Safety and accuracy of pedicle screws and constructs placed in infantile and juvenile patients.
Retrospective review. To determine the safety of pedicle screws placed in infantile and juvenile patients younger than 10 years of age, and to evaluate the accuracy and the incidence of short and long-term (>2-year follow-up) complications for the screws and construct utilized. Although much has been written regarding the use of pedicle screws for the treatment of adult and adolescent spinal deformities, few studies have examined complication rates with regard to pedicle screws placed for pediatric spinal deformities in patients younger than 10 years of age. Eighty-eight patients treated with 948 pedicle screws placed for a variety of pediatric spinal deformities were performed at a single institution. We evaluated the accuracy of pedicle screw placement via radiographic review by two spinal surgeons not involved in the surgical treatment. The average age at surgery was 6.8 year (range, 1 + 11 to 9 + 11 year). Five hundred ninety-four pedicle screws were placed in the thoracic spine and 354 screws in the lumbar spine. Three screws (0.32%) violated the lateral wall of the pedicle, two screws (0.21%) violated the inferior wall, and three screws (0.32%) were suspected of medial wall violation for a total of eight screws (0.84%) malpositioned. Although short-term complications occurred in nine patients (10.2%) (four-wound infection, two-foot drop, two-respiratory problems, first-sixth cranial nerve palsy), there were no insertion or short-term complications specifically related to the use of pedicle screws. Long-term complications occurred in nine patients (10.2%) (three-deformity progression, four-growing rod breakage), whereas two patients required revision surgery because of pullout and prominence of proximal thoracic pedicle screws (n = 4) placed in growing rod constructs (2.3% of patients, 0.4% of screws). There were no intraoperative or short-term pedicle screw insertion-related complications and a very low long-term complication rate (2.3% of patients, 0.4% of screws) specifically related to the use of pedicle screws in infantile and juvenile spinal deformity patients. More than 99% of screws were accurately placed.


Forward and backward unidirectional scattering from plasmonic coupled wires.
We analyze the resonant electromagnetic response of sub-wavelength plasmonic dimers formed by two silver strips separated by a thin dielectric spacer and embedded in a uniform dielectric media. We demonstrate that the off-resonant electric and resonant, geometric shape-leveraged, magnetic polarizabilities of the dimer element can be designed to have close absolute values in a certain spectral range, resulting in a predominantly unidirectional scattering of the incident field due to pronounced magneto-electric interference. Switching between forward and backward directionality can be achieved with a single element by changing the excitation wavelength, with the scattering direction defined by the relative phases of the polarizabilities. We extend the analysis to some periodic configurations, including the specific case of a perforated metal film, and discuss the differences between the observed unidirectional scattering and the extraordinary transmission effect. The unidirectional response can be preserved and enhanced with periodic arrays of dimers and can find applications in nanoantenna devices, integrated optic circuits, sensors with nanoparticles, photovoltaic systems, or perfect absorbers; while the option of switching between forward and backward unidirectional scattering may create interesting possibilities for manipulating optical pressure forces.


Change in physical function among women as they age: findings from the Australian Longitudinal Study on Women's Health.
Decline in physical function is common in older age, with important consequences for health-related quality of life, health care utilisation, and mortality. This study aimed to identify patterns of change in physical functioning (PF) for women in later life. PF was measured longitudinally using the ten-item subscale of the Medical Outcomes Study 36-item Short Form Health Survey, for 10 515 participants of the Australian Longitudinal Study on Women's Health, who completed at least two surveys between 1999 (aged 73-78 years) and 2011 (aged 85-90 years). Conditional and unconditional latent profile analysis was conducted separately for deceased and surviving subgroups of women to uncover latent patterns of change in PF scores over time. Four patterns of change were identified for women who were still alive in 2011 (N = 5928), and four similar classes for deceased women (N = 4587): (1) 'poor PF' representing women with low PF scores, (2) 'moderate PF', (3) 'high PF', and (4) 'very high PF', where scores remained very high. All patterns exhibited a decrease in PF over time. Factors which predict low PF included sedentary levels of exercise, obese and overweight BMI, difficulty managing on income, and lower education. The results provided evidence for a gradual decrease in PF for all women with age; however, there was no evidence for an increased rate of decline prior to death.


Vasoactivity and Vasoconstriction Changes in Cattle Related to Time off Toxic Endophyte-Infected Tall Fescue.
Previous research has indicated that serotonergic and α-adrenergic receptors in peripheral vasculature are affected by exposure of cattle grazing toxic endophyte-infected (E+; Epichlöe coenophialia) tall fescue (Lolium arundinaceum). The objective of this experiment was to determine the period of time necessary for the vascular effects of ergot alkaloids to subside. Two experiments were conducted to investigate changes in vascular contractile response and vasoconstriction over time relative to removal from an ergot alkaloid-containing E+ tall fescue pasture. In Experiment 1, lateral saphenous vein biopsies were conducted on 21 predominantly Angus steers (357 ± 3 kg body weight) at 0 (n = 6), 7 (n = 6), 14 (n = 5), or 28 days (n = 4) after removal from grazing pasture (3.0 ha; endpoint ergovaline + ergovalinine = 1.35 mg/kg DM) for 126 days. In Experiment 2, lateral saphenous veins were biopsied from 24 Angus-cross steers (361 ± 4 kg body weight) at 0, 21, 42, and 63 days (n = 6 per time point) following removal from grazing tall fescue pastures (3.0 ha; first 88 days endpoint ergovaline + ergovalinine = 0.15 mg/kg DM; last 18 days endpoint ergovaline + ergovalinine = 0.57 mg/kg DM) for 106 total days. Six steers (370 ± 18 kg body weight) off of bermudagrass pasture for the same time interval were also biopsied on Day 0 and Day 63 (n = 3 per time point). Additionally, in Experiment 2, cross-sectional ultrasound scans of caudal artery at the fourth coccygeal vertebra were taken on Days 0, 8, 15, 21, 29, 36, 42, and 45 to determine mean artery luminal area to evaluate vasoconstriction. In both experiments, steers were removed from pasture and housed in a dry lot and fed a corn silage diet for the duration of biopsies and ultrasound scans. Biopsied vessels used to evaluate vasoactivity were cleaned, incubated in a multimyograph, and exposed to increasing concentrations of 4-Bromo-3,6-dimethoxybenzocyclobuten-1-yl) methylamine hydrobromide (TCB2; 5HT2A agonist), guanfacine (GF; α2A-adrenergic agonist), and (R)-(+)-m-nitrobiphenyline oxalate (NBP; α2C-adrenergic agonist) in both experiments and ergovaline (ERV) and ergotamine (ERT) in Experiments 1 and 2, respectively. In Experiment 1, days off pasture × agonist concentration was not significant (p > 0.1) for all four compounds tested. In Experiment 2, GF, NBP, TCB2 and ERT were significant for days off pasture × agonist concentration interaction (p < 0.02) and vasoactivity increased over time. Vasoactivity to agonists was reduced (p < 0.05) when steers were initially removed from E+ tall fescue pasture compared to bermudagrass, but did not differ by Day 63 for any variable. Luminal areas of caudal arteries in steers grazed on E+ tall fescue relaxed and were similar to steers that had grazed bermudagrass for 36 days on non-toxic diet (p = 0.15). These data demonstrate changes in peripheral vasoactivity and recovery from vasoconstriction occur beyond five weeks off toxic pasture and 5HT2A receptors appear to be more dramatically affected in the lateral saphenous vein by grazing E+ tall fescue pasture than adrenergic receptors.


[Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. (A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes)].
This Russian translation and reprint of the original article published with authors permissions. Original article published in the Diabetes Care. 2006;29(8). Translation to Russian prepared by Yu. Sych. An abridged version of the article was prepared by A. Gorbovskaya. These recommendations and the algorithm are based on data from clinical studies of various treatment options for type 2 diabetes and on the personal experience of consensus participants, taking into account the main goal of treatment - to achieve and maintain glucose levels as close as possible to glycemia in healthy people. The lack of evidence of high levels of glycemia obtained in comparative clinical trials with a direct comparison of different treatment options for diabetes remains the main obstacle to isolating one main class of drugs or combination of drugs that have advantages over others.


Comparison of first-attempt success between tibial and humeral intraosseous insertions during out-of-hospital cardiac arrest.
Intraosseous (IO) needle insertion is often utilized in the adult population for critical resuscitation purposes. Standard insertion sites include the proximal humerus and proximal tibia, for which limited comparison data are available. This study compared the frequencies of IO first-attempt success between humeral and tibial sites in out-of-hospital cardiac arrest. This observational study was conducted in an urban setting between August 28, 2009, and October 31, 2009, and included all medical cardiac arrest patients for whom resuscitative efforts were performed. Cardiac arrest protocols stipulate that paramedics insert an IO line for initial vascular access. During the first month of the study, the proximal humerus was the preferred primary insertion site, whereas the tibia was preferred throughout the second month. The primary outcome was first-attempt success, defined as secure IO needle position in the marrow cavity and normal fluid flow. Any needle dislodgment during resuscitation was also recorded. The association between first-attempt IO success and initial IO insertion location was analyzed using a test of independent proportions and 95% confidence intervals (CIs) for the difference in proportions. There were 88 cardiac arrest patients receiving IO placement, with 58 (65.9%) patients receiving their initial IO attempt in the tibia. The rate of first-time IO success at the tibia was significantly higher than that observed at the humerus (89.7% vs. 60.0%; p < 0.01). There were 18 initial successes at the humerus; for six (33.3%) of these, the needle became dislodged during resuscitation, compared with 52 initial successes at the tibia, with three (5.8%) dislodgments. The rate of total success for initial IO placements was significantly lower for the humerus (40.0%) compared with that for the tibia (84.5%; p < 0.01) during resuscitation efforts. In this subset of patients, tibial IO needle placement appeared to be a more effective insertion site than the proximal humerus. Success rates were higher with a lower incidence of needle dislodgments. Further randomized studies are required in order to validate these results.


Negative cognition, depressed mood, and paranoia: a longitudinal pathway analysis using structural equation modeling.
The role of negative cognition and effect in maintaining psychotic symptoms is increasingly recognized but has yet to be substantiated though longitudinal analysis. Based on an a priori theoretical model, we hypothesized that negative cognition and depressed mood play a direct causal role in maintaining paranoia in people with psychosis and that the effect of mood is mediated by negative cognition. We used data from the 301 patients in the Prevention of Relapse in Psychosis Trial of cognitive behavior therapy. They were recruited from consecutive Community Mental Health Team clients presenting with a recent relapse of psychosis. The teams were located in inner and outer London and the rural county of Norfolk, England. The study followed a longitudinal cohort design, with initial measures repeated at 3 and 12 months. Structural equation modeling was used to investigate the direction of effect between negative cognition, depressed mood, and paranoia. Overall fit was ambiguous in some analyses and confounding by unidentified variables cannot be ruled out. Nevertheless, the most plausible models were those incorporating pathways from negative cognition and depressed mood to paranoid symptoms: There was no evidence whatsoever for pathways in the reverse direction. The link between depressed mood and paranoia appeared to be mediated by negative cognition. Our hypotheses were thus corroborated. This study provides evidence for the role of negative cognition in the maintenance of paranoia, a role of central relevance, both to the design of psychological interventions and to the conceptualizations of psychosis.


Repositioning for treating pressure ulcers.
Pressure, from lying or sitting on a particular part of the body results in reduced oxygen and nutrient supply, impaired drainage of waste products and damage to cells. If a patient with an existing pressure ulcer continues to lie or bear weight on the affected area, the tissues become depleted of blood flow and there is no oxygen or nutrient supply to the wound, and no removal of waste products from the wound, all of which are necessary for healing. Patients who cannot reposition themselves require assistance. International best practice advocates the use of repositioning as an integral component of a pressure ulcer management strategy. This review has been conducted to clarify the role of repositioning in the management of patients with pressure ulcers. To assess the effects of repositioning patients on the healing rates of pressure ulcers. For this second update we searched the Cochrane Wounds Group Specialised Register (searched 23 May 2012); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5); Ovid MEDLINE (2010 to May Week 2 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations May 22, 2012); Ovid EMBASE (2010 to 2012 Week 20); and EBSCO CINAHL (2010 to 16 May 2012). We considered randomised controlled trials (RCTs) comparing repositioning with no repositioning, or RCTs comparing different repositioning techniques, or RCTs comparing different repositioning frequencies for the review. Controlled clinical trials (CCTs) were only to be considered in the absence of RCTs. Two authors independently assessed titles and, where available, abstracts of the studies identified by the search strategy for their eligibility. We obtained full versions of potentially relevant studies and two authors independently screened these against the inclusion criteria. We identified no studies that met the inclusion criteria. Despite the widespread use of repositioning as a component of the management plan for individuals with existing pressure ulcers, no randomised trials exist that assess the effects of repositioning patients on the healing rates of pressure ulcers. Therefore, we cannot conclude whether repositioning patients improves the healing rates of pressure ulcers. The effect of repositioning on pressure ulcer healing needs to be evaluated.


Submillisecond optical reporting of membrane potential in situ using a neuronal tracer dye.
A major goal in neuroscience is the development of optical reporters of membrane potential that are easy to use, have limited phototoxicity, and achieve the speed and sensitivity necessary for detection of individual action potentials in single neurons. Here we present a novel, two-component optical approach that attains these goals. By combining DiO, a fluorescent neuronal tracer dye, with dipicrylamine (DPA), a molecule whose membrane partitioning is voltage-sensitive, optical signals related to changes in membrane potential based on FRET (Förster resonance energy transfer) are reported. Using DiO/DPA in HEK-293 cells with diffraction-limited laser spot illumination, depolarization-induced fluorescence changes of 56% per 100 mV (tau approximately 0.1 ms) were obtained, while in neuronal cultures and brain slices, action potentials (APs) generated a Delta F/F per 100 mV of >25%. The high sensitivity provided by DiO/DPA enabled the detection of subthreshold activity and high-frequency APs in single trials from somatic, axonal, or dendritic membrane compartments. Recognizing that DPA can depress excitability, we assayed the amplitude and duration of single APs, burst properties, and spontaneous firing in neurons of primary cultures and brain slices and found that they are undetectably altered by up to 2 microm DPA and only slightly perturbed by 5 microm DPA. These findings substantiate a simple, noninvasive method that relies on a neuronal tracer dye for monitoring electrical signal flow, and offers unique flexibility for the study of signaling within intact neuronal circuits.


Lung transplantation in children. Specific aspects.
Lung transplantation has become in recent years a therapeutic option for infantswith terminal lung disease with similar results to transplantation in adults.In Spain, since 1996 114 children lung transplants have been performed; this corresponds to3.9% of the total transplant number.The most common indication in children is cystic fibrosis, which represents between 70-80% of the transplants performed in adolescents. In infants common indications areinterstitial lung disease and pulmonary hypertension.In most children a sequential double lung transplant is performed, generally with the help ofextracorporeal circulation. Lung transplantation in children presents special challenges in monitoring and follow-up, especially in infants, given the difficulty in assessing lung function and performing transbronchial biopsies.There are some more specific complications in children like postransplant lymphoproliferative syndrome or a greater severity of respiratory virus infections .After lung transplantation children usually experiment a very important improvement in their quality of life. Eighty eight per cent of children have no limitations in their activity after 3 years of transplantation.According to the registry of the International Society for Heart & Lung Transplantation (ISHLT) survival at 5 years of transplantation is 54% and at 10 years is around 35%.


A detailed comparison of the cytoarchitectonic and myeloarchitectonic maps of the human neocortex produced by the Vogt-Vogt school.
The comprehensive research programme of the Vogt-Vogt (V-V) school, which was active during the period 1900-1970, included detailed cytoarchitectonic and myeloarchitectonic analyses of the human cerebral cortex, with the aim to integrate the data obtained into a map, showing a parcellation of the human cerebral cortex into fundamental structural and potentially functional units. The cytoarchitectonic V-V analyses yielded two maps of the human cerebral cortex, the famous map of Brodmann (Vergleichende Lokalisationslehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund des Zellenbaues. Barth, Leipzig, 1909), Brodmann (in: Bruns P (ed) Neue deutsche Chirurgie, Enke, Stuttgart, 1914), and the less known, but more detailed map of Sarkisov et al. (Cytoarchitecture of the human cortex cerebri. Medgiz, Moscow, 1949). Sarkisov et al. used in their cytoarchitectonic parcellation of the cortex the same numbering scheme as Brodmann. They confirmed the presence of most of the areas delineated by the latter, but they subdivided several of these areas into two or more separate areas or subareas. Within the realm of the myeloarchitectonic V-V analyses, numerous meticulous studies of the cortex of individual cerebral lobes were carried out, but these were not united into a single map. Consequently, the envisioned integration of cytoarchitectonic and myeloarchitectonic data mentioned above was never realized. Some years ago, we (Nieuwenhuys et al. in Brain Struct Funct 220:2551-2573, 2015a, Nieuwenhuys et al. in Brain Struct Funct 220:3753-3755, 2015b) reanalyzed the V-V myeloarchitectonic data, and succeeded in constructing a complete myeloarchitectonic map of the human neocortex from these data. Because the data provided by the V-V school were derived from many different brains, a standard brain had to be introduced as a template to which all data available could be transferred. As such the MNI305 template was selected. Having made available now the cytoarchitectonic maps of Brodmann and Sarkisov et al. and the recently prepared myeloarchitectonic map, an attempt is made here to realize at last the original aim of the V-V school, viz. the preparation of a single, combined (cyto + myelo) architectonic map of the human cortex. To this end, the following three steps have been made. First, Brodmann's (BR) map, and the map of Sarkisov et al. (SA) were harmoniously transferred to the same template brain as the one used during the construction of our myeloarchitectonic map. Second, the standardized BR and our myeloarchitectonic (NI) map were compared, and the data contained within these maps were integrated into a single standardized combined BR-NI map (Fig. 11). The standardized SA and NI maps were subjected to the same procedure (Fig. 12). Finally, the standardized combined BR-NI and SA-NI maps were united into a single combined BR-SA-NI map (Fig. 13). This map renders it possible to make direct comparisons between the results of the architectonic studies of the V-V school and current parcellations of the human neocortex.


'You have to be almost dead before they ever really work on you in prison': A qualitative study of formerly incarcerated women's health care experiences during incarceration in Louisiana, U.S.
Globally, the rate of incarceration among women is rising, and in the U.S., women's incarceration has grown at twice the rate for men over the last four decades. Louisiana has the second highest rate of incarceration in the U.S. There is evidence that men in Louisiana prisons do not receive adequate healthcare, but little is known about their women counterparts. We aimed to document formerly incarcerated women's experiences with receiving healthcare during incarceration in Louisiana to inform policy and practice change. In partnership with two community-based organisations in New Orleans, Louisiana, between August 2016 and April 2018, we conducted semi-structured 1-hr interviews with 22 formerly incarcerated women who had been incarcerated in the state for at least one consecutive year. A convenience sample of participants was recruited through community-based organisations' re-entry and health programmes. Our interview guide included questions about experiences with accessing care, reproductive health needs, interactions with providers and preventive care during incarceration. We used applied thematic analysis techniques to interpret data. Over 90% of interviewees identified as Black. Their mean age was 50.7. The average length of incarceration was 8.4 years. Participants reported multiple barriers to accessing care including punishment for seeking care, long wait times, costs, lack of respect from providers and health concerns being dismissed. Participants reported limited mental health, preventive and dental services; an insufficient number of providers; and poor health outcomes as a result of delayed care. Overall, women did not have access to adequate, timely care during incarceration. Findings suggest a need for policy changes related to the provision of carceral healthcare services and external oversight of prison conditions and healthcare delivery. Further research into women's experiences of ageing during incarceration and tailored transitional health models is needed.


Aging and mental health in the decade ahead: what psychologists need to know.
Until relatively recently, most psychologists have had limited professional involvement with older adults. With the baby boomers starting to turn 65 years old in 2011, sheer numbers of older adults will continue to increase. About 1 in 5 older adults has a mental disorder, such as dementia. Their needs for mental and behavioral health services are not now adequately met, and the decade ahead will require an approximate doubling of the current level of psychologists' time with older adults. Public policy in the coming decade will face tensions between cost containment and facilitation of integrated models of care. Most older adults who access mental health services do so in primary care settings, where interdisciplinary, collaborative models of care have been found to be quite effective. To meet the needs of the aging population, psychologists need to increase awareness of competencies for geropsychology practice and knowledge regarding dementia diagnosis, screening, and services. Opportunities for psychological practice are anticipated to grow in primary care, dementia and family caregiving services, decision-making-capacity evaluation, and end-of-life care. Aging is an aspect of diversity that can be integrated into psychology education across levels of training. Policy advocacy for geropsychology clinical services, education, and research remains critical. Psychologists have much to offer an aging society.


Different ornaments signal male health and MHC variation in two populations of a warbler.
Male traits that signal health and vigour are used by females to choose better quality mates, but in some cases the male trait selected by females differs among populations. Multiple male traits can be maintained through female mate choice if both traits are equally honest indicators of male quality, but tests of this prediction are rare. By choosing males based on such traits, females could gain direct benefits from males (assistance with parental care), but when females choose extra-pair mates based on these traits, females gain only male sperm, and potentially indirect genetic benefits for their offspring. In common yellowthroats (Geothylpis trichas), female choice of extra-pair mates targets two different plumage ornaments: the black mask in a Wisconsin population and the yellow bib in a New York population. Previously, we found that the black mask in Wisconsin is related to greater major histocompatibility complex (MHC) class II variation, which in turn signals better survival and disease resistance. In this study, we examined the signalling function of the yellow bib in New York to test whether it signals the same aspects of male quality as the black mask in Wisconsin. As predicted, we found that the yellow bib in New York is most closely associated with MHC variation, which also signals survival and resistance to blood parasites. Thus, the ornament preferred by females differs between the two populations, but the different ornaments signal similar aspects of male health and genetic quality, specifically information regarding MHC variation and potential indirect genetic benefits to females.


Partial Unweighting in Obese Persons Enhances Tactile Transmission From the Periphery to Cortical Areas: Impact on Postural Adjustments.
Tactile plantar information is known to play an important role in balance maintenance and to contribute to the setting of anticipatory postural adjustments (APAs) prior to stepping. Previous studies have suggested that somatosensory processes do not function optimally for obese individuals due to the increased pressure of the plantar sole resulting in balance issues. Here, we investigated whether decreasing the compression of the mechanoreceptors by unweighting the plantar sole would enhance tactile sensory processes leading to an increased stability and an accurate setting of the APAs in obese individuals. More specifically, we tested the hypothesis that the somatosensory cortex response to electric stimulation (SEP) of the plantar sole in standing obese persons will be greater with reduced body weight than with their effective weight. The level of unweighting was calculated for each participant to correspond to a healthy body mass index. We showed an increase SEP amplitude in the unweighted condition compared to the effective body weight for all participants. This increase can be explained by the reduction of weight itself but also by the modified distribution of the pressure exerted onto the foot sole. Indeed, in the unweighted condition, the vertical ground reaction forces are evenly distributed over the surface of the foot. This suggests that decreasing and equalizing the pressure applied on the plantar mechanoreceptors results in an increase in somatosensory transmission and sensory processes for obese persons when unweighted. These sensory processes are crucial prior to step initiation and for setting the anticipatory postural adjustments (i.e., thrust). These cortical changes could have contributed to the observed changes in the spatiotemporal characteristics of the thrust prior to step initiation.


The Effect of Acupressure on Physiological Parameters of Myocardial Infarction Patients: A Randomized Clinical Trial.
Myocardial infarction is a major complication of coronary heart disease, and due to high mortality, is a part of important medical emergencies. Today, complementary and alternative medicine, as nonpharmacological and health promotion methods is considered. Therefore, this study was designed to evaluate the effectiveness of acupressure on physiological parameters of patients with myocardial infarction. This clinical trial was carried out among two groups and three stages in 2015. Study participants included 64 patients hospitalized in Iran, Isfahan Shahid Chamran hospital. Acupressure in five points and at any point for 2 minutes, twice per day for 3 days was done in the experimental group and as the same at a false point for the control group. Physiological parameters were recorded before, immediately, and 30 minutes after intervention. Data were analyzed using SPSS 20 and independent t-tests, Chi-square, Mann-Whitney test, repeated-measurements analysis of variance. Independent t-test immediately and 30 minutes after the intervention showed that mean systolic blood pressure and arterial oxygen saturation in the intervention group were significantly lower and higher than the control group, respectively; however, mean diastolic blood pressure and heart rate were not significantly different. However, 30 minutes after intervention, diastolic blood pressure and heart rate were significantly lower in the intervention group. Acupressure in five points of body had a positive effect on physiological parameters, and showed that after a short time of interventions these parameters lead to promotion over time.


Dorsal premotor cortex exerts state-dependent causal influences on activity in contralateral primary motor and dorsal premotor cortex.
During voluntary action, dorsal premotor cortex (PMd) may exert influences on motor regions in both hemispheres, but such interregional interactions are not well understood. We used transcranial magnetic stimulation (TMS) concurrently with event-related functional magnetic resonance imaging to study such interactions directly. We tested whether causal influences from left PMd upon contralateral (right) motor areas depend on the current state of the motor system, involving regions engaged in a current task. We applied short bursts (360 ms) of high- or low-intensity TMS to left PMd during single isometric left-hand grips or during rest. TMS to left PMd affected activity in contralateral right PMd and primary motor cortex (M1) in a state-dependent manner. During active left-hand grip, high (vs. low)-intensity TMS led to activity increases in contralateral right PMd and M1, whereas activity decreases there due to TMS were observed during no-grip rest. Analyses of condition-dependent functional coupling confirmed topographically specific stronger coupling between left PMd and right PMd (and right M1), when high-intensity TMS was applied to left PMd during left-hand grip. We conclude that left PMd can exert state-dependent interhemispheric influences on contralateral cortical motor areas relevant for a current motor task.


Providing self-healing ability for wireless sensor node by using reconfigurable hardware.
Wireless sensor networks (WSNs) have received tremendous attention over the past ten years. In engineering applications of WSNs, a number of sensor nodes are usually spread across some specific geographical area. Some of these nodes have to work in harsh environments. Dependability of the Wireless Sensor Network (WSN) is very important for its successful applications in the engineering area. In ordinary research, when a node has a failure, it is usually discarded and the network is reorganized to ensure the normal operation of the WSN. Using appropriate WSN re-organization methods, though the sensor networks can be reorganized, this causes additional maintenance costs and sometimes still decreases the function of the networks. In those situations where the sensor networks cannot be reorganized, the performance of the whole WSN will surely be degraded. In order to ensure the reliable and low cost operation of WSNs, a method to develop a wireless sensor node with self-healing ability based on reconfigurable hardware is proposed in this paper. Two self-healing WSN node realization paradigms based on reconfigurable hardware are presented, including a redundancy-based self-healing paradigm and a whole FPAA/FPGA based self-healing paradigm. The nodes designed with the self-healing ability can dynamically change their node configurations to repair the nodes' hardware failures. To demonstrate these two paradigms, a strain sensor node is adopted as an illustration to show the concepts. Two strain WSN sensor nodes with self-healing ability are developed respectively according to the proposed self-healing paradigms. Evaluation experiments on self-healing ability and power consumption are performed. Experimental results show that the developed nodes can self-diagnose the failures and recover to a normal state automatically. The research presented can improve the robustness of WSNs and reduce the maintenance cost of WSNs in engineering applications.


Confusing cause and effect: energy-entropy compensation in the preferential solvation of a nonpolar solute in dimethyl sulfoxide/water mixtures.
We performed molecular simulations to analyze the thermodynamics of methane solvation in dimethyl sulfoxide (DMSO)/water mixtures (298 K, 1 atm). Two contributions to the interaction thermodynamics are studied separately: (i) the introduction of solute-solvent interactions (primary contribution) and (ii) the solute-induced disruption of cohesive solvent-solvent interactions (secondary contribution). The energy and entropy changes of the secondary contribution always exactly cancel in the free energy (energy-entropy compensation), hence only the primary contribution is important for understanding changes of the free energy. We analyze the physical significance of the solute-solvent energy and solute-solvent entropy associated with the primary contribution and discuss how to obtain these quantities from experiments combining solvation thermodynamic and solvent equation of state data. We show that the secondary contribution dominates changes in the methane solvation entropy and enthalpy: below 30 mol % DMSO in the mixture, methane, because of more favorable dispersion interactions with DMSO molecules, preferentially attracts DMSO molecules, which, in response, release water molecules into the bulk, causing an increase in the entropy. This large energy-entropy compensating process easily causes a confusion in the cause for and the effect of preferred methane-DMSO interactions. Methane-DMSO dispersion interactions are the cause, and the entropy change is the effect. Procedures that infer thermodynamic driving forces from analyses of the solvation entropies and enthalpies should therefore be used with caution.


A new approach to follow a single extracellular vesicle-cell interaction using optical tweezers.
Extracellular vesicles (EVs) are spherical membrane structures released by most cells. These highly conserved mediators of intercellular communication carry proteins, lipids, and nucleic acids, and transfer these cellular components between cells by different mechanisms, such as endocytosis, macropinocytosis, or fusion. However, the temporal and spatial dynamics of vesicle-cell interactions still remain largely unexplored. Here we used optical tweezers to drive single EVs produced by microglial cells onto the surface of astrocytes or microglia in primary culture. By visualizing single EV-cell contacts, we observed that microglial vesicles displayed different motilities on the surface of astrocytes compared with microglia. After contact, EVs positioned on astrocytes displayed some minor oscillatory motion around the point of adhesion, while vesicles dragged to microglia displayed quite regular directional movement on the plasma membrane. Both the adhesion and motion of vesicles on glial cells were strongly reduced by cloaking phosphatidylserine (PS) residues, which are externalized on the vesicle membrane and act as determinants for vesicle recognition by target cells. These data identify optical manipulation as a powerful tool to monitor in vitro vesicle-cell dynamics with high temporal and spatial resolution and to determine in a quantitative manner the contribution of surface receptors/extracellular protein ligands to the contact.


Reoxygenation enhances tumour necrosis factor alpha-induced degradation of the extracellular matrix produced by chondrogenic cells.
Mesenchymal stem cells (MSCs) have been considered as a potential source for cell-based therapies in arthritic diseases for both their chondrogenic and anti-inflammatory properties. Thus, we examined how MSC-based neocartilage responds to tumour necrosis factor alpha (TNF-α) compared to articular chondrocyte (AC)-based neocartilage. Since oxygen tension is altered in arthritic joints, we also examined how increased oxygen tension influences this process. Monolayer-expanded healthy human ACs and bone marrow MSCs were cultured in chondrogenic medium in three-dimensional culture under hypoxia. They were then exposed to TNF-α under hypoxic or increased oxygen tension. We found no inherent anti-inflammatory potential of MSC-derived neocartilage as it pertains to the enzymes studied here: more degradative enzymes were upregulated by TNF-α in MSCs than in ACs, regardless of the oxygen tension. MSCs were also more sensitive to reoxygenation during TNF-α exposure, as indicated by increased proteoglycan loss, increased aggrecanase-generated metabolites, and further upregulation of the major aggrecanases, ADAMTS4 and ADAMTS5. There was also evidence of matrix metalloproteinase (MMP)-mediated aggrecan interglobular domain cleavage and type II collagen loss in response to TNF-α in both MSCs and ACs, but more MMPs were further upregulated by reoxygenation in MSCs than in ACs. Our study provides further evidence that consideration of oxygen tension is essential for studying cartilage degradation; for example, neocartilage produced from MSCs may be more sensitive to the negative effects of repeated hypoxia/reoxygenation events than AC-derived neocartilage. Consideration of the differences in responses may be important for cell-based therapies and selection of adjunctive chondroprotective agents.


Systematic analysis of insertions and deletions specific to nematode proteins and their proposed functional and evolutionary relevance.
Amino acid insertions and deletions in proteins are considered relatively rare events, and their associations with the evolution and adaptation of organisms are not yet understood. In this study, we undertook a systematic analysis of over 214,000 polypeptides from 32 nematode species and identified insertions and deletions unique to nematode proteins in more than 1000 families and provided indirect evidence that these alterations are linked to the evolution and adaptation of nematodes. Amino acid alterations in sequences of nematodes were identified by comparison with homologous sequences from a wide range of eukaryotic (metzoan) organisms. This comparison revealed that the proteins inferred from transcriptomic datasets for nematodes contained more deletions than insertions, and that the deletions tended to be larger in length than insertions, indicating a decreased size of the transcriptome of nematodes compared with other organisms. The present findings showed that this reduction is more pronounced in parasitic nematodes compared with the free-living nematodes of the genus Caenorhabditis. Consistent with a requirement for conservation in proteins involved in the processing of genetic information, fewer insertions and deletions were detected in such proteins. On the other hand, more insertions and deletions were recorded for proteins inferred to be involved in the endocrine and immune systems, suggesting a link with adaptation. Similarly, proteins involved in multiple cellular pathways tended to display more deletions and insertions than those involved in a single pathway. The number of insertions and deletions shared by a range of plant parasitic nematodes were higher for proteins involved in lipid metabolism and electron transport compared with other nematodes, suggesting an association between metabolic adaptation and parasitism in plant hosts. We also identified three sizable deletions from proteins found to be specific to and shared by parasitic nematodes, which, given their uniqueness, might serve as target candidates for drug design. This study illustrates the significance of using comparative genomics approaches to identify molecular elements unique to parasitic nematodes, which have adapted to a particular host organism and mode of existence during evolution. While the focus of this study was on nematodes, the approach has applicability to a wide range of other groups of organisms.


Indications for adjuvant radiation therapy in breast cancer: a review of the evidence and recommendations for clinical practice.
Radiation therapy (RT) plays an important role in the curative management of all stages of breast cancer. The optimal application of adjuvant RT is an area of continuous investigation, and the indications for treatment are refined with each new trial. This article reviews the evidence for adjuvant RT across five distinct clinical scenarios, with additional discussion of RT targets, techniques, and doses where appropriate.


Transmembrane 6 superfamily member 2 gene E167K variant impacts on steatosis and liver damage in chronic hepatitis C patients.
Steatosis and inherited host factors influence liver damage progression in chronic hepatitis C (CHC). The transmembrane 6 superfamily member 2 (TM6SF2) gene E167K variant increases liver fat and risk of progressive steatohepatitis by interfering with lipoprotein secretion. Our aim was to determine whether the E167K variant affects histological severity of steatosis, necroinflammation, and fibrosis in a cross-sectional cohort of 815 Italian therapy-naïve CHC patients. The association with clinically significant fibrosis was replicated in 645 Swiss/German patients. The TM6SF2 E167K variant was genotyped by TaqMan assays, steatosis graded according to the nonalcoholic fatty liver disease activity score, and necroinflammation and fibrosis graded and staged according to Ishak in Italian, and to Metavir in Swiss/German patients. The E167K variant was detected in 69 (9%) Italian patients and was associated with more severe steatosis, independently of confounders (P = 0.038). The association between E167K and steatosis severity was present in patients not infected by genotype 3 (G3) HCV (P = 0.031), but not in those infected by G3 HCV (P = 0.58). Furthermore, the E167K variant was associated with more severe necroinflammation (Ishak grade; adjusted P = 0.037) and nearly associated with more severe fibrosis (Ishak stage; adjusted P = 0.058). At multivariate logistic regression analysis, the E167K variant was independently associated with histologically probable or definite cirrhosis (Ishak stage S6; odds ratio [OR]: 2.19; 95% confidence interval [CI]: 1.18-3.93; P = 0.010). After further conditioning for steatosis and necroinflammation, the E167K variant remained associated with cirrhosis (OR, 3.15; 95% CI: 1.60-5.99; P < 0.001). In Swiss/German patients, the E167K variant was independently associated with clinically significant fibrosis Metavir stage F2-F4 (OR, 1.81; 95% CI: 1.12-3.02; P = 0.016). TM6SF2 E167K variant impacts on steatosis severity and is associated with liver damage and fibrosis in patients with CHC.


Smokers run increased risk of developing anti-natalizumab antibodies.
Smoking may contribute to the induction of neutralizing antibodies to interferon β-1a. In this study, we aimed to investigate the influence of smoking on the risk of developing antibodies to natalizumab, another biological drug in the treatment of multiple sclerosis. This report is based on 1338 natalizumab-treated multiple sclerosis patients included in either of two Swedish case-control studies in which information on smoking habits was collected. Using logistic regression, patients with different smoking habits were compared regarding risk of developing anti-natalizumab antibodies, by calculating odds ratios with 95% confidence intervals. Compared with nonsmokers, the odds ratio of developing anti-natalizumab antibodies was 2.4 (95% CI 1.2-4.4) for patients who smoked at the time of screening, and a significant trend showed higher risk of developing antibodies with higher intensity of smoking. When smoking within two years prior to screening was considered, the odds ratio of developing anti-natalizumab antibodies was 2.7 (1.5-5.1). The finding strengthens our hypothesis of the lungs as immune-reactive organs on irritation in relation to autoimmune responses, and may also be of clinical relevance since antibodies against natalizumab abrogate the therapeutic effect of the treatment.


Bee venom ameliorates ovalbumin induced allergic asthma via modulating CD4+CD25+ regulatory T cells in mice.
Asthma is a potentially life-threatening inflammatory disease of the lung characterized by the presence of large numbers of CD4+ T cells. These cells produce the Th2 and Th17 cytokines that are thought to orchestrate the inflammation associated with asthma. Bee venom (BV) has traditionally been used to relieve pain and to treat chronic inflammatory diseases. Recent reports have suggested that BV might be an effective treatment for allergic diseases. However, there are still unanswered questions related to the efficacy of BV therapy in treating asthma and its therapeutic mechanism. In this study, we evaluated whether BV could inhibit asthma and whether BV inhibition of asthma could be correlated with regulatory T cells (Treg) activity. We found that BV treatment increased Treg populations and suppressed the production of Th1, Th2 and Th17-related cytokines in an in vitro culture system, including IL2, IL4, and IL17. Interestingly, production of IL10, an anti-inflammatory cytokine secreted by Tregs, was significantly augmented by BV treatment. We next evaluated the effects of BV treatment on allergic asthma in an ovalbumin (OVA)-induced mouse model of allergic asthma. Cellular profiling of the bronchoalveolar lavage (BAL) and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly lowered following BV treatment. BV also ameliorated airway hyperresponsiveness, a hallmark symptom of asthma. In addition, IL4 and IL13 levels in the BAL fluid were decreased in the BV treated group. Surprisingly, the beneficial effects of BV treatment on asthma were eradicated following Treg depletion by anti-CD25 antibody injection, suggesting that the major therapeutic targets of BV were Tregs. These results indicate that BV efficiently diminishes bronchial inflammation in an OVA-induced allergic asthma murine model, and that this effect might correlate with Tregs, which play an important role in maintaining immune homeostasis and suppressing the function of other T cells to limit the immune response. These results also suggest that BV has potential therapeutic value for controlling allergic asthma responses.


Influenza vaccination as secondary prevention for cardiovascular disease: a science advisory from the American Heart Association/American College of Cardiology.
Evidence from cohort studies and a randomized clinical trial indicates that annual vaccination against seasonal influenza prevents cardiovascular morbidity and all-cause mortality in patients with cardiovascular conditions. The American Heart Association and American College of Cardiology recommend influenza immunization with inactivated vaccine (administered intramuscularly) as part of comprehensive secondary prevention in persons with coronary and other atherosclerotic vascular disease (Class I, Level B). Immunization with live, attenuated vaccine (administered intranasally) is not currently recommended [corrected] for persons with cardiovascular conditions. It is important to note that influenza vaccination coverage levels overall and in this population remain well below national goals and are marked by disparities across different age and ethnic groups. One of the barriers to vaccination for patients with cardiovascular disease is that cardiology practices frequently do not stock and administer influenza vaccine. Healthcare providers who treat individuals with cardiovascular disease can help improve influenza vaccination coverage rates by providing and strongly recommending vaccination to their patients before and throughout the influenza season.


The consequences of poaching and anthropogenic change for forest elephants.
Poaching has devastated forest elephant populations (Loxodonta cyclotis), and their habitat is dramatically changing. The long-term effects of poaching and other anthropogenic threats have been well studied in savannah elephants (Loxodonta africana), but the impacts of these changes for Central Africa's forest elephants have not been discussed. We examined potential repercussions of these threats and the related consequences for forest elephants in Central Africa by summarizing the lessons learned from savannah elephants and small forest elephant populations in West Africa. Forest elephant social organization is less known than the social organization of savannah elephants, but the close evolutionary history of these species suggests that they will respond to anthropogenic threats in broadly similar ways. The loss of older, experienced individuals in an elephant population disrupts ecological, social, and population parameters. Severe reduction of elephant abundance within Central Africa's forests can alter plant communities and ecosystem functions. Poaching, habitat alterations, and human population increase are probably compressing forest elephants into protected areas and increasing human-elephant conflict, which negatively affects their conservation. We encourage conservationists to look beyond documenting forest elephant population decline and address the causes of these declines when developing conversation strategies. We suggest assessing the effectiveness of the existing protected-area networks for landscape connectivity in light of current industrial and infrastructure development. Longitudinal assessments of the effects of landscape changes on forest elephant sociality and behavior are also needed. Finally, lessons learned from West African elephant population loss and habitat fragmentation should be used to inform strategies for land-use planning and managing human-elephant interactions.


Activity-dependent acceleration of endocytosis at a central synapse.
Accumulated evidence indicates the existence of rapid and slow endocytosis at many synapses. It has been proposed that rapid endocytosis is activated by intense stimulation when vesicle recycling needs to be speeded up to supply vesicles at hippocampal synapses. However, the evidence, as obtained with imaging techniques, which are somewhat indirect in indicating rapid endocytosis, is controversial. Furthermore, a slower time course of endocytosis is often found after more intense nerve activity, casting doubt on the role of rapid endocytosis at synapses. Here, we addressed this issue at a mammalian central synapse, the calyx of Held, using a capacitance measurement technique that provides a higher time resolution than imaging techniques. We found that rapid endocytosis with a time constant of approximately 1-2 s was activated during intense nerve activity. Reducing the presynaptic calcium current or buffering the intracellular calcium with EGTA significantly inhibited rapid endocytosis, suggesting that calcium triggers rapid endocytosis. During intense stimulation, rapid endocytosis retrieved up to approximately eight vesicles per second per active zone, approximately eightfold larger than reported in the hippocampus, and thus played a dominant role during and within 3 s after intense stimulation. Slow endocytosis became dominant 3 s after intense stimulation likely because of the fall of the intracellular calcium level that deactivated rapid endocytosis. These results underscore the importance of calcium-triggered rapid endocytosis, which offers the nerve terminal the plasticity to speed up vesicle cycling during intense nerve activity.


Glomerular cell cross-talk influences composition and assembly of extracellular matrix.
The glomerular basement membrane (GBM) is a specialized extracellular matrix (ECM) compartment within the glomerulus that contains tissue-restricted isoforms of collagen IV and laminin. It is integral to the capillary wall and therefore, functionally linked to glomerular filtration. Although the composition of the GBM has been investigated with global and candidate-based approaches, the relative contributions of glomerular cell types to the production of ECM are not well understood. To characterize specific cellular contributions to the GBM, we used mass spectrometry-based proteomics to analyze ECM isolated from podocytes and glomerular endothelial cells in vitro. These analyses identified cell type-specific differences in ECM composition, indicating distinct contributions to glomerular ECM assembly. Coculture of podocytes and endothelial cells resulted in an altered composition and organization of ECM compared with monoculture ECMs, and electron microscopy revealed basement membrane-like ECM deposition between cocultured cells, suggesting the involvement of cell-cell cross-talk in the production of glomerular ECM. Notably, compared with monoculture ECM proteomes, the coculture ECM proteome better resembled a tissue-derived glomerular ECM dataset, indicating its relevance to GBM in vivo. Protein network analyses revealed a common core of 35 highly connected structural ECM proteins that may be important for glomerular ECM assembly. Overall, these findings show the complexity of the glomerular ECM and suggest that both ECM composition and organization are context-dependent.


Maternal cortisol stimulates neurogenesis and affects larval behaviour in zebrafish.
Excess glucocorticoid transferred from stressed mother to the embryo affects developing vertebrate offspring, but the underlying programming events are unclear. In this study, we tested the hypothesis that increased zygotic glucocorticoid deposition, mimicking a maternal stress scenario, modifies early brain development and larval behaviour in zebrafish (Danio rerio). Cortisol was microinjected into the yolk at one cell-stage, to mimic maternal transfer, and the larvae [96 hours post-fertilization (hpf)] displayed increased activity in light and a reduction in thigmotaxis, a behavioural model for anxiety, suggesting an increased propensity for boldness. This cortisol-mediated behavioural phenotype corresponded with an increase in primary neurogenesis, as measured by incorporation of EdU at 24 hpf, in a region-specific manner in the preoptic region and the pallium, the teleostean homolog of the hippocampus. Also, cortisol increased the expression of the proneural gene neurod4, a marker of neurogenesis, in a region- and development-specific manner in the embryos. Altogether, excess zygotic cortisol, mimicking maternal stress, affects early brain development and behavioural phenotype in larval zebrafish. We propose a key role for cortisol in altering brain development leading to enhanced boldness, which may be beneficial in preparing the offspring to a stressful environment and enhancing fitness.


Dominance of ErbB-1 heterodimers in lung epithelial cells overexpressing ErbB-2. Both ErbB-1 and ErbB-2 contribute significantly to tumorigenicity.
This article examines differential expression and heterodimer formation of ErbB family members in tumorigenic and nontumorigenic human bronchial epithelial cells (HBECs). This cell system was developed previously as a model for lung adenocarcinoma by overexpression of c-erbB-2 in nontumorigenic, T antigen-immortalized HBECs. Earlier studies demonstrated that a tumorigenic clone from T antigen-immortalized nontumorigenic cells overexpressing ErbB-2 endogenously produced high levels of transforming growth factor (TGF)-alpha, and that reducing TGF-alpha by 93% eliminated tumorigenicity. In the present report, comparison of ErbB species between the tumorigenic cells (E6T) and their nontumorigenic derivatives (E6TA) demonstrated all four receptors in both cell types. However, in E6TA cells, ErbB-3 and -4 were present primarily in ErbB-1 heterodimers, suggesting that ErbB-1 is a preferred heterodimer partner within this cell system, expressing endogenous ErbB receptors and ligands and overexpressing ErbB-2. The ErbB-1/-2 species was present at high levels in E6T and absent in E6TA cells. Mitogen-activated protein kinase activity was elevated in E6T relative to E6TA. Elevated activity was eliminated by blocking surface expression of either ErbB-1 or ErbB-2. Endoplasmic reticulum trapping of ErbB-1 eliminated tumorigenicity, whereas ErbB-2 internalization was selected against during tumor formation. These data demonstrate the importance of TGF-alpha-mediated signaling through the ErbB-1/-2 heterodimer in development of the tumorigenic phenotype. This work further suggests that ErbB-3 and -4 species may also contribute to tumorigenic conversion and that their expression levels may be increased by signaling initiated by TGF-alpha.


Heating without heat: Thermodynamics of passive energy filters between finite systems.
Passive filters allowing the exchange of particles in a narrow band of energy are currently used in microrefrigerators and energy transducers. In this Rapid Communication, we analyze their thermal properties using linear irreversible thermodynamics and kinetic theory, and discuss a striking phenomenon: the possibility of simultaneously increasing or decreasing the temperatures of two systems without any supply of energy. This occurs when the filter induces a flow of particles whose energy is between the average energies of the two systems. Here we show that this selective transfer of particles does not need the action of any sort of Maxwell demon and can be carried out by passive filters without compromising the second law of thermodynamics. This phenomenon allows us to design cycles between two reservoirs at temperatures T_{1}<T_{2} that are able to reach temperatures below T_{1} or above T_{2}.


A model long-term care hospice unit: care, community, and compassion.
The purpose of this study was to investigate the factors that influenced the quality of care of terminally ill nursing home residents on a hospice unit in a city and county long-term care facility. The findings disclosed that the hospice team had created a cultural environment in which care, community, and compassion were the predominant components of their philosophy of palliative care. Communication at all levels-among staff, family, friends, and residents-was found to be a core hospice value, essential to community development. The results of this study illustrate that exemplary palliative care can be provided when an interdisciplinary team is dedicated to creating an environment where the principles of palliative care can be fully implemented. The authors conclude that there is a developing role for geriatric nurses to participate in further defining and providing palliative care for older people in their homes, hospitals, nursing homes, and residential care.


Determining the HPV vaccine schedule for a HIV-infected population in sub Saharan Africa, a commentary.
Epidemiological studies have established human papillomavirus (HPV) infection as the central cause of invasive cervical cancer (ICC) and its precursor lesions. HIV is associated with a higher prevalence and persistence of a broader range of high-risk HPV genotypes, which in turn results in a higher risk of cervical disease. Recent WHO HPV vaccination schedule recommendations, along with the roll out of HAART at an earlier CD4 count within the female HIV-infected population, may have programmatic implications for sub Saharan Africa. This communication identifies research areas, which will need to be addressed for determining a HPV vaccine schedule for this population in sub Saharan Africa. A review of WHO latest recommendations and the evidence concerning one-dose HPV vaccine schedules was undertaken. For females ≥15 years at the time of first dose and immunocompromised and/or HIV-infected, a 3-dose schedule (0, 1-2, 6 months) is recommended for all three vaccines. There is some evidence that there is similar protection against HPV 16 and 18 infection from a single vaccination than from two or three doses, however there is no cross protection conferred to other genotypes. There is a need for periodic prevalence studies to determine the vaccination coverage of bivalent, quadrivalent and nonavalent vaccine targeted oncogenic HPV genotypes in women with CIN 3 or ICC at national level. In light of the increasing number of sub Saharan HIV-infected girls initiating HAART at a CD4 count above 350 mm3, there are a number of clinical, virological and public health research gaps to address before a tailored vaccine schedule can be established for this population.


Evaluation of Mangosteen juice blend on biomarkers of inflammation in obese subjects: a pilot, dose finding study.
The ability to reduce inflammation in overweight and obese individuals may be valuable in preventing the progression to metabolic syndrome with associated risks for heart disease and diabetes. The purpose of this study was to evaluate the effect of multiple dosages of a proprietary Mangosteen Juice blend on indicators of inflammation and antioxidant levels in obese patients with elevated C-reactive protein (CRP) levels. The study was an 8 week randomized, double-blind, placebo-controlled study with a pre-study 2 week washout period. The study included four groups including placebo and three difference doses of the test product, XanGo Juice: 3, 6 or 9 oz twice daily. The primary outcome measure of this study was high-sensitivity (HS)-CRP. Secondary outcome measures included other biochemical indicators of inflammation, anthropomorphic measures and a safety evaluation. One hundred twenty two (122) persons were screened for the study, 44 were randomized and 40 completed the study. HS-CRP measurements dropped after 8 weeks treatment compared to baseline in all 3 dose groups and increased in the placebo group. The changes from baseline were not significant but the comparison of change from baseline was significant for the 18 oz group when compared to placebo (p = 0.02). Other markers of inflammation (inflammatory cytokines) and a marker for lipid peroxidation (F2 isoprostane) did not show any significant differences when compared with placebo. There was a trend towards a decrease in BMI in the juice groups. There were no side effects reported in any of the groups and none of the laboratory or EKG safety assessments indicated clinically significant changes for any subject. In this pilot, dose-finding study, a proprietary mangosteen juice blend (XanGo Juice) reduced CRP levels (increased change from baseline) compared to placebo for those taking the highest dose of 18 oz per day. Further studies with a larger population are required to confirm and further define the benefits of this juice. The juice was administered safely. ISRCTN9300027.


Constraining eye movement when redirecting walking trajectories alters turning control in healthy young adults.
Humans use a specific steering synergy, where the eyes and head lead rotation to the new direction, when executing a turn or change in direction. Increasing evidence suggests that eye movement is critical for turning control and that when the eyes are constrained, or participants have difficulties making eye movements, steering control is disrupted. The purpose of the current study was to extend previous research regarding eye movements and steering control to a functional walking and turning task. This study investigated eye, head, trunk, and pelvis kinematics of healthy young adults during a 90° redirection of walking trajectory under two visual conditions: Free Gaze (the eyes were allowed to move naturally in the environment), and Fixed Gaze (participants were required to fixate the eyes on a target in front). Results revealed significant differences in eye, head, and trunk coordination between Free Gaze and Fixed Gaze conditions (p < 0.001). During Free Gaze, the eyes led reorientation followed by the head and trunk. Intersegment timings between the eyes, head, and trunk were significantly different (p < 0.05). In contrast, during Fixed Gaze, the segments moved together with no significant differences between segment onset times. In addition, the sequence of segment rotation during Fixed Gaze suggested a bottom-up postural perturbation control strategy in place of top-down steering control seen in Free Gaze. The results of this study support the hypothesis that eye movement is critical for the release of the steering synergy for turning control.


Effect of alkali ions on optical properties of flavins: vibronic spectra of cryogenic M+lumichrome ions (M = Li-Cs) in the gas phase.
The photochemical properties of flavins depend sensitively on their environment and are strongly modified by coordination with metal ions. Herein, the electronic spectra of cold complexes of the smallest flavin molecule (lumichrome, LC, C12N4O2H10) with alkali ions (M+LC, M = Li-Cs) are measured by photodissociation in the visible range (VISPD) in a cryogenic ion trap coupled to a tandem mass spectrometer and an electrospray ionization source. The observed vibronic spectra of all ions are assigned to the optically bright S1 ← S0 (ππ*) transition of the most stable O4 isomer of M+LC by comparison with quantum chemical calculations at the PBE0/cc-pVDZ level coupled to multidimensional Franck-Condon simulations. The rich vibronic spectra indicate substantial geometry changes upon S1 excitation. Large red shifts of the S1 origins upon metal complexation and progressions in the intermolecular in-plane metal stretch and bend modes demonstrate that the strength of the metal-flavin interaction in M+LC(O4) strongly increases by S1 excitation. The stronger M+LC bond in the S1 state of M+LC(O4) is rationalized by the charge reorganization upon ππ* excitation of the LC chromophore. The computations confirm that the optical properties of LC can be strongly modulated by metalation via both the type and binding site of the metal ion.


Headspace volatile markers for sensitivity of cocoa (Theobroma cacao L.) somatic embryos to cryopreservation.
The mechanisms that reduce the viability of plant somatic embryos following cryopreservation are not known. The objective of the present study was to evaluate the sensitivity of cocoa (Theobroma cacao L.) somatic embryos at different stages of an encapsulation-dehydration protocol using stress-related volatile hydrocarbons as markers of injury and recovery. The plant stress hormone ethylene and volatile hydrocarbons derived from hydroxyl radicals (methane) and lipid peroxidation (ethane) were determined using gas chromatography headspace analysis. Ethylene and methane were the only volatiles detected, with both being produced after each step of the cryogenic protocol. Ethylene production was significantly reduced following exposure to liquid nitrogen, but then increased in parallel with embryo recovery. In contrast, the production of methane was cyclic during recovery, with the first cycle occurring earlier for embryos recovered from liquid nitrogen and desiccation than those recovered from earlier steps in the protocol. These results suggest that loss of somatic embryo viability during cryopreservation may be related to the oxidative status of the tissue, and its capacity to produce ethylene. This study has demonstrated that headspace volatile analysis provides a robust non-destructive analytical approach for assessing the survival and recovery of plant somatic embryos following cryopreservation.


Healthy active living: a residence community-based intervention to increase physical activity and healthy eating during the transition to first-year university.
To examine the effects of a Healthy Active Living (HAL) community intervention on moderate-to-vigorous physical activity (MVPA), fruit and vegetable consumption (FVC), and psychosocial mediators of physical activity among students transitioning into university. Sixty undergraduate students were assigned to reside in either the HAL community or no-treatment control residence and completed questionnaire measures at the beginning and end of the academic year. Students living in the HAL community reported significantly more MVPA (F[1, 58]=19.93, p<.001, ηp2=.26) and greater FVC (F[1, 56]=3.12, p=.08, ηp2=.05) compared with controls. Participants in the HAL condition also scored significantly higher in action planning (F[1, 58]=4.79, p<.05, ηp2=.08), partially mediating the effect of the intervention on MVPA. A peer-delivered healthy lifestyles intervention targeting first-year university students appears to be effective in preserving or enhancing health behaviors and cognitions during their transition into university life.


Behavioral responses by grey seals (Halichoerus grypus) to high frequency sonar.
The use of high frequency sonar is now commonplace in the marine environment. Most marine mammals rely on sound to navigate, and for detecting prey, and there is the potential that the acoustic signals of sonar could cause behavioral responses. To investigate this, we carried out behavioral response tests with grey seals to two sonar systems (200 and 375 kHz systems). Results showed that both systems had significant effects on the seals behavior; when the 200 kHz sonar was active, seals spent significantly more time hauled out and, although seals remained swimming during operation of the 375 kHz sonar, they were distributed further from the sonar. The results show that although peak sonar frequencies may be above marine mammal hearing ranges, high levels of sound can be produced within their hearing ranges that elicit behavioral responses; this has clear implications for the widespread use of sonar in the marine environment.


The diagnostic accuracy of 256-row computed tomographic angiography compared with invasive coronary angiography in patients with suspected coronary artery disease.
To assess the diagnostic accuracy of 256-row computed tomographic angiography (CTA) in patients with suspected coronary artery disease (CAD). Non-invasive imaging of the coronary artery by CTA has increasingly been used in recent years. The accuracy of 256-row CTA has not yet been studied. We sought to assess the accuracy of 256-row CTA compared with invasive coronary angiography (ICA) in the diagnosis and assessment of CAD. We prospectively evaluated 104 consecutive individuals who accepted CTA and then underwent ICA. The presence of stenosis > or =50% was considered obstructive. The diagnostic accuracy of CTA for detecting obstructive stenosis was compared with that of ICA. The area under the receiver-operating-characteristic curve (AUC) was used to evaluate the diagnostic accuracy of CTA relative to ICA. A total of 86 patients had obstructive CAD. The patient-based analysis of CTA for detecting stenosis > or =50% according to ICA revealed an AUC of 0.744 [95% confidence interval (CI), 0.572-0.916], with a sensitivity of 98.8%, a specificity of 50%, a positive predictive value (PPV) of 92.4%, and a negative predictive value (NPV) of 87.5%. The segment-based analysis revealed an AUC of 0.915 (95% CI, 0.847-0.982), with a sensitivity of 93.5%, a specificity of 95%, a PPV of 77.6%, and an NPV of 98.7%. The vessel-based analysis revealed an AUC of 0.887 (95% CI, 0.808-0.966), with a sensitivity of 94.3%, a specificity of 87.3%, a PPV of 82.7%, and an NPV of 95.9%. 256-Row CTA is a highly sensitive test of CAD and has a high predictive value. 256-Row CTA may be a potential alternative to detect coronary artery stenosis and rule out CAD in suspected patients.


Selective attention to affective stimuli and clinical depression among youths: role of anxiety and specificity of emotion.
Cognitive models of psychopathology posit that the content or focus of information-processing biases (e.g., attentional biases) is disorder specific: Depression is hypothesized to be characterized by attentional biases specifically for depression-relevant stimuli (e.g., sad facial expressions), whereas anxiety should relate particularly to attentional biases to threat-relevant stimuli (e.g., angry faces). However, little research has investigated this specificity hypothesis and none with a sample of youths. The present study examined attentional biases to emotional faces (sad, angry, and happy compared with neutral) in groups of pure depressed, pure anxious, comorbid depressed and anxious, and control youths (ages 9-17 years; N = 161). Consistent with cognitive models, pure depressed and pure anxious youths exhibited attentional biases specifically to sad and angry faces, respectively, whereas comorbid youths exhibited attentional biases to both facial expressions. In addition, control youths exhibited attentional avoidance of sad faces, and comorbid boys avoided happy faces. Overall, findings suggest that cognitive biases and processing of particular emotional information are specific to pure clinical depression and anxiety, and results inform etiological models of potentially specific processes that are associated with internalizing disorders among youths.


Preservation of duplicate genes by complementary, degenerative mutations.
The origin of organismal complexity is generally thought to be tightly coupled to the evolution of new gene functions arising subsequent to gene duplication. Under the classical model for the evolution of duplicate genes, one member of the duplicated pair usually degenerates within a few million years by accumulating deleterious mutations, while the other duplicate retains the original function. This model further predicts that on rare occasions, one duplicate may acquire a new adaptive function, resulting in the preservation of both members of the pair, one with the new function and the other retaining the old. However, empirical data suggest that a much greater proportion of gene duplicates is preserved than predicted by the classical model. Here we present a new conceptual framework for understanding the evolution of duplicate genes that may help explain this conundrum. Focusing on the regulatory complexity of eukaryotic genes, we show how complementary degenerative mutations in different regulatory elements of duplicated genes can facilitate the preservation of both duplicates, thereby increasing long-term opportunities for the evolution of new gene functions. The duplication-degeneration-complementation (DDC) model predicts that (1) degenerative mutations in regulatory elements can increase rather than reduce the probability of duplicate gene preservation and (2) the usual mechanism of duplicate gene preservation is the partitioning of ancestral functions rather than the evolution of new functions. We present several examples (including analysis of a new engrailed gene in zebrafish) that appear to be consistent with the DDC model, and we suggest several analytical and experimental approaches for determining whether the complementary loss of gene subfunctions or the acquisition of novel functions are likely to be the primary mechanisms for the preservation of gene duplicates. For a newly duplicated paralog, survival depends on the outcome of the race between entropic decay and chance acquisition of an advantageous regulatory mutation. Sidow 1996(p. 717) On one hand, it may fix an advantageous allele giving it a slightly different, and selectable, function from its original copy. This initial fixation provides substantial protection against future fixation of null mutations, allowing additional mutations to accumulate that refine functional differentiation. Alternatively, a duplicate locus can instead first fix a null allele, becoming a pseudogene. Walsh 1995 (p. 426) Duplicated genes persist only if mutations create new and essential protein functions, an event that is predicted to occur rarely. Nadeau and Sankoff 1997 (p. 1259) Thus overall, with complex metazoans, the major mechanism for retention of ancient gene duplicates would appear to have been the acquisition of novel expression sites for developmental genes, with its accompanying opportunity for new gene roles underlying the progressive extension of development itself. Cooke et al. 1997 (p. 362)


A barley PHD finger transcription factor that confers male sterility by affecting tapetal development.
Controlling pollen development is of major commercial importance in generating hybrid crops and selective breeding, but characterized genes for male sterility in crops are rare, with no current examples in barley. However, translation of knowledge from model species is now providing opportunities to understand and manipulate such processes in economically important crops. We have used information from regulatory networks in Arabidopsis to identify and functionally characterize a barley PHD transcription factor MALE STERTILITY1 (MS1), which expresses in the anther tapetum and plays a critical role during pollen development. Comparative analysis of Arabidopsis, rice and Brachypodium genomes was used to identify conserved regions in MS1 for primer design to amplify the barley MS1 gene; RACE-PCR was subsequently used to generate the full-length sequence. This gene shows anther-specific tapetal expression, between late tetrad stage and early microspore release. HvMS1 silencing and overexpression in barley resulted in male sterility. Additionally, HvMS1 cDNA, controlled by the native Arabidopsis MS1 promoter, successfully complemented the homozygous ms1 Arabidopsis mutant. These results confirm the conservation of MS1 function in higher plants and in particular in temperate cereals. This has provided the first example of a characterized male sterility gene in barley, which presents a valuable tool for the future control of male fertility in barley for hybrid development.


How music alters a kiss: superior temporal gyrus controls fusiform-amygdalar effective connectivity.
While watching movies, the brain integrates the visual information and the musical soundtrack into a coherent percept. Multisensory integration can lead to emotion elicitation on which soundtrack valences may have a modulatory impact. Here, dynamic kissing scenes from romantic comedies were presented to 22 participants (13 females) during functional magnetic resonance imaging scanning. The kissing scenes were either accompanied by happy music, sad music or no music. Evidence from cross-modal studies motivated a predefined three-region network for multisensory integration of emotion, consisting of fusiform gyrus (FG), amygdala (AMY) and anterior superior temporal gyrus (aSTG). The interactions in this network were investigated using dynamic causal models of effective connectivity. This revealed bilinear modulations by happy and sad music with suppression effects on the connectivity from FG and AMY to aSTG. Non-linear dynamic causal modeling showed a suppressive gating effect of aSTG on fusiform-amygdalar connectivity. In conclusion, fusiform to amygdala coupling strength is modulated via feedback through aSTG as region for multisensory integration of emotional material. This mechanism was emotion-specific and more pronounced for sad music. Therefore, soundtrack valences may modulate emotion elicitation in movies by differentially changing preprocessed visual information to the amygdala.


Streamlined and Abundant Bacterioplankton Thrive in Functional Cohorts.
While fastidious microbes can be abundant and ubiquitous in their natural communities, many fail to grow axenically in laboratories due to auxotrophies or other dependencies. To overcome auxotrophies, these microbes rely on their surrounding cohort. A cohort may consist of kin (ecotypes) or more distantly related organisms (community) with the cooperation being reciprocal or nonreciprocal and expensive (Black Queen hypothesis) or costless (by-product). These metabolic partnerships (whether at single species population or community level) enable dominance by and coexistence of these lineages in nature. Here we examine the relevance of these cooperation models to explain the abundance and ubiquity of the dominant fastidious bacterioplankton of a dimictic mesotrophic freshwater lake. Using both culture-dependent (dilution mixed cultures) and culture-independent (small subunit [SSU] rRNA gene time series and environmental metagenomics) methods, we independently identified the primary cohorts of actinobacterial genera "Candidatus Planktophila" (acI-A) and "Candidatus Nanopelagicus" (acI-B) and the proteobacterial genus "Candidatus Fonsibacter" (LD12). While "Ca Planktophila" and "Ca. Fonsibacter" had no correlation in their natural habitat, they have the potential to be complementary in laboratory settings. We also investigated the bifunctional catalase-peroxidase enzyme KatG (a common good which "Ca Planktophila" is dependent upon) and its most likely providers in the lake. Further, we found that while ecotype and community cooperation combined may explain "Ca Planktophila" population abundance, the success of "Ca. Nanopelagicus" and "Ca. Fonsibacter" is better explained as a community by-product. Ecotype differentiation of "Ca. Fonsibacter" as a means of escaping predation was supported but not for overcoming auxotrophies.IMPORTANCE This study examines evolutionary and ecological relationships of three of the most ubiquitous and abundant freshwater bacterial genera: "Ca Planktophila" (acI-A), "Ca. Nanopelagicus" (acI-B), and "Ca. Fonsibacter" (LD12). Due to high abundance, these genera might have a significant influence on nutrient cycling in freshwaters worldwide, and this study adds a layer of understanding to how seemingly competing clades of bacteria can coexist by having different cooperation strategies. Our synthesis ties together network and ecological theory with empirical evidence and lays out a framework for how the functioning of populations within complex microbial communities can be studied.


Design, Development, and Temporal Evaluation of a Magnetic Resonance Imaging-Compatible In Vitro Circulation Model Using a Compliant Abdominal Aortic Aneurysm Phantom.
Biomechanical characterization of abdominal aortic aneurysms (AAAs) has become commonplace in rupture risk assessment studies. However, its translation to the clinic has been greatly limited due to the complexity associated with its tools and their implementation. The unattainability of patient-specific tissue properties leads to the use of generalized population-averaged material models in finite element analyses, which adds a degree of uncertainty to the wall mechanics quantification. In addition, computational fluid dynamics modeling of AAA typically lacks the patient-specific inflow and outflow boundary conditions that should be obtained by nonstandard of care clinical imaging. An alternative approach for analyzing AAA flow and sac volume changes is to conduct in vitro experiments in a controlled laboratory environment. In this study, we designed, built, and characterized quantitatively a benchtop flow loop using a deformable AAA silicone phantom representative of a patient-specific geometry. The impedance modules, which are essential components of the flow loop, were fine-tuned to ensure typical intraluminal pressure conditions within the AAA sac. The phantom was imaged with a magnetic resonance imaging (MRI) scanner to acquire time-resolved images of the moving wall and the velocity field inside the sac. Temporal AAA sac volume changes lead to a corresponding variation in compliance throughout the cardiac cycle. The primary outcome of this work was the design optimization of the impedance elements, the quantitative characterization of the resistive and capacitive attributes of a compliant AAA phantom, and the exemplary use of MRI for flow visualization and quantification of the deformed AAA geometry.


Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment.
Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P = .07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4 cell count was above 0.200 x 10(9)/L (200 cells/microL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P = .02; Mantel-Haenszel chi(2) test). Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score > or = 0.5) or with relatively preserved immunological status (ie, CD4+ cell count > 0.200 x 10(9)/L).


Joint digital-optical design of superresolution multiframe imaging systems.
Typical electro-optic imaging systems produce image aliasing artifacts. Superresolution algorithms process multiple aliased images to yield a single high-resolution image. We design imaging systems by jointly optimizing the optics and postprocessing to maximize such multiframe imaging performance. We describe efficient software methods that can be used to perform joint design by use of commercially available lens design software.


Physical activity dose-response effects on outcomes of depression and anxiety.
The purpose of this study was to examine the scientific evidence for a dose-response relation of physical activity with depressive and anxiety disorders. Computer database searches of MEDLINE, PsychLit, and Internet and personal retrieval systems to locate population studies, randomized controlled trials (RCTs), observational studies, and consensus panel judgments were conducted. Observational studies demonstrate that greater amounts of occupational and leisure time physical activity are generally associated with reduced symptoms of depression. Quasi-experimental studies show that light-, moderate-, and vigorous-intensity exercise can reduce symptoms of depression. However, no RCTs have varied frequency or duration of exercise and controlled for total energy expenditure in studies of depression or anxiety. Quasi-experimental and RCTs demonstrate that both resistance training and aerobic exercise can reduce symptoms of depression. Finally, the relation of exercise dose to changes in cardiorespiratory fitness is equivocal with some studies showing that fitness is associated with reduction of symptoms and others that have demonstrated reduction in symptoms without increases in fitness. All evidence for dose-response effects of physical activity and exercise come from B and C levels of evidence. There is little evidence for dose-response effects, though this is largely because of a lack of studies rather than a lack of evidence. A dose-response relation does, however, remain plausible.


The human EKC/KEOPS complex is recruited to Cullin2 ubiquitin ligases by the human tumour antigen PRAME.
The human tumour antigen PRAME (preferentially expressed antigen in melanoma) is frequently overexpressed during oncogenesis, and high PRAME levels are associated with poor clinical outcome in a variety of cancers. However, the molecular pathways in which PRAME is implicated are not well understood. We recently characterized PRAME as a BC-box subunit of a Cullin2-based E3 ubiquitin ligase. In this study, we mined the PRAME interactome to a deeper level and identified specific interactions with OSGEP and LAGE3, which are human orthologues of the ancient EKC/KEOPS complex. By characterizing biochemically the human EKC complex and its interactions with PRAME, we show that PRAME recruits a Cul2 ubiquitin ligase to EKC. Moreover, EKC subunits associate with PRAME target sites on chromatin. Our data reveal a novel link between the oncoprotein PRAME and the conserved EKC complex and support a role for both complexes in the same pathways.


Lysine and novel hydroxylysine lipids in soil bacteria: amino acid membrane lipid response to temperature and pH in Pseudopedobacter saltans.
Microbial decomposition of organic matter is an essential process in the global carbon cycle. The soil bacteria Pseudopedobacter saltans and Flavobacterium johnsoniae are both able to degrade complex organic molecules, but it is not fully known how their membrane structures are adapted to their environmental niche. The membrane lipids of these species were extracted and analyzed using high performance liquid chromatography-electrospray ionization/ion trap/mass spectrometry (HPLC-ESI/IT/MS) and high resolution accurate mass/mass spectrometry (HRAM/MS). Abundant unknown intact polar lipids (IPLs) from P. saltans were isolated and further characterized using amino acid analysis and two dimensional nuclear magnetic resonance (NMR) spectroscopy. Ornithine IPLs (OLs) with variable (hydroxy) fatty acid composition were observed in both bacterial species. Lysine-containing IPLs (LLs) were also detected in both species and were characterized here for the first time using HPLC-MS. Novel LLs containing hydroxy fatty acids and novel hydroxylysine lipids with variable (hydroxy) fatty acid composition were identified in P. saltans. The confirmation of OL and LL formation in F. johnsoniae and P. saltans and the presence of OlsF putative homologs in P. saltans suggest the OlsF gene coding protein is possibly involved in OL and LL biosynthesis in both species, however, potential pathways of OL and LL hydroxylation in P. saltans are still undetermined. Triplicate cultures of P. saltans were grown at three temperature/pH combinations: 30°C/pH 7, 15°C/pH 7, and 15°C/pH 9. The fractional abundance of total amino acid containing IPLs containing hydroxylated fatty acids was significantly higher at higher temperature, and the fractional abundance of lysine-containing IPLs was significantly higher at lower temperature and higher pH. These results suggest that these amino acid-containing IPLs, including the novel hydroxylysine lipids, could be involved in temperature and pH stress response of soil bacteria.


TREM2 deficiency impairs chemotaxis and microglial responses to neuronal injury.
Sequence variations in the triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to an increased risk for neurodegenerative disorders such as Alzheimer's disease and frontotemporal lobar degeneration. In the brain, TREM2 is predominantly expressed in microglia. Several disease-associated TREM2 variants result in a loss of function by reducing microglial phagocytosis, impairing lipid sensing, preventing binding of lipoproteins and affecting shielding of amyloid plaques. We here investigate the consequences of TREM2 loss of function on the microglia transcriptome. Among the differentially expressed messenger RNAs in wild-type and Trem2-/- microglia, gene clusters are identified which represent gene functions in chemotaxis, migration and mobility. Functional analyses confirm that loss of TREM2 impairs appropriate microglial responses to injury and signals that normally evoke chemotaxis on multiple levels. In an ex vivo organotypic brain slice assay, absence of TREM2 reduces the distance migrated by microglia. Moreover, migration towards defined chemo-attractants is reduced upon ablation of TREM2 and can be rescued by TREM2 re-expression. In vivo, microglia lacking TREM2 migrate less towards injected apoptotic neurons, and outgrowth of microglial processes towards sites of laser-induced focal CNS damage in the somatosensory cortex is slowed. The apparent lack of chemotactic stimulation upon depletion of TREM2 is consistent with a stable expression profile of genes characterizing the homoeostatic signature of microglia.


Mortality rates associated with crown health for eastern forest tree species.
The condition of tree crowns is an important indicator of tree and forest health. Crown conditions have been evaluated during inventories of the US Forest Service Forest Inventory and Analysis (FIA) program since 1999. In this study, remeasured data from 55,013 trees on 2616 FIA plots in the eastern USA were used to assess the probability of survival among various tree species using the suite of FIA crown condition variables. Logistic regression procedures were employed to develop models for predicting tree survival. Results of the regression analyses indicated that crown dieback was the most important crown condition variable for predicting tree survival for all species combined and for many of the 15 individual species in the study. The logistic models were generally successful in representing recent tree mortality responses to multiyear infestations of beech bark disease and hemlock woolly adelgid. Although our models are only applicable to trees growing in a forest setting, the utility of models that predict impending tree mortality goes beyond forest inventory or traditional forestry growth and yield models and includes any application where managers need to assess tree health or predict tree mortality including urban forest, recreation, wildlife, and pest management.


Imparting biomimetic ion-gating recognition properties to electrodes with a hydrogen-bonding structured core-shell nanoparticle network.
This paper presents findings of the creation of biomimetic ion-gating properties with core-shell nanoparticle network architectures. The architectures were formed by hydrogen-bonding linkages via an exchange-cross-linking-precipitation reaction pathway using gold nanoparticles capped with thiolate shell and alkylthiols terminated with carboxylic groups as model building blocks. Such network assemblies have open frameworks in which void space is in the form of a channel or chamber with the nanometer-sized cores defining its size, the geometric arrangement defining its shape, and the shell structures defining its chemical specificity. The formation of the network linkages via head-to-head hydrogen-bonded carboxylic terminals and the reversible pH-tuned structural properties between neutral and ionic states were characterized using infrared reflectance spectroscopic technique. The biomimetic ion-gating properties were demonstrated by measuring the pH-tuned network "open-close" responses to charged redox probes. Such redox responses were shown to depend on the degree of protonation-deprotonation of carboxylic groups at the interparticle linkages, core sizes of the nanoparticles, and charges of the redox probes. Differences in structural networking, pH-tuning, and electrochemical gating properties were identified between the network films derived from nanoparticles of two different core sizes (2 and 5 nm). The mechanistic correlation of these structural properties was discussed. These findings have added a new pathway to the current approaches to biomimetic molecular recognition via design of core-shell nanoparticle architectures at both nanocrystal and molecular scales.