Oxidative Stress and Dietary Fat Type in Relation to Periodontal Disease.
Oxidative stress is one of the main factors studied to explain the pathophysiological mechanisms of inflammatory conditions, such as periodontitis. In this respect, nutrition may be of great importance. Actually, research on nutrients' effects on periodontal diseases has expanded to include those influencing the redox status, which correlates to the inflammatory process. Dietary fat or lipids are often blamed as the major source of excess energy. Consequently, when caloric intake exceeds energy expenditure, the resultant substrate-induced increase in citric acid cycle activity generates an excess of reactive oxygen species (ROS). In addition, dietary fatty acid intake influences in relative fatty acid composition of biological membranes determining its susceptibility to oxidative alterations. From this standpoint, here, we reviewed studies analyzing the dietary fat role in periodontal disease. Research data suggest that periodontal health could be achieved by main dietary strategies which include substitution of saturated fats with monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA. Maybe in the future, we should analyze the diet and provide some advice to periodontitis patients to improve treatment outcomes.


Self-help groups reduce mortality risk: a 5-year follow-up study of alcoholics in the Tokyo metropolitan area.
The present study aimed to determine whether alcoholics who attend self-help groups experience fewer deaths than those who do not. Subjects were patients from the Alcoholism Treatment Program (ATP) of Matsuzawa hospital. A cohort of alcoholic patients recruited into a prospective study was followed from April 1994 to March 1999. A total of 469 alcoholic patients met the International Classification of Diseases (10th edition) criteria for alcohol dependency. Of these, 94 patients refused to participate in the study, leaving a total of 375 participants. After discharge from the ATP and a complete explanation of the present study, subjects decided whether to attend a self-help group (SHG) or not. The SHG comprised 208 subjects, and the non-self-help group (NSHG) comprised 167 subjects. Outcomes were evaluated with regard to death during follow-up for a mean of 2.4 years. Death was ascertained through the records of the Setagaya Department of Health and Welfare center, Matsuzawa hospital and other hospitals, and through personal contact with informants, relatives, and significant others of subjects. Deaths were confirmed for 47 NSHG subjects and only five SHG subjects. NSHG displayed a significantly decreased cumulative survival compared with SHG (P < 0.0001). Cox proportion hazard analysis was used to examine variables that may help to predict mortality among alcoholics. Alcoholics who attended self-help groups differed from those who did not, with regard to mortality experience. Attending a self-help group represented the most important predictor of prognosis for alcoholics.


The Escherichia coli K-12 MntR miniregulon includes dps, which encodes the major stationary-phase DNA-binding protein.
Escherichia coli MntR protein is the Mn(2+)-responsive transcriptional repressor of the MntH manganese transporter. We have used chromatin immunoprecipitation to determine the distribution of Mn(2+)-MntR across the entire E. coli chromosome in vivo, and we report that MntR binds to only four targets, adjacent to the mntH, mntR, yebN, and dps genes. Unexpectedly, we found that dps expression is directly repressed by Mn(2+)-MntR.


A comparative study on the effects of a pesticide (cypermethrin) and two metals (copper, lead) to serum biochemistry of Nile tilapia, Oreochromis niloticus.
The present study was designed to compare the responses in freshwater fish Oreochromis niloticus exposed to a synthetic pyrethroid, cypermethrin (CYP); an essential metal, copper (Cu); and a nonessential metal, lead (Pb). Fish were exposed to 0.05 μg/l CYP, 0.05 mg/l Cu, and 0.05 mg/l Pb for 4 and 21 days, and the alterations in serum enzyme activities, metabolite, and ion levels were determined. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities increased in response to CYP, Cu, and Pb exposures at both exposure periods. While elevations in alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities and in cholesterol level were observed in pesticide-exposed fish at 4 and 21 days, they increased in Cu- and Pb-exposed fish at 21 days. Although metal-exposed fish showed increases in cortisol and glucose levels at 4 days followed by a return to control levels at the end of the exposure period, their levels elevated in pesticide-exposed fish at both exposure periods. Total protein levels decreased in Pb- and pesticide-exposed fish at 21 days. Na⁺ and Cl⁻ levels decreased in pesticide-exposed fish at both exposure periods and in Cu- and Pb-exposed fish at 21 days. The exposures of pesticide and metals caused an elevation in K⁺ level at the end of the exposure period. The present study showed that observed alterations in all serum biochemical parameters of fish-treated pesticide were higher than those in fish exposed to metals.


Characteristics of female sex workers in southern India willing and unwilling to participate in a placebo gel trial.
Respondent-driven sampling was used to recruit female sex workers (FSWs) for a community survey conducted in southern India. After survey completion, participants were given a brochure describing a clinical trial that entailed daily use of a placebo vaginal gel for four months. This study assessed predictors of screening among survey respondents, predictors of enrollment among those eligible for the trial, and predictors of visit attendance and retention among those enrolled. FSWs who reported having symptoms of sexually transmitted infections (STI), engaging in sex work in the past month, and living in a subdistrict easily accessible by public transportation with a high concentration of FSWs, were more likely to screen. FSWs who had never been tested for HIV were more likely to enroll. This analysis suggests that the primary reason FSWs participated in the trial was a desire for health care-not other factors hypothesized to be important, e.g., HIV risk perception and poverty status.


Occupational therapy services for adult neurological clients in Queensland and therapists' use of telehealth to provide services.
Occupational therapy is an important component of neurological rehabilitation. Clients in rural areas have fewer opportunities to receive rehabilitation than those in metropolitan areas. Telehealth is a potential method of closing these gaps in service delivery, although research into telehealth applications for neurological rehabilitation is extremely limited. To assist in the development of appropriate telehealth applications, this study aimed to identify the nature of occupational therapy services for neurological rehabilitation in areas of Queensland other than the capital city of Brisbane, the barriers to service delivery, and the current uses of various information and communication technologies among occupational therapists. A self-administered questionnaire was sent to occupational therapists working in adult neurological rehabilitation in all areas of Queensland other than the capital city of Brisbane. Contact details were obtained from OT AUSTRALIA Queensland. Responses were received from 39 eligible participants. The client's home was the most frequent setting in which participants saw clients. Home visits and modifications, equipment prescription, client/family education, and activities of daily living assessment and retraining were the most common interventions provided by participants. Frequently identified barriers to service provision included travelling distance to clients, large workloads and limited resources. Telephone, email, fax, the Internet and videoconferencing were available in most workplaces. Few participants used the Internet or videoconferencing for purposes other than continuing professional development. Home-based assessment and intervention appear to be frequent components of occupational therapy practice among therapists working in neurological rehabilitation. The use of telehealth to provide direct home-based client services is currently limited, but should be explored as a possible solution to overcome some of the identified barriers to occupational therapy service provision for clients with neurological conditions in rural and remote areas.


100 days with scans of the same Catphan phantom on the same CT scanner.
Quality control (QC) of CT scanners is important to evaluate image quality and radiation dose. Different QC phantoms for testing image quality parameters on CT are commercially available, and Catphan phantoms are widely used for this purpose. More data from measured image quality parameters on CT are necessary to assess test methods, tolerance levels, and test frequencies. The aim of this study was to evaluate the stability of essential image quality parameters for axial and helical scans on one CT scanner over time. A Catphan 600 phantom was scanned on a Philips Ingenuity CT scanner for 100 days over a period of 6 months. At each day of testing, one helical scan covering the entire phantom and four axial scans covering four different modules in the phantom were performed. All images were uploaded into Image Owl for automatic analysis of CT numbers, modular transfer function (MTF), low-contrast resolution, noise, and uniformity. In general, the different image quality parameters for both scan techniques were stable over time compared to given tolerance levels. Average measured CT numbers differed between axial and helical scans, while MTF was almost identical for helical and axial scans. Axial scans had better low-contrast resolution and less noise than helical scans. The uniformity was relatively similar for axial and helical scans. Most standard deviations of measured values were larger for helical scans compared to axial scans. Test results in this study were stable over time for both scan techniques, but further studies on different CT scanners are required to confirm that this also holds true for other systems.


Local spatial clustering in youths' use of tobacco, alcohol, and marijuana in Boston.
Understanding geographic variation in youth drug use is important for both identifying etiologic factors and planning prevention interventions. However, little research has examined spatial clustering of drug use among youths by using rigorous statistical methods. The purpose of this study was to examine spatial clustering of youth use of tobacco, alcohol, and marijuana. Responses on tobacco, alcohol, and marijuana use from 1,292 high school students ages 13-19 who provided complete residential addresses were drawn from the 2008 Boston Youth Survey Geospatial Dataset. Response options on past month use included "none," "1-2," "3-9," and "10 or more." The response rate for each substance was approximately 94%. Spatial clustering of youth drug use was assessed using the spatial Bernoulli model in the SatScan™ software package. Approximately 12%, 36%, and 18% of youth reported any past-month use of tobacco, alcohol, and/or marijuana, respectively. Two clusters of elevated past tobacco use among Boston youths were generated, one of which was statistically significant. This cluster, located in the South Boston neighborhood, had a relative risk of 5.37 with a p-value of 0.00014. There was no significant localized spatial clustering in youth past alcohol or marijuana use in either the unadjusted or adjusted models. Significant spatial clustering in youth tobacco use was found. Finding a significant cluster in the South Boston neighborhood provides reason for further investigation into neighborhood characteristics that may shape adolescents' substance use behaviors. This type of research can be used to evaluate the underlying reasons behind spatial clustering of youth substance and to target local drug abuse prevention interventions and use.


Sinus node dysfunction in patients with Fontan circulation: could heart rate variability be a predictor for pacemaker implantation?
Sinus node dysfunction (SND) causes significant morbidity in patients after Fontan surgery. Heart rate variability (HRV) reflects the autonomic regulation of the heart, and changes in HRV have been associated with SND in adults. We aimed to study whether changes in HRV could be detected in 24-h electrocardiographic (ECG) recordings in Fontan patients with SND. We compared HRV results from two patient groups; patients with Fontan circulation who later required a pacemaker due to severe SND (n = 12) and patients with Fontan circulation and SND, without indication for pacemaker treatment (n = 11), with two control groups; patients with Fontan circulation without SND (n = 90) and healthy controls (n = 66). The Poincaré plot index SD2 (representing changes in heart rate over 24-h) and the very low-frequency (VLF) HRV component were significantly higher in both SND groups, both compared with healthy controls and patients with Fontan circulation without SND. In SND patients with pacemakers, SD2 and VLF were slightly reduced compared to SND patients without pacemaker (p = 0.06). In conclusion, in Fontan patients with SND the HRV is significantly higher compared to healthy controls and Fontan patients without SND. However, in patients with severe SND requiring pacemaker, SD2 and VLF tended to be lower than in patients with SND without pacemaker, which could indicate a reduced diurnal HRV in addition to the severe bradycardia. This is a small study, but our results indicate that HRV analysis might be a useful method in the follow-up of Fontan patients regarding development of SND.


Sox9+ ductal cells are multipotent progenitors throughout development but do not produce new endocrine cells in the normal or injured adult pancreas.
One major unresolved question in the field of pancreas biology is whether ductal cells have the ability to generate insulin-producing β-cells. Conclusive examination of this question has been limited by the lack of appropriate tools to efficiently and specifically label ductal cells in vivo. We generated Sox9CreER(T2) mice, which, during adulthood, allow for labeling of an average of 70% of pancreatic ductal cells, including terminal duct/centroacinar cells. Fate-mapping studies of the Sox9(+) domain revealed endocrine and acinar cell neogenesis from Sox9(+) cells throughout embryogenesis. Very small numbers of non-β endocrine cells continue to arise from Sox9(+) cells in early postnatal life, but no endocrine or acinar cell neogenesis from Sox9(+) cells occurs during adulthood. In the adult pancreas, pancreatic injury by partial duct ligation (PDL) has been suggested to induce β-cell regeneration from a transient Ngn3(+) endocrine progenitor cell population. Here, we identify ductal cells as a cell of origin for PDL-induced Ngn3(+) cells, but fail to observe β-cell neogenesis from duct-derived cells. Therefore, although PDL leads to activation of Ngn3 expression in ducts, PDL does not induce appropriate cues to allow for completion of the entire β-cell neogenesis program. In conclusion, although endocrine cells arise from the Sox9(+) ductal domain throughout embryogenesis and the early postnatal period, Sox9(+) ductal cells of the adult pancreas no longer give rise to endocrine cells under both normal conditions and in response to PDL.


Novel Application of Junction Trees to the Interpretation of Epigenetic Differences among Lung Cancer Subtypes.
In this era of precision medicine, understanding the epigenetic differences in lung cancer subtypes could lead to personalized therapies by possibly reversing these alterations. Traditional methods for analyzing microarray data rely on the use of known pathways. We propose a novel workflow, called Junction trees to Knowledge (J2K) framework, for creating interpretable graphical representations that can be derived directly from in silico analysis of microarray data. Our workflow has three steps, preprocessing (discretization and feature selection), construction of a Bayesian network and, its subsequent transformation into a Junction tree. We used data from the Cancer Genome Atlas to perform preliminary analyses of this J2K framework. We found relevant cliques of methylated sites that are junctions of the network along with potential methylation biomarkers in the lung cancer pathogenesis.


High-density mapping of left atrial endocardial activation during sinus rhythm and coronary sinus pacing in patients with paroxysmal atrial fibrillation.
This study was designed to record global high-density maps of left atrial endocardial activation during sinus rhythm and coronary sinus pacing. Noncontact mapping of the left atrium was performed in nine patients with paroxysmal atrial fibrillation undergoing pulmonary vein ablation procedures. High-density isopotential and isochronal activation maps were superimposed on three-dimensional reconstructions of left atrial geometry. Mapping was repeated during pacing from sites within the coronary sinus. Earliest left atrial endocardial activation occurred anterior to the right pulmonary veins in seven patients and on the anterosuperior septum in two patients. A line of conduction block was seen in the posterior wall and inferior septum in all patients. The direction of activation in the left atrial myocardium overlying the coronary sinus was different from the electrogram sequence in the coronary sinus catheter in 6 of 9 patients. During coronary sinus pacing, activation entered the left atrium a mean (SD) of 41 (13) ms after the pacing stimulus at a site 12 (10) mm from the endocardium overlying the pacing electrode. Lines of conduction block were present in the posterior wall and inferior septum. In patients with paroxysmal atrial fibrillation, lines of conduction block are present in the left atrium during sinus rhythm and coronary sinus pacing. Electrograms recorded in the coronary sinus infrequently correspond to the direction of activation in the overlying left atrial myocardium.


Sexual orientation, gender, and attempted suicide among adolescent psychiatric inpatients.
Lesbian, gay, bisexual, and queer (LGBQ) and female youth report disproportionately high rates of attempted suicide. Previous studies have not addressed the association between sexual orientation, gender, and attempted suicide among adolescent psychiatric inpatients. This study examined LGBQ orientation as a correlate of attempted suicide above and beyond other risk factors (e.g., age, rurality, trauma exposure, psychopathology), and also examined the interaction between gender and sexual orientation with regard to attempted suicide. We conducted a chart review study that included 550 adolescent psychiatric inpatients admitted to a public psychiatric hospital. Adolescents completed standardized intake assessments and self-report measures of sociodemographics, history of attempted suicide, psychopathology, and trauma history. Sexual orientation, gender, and their interaction were evaluated as predictors of attempted suicide using sequential logistic regression. LGBQ youth were more than 3 times more likely (odds ratio [OR] = 3.08) than non-LGBQ peers to have attempted suicide, and female youth were more than twice as likely to have attempted suicide compared with male patients (OR = 2.44). There was not a significant LGBQ orientation by gender interaction. These findings demonstrate the importance of LGBQ orientation and female gender as risk factors for suicidal behavior in a sample of adolescent psychiatric inpatients. Although limited by the self-report and retrospective nature of the data collected, these findings suggest the importance of initial and ongoing assessment of gender, sexual orientation, and suicidality in inpatient youth and the need for additional research to inform effective intervention efforts in this high-risk population. (PsycINFO Database Record


Linking cortical spike pattern codes to auditory perception.
Abstract Neurometric analysis has proven to be a powerful tool for studying links between neural activity and perception, especially in visual and somatosensory cortices, but conventional neurometrics are based on a simplistic rate-coding hypothesis that is clearly at odds with the rich and complex temporal spiking patterns evoked by many natural stimuli. In this study, we investigated the possible relationships between temporal spike pattern codes in the primary auditory cortex (A1) and the perceptual detection of subtle changes in the temporal structure of a natural sound. Using a two-alternative forced-choice oddity task, we measured the ability of human listeners to detect local time reversals in a marmoset twitter call. We also recorded responses of neurons in A1 of anesthetized and awake ferrets to these stimuli, and analyzed these responses using a novel neurometric approach that is sensitive to temporal discharge patterns. We found that although spike count-based neurometrics were inadequate to account for behavioral performance on this auditory task, neurometrics based on the temporal discharge patterns of populations of A1 units closely matched the psychometric performance curve, but only if the spiking patterns were resolved at temporal resolutions of 20 msec or better. These results demonstrate that neurometric discrimination curves can be calculated for temporal spiking patterns, and they suggest that such an extension of previous spike count-based approaches is likely to be essential for understanding the neural correlates of the perception of stimuli with a complex temporal structure.


Microleakage evaluation of core buildup composite resins with total-etch and self-etch adhesive systems.
Core buildup composite resins with prefabricated posts are commonly used to restore endodontically treated teeth. This study compared the sealing ability of Core Max II and Panavia F2.0 cement with total-etch and self-etch adhesive systems. Sixty recently extracted human second premolar teeth were chosen and their crowns were cut 3 mm above the CEJ. After preparing proximal boxes (4+/-1 mm buccolingually and 3 mm occlusogingivally dimensions) and finishing root canal therapy, the teeth were randomly divided into four groups (n=15): groups 1 and 2, Core Max II without and with total-etch adhesive; groups 3 and 4, Clearfil photocore composite, A2 shade, and Panavia F2.0 cement without and with self-etch adhesive respectively. The Dentatus posts (# 2 Long) were used in canals approximately 8 mm depth. According to manufacturer guidelines, pins were cemented and cores were restored. After keeping the specimens for 24 hours at 37 degrees C and 100% humidity, they were thermally cycled for 500 cycles, sealed with nail varnish except 1 mm beyond the margins of restoration, and then immersed in a 0.5% fuschin basic for 24 hours. Samples were embedded in clear epoxy resin, sectioned mesiodistally, and observed at 20x magnification. The microleakage was assessed under stereomicroscope and the results were recorded in percentage of dye penetration to the whole path from the cavosurface margin of the proximal boxes to the end of the post. Analysis of variance and the Tukey test were used to evaluate the data (p=0.05). Groups 1 and 4 had the highest and the lowest values of microleakage respectively. Microleakage of Panavia F2.0 cement was lower than for Core Max II and for both cements using adhesive made the microleakage smaller than without it (p<0.05). Application of adhesive using Core Max II cement and Panavia F2.0 cement is strongly recommended to decrease microleakage. Self-etch adhesive performed better than total-etch adhesive. With regards to microleakage, the self-etching primer displayed better sealing than that obtained with the total-etching, two-step dental adhesive.


Role of Pseudomonas aeruginosa pili in acute pulmonary infection.
The role of piliation in the development and course of acute pulmonary infection was examined using infant BALB/cByJ mice inoculated by intranasal instillation of isogenic Pil+ and Pil- mutants of Pseudomonas aeruginosa PA1244, PAK, and PAO1. The piliated strains caused more cases of pneumonia, bacteremia, and mortality than the nonpiliated strains (chi-square analysis, alpha = 0.001). The piliated strains were more often associated with severe diffuse pneumonias, while the nonpiliated organisms resulted in less severe, focal pneumonias, although these differences did not achieve statistical significance. Purified pilin protein used to inoculate the mice resulted in local inflammatory changes. The nonpiliated strain PA1244-NP was as virulent as the piliated strain PAO1, suggesting that expression of other virulence factors are also important in the development of acute pneumonia. This infant mouse model of pulmonary infection appears to be a useful system for the analysis of P. aeruginosa virulence factors involved in the pathogenesis of pneumonia.


Universal ribotyping method using a chemically labelled oligonucleotide probe mixture.
Some of the present problems in ribotyping are associated with a lack of uniform reactivity of probes when bacterial DNAs are of phylogenetically diverse origins. To overcome these problems, a set of five oligonucleotides (referred to as OligoMix5) was selected to react with conserved sequences located near both extremities of rrs (16S rRNA gene) and near both extremities and the middle of rrl (23S rRNA gene). DNA samples from 13 bacterial species selected to represent various phylogenetic branches within the Eubacteria were cleaved by a restriction endonuclease and electrophoresed in 0.8% agarose, and the fragments were vacuum-transferred to nylon membranes and hybridized with digoxigenin-labelled OligoMix5, plasmid DNA from pKK3535 (cloned rrn operon from Escherichia coli) or pBA2 (cloned rrs from Bacillus subtilis), or acetylamino-fluorene-labelled E. coli 16 + 23S rRNA. The results showed OligoMix5 to visualize patterns in DNA from phylogenetically diverse bacteria with comparable intensity. Banding patterns (not band intensity) obtained with OligoMix5 were identical with those obtained with 16 + 23S rRNA or plasmid pKK3535 for each strain studied and represented complete ribotypes. For DNA from Gram-positive bacteria, complete ribotypes were observed after prolonged enzymatic detection of bands when probes were either E. coli 16 + 23S rRNA or pKK3535. Patterns given by plasmid pBA2 were subsets of the complete ribotypes for 9/13 strains. Each oligonucleotide of the OligoMix5 set was used as a probe to determine its contribution to the complete ribotype. The five oligonucleotide probes, used individually, visualized one to four patterns per DNA sample. Use of DNA from Xenorhabdus sp. CIP 105189 cleaved by EcoRI is suggested to control the quality of the oligonucleotide probes composing OligoMix5. Probe OligoMix5 was found to be an essential tool for ribotyping phylogenetically diverse eubacteria.


2-Degree-of-freedom Robot Path Planning using Cooperative Neural Fields.
This paper proposes a neural network solution to path planning by two degree-of-freedom (DOF) robots. The proposed network is a two-dimensional sheet of neurons forming a distributed representation of the robot's workspace. Lateral interconnections between neurons are "cooperative," so that the field exhibits oscillatory behavior. This paper shows how that oscillatory behavior can be used to solve the path-planning problem. The results reported show that the proposed neural network finds the variational solution of Bellman's dynamic programming equation.


Clinical significance of neutrophil gelatinase-associated lipocalin in Crimean-Congo hemorrhagic Fever.
Neutrophil gelatinase-associated lipocalin (NGAL), which is an important prognostic marker for sepsis and inflammatory diseases, is mostly released from neutrophils. Crimean-Congo hemorrhagic fever (CCHF) patients are generally neutropenic. We aimed to investigate whether there is a change in serum NGAL level and to investigate its effect on the recovery time (RT) during the course of CCHF. A total of 40 CCHF patients (19 females and 21 males) and 34 healthy controls (17 females and 17 males) were included in the study. The serum NGAL level and biochemical and hematological parameters were checked. The NGAL level of CCHF patients was significantly higher than that of the healthy controls (P < 0.001). A multivariate analysis showed that the independent prognostic factor for the prediction of the RT is the NGAL level (odds ratio [OR] 0.3, 95% confidence interval [Cl] 0.1-0.4, P < 0.001). An elevated NGAL level was found to be associated with an increased RT in CCHF patients. The NGAL levels of CHHF patients might be elevated due to increased cytokine release, the presence of a tissue injury, and the release of immature neutrophils from the bone marrow into the peripheral stream. This may be a good prognostic factor in CHHF patients.


Warming alters the body shape of European perch Perca fluviatilis.
The consequences of elevated temperature on body shape were investigated by comparing European perch Perca fluviatilis from the Forsmark area of the Baltic Sea to P. fluviatilis from a nearby Biotest enclosure. The Biotest is a man-made enclosure within the Baltic Sea that has received warm water from a nuclear power plant since 1980, resulting in temperatures that are elevated 5-10 °C relative to the surrounding Baltic Sea. Sampled fish ranged from young-of-the-year to 14 years. Geometric morphometrics and multivariate statistical analysis revealed significant morphological differences between individuals of P. fluviatilis from these two habitats. Most importantly, relative shape changed with size, with small individuals of P. fluviatilis from Biotest being characterized by a deeper body shape and a larger caudal peduncle than the smaller Baltic individuals. In large specimens, smaller differences were found with Biotest individuals being more slender than Baltic individuals. These results show that, in order to have a full understanding of the biological effects of elevated temperatures, studies that cover the entire size range of organisms will be important. Apart from the direct influence of temperature on growth rate and body shape, other ecological factors affected by temperature are discussed as possible contributors to the observed differences between the two populations.


Terahertz wave propagation in one-dimensional periodic dielectrics.
We demonstrate the temporal evolution of terahertz (THz) wave propagation in one-dimensional periodic dielectrics. Distributed Bragg reflectors and a resonant cavity are investigated: The structures involve air gaps interleaved between polymer films. Transmitted and reflected broadband THz waves are measured by means of THz time-domain spectroscopy. The experimental results agree well with transfer matrix calculations.


Congenital and neonatal malaria in a rural Kenyan district hospital: an eight-year analysis.
Malaria remains a significant burden in sub-Saharan Africa. However, data on burden of congenital and neonatal malaria is scarce and contradictory, with some recent studies reporting a high burden. Using prospectively collected data on neonatal admissions to a rural district hospital in a region of stable malaria endemicity in Kenya, the prevalence of congenital and neonatal malaria was described. From 1st January 2002 to 31st December 2009, admission and discharge information on all neonates admitted to Kilifi District Hospital was collected. At admission, blood was also drawn for routine investigations, which included a full blood count, blood culture and blood slide for malaria parasites. Of the 5,114 neonates admitted during the eight-year surveillance period, blood slide for malaria parasites was performed in 4,790 (93.7%). 18 (0.35%) neonates with Plasmodium falciparum malaria parasitaemia, of whom 11 were admitted within the first week of life and thus classified as congenital parasitaemia, were identified. 7/18 (39%) had fever. Parasite densities were low, ≤50 per μl in 14 cases. The presence of parasitaemia was associated with low haemoglobin (Hb) of <10 g/dl (χ² 10.9 P = 0.001). The case fatality rate of those with and without parasitaemia was similar. Plasmodium falciparum parasitaemia was identified as the cause of symptoms in four neonates. Congenital and neonatal malaria are rare in this malaria endemic region. Performing a blood slide for malaria parasites among sick neonates in malaria endemic regions is advisable. This study does not support routine treatment with anti-malarial drugs among admitted neonates with or without fever even in a malaria endemic region.


Gender differences in hip and ankle joint kinematics on knee abduction during running.
The knee is the most common site of running injuries, particularly prevalent in females. The purpose of this study was to clarify gender differences in the lower extremity kinematics during running, with a specific emphasis on the relationships between the distal and proximal factors and the knee joint kinematics. Eleven female and 11 male runners participated in this study. Three-dimensional marker positions were recorded with a motion analysis system while the subjects ran along a 25 m runway at a speed of 3.5 m/s. Kinematic variables were analyzed for the stance phase of the right leg. Female runners demonstrated significantly greater peak knee abduction (P<0.05), hip adduction (P<0.01) and internal rotation (P<0.05), whereas male runners demonstrated significantly greater peak rearfoot eversion (P<0.01). The knee abduction angles were positively correlated with hip adduction angles (r=0.49, P<0.05) and negatively correlated with rearfoot eversion (r= -0.69, P<0.001). There was no significant difference in normalised step width between genders (P>0.05). Smaller rearfoot eversion and greater hip adduction related closely to the greater knee abduction as the distal and proximal factors, respectively. These relationships are thought to be the compensatory joint motions in the frontal plane, because there was no significant difference in the normalised step width between females and males. The current results suggest that if the step width is identical, the subjects with greater knee abduction had smaller rearfoot eversion to compensate for greater hip adduction, which were more apparent in females. This explains greater knee abduction found in female runners, which can be linked to a high risk of knee injury.


A Narrowband Spintronic Terahertz Emitter Based on Magnetoelastic Heterostructures.
Narrowband terahertz (THz) radiation is crucial for high-resolution spectral identification, but a narrowband THz source driven by a femtosecond (fs) laser has remained scarce. Here, it is computationally predicted that a metal/dielectric/magnetoelastic heterostructure enables converting a fs laser pulse into a multicycle THz pulse with a narrow linewidth down to ∼1.5 GHz, which is in contrast to the single-cycle, broadband THz pulse from the existing fs-laser-excited emitters. It is shown that such narrowband THz pulse originates from the excitation and long-distance transport of THz spin waves in the magnetoelastic film, which can be enabled by a short strain pulse obtained from fs laser irradiation of the metal film when the thicknesses of the metal and magnetoelastic films both fall into a specific range. These results therefore reveal an approach to achieving optical generation of narrowband THz pulse based on heterostructure design, which also has implications in the design of THz magnonic devices.


Educational and Training Interventions Aimed at Healthcare Workers in the Detection and Management of People With Mental Health Conditions in South and South-East Asia: A Systematic Review.
Background: To bridge significant mental health treatment gaps, it is essential that the healthcare workforce is able to detect and manage mental health conditions. We aim to synthesise evidence of effective educational and training interventions aimed at healthcare workers to increase their ability to detect and manage mental health conditions in South and South-East Asia. Methods: Systematic review of six electronic academic databases from January 2000 to August 2020 was performed. All primary research studies were eligible if conducted among healthcare workers in South and South-East Asia and reported education and training interventions to improve detection and management of mental health conditions. Quality of studies were assessed using Modified Cochrane Collaboration, ROBINS-I, and Mixed Methods Appraisal Tools and data synthesised by narrative synthesis. Results are reported according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. A review protocol was registered with the PROSPERO database (CRD42020203955). Findings: We included 48 of 3,654 screened articles. Thirty-six reported improvements in knowledge and skills in the detection and management of mental health conditions. Training was predominantly delivered to community and primary care health workers to identify and manage common mental health disorders. Commonly used training included the World Health Organization's mhGAP guidelines (n = 9) and Cognitive Behavioural Therapy (n = 8) and were successfully tailored and delivered to healthcare workers. Digitally delivered training was found to be acceptable and effective. Only one study analysed cost effectiveness. Few targeted severe mental illnesses and upskilling mental health specialists or offered long-term follow-up or supervision. We found 21 studies were appraised as low/moderate and 19 as high/critical risk of bias. Interpretation: In low resource country settings, upskilling and capacity building of primary care and community healthcare workers can lead to better detection and management of people with mental health disorders and help reduce the treatment gap. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020203955.


Expression of Clostridium difficile toxins A and B and their sigma factor TcdD is controlled by temperature.
Growth temperature was found to control the expression of toxins A and B in Clostridium difficile VPI 10463, with a maximum at 37 degrees C and low levels at 22 and 42 degrees C in both peptone yeast (PY) and defined media. The up-regulation of toxin A and B mRNA and protein levels upon temperature upshift from 22 to 37 degrees C followed the same kinetics, showing that temperature control occurred at the level of transcription. Experiments with Clostridium perfringens using gusA as a reporter gene demonstrated that both toxin gene promoters were temperature controlled and that their high activity at 37 degrees C was dependent on the alternative sigma factor TcdD. Furthermore, tcdD was found to be autoinduced at 37 degrees C. Glucose down-regulated all these responses in the C. perfringens constructs, similar to its impact on toxin production in C. difficile PY broth cultures. C. difficile proteins induced at 37 degrees C and thus coregulated with the toxins by temperature were demonstrated by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and identified as enzymes involved in butyric acid production and as electron carriers in oxidation-reduction reactions. The regulation of toxin production in C. difficile by temperature is a novel finding apparently reflecting an adaptation of the expression of its virulence to mammalian hosts.


P2X7 Receptor Inhibition Improves CD34 T-Cell Differentiation in HIV-Infected Immunological Nonresponders on c-ART.
Peripheral CD4+ T-cell levels are not fully restored in a significant proportion of HIV+ individuals displaying long-term viral suppression on c-ART. These immunological nonresponders (INRs) have a higher risk of developing AIDS and non-AIDS events and a lower life expectancy than the general population, but the underlying mechanisms are not fully understood. We used an in vitro system to analyze the T- and B-cell potential of CD34+ hematopoietic progenitor cells. Comparisons of INRs with matched HIV+ patients with high CD4+ T-cell counts (immune responders (IRs)) revealed an impairment of the generation of T-cell progenitors, but not of B-cell progenitors, in INRs. This impairment resulted in the presence of smaller numbers of recent thymic emigrants (RTE) in the blood and lower peripheral CD4+ T-cell counts. We investigated the molecular pathways involved in lymphopoiesis, focusing particularly on T-cell fate specification (Notch pathway), survival (IL7R-IL7 axis) and death (Fas, P2X7, CD39/CD73). P2X7 expression was abnormally strong and there was no CD73 mRNA in the CD34+ cells of INRs, highlighting a role for the ATP pathway. This was confirmed by the demonstration that in vitro inhibition of the P2X7-mediated pathway restored the T-cell potential of CD34+ cells from INRs. Moreover, transcriptomic analysis revealed major differences in cell survival and death pathways between CD34+ cells from INRs and those from IRs. These findings pave the way for the use of complementary immunotherapies, such as P2X7 antagonists, to restore T-cell lymphopoiesis in INRs.


Perceived Difficulty of Performing Selected HIV/AIDS Preventive Behaviors and Life Satisfaction: Is there a Relationship for African American Adolescents?
Research on the relationship between adolescent health risk behaviors, sexual risk behaviors in particular, and perceived life satisfaction is emerging. Some researchers suggest that life satisfaction has been a neglected component of adolescent health research. African American adolescents aged 13-18 (n = 1,658) from four matched, mid-sized cities in the northeastern and southeastern USA, completed a self-report questionnaire via Audio Computer Assisted Self-Interview. Analyses were conducted to examine relationships between perceived difficulty in performing HIV/AIDS preventive behavior and perceived life satisfaction, while controlling for socioeconomic status. Results suggest that perceived life satisfaction is related to perceived difficulty in performing HIV/AIDS preventive behaviors, for both males and females, with variability in the magnitude of associations by gender. Further research is necessary to identify the particular characteristics of youth and specific aspects of adolescent life satisfaction associated with perceived difficulty in performing HIV/AIDS preventive behavior to develop gender-appropriate and culturally-sensitive quality of life/health promotion programs.


Availability of services for subjects of sexual assault in genitourinary medicine clinics.
The aim of this study is to gain an understanding of the services available to subjects of sexual assault at genitourinary medicine (GU medicine) clinics throughout the United Kingdom, and to determine whether these services are adequate. By means of a questionnaire, consultants in 106 clinics provided information on the number of patients who reported sexual assault and the services available to them. The study found a marked regional variation in attendances by subjects of sexual assault. However, only a minority of clinics kept accurate data (36.7% regarding female victims and 37.75% regarding male victims). The number of subjects who were aged under 16 years was disproportionately high (under 16s: 6.9% of female victims and 1.2% male victims; 16 and over: 1.3% of female victims and 0.14% of male victims). This survey highlights deficiencies in services that need to be addressed by clinics, management and the speciality.


Young children's analogical problem solving: gaining insights from video displays.
This study examined how toddlers gain insights from source video displays and use the insights to solve analogous problems. The sample of 2- and 2.5-year-olds viewed a source video illustrating a problem-solving strategy and then attempted to solve analogous problems. Older, but not younger, toddlers extracted the problem-solving strategy depicted in the video and spontaneously transferred the strategy to solve isomorphic problems. Transfer by analogy from the video was evident only when the video illustrated the complete problem goal structure, including the character's intention and the action needed to achieve a goal. The same action isolated from the problem-solving context did not serve as an effective source analogue. These results illuminate the development of early representation and processes involved in analogical problem solving. Theoretical and educational implications are discussed.


Towards a Computable Data Corpus of Temporal Correlations between Drug Administration and Lab Value Changes.
The analysis of electronic health records for an automated detection of adverse drug reactions is an approach to solve the problems that arise from traditional methods like spontaneous reporting or manual chart review. Algorithms addressing this task should be modeled on the criteria for a standardized case causality assessment defined by the World Health Organization. One of these criteria is the temporal relationship between drug intake and the occurrence of a reaction or a laboratory test abnormality. Appropriate data that would allow for developing or validating related algorithms is not publicly available, though. In order to provide such data, retrospective routine data of drug administrations and temporally corresponding laboratory observations from a university clinic were extracted, transformed and evaluated by experts in terms of a reasonable time relationship between drug administration and lab value alteration. The result is a data corpus of 400 episodes of normalized laboratory parameter values in temporal context with drug administrations. Each episode has been manually classified whether it contains data that might indicate a temporal correlation between the drug administration and the change of the lab value course, whether such a change is not observable or whether a decision between those two options is not possible due to the data. In addition, each episode has been assigned a concordance value which indicates how difficult it is to assess. This is the first open data corpus of a computable ground truth of temporal correlations between drug administration and lab value alterations. The main purpose of this data corpus is the provision of data for further research and the provision of a ground truth which allows for comparing the outcome of other assessments of this data with the outcome of assessments made by human experts. It can serve as a contribution towards systematic, computerized ADR detection in retrospective data. With this lab value curve data as a basis, algorithms for detecting temporal relationships can be developed, and with the classification made by human experts, these algorithms can immediately be validated. Due to the normalization of the lab value data, it allows for a generic approach rather than for specific or solitary drug/lab value combinations.


Ab initio modeling of the bonding of benzotriazole corrosion inhibitor to reduced and oxidized copper surfaces.
The bonding of benzotriazole-an outstanding corrosion inhibitor for copper-on reduced and oxidized copper surfaces is discussed on the basis of density functional theory (DFT) calculations. Calculations reveal that benzotriazole is able to bond with oxide-free and oxidized copper surfaces and on both of them it bonds significantly stronger to coordinatively unsaturated Cu sites. This suggests that benzotriazole is able to passivate the reactive under-coordinated surface sites that are plausible microscopic sites for corrosion attack. Benzotriazole can adsorb in a variety of different forms, yet it forms a strong molecule-surface bond only in deprotonated form. The bonding is even stronger when the deprotonated form is incorporated into organometallic adcomplexes. This is consistent with existing experimental evidence that benzotriazole inhibits corrosion by forming protective organometallic complexes. It is further shown that adsorption of benzotriazole considerably reduces the metal work function, which is a consequence of a large permanent molecular dipole and a properly oriented adsorption structure. It is argued that such a pronounced effect on the work function might be relevant for corrosion inhibition, because it should diminish the anodic corrosion reaction, which is consistent with existing experimental evidence that benzotriazole, although a mixed type inhibitor, predominantly affects the anodic reaction.


Progressive pseudorheumatoid dysplasia involving a novel WISP3 mutation and sacroiliac and hip arthritis: A case report and literature review.
Progressive pseudorheumatoid dysplasia (PPRD) is a rare autosomal recessive genetic disease caused by mutations in the Wnt1-inducible signaling pathway protein 3 gene. PPRD is considered a noninflammatory disease, and involvement of the sacroiliac joint and hip arthritis have not been reported previously. We report a case of PPRD in an 11-year-old boy, who presented with bilateral pain and swelling in the knees, elbows, and ankles, and bilateral pain without swelling in the shoulders, wrists, knuckles, and proximal and distal interphalangeal joints for the past 5 years. He had been misdiagnosed with juvenile idiopathic arthritis for more than 6 years. The correct PPRD diagnosis was made using whole-exome sequencing for Wnt1-inducible signaling pathway protein 3 gene mutations (c.589 + 2T>C and c.721T>G; both mutations have rarely been reported) and magnetic resonance imaging examination; moreover, the latter showed inflammation of the sacroiliac joint and hip joint. The patient was administered supplemental calcium, active vitamin D, and glucosamine sulfate. The patient experienced alleviation of joint pain following treatment initiation; however, joint motion improvement was not obvious. Above all, the long-term use of biologic or targeted synthetic disease-modifying antirheumatic drugs in the future was avoided. The findings of the inflammatory aspects in PPRD will enrich our understanding of this rheumatological disease.


Learning Probabilistic Inference through Spike-Timing-Dependent Plasticity.
Numerous experimental data show that the brain is able to extract information from complex, uncertain, and often ambiguous experiences. Furthermore, it can use such learnt information for decision making through probabilistic inference. Several models have been proposed that aim at explaining how probabilistic inference could be performed by networks of neurons in the brain. We propose here a model that can also explain how such neural network could acquire the necessary information for that from examples. We show that spike-timing-dependent plasticity in combination with intrinsic plasticity generates in ensembles of pyramidal cells with lateral inhibition a fundamental building block for that: probabilistic associations between neurons that represent through their firing current values of random variables. Furthermore, by combining such adaptive network motifs in a recursive manner the resulting network is enabled to extract statistical information from complex input streams, and to build an internal model for the distribution p (*) that generates the examples it receives. This holds even if p (*) contains higher-order moments. The analysis of this learning process is supported by a rigorous theoretical foundation. Furthermore, we show that the network can use the learnt internal model immediately for prediction, decision making, and other types of probabilistic inference.


Relations between childhood traumatic experiences, dissociation, and cognitive models in obsessive compulsive disorder.
Previous studies have indicated that obsessive compulsive disorder (OCD) is associated with childhood traumatic experiences and higher levels of dissociation. Dissociative tendency may arise when individual attempt to incorporate adverse experiences into cognitive schema. We investigated the possible links among childhood trauma, dissociation, and cognitive processes. We evaluated 95 patients with OCD using the Beck Depression Inventory (BDI), Thought-Action Fusion Scale (TAFS), Metacognitions Questionnaire (MCQ-30), White Bear Suppression Inventory (WBSI), Dissociative Experiences Scale (DES), and Childhood Trauma Questionnaire (CTQ-28). The CTQ-28 total scores were not associated with Y-BOCS total, Y-BOCS insight, BDI, TAFS, MCQ-30, and WBSI scores. The TAFS Total, MCQ-30, WBSI, and BDI scores were significantly associated with DES scores. Regression analysis revealed that MCQ-30 and WBSI scores significantly predicted the DES scores. These results suggest that in spite of pathological connotation of dissociative experiences, dissociation may primarily constitute a cognitive trait which is strongly associated with cognitive processes.


A bioink blend for rotary 3D bioprinting tissue engineered small-diameter vascular constructs.
3D bioprinted vascular constructs have gained increased interest due to their significant potential for creating customizable alternatives to autologous vessel grafts. In this study, we developed a new approach for biofabricating fibrin-based vascular constructs using a novel rotary 3D bioprinter developed in our lab. We formulated a new bioink by incorporating fibrinogen with gelatin to achieve a desired shear-thinning property for rotary bioprinting. The blending of heat-treated gelatin with fibrinogen turned unprintable fibrinogen into a printable biomaterial for vessel bioprinting by leveraging the favorable rheological properties of gelatin. We discovered that the heat-treatment of gelatin remarkably affects the rheological properties of a gelatin-fibrinogen blended bioink, which in turn influences the printability of the ink. Further characterizations revealed that not only concentration of the gelatin but the heat treatment also affects cell viability during printing. Notably, the density of cells included in the bioinks also influenced printability and tissue volumetric changes of the printed vessel constructs during cultures. We observed increased collagen deposition and construct mechanical strength during two months of the cultures. The burst pressure of the vessel constructs reached 1110 mmHg, which is about 52% of the value of the human saphenous vein. An analysis of the tensile mechanical properties of the printed vessel constructs unveiled an increase in both the circumferential and axial elastic moduli during cultures. This study highlights important considerations for bioink formulation when bioprinting vessel constructs. STATEMENT OF SIGNIFICANCE: There has been an increased demand for small-diameter tissue-engineered vascular grafts. Vascular 3D bioprinting holds the potential to create equivalent vascular grafts but with the ability to tailor them to meet patient's needs. Here, we presented a new and innovative 3D rotary bioprinter and a new bioink formulation for printing vascular constructs using fibrinogen, a favorable biomaterial for vascular tissue engineering. The bioink was formulated by blending fibrinogen with a more printable biomaterial, gelatin. The systematic characterization of the effects of heat treatment and gelatin concentration as well as bioink cell concentration on the printability of the bioink offers new insight into the development of printable biomaterials for tissue biofabrication.


A new variant ligament of the atlantooccipital joint: the lateral oblique atlantooccipital ligament.
During routine dissection of the anterior craniocervical junction (CCJ), a variant ligament just anterior to the articular capsule of the atlantooccipital joint was observed. To our knowledge, no literature has previously described this ligament. Therefore, the aim of this study was to clarify the anatomy, incidence, and biomechanics of this undescribed structure of the anterior atlantooccipital joint. Twenty-six sides from 13 fresh-frozen adult cadavers were used for this study and the morphology of the variant ligament examined. When present, its length, width, thickness, and the angle from the midline of the CCJ were measured. The variant ligament identified, when present, is distinct and located anterior to the atlantooccipital joint capsule traveling between the occipital bone and the transverse process of the atlas. The ligament was found on 12 of 26 sides (46.2%). The mean length of the ligament was 32.0 ± 5.5 mm. The ligament became taut with contralateral lateral flexion and the ipsilateral rotation of the atlantooccipital joint. We propose that this ligament may be termed the lateral oblique atlantooccipital ligament. To date, this structure has not been described in any textbooks or reports in the extant medical literature. Although its function is not clear, based on its course and connections, it might function as a secondary stabilizer of the atlantooccipital joint. As the stability of the craniocervical junction is of paramount importance, knowledge of normal and variant anatomical structures in this region is important for the surgeon treating patients with pathology of this region. These slides can be retrieved under Electronic Supplementary Material.


The effects of gender and catechol O-methyltransferase (COMT) Val108/158Met polymorphism on emotion regulation in velo-cardio-facial syndrome (22q11.2 deletion syndrome): An fMRI study.
Velo-cardio-facial syndrome (VCFS) is caused by a micro-deletion of over 40 genes at the q11.2 locus of chromosome 22 and is a risk factor for the development of schizophrenia and other psychiatric disorders. COMT, one of the genes located in the deleted region, has been considered as a major candidate gene for genetic susceptibility in psychiatric diseases. Its functional polymorphism Val108/158Met has been shown to affect prefrontal function and working memory and has been associated with emotional dysregulation. We utilized a functional magnetic resonance imaging (fMRI) event-related paradigm to asses COMT genotype and gender-moderated effects on the neural activation that are elicited by viewing emotionally salient images charged with pleasant, unpleasant, and neutral content. Since estrogen down-regulates COMT activity resulting in lower COMT activity in women than men, we hypothesized an allele-by-gender interaction effect on neural activation. Participants included 43 VCFS individuals (Val/male=9, Val/female=17, Met/male=9, Met/female=8). We observed a gender effect on processing positive emotions, in that girls activated the cingulate gyrus more than boys did. We further observed a significant gender-by-allele interaction effect on neural function specific to the frontal lobe during the processing of pleasant stimuli, and specific to limbic regions during the processing of unpleasant stimuli. Our results suggest that in VCFS, the effect of the COMT Val108/158Met polymorphism is moderated by gender during the processing of emotional stimuli and could contribute to the understanding of the way in which this COMT polymorphism affects vulnerability to neuropsychiatric disorders.


Highly birefringent microstructured fibers with enhanced sensitivity to hydrostatic pressure.
We designed, manufactured and characterized two birefringent microstructured fibers that feature a 5-fold increase in polarimetric sensitivity to hydrostatic pressure compared to the earlier reported values for microstructured fibers. We demonstrate a good agreement between the finite element simulations and the experimental values for the polarimetric sensitivity to pressure and to temperature. The sensitivity to hydrostatic pressure has a negative sign and exceeds -43 rad/MPa x m at 1.55 microm for both fibers. In combination with the very low sensitivity to temperature, this makes our fibers the candidates of choice for the development of microstructured fiber based hydrostatic pressure measurement systems.


Transcriptomic landscape of acute promyelocytic leukemia reveals aberrant surface expression of the platelet aggregation agonist Podoplanin.
Acute promyelocytic leukemia (APL) is a medical emergency because of associated lethal early bleeding, a condition preventable by prompt diagnosis and therapeutic intervention. The mechanisms underlying the hemostatic anomalies of APL are not completely elucidated. RNA-sequencing-based characterization of APL (n = 30) was performed and compared to that of other acute myeloid leukemia (n = 400) samples and normal promyelocytes. Perturbations in the transcriptome of coagulation and fibrinolysis-related genes in APL extend beyond known culprits and now include Thrombin, Factor X and Urokinase Receptor. Most intriguingly, the Podoplanin (PDPN) gene, involved in platelet aggregation, is aberrantly expressed in APL promyelocytes and is the most distinctive transcript for this disease. Using an antibody panel optimized for AML diagnosis by flow cytometry, we also found that PDPN was the most specific surface marker for APL, and that all-trans retinoic acid therapy rapidly decreases its expression. Functional studies showed that engineered overexpression of this gene in human leukemic cells causes aberrant platelet binding, activation and aggregation. PDPN-expressing primary APL cells, but not PDPN-negative primary leukemias, specifically induce platelet binding, activation and aggregation. Finally, PDPN expression on leukemia cells in a xenograft model was associated with thrombocytopenia and prolonged bleeding time in vivo. Together our results suggest that PDPN may contribute to the hemostatic perturbations found in APL.


Ginkgolide A Prevents the Amyloid-β-Induced Depolarization of Cortical Neurons.
Utilizing the N-methyl-d-aspartate (NMDA) receptor antagonist as a strategy, memantine is the only agent available for clinically treating mild to severe Alzheimer's disease (AD). Our aim was to develop novel similar herb-based drugs. Using a screening platform, ginkgolide A (GA), a pure compound extracted from Ginkgo biloba, was found to attenuate amyloid β (Aβ)-induced abnormal depolarization in mouse primary cortical neurons. Using receptor agonists, it was determined that GA inhibits both NMDA receptors and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Furthermore, the Aβ-induced increase in c-Jun N-terminal kinase phosphorylation in neurons was prevented by GA. Body weight, glutamate oxaloacetate transaminase, glutamic-pyruvic transaminase, liver histology, and kidney histology were similar when the wild-type/AD animal model mice with and without GA treatment were compared. This pure compound improves the memory of wild-type mice. Our findings indicate that GA has great potential clinically for the treatment of AD because it might target NMDA receptors just like memantine.


The power and promise of genetic mapping from Plasmodium falciparum crosses utilizing human liver-chimeric mice.
Genetic crosses are most powerful for linkage analysis when progeny numbers are high, parental alleles segregate evenly and numbers of inbred progeny are minimized. We previously developed a novel genetic crossing platform for the human malaria parasite Plasmodium falciparum, an obligately sexual, hermaphroditic protozoan, using mice carrying human hepatocytes (the human liver-chimeric FRG NOD huHep mouse) as the vertebrate host. We report on two genetic crosses-(1) an allopatric cross between a laboratory-adapted parasite (NF54) of African origin and a recently patient-derived Asian parasite, and (2) a sympatric cross between two recently patient-derived Asian parasites. We generated 144 unique recombinant clones from the two crosses, doubling the number of unique recombinant progeny generated in the previous 30 years. The allopatric African/Asian cross has minimal levels of inbreeding and extreme segregation distortion, while in the sympatric Asian cross, inbred progeny predominate and parental alleles segregate evenly. Using simulations, we demonstrate that these progeny provide the power to map small-effect mutations and epistatic interactions. The segregation distortion in the allopatric cross slightly erodes power to detect linkage in several genome regions. We greatly increase the power and the precision to map biomedically important traits with these new large progeny panels.


Sarcopenia in patients with hip fracture: A multicenter cross-sectional study.
Sarcopenia is prevalent in older persons and is a risk factor for falls, fractures, and mortality. The aim of this study was to determine a) the feasibility of determining sarcopenia in patients with acute hip fracture, b) the prevalence of sarcopenia and c) associations of sarcopenia with nutritional status and comorbidities. A multicenter cross-sectional study on sarcopenia in male and female patients with acute hip fracture. Participants were previously ambulatory and living in the community. Sarcopenia was assessed postoperatively with muscle mass estimated by anthropometry using triceps skinfold, arm circumference, height, weight and sex. Grip strength was measured by Jamar dynamometer and pre-fracture mobility was by self-report using the New Mobility Score. Out of 282 patients, 202 were assessed for sarcopenia of whom 74 (37%) were diagnosed as sarcopenic. Sarcopenia was associated with age, odds ratio (OR) 1.4 per 5 years, 95% confidence interval (CI) [1.1, 1.8], ASA Physical Status Classification System score, OR 2.3 per point, 95% CI [1.3, 4.3] and number of medications at discharge, OR 1.2 per medication, 95% CI [1.0, 1.3] and inversely associated with BMI, OR 0.8, 95% CI [0.7, 0.9] and serum albumin, OR 0.9, 95% CI [0.8,1.0]. Thirty-seven percent of assessed subjects were diagnosed with sarcopenia. Our data demonstrates that the prevalence of sarcopenia is associated with older age, malnutrition and comorbidities. Determining sarcopenia at the bedside was feasible in postoperative hip fracture patients by using grip strength, estimation of muscle mass by anthropometry and self-reported mobility.


Prefrontal cortical abnormalities in currently depressed versus currently remitted patients with major depressive disorder.
Previous neuromorphometric investigations of major depressive disorder (MDD) have reported abnormalities in gray matter in several regions, although the results have been inconsistent across studies. Some discrepancies in the results across studies may reflect design limitations such as small sample sizes, whereas others may reflect biological variability that potentially manifests as differences in clinical course. For example, it remains unclear whether the abnormalities found in persistently depressed MDD subjects extend to or persist in patients who experience prolonged remission. The aim of the present study was to investigate gray matter (GM) differences in unmedicated, currently-depressed participants (dMDD) and unmedicated, currently-remitted (rMDD) participants with MDD compared to healthy controls (HC). The GM density and volume were compared across groups using voxel-based morphometry, a quantitative neuroanatomical technique, and high-resolution MRI images from 107 HC, 58 dMDD and 27 rMDD subjects. Relative to the HC group the dMDD group had reduced GM in the dorsal anterolateral (DALPFC), the dorsomedial (DMPFC) and the ventrolateral prefrontal cortex (VLPFC). Relative to the rMDD group the dMDD group showed reduced GM in the DALPFC, the VLPFC, the anterior cingulate cortex (ACC), the precuneus and the inferior parietal lobule. No regions were identified in which the rMDD group showed significantly lower GM compared to the HC group after p-values were corrected for the number of comparisons performed. In unmedicated patients in the depressed phase of MDD, we found evidence of morphometric abnormalities in DALPFC and in medial prefrontal cortical regions belonging to the visceromotor network. These findings, along with the absence of GM abnormalities in the remitted sample imply a possible link between greater GM tissue and better clinical outcome. Consistent with other neuroimaging and post-mortem neuropathological studies of MDD, we also found evidence of decreased white matter in patients with dMDD and rMDD.


Eye movement disorders are different in Parkin-linked and idiopathic early-onset PD.
Parkin gene mutations are the most common cause of early-onset parkinsonism. Patients with Parkin mutations may be clinically indistinguishable from patients with idiopathic early-onset Parkinson disease (EOPD) without Parkin mutations. Eye movement disorders have been shown to differentiate parkinsonian syndromes, but have never been systematically studied in Parkin mutation carriers. Eye movements were recorded in symptomatic (n = 9) and asymptomatic Parkin mutation carriers (n = 13), patients with idiopathic EOPD (n = 14), and age-matched control subjects (n = 27) during established oculomotor tasks. Both patients with EOPD and symptomatic Parkin mutation carriers showed hypometric prosaccades toward visual stimuli, as well as deficits in suppressing reflexive saccades toward unintended targets (antisaccade task). When directing gaze toward memorized target positions, patients with EOPD exhibited hypometric saccades, whereas symptomatic Parkin mutation carriers showed normal saccades. In contrast to patients with EOPD, the symptomatic Parkin mutation carriers showed impaired tracking of a moving target (reduced smooth pursuit gain). The asymptomatic Parkin mutation carriers did not differ from healthy control subjects in any of the tasks. Although clinically similarly affected, symptomatic Parkin mutation carriers and patients with idiopathic EOPD differed in several oculomotor tasks. This finding may point to distinct anatomic structures underlying either condition: dysfunctions of cortical areas involved in smooth pursuit (V5, frontal eye field) in Parkin-linked parkinsonism vs greater impairment of basal ganglia circuits in idiopathic Parkinson disease.


The effects of pH and pCO2 on photosynthesis and respiration in the diatom Thalassiosira weissflogii.
The response of marine phytoplankton to the ongoing increase in atmospheric pCO2 reflects the consequences of both increased CO2 concentration and decreased pH in surface seawater. In the model diatom Thalassiosira weissflogii, we explored the effects of varying pCO2 and pH, independently and in concert, on photosynthesis and respiration by incubating samples in water enriched in H218O. In long-term experiments (~6-h) at saturating light intensity, we observed no effects of pH or pCO2 on growth rate, photosynthesis or respiration. This absence of a measurable response reflects the very small change in energy used by the carbon concentrating mechanism (CCM) compared to the energy used in carbon fixation. In short-term experiments (~3 min), we also observed no effects of pCO2 or pH, even under limiting light intensity. We surmise that in T. weissflogii, it is the photosynthetic production of NADPH and ATP, rather than the CO2-saturation of Rubisco that controls the rate of photosynthesis at low irradiance. In short-term experiments, we observed a slightly higher respiration rate at low pH at the onset of the dark period, possibly reflecting the energy used for exporting H+ and maintaining pH homeostasis. Based on what is known of the biochemistry of marine phytoplankton, our results are likely generalizable to other diatoms and a number of other eukaryotic species. The direct effects of ocean acidification on growth, photosynthesis and respiration in these organisms should be small over the range of atmospheric pCO2 predicted for the twenty-first century.


Early exposure of 17α-ethynylestradiol and diethylstilbestrol induces morphological changes and alters ovarian steroidogenic pathway enzyme gene expression in catfish, Clarias gariepinus.
Environmental estrogens are major cause of endocrine disruption in vertebrates, including aquatic organisms. Teleosts are valuable and popular models for studying the effects of endocrine disrupting chemicals (EDCs) in the environment. In the present study, we investigated the changes caused by exposure to the synthetic estrogens 17α-ethynylestradiol (EE2 ) and diethylstilbesterol (DES) during early stages of growth and sex differentiation of air-breathing catfish, Clarias gariepinus, at the morphological, histological, and molecular levels. Catfish hatchlings, 0 day post hatch (dph) were exposed continuously to sublethal doses of EE2 (50 ng/L) and DES (10 ng/L) until 50 dph and subsequently monitored for ovarian structural changes and alteration in the gene expression of steroidogenic enzymes till adulthood. Treated fish exhibited morphological deformities such as spinal curvature, stunted growth, and yolk-sac fluid retention. In addition to ovarian atrophy, DES-treated fish showed either rudimentary or malformed ovaries. Detailed histological studies revealed precocious oocyte development as well as follicular atresia. Further, transcript levels of various steroidogenic enzyme and transcription factor genes were altered in response to EE2 and DES. Activity of the rate-limiting enzyme of estrogen biosynthesis, aromatase, in the ovary as well as the brain of treated fish was in accordance with transcript level changes. These developmental and molecular effects imparted by EE2 and DES during early life stages of catfish could demonstrate the deleterious effects of estrogen exposure and provide reliable markers for estrogenic EDCs exposure in the environment.


Comparative analysis of antibody and cell-mediated autoimmunity to transaldolase and myelin basic protein in patients with multiple sclerosis.
Antibody and T cell-mediated immune responses to oligodendroglial autoantigens transaldolase (TAL) and myelin basic protein (MBP) were examined in patients with multiple sclerosis (MS). Immunohistochemical studies of postmortem brain sections revealed decreased staining by MBP- and TAL-specific antibodies in MS plaques, indicating a concurrent loss of these antigens from demyelination sites. By Western blot high titer antibodies to human recombinant TAL were found in 29/94 sera and 16/23 cerebrospinal fluid samples from MS patients. Antibodies to MBP were undetectable in sera or cerebrospinal fluid of these MS patients. Proliferative responses to human recombinant TAL (stimulation index [SI] = 2.47+/-0.3) were significantly increased in comparison to MBP in 25 patients with MS (SI = 1.37+/-0.1; P < 0.01). After a 7-d stimulation of PBL, utilization of any of 24 different T cell receptor Vbeta gene segments in response to MBP was increased less than twofold in the two control donors and six MS patients investigated. In response to TAL-H, while skewing of individual Vbeta genes was also less than twofold in healthy controls, usage of specific Vbeta gene segments was differentially increased ranging from 2.5 to 65.9-fold in patients with MS. The results suggest that TAL may be a more potent immunogen than MBP in MS.


Comparison of constitutive and inducible levels of expression of peroxisomal beta-oxidation and catalase genes in liver and extrahepatic tissues of rat.
Previous studies from our laboratories have shown that carcinogenic peroxisome proliferators significantly increase the mRNA levels of peroxisomal beta-oxidation genes in the rat liver by enhancing the transcriptional activity. Because of a good correlation between the inducibility of peroxisome proliferation and carcinogenicity of this class of xenobiotics, we proposed that sustained induction of peroxisomal beta-oxidation system and the resultant oxidative stress form the basis for carcinogenesis. Since this concept implies that tumors should develop only in tissues which display maximal peroxisome proliferation, we have now assessed the degree to which catalase and the three beta-oxidation genes are expressed in liver and 12 extrahepatic tissues of adult rats fed for 2 weeks a diet containing 0.025% ciprofibrate (w/w), a peroxisome proliferator. In the ciprofibrate-treated rats, the levels of catalase mRNA increased to less than 2-fold in liver, kidney, intestine, and heart, but no change was detected in other tissues. The mRNA levels of the three genes of beta-oxidation system in the liver of adult rats treated with ciprofibrate increased greater than 20-fold. In contrast, in the kidney, small intestine, and heart the increases in the mRNA levels of all three beta-oxidation genes were small and varied from 2- to 4-fold following ciprofibrate treatment. Ciprofibrate did not significantly increase the levels of these mRNAs in the other nine tissues. These results correlated well with the levels of peroxisomal beta-oxidation activity, peroxisome volume density, and the immunologically quantified proteins in various tissues. These results provide evidence for the presence of beta-oxidation enzymes in peroxisomes of many tissues of rat and for tissue (cell)-specific differences in the inducibility of mRNAs of these beta-oxidation genes. The marked inducibility of beta-oxidation genes in liver and subsequent development of liver tumors support the hypothesis that tumors develop in tissues that show inducibility of peroxisome proliferation vis a vis beta-oxidation system following exposure to peroxisome proliferators.


Expression of the cancer-associated DNA polymerase ε P286R in fission yeast leads to translesion synthesis polymerase dependent hypermutation and defective DNA replication.
Somatic and germline mutations in the proofreading domain of the replicative DNA polymerase ε (POLE-exonuclease domain mutations, POLE-EDMs) are frequently found in colorectal and endometrial cancers and, occasionally, in other tumours. POLE-associated cancers typically display hypermutation, and a unique mutational signature, with a predominance of C > A transversions in the context TCT and C > T transitions in the context TCG. To understand better the contribution of hypermutagenesis to tumour development, we have modelled the most recurrent POLE-EDM (POLE-P286R) in Schizosaccharomyces pombe. Whole-genome sequencing analysis revealed that the corresponding pol2-P287R allele also has a strong mutator effect in vivo, with a high frequency of base substitutions and relatively few indel mutations. The mutations are equally distributed across different genomic regions, but in the immediate vicinity there is an asymmetry in AT frequency. The most abundant base-pair changes are TCT > TAT transversions and, in contrast to human mutations, TCG > TTG transitions are not elevated, likely due to the absence of cytosine methylation in fission yeast. The pol2-P287R variant has an increased sensitivity to elevated dNTP levels and DNA damaging agents, and shows reduced viability on depletion of the Pfh1 helicase. In addition, S phase is aberrant and RPA foci are elevated, suggestive of ssDNA or DNA damage, and the pol2-P287R mutation is synthetically lethal with rad3 inactivation, indicative of checkpoint activation. Significantly, deletion of genes encoding some translesion synthesis polymerases, most notably Pol κ, partially suppresses pol2-P287R hypermutation, indicating that polymerase switching contributes to this phenotype.


Medical graduates' early career choices of specialty and their eventual specialty destinations: UK prospective cohort studies.
To report on doctors' early choices of specialty at selected intervals after qualification, and eventual career destinations. Questionnaire surveys. United Kingdom. Total of 15 759 doctors who qualified in 1974, 1977, 1983, 1993, and 1996, and their career destinations 10 years after graduation. 15 759 doctors were surveyed one and three years after graduation and 12 108 five years after graduation. Career preferences at years 1, 3, and 5, and destinations at 10 years, were known for, respectively, 64% (n=10 154), 62% (n=9702), and 61% (n=7429) of the survey population. In the 1993 and 1996 cohorts, career destinations matched with year 1 choices for 54% (1890/3508) of doctors in year 1, 70% (2494/3579) in year 3, and 83% (2916/3524) in year 5. Corresponding results for the earlier cohorts (1974-83) were similar: 53% (3310/6264), 74% (4233/5752), and 82% (2976/3646). The match rates varied by specialty; for example, the rates were consistently high for surgery. Career destinations matched with year 1 choices for 74% (722/982) of doctors who specified a definite (rather than probable or uncertain) specialty choice in their first postgraduate year. About half of those who chose a hospital specialty but did not eventually work in it were working in general practice by year 10. Ten years after qualification about a quarter of doctors were working in a specialty that was different from the one chosen in their third year after graduation. This stayed reasonably constant across graduation cohorts despite the changes in training programmes over time. Subject to the availability of training posts, postgraduate training should permit those who have made early, definite choices to progress quickly into their chosen specialty, while recognising the need for flexibility for those who choose later.


A multiscale analysis of nutrient transport and biological tissue growth in vitro.
In this paper, we consider the derivation of macroscopic equations appropriate to describe the growth of biological tissue, employing a multiple-scale homogenization method to accommodate explicitly the influence of the underlying microscale structure of the material, and its evolution, on the macroscale dynamics. Such methods have been widely used to study porous and poroelastic materials; however, a distinguishing feature of biological tissue is its ability to remodel continuously in response to local environmental cues. Here, we present the derivation of a model broadly applicable to tissue engineering applications, characterized by cell proliferation and extracellular matrix deposition in porous scaffolds used within tissue culture systems, which we use to study coupling between fluid flow, nutrient transport, and microscale tissue growth. Attention is restricted to surface accretion within a rigid porous medium saturated with a Newtonian fluid; coupling between the various dynamics is achieved by specifying the rate of microscale growth to be dependent upon the uptake of a generic diffusible nutrient. The resulting macroscale model comprises a Darcy-type equation governing fluid flow, with flow characteristics dictated by the assumed periodic microstructure and surface growth rate of the porous medium, coupled to an advection-reaction equation specifying the nutrient concentration. Illustrative numerical simulations are presented to indicate the influence of microscale growth on macroscale dynamics, and to highlight the importance of including experimentally relevant microstructural information to correctly determine flow dynamics and nutrient delivery in tissue engineering applications.


A qualitative evidence synthesis using meta-ethnography to understand the experience of living with pelvic organ prolapse.
Pelvic organ prolapse (POP) affects the lives of many people. We aimed to systematically search for, identify and synthesize qualitative research that explores what it is like to live with POP and make this knowledge available for healthcare improvement. We systematically searched Medline, PsychInfo, Embase and CINAHL, from inception to March 2020, for qualitative research exploring the experience of living with POP. We used meta-ethnography to synthesize findings. This is a conceptual approach to qualitative evidence synthesis. We used the recent guidelines for reporting meta-ethnography. We screened 3103 titles and 255 abstracts and included 37 primary studies. These incorporated the experience of 777 women, (aged 18 to 95 years) from a range of countries. We organized 162 ideas into 27 conceptual categories and 10 themes. We developed a conceptual model that helps us to understand the experience of pelvic organ prolapse. This model indicates that (1) the physical losses of POP are intricately linked to loss of identity; (2) women conceptualized POP as part of womanhood, yet also its thief; (3) there is a vicious cycle of taboo, silence and misunderstanding about POP and its treatment; (4) this silence is exacerbated by a feeling that POP is not taken seriously in healthcare. This meta-ethnography helps us to understand the experience of living with a POP. Our model illustrates the complex process of healthcare decision making. Further studies to explore the complexity of decision making from the perspective of patient and health professional are timely.


Aqueous benzene-diols react with an organic triplet excited state and hydroxyl radical to form secondary organic aerosol.
Chemical processing in atmospheric aqueous phases, such as cloud and fog drops, can play a significant role in the production and evolution of secondary organic aerosol (SOA). In this work we examine aqueous SOA production via the oxidation of benzene-diols (dihydroxy-benzenes) by the triplet excited state of 3,4-dimethoxybenzaldehyde, (3)DMB*, and by hydroxyl radical, ˙OH. Reactions of the three benzene-diols (catechol (CAT), resorcinol (RES) and hydroquinone (HQ)) with (3)DMB* or ˙OH proceed rapidly, with rate constants near diffusion-controlled values. The two oxidants exhibit different behaviors with pH, with rate constants for (3)DMB* increasing as pH decreases from pH 5 to 2, while rate constants with ˙OH decrease in more acidic solutions. Mass yields of SOA were near 100% for all three benzene-diols with both oxidants. We also examined the reactivity of atmospherically relevant mixtures of phenols and benzene-diols in the presence of (3)DMB*. We find that the kinetics of phenol and benzene-diol loss, and the production of SOA mass, in mixtures are generally consistent with rate constants determined in experiments containing a single phenol or benzene-diol. Combining our aqueous kinetic and SOA mass yield data with previously published gas-phase data, we estimate a total SOA production rate from benzene-diol oxidation in a foggy area with significant wood combustion to be nearly 0.6 μg mair(-3) h(-1), with approximately half from the aqueous oxidation of resorcinol and hydroquinone, and half from the gas-phase oxidation of catechol.


Evaluating Mental Health Literacy in the Workplace: Development and Psychometric Properties of a Vignette-Based Tool.
Purpose Early intervention and support for workers with mental health problems may be influenced by the mental health literacy of the worker, their colleagues and their supervisor. There are gaps, however, in our understanding of how to develop and evaluate mental health literacy within the context of the workplace. The purpose of this study was to evaluate the psychometric properties of a new Mental Health Literacy tool for the Workplace (MHL-W). Methods The MHL-W is a 16-question, vignette-based tool specifically tailored for the workplace context. It includes four vignettes featuring different manifestations of mental ill-health in the workplace, with parallel questions that explore each of the four dimensions of mental health literacy. In order to establish reliability and construct validity, data were collected from 192 healthcare workers who were participating in a mental health training project. Baseline data was used to examine the scale's internal consistency, factor structure and correlations with general knowledge ratings, confidence ratings, attitudes towards people with mental illness, and attitudes towards seeking help. Paired t-tests were used to examine pre and post intervention scores in order to establish responsiveness of the scale. Results There was strong support for internal consistency of the tool and a one-factor solution. As predicted, the scores correlated highly with an overall rating of knowledge and confidence in addressing mental health issues, and moderately with attitudes towards seeking professional help and (decreased) stigmatized beliefs. It also appears to be responsive to change. Conclusions The MHL-W scale is promising tool to track the need for and impact of mental health education in the workplace.


The osmium-ethyl gallate procedure is superior to silver impregnations for mapping neuronal pathways.
Ganglia processed through the osmium-ethyl gallate procedure (OEG)19 retain more structural integrity than those processed through various silver impregnation methods. However, the OEG method continues to be neglected by most neuroanatomists. Both types of procedures have been used to trace large neuronal tracts, but during silver impregnation the neuropils lose many of their identifying characteristics. We demonstrate here the advantages of the OEG procedure by comparing it with two silver techniques, Rowell's and Holmes's. The OEG method yields consistent and reliable results and is easier to carry out than silver protocols. Most importantly, the better preservation of the neuropils has led to the discovery and study of regional specializations that were previously undetected from silver preparations.


Effect of Coffee Consumption on Renal Outcome: A Systematic Review and Meta-Analysis of Clinical Studies.
Drinking coffee is one of the most common daily habits, especially in the developed world. Along with caffeine, coffee has various ingredients that have been suggested to have beneficial effects, including antioxidant, antiinflammatory, anticarcinogenic, antithrombotic and antifibrotic effects. In this systematic review and meta-analysis, we investigated the relationship between coffee intake and chronic kidney disease (CKD) related outcomes. Literature search was performed through PubMed/Medline, Web of Science, Embase (Elsevier), and the Cochrane Central Register of Controlled Trials (Wiley) from 1960 to February 2020. Incidence of CKD, the progression of CKD, and CKD-associated mortality have been evaluated in relation to coffee consumption and the amount of consumption. The Newcastle-Ottawa scale was used for quality assessment of included studies. 12 studies were included in the analysis (7 prospective, 5 cross-sectional) involving 505,841 subjects. 7 studies investigated the relationship between coffee consumption and incident CKD and showed that coffee consumption was associated with a significant decrease in the risk for incident CKD outcome (RR 0.86, 95% CI 0.76 to 0.97, P = .01) with a greater decrease in individuals taking ≥2 cups/day compared to those who drank ≤1 cup/day. There was a significantly lower risk of incident end stage kidney disease (ESKD) in coffee users (HR 0.82, 95% CI 0.72 to 0.94, P = .005). Coffee consumption was also associated with a lower risk of albuminuria (OR 0.81, 95% CI 0.68 to 0.97, P = .02). Overall, the risk of death related to CKD was lower in coffee users (HR 0.72, 95% CI 0.54 to 0.96, P = .02). Coffee intake was dose-dependently associated with lower incident CKD, ESKD, and albuminuria.


Diploid and polyploid cytotype distribution in Melampodium cinereum and M. leucanthum (Asteraceae, Heliantheae).
Previous chromosomal studies within Melampodium (Asteraceae, Heliantheae) of Mexico and Central America have documented chromosome numbers n = 9, 10, 11, 12, 18, 20, 23, 25 ± 1, 27, 30, and 33. Some species also have been shown to exhibit infra- and interpopulational polyploidy. The presence of cytotype mixtures is especially pronounced in the white-rayed complex, which occurs in the southwestern United States and adjacent Mexico. This group includes M. cinereum (n = 10 and 20), M. leucanthum (n = 10 and 20), and M. argophyllum (n = 30). Cytotype distribution has been newly analyzed in 415 plants from 152 populations and added to existing data from 185 plants from 113 populations, yielding information from a total of 600 individuals from 265 populations. Within M. cinereum and M. leucanthum are parapatric distributions of cytotypes, with tetraploids centered in the eastern and diploids in the western portions of their ranges. Tetraploids are most likely of autopolyploid origin, forming recurrently, with adaptations that allow colonization and establishment in new ecological regions. Contact zones are relatively narrow and only two triploid individuals have been detected. The tetraploid cytotypes probably extended eastward into central and southern Texas to the natural barriers at the edge of the Edward's Plateau in M. leucanthum and the low sandy plains in M. cinereum. The hexaploid M. argophyllum is interpreted as a relict surviving in the low mountains of northern Mexico; it may be an allopolyploid of hybrid origin between ancestors of the evolutionary lines that eventually yielded M. cinereum and M. leucanthum.


Astaxanthin as a Putative Geroprotector: Molecular Basis and Focus on Brain Aging.
In recent years, the scientific interest in natural compounds with geroprotective activities has grown exponentially. Among the various naturally derived molecules, astaxanthin (ASX) represents a highly promising candidate geroprotector. By virtue of the central polyene chain, ASX acts as a scavenger of free radicals in the internal membrane layer and simultaneously controls oxidation on the membrane surface. Moreover, several studies have highlighted ASX's ability to modulate numerous biological mechanisms at the cellular level, including the modulation of transcription factors and genes directly linked to longevity-related pathways. One of the main relevant evolutionarily-conserved transcription factors modulated by astaxanthin is the forkhead box O3 gene (FOXO3), which has been recognized as a critical controller of cell fate and function. Moreover, FOXO3 is one of only two genes shown to robustly affect human longevity. Due to its tropism in the brain, ASX has recently been studied as a putative neuroprotective molecule capable of delaying or preventing brain aging in different experimental models of brain damage or neurodegenerative diseases. Astaxanthin has been observed to slow down brain aging by increasing brain-derived neurotrophic factor (BDNF) levels in the brain, attenuating oxidative damage to lipids, protein, and DNA and protecting mitochondrial functions. Emerging data now suggest that ASX can modulate Nrf2, FOXO3, Sirt1, and Klotho proteins that are linked to longevity. Together, these mechanisms provide support for a role of ASX as a potential geroneuroprotector.


A study on the relationship of sexual satisfaction and common contraceptive methods employed by the couples.
Sexual relationship is a basis for mental health and continuity of the healthy generation. Enjoying the healthy body and mind will cause the sexual relationships to run their normal course in life. One of the problems that couples are faced within their sexual relationships is the issue of employing family planning methods. Studies have revealed that contraceptive methods are in connection with the sexual function and health in different ways. This study was aimed to determine the mean and the relation of scores of sexual satisfaction of men and women with the common contraceptive methods. This was a descriptive-correlative study. Samples included 280 individuals (140 couples) to use the common contraceptive methods including withdrawal method, tubal ligation in women, oral contraceptive method, condom, vasectomy, IUD and injection contraceptive method. Tools for gathering the data were Female Sexual Function Index (FSFI) and the questionnaire provided by Dr. Abdo on sexual satisfaction in men in 2004. The validity and reliability of these questionnaires were approved by researches conducted in worldwide and Iran. Descriptive and inferential statistic methods were applied in analyzing the data. The results suggested a significant statistic relation between scores of men's sexual satisfaction and separate contraceptive methods (p = 0.001) whereas this relation was not observed between the women's scores of sexual satisfaction and the contraceptive methods. According to the results of the present study, training family planning counselors in relation to choose suitable contraceptive method, in view of its probable effects on the couple's sexual satisfaction, seems essential.


Case-control study of risk factors for incident HIV infection in rural Uganda.
To identify risk factors associated with HIV incidence in a rural Ugandan population. Case-control study. Men and women who seroconverted between 1990 and 1997 (cases) and seronegative subjects (controls) were drawn from a general population cohort of approximately 5000 adults in rural, southwestern Uganda. Information on risk factors was ascertained through a detailed interview and physical examination by clinicians who were blind to the study subjects' HIV status. All patients were interviewed within 2 years of their estimated date of seroconversion. Data were available on 130 men (37 cases, 93 controls) and 133 women (46 cases, 87 controls). There was a significantly higher risk of infection in men (odds ratio [OR], 6.51; 95% confidence interval [CI], 1.06-39.84) and women (OR, 4.75; 95% CI, 1.26-17.9) who were unmarried and in a steady relationship, and in men who were divorced, separated, or widowed (OR, 4.33; 95% CI, 1.32-14.25) compared with those who were married. There was a significantly higher risk of HIV infection in men (OR, 3.78; 95% CI, 1.20-11.93) and women (OR, 20.78; 95% CI, 2.94-141.2) who reported > or =5 lifetime sexual partners compared with those who reported at most 1 partner. For men, there was an increased risk of infection associated with receiving increasing numbers of injections in the 6 months prior to interview (p < .001 for trend). Women reporting sex against their will in the year prior to interview were at higher risk of infection (OR, 7.84; 95% CI, 1.29-47.86; p = .020). The strongest risk factor for HIV incidence in this rural Ugandan population is lifetime sexual partners. The increased risks found for women reporting coercive sex and men reporting injections require further investigation.