department of General Surgery at the tertiary center of India. The calculated sample size was 298. Variations of the cystic artery, CD, and gall bladder along with intraoperative and postoperative complications were noted. The comparative analysis of intraoperative and postoperative complications and a subgroup analysis between anatomical variants and normal patients were performed. The most common variations were found in cystic arteries (16.8%). CD anomalies were present in 11.4% of patients, and gall bladder anomalies were the least common of all (5.4%). Intraoperative and postoperative complications were compared between patients with anatomical variations and normal anatomy. Intraoperative complications in patients with anatomical variations were significantly higher. Bile leak (15.7% vs. 6.4%) (P=0.01), haemorrhage (16.8% vs. 1.9%) (P-value <0.001), conversion to open (3 vs. 0 patients) (P-value =0.03). Subgroup analysis revealed a strong association between intraoperative haemorrhage and bile leak with cystic artery and CD anomalies, respectively. Cystic artery anomalies are the most common variations. Patients with anatomical variations had significant intraoperative and postoperative complications compared to patients with normal anatomy.


Modelling European regional FDI flows using a Bayesian spatial Poisson interaction model.
This paper presents an empirical study of spatial origin and destination effects of European regional FDI dyads. Recent regional studies primarily focus on locational determinants, but ignore bilateral origin- and intervening factors, as well as associated spatial dependence. This paper fills this gap by using observations on interregional FDI flows within a spatially augmented Poisson interaction model. We explicitly distinguish FDI activities between three different stages of the value chain. Our results provide important insights on drivers of regional FDI activities, both from origin and destination perspectives. We moreover show that spatial dependence plays a key role in both dimensions.


Effect of prenatal exposure to diesel exhaust on dopaminergic system in mice.
Diesel exhaust (DE) is composed of particles and gaseous compounds. It has been reported that DE causes pulmonary and cardiovascular disease. We have previously reported that fetal exposure to DE had deleterious effects to the reproductive system of mice offspring. However, there is still little known about the effects of prenatal exposure to DE to the central nervous system (CNS). In the present study, we found that prenatal exposure to DE induced reduction of locomotion, furthermore, dopamine (DA) turnover was significantly decreased in the striatum and nucleus accumbens. These results suggest that prenatal exposure to DE has an effect on the CNS. Hypolocomotion could be due to a decrease in DA turnover associated with DA nervous system abnormality. The present study provides the possibility that maternally inhaled DE might influence the development of central dopaminergic system and result in behavior disorder.


Inhibition by cadmium of thymidine metabolism in concanavalin A-activated murine splenocytes.
Cadmium has been shown to cause significant inhibition of lymphocyte metabolism, including DNA synthesis, in both in vitro and in vivo studies. In order to understand more clearly the modification of DNA synthesis, this study has examined the metabolism of radiolabelled thymidine in splenocytes exposed to cadmium in vitro. T-lymphocyte-enriched splenocytes were incubated for 48 h with or without Conconavalin A. Cadmium (10 microM) was present during the full period of culture or added at various times after the initiation of the culture. Thymidine metabolism was assessed by examining intracellular metabolite pools, incorporation into DNA, thymidine kinase activity and thymidine membrane transport. Cadmium had little effect on any of these parameters in non-mitogen-stimulated cells. However, in concanavalin A-stimulated cells exposed to cadmium for the full period of culture, the changes in thymidine metabolism normally associated with mitogen activation including increased thymidine incorporation into DNA, expansion of the thymidine di- and triphosphate pools and increased thymidine kinase activity did not occur. Some membrane transport of thymidine did occur but it was less than that of non-cadmium-exposed concanavalin A-stimulated cells. Approximately 90% inhibition of thymidine incorporation into DNA occurs when cadmium is added any time during the first 26 h of culture. When cadmium is present only during the final 6 h of culture, the incorporation is inhibited by approximately 60%. Furthermore, the presence of cadmium during only the last 2 h of culture was shown to inhibit the membrane transport of thymidine, but had no effect on thymidine kinase activity.(ABSTRACT TRUNCATED AT 250 WORDS)


Less-Affected Hand Function Is Associated With Independence in Daily Living: A Longitudinal Study Poststroke.
The upper extremity (UE) ipsilateral to the brain lesion is mildly affected poststroke. It is unclear whether patients perceive this, and the association between less-affected hand function and independence in activities of daily living (ADL) is unknown. We aimed to (1) assess longitudinal changes in function, dexterity, grip strength, and self-perception of the less-affected UE, (2) compare them to the normative data, and (3) determine the association of both UEs to ADL during the first 6 months poststroke. Consecutive adults following a first stroke were assessed on rehabilitation admission (T1), 6 weeks (T2), and 6 months (T3) poststroke onset. Box and block test assessed function of both UEs. The functional dexterity test (FDT) and Jamar Dynamometer assessed dexterity and grip strength of the less-affected UE. The functional independence measure assessed ADL, and instrumental ADL was assessed at T3. Spearman correlations and multiple regression models were used. Participants were assessed at T1 (N=87), T2 (N=82), and T3 (N=68). At T1, less-affected UE deficits were apparent (median [interquartile range] box and block test-45 [35-53] blocks, FDT-44.5 [33.3-60.8] seconds, grip-25.5 [16.2-33.9] kilograms), but only 19.5% of the participants self-perceived this. Less-affected hand function significantly improved with 32% and 33% achieving a minimal clinically important difference for box and block test at T2 and T3, respectively. Dexterity improved significantly between T1 and T2 (P<0.001, no established minimal clinically important difference) and grip strength improved significantly between T2 and T3; 3.4% achieving a minimal clinically important difference (P<0.01). At T3, most participants did not reach the norms (box and block test-67.4 blocks, FDT-32.2 seconds, grip-40.5 kilograms). Both the less- and more-affected UEs explained a large portion of the variance of ADL at all time-points, after controlling for age, days-since-stroke-onset, stroke type, and cognition. Despite some improvement, the less-affected UE at 6 months poststroke remained below norms, explaining difficulties in ADL and instrumental ADL. Further research is needed.


Event centrality, transitional impact and symptoms of posttraumatic stress in a clinical sample.
Background and Objectives: There is growing research indicating that event centrality strongly predicts posttraumatic stress disorder (PTSD). However, there is not much research on what makes a traumatic event central to one's life story. One reason a traumatic memory becomes a reference point for one's life story is that it brings about significant changes in one's life. This study investigated the relationships between transitional impact of an event, event centrality, and PTSD symptoms. Specifically, it tested whether higher negative changes were associated with higher levels of event centrality and PTSD symptoms. It also investigated whether event centrality mediated the relationship between transitional impact and PTSD severity.Methods: 101 individuals diagnosed with PTSD completed the Transitional Impact Scale (TIS), Centrality of Event Scale, and Impact of Event Scale-Revised regarding their traumatic experiences. Furthermore, they responded to the Posttraumatic Stress Disorder Symptom Scale-Self Report (PSS-SR), Traumatic Events Checklist (TELC), and Beck Anxiety Inventory (BAI).Results and Conclusions: Results indicate that (a) the TIS had valid and reliable psychometric properties in a PTSD sample, (b) most of the traumatic events received high negative psychological and material change scores, and (c) event centrality mediated the relationship between transitional impact and PTSD severity.


Intrinsic properties of rostral ventrolateral medulla presympathetic and bulbospinal respiratory neurons of juvenile rats are not affected by chronic intermittent hypoxia.
The presympathetic neurons in the rostral ventrolateral medulla (RVLM) are considered to be the source of the sympathetic activity, and there is experimental evidence that these cells present intrinsic autodepolarization. There is also evidence that an important respiratory neuronal population located in the RVLM/Bötzinger complex (BötC) corresponds to augmenting expiratory neurons (aug-E), which send projections to the phrenic nucleus in the spinal cord. However, the pacemaker activity of presympathetic neurons and the intrinsic properties of aug-E neurons had not been evaluated in brainstem slices of juvenile rats (postnatal day 35). Chronic intermittent hypoxia (CIH) is a sympathetic-mediated hypertension model, which seems to produce an associated increase in the activity of aug-E neurons. In this study, we evaluated the effects of CIH on the intrinsic properties of RVLM/BötC presympathetic and phrenic nucleus-projecting neurons (aug-E) in brainstem slices of juvenile rats (postnatal day 35). We observed that all presympathetic neurons presented spontaneous action potential firing (n = 18), which was not abolished by ionotropic receptor antagonism. In addition, exposure to 10 days of CIH produced no changes in their intrinsic passive properties, firing pattern or excitability. Most aug-E neurons presented spontaneous firing in control conditions (13 of 15 neurons), and this characteristic was preserved after blocking fast synaptic transmission (12 of 15 neurons), clearly demonstrating their intrinsic pacemaker activity. Chronic intermittent hypoxia also produced no changes in intrinsic passive properties, frequency and pattern of discharge or excitability of the aug-E neurons. The present study shows that: (i) it is possible to record the electrophysiological properties of RVLM/BötC presympathetic and aug-E neurons in brainstem slices from juvenile rats; (ii) these neurons present characteristics of intrinsic pacemakers; and (iii) their intrinsic properties were not altered by chronic intermittent hypoxia.


Myelodysplastic syndrome and successful pregnancy.
A case of successful pregnancy in a 47-year-old Omani grand-multipara who had Myelodysplastic Syndrome (MDS) is described for the first time in Oman. A review of the literature suggests that in Japan the problem may be more common than elsewhere. The unusual features in the case reported here include, improvement in haematological parameters during the pregnancy contrary to expectation, and in addition, the religious and cultural factors that intruded into the clinical decision making process. Suggestions to combat the latter factors are made.


Psychological care for people with melanoma: what, when, why and how?
To provide an update on the psychosocial challenges faced by people with melanoma, and ways of addressing barriers to supportive care. Refereed journal articles, scholarly texts, monographs. Psychological needs of people with melanoma frequently go undetected and unmet. Approximately 30% of all patients diagnosed with melanoma report levels of psychological distress, indicating the need for clinical assessment and support. Psychological interventions using a range of therapeutic approaches can improve quality of life and enhance resilience in people with melanoma, including reducing anxiety and depression. Nurses can help institute and promote supportive care programs that incorporate these interventions.


Effect of three obturation techniques on the filling of lateral canals and the main canal.
The three-dimensional obturation of the root canal system is widely accepted as a key factor for successful endodontic therapy. The purpose of this study was to evaluate the obturation of lateral canals and the main canal using three gutta-percha sealer techniques: cold lateral condensation, warm lateral condensation, and warm vertical condensation. Sixty epoxied blocks with five lateral canals placed at varying angles from the main canal were used. Each experimental group was treated by a board-certified endodontist with training and clinical experience in that obturation technique. There was no statistically significant difference (p < 0.05) between the obturation techniques in the ratio of the void area to the gutta-percha-plus-sealer area for the main canal. There was significantly (p < 0.001) more sealer in the lateral canals for the two lateral condensation techniques. The warm obturation techniques had significantly (p < 0.001) more gutta-percha in the lateral canals.


Goals for Adherence with Low-cost Incentives (GOALS): a protocol for a randomized controlled trial evaluating the impact of small airtime incentives on ART adherence among young people living with HIV in Kampala, Uganda.
Treatment outcomes of HIV-positive individuals are threatened by low antiretroviral therapy (ART) adherence, a problem that is particularly acute among youth. Incentives are a promising tool to support ART adherence, but traditional incentive designs rewarding uniformly high levels of the desired health behavior may demotivate those with low levels of the behavior. In this study, we investigate the effectiveness of alternative approaches to target-setting for incentive eligibility using subgoals (i.e., individual-specific, interim targets leading up to the optimal target). We will enroll 628 HIV-positive youth between ages 15 and 30 into a 3-year randomized controlled trial. Participants will be randomized 1:1:1:1 to a control arm or one of three intervention arms (n = 157 each) that allow them to enter a prize drawing for small incentives if their ART adherence meets the given goal. In the first arm (T1, assigned subgoal), goals will be externally assigned and adapted to their initial adherence level. In the second arm (T2, participatory subgoal), participants can set their own interim goals. In the third arm (T3, fixed goal), all participants must reach the same target goal of 90% adherence. T1 and T2 participants are required to reach 90% adherence by month 12 to participate in a larger prize drawing. The control group receives the usual standard of care. All four groups will receive weekly motivational messages; the three treatment groups will additionally receive reminders of their upcoming prize drawing. Adherence will be measured continuously throughout the intervention period using electronic devices and for 12 months post-intervention. Surveys will be conducted at baseline and every 6 months. Viral loads will be measured annually. The primary outcome is Wisepill-measured adherence and a binary measure for whether the person took at least 90% of their pills. The secondary outcome is the log-transformed viral load as a continuous measure. Our study is one of the first to apply insights about the psychology and behavioral economics of goal-setting to the design of incentives, by testing whether conditioning the eligibility threshold for incentives on subgoals (interim goals leading up to the ultimate, high goal) improves motivation and adherence more than setting a uniformly highly goal, and a comparison group. ClinicalTrials.gov NCT05378607. Date of registration: May 18, 2022.


[Characterization of antiserum after co-immunized with adhesins expressing ClfA, FnBPA-A and FnBPA-BCD of Staphylococus aureus].
To compare the antigenicity, adhesion inhibition activity and immune protection of the serum immunized with recombinant adhesins Clumping factor A (CfA), Fibronection binding protein A-A ( FnBPA-A) and Fibronection binding protein A-BCD (FnBPA-BCD) of Staphylococcus aureus. ClfA, FnBPA-A and FnBPA-BCD genes were expressed and the resulting recombinant proteins were induced and purified. After immunizing mice with these purified proteins in combination or alone, the serum antibodies of mice were analyzed and compared for their antigenicity, adhesion inhibition activity and immune protection. The recombinant FnBPA-BCD protein had better fibronection (Fn) binding ability than that of fibrinogen (Fg) binding and ClfA. FnBPA-A had better binding capacity to Fg than that of FnBPA-BCD. The antibody titer induced by ClfA and FnBPA-A were better than that of FnBPA-BCD, and three proteins co-immunization group had better antibody titer and adhesion inhibition to Staphylococcus aureus than those of single recombinant protein immunization group (P < 0.05). The immune protection rate for both ClfA and three proteins co-immunization group were 100% and for FnBPA-A and FnBPA-BCD immunization group the immune protection rate were 80% and 50%, respectively. Our data suggest that coimmunization with these 3 recombinant proteins helps to achieve better immune effect.


Sex differences in spatial learning and memory and hippocampal long-term potentiation at perforant pathway-dentate gyrus (PP-DG) synapses in Wistar rats.
Recent studies show that gender may have a significant impact on brain functions. However, the reports of sex effects on spatial ability and synaptic plasticity in rodents are divergent and controversial. Here spatial learning and memory was measured in male and female rats by using Morris water maze (MWM) task. Moreover, to assess sex difference in hippocampal synaptic plasticity we examined hippocampal long-term potentiation (LTP) at perforant pathway-dentate gyrus (PP-DG) synapses. In MWM task, male rats outperformed female rats, as they had significantly shorter swim distance and escape latency to find the hidden platform during training days. During spatial reference memory test, female rats spent less time and traveled less distance in the target zone. Male rats also had larger LTP at PP-DG synapses, which was evident in the high magnitude of population spike (PS) potentiation and the field excitatory post synaptic potentials (fEPSP) slope. Taken together, our results suggest that sex differences in the LTP at PP-DG synapses, possibly contribute to the observed sex difference in spatial learning and memory.


Use of external orthotic helmet therapy in positional plagiocephaly.
Positional plagiocephaly is the most common type of cranial asymmetry affecting infants. We aimed to investigate the effectiveness of helmet therapy compared to no helmet therapy in treating positional plagiocephaly in infants under the age of 1year. This retrospective review was conducted in an Australian paediatric hospital and included 171 patients recruited from outpatient clinics. Only 30 patients had positional plagiocephaly scores recorded at first and final consultations while 39 patients had diagonal measurements recorded at both visits. The mean age was 7.38months at initial consultation with a mean follow-up duration of 5.85months. Those who had helmet therapy had a significantly greater reduction in diagonal difference than those who did not use helmets (p=0.011). Therefore, there may be a role for helmet therapy in the treatment of severe positional plagiocephaly.


NHS-POx-loaded patch versus fibrin sealant patch in a porcine robotic liver bleeding model.
The management of bleeding is paramount to any surgical procedure. With the increased use of less invasive laparoscopic and robotic methods, achieving hemostasis can be challenging since the surgeons cannot manually apply hemostatic agents directly onto bleeding tissue. In this study, we assessed the use of a pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with poly(2-oxazoline) (NHS-POx) for hemostasis in robotic liver resection in a porcine bleeding model. The NHS-POx-loaded patch (GATT-Patch), was first evaluated in a Feasibility Study to treat surgical bleeding in 10 lesions, followed by a Comparative Study in which the NHS-POx patch was compared to a standard-of-care fibrin sealant patch (TachoSil), in 36 lesions (superficial, resection, or deep injuries mimicking metastasectomies). For each lesion type, the NHS-POx and fibrin sealant patches were used in an alternating fashion with 18 lesions treated with NHS-POx and 18 with the fibrin patch. Animal preparation and surgical procedures were consistent across studies. The primary outcome was time to hemostasis (TTH) within 3 min for the Feasibility Study and within 5 min for the Comparative Study. In the Feasibility Study, 8 of the 10 NHS-POx-treated lesions achieved hemostasis at 30 s and 3 min. In the Comparative Study, all 18 NHS-POx patch-treated lesions and 9 of the 18 fibrin sealant patch-treated lesions achieved hemostasis at 5 min. Median TTH with NHS-POx vs fibrin sealant patch was 30 vs 300 s (P < 0.001). In this animal study, hemostasis during robotic liver surgery was achieved faster and more often with the NHS-POx loaded vs fibrin sealant patch.


Repurposing MDZ as a tool for tissue regeneration in dental cells.
Several recent studies have focused on the utility of drug repurposing to expand clinical application of approved therapeutics. Here, we investigate the efficacy of midazolam (MDZ) and cytokines for regenerating calcified tissue, using immortalized porcine dental pulp (PPU7) and mouse skeletal muscle derived myoblast (C2C12) cells, with the goal of repurposing MDZ as a new treatment to facilitate calcified tissue regeneration. We noted that PPU7 and C2C12 cells cultured with various MDZ regimens displayed increased bone morphogenic protein (BMP-2), transforming growth factor beta (TGF-β), and alkaline phosphatase activity. These increases were highest in PPU7 cells cultured with MDZ alone, and in C2C12 cells cultured with MDZ and BMP-2. PPU7 cells cultured under these conditions demonstrated markedly elevated expression of odontoblastic gene markers, indicating their likely differentiation into odontoblasts. Expression levels of osteoblastic gene markers also increased in C2C12 cells, suggesting that MDZ potentiates the effect of BMP-2, inducing osteoblast differentiation in these cells. Newly formed calcified deposits in both PPU7 and C2C12 cells were identified as hydroxyapatite via crystallographic and crystal engineering analyses. MDZ increases ALP activity, inducing expression of specific marker genes for both odontoblasts and osteoblasts while promoting hydroxyapatite production in both PPU7 and C2C12 cells. These responses were cell type specific. MDZ treatment alone could induce these changes in PPU7 cells, but C2C12 cell differentiation required BMP-2 addition.


Serum amyloid protein A in inflammatory bowel disease: from bench to bedside.
Inflammatory bowel diseases (IBD) is featured by gastrointestinal inflammation and a disease course with alternating recurrence and remission. The global burden caused by IBD has significantly boosted in recent years, necessitating treatment optimization. Serum amyloid A (SAA) is a class of 104 amino acid conservative acute-phase proteins, which is essential in immune-mediated inflammatory processes, like IBD. The SAA monomeric structure is composed of four α-helical regions and a C-terminal amorphous tail. Its disordered structure enables multiple bindings to different ligands and permits multiple functions. It has been proven that SAA has dual roles in the inflammatory process. SAA stimulates the pro-inflammatory cytokine expression and promotes the pathogenic differentiation of TH17 cells. In addition, SAA can remove toxic lipids produced during inflammatory responses and membrane debris from dead cells, redirect HDL, and recycle cholesterol for tissue repair. In IBD, SAA acts on gut epithelium barriers, induces T-cell differentiation, and promotes phagocytosis of Gram-negative bacteria. Owing to the tight connection between SAA and IBD, several clinical studies have taken SAA for a biomarker for diagnosis, assessing disease activity, and predicting prognosis in IBD. Furthermore, 5-MER peptide, a drug specifically targeting SAA, has shown anti-inflammatory effects in some SAA-dependent animal models, providing novel insights into the therapeutic targets of IBD.


Leydig cell hypogenesis: a rare cause of male pseudohermaphroditism and a pathological model for the understanding of normal sexual differentiation.
We describe a patient who presented for treatment of primary amenorrhea and was found to have male pseudohermaphroditism due to Leydig cell hypogenesis. This rare disorder is characterized by ambiguous genitalia with a normal clitoris, labioscrotal folds, a urogenital sinus and inguinal or intra-abdominal testes microscopically devoid of mature Leydig cells. The diagnosis is made biochemically by the presence of low testosterone and estradiol values with elevated luteinizing hormone levels in the absence of other significant hormonal changes. The clinical and laboratory features of this disorder offer support for human developmental concepts derived from animal models.


Functional magnetic resonance imaging of the human cervical spinal cord with stimulation of different sensory dermatomes.
Functional MR imaging (fMRI) of the cervical spinal cord was carried out in 13 healthy volunteers. A cold stimulus was applied, at different times, to three different sensory dermatome regions overlying the right hand and forearm: the thumb side of the palm, the little finger side of the palm, and the forearm below the elbow. Stimulation of these areas is expected to involve the 6(th), 8(th), and 5(th) cervical spinal cord segments respectively. Whereas true activations are expected to correspond to the region being stimulated, false activations such as arising from noise and motion, are not. The results demonstrate that clustering of active pixels into groups based on their intensity time courses discriminates false activations from true activations. Following clustering, the distribution of activity observed with fMRI matched the expected regions of neuronal activation with the different areas of stimulation on the hand and forearm.


Immunological biomarkers associated with brain structure and executive function in late-life depression: exploratory pilot study.
Several immunological biomarkers are altered in late-life major depressive disorder (LLD). Immunological alterations could contribute to LLD's consequences, but little is known about the relations between specific immunological biomarkers and brain health in LLD. We performed an exploratory pilot study to identify, from several candidates, the specific immunological biomarkers related to important aspects of brain health that are altered in LLD (brain structure and executive function). Adults (n = 31) were at least 60 years old and had major depressive disorder. A multiplex immunoassay assessed 13 immunological biomarkers, and we examined their associations with structural MRI (grey matter volume and white matter hyperintensity volume (WMH)) and executive function (Color-Word Interference and Trail-Making tests) measures. Vascular endothelial growth factor (VEGF) and the chemokine eotaxin had significant negative associations with grey matter volume (VEGF: n = 31, r = -0.65; eotaxin: n = 29, r = -0.44). Tumor necrosis factor alpha (TNF-α) had a significant positive relationship with WMHs (n = 30, r = 0.52); interferon-γ (IFN-γ) and macrophage inflammatory protein-1α (MIP-1α) were also significantly associated with WMHs (IFN-γ: n = 31, r = 0.48; MIP-1α: n = 29, r = 0.45). Only eotaxin was associated with executive function (set-shifting performance as measured with the Trail-making test: n = 33, r = -0.43). Immunological markers are associated with brain structure in LLD. We found the immunological correlates of grey and white matter differ. Prospective studies are needed to evaluate whether these immunological correlates of brain health increase the risk of LLD's consequences. Eotaxin, which correlated with both grey matter volume and set-shifting performance, may be particularly relevant to neurodegeneration and cognition in LLD. Copyright © 2016 John Wiley & Sons, Ltd.


Study of the Endogenous CRAC Channel Using shRNA-Mediated Gene Silencing.
The Ca2+ release-activated Ca2+ (CRAC) current is a major signaling event in non-excitable cells whereby Ca2+ store depletion activates Ca2+ entry across the plasma membrane from the extracellular space. Stromal interaction molecule 1 (STIM1) and Orai1 proteins are the key molecular players of the CRAC channel. Previous studies have linked activity of this channel to many physiological functions, and dysregulation of the CRAC channel has been associated with various diseases. In the absence of inducible tissue-specific knockout mice, in vivo knockdown studies examining the endogenous function of CRAC channel proteins, STIM1 and Orai1, are a challenge. In this chapter, we describe a lentiviral delivery system of shRNA-mediated gene silencing that has proven successful in studying the endogenous CRAC channel in vivo.


Effects of noise and noise reduction processing on the operation of the Nucleus-22 cochlear implant processor.
Cochlear implants, like other types of auditory sensory aids, become increasingly ineffective with increasing ambient noise levels. One method of signal processing to reduce additive random wideband noise, the INTEL method, has been used to good effect as an input preprocessor for the Nucleus-22 cochlear implant. The implant's own signal processor estimates and encodes pitch frequency and the frequencies of Formants 1 and 2. The study reported here shows that additive noise results in substantial deviations in formant frequency estimates from those that would be observed in the absence of noise. When noisy speech is preprocessed by the INTEL method to reduce noise intensity, the deviations in the frequency estimates for Formant 2 are substantially reduced.


Retroperitoneal lymphadectomy: indications, complications and expectations.
The use of retroperitoneal lymphadenectomy in the management of 152 patients with nonseminomatous germ cell tumors of the testis treated at Anderson Hospital has been reviewed. Complications consisting of wound infection (six cases), acute pancreatitis (two cases), lymphocyst formation (two cases), and chylous ascites (one case) developed in 6.4% of patients. Although ejaculatory impotence is common postoperatively, only 12 marriage units were desirous of having children and 7 of these have had uncomplicated and successful pregnancies. No instances of erectile impotence developed in this series. The indications for the procedure have been defined with regard to accurate staging, combined therapy, and, in selected instances of advanced disease, as a means of monitoring the effects of chemotherapy. The importance of this operative procedure in the multimodal management of patients with nonseminomatous germ cell tumors of the testis cannot be overemphasized.


Characterization of spexin (SPX) in chickens: molecular cloning, functional analysis, tissue expression and its involvement in appetite regulation.
Spexin (SPX) is a conservative tetradecapeptide which has been proven to participate in multiple physiological processes, including anxiety, feed intake, and energy metabolism in fish and mammals. However, whether SPX exists and functions in birds remain largely unknown. Using chicken (c-) as a model, the full-length cDNA encoding cSPX precursor was cloned, and it was predicted to generate a mature peptide with 14 amino acids conserved across vertebrates. The pGL4-SRE-luciferase reporter system-based functional analysis demonstrated that cSPX was effective in activating chicken galanin type Ⅱ receptor (cGALR2), cGALR2-like receptor (cGALR2L) and galanin type Ⅲ receptor (cGALR3), thus to stimulate intracellular MAPK/ERK signaling pathway. Quantitative real-time PCR revealed that SPX was widely expressed in chicken tissues, especially abundant in the central nervous system, pituitary, testes, and pancreas. Interestingly, it was noted that chicken hypothalamic SPX mRNA could be up-regulated by 24-h and 36-h fasting, heralding its latent capacity in appetite regulation. In accordance with this speculation, peripheral injection of cSPX was proved to be functional in reducing feed intake of 3-wk-old chicks. Furthermore, we found that cSPX could reduce the expression of AgRP and MCH, with a concurrent rise in CART1 mRNA level in the hypothalamic of chicks. Collectively, our findings not only provide the evidences that SPX can act as a satiety factor by orchestrating the expression of key feeding regulators in the chicken hypothalamus but also help to facilitate a better understanding of its functional evolution across vertebrates.


Fasting serum growth hormone and insulin-like growth factor-I and -II concentrations in women with leiomyomata uteri treated with leuprolide acetate or placebo.
Eighteen patients with leiomyomata uteri were randomized to receive either leuprolide acetate depot (n = 9) 3.75 mg intramuscularly (IM) or placebo (n = 9) IM every 4 weeks for four injections. Leuprolide acetate treated patients demonstrated a reduction in mean uterine volume of 34% and a decrease in serum estradiol (E2) concentrations from 120 +/- 21 pg/mL (mean +/- standard error) to 16 +/- 9 pg/mL. Leuprolide acetate treated patients also demonstrated significant decreases in serum growth hormone (GH) (3.0 +/- 0.4 ng/mL versus 1.4 +/- 0.4 ng/mL) and insulin-like growth factor-I (IGF-I) concentrations (3.3 +/- 0.4 U/mL versus 1.3 +/- 0.2 U/mL) over the 12 week treatment period. Serum IGF-II levels did not change. Mean uterine volume and serum E2, GH, IGF-I, and IGF-II concentrations did not change in placebo-treated patients. These data suggest that hypoestrogenism is associated with decreases in circulating GH and IGF-I.


A novel multifunctional anti-CEA-IL15 molecule displays potent antitumor activities.
Interleukin-15 (IL-15) is an immunomodulatory cytokine. It can activate and expand cytotoxic CD8 T lymphocytes and natural killer cells, leading to potent antitumor effects. Various forms of IL-15 are now in different stages of development for cancer immunotherapy. One of the major issues with IL-15 or IL15-IL15Rα fusion is high toxicity due to systemic activation of immune cells. In this study, we engineered a nanobody-cytokine fusion molecule, anti-CEA-IL15, in which an anti-CEA nanobody was linked to an IL15Rα-IL15 fusion. The nanobody-cytokine fusion exhibited multiple mechanisms to kill tumor cells, including promoting immune cell proliferation and directing antibody-dependent cytotoxicity against CEA-positive tumor cells. In xenograft models, anti-CEA-IL15 was localized in the tumor microenvironment and exhibited more potent antitumor activities than non-targeting IL-15, supporting potential application of this multifunctional fusion molecule in tumor immunotherapy. We generated and validated a tumortargeting fusion protein, anti-CEA-IL15, which has potent cytokine activity to activate and mobilize the immune system to fight cancer cells. Such strategies may also be applied to other cytokines and tumor-targeting molecules to increase antitumor efficacy.


Subthalamic nucleus activity in the awake hemiparkinsonian rat: relationships with motor and cognitive networks.
Oscillatory activity in both beta and gamma ranges has been recorded in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients and linked to motor function, with beta activity considered antikinetic, and gamma activity, prokinetic. However, the extent to which nonmotor networks contribute to this activity is unclear. This study uses hemiparkinsonian rats performing a treadmill walking task to compare synchronized STN local field potential (LFP) activity with activity in motor cortex (MCx) and medial prefrontal cortex (mPFC), areas involved in motor and cognitive processes, respectively. Data show increases in STN and MCx 29-36 Hz LFP spectral power and coherence after dopamine depletion, which are reduced by apomorphine and levodopa treatments. In contrast, recordings from mPFC 3 weeks after dopamine depletion failed to show peaks in 29-36 Hz LFP power. However, mPFC and STN both showed peaks in the 45-55 Hz frequency range in LFP power and coherence during walking before and 21 days after dopamine depletion. Interestingly, power in this low gamma range was transiently reduced in both mPFC and STN after dopamine depletion but recovered by day 21. In contrast to the 45-55 Hz activity, the amplitude of the exaggerated 29-36 Hz rhythm in the STN was modulated by paw movement. Furthermore, as in PD patients, after dopamine treatment a third band (high gamma) emerged in the lesioned hemisphere. The results suggest that STN integrates activity from both motor and cognitive networks in a manner that varies with frequency, behavioral state, and the integrity of the dopamine system.


Risk Analysis: Celebrating the Accomplishments and Embracing Ongoing Challenges.
As part of the celebration of the 40th anniversary of the Society for Risk Analysis and Risk Analysis: An International Journal, this essay reviews the 10 most important accomplishments of risk analysis from 1980 to 2010, outlines major accomplishments in three major categories from 2011 to 2019, discusses how editors circulate authors' accomplishments, and proposes 10 major risk-related challenges for 2020-2030. Authors conclude that the next decade will severely test the field of risk analysis.


Enhancement of Drug Sensitivity by Knockdown of HIF-1α in Gastric Carcinoma Cells.
In this study, the effects of hypoxia-inducible factor-1α (HIF-1α) on gastric carcinoma (GC) drug resistance through apoptosis-related genes are investigated. First, HIF-1α-specific siRNA was synthetized and transfected into drug-resistant GC cell line OCUM-2MD3/L-OHP. Then MTT assay was applied to test the inhibition rate of GC cells by 5-fluorouracil (5-FU) and oxaliplatin (L-OHP). After that, flow cytometry (FCM) was applied to measure apoptosis rate. qPCR and Western blot assay were employed to detect HIF-1α and apoptosis-related genes. Results showed that HIF-1α in OCUM-2MD3/L-OHP cells was higher than that in OCUM-2MD3 and gastric epithelial cells. After HIF-1α-siRNA transfection, inhibition rates of 5-FU and L-OHP to tumor cells increased significantly. FCM results showed that apoptosis rate of OCUM-2MD3/L-OHP cells increased significantly. After HIF-1α-siRNA transfection, survivin and Bcl-2 decreased, whereas Bax, caspase 3, and caspase 8 increased significantly. Results from this study seem to confirm that HIF-1α getting involved in GC drug resistance is possibly due to its regulation of some apoptosis-related genes. HIF-1α may be a potential target to reverse drug resistance of GC.


The expression and role of TRPV2 in esophageal squamous cell carcinoma.
Transient receptor potential vanilloid 2 (TRPV2) was recently shown to be involved in migrant potentials. The present study aimed to investigate its role in esophageal squamous cell carcinoma (ESCC). Knockdown experiments were conducted using TRPV2 siRNA in human ESCC cell lines, and anti-tumor effects were analyzed. The gene expression profiles of cells were analyzed using a microarray method. An immunohistochemical staining was performed on 62 primary tumor samples. TRPV2 overexpression was observed in TE15 and KYSE170 cells. TRPV2 depletion suppressed proliferation, cell cycle progression, and invasion/migration ability, and induced apoptosis. A pathway analysis of microarray data showed that TRPV2 depletion down-regulated WNT/β-catenin signaling-related genes and basal cell carcinoma signaling-related genes. The suppression of tumor functions, such as proliferation, invasion, and angiogenesis, was predicted in the ontology analysis. Immunohistochemical analysis revealed a correlation between strong TRPV2 expression and a poor prognosis in ESCC patients. The present results suggest that TRPV2 regulates cancer progression by affecting WNT/β-catenin or basal cell carcinoma signaling, and that TRPV2 strong expression is associated with a worse prognosis in ESCC patients. These results provide an insight into the role of TRPV2 as a novel therapeutic target or biomarker for ESCC.


Conservative therapy of plantar puncture wounds.
In order to define the natural history and complication rate of plantar puncture wounds receiving conservative initial therapy, a prospective, uncontrolled case series study with standardized protocol was conducted in a university hospital emergency department. The eligible patients were between the ages of 18-59 years and presented within 24 hours of sustaining an uncomplicated plantar puncture wound without preexisting impediments to wound healing or wound assessment. Patients were treated with surface cleansing alone and were kept non-weight bearing for 24 hours. Patients were followed by telephone at 48 hours, 1 week, 1 month, and 6 months. Five infections and two retained foreign bodies occurred in 63 patients, for a complication rate of 11.9%. Only the presence of symptoms 48 hours postinjury was associated with a higher risk of complication. No findings at initial presentation predicted a subsequent complication.


Utilization of two improved enzyme immunoassays based on avidin-biotin interaction for the detection of Salmonella.
Based on a strong interaction between avidin and biotin, two enzyme immunoassays have been modified and tested for the detection of Salmonella typhimurium in foodstuffs. In both assays, the antigen containing sample was first reacted with antibody to Salmonella which was precoated on a polystyrene microtiter plate. The bound antigen was then allowed to react with an appropriate amount of biotinylated antibody. In the first procedure, the presence of Salmonella was quantified by using peroxidase-labeled avidin. In the latter, avidin acted as a bridge between the biotinylated antibody and the biotinylated peroxidase. Samples containing 10(3) and 10(4) cells/ml of the Salmonella virulent strain, respectively, were detectable by these two methods. The results thus compared favorably with the detection limit of the standard ELISA (10(5) cells/ml). The superiority of the modified ELISA's utilizing biotin/avidin interactions was also demonstrated for the detection of Salmonella in artificially contaminated food samples inoculated with only 2-5 Salmonella cells followed by two incubation steps. No significant interference of E. coli (up to 5 x 10(6) cells/ml) was observed in the quantification of Salmonella cells.


Chemical modification of histidyl and lysyl residues in yeast enolase.
Modification of yeast enolase (2-phospho-D-glycerate hydro-lyase, EC 220.127.116.11) by diethyl pyrocarbonate at either pH 6.1 or 6.6 caused a biphasic inactivation of the enzyme. In the presence of excess Mg2+, either an equilibrium mixture of substrates or 3-phosphoglycerate, a competitive inhibitor, prevented the second slower phase of inactivation, but had no effect on the first rapid phase. Complete inactivation by diethyl pyrocarbonate correlates with the modification of six histidyl residues/subunit, while 3-phosphoglycerate protects two histidyl residues/subunit from modification. Modification of enolase by two lysine-specific reagents, 2,4,6-trinitrobenzenesulfonate and pyridoxal 5'-phosphate, at pH 8.3 caused a slow loss of enzyme activity. However, substrates did not significantly protect against inactivation by either reagent, and inactivation with 2,4,6-trinitrobenzenesulfonate correlates with the modification of 18 lysyl residues/enzyme subunit.


Difference in cytokine production and cell activation between adenoidal lymphocytes and peripheral blood lymphocytes of children with otitis media.
We evaluated the immunological potential of adenoidal lymphocytes from children with recurrent otitis media. Interleukin-4 release and CD69 expression were lower in adenoidal lymphocytes than in peripheral blood lymphocytes (PBL). Our results suggest that there may be a difference between the immunological potential of adenoidal lymphocytes and that of PBL in children with otitis.


Tolerance, taxonomic and phylogenetic studies of some bacterial isolates involved in bioremediation of crude oil polluted soil in the southern region of Nigeria.
Indigenous bacteria play vital roles in the bioremediation of crude oil polluted soils. The effectiveness of the bioremediation process depends on the tolerance, characteristics and biodiversity of the bacteria isolates. Bacteria strains were isolated from crude-oil polluted sites in different locations in the southern region of Nigeria namely: Azikoro and Otukpoti (Bayelsa state); Ologbo and Benin (Edo State) and non-polluted soil was collected from Ibadan (Oyo state). Tolerance study was conducted for 96 h s. Isolation and characterization of the most effective isolate from each location was done using cultural, physico-chemical and molecular methods. The tolerance level of the isolates from the different oil-polluted soils and their comparative growth performance on crude oil supplemented media decreases in the order: Azikoro - Ologbo - Otukpoti - Benin. MATS analysis showed that cell surfaces of Azikoro, Ologbo and Otukpoti strains exhibited 58-63 % adhesion to n-hexadecane and are hydrophobic strains while Benin strain possess 38% adhesion to n-hexadecane and are hydrophilic. The cell surfaces of isolates from Azikoro, Ologbo and Otukpoti are highly Lewis-acidic while that from Benin is highly Lewis-basic. Isolates from Benin-3, Ologbo-1, and Otukpoti-1 were shown to be gram positive while that from Azikoro was gram negative. 16S rDNA fingerprinting confirmed the identities of the isolates as follows: Paenalcaligenes suwonesis with accession numbers NR-133804.1 from Azikoro spillage site (93.77%); Lactobacillus nagelii with accession number NR-158108.1 (91.30%) from Benin spillage site; Lactobacillus fermentum with accession number NR-104927.1 (96.70%) from Ologbo and Otukpoti spillage sites. Phylogenetic analysis putatively categorized the isolates from Otukpoti and Ologbo in close association belonging to same homology while Benin isolate is a subgroup. The characteristics and biodiversity of all the isolated bacteria from the regions possibly justifies their involvement in the bioremediation of petroleum hydrocarbons.


An integrated village maternity service to improve referral patterns in a rural area in West-Java.
The Regionalization of Perinatal Care, an intervention study carried out in Tanjungsari, a subdistrict in rural West Java, aimed to develop a comprehensive maternal health program to improve maternal and perinatal health outcomes. The main inputs included training at all levels of the health care system (informal and formal) and the establishment of birthing homes in villages to make services more accessible. Special attention was given to referral, transportation, communication and appropriate case management, A social marketing program was conducted to inform people of the accessible birthing homes for clean delivery, located near the women, and with better transportation and communications to referral facilities should complications arise. The study design was longitudinal, following all pregnant women from early pregnancy until 42 days postpartum in an intervention and a comparison area. The population was +/- 90,000 in the intervention area and 40,000 in the comparison area. Inclusion criteria were all mother and infant units delivered between June 1st, 1992 and May 31st, 1993. Analysis showed the following results: Most women sought antenatal care (> 95%). In Tanjungsari, nearly 90% sought such care from professional providers as versus 75% in the control area of Cisalak. Most women with bleeding or bleeding and edema during pregnancy sought professional assistance in both the study and control areas. However, fever for more than 3 days received more attention in the study area versus control area (93 vs. 69%). Greater than 85% of deliveries in both areas were conducted by TBAs. However, in the study area, nearly one-third of those with intrapartum complications (17%) delivered in a health facility compared to one-tenth in the control area. This meant a hospital delivery, primarily with assistance of a doctor or doctor/midwife combination. Overall referral rates by TBAs were low -13% of women with complications in Tanjungsari and 6% in Cisalak. More women with intrapartum complications were referred in the study area than in the control, and more complied when referred. Women who suffered intrapartum complications were more likely to have a perinatal death. Perinatal deaths declined in Tanjungsari, but not significantly. However, the trend over the period of the intervention shows an improvement in the deliveries managed by TBAs with more deaths resulting in the hands of professionals. Either women were arriving too late or the quality of care could not meet the needs. There was no change in the levels or place of perinatal deaths in Cisalak.


Evaluation of spot urine as an alternative to 24h urine collection for determination of biomarkers of exposure to cigarette smoke in adult smokers.
Exposure to cigarette smoke in adult smokers (SM) can be determined by measuring urinary excretion of selected smoke constituents or metabolites. Complete 24h urine collections are difficult to achieve in ambulatory clinical studies; therefore spot urine (SU) might be a useful alternative. The objective of this study was to evaluate the optimum time for SU collections, and to predict 24h urine biomarker excretion from SU collections. SU samples were collected at three time points (early morning, post-lunch and evening) along with 24h collections in 37 healthy adult smokers. Nicotine and its five metabolites (nicotine equivalents, NE), metabolites of NNK (NNAL), pyrene (1-OHP), acrolein (HPMA), benzene (S-PMA) and butadiene (MHBMA) were measured in 24h and SU samples. Correlation and agreement between creatinine-adjusted SU and 24h urine collections were determined from the Pearson product-moment correlation, Bland-Altman and Lin's concordance correlation analyses. A random effect regression model was used to calculate the 24h biomarker excretion from SU collections. There were no significant differences (p>0.05) between the three SU collections for the selected biomarkers of exposure except for 3-HPMA, which showed a diurnal variation. Good correlation and statistical agreements were observed for creatinine-adjusted SU (all three time points) and 24h for most of the selected biomarkers. 24h biomarker excretion could be estimated for most of the biomarkers based on the regression model, with the early morning SU collections giving the best results for tobacco specific biomarkers NE (R(2)=0.66) and NNAL (R(2)=0.6). SU is a useful alternative to 24h urine collections for most of the selected biomarkers of exposure to cigarette smoke. The early morning SU appears to be the most feasible and practical option as an alternative to 24h collections.


Measuring the effect of nurse practitioner (NP)-led care on health-related quality of life in adult patients with atrial fibrillation: study protocol for a randomized controlled trial.
Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity, mortality, and healthcare resource use. The prevalence of AF is increasing with a growing and aging population, and timely access to care for these patients is a concern. Nontraditional models of care delivery, such as nurse practitioner (NP)-led clinics, may improve access to care and quality of care, but they require formal assessment. The objective of this study is to assess the effect of NP-led care on the health-related quality of life (HRQoL) of adult patients with AF. We plan a randomized controlled trial comparing NP-led care vs. standard care. Inclusion criteria are ≥18 years of age, documented nonvalvular AF, willingness to give informed consent, and capacity to complete questionnaires. Patients referred for electrophysiological intervention who are clinically unstable or unable to attend follow-up visits will not be eligible to participate. Patients will be asked for verbal consent during the initial triage phone call from the nurse. Randomization will occur via a secure website. The intervention includes an NP consult, including medical history, physical examination, patient teaching, treatment plan, and follow-up at 3 and 6 months. The control arm involves usual cardiologist consultation with follow-up determined by the cardiologist's practice pattern. The primary outcome will be the difference in change in Atrial Fibrillation Effect on Quality of Life Survey scores at 6 months between groups. Secondary outcomes will include difference in change of EQ-5D scores at 6 months between groups, difference in composite outcomes of death resulting from cardiovascular cause, hospitalizations and emergency department visits between groups, and satisfaction with NP-led care measured by the Consultant Satisfaction Questionnaire. A sample size of 70 per group will ensure adequate power despite a potential 10% loss to follow-up. Our study will determine the effect of NP-led AF care on HRQoL in patients with AF, as well as measure its impact on relevant outcomes such as death, hospitalization, and emergency department visits. Our findings may have implications for delivery of care to patients with AF. ClincalTrials.gov, NCT02745236 . Registered on 16 April 2016.


Process quality indicators in family medicine: results of an international comparison.
The aim of our study was to describe variability in process quality in family medicine among 31 European countries plus Australia, New Zealand, and Canada. The quality of family medicine was measured in terms of continuity, coordination, community orientation, and comprehensiveness of care. The QUALICOPC study (Quality and Costs of Primary Care in Europe) was carried out among family physicians in 31 European countries (the EU 27 except for France, plus Macedonia, Iceland, Norway, Switzerland, and Turkey) and three non-European countries (Australia, Canada, and New Zealand). We used random sampling when national registers of practitioners were available. Regional registers or lists of facilities were used for some countries. A standardized questionnaire was distributed to the physicians, resulting in a sample of 6734 participants. Data collection took place between October 2011 and December 2013. Based on completed questionnaires, a three-dimensional framework was established to measure continuity, coordination, community orientation, and comprehensiveness of care. Multilevel linear regression analysis was performed to evaluate the variation of quality attributable to the family physician level and the country level. None of the 34 countries in this study consistently scored the best or worst in all categories. Continuity of care was perceived by family physicians as the most important dimension of quality. Some components of comprehensiveness of care, including medical technical procedures, preventive care and health care promotion, varied substantially between countries. Coordination of care was identified as the weakest part of quality. We found that physician-level characteristics contributed to the majority of variation. A comparison of process quality indicators in family medicine revealed similarities and differences within and between countries. The researchers found that the major proportion of variation can be explained by physicians' characteristics.


Effect of an abiotic disturbance on a lotic predator-prey interaction.
A model derived from marine research, and recently applied to stream communities, suggests that community structure is more likely to be influenced by predators in benign versus harsh abiotic regimes. Experiments were conducted to determine if increasing the harshness of a particular regime would alter the impact of a stream invertebrate predator on prey densities in field enclosures. Density of a stonefly predator, Kogotus nonus, was varied in containers exposed to low (benign) and high (harsh) levels of fine sediment. As predicted by the model, the harsher regime eliminated predator effects in two of three experiments. In the third experiment, however, high levels of sediment actually enhanced the impact of the predator on the prey community. A consideration of the possible mechanisms underlying this model led to the conclusion that increasing the harshness of a regime can be expected to produce outcomes ranging from elimination to enhancement of predator effects, depending on how the regime is perceived by the predator versus the prey.


Prioritizing abandoned coal mine reclamation projects within the contiguous United States using geographic information system extrapolation.
Coal mine reclamation projects are very expensive and require coordination of local and federal agencies to identify resources for the most economic way of reclaiming mined land. Location of resources for mine reclamation is a spatial problem. This article presents a methodology that allows the combination of spatial data on resources for the coal mine reclamation and uses GIS analysis to develop a priority list of potential mine reclamation sites within contiguous United States using the method of extrapolation. The extrapolation method in this study was based on the Bark Camp reclamation project. The mine reclamation project at Bark Camp, Pennsylvania, USA, provided an example of the beneficial use of fly ash and dredged material to reclaim 402,600 sq mi of a mine abandoned in the 1980s. Railroads provided transportation of dredged material and fly ash to the site. Therefore, four spatial elements contributed to the reclamation project at Bark Camp: dredged material, abandoned mines, fly ash sources, and railroads. Using spatial distribution of these data in the contiguous United States, it was possible to utilize GIS analysis to prioritize areas where reclamation projects similar to Bark Camp are feasible. GIS analysis identified unique occurrences of all four spatial elements used in the Bark Camp case for each 1 km of the United States territory within 20, 40, 60, 80, and 100 km radii from abandoned mines. The results showed the number of abandoned mines for each state and identified their locations. The federal or state governments can use these results in mine reclamation planning.


The mych gene is required for neural crest survival during zebrafish development.
Among Myc family genes, c-Myc is known to have a role in neural crest specification in Xenopus and in craniofacial development in the mouse. There is no information on the function of other Myc genes in neural crest development, or about any developmental role of zebrafish Myc genes. We isolated the zebrafish mych (myc homologue) gene. Knockdown of mych leads to severe defects in craniofacial development and in certain other tissues including the eye. These phenotypes appear to be caused by cell death in the neural crest and in the eye field in the anterior brain. Mych is a novel factor required for neural crest cell survival in zebrafish.


Three distinct genomic subtypes of head and neck squamous cell carcinoma associated with clinical outcomes.
Heterogeneity of head and neck squamous cell carcinomas (HNSCCs) results in unpredictable outcomes for patients with similar stages of cancer. Beyond the role of human papilloma virus (HPV), no validated molecular marker of HNSCCs has been established. Thus, clinically relevant molecular subtypes are needed to optimize HNSCC therapy. The purpose of this study was to identify subtypes of HNSCC that have distinct biological characteristics associated with clinical outcomes and to characterize genomic alterations that best reflect the biological and clinical characteristics of each subtype. We analyzed gene expression profiling data from pan-SCC tissues including cervical SCC, esophageal SCC, lung SCC, and HNSCC (n = 1346) to assess the similarities and differences among SCCs and to identify molecular subtypes of HNSCC associated with prognosis. Subtype-specific gene expression signatures were identified and used to construct predictive models. The association of the subtypes with prognosis was validated in two independent cohorts of patients. Pan-SCC analysis identified three novel subtypes of HNSCC. Subtype 1 had the best prognosis and was similar to cervical SCC, whereas subtype 3 had the worst prognosis and was similar to lung SCC. Subtype 2 had a moderate prognosis. The 600-gene signature associated with the three subtypes significantly predicted prognosis in two independent validation cohorts. These three subtypes also were associated with potential benefit of immunotherapy. We identified three clinically relevant HNSCC molecular subtypes. Independent prospective studies to assess the clinical utility of the subtypes and associated gene signature are warranted.


Ir(I)-catalyzed intermolecular regio- and enantioselective hydroamination of alkenes with heteroaromatic amines.
A cationic Ir(I)-C(3)-TUNEPHOS complex catalyzed an intermolecular hydroamination of styrene derivatives with various heteroaromatic amines. The reaction gave Markovnikov products with perfect regioselectivity and good enantioselectivity under solvent-free conditions.


[Molecular mechanisms of atrial fibrillation: potential role of microRNAs as new therapeutic targets and potential biomarkers].
Atrial fibrillation represents the most common form of clinical arrhythmia in daily routine. However, current therapeutic options are still limited and a better understanding of the underlying molecular mechanisms is expected to contribute to the development of new therapeutic strategies. The scientific field of microRNA research has received a lot of attention in recent years, especially regarding cardiovascular research. This article gives a brief overview of the most recent developments in microRNA research in the field of atrial fibrillation and atrial remodelling processes. Furthermore, the clinical perspective of microRNAs as new therapeutic targets and as potential biomarkers is discussed.


Spatially variable propagule pressure and herbivory influence invasion of chaparral shrubland by an exotic grass.
Although numerous studies have identified mechanisms that either resist or facilitate biological invasions, few studies have explicitly tested how resisting and facilitating mechanisms interact to drive invasion success. In California, USA, undisturbed Mediterranean-type shrublands have resisted invasion by the perennial tussock grass Cortaderia jubata. In some cases, however, this resistance has been spectacularly breached even in the absence of large-scale disturbance. I tested the hypothesis that these invasions are facilitated by local reductions in the strength of biotic resistance. I evaluated invasive success using C. jubata seed and seedling additions at different microhabitats: the edge of a chaparral stand, under shrub canopy at different distances from the stand edge, and in canopy gaps within the stand. When left exposed to mammalian herbivores, seedling survivorship decreased sharply from nearly 40% on the stand edge to zero just 10 m into the stand. When transplants were protected from herbivory, however, distance from the edge had no significant influence on transplant survivorship. Seedling emergence was also greater on the edge and in canopy gaps than under the canopy, but these differences were not caused by differences in herbivory. The flux of invasive propagules reaching the soil surface was immense and greater along the edge and within gaps than under the stand canopy. Mirroring these patterns, naturally occurring seedling abundance declined dramatically with distance from the stand edge, and seedlings were far more common within stand gaps than would be expected given gap frequency within the stand. Despite strong biotic resistance to invasion within the stand, the cover of C. jubata has increased 20% over the last 9 years. These results suggest that the relative amount of susceptible edge habitat and the supply of invasive propagules can facilitate invasion even in the face of strong local biotic resistance.


Increased bioavailability of cyclic guanylate monophosphate prevents retinal ganglion cell degeneration.
The nitric oxide - guanylyl cyclase-1 - cyclic guanylate monophosphate (NO-GC-1-cGMP) pathway has emerged as a potential pathogenic mechanism for glaucoma, a common intraocular pressure (IOP)-related optic neuropathy characterized by the degeneration of retinal ganglion cells (RGCs) and their axons in the optic nerve. NO activates GC-1 to increase cGMP levels, which are lowered by cGMP-specific phosphodiesterase (PDE) activity. This pathway appears to play a role in both the regulation of IOP, where reduced cGMP levels in mice leads to elevated IOP and subsequent RGC degeneration. Here, we investigated whether potentiation of cGMP signaling could protect RGCs from glaucomatous degeneration. We administered the PDE5 inhibitor tadalafil orally (10 mg/kg/day) in murine models of two forms of glaucoma - primary open angle glaucoma (POAG; GC-1-/- mice) and primary angle-closure glaucoma (PACG; Microbead Occlusion Model) - and measured RGC viability at both the soma and axon level. To determine the direct effect of increased cGMP on RGCs in vitro, we treated axotomized whole retina and primary RGC cultures with the cGMP analogue 8-Br-cGMP. Tadalafil treatment increased plasma cGMP levels in both models, but did not alter IOP or mean arterial pressure. Nonetheless, tadalafil treatment prevented degeneration of RGC soma and axons in both disease models. Treatment of whole, axotomized retina and primary RGC cultures with 8-Br-cGMP markedly attenuated both necrotic and apoptotic cell death pathways in RGCs. Our findings suggest that enhancement of the NO-GC-1-cGMP pathway protects the RGC body and axon in murine models of POAG and PACG, and that enhanced signaling through this pathway may serve as a novel glaucoma treatment, acting independently of IOP.


Waol A, trans-dihydrowaol A, and cis-dihydrowaol A: polyketide-derived γ-lactones from a Volutella species.
An organic extract of a filamentous fungus (MSX 58801), identified as a Volutella sp. (Hypocreales, Ascomycota), displayed moderate cytotoxic activity against NCI-H460 human large cell lung carcinoma. Bioactivity-directed fractionation led to the isolation of three γ-lactones having the furo[3,4-b]pyran-5-one bicyclic ring system [waol A (1), trans-dihydrowaol A (2), and cis-dihydrowaol A (3)]. The structures were elucidated using a set of spectroscopic and spectrometric techniques; the absolute configuration of 2 was established via a modified Mosher's ester method. Compounds 1 and 2 were evaluated for cytotoxicity against a human cancer cell panel.


On the embryotoxic effects of benzene and its alkyl derivatives in mice, rats and rabbits.
Groups of CFY rats were exposed to inhalation of ethylbenzene at 600, 1200 or 2400 mg/m3 or xylene at 250, 1900 or 3400 mg/m3 or Aromatol at 500, 1000 or 2000 mg/m3 atmospheric concentration for 24 h/day from day 7 to day 15 of pregnancy, or for 2-4 hours only on the 18th or 20th day of gestation. CFLP mice and NZ rabbits were exposed to inhalation of 500 mg/m3 or 1000 mg/m3 benzene, toluene, ortho-, meta-, para-xylene, ethylbenzene, xylene or Aromatol for 24 h/day from day 6 to day 15 of pregnancy. Untreated animals and groups inhaling pure air served as controls. All components of the xylene and Aromatol crossed the placenta and were present in fetal blood and amniotic fluid, as well. The maternal toxic effects at all solvents were moderate and dose dependent. All solvents (at higher concentrations) brought about skeletal and weight retardation in fetuses of rats and mice. At highest concentration some solvents increased the post-implantation loss in rats and mice. All solvents caused spontaneous abortion in rabbits at 1000 mg/m3 atmospheric concentration. Only ethylbenzene and Aromatol increased the malformation rate in rats and mice. No other solvent applied proved to be teratogenic either in mice, rats or rabbits.


Multisensory integration of orally-sourced gustatory and olfactory inputs to the posterior piriform cortex in awake rats.
Flavour refers to the sensory experience of food, which is a combination of sensory inputs sourced from multiple modalities during consumption, including taste and odour. Previous work has demonstrated that orally-sourced taste and odour cues interact to determine perceptual judgements of flavour stimuli, although the underlying cellular- and circuit-level neural mechanisms remain unknown. We recently identified a region of the piriform olfactory cortex in rats that responds to both taste and odour stimuli. Here, we investigated how converging taste and odour inputs to this area interact to affect single neuron responsiveness ensemble coding of flavour identity. To accomplish this, we recorded spiking activity from ensembles of single neurons in the posterior piriform cortex (pPC) in awake, tasting rats while delivering taste solutions, odour solutions and taste + odour mixtures directly into the oral cavity. Our results show that taste and odour inputs evoke highly selective, temporally-overlapping responses in multisensory pPC neurons. Comparing responses to mixtures and their unisensory components revealed that taste and odour inputs interact in a non-linear manner to produce unique response patterns. Taste input enhances trial-by-trial decoding of odour identity from small ensembles of simultaneously recorded neurons. Together, these results demonstrate that taste and odour inputs to pPC interact in complex, non-linear ways to form amodal flavour representations that enhance identity coding. KEY POINTS: Experience of food involves taste and smell, although how information from these different senses is combined by the brain to create our sense of flavour remains unknown. We recorded from small groups of neurons in the olfactory cortex of awake rats while they consumed taste solutions, odour solutions and taste + odour mixtures. Taste and smell solutions evoke highly selective responses. When presented in a mixture, taste and smell inputs interacted to alter responses, resulting in activation of unique sets of neurons that could not be predicted by the component responses. Synergistic interactions increase discriminability of odour representations. The olfactory cortex uses taste and smell to create new information representing multisensory flavour identity.


Lymphocytotoxic T lymphocytes in a patient with B-chronic lymphocytic leukemia and pure red cell aplasia.
The peripheral blood T cells of a hypertransfused patient with B-chronic lymphocytic leukemia and pure red cell aplasic were found to exhibit unusual spontaneous cytotoxic activity in vitro. The patient's E-rosette positive cells were cytotoxic for K562 (cultured human erythroleukemia cells) and allogeneic B and T lymphocytes freshly isolated from the peripheral blood of normal and CLL donors. They failed to kill autologous B cells, erythroid progenitors present in allogeneic bone marrow, and a number of cultured human tumor cells (Malme, CAKI) even after prolonged (36 h) co-culture. Peripheral blood T cells isolated from normal controls, other CLL patients, and hypertransfused individuals (n = 13) did not exhibit spontaneous lymphocytotoxic activity. Circulating cytotoxic T cells having the ability to kill freshly isolated allogeneic lymphocytes have, heretofore, not been reported in humans. Our findings suggest that among this patient's peripheral blood T cells, there exists a subpopulation of lymphocytotoxic cells that closely resemble cytotoxic T cells generated in vitro after priming with allogeneic target cells. Although the lymphocytotoxic cells could have been induced in this patient by previous HLA-mismatched transfusions, it is possible they may have arisen spontaneously and underly the patient's erythroblastopenic state.


Cyclic GMP increases the rate of the calcium extrusion pump in intact human platelets but has no direct effect on the dense tubular calcium accumulation system.
Sodium nitroprusside (SNP) and other agents that elevate cGMP levels are known to inhibit the aggregation of human platelets. Published data suggest that cGMP attenuation of agonist-induced Ca2+ transients is involved in this effect. The present study shows that elevation of cGMP increases the rate of the Ca2+ extrusion pump located in the plasma membrane (PM) but does not have a direct effect on the Ca2+ accumulating pump of the dense tubules (DT). The study verifies that SNP can specifically elevate the cGMP level in the platelet. The kinetics of the Ca2+ extrusion system were studied in situ in platelets overloaded with the cytoplasmic Ca2+ indicator quin2 according to a published protocol developed in this laboratory. Elevation of cGMP by means of (10 microM) SNP increased the Vm of the Ca(2+)-ATPase pump by 63%, without affecting its Km (66-80 nM) or Hill coefficient (1.6-1.8). Dibutyryl-cGMP (Bt2-cGMP), preincubated for 45 min at 1 mM, increased the Vm by a factor of 2.2 +/- 0.4. The experiments did not give any indication that SNP or Bt2-cGMP change the rate of the Na+/Ca2+ exchanger which makes a minor contribution to Ca2+ extrusion in the studied [Ca2+]cyt range. The rate constant for passive leakage of Ca2+ across the PM was increased by 32 +/- 4% by SNP and 90 +/- 34% by Bt2-cGMP. The net result is that the free Ca2+ in the cytoplasm ([Ca2+]cyt) at 'rest' is lowered from control values of 112 nM to 89 nM or 80 nM, respectively. The kinetics of Ca2+ uptake by the dense tubules were determined in situ using the fluorescence of chlorotetracycline (CTC) according to protocols developed in this laboratory. Analysis showed that SNP and Bt2-cGMP had no effect on the Vm or Km of the dense tubular pump, and did not affect the rate constant for passive leakage. The agents did decrease resting [Ca2+]dt by 25% or 30%, respectively, but this result can be explained purely in terms of the reduced [Ca2+]cyt. The effects of cGMP (vs. cAMP) on the PM and DT pumps are closely correlated with reported effects of cGMP/cAMP induced phosphorylation of a protein of the molecular weight of the PM pump and a 22 kDa activator of the DT pump. Cyclic AMP increases the rate of both the PM and the DT pumps, whereas cGMP increases the rate of the PM pump only.(ABSTRACT TRUNCATED AT 400 WORDS)


Effect of undernutrition in foetal life on energy expenditure during gestation in ewes.
The long-term effect of early life undernutrition on late gestation energy expenditure (EEgest) was investigated in sheep. Ewes were fed either adequate (100%) or restricted (60%) energy and protein during late foetal life as well as during last trimester of gestation later in life, resulting in three groups: Adequate-Adequate (AA, n = 5), Adequate-Restricted (AR, n = 5) and Restricted-Restricted (RR, n = 5). At two weeks pre-partum, EEgest were calculated from respiratory gaseous exchange and nitrogen excreted in urine and further it was partitioned to energy expenditure for conceptus development (EEconceptus) and homeorhetic adaptations in maternal metabolism (EEhomeorhetic). Late gestational energy and protein restriction reduced the EEgest in the AR ewes (4.1 MJ x d(-1)) but not in the RR ewes (5.2 MJ x d(-1)) compared with the AA ewes (6.8 MJ x d(-1)). Based on conceptus-weight, no significant difference was found in EEhomeorhetic among the groups; 172, 175 and 169 kJ/kg x d(-1) in AA, AR and RR ewes, respectively. However, EEconceptus was significantly lower in AR (135 kJ/kg x d(-1)) in comparison with AA (298 kJ/kg x d(-1)) and RR (252 kJ/kg x d(-1)) ewes. In conclusion, exposure nutrient restriction in early life impairs the ability of ewes to respond to nutritional restriction in terms of energy expenditure of gestation.


Apolipoprotein A-I Limits the Negative Effect of Tumor Necrosis Factor on Lymphangiogenesis.
Lymphatic endothelial dysfunction underlies the pathogenesis of many chronic inflammatory disorders. The proinflammatory cytokine tumor necrosis factor (TNF) is known for its role in disrupting the function of the lymphatic vasculature. This study investigates the ability of apolipoprotein (apo) A-I, the principal apolipoprotein of high-density lipoproteins, to preserve the normal function of lymphatic endothelial cells treated with TNF. TNF decreased the ability of lymphatic endothelial cells to form tube-like structures. Preincubation of lymphatic endothelial cells with apoA-I attenuated the TNF-mediated inhibition of tube formation in a concentration-dependent manner. In addition, apoA-I reversed the TNF-mediated suppression of lymphatic endothelial cell migration and lymphatic outgrowth in thoracic duct rings. ApoA-I also abrogated the negative effect of TNF on lymphatic neovascularization in an ATP-binding cassette transporter A1-dependent manner. At the molecular level, this involved downregulation of TNF receptor-1 and the conservation of prospero-related homeobox gene-1 expression, a master regulator of lymphangiogenesis. ApoA-I also re-established the normal phenotype of the lymphatic network in the diaphragms of human TNF transgenic mice. ApoA-I restores the neovascularization capacity of the lymphatic system during TNF-mediated inflammation. This study provides a proof-of-concept that high-density lipoprotein-based therapeutic strategies may attenuate chronic inflammation via its action on lymphatic vasculature.


The effect of right temporal lobe lesions on matching of smells.
Thirty patients with bitemporal lobe epilepsy, 14 patients with right temporal lobe epilepsy, 14 patients with left temporal lobe epilepsy, 14 patients who had right temporal lobectomy, 10 patients who had left temporal lobectomy and 12 patients who had lobectomy involving frontal or fronto-parietal regions were tested for their ability to match smells. A simple matching technique was used. It was found that patients with right temporal lobe lesions had difficulty in matching smells. There was no significant difference between the right temporal lobe epilepsy group and the right temporal lobectomy group. The implications of these findings are discussed.


Combined urea-thin layer chromatography and silver nitrate-thin layer chromatography for micro separation and determination of hard-to-detect branched chain fatty acids in natural lipids.
A simple, fast and efficient procedure was developed for micro separation and enrichment of branched chain fatty acids (BCFA) from natural products using successive thin layer chromatography (TLC) technique coupling novel urea-TLC with AgNO3-TLC, which rely on the formation of urea adduction and AgNO3 bonding in methanol. These natural lipids contain a significant amount of straight chain fatty acids (FA). Fresh and fast urea-TLC and AgNO3-TLC plate making techniques were developed with more even coating and less coating material contamination before being utilized for separation. Goat milk fat was used as a model. Various experimental parameters that affect urea-TLC and AgNO3-TLC separation of BCFA were investigated and optimized, including coating of urea, concentration of original oil sample, mobile phase and sample application format. High efficiency of removal of straight chain FA was achieved with a low amount of sample in an easy and fast way. A total BCFA mix with much higher purity than previous studies was successfully achieved. The developed method has also been applied for the concentration and analysis of BCFA in cow milk fat and Anchovy oil.