ATBF1-A protein, but not ATBF1-B, is preferentially expressed in developing rat brain.
The ATBF1 gene encodes transcription factors containing four homeodomains and multiple zinc finger motifs. However, the gene products have yet to be identified and the role remains unknown in vivo. In this study, we raised an antiserum for ATBF1 and found high levels of expression of ATBF1 in developing rat brain. Western and Northern blot analyses detected a 400 kDa protein and 12.5 kb mRNA in developing rat brain, respectively; both corresponding to ATBF1-A but not the B isoform. The protein was highly expressed in the midbrain and diencephalon and mRNA was highly expressed in the brainstem, mostly in embryo and neonatal brain. Immunohistochemistry identified postmitotic neurons in the brainstem as the major site of ATBF1 expression, and the expression levels varied depending on age of and location in the brain. Expression was transient and weak in the precursor cells at early neurogenesis. ATBF1 decreased postnatally, but remained in mature neurons, including those expressing DOPA decarboxylase (DDC). High levels of ATBF1 were expressed in precursor cells in accordance with neurogenesis and were continued to the mature neurons in specific areas such as the inferior colliculus. Expression was not significant from precursor cells to mature neurons in the cerebral cortex and hippocampus. ATBF1 and its Drosophila homolog, Zfh-2, are known to regulate cell differentiation and proliferation via the interaction with either of the basic helix-loop-helix transcription factors, c-myb, or the DDC gene. Together with these reported functions the expression features detected here suggest that ATBF1 may participate in the regulation of neuronal cell maturation or region-specific central nervous system differentiation.


A family of candidate taste receptors in human and mouse.
The gustatory system of mammals can sense four basic taste qualities, bitter, sweet, salty and sour, as well as umami, the taste of glutamate. Previous studies suggested that the detection of bitter and sweet tastants by taste receptor cells in the mouth is likely to involve G-protein-coupled receptors. Although two putative G-protein-coupled bitter/sweet taste receptors have been identified, the chemical diversity of bitter and sweet compounds leads one to expect that there is a larger number of different receptors. Here we report the identification of a family of candidate taste receptors (the TRBs) that are members of the G-protein-coupled receptor superfamily and that are specifically expressed by taste receptor cells. A cluster of genes encoding human TRBs is located adjacent to a Prp gene locus, which in mouse is tightly linked to the SOA genetic locus that is involved in detecting the bitter compound sucrose octaacetate. Another TRB gene is found on a human contig assigned to chromosome 5p15, the location of a genetic locus (PROP) that controls the detection of the bitter compound 6-n-propyl-2-thiouracil in humans.


Surveillance of Congenital Heart Defects among Adolescents at Three U.S. Sites.
The prevalence, co-morbidities, and healthcare utilization in adolescents with congenital heart defects (CHDs) is not well understood. Adolescents (11 to 19 years old) with a healthcare encounter between January 1, 2008 (January 1, 2009 for MA) and December 31, 2010 with a CHD diagnosis code were identified from multiple administrative data sources compiled at 3 US sites: Emory University, Atlanta, Georgia (EU); Massachusetts Department of Public Health (MA); and New York State Department of Health (NY). The estimated prevalence for any CHD was 4.77 (EU), 17.29 (MA), and 4.22 (NY) and for severe CHDs was 1.34 (EU), 3.04 (MA), and 0.88 (NY) per 1,000 adolescents. Private or commercial insurance was the most common insurance type for EU and NY, and Medicaid for MA. Inpatient encounters were more frequent in severe CHDs. Cardiac co-morbidities included rhythm and conduction disorders at 20% (EU), 46% (MA), and 9% (NY) as well as heart failure at 3% (EU), 15% (MA), and 2% (NY). Leading noncardiac co-morbidities were respiratory/pulmonary (22% EU, 34% MA, 16% NY), infectious disease (17% EU, 22% MA, 20% NY), non-CHD birth defects (12% EU, 23% MA, 14% NY), gastrointestinal (10% EU, 28% MA, 13% NY), musculoskeletal (10% EU, 32% MA, 11% NY), and mental health (9% EU, 30% MA, 11% NY). In conclusion, this study used a novel approach of uniform CHD definition and variable selection across administrative data sources in 3 sites for the first population-based CHD surveillance of adolescents in the United States. High resource utilization and co-morbidities illustrate ongoing significant burden of disease in this vulnerable population.


Toward Understanding Bacterial Ice Nucleation.
Bacterial ice nucleators (INs) are among the most effective ice nucleators known and are relevant for freezing processes in agriculture, the atmosphere, and the biosphere. Their ability to facilitate ice formation is due to specialized ice-nucleating proteins (INPs) anchored to the outer bacterial cell membrane, enabling the crystallization of water at temperatures up to -2 °C. In this Perspective, we highlight the importance of functional aggregation of INPs for the exceptionally high ice nucleation activity of bacterial ice nucleators. We emphasize that the bacterial cell membrane, as well as environmental conditions, is crucial for a precise functional INP aggregation. Interdisciplinary approaches combining high-throughput droplet freezing assays with advanced physicochemical tools and protein biochemistry are needed to link changes in protein structure or protein-water interactions with changes on the functional level.


Forests and climate change: forcings, feedbacks, and the climate benefits of forests.
The world's forests influence climate through physical, chemical, and biological processes that affect planetary energetics, the hydrologic cycle, and atmospheric composition. These complex and nonlinear forest-atmosphere interactions can dampen or amplify anthropogenic climate change. Tropical, temperate, and boreal reforestation and afforestation attenuate global warming through carbon sequestration. Biogeophysical feedbacks can enhance or diminish this negative climate forcing. Tropical forests mitigate warming through evaporative cooling, but the low albedo of boreal forests is a positive climate forcing. The evaporative effect of temperate forests is unclear. The net climate forcing from these and other processes is not known. Forests are under tremendous pressure from global change. Interdisciplinary science that integrates knowledge of the many interacting climate services of forests with the impacts of global change is necessary to identify and understand as yet unexplored feedbacks in the Earth system and the potential of forests to mitigate climate change.


ARNi: A Novel Approach to Counteract Cardiovascular Diseases.
Cardiovascular diseases (CVDs) still represent the greatest burden on healthcare systems worldwide. Despite the enormous efforts over the last twenty years to limit the spread of cardiovascular risk factors, their prevalence is growing and control is still suboptimal. Therefore, the availability of new therapeutic tools that may interfere with different pathophysiological pathways to slow the establishment of clinical CVDs is important. Previously, the inhibition of neurohormonal systems, namely the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system, has proven to be useful in the treatment of many CVDs. Attempts have recently been made to target an additional hormonal system, that of the natriuretic peptides (NPs), which, when dysregulated, can also play a role in the development CVDs. Indeed, a new class of drug, the angiotensin receptor-neprilysin inhibitors (ARNi), has the ability to counteract the effects of angiotensin II as well as to increase the activity of NPs. ARNi have already been proven to be effective in the treatment of heart failure with reduced ejection fraction. New evidence has suggested that, in the next years, the field of ARNi application will widen to include other CVDs, such as heart failure, with preserved ejection fraction and hypertension.


Atmospheric pressure-ion drift chemical ionization mass spectrometry for detection of trace gas species.
This paper describes atmospheric pressure-ion drift chemical ionization mass spectrometry (AP-ID-CIMS) for monitoring of ambient trace species. Operation of the drift tube at atmospheric pressure allows a significantly longer ion-molecule reaction time and eliminates dilution of the ambient samples, while a well-defined electric field inside the drift tube provides the benefits to confine the flight path and velocity of reagent/product ions, to break down ion clusters, and to control the ion-molecule reaction time. The AP-ID-CIMS exhibits advantages over the conventional low pressure ID-CIMS and flow tube AP-CIMS, improving the detection sensitivity by 3 orders of magnitude and a factor of 3, respectively. We demonstrate that the AP-ID-CIMS allows quantification of sulfuric acid concentrations and is capable of detecting gaseous sulfuric acid with a detection limit of less than 10(5) molecules cm(-3), on the basis of 3sigma of the baseline noise and an integration time of 12 s. A field evaluation of the AP-ID-CIMS is presented for ambient H(2)SO(4) measurements.


A prognostic index for the clinical management of patients with advanced prostatic cancer: a British Prostate Study Group investigation.
Patients with histologically proven carcinoma of the prostate (n = 186) were initially assessed and followed up according to the standardized protocol of the British Prostate Study Group, urologists from which contributed patients to this investigation. These patients were given either endocrine therapy or orchidectomy as first line treatment; the ratio of the number of patients receiving these two treatments was similar in each group of subjects compared for survival. Prognostic indices were derived for all patients and for those classified according to the presence (M1) or absence (M0) of metastases. The prognostic indices were derived from clinical and hormone data obtained at initial presentation. Whereas the degree of tumor differentiation and plasma testosterone concentrations were significant prognostic factors in both M0 and M1 disease, growth hormone was only significant in M1 patients, where age was also of borderline significance; elevated growth hormone, higher Gleason grade, younger age, and lower testosterone indicated a poorer prognosis in M1 patients. These findings indicated the feasibility of selecting a poor prognostic group of patients that may derive benefit from a more aggressive therapy.


Improving the oral health of Alaska Natives.
There is a high prevalence of oral disease in the Alaska Native population, much of which goes untreated, creating a large discrepancy between the level of their oral health and that of the general population. The causes of this discrepancy are multiple--a major cause being the lack of access to care, especially in remote Alaska Native villages. Improving the oral health status of Alaska Natives will require treatment of current disease and initiation of an effective program to prevent oral disease. Cooperation between the Alaska Native organizations, dental health aides, the dental profession, and the government will be important. A strategy that combines addressing the disease currently present and preventing the occurrence of disease in the long run is the only strategy that offers a sustainable solution.


Distance geometry analysis of the benzodiazepine binding site.
The in vitro binding constants to brain benzodiazepine receptor are known for a variety of benzodiazepines and also for four other different classes of strongly binding compounds. The binding data for a total of 29 drugs selected from these 5 classes was used to deduce a possible binding site model consisting of 15 site points and only 5 adjustable energy parameters. Even though some of the chemical structures differed radically, it was possible to fit the experimental data with a root mean square deviation of 1.1 kcal/mole. Apparently 5 non-hydrogen atoms in each ligand can occupy corresponding points in the site, and thus constitute a possible benzodiazepine pharmacophore.


Vector and nonvector insect feeding reduces subsequent plant susceptibility to virus transmission.
The interactions of vector-virus-plant have important ecological and evolutionary implications. While the tripartite interactions have received some attention, little is known about whether vector infestation affects subsequent viral transmission and infection. Working with the whitefly Bemisia tabaci, begomovirus and tobacco/tomato, we demonstrate that pre-infestation of plants by the whitefly vector reduced subsequent plant susceptibility to viral transmission. Pre-infestation by the cotton bollworm, a nonvector of the virus, likewise repressed subsequent viral transmission. The two types of insects, with piercing and chewing mouthparts, respectively, activated different plant signaling pathways in the interactions. Whitefly pre-infestation activated the salicylic acid (SA) signaling pathway, leading to deposition of callose that inhibited begomovirus replication/movement. Although cotton bollworm infestation elicited the jasmonic acid (JA) defense pathway and was beneficial to virus replication, the pre-infested plants repelled whiteflies from feeding and so decreased virus transmission. Experiments using a pharmaceutical approach with plant hormones or a genetic approach using hormone transgenic or mutant plants further showed that SA played a negative but JA played a positive role in begomovirus infection. These novel findings indicate that both vector and nonvector insect feeding of a plant may have substantial negative consequences for ensuing viral transmission and infection.


Kinked-helices model of the nicotinic acetylcholine receptor ion channel and its complexes with blockers: simulation by the Monte Carlo minimization method.
A model of the nicotinic acetylcholine receptor ion channel was elaborated based on the data from electron microscopy, affinity labeling, cysteine scanning, mutagenesis studies, and channel blockade. A restrained Monte Carlo minimization method was used for the calculations. Five identical M2 segments (the sequence EKMTLSISVL10LALTVFLLVI20V) were arranged in five-helix bundles with various geometrical profiles of the pore. For each bundle, energy profiles for chlorpromazine, QX-222, pentamethonium, and other blocking drugs pulled through the pore were calculated. An optimal model obtained allows all of the blockers free access to the pore, but retards them at the rings of residues known to contribute to the corresponding binding sites. In this model, M2 helices are necessarily kinked. They come into contact with each other at the cytoplasmic end but diverge at the synaptic end, where N-termini of M1 segments may contribute to the pore. The kinks disengage alpha-helical H-bonds between Ala12 and Ser8. The uncoupled lone electron pairs of Ser8 carbonyl oxygens protrude into the pore, forming a hydrophilic ring that may be important for the permeation of cations. A split network of H-bonds provides a flexibility to the chains Val9-Ala12, the numerous conformations of which form only two or three intrasegment H-bonds. The cross-ectional dimensions of the interface between the flexible chains vary essentially at the level of Leu11. We suggest that conformational transitions in the chains Val9-Ala12 are responsible for the channel gating, whereas rotations of more stable alpha-helical parts of M2 segments may be necessary to transfer the channel in the desensitized state.


Role of renal medullary adenosine in the control of blood flow and sodium excretion.
This study determined the levels of adenosine in the renal medullary interstitium using microdialysis and fluorescence HPLC techniques and examined the role of endogenous adenosine in the control of medullary blood flow and sodium excretion by infusing the specific adenosine receptor antagonists or agonists into the renal medulla of anesthetized Sprague-Dawley rats. Renal cortical and medullary blood flows were measured using laser-Doppler flowmetry. Analysis of microdialyzed samples showed that the adenosine concentration in the renal medullary interstitial dialysate averaged 212 +/- 5.2 nM, which was significantly higher than 55.6 +/- 5.3 nM in the renal cortex (n = 9). Renal medullary interstitial infusion of a selective A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 300 pmol. kg-1. min-1, n = 8), did not alter renal blood flows, but increased urine flow by 37% and sodium excretion by 42%. In contrast, renal medullary infusion of the selective A2 receptor blocker 3, 7-dimethyl-1-propargylxanthine (DMPX; 150 pmol. kg-1. min-1, n = 9) decreased outer medullary blood flow (OMBF) by 28%, inner medullary blood flows (IMBF) by 21%, and sodium excretion by 35%. Renal medullary interstitial infusion of adenosine produced a dose-dependent increase in OMBF, IMBF, urine flow, and sodium excretion at doses from 3 to 300 pmol. kg-1. min-1 (n = 7). These effects of adenosine were markedly attenuated by the pretreatment of DMPX, but unaltered by DPCPX. Infusion of a selective A3 receptor agonist, N6-benzyl-5'-(N-ethylcarbonxamido)adenosine (300 pmol. kg-1. min-1, n = 6) into the renal medulla had no effect on medullary blood flows or renal function. Glomerular filtration rate and arterial pressure were not changed by medullary infusion of any drugs. Our results indicate that endogenous medullary adenosine at physiological concentrations serves to dilate medullary vessels via A2 receptors, resulting in a natriuretic response that overrides the tubular A1 receptor-mediated antinatriuretic effects.


Burn-induced cardiac dysfunction increases length of stay in pediatric burn patients.
The aim of this study was to evaluate cardiac function and clinical outcomes in perioperative pediatric burn patients. Transesophageal echocardiography data were collected on 40 patients from 2004 to 2007. Of the 40 patients who received exams, a complete set of cardiac parameters and outcome variables was obtained in 26 patients. The mean age of the patients was 9.7 ± 0.9 years, and the mean TBSA burn size was 64 ± 3%. Patients were divided into two groups based on systolic function. One group represented patients with ejection fractions of >50% and the other ≤50%. Clinical variables were then compared among the groups. In our cohort, systolic dysfunction was observed in 62% of patients (EF ≤ 50%). Systolic dysfunction was associated with a statistically significant increase in number of surgeries, ventilator days, and length of stay in the intensive care unit. The length of stay in patients with preserved systolic function and those with systolic dysfunction was 34.3 ± 3.3 days and 67.2 ± 4.0 days, respectively. Diastolic function measurements were obtained in 65%, and 88% had evidence of diastolic dysfunction. Diastolic dysfunction was not associated with any statistically significant correlations. This study lends evidence to the well-supported basic science models showing cardiac dysfunction after burns. Additionally, it shows that cardiac dysfunction can have clinical consequences. To our knowledge, this is the first study that shows the clinical sequelae of systolic dysfunction in the perioperative pediatric burn population.


National Survey of Point-of-Care Ultrasound Scholarly Tracks in Emergency Medicine Residency Programs.
Residency scholarly tracks are educational programs, designed to help trainees develop an area of expertise. Although the breadth of residency point-of-care ultrasound (POCUS) education has developed considerably in recent years, there is no literature to date describing scholarly tracks specifically in POCUS. In this study we sought to determine the prevalence, characteristics, and outcomes of POCUS scholarly tracks in emergency medicine (EM). This was a cross-sectional survey of EM residency programs accredited by the Accreditation Council for Graduate Medical Education. Surveys were distributed between March-August 2020 using a listserv followed by targeted emails to residency and ultrasound leadership. We summarized data using descriptive statistics, and performed logistic regression to identify factors associated with a POCUS scholarly track. Of 267 residency programs 199 (74.5%) completed the survey. Fifty-seven (28.6%) had a POCUS scholarly track as of the 2019-2020 academic year. Scholarly tracks in POCUS were more common in university-based/academic sites and larger residency programs. Of the 57 programs with POCUS scholarly tracks, 48 (84.2%) required residents to present at least one POCUS lecture, 45 (78.9%) required residents to serve as instructor at a hands-on workshop, and 42 (73.7%) required residents to participate in quality assurance of departmental POCUS scans. Only 28 (49.1%) tracks had a structured curriculum, and 26 (45.6%) required POCUS research. In total, 300 EM residents completed a POCUS scholarly track over the past three academic years, with a median of 4 (2-9) per program. Seventy-five (25.0%) proceeded to a clinical ultrasound fellowship after residency graduation, with a median of 1 (interquartile range 0-2) per program. A total of 139 POCUS-specific abstracts (median 2 [0-3]) and 80 peer-reviewed manuscripts (median 1 [0-2]) were published by scholarly track residents over the past three years. This survey study describes the current prevalence, characteristics, and outcomes of POCUS scholarly tracks across EM residency programs. The results may inform the decisions of residency programs to create these tracks.


Social demographic change and autism.
Parental age at child's birth--which has increased for U.S. children in the 1992-2000 birth cohorts--is strongly associated with an increased risk of autism. By turning a social demographic lens on the historical patterning of concordance among twin pairs, we identify a central mechanism for this association: de novo mutations, which are deletions, insertions, and duplications of DNA in the germ cells that are not present in the parents' DNA. Along the way, we show that a demographic eye on the rising prevalence of autism leads to three major discoveries. First, the estimated heritability of autism has been dramatically overstated. Second, heritability estimates can change over remarkably short periods of time because of increases in germ cell mutations. Third, social demographic change can yield genetic changes that, at the population level, combine to contribute to the increased prevalence of autism.


Serum levels of brain-derived neurotrophic factor in schizophrenia on a hypocaloric diet.
Dietary factors influence BDNF in animal studies, but there is no comparable data in clinical populations. We examined the effect of a dietary intervention on BDNF serum levels in 67 DSM-IV schizophrenic outpatients (51 males and 16 females). Two groups were assessed in a cross-sectional study: one on a hypocaloric diet (HD) and the other not on a hypocaloric diet. Weight, height and BMI data were collected concurrently with 5-ml blood sampling of each subject. BDNF levels were measured with a sandwich-ELISA. The blood sample was obtained a minimum of one month after the exposure to dietary intervention. Serum BDNF levels were significantly higher in patients on the HD (p=0.023). Additional research examining the interaction among patterns of nutritional food behavior and underlying physiopathology may result in insights upon which evidence-based decisions regarding dietary interventions can be made in people identified with major psychiatric disorders, such as schizophrenia.


Reversal of DIRECT-ACTING Oral Anticoagulants in Urgent Surgery of the Proximal Aorta: case Series and Review of the literature.
Proximal aorta interventions impose significant bleeding risk. Patients on concomitant anticoagulation regimens compound the risk of bleeding in any surgery, but especially cardiothoracic interventions. The employment of direct-acting oral anticoagulants (DOAC), namely those that target clotting factors II or X, has expanded at a precipitous rate over the last decade. The emergence of their reversal agents has followed slowly, leaving clinicians with management dilemmas in urgent surgery. We discuss current reversal strategies based on the available published data and our experience with proximal aortic surgery in patients taking DOACs. We performed a review of literature and present three cases from our experience to offer insight into management strategies that have been historically successful. A review of literature was conducted via PubMed with the following search string: (NOAC or DOAC or TSOAC) and (aorta or aortic or (Stanford and type and a)). We present three case presentations that illustrate the importance of DOAC identification and offer management strategies in mitigating associated bleeding risks in urgent or emergent surgeries. Treatment teams should be aware of the technical limitations of identifying and reversing DOACs. In view of the tendency toward publishing positive outcomes, more scientific rigor is required in the area of emergency DOAC reversal strategies.


Effect of decapitation and stress on some plasma electrolyte levels in rats.
Male Sprague-Dawley rats carrying indwelling jugular catheters were used to compare two methods of blood collection, catheterization or decapitation, for obtaining the plasma levels of several electrolytes. Decapitation resulted in higher levels of Ca2+, Mg2+, and K+ (18%, 23%, and 35% respectively) compared to catheter values. In a second experiment, catheterized rats were used to examine the effect of immobilization and footshock on plasma electrolytes. Both forms of stress elevated Mg2+, whereas only immobilization elevated Ca2+. Post-stress K+ levels were significantly different than control values. These experiments demonstrate that catheterization must be used to obtain true plasma electrolyte levels, and that electrolytes may be selectively altered depending on the nature of the stressor.


High magnetic hardness for the canted antiferromagnetic, ferroelectric, and ferroelastic layered perovskite-like (C2H5NH3)2[Fe(II)Cl4].
An unusual high magnetic hardness for the layered perovskite-like (C2H5NH3)2[Fe(II)Cl4], in addition to its already found canted antiferromagnetism, ferroelasticity, and ferroelectricity, which are absent for (CH3NH3)2[Fe(II)Cl4], has been observed. The additional CH2 in the ethylammonium compared to methylammonium allows more degrees of freedom and therefore numerous phase transitions which have been characterized by single-crystal structure determinations from 383 to 10 K giving the sequence from tetragonal to orthorhombic to monoclinic (I4/mmm ↔ P42/ncm ↔ Pccn ↔ Pcab ↔ C2/c) accompanied by both tilting and rotation of the FeCl6 octahedra. The magnetic properties on single crystal and powder samples at high temperature are similar for both compounds, but at TN (C2H5NH3)2[Fe(II)Cl4] is a proper canted antiferromagnet unlike the hidden canting observed for (CH3NH3)2[Fe(II)Cl4]. The canting angle is 0.6° toward the c-axis, and thus the moments lie in the easy plane of the iron-chloride layer defined by a critical exponent β = 0.18. The isothermal magnetizations for the field along the three orthogonal crystallographic axes show wider hysteresis for H ∥ c and is present at all temperature below 98 K. The coercive field increases as the temperature is lowered, and at T < 20 K it is difficult to reverse all the moments with the available 50 kOe of the SQUID for both single crystal and powder samples. The shape of the virgin magnetization after zero-field-cool (ZFC) indicates that the high coercive field is due to domain wall pinning. Thus, there are unusual associated anomalies such as asymmetric hysteresis and history dependence. The difference in magnetic hardness of the two compounds suggests that magnetic, electric, and elastic domains are intricately manifested and therefore raise the key question of how the different domains interact.


Adiposity and Reproductive Cycling Status in Zoo African Elephants.
The majority of zoo African elephants exhibit abnormal reproductive cycles, but it is unclear why. Acyclicity has been positively associated with body condition scores. The objective of this study was to measure body composition and examine the relationship between adiposity and cyclicity status, mediated by glucose, insulin, leptin, and inflammation. Body composition was assessed by deuterium dilution in 22 African elephants. Each elephant was weighed and given deuterated water orally (0.05 mL/kg), and blood was collected from the ear prior to and five times after deuterium administration. Glucose, insulin, leptin, and proinflammatory biomarker concentrations in serum were determined. Body fat percentage ranged from 5.24% to 15.97%. Fat adjusted for fat free mass (FFM) and age was not significantly associated with cyclicity status (P = 0.332). Age was the strongest predictor of cyclicity status (P = 0.040). Fat was correlated with weight (ρ = 0.455, P = 0.044) and when adjusted for FFM with circulating glucose (ρ = 0.520, P = 0.022) and showed a trend for association with leptin (unadjusted: ρ = 0.384, P = 0.095; adjusted for FFM: ρ = 0.403, P = 0.087). Deuterium dilution appears to be an available technique to measure body composition in African elephants. In this sample, fat was not associated with cyclicity status, and age may be more important to cyclicity status.


Reduction in subventricular zone-derived olfactory bulb neurogenesis in a rat model of Huntington's disease is accompanied by striatal invasion of neuroblasts.
Huntington's disease (HD) is an inherited progressive neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the huntingtin gene (HTT). The primary neuropathology of HD has been attributed to the preferential degeneration of medium spiny neurons (MSN) in the striatum. Reports on striatal neurogenesis have been a subject of debate; nevertheless, it should be considered as an endogenous attempt to repair the brain. The subventricular zone (SVZ) might offer a close-by region to supply the degenerated striatum with new cells. Previously, we have demonstrated that R6/2 mice, a widely used preclinical model representing an early onset HD, showed reduced olfactory bulb (OB) neurogenesis but induced striatal migration of neuroblasts without affecting the proliferation of neural progenitor cell (NPCs) in the SVZ. The present study revisits these findings, using a clinically more relevant transgenic rat model of late onset HD (tgHD rats) carrying the human HTT gene with 51 CAG repeats and mimicking many of the neuropathological features of HD seen in patients. We demonstrate that cell proliferation is reduced in the SVZ and OB of tgHD rats compared to WT rats. In the OB of tgHD rats, although cell survival was reduced, the frequency of neuronal differentiation was not altered in the granule cell layer (GCL) compared to the WT rats. However, an increased frequency of dopamenergic neuronal differentiation was noticed in the glomerular layer (GLOM) of tgHD rats. Besides this, we observed a selective proliferation of neuroblasts in the adjacent striatum of tgHD rats. There was no evidence for neuronal maturation and survival of these striatal neuroblasts. Therefore, the functional role of these invading neuroblasts still needs to be determined, but they might offer an endogenous alternative for stem or neuronal cell transplantation strategies.


Pro-apoptotic activity of novel Isatin-Schiff base copper(II) complexes depends on oxidative stress induction and organelle-selective damage.
We characterized the pro-apoptotic activity of two new synthesized isatin-Schiff base copper(II) complexes, obtained from isatin and 1,3-diaminopropane or 2-(2-aminoethyl)pyridine: (Cu(isapn)) and (Cu(isaepy)(2)), respectively. We demonstrated that these compounds trigger apoptosis via the mitochondrial pathway. The early induction of the p53/p21 system indicates a role for p53 in cell death, however, experiments carried out with small interfering RNA against p53, or with cells lacking p53, support that a p53-independent mechanism can also occur. The extent of apoptosis mirrors the kinetics of intracellular copper uptake. Particularly, Cu(isaepy)(2) enters the cells more efficiently and specifically damages nuclei and mitochondria, as evidenced by atomic absorption analysis of copper content and by the extent of nuclear and mitochondrial integrity. Conversely, Cu(isapn), although less permeable, induces a wide-spread oxidative stress, as demonstrated by analyses of reactive oxygen species concentration, and oxidation of proteins and lipids. The increase of the antioxidant defense, through the overexpression of Cu,Zn-SOD, partially counteracts cell death; whereas retinoic acid-mediated differentiation completely rescues cells from apoptosis induced by both compounds. The activation of JNK- and Akt-mediated phosphorylative pathways has been found to be not functional for apoptosis induction. On the contrary, apoptosis significantly decreased when the analogous zinc complex was used or when Cu(isaepy)(2) was incubated in the presence of a copper chelator. Altogether, our data provide evidence for a dual role of these copper(II) complexes: they are able to vehicle copper into the cell, thus producing reactive oxygen species, and could behave as delocalized lipophilic cation-like molecules, thus specifically targeting organelles.


Clinical evaluation of motion and position sense in the upper extremities of the elderly using motion analysis system.
The purpose of this study was to measure kinesthetic accuracy in healthy older adults by using arm position and motion matching tests. We investigated the effect of task type, joint angle, and matching arm results on kinesthetic accuracy in the upper extremities of 17 healthy right-handed older adults. Blinded subjects were asked to match positions and motions at four reference joint angles: 1) shoulder flexion, 0°-60°; 2) elbow flexion, 90°-135°; 3) wrist extension, 0°-50° in the sagittal plane; and 4) shoulder abduction, 0°-60° in the frontal plane. The absolute difference in angular displacement between the reference and matching arms was calculated to determine kinesthetic accuracy. Results showed that subjects were more accurate at matching motion than position tasks (P=0.03). Shoulder and elbow joints were more sensitive than wrist joints in perceiving passive positions and motions (P<0.05). The effect of the matching arm was found only when matching the joint angles of shoulder abduction and wrist extension (P<0.01). These results are comparable to findings of other studies that used machine-generated kinesthetic stimuli. The manual measurement of kinesthetic accuracy could be effective as a preliminary screening tool for therapists in clinical settings.


Historiographic analysis of the Jamaican 'Shakatani' scotoma from the short stories of Erna Brodber.
To use historiography in the analysis of the fictional writings of a Jamaican novelist to identify aspects of psychopathology of Jamaican people. Each of 12 stories of "The World is a High Hill" by novelist Erna Brodber was assigned an explanatory title and a 'psychic centrality'. A narrative qualitative analysis of the fourteen main themes of each story was created using a Lickert scale, calculating the psychopathological penetrance or weighted significance of each theme. The four main psychic centrality containments that emerged from this analysis were the black/white racial paradox (n = 4, 33%) and the partisan/political paradox (n = 1, 8%), the sexual/duplicity paradox (n = 5, 43%) and the social/spiritual paradox (n = 2, 17%). Five of fourteen themes reached maximal penetrance: family (92%), representation of generations with families (92%), issues of intimacy (92%), sex (75%) and issues of dependency (67%). Seven themes - personal and social conflicts (64%), issues of child development (53%), sexual identity (50%), pregnancy (48%), and political (42%), racial (36%), and religious (33%) conflicts reached moderate penetrance. The two themes of migration (30%) and homosexuality (14%) reached minimal penetrance. The analysis reveals a profound and practical historiographic representation of the contemporary scotoma that currently paralyses many Jamaicans as a product of the enslavement of Africans in the New World, and mirrors the clinical syndrome of personality disorder revealed from contemporary Jamaican medical research.


Affinity purification and comparative analysis of two distinct human uracil-DNA glycosylases.
Evidence is presented on two forms of uracil-DNA glycosylase (UDG1 and UDG2) that exist in human cells. We have developed an affinity technique to isolate uracil-DNA glycosylases from HeLa cells. This technique relies on the use of a uracil-DNA glycosylase inhibitor (Ugi) produced by the Bacillus subtilis bacteriophage, PBS2. Affinity-purified preparations of uracil-DNA glycosylase, derived from total HeLa cell extracts, reveal a group of bands in the 36,000 molecular weight range and a single 30,000 molecular weight band when analyzed by SDS-PAGE and silver staining. In contrast, only the 30,000 molecular weight band is seen in HeLa mitochondrial preparations. Separation of HeLa cell nuclei from the postnuclear supernatant reveals that uracil-DNA glycosylase activity is evenly distributed between the nuclear compartment and the postnuclear components of the cell. Immunostaining of a nuclear extract with antisera to UDG1 indicates that the nuclear associated uracil-DNA glycosylase activity is not associated with the highly conserved uracil-DNA glycosylase, UDG1. With the use of Ugi-Sepharose affinity chromatography, we show that a second and distinct uracil-DNA glycosylase is associated with the nuclear compartment. Immunoblot analysis, utilizing antisera generated against UDG1, reveals that the 30,000 molecular weight protein and a protein in the 36,000 range share common epitopes. Cycloheximide treatment of HeLa cells indicates that upon inhibition of protein synthesis, the higher molecular weight species disappears and is apparently post-translationally processed into a lower molecular weight form. This is substantiated by mitochondrial import studies which reveal that in vitro expressed UDG1 becomes resistant to trypsin treatment within 15 min of incubation with mitochondria. Within this time frame, a lower molecular weight form of uracil-DNA glycosylase appears and is associated with the mitochondria. Antibodies generated against peptides from specific regions of the cyclin-like uracil-DNA glycosylase (UDG2), demonstrate that this nuclear glycosylase is a phosphoprotein with a molecular weight in the range of 36,000. SDS-PAGE analysis of Ugi affinity-purified and immunoprecipitated UDG2 reveals two closely migrating phosphate-containing species, indicating that UDG2 either contains multiple phosphorylation sites (resulting in heterogeneous migration) or that two distinct forms of UDG2 exist in the cell. Cell staining of various cultured human cell lines corroborates the finding that UDG1 is largely excluded from the nucleus and that UDG2 resides mainly in the nucleus. Our results indicate that UDG1 is targeted to the mitochondria and undergoes proteolytic processing typical of resident mitochondrial proteins that are encoded by nuclear DNA. These results also indicate that the cyclin-like uracil-DNA glycosylase (UDG2) may be a likely candidate for the nuclear located base-excision repair enzyme.


Time-dependent outward current in guinea pig ventricular myocytes. Gating kinetics of the delayed rectifier.
Several conflicting models have been used to characterize the gating behavior of the cardiac delayed rectifier. In this study, whole-cell delayed rectifier currents were measured in voltage-clamped guinea pig ventricular myocytes, and a minimal model which reproduced the observed kinetic behavior was identified. First, whole-cell potassium currents between -10 and +70 mV were recorded using external solutions designed to eliminate Na and Ca currents and two components of time-dependent outward current were found. One component was a La3(+)-sensitive current which inactivated and resembled the transient outward current described in other cell types; single-channel observations confirmed the presence of a transient outward current in these guinea pig ventricular cells (gamma = 9.9 pS, [K]o = 4.5 mM). Analysis of envelopes of tail amplitudes demonstrated that this component was absent in solutions containing 30-100 microM La3+. The remaining time-dependent current, IK, activated with a sigmoidal time course that was well-characterized by three time constants. Nonlinear least-squares fits of a four-state Markovian chain model (closed - closed - closed - open) to IK activation were therefore compared to other models previously used to characterize IK gating: n2 and n4 Hodgkin-Huxley models and a Markovian chain model with only two closed states. In each case the four-state model was significantly better (P less than 0.05). The failure of the Hodgkin-Huxley models to adequately describe the macroscopic current indicates that identical and independent gating particles should not be assumed for this K channel. The voltage-dependent terms describing the rate constants for the four-state model were then derived using a global fitting approach for IK data obtained over a wide range of potentials (-80 to +70 mV). The fit was significantly improved by including a term representing the membrane dipole forces (P less than 0.01). The resulting rate constants predicted long single-channel openings (greater than 1 s) at voltages greater than 0 mV. In cell-attached patches, single delayed rectifier channels which had a mean chord conductance of 5.4 pS at +60 mV ([K]o = 4.5 mM) were recorded for brief periods. These channels exhibited behavior predicted by the four-state model: long openings and latency distributions with delayed peaks. These results suggest that the cardiac delayed rectifier undergoes at least two major transitions between closed states before opening upon depolarization.


A prospective evaluation of lung volume reduction surgery in 200 consecutive patients.
Though numerous studies have demonstrated the short-term efficacy of lung volume reduction surgery (LVRS) in select patients with emphysema, the longer-term follow-up studies are just being reported. The primary objectives of this study were to assess long-term health-related quality of life, satisfaction, physiologic status, and survival of patients following LVRS. We used a prospective cohort study design to assess the first 200 patients undergoing bilateral LVRS (from 1993 to 1998), with follow-up through the year 2000. Each patient served as his own control, initially receiving optimal medical management including exercise rehabilitation before undergoing surgery. Preoperative postrehabilitation data were used as the baseline for comparisons with postoperative data. The primary end points were the effects of LVRS on dyspnea (modified Medical Research Council dyspnea sale), general health-related quality of life (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]), patient satisfaction, and survival. The secondary end points were the effects of LVRS on pulmonary function, exercise capacity, and supplemental oxygen requirements. A tertiary care urban university-based referral center. Eligibility requirements for LVRS included disabling dyspnea due to marked airflow obstruction, thoracic hyperinflation, and heterogeneously distributed emphysema that provided target areas for resection. Patients were assessed at 6 months, 3 years, and 5 years after surgery. Preoperative pulmonary rehabilitation and bilateral stapling LVRS. The 200 patients accrued 735 person-years (mean +/- SD, 3.7 +/- 1.6 years; median, 4.0 years) of follow-up. Over the three follow-up periods, an average of > 90% of evaluable patients completed testing. Six months, 3 years, and 5 years after surgery, dyspnea scores were improved in 81%, 52%, and 40% of patients, respectively. Dyspnea scores were the same or improved in 96% (6 months), 82% (3 years), and 74% (5 years) of patients. Improvements in SF-36 physical functioning were demonstrated in 93% (6 months), 78% (3 years), and 69% (5 years) of patients. Good-to-excellent satisfaction with the outcomes was reported by 96% (6 months), 89% (3 years), and 77% (5 years) of patients. The FEV(1) was improved in 92% (6 months), 72% (3 years), and 58% (5 years) of patients. Changes in dyspnea and general health-related quality-of-life scores, and patient satisfaction scores were all significantly correlated with changes in FEV(1). Following surgery, the median length of hospital stay in survivors was 9 days. The 90-day postoperative mortality was 4.5%. Annual Kaplan-Meier survival through 5 years after surgery was 93%, 88%, 83%, 74%, and 63%, respectively. During follow-up, 15 patients underwent subsequent lung transplantation. In stringently selected patients, LVRS resulted in substantial beneficial effects over and above those achieved with optimized medical therapy. The duration of improvement was at least 5 years in the majority of survivors.


Evidence evaluation: a response to the court of appeal judgment in R v T.
This is a discussion of a number of issues that arise from the recent judgment in R v T [1]. Although the judgment concerned with footwear evidence, more general remarks have implications for all disciplines within forensic science. Our concern is that the judgment will be interpreted as being in opposition to the principles of logical interpretation of evidence. We reiterate those principles and then discuss several extracts from the judgment that may be potentially harmful to the future of forensic science. A position statement with regard to evidence evaluation, signed by many forensic scientists, statisticians and lawyers, has appeared in this journal [2] and the present paper expands on the points made in that statement.


A computational proposal for designing structured RNA pools for in vitro selection of RNAs.
Although in vitro selection technology is a versatile experimental tool for discovering novel synthetic RNA molecules, finding complex RNA molecules is difficult because most RNAs identified from random sequence pools are simple motifs, consistent with recent computational analysis of such sequence pools. Thus, enriching in vitro selection pools with complex structures could increase the probability of discovering novel RNAs. Here we develop an approach for engineering sequence pools that links RNA sequence space regions with corresponding structural distributions via a "mixing matrix" approach combined with a graph theory analysis. We define five classes of mixing matrices motivated by covariance mutations in RNA; these constructs define nucleotide transition rates and are applied to chosen starting sequences to yield specific nonrandom pools. We examine the coverage of sequence space as a function of the mixing matrix and starting sequence via clustering analysis. We show that, in contrast to random sequences, which are associated only with a local region of sequence space, our designed pools, including a structured pool for GTP aptamers, can target specific motifs. It follows that experimental synthesis of designed pools can benefit from using optimized starting sequences, mixing matrices, and pool fractions associated with each of our constructed pools as a guide. Automation of our approach could provide practical tools for pool design applications for in vitro selection of RNAs and related problems.


Pyridinium bis-(pyridine-κN)tetra-kis-(thio-cyanato-κN)ferrate(III).
In the title compound, (C5H6N)[Fe(NCS)4(C5H5N)2], the Fe(III) ion is coordinated by four thio-cyanate N atoms and two pyridine N atoms in a trans arrangement, forming an FeN6 polyhedron with a slightly distorted octa-hedral geometry. Charge balance is achieved by one pyridinium cation bound to the complex anion via N-H⋯S hydrogen bonding. The asymmetric unit consists of one Fe(III) cation, four thio-cyanate anions, two coordinated pyridine mol-ecules and one pyridinium cation. The structure exhibits π-π inter-actions between pyridine rings [centroid-centroid distances = 3.7267 (2), 3.7811 (2) and 3.8924 (2) Å]. The N atom and a neighboring C atom of the pyridinium cation are statistically disordered with an occupancy ratio of 0.58 (2):0.42 (2).


Thermoresponsive magnetic colloidal gels via surface-initiated polymerisation from functional microparticles.
Novel magnetothermally responsive core-shell microparticles have been synthesized. The aqueous suspensions of these particles exhibit fast thermoreversible fluid-to-gel transitions and retain good magnetic properties. Rheological measurements demonstrated that the viscoelasticity of the prepared particle gels can be tuned, enabling these gels to have the mechanical properties that should facilitate their applications as 3D cell scaffolds for in vitro expansion of cells. Also, it was found that the responsive particles could be used in repeated heating-cooling cycles without marked changes in gel elasticity. PrestoBlue viability assays of 3T3 fibroblasts and human mesenchymal stem cells cultured within the colloidal gel showed that the cells remained viable and proliferated, with significant increases in cell numbers over extended culture times. Confocal microscopy images of 3T3 cells cultured within the colloidal gel demonstrated that cells adhered, spread and retained their normal morphologies during proliferation. Furthermore, magnetic separation allowed efficient recovery of cells after their expansion in vitro without need for enzyme-mediated release steps. Trypsin-free cell passages were performed allowing multiple growth, separation and reloading of cells within the colloidal gels. Overall, the results suggest this colloidal gel has potential as a 3D scaffold for in vitro expansion of a variety of cell types and for enzyme free cell harvesting.


Aspirin-tolerant asthmatics generate more lipoxins than aspirin-intolerant asthmatics.
Asthma is characterized by chronic airway inflammation resulting from overproduction of pro-inflammatory mediators, such as leukotrienes (LT). The authors questioned the biosynthetic capacity of asthmatic patients for lipoxins (LX) and 15-epimer lipoxins (15-epi-LX), endogenous regulators of inflammatory responses that inhibit pro-inflammatory events. Levels of LXA4, 15-epi-LXA4 and LTC4 were determined in 14 clinically characterized aspirin-intolerant asthmatics (AIA), 11 aspirin-tolerant asthmatics (ATA) and eight healthy volunteers using a stimulated whole blood protocol. Both LXA4 and 15-epi-LXA4 were generated in whole blood activated by the divalent cation ionophore, A23187. Higher levels of LXA4 were produced in ATA than either AIA or healthy volunteers. Exposure of AIA whole blood to interleukin-3 prior to A23187 did not elevate their reduced capacity to generate LXA4. Generation of a bronchoconstrictor, LTC4, was similar in both AIA and ATA. Consequently, the ratio of LXA4:LTC4 quantitatively favoured the bronchoconstrictor for AIA and differed from both ATA and healthy subjects. In addition, the capacity for 15-epi-LXA4 generation was also diminished in AIA, since whole blood stimulated in the presence of aspirin gave increased levels only in samples from ATA. The present results indicate that asthmatics possess the capacity to generate both lipoxins and 15-epimer-lipoxins, but aspirin-intolerant asthmatics display a lower biosynthetic capacity than aspirin-tolerant asthmatics for these potentially protective lipid mediators. This previously unappreciated, diminished capacity for lipoxin formation by aspirin-intolerant asthmatic patients may contribute to their more severe clinical phenotype, and represents a novel paradigm for the development of chronic inflammatory disorders.


Etiology, pattern, and treatment of nose fractures: A 10-year cross-sectional cohort retrospective study.
Determining the etiology, epidemiology, pattern, and treatment of nasal bone fractures and the associated soft tissue injuries in a population will be beneficial for the prevention, rapid and correct diagnosis, and adequate management of this pathology in order to minimize postoperative complications. This study retrospectively evaluated the patients admitted and treated for nasal bone fractures in a university clinic of oral and maxillofacial surgery in Romania over a 10-year period. Following statistical analysis, evaluation and correlation of the monitored variables, a P value < 0.05 was considered statistically significant. Nasal bone fractures had the highest incidence among men (88.30%), aged 20-29 years (33.33%), with no education (33.33%), interpersonal violence being the main cause in this category of patients (P = 0.004; P = 0.005; P = 0.005). In urban environment (55.9%), nasal bone fractures through aggression and road traffic accidents were predominant, while in rural areas (44.10%), those caused by domestic accidents and animal attacks prevailed (P = 0.551). Nondisplaced (81.10%), closed (85.60%) and involving the nasal septum fractures (51.35%) were preponderant. Hematoma was the most frequent associated soft tissue injury (86.49%), its incidence being increased in the case of displaced (P = 1.000) and open fractures (P = 0.692). The most frequent treatment method was close nasal reduction (CNR) + closed septoplasty (51.35%). The most frequent complication was malunion (7.2%), secondary to CNR without septoplasty (P = 0.037). The main etiology of nasal bone fractures was interpersonal violence, which mainly affected men, aged 20-39 years, with a low level of education, living in urban areas. Implementing laws to fight interpersonal aggression and increase the education level of the population would lead to a considerable reduction in the incidence of this pathology. Patients treated by CNR + closed septoplasty and ORIF had the best postoperative evolution. Immediate septoplasty in the case of associated septal fractures significantly decreased the rate of postoperative complications.


The complete DNA sequence of varicella-zoster virus.
The entire DNA sequence of varicella-zoster virus (VZV) was determined using the M13-dideoxynucleotide technology. The genome is variable in size, but the sequence which was obtained comprises 124884 bp. Analysis of the sequence indicated that the genome contains 70 genes distributed about equally between the two DNA strands. The genes are organized compactly, but regions of overlap between protein-coding regions are not extensive. Many of the genes are arranged in 3'-coterminal families, and at least one is spliced. The discerned organization of VZV genes and that deduced for herpes simplex virus type 1 (HSV-1) from published transcript mapping data indicate that these two members of the Alphaherpesvirinae are very similar in gene layout. Comparisons of the predicted amino acid sequences of VZV proteins with those available for HSV-1 proteins generally suggest evolution from an ancestral genome, and allow the functions of several VZV genes to be deduced, although limited regions where the genomes differ in functional organization were also identified.


Facing quantum mechanical reality.
Two recent precision experiments provide conclusive evidence against any local hidden variables theory and in favor of standard quantum mechanics. Therefore the epistemology and the ontology of quantum mechanics must now be taken more seriously than ever before. The consequences of the standard interpretation of quantum mechanics are summarized in nontechnical language. The implications of the finiteness of Planck's constant (h > 0) for the quantum world are as strange as the implications of the finiteness of the speed of light (c < infinity for space and time in relativity theory. Both lead to realities beyond our common experience that cannot be rejected.


Robustness of Measurement, Discrimination Games, and Accessible Information.
We introduce a resource theory of measurement informativeness. This allows us to define an associated quantifier, which we call the robustness of measurement. It describes how much "noise" must be added to a measurement before it becomes completely uninformative. We show that this geometric quantifier has operational significance in terms of the advantage the measurement provides over guessing at random in a suitably chosen state discrimination game and that it is the single-shot generalization of the accessible information of a certain quantum-to-classical channel. Using this insight, we further show that the recently introduced robustness of asymmetry or coherence is the single-shot generalization of the accessible information of an ensemble. Finally, we discuss more generally the connection between robustness-based measures, discrimination problems, and information-theoretic quantities.


Evaluation of malaria control programme in three selected districts of Assam, India.
To ensure that the activities of Malaria Control Programme were taking place in effective and judicious manner, an intensive monitoring and supervision of various activities of the programme were carried out in Karbi-Anglong, Cachar and Nagaon districts of Assam, India during July-October 2007. Questionnaire-based protocol prepared by the National Vector Borne Disease Control Programme was used to evaluate the activities. Sixteen villages belonging to five different Primary Health Centres (PHCs) of three districts were selected for investigations. Results of monitoring of indoor residual spraying (IRS) revealed inadequate spraying coverage. Although recorded to be about 69-99%, but apparently it was 17-43% in the districts investigated. Cross-examination of 180 blood smears (90 positive and negative each) in the laboratories of the study PHCs, revealed discrepancy in the results of 67 blood smears. Maximum (44%) discrepancy was observed in positive blood smears and 30% in negative blood smears. Out of 22 Accredited Social Health Activists (ASHA) interrogated, none was found involved in antimalaria activities. However, out of 13 fever treatment depots monitored, one was found partially functional. Criteria laid down for preparation of micro action plan were not followed properly in any of the districts sruveyed. Various important components of the programme like constitution of Village Health Sanitation Committee, information education communication (IEC) activities, capacity building, use of larvivorous fishes, supervision, etc. were not exercised properly. However, 100% community acceptance was recorded for insecticide-treated bed nets in the villages surveyed. Indiscriminate use of rapid diagnostic test kits yielded poor and unsatisfactory response. Declining trend of malaria was observed during 2002-06 in Districts Nagaon and Karbi-Anglong (up to 2005). In District Cachar, however, a little increasing trend was observed during 2002-04. The results of this investigation revealed that the malaria control programme had been jeopardized seriously due to improper implementation of vector control measures, lack of adequate professional support and varied commitment on the part of the State Government. It can be concluded that long-term malaria control strategy should be based on generation of increased awareness on the disease and various methods of its control, health care access and administrative commitment for increased prosperity in resource-poor settings. The observation also necessitates further in-depth evaluation with appropriate regular active surveillance round the year with prompt detection and treatment facilities in order to control malaria effectively in these districts.


Demographic differences in willingness to share electronic health records in the All of Us Research Program.
Participant willingness to share electronic health record (EHR) information is central to success of the National Institutes of Health All of Us Research Program (AoURP). We describe the demographic characteristics of participants who decline access to their EHR data. We included participants enrolling in AoURP between June 6, 2017 and December 31, 2019 through the Trans-American Consortium for the Health Care Systems Research Network (TACH). TACH is a consortium of health care systems spanning 6 states, and an AoURP research partner. We analyzed data for 25 852 participants (89.3% of those enrolled). Mean age = 52.0 years (SD 16.8), with 66.5% White, 18.7% Black/African American, 7.7% Hispanic, 32.5% female, and 76% with >a high school diploma. Overall, 2.3% of participants declined to share access to their EHR data (range across TACH sites = 1.3% to 3.5%). Younger age, female sex, and education >high school were significantly associated with decline to share EHR data, odds ratio (95% confidence interval) = 1.26 (1.19-1.33), 1.74 (1.42-2.14), and 2.44 (1.86-3.21), respectively. Results were similar when several sensitivity analyses were performed. AoURP seeks a dataset reflecting our nation's diversity in all aspects of participation. Those under-represented in biomedical research may be reluctant to share access to their EHR data. In our data, race and ethnicity were not independently related to participant decision to decline access to their EHR information. Results suggest that the value of the AoURP dataset is unlikely to be constrained by the size or the racial/ethnic composition of this subgroup.


Osteoporosis and inflammation.
Osteoporosis represents a major healthcare burden, affecting approximately 10 million people aged over 50 years in the United States and with another 30 million or more at risk. One of the major contributing factors to osteoporosis is withdrawal of estrogen during menopause in women. Human and animal experiments have implicated pro-inflammatory cytokines as primary mediators of the accelerated bone loss at menopause including interleukin-1, tumor necrosis factor-alpha, and interleukin-6. Increased production of pro-inflammatory cytokines is associated with osteoclastic bone resorption in a number of disease states including rheumatoid arthritis, periodontitis, and multiple myeloma; estrogen withdrawal is associated with increased production of pro-inflammatory cytokines, and exposure of bone cultures to supernatants from activated leukocytes is associated with increased bone resorption. A major advance has been the discovery of RANKL, its receptor RANK, and the endogenous inhibitor osteoprotegerin. The binding of RANKL to RANK is essential for the differentiation and activation of osteoclasts and mediates the actions of essentially all known stimulators of osteoclastic bone resorption. RANKL expression is heightened in post- compared with pre-menopausal women, and this effect is attenuated by estrogen replacement therapy. RANKL is also a therapeutic target; a human antibody with high specificity and affinity to RANKL is currently under clinical evaluation for the treatment of osteoporosis in post-menopausal women and of metastatic bone disease in cancer patients with bone metastasis. Early data are promising.


A Lie-Theoretic Perspective on O(n) Mass Matrix Inversion for Serial Manipulators and Polypeptide Chains.
Over the past several decades a number of O(n) methods for forward and inverse dynamics computations have been developed in the multi-body dynamics and robotics literature. A method was developed in 1974 by Fixman for O(n) computation of the mass-matrix determinant for a serial polymer chain consisting of point masses. In other recent papers, we extended this method in order to compute the inverse of the mass matrix for serial chains consisting of point masses. In the present paper, we extend these ideas further and address the case of serial chains composed of rigid-bodies. This requires the use of relatively deep mathematics associated with the rotation group, SO(3), and the special Euclidean group, SE(3), and specifically, it requires that one differentiates functions of Lie-group-valued argument.


Gliogenesis in postnatal rat optic nerve: LC1 + microglia and S100-beta + astrocytes.
Lipocortin 1 (LC1) and S100-beta, two Ca(2+)-binding proteins that serve as specific markers for microglia and astrocytes, respectively, have been used to study postnatal gliogenesis in the rat optic nerve. Computerized image analysis was used to quantify and map the stained and unstained glia in transverse sections (10 microns thick) taken 1-2 mm from the chiasm in optic nerves from rat pups at postnatal day 0 (P0), P7, P14, P21, P28, P38 and adults. The number of astrocytes was remarkably constant (100 per section) at all ages. Because the area of the nerve increases 10-fold from P0 to adult, the population density of astrocytes begins al > 5000 mm-2 and drops to 400 mm-2 in the mature nerve; however, because the nerve length increases two-fold, the number of astrocytes doubles over the same period. In contrast, the number of LC1 + cells per section initially is sparse (4 at P0), increases rapidly up to 36 at P21 and levels off at 49 in adults. The microglia population density is relatively stable throughout development (200-300 mm-2) except during the peak of oligodendroblast apoptosis (P21) when it rises to 450 mm-2. Neonatally, LC1 immunoreactivity predominantly labels spherical-ameboid cells; but by P28 they are replaced by mature ramified microglia. The number of unstained cells (putative oligodendrocytes) per section increases from 11 at P0 to a peak of 308 at P21, and declines slightly to 269 in adults. While generally confirming concepts of astrocyte and oligodendrocyte ontogeny from the literature, the present report adds considerable detail regarding microglia, which often have been ignored. Microglia identified by LC1 immunoreactivity comprise 12% of the glia in adult optic nerve near the chiasm.


Monogamy without biparental care in a dwarf antelope.
The only widely accepted explanations for the evolution of monogamy in mammals have been based on the benefits of biparental care of offspring. This is probably because, unless biparental care is important, the most competitive males would be expected to monopolize more than one female. This study investigates whether males are important for offspring survival in a monogamous dwarf antelope, Kirk's dik-dik (Madoqua kirkii), by testing three hypotheses that have been proposed to account for monogamy in mammals. In dik-diks, males could help their mates and young by: (i) defending resources; (ii) defending against infanticide by other males; and (iii) reducing predation risk. Because territorial defence was mainly sex-specific, males did not defend resources for their mates or offspring. Males also made no attempt to kill infants they had not sired, so there is no risk of infanticide. Nor was there any evidence that males reduced predation risk: females were not alerted to an approaching predator sooner when males were present, and only mothers responded to playbacks of the call of a predator which preys on juvenile but not adult dik-diks. This is the first conclusive evidence of the absence of paternal care in any monogamous mammal.


Immunohistochemical localization of vascular endothelial growth factor in colonic mucosa of patients with inflammatory bowel disease.
Significantly enhanced serum levels of VEGF (vascular endothelial growth factor) were found in patients with inflammatory bowel disease. Peripheral blood mononuclear cells have been identified as one of the origins of the circulating VEGF. The present investigation examines the localization of VEGF at the site of inflammation in colonic mucosa of patients with Crohn's disease and ulcerative colitis. Immunohistochemical localization of VEGF and immunostaining for leukocytes were performed in colonic mucosal biopsies of 41 patients with Crohn's disease, 26 patients with ulcerative colitis and normal mucosal specimens of 5 patients with irritable bowel syndrome. Measurement of immunohistochemical staining for VEGF and for leukocytes within the epithelium and the lamina propria was performed separately by area morphometry using a computerized cell analysis system. In both patients with Crohn's disease and ulcerative colitis immunohistochemical staining for VEGF within the lamina propria of inflamed colonic mucosa was significantly higher compared with noninflamed mucosa (Crohn's disease: 4.26% vs. 0.07%, P < 0.001; ulcerative colitis: 3.68% vs. 0.32%, P = 0.001). There was a significant correlation between immunostaining for leukocytes and VEGF within the lamina propria in both patients with Crohn's disease (r = 0.73, P < 0.05)) and ulcerative colitis (r = 0.67, P < 0.05). In Crohn's disease immunostaining for VEGF within the epithelium was significantly higher in inflamed mucosa compared with noninflamed mucosa (9.85% vs. 0.63%, P < 0.001). In contrast, strong immunostaining for VEGF has been observed in the epithelium of noninflamed mucosa (7.60%, P < 0.003), as well as in inflamed mucosa of patients with active ulcerative colitis (9.68%, P < 0.002) compared with noninflamed mucosa of patients with inactive ulcerative colitis (1.39%). The present data indicate, that the increased VEGF expression within the epithelium and the interstitial accumulation of VEGF-producing leukocytes in inflamed mucosa may play an important role in the inflammatory mechanisms of Crohn's disease and ulcerative colitis.


Potassium channels in Myxicola giant axons.
This article describes an initial step in the study of potassium ion (K+) channel properties and their role in the control of patterns of action potential frequency. The purpose of the study was to determine the effect of the K+ channel blocker 4-aminopyridine on the conductance of the K+ channels in Myxicola. If this pharmacologic agent modifies one or more of the multiple kinetic components of the K+ channel conductance, it may be expected to alter the physiological properties of normal and pathological nerve fibers. Experiments were performed on 19 internally perfused voltage-clamped Myxicola infundibulum giant axons. After accounting for the time-dependent accumulation of K+ in the surrounding periaxonal spaces, the K+ conductance activates biphasically. The external application of 4-aminopyridine (20 mmol/L) specifically blocks the fast component of activation of the K+ conductance.


Ectoparasitic infestation of the lashes.
Phthirus pubis, commonly known as the crab louse, has as its habitat the pubic and inguinal regions of the body. Transfer between hosts is most commonly a result of sexual contact. On occasion, Phthirus pubis will leave its usual seat of predilection and infest other hair-bearing body parts. When infestation of the eyelashes occurs, it is known as phthiriasis palpebrarum. The case presented is an example of phthiriasis palpebrarum in a young female, apparently contracted as a result of transfer from the genital region of an affected male by hand contact.


Time-Temperature Integrating Optical Sensors Based on Gradient Colloidal Crystals.
Manipulation-free and autonomous recording of temperature states for extended periods of time is of increasing importance for food spoilage and battery safety assessment. An optical readout is preferred for low-tech visual inspection. Here, a concept for time-temperature integrators based on colloidal crystals is introduced. Two unique features in this class of advanced materials are combined: 1) the film-formation kinetics can be controlled by orders of magnitude based on mixtures of particles with distinct glass transition temperatures. 2) A gradual variation of the particle mixture along a linear gradient of the colloidal crystal enables local readout. Tailor-made latex particles of identical size but different glass transition temperatures provide a homogenous photonic stopband. The disappearance of this opalescence is directly related to the local particle ratio and the exposure to a time and temperature combination. This sensing material can be adjusted to report extended intermediate and short excessive temperature events, which makes it specifically suitable for long-term tracing and threshold applications.


[Effects of a neuropsychology program based on mindfulness on Alzheimer's disease: randomized double-blind clinical study].
The purpose of this research was to assess effects of a mindfulness based neuropsychological intervention on the clinical course of Alzheimer's disease. A two year randomized and double blind clinical trial was conducted on 127 probable Alzheimer's disease patients, according to NINCDS-ADRDA scale. Patients were grouped into three experimental groups (cognitive stimulation, progressive muscular relaxation, and mindfulness) plus a control group. All participants were receiving donepezil. Cognitive skills were assessed with CAMCOG and MMSE, functional area with RDRS-2, and NPI was used for psychopathology screening. Three treatment sessions per week were carried out for two years, and follow up measurements were taken every six months. The global cognitive function, functionality and behavioral disorders measurements indicated that patients from the experimental group based on mindfulness were stable during the two years, while patients from the control group, as well as the other experimental groups, showed a mild but significant worsening of their mental capacities. The mindfulness based neuropsychological program showed better cognitive and functional stability, as well as significant improvement in the psychopathological condition of mild to moderate Alzheimer' patients. These results support the idea that a mindfulness based intervention can produce a clinically relevant improvement in the treatment of dementia. More research is needed to confirm these data.


HIV vaccines in infants and children: past trials, present plans and future perspectives.
This review will address the recent history in HIV vaccine trials in the pediatric population while giving due respect to the pediatric vaccine successes achieved over the past decades. Success and failure seen when utilizing the neonatal macaque model of SIV infection and the ramifications of these studies will be discussed. The short list of pediatric HIV vaccine trials currently in progress and those in early planning stages will be reviewed. Finally, future perspectives on the impact of a vaccine that could be used to potentially avert mother-to-child transmission of HIV and lead ultimately to the establishment of immunity throughout adolescence and beyond will be presented.


Elucidating the structure-function attributes of a trypanosomal arginyl-tRNA synthetase.
Aminoacyl-tRNA synthetases (aaRSs) are fundamental components of the protein translation machinery. In light of their pivotal role in protein synthesis and structural divergence among species, they have always been considered potential targets for the development of antimicrobial compounds. Arginyl-tRNA synthetase from Trypanosoma cruzi (TcArgRS), the parasite responsible for causing Chagas Disease, contains a 100-amino acid insertion that was found to be completely absent in the human counterpart of similar length, as ascertained from multiple sequence alignment results. Thus, we were prompted to perform a preliminary characterization of TcArgRS using biophysical, biochemical, and bioinformatics tools. We expressed the protein in E. coli and validated its in-vitro enzymatic activity. Additionally, analysis of DTNB kinetics, Circular dichroism (CD) spectra, and ligand-binding studies using intrinsic tryptophan fluorescence measurements aided us to understand some structural features in the absence of available crystal structures. Our study indicates that TcArgRS can discriminate between L-arginine and its analogues. Among the many tested substrates, only L-canavanine and L-thioarginine, a synthetic arginine analogue exhibited notable activation. The binding of various substrates was also determined using in silico methods. This study may provide a viable foundation for studying small compounds that can be targeted against TcArgRS.


Reductive effect of ursodeoxycholic acid on bilirubin levels in neonates on phototherapy.
Phototherapy is paramount in the management of high total serum bilirubin (TSB). Whether its effectiveness can be improved with ursodeoxycholic acid (UDCA) has not been evaluated among newborns of African descent. A double-blind-controlled study was used to evaluate the effect of UDCA on the management of high TSB in neonates. Recruited neonates were categorized into the experimental group (given UDCA plus phototherapy) and the control group (phototherapy and plain syrup), and their TSB and conjugated bilirubin levels were measured. The data were analyzed using SPSS version 20. Statistical significance was set at a p-value of <0.05. The mean (SD) percentage reductions in TSB after 24 hrs were 40.73% (18.1) and 10.21% (7.1) in the experimental and control groups, respectively, and the difference was statistically significant (p=0.001). The mean (SD) durations on therapy were 3.0 days (0.58) in the experimental group and 5.5 days (1.35) in the control group (p=0.001). Phototherapy is still effective in the management of neonatal hyperbilirubinemia, but inclusion of UDCA accentuates the reductive effect of phototherapy on the TSB in neonates, reducing the duration of treatment and in-patient care.


Histone HIST1H1C/H1.2 regulates autophagy in the development of diabetic retinopathy.
Autophagy plays critical and complex roles in many human diseases, including diabetes and its complications. However, the role of autophagy in the development of diabetic retinopathy remains uncertain. Core histone modifications have been reported involved in the development of diabetic retinopathy, but little is known about the histone variants. Here, we observed increased autophagy and histone HIST1H1C/H1.2, an important variant of the linker histone H1, in the retinas of type 1 diabetic rodents. Overexpression of histone HIST1H1C upregulates SIRT1 and HDAC1 to maintain the deacetylation status of H4K16, leads to upregulation of ATG proteins, then promotes autophagy in cultured retinal cell line. Histone HIST1H1C overexpression also promotes inflammation and cell toxicity in vitro. Knockdown of histone HIST1H1C reduces both the basal and stresses (including high glucose)-induced autophagy, and inhibits high glucose induced inflammation and cell toxicity. Importantly, AAV-mediated histone HIST1H1C overexpression in the retinas leads to increased autophagy, inflammation, glial activation and neuron loss, similar to the pathological changes identified in the early stage of diabetic retinopathy. Furthermore, knockdown of histone Hist1h1c by siRNA in the retinas of diabetic mice significantly attenuated the diabetes-induced autophagy, inflammation, glial activation and neuron loss. These results indicate that histone HIST1H1C may offer a novel therapeutic target for preventing diabetic retinopathy.


Adaptive Tracking Control of State Constraint Systems Based on Differential Neural Networks: A Barrier Lyapunov Function Approach.
The aim of this article is to investigate the trajectory tracking problem of systems with uncertain models and state restrictions using differential neural networks (DNNs). The adaptive control design considers the design of a nonparametric identifier based on a class of continuous artificial neural networks (ANNs). The design of adaptive controllers used the estimated weights on the identifier structure yielding a compensating structure and a linear correction element on the tracking error. The stability of both the identification and tracking errors, considering the DNN, uses a barrier Lyapunov function (BLF) that grow to infinity whenever its arguments approach some finite limits for the state satisfying some predefined ellipsoid bounds. The analysis guarantees the semi-globally uniformly ultimately bounded (SGUUB) solution for the tracking error, which implies the achievement of an invariant set. The suggested controller produces closed-loop bounded signals. This article also presents the comparison between the tracking states forced by the adaptive controller estimated with the DNN based on BLF and quadratic Lyapunov functions as well. The effectiveness of the proposal is demonstrated with a numerical example and an implementation in a real plant (mass-spring system). This comparison confirmed the superiority of the suggested controller based on the BLF using the estimates of the upper bounds for the system states.


Fenestrated stent grafts for the treatment of complex aortic aneurysm disease: A mature treatment paradigm.
The introduction of fenestrated stent grafts (SGs) to treat abdominal aortic aneurysms (AAAs) with short proximal necks began in 1999. Nowadays, the whole visceral aorta can be treated totally by endovascular means. The established use of fenestrated devices to treat complex AAAs as a first-line management option has been previously reported. An up-to-date evaluation of the literature was performed including all types of publications regarding the use of fenestrated technology to repair complex AAAs. Fenestrated repair is now an established alternative to hybrid/chimney/snorkel repairs. However, specific criteria and prerequisites are required for the use and improvement of this method. Multiple device morphologies have been used incorporating the visceral arteries in various combinations. This modular strategy connects different devices (bridging covered stents and bifurcated SGs) with the aortic main body, thus excluding the aneurysm from the circulation. Precise deployment of the fenestrated SG is mandatory for successful visceral vessel revascularization. Accurate SG sizing and customization, a high level of technical skill, and facilities with modern imaging techniques including 3D road mapping and dedicated hybrid rooms are required. Most experience has been with the custom-made Zenith Cook platform, although off-the-shelf devices have been recently implanted. More complex repairs have been performed over the last few years, but device complexity has also increased. Perioperative, mid-term, and a few recently reported long-term results are encouraging. Secondary interventions remain the main problem, similar to that observed after traditional endovascular abdominal aortic aneurysm repair (EVAR).


Has America's tide of violence receded for good?
Experts in the young field of violence epidemiology blame guns and crack cocaine for America's deadly crime surge in the early 1990s. Explaining the subsequent decline in violent crime rates has been more difficult, however. Some of the factors that seem to have helped squelch crime could be temporary, such as low unemployment rates. But others, including a growing intolerance for violence as a means of settling interpersonal disputes, seem to have become cultural norms.


Risk factors for predicting central lymph node metastasis in papillary thyroid microcarcinoma (CN0): a study of 273 resections.
The role of routine central lymph node dissection (CLND) for clinically central lymph node negative (CN0) papillary thyroid microcarcinoma (PTMC) remains uncertain. We aim to determine the predictive factors for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma. A total of 273 patients diagnosed with clinically central lymph node negative PTMC from 2014 to 2016 were included. The predictive risk factors for CLNM were analyzed with respect to age, sex, tumor size, tumor multifocal, lymphadenectasis of lateral neck, capsular invasion, extra capsular spread (ECS), coexistence of chronic lymphocytic thyroiditis (Hashimoto thyroiditis, HT) and nodular goiter (NG), BRAFV600E mutation and subtype of papillary thyroid carcinoma (PTC). Univariate and multivariate analyses were performed to identify the risk factors for CLNM. Among the 273 patients, the CLNM occurred in 80 patients (29.3%). By univariate and multivariate analyses, tumor size (OR 2.07; p<0.001), multifocal (OR 2.67; p<0.004), lymphadenectasis of lateral neck (OR 9.28; p<0.001), tumor extent (OR 42.01; p<0.001) were independently correlated with CLNM. In further study, dorsal part of solitary lesion (OR: 16.312, 95%CI: 3.349-79.455, p=0.001), capsular invasion (OR: 42.012, 95% CI: 5.209-338.861, p<0.001), 6<D≤9 (OR: 8.400, 95% CI: 1.866-37.807, p=0.006) and D=1 (OR: 11.455, 95% CI: 2.500-52.480, p=0.002) were more tended to have CLNM. A prophylactic central lymph node dissection should be considered particularly to PTMC patients with each of tumor size > 6 mm, dorsal part of solitary lesion, multifocal, lymphadenectasis of lateral neck and capsular invasion.


Evidence of highly active cobalt oxide catalyst for the Fischer-Tropsch synthesis and CO2 hydrogenation.
Hydrogenations of CO or CO2 are important catalytic reactions as they are interesting alternatives to produce fine chemical feedstock hence avoiding the use of fossil sources. Using monodisperse nanoparticle (NP) catalysts, we have studied the CO/H2 (i.e., Fischer-Tropsch synthesis) and CO2/H2 reactions. Exploiting synchrotron based in situ characterization techniques such as XANES and XPS, we were able to demonstrate that 10 nm Co NPs cannot be reduced at 250 °C while supported on TiO2 or SiO2 and that the complete reduction of cobalt can only be achieved at 450 °C. Interestingly, cobalt oxide performs better than fully reduced cobalt when supported on TiO2. In fact, the catalytic results indicate an enhancement of 10-fold for the CO2/H2 reaction rate and 2-fold for the CO/H2 reaction rate for the Co/TiO2 treated at 250 °C in H2 versus Co/TiO2 treated at 450 °C. Inversely, the activity of cobalt supported on SiO2 has a higher turnover frequency when cobalt is metallic. The product distributions could be tuned depending on the support and the oxidation state of cobalt. For oxidized cobalt on TiO2, we observed an increase of methane production for the CO2/H2 reaction whereas it is more selective to unsaturated products for the CO/H2 reaction. In situ investigation of the catalysts indicated wetting of the TiO2 support by CoO(x) and partial encapsulation of metallic Co by TiO(2-x).


Effect of acute standing and prolonged upright activity on left ventricular hemodynamics, systolic and diastolic intervals, and QT-QS2 relationship.
It is generally accepted that upright posture decreases preload and afterload, which could alter left ventricular (LV) performance. It is not known if changes occurring with acute standing persist after prolonged ambulatory activity (amb-act). In seven normal subjects echocardiographic end-diastolic and end-systolic diameters, percent shortening of the internal diameter (% delta D) and end-systolic wall stress (ES-WS), radionuclide diastolic volume and ejection fraction, preejection period over left ventricular ejection time (PEP/LVET), and diastolic time and QT-QS2 were measured supine, within 1 to 2 minutes after standing and after prolonged (60 minutes) amb-act. In addition, serial measurements were performed in PEP/LVET for 105 minutes at 15-minute intervals. With acute standing, end-diastolic diameter, diastolic volume, and ES-WS decreased (p less than 0.01); heart rate and PEP/LVET increased (p less than 0.01); while % delta D and ejection fraction remained unchanged. There was an inverse correlation between change in PEP/LVET and diastolic diameter (r = -0.59), but no correlation between PEP/LVET and ES-WS. The diastolic time per beat and per minute decreased (375 +/- 115 msec from 519 +/- 176 msec [p less than 0.01] and 31.3 +/- 4.2 sec/min from 33.7 +/- 4.5 sec/min [p less than 0.01]). The QT-QS2 increased when compared to supine (-7 +/- 7.6 msec from -22 +/- 7.7 msec [p less than 0.005]), but the QT-QS2 relationship remained normal (QT less than or equal to QS2). All the dynamic changes that occurred with acute standing tended to persist during prolonged amb-act.


A Graph Gaussian Embedding Method for Predicting Alzheimer's Disease Progression With MEG Brain Networks.
Characterizing the subtle changes of functional brain networks associated with the pathological cascade of Alzheimer's disease (AD) is important for early diagnosis and prediction of disease progression prior to clinical symptoms. We developed a new deep learning method, termed multiple graph Gaussian embedding model (MG2G), which can learn highly informative network features by mapping high-dimensional resting-state brain networks into a low-dimensional latent space. These latent distribution-based embeddings enable a quantitative characterization of subtle and heterogeneous brain connectivity patterns at different regions, and can be used as input to traditional classifiers for various downstream graph analytic tasks, such as AD early stage prediction, and statistical evaluation of between-group significant alterations across brain regions. We used MG2G to detect the intrinsic latent dimensionality of MEG brain networks, predict the progression of patients with mild cognitive impairment (MCI) to AD, and identify brain regions with network alterations related to MCI.


Parallel path mechanisms lead to nonmonotonic force-velocity curves and an optimum load for molecular motor function.
Molecular motors convert chemical potential energy into mechanical work and perform a great number of critical biological functions. Examples include the polymerization and manipulation of nucleic acids, the generation of cellular motility and contractility, the formation and maintenance of cell shape, and the transport of materials within cells. The mechanisms underlying these molecular machines are varied, but are almost always considered in the context of a single kinetic pathway that describes motor stepping. However, the multidimensional nature of protein energy landscapes suggests the possibility of multiple reaction pathways connecting two states. Here we investigate the properties of a hypothetical molecular motor able to utilize parallel translocation mechanisms. We explore motor velocity and force dependence as a function of the energy landscape of each path and reveal the potential for such a mechanism to result in negative differential conductance. More specifically, regimes exist where increasing opposing force leads to increased velocity and an optimum load for motor function. We explore how the presence of this optimum depends on the rates of the individual paths and show that the distribution of stepping times characterized by the randomness parameter may be used to test for parallel path mechanisms. Last, we caution that experimental data consisting solely of measurements of velocity as a function of ATP concentration and force cannot be used to eliminate the possibility of such a parallel path mechanism.


Baseline EEG abnormalities in mild traumatic brain injury from the BIMA study.
The Brain Injury and Mechanisms of Action of HBO₂ for Persistent Post-Concussive Symptoms after Mild Traumatic Brain Injury (BIMA), sponsored by the Department of Defense, is a randomized, double-blind, sham-controlled trial of hyperbaric oxygen (HBO₂) in service members with persistent post-concussive symptoms following mild TBI, undergoing comprehensive assessments. The clinical EEG was assessed by neurologists for slow wave activity, ictal/interictal epileptiform abnormalities, and background periodic discharges. There is scant literature about EEG findings in this population, so we report baseline clinical EEG results and explore associations with other evaluations, including demographics, medication, neurological assessments, and clinical MRI outcomes. Seventy-one participants were enrolled: median age 32 years, 99% male, 49% comorbid PTSD, 28% with mTBI in the previous year, 32% blast injuries only, and 73% multiple injuries. All participants reported medication use (mean medications = 8, SD = 5). Slowing was present in 39%: generalized 37%, localized 8%, both 6%. No other abnormalities were identified. Slowing was not significantly associated with demographics, medication or neurological evaluation. Participants without EEG abnormalities paradoxically had significantly higher number of white matter hyperintensities as identified on MRI (p = 0.003). EEG slowing is present in more than one-third of participants in this study without evidence of associations with demographics, medications or neurological findings. ClinicalTrials.gov Identifier: NCT01611194; https://clinicaltrials.gov/show/NCT01611194.


Genetic mapping of the cloned subgroup A avian sarcoma and leukosis virus receptor gene to the TVA locus.
A chicken gene conferring susceptibility to subgroup A avian sarcoma and leukosis viruses (ASLV-A) was recently identified by a gene transfer strategy. Classical genetic approaches had previously identified a locus, TVA, that controls susceptibility to ASLV-A. Using restriction fragment length polymorphism (RFLP) mapping in inbred susceptible (TVA*S) and resistant (TVA*R) chicken lines, we demonstrate that in 93 F2 progeny an RFLP for the cloned receptor gene segregates with TVA. From these analyses we calculate that the cloned receptor gene lies within 5 centimorgans of TVA, making it highly probable that the cloned gene is the previously identified locus TVA. The polymorphism that distinguishes the two alleles of TVA in these inbred lines affects the encoded amino acid sequence of the region of Tva that encompasses the viral binding domain. However, analysis of the genomic sequence encoding this region of Tva in randomly bred chickens suggests that the altered virus binding domain is not the basis for genetic resistance in the chicken lines analyzed.


A Comparison of the Mental Health and Well-Being of Sexual Minority and Heterosexual First-Year Medical Students: A Report From the Medical Student CHANGE Study.
Research is lacking on psychological distress and disorder among sexual minority medical students (students who identify as nonheterosexual). If left unaddressed, distress may result in academic and professional difficulties and undermine workforce diversity goals. The authors compared depression, anxiety, and self-rated health among sexual minority and heterosexual medical students. This study included 4,673 first-year students who self-reported sexual orientation in the fall 2010 baseline survey of the Medical Student Cognitive Habits and Growth Evaluation Study, a national longitudinal cohort study. The authors used items from published scales to measure depression, anxiety, self-rated health, and social stressors. They conducted bivariate and multivariate analyses to estimate the association between sexual identity and depression, anxiety, and self-rated health. Of 4,673 students, 232 (5.0%) identified as a sexual minority. Compared with heterosexual students, after adjusting for relevant covariates, sexual minority students had greater risk of depressive symptoms (adjusted relative risk [ARR] = 1.59 [95% confidence interval, 1.24-2.04]), anxiety symptoms (ARR = 1.64 [1.08-2.49]), and low self-rated health (ARR = 1.77 [1.15-2.60]). Sexual minority students were more likely to report social stressors, including harassment (22.7% versus 12.7%, P < .001) and isolation (53.7% versus 42.8%, P = .001). Exposure to social stressors attenuated but did not eliminate the observed associations between minority sexual identity and mental and self-reported health measures. First-year sexual minority students experience significantly greater risk of depression, anxiety, and low self-rated health than heterosexual students. Targeted interventions are needed to improve mental health and well-being.


Identification of tail binding effect of kinesin-1 using an elastic network model.
Kinesin is a motor protein that delivers cargo inside a cell. Kinesin has many different families, but they perform basically same function and have same motions. The walking motion of kinesin enables the cargo delivery inside the cell. Autoinhibition of kinesin is important because it explains how function of kinesin inside a cell is stopped. Former researches showed that tail binding is related to autoinhibition of kinesin. In this work, we performed normal mode analysis with elastic network model using different conformation of kinesin to determine the effect of tail binding by considering four models such as functional form, autoinhibited form, autoinhibited form without tail, and autoinhibited form with carbon structure. Our calculation of the thermal fluctuation and cross-correlation shows the change of tail-binding region in structural motion. Also strain energy of kinesin showed that elimination of tail binding effect leads the structure to have energetically similar behavior with the functional form.


Induction of tumors in mice by genomic hypomethylation.
Genome-wide DNA hypomethylation occurs in many human cancers, but whether this epigenetic change is a cause or consequence of tumorigenesis has been unclear. To explore this phenomenon, we generated mice carrying a hypomorphic DNA methyltransferase 1 (Dnmt1) allele, which reduces Dnmt1 expression to 10% of wild-type levels and results in substantial genome-wide hypomethylation in all tissues. The mutant mice were runted at birth, and at 4 to 8 months of age they developed aggressive T cell lymphomas that displayed a high frequency of chromosome 15 trisomy. These results indicate that DNA hypomethylation plays a causal role in tumor formation, possibly by promoting chromosomal instability.


Does acute stress disorder predict post-traumatic stress disorder in traffic accident victims? Analysis of a self-report inventory.
The objective of this study was to account for acute stress disorder (ASD) and post-traumatic stress disorder (PTSD) morbidity in a self-report survey of traffic accident victims and to evaluate the relationship between ASD and PTSD in this sample, and furthermore, to find both a model of independent variables accounting for variance in ASD and PTSD symptom level. Ninety patients, treated at an emergency ward after traffic accidents, participated in this longitudinal self-report survey. ASD was assessed using the Acute Stress Disorder Scale (ASDS) and PTSD was assessed at 6-8 months follow-up using the Posttraumatic Diagnostic Scale (PDS). Twenty-five patients (28%) met the cutoff scores for ASDS. Fifteen patients (17%) fulfilled criteria for PTSD according to the PDS. ASD was only able to predict 50% of patients who later developed high levels of PTSD symptomatology. A model of three variables explained 35% of the variance in ASD symptom level. Two variables explained 40% of the variance in PTSD symptom level. In both regression models, dissatisfaction with social support was associated with a higher symptom level. The results from this study reflect already voiced problems with the ASD diagnosis. The lack of precision in predicting who will develop PTSD is pronounced in this study. The acute traumatic symptom level explains a large part of the variance in PTSD symptom level. However, other variables also seem to play an important role.