Membranes by the Numbers

Many of the most important processes in cells take place on and across membranes. With the rise of an impressive array of powerful quantitative methods for characterizing these membranes, it is an opportune time to reflect on the structure and function of membranes from the point of view of biological numeracy. To that end, in this article, I review the quantitative parameters that characterize the mechanical, electrical and transport properties of membranes and carry out a number of corresponding order of magnitude estimates that help us understand the values of those parameters.Comment: 27 pages, 12 figure

Proposal of a framework for evaluating military surveillance systems for early detection of outbreaks on duty areas

<p>Abstract</p> <p>Background</p> <p>In recent years a wide variety of epidemiological surveillance systems have been developed to provide early identification of outbreaks of infectious disease. Each system has had its own strengths and weaknesses. In 2002 a Working Group of the Centers for Disease Control and Prevention (CDC) produced a framework for evaluation, which proved suitable for many public health surveillance systems. However this did not easily adapt to the military setting, where by necessity a variety of different parameters are assessed, different constraints placed on the systems, and different objectives required. This paper describes a proposed framework for evaluation of military syndromic surveillance systems designed to detect outbreaks of disease on operational deployments.</p> <p>Methods</p> <p>The new framework described in this paper was developed from the cumulative experience of British and French military syndromic surveillance systems. The methods included a general assessment framework (CDC), followed by more specific methods of conducting evaluation. These included Knowledge/Attitude/Practice surveys (KAP surveys), technical audits, ergonomic studies, simulations and multi-national exercises. A variety of military constraints required integration into the evaluation. Examples of these include the variability of geographical conditions in the field, deployment to areas without prior knowledge of naturally-occurring disease patterns, the differences in field sanitation between locations and over the length of deployment, the mobility of military forces, turnover of personnel, continuity of surveillance across different locations, integration with surveillance systems from other nations working alongside each other, compatibility with non-medical information systems, and security.</p> <p>Results</p> <p>A framework for evaluation has been developed that can be used for military surveillance systems in a staged manner consisting of initial, intermediate and final evaluations. For each stage of the process parameters for assessment have been defined and methods identified.</p> <p>Conclusion</p> <p>The combined experiences of French and British syndromic surveillance systems developed for use in deployed military forces has allowed the development of a specific evaluation framework. The tool is suitable for use by all nations who wish to evaluate syndromic surveillance in their own military forces. It could also be useful for civilian mobile systems or for national security surveillance systems.</p

Influence of an outpatient multidisciplinary pain management program on the health-related quality of life and the physical fitness of chronic pain patients

BACKGROUND: Approximately 10 to 20 percent of the population is suffering from chronic pain. Since this represents a major contribution to the costs of the health care system, more efficient measures and interventions to treat these patients are sought. RESULTS: The development of general health and physical activity of patients with chronic pain was assessed in an interdisciplinary outpatient pain management program (IOPP). 36 patients with an average age of 48 years were included in the IOPP. Subjective assessment of well-being was performed at five time points (baseline, post intervention and 3, 6, and 12 months thereafter) by using standardized questionnaires. The study focused on the quality of life survey Medical Outcomes Study Short Form-36, which is a validated instrument with established reliability and sensitivity. In addition, the patients participated in physical assessment testing strength, power, endurance, and mobility. Prior to therapy a substantial impairment was found on different levels. Marked improvements in the psychological parameters were obtained by the end of the program. No success was achieved with regard to the physical assessments. CONCLUSION: Although many different studies have evaluated similar programs, only few of them have attained positive results such as improvements of general quality of life or of physical strength. Often no difference from the control group could be detected only some months after the intervention. In the present study no significant persistent improvement of well-being occurred. Possible reasons are either wrong instruments, wrong selection of patients or wrong interventions

Metabolic syndrome, psychological status and quality of life in obesity: the QUOVADIS Study

Objective: We aimed to investigate the association of the clinical variables of the metabolic syndrome (MS) and psychological parameters on health-related quality of life (HRQL) in obesity. In particular, our aim was to investigate the relative impact of physical symptoms, somatic diseases and psychological distress on both the physical and the mental domains of HRQL. Design: Cross-sectional study. Subjects: A cohort of 1822 obese outpatients seeking treatment in medical centers. Measurements: HRQL was measured by the standardized summary scores for physical (PCS) and mental (MCS) components of the Short Form 36 Health Survey (SF-36). Patients were grouped according to tertiles of PCS and MCS. Metabolic and psychological profiles of PCS and MCS tertiles were compared by discriminant analysis. Results: The profile of metabolic and psychological variables was tertile-specific in 62.4 and 68.3% of patients in the lowest and highest tertiles of PCS, respectively, while concordance was low in the mid-tertile (32.8%). Concordance was very high in the lowest (74.4%) and in the highest (75.5%) tertiles of MCS, and was fair in the mid-tertile (53.2%). The main correlates of PCS were obesity-specific and general psychological well-being, BMI, body uneasiness, binge eating, gender and psychiatric distress. Only hypertension and hyperglycemia qualified as correlates among the components of MS. The components of MS did not define MCS. Conclusions: Psychological well-being is the most important correlate of HRQL in obesity, both in the physical and in the mental domains, whereas the features of MS correlate only to some extent with the physical domain of HRQL

Validation of two generic patient-reported outcome measures in patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Prior to using a generic patient-reported outcome measure (PRO), the measure should be validated within the target population. The purpose of the current study was to validate two generic measures in patients with type 2 diabetes.</p> <p>Methods</p> <p>Patients with type 2 diabetes in Scotland and England completed two generic measures: EQ-5D and Psychological General Well-Being Index (PGWB). Two diabetes-specific measures were administered: ADS and DSC-R. Analyses assessed reliability and validity.</p> <p>Results</p> <p>There were 130 participants (53 Scotland; 77 England; 64% male; mean age = 55.7 years). Responses on the EQ-5D and PGWB reflected moderate impairment consistent with previous diabetes samples: mean EQ-5D Index score, 0.75; EQ-5D VAS, 68.8; PGWB global score, 67.9. All scales of the PGWB demonstrated good internal consistency reliability (Cronbach's alpha = 0.77 to 0.97). The EQ-5D and PGWB demonstrated convergent validity through significant correlations with the ADS (r = 0.48 to 0.61), DSC-R scales (r = 0.33 to 0.81 except ophthalmology subscale), and Body Mass Index (r = 0.15 to 0.38). The EQ-5D and PGWB discriminated between groups of patients known to differ in diabetes-related characteristics (e.g., history of hypoglycemia).</p> <p>Conclusion</p> <p>Results support the use of the EQ-5D and PGWB among patients with type 2 diabetes, possibly in combination with condition-specific measures.</p

Human Integrin α3β1 Regulates TLR2 Recognition of Lipopeptides from Endosomal Compartments

Toll-like receptor (TLR)-2/TLR1 heterodimers recognize bacterial lipopeptides and initiate the production of inflammatory mediators. Adaptors and co-receptors that mediate this process, as well as the mechanisms by which these adaptors and co-receptors function, are still being discovered.Using shRNA, blocking antibodies, and fluorescent microscopy, we show that U937 macrophage responses to the TLR2/1 ligand, Pam(3)CSK(4), are dependent upon an integrin, α(3)β(1). The mechanism for integrin α(3)β(1) involvement in TLR2/1 signaling is through its role in endocytosis of lipopeptides. Using inhibitors of endosomal acidification/maturation and physical tethering of the ligand, we show that the endocytosis of Pam(3)CSK(4) is necessary for the complete TLR2/1-mediated pro-inflammatory cytokine response. We also show that TLR2/1 signaling from the endosome results in the induction of different inflammatory mediators than TLR2/1 signaling from the plasma membrane.Here we identify integrin α(3)β(1) as a novel regulator for the recognition of bacterial lipopeptides. We demonstrate that induction of a specific subset of cytokines is dependent upon integrin α(3)β(1)-mediated endocytosis of the ligand. In addition, we address an ongoing controversy regarding endosomal recognition of bacterial lipopeptides by demonstrating that TLR2/1 signals from within endosomal compartments as well as the plasma membrane, and that downstream responses may differ depending upon receptor localization. We propose that the regulation of endosomal TLR2/1 signaling by integrin α(3)β(1) serves as a mechanism for modulating inflammatory responses

Assessing positive mental health in people with chronic physical health problems: correlations with socio-demographic variables and physical health status

Background: A holistic perspective on health implies giving careful consideration to the relationship between physical and mental health. In this regard the present study sought to determine the level of Positive Mental Health (PMH) among people with chronic physical health problems, and to examine the relationship between the observed levels of PMH and both physical health status and socio-demographic variables. Methods: The study was based on the Multifactor Model of Positive Mental Health (Lluch, 1999), which comprises six factors: Personal Satisfaction (F1), Prosocial Attitude (F2), Self-control (F3), Autonomy (F4), Problem-solving and Self-actualization (F5), and Interpersonal Relationship Skills (F6). The sample comprised 259 adults with chronic physical health problems who were recruited through a primary care center in the province of Barcelona (Spain). Positive mental health was assessed by means of the Positive Mental Health Questionnaire (Lluch, 1999). Results: Levels of PMH differed, either on the global scale or on specific factors, in relation to the following variables: age: global PMH scores decreased with age (r=-0.129; p=0.038); b) gender: men scored higher on F1 (t=2.203; p=0.028) and F4 (t=3.182; p=0.002), while women scored higher on F2 (t -3.086; p=0.002) and F6 (t=-2.744; p=0.007); c) number of health conditions: the fewer the number of health problems the higher the PMH score on F5 (r=-0.146; p=0.019); d) daily medication: polymedication patients had lower PMH scores, both globally and on various factors; e) use of analgesics: occasional use of painkillers was associated with higher PMH scores on F1 (t=-2.811; p=0.006). There were no significant differences in global PMH scores according to the type of chronic health condition. The only significant difference in the analysis by factors was that patients with hypertension obtained lower PMH scores on the factor Autonomy (t=2.165; p=0.032). Conclusions: Most people with chronic physical health problems have medium or high levels of PMH. The variables that adversely affect PMH are old age, polypharmacy and frequent consumption of analgesics. The type of health problem does not influence the levels of PMH. Much more extensive studies with samples without chronic pathology are now required in order to be able to draw more robust conclusions

Cholesterol Induces Specific Spatial and Orientational Order in Cholesterol/Phospholipid Membranes

In lipid bilayers, cholesterol facilitates the formation of the liquid-ordered phase and enables the formation of laterally ordered structures such as lipid rafts. While these domains have an important role in a variety of cellular processes, the precise atomic-level mechanisms responsible for cholesterol's specific ordering and packing capability have remained unresolved

Mapping Connectivity Damage in the Case of Phineas Gage

White matter (WM) mapping of the human brain using neuroimaging techniques has gained considerable interest in the neuroscience community. Using diffusion weighted (DWI) and magnetic resonance imaging (MRI), WM fiber pathways between brain regions may be systematically assessed to make inferences concerning their role in normal brain function, influence on behavior, as well as concerning the consequences of network-level brain damage. In this paper, we investigate the detailed connectomics in a noted example of severe traumatic brain injury (TBI) which has proved important to and controversial in the history of neuroscience. We model the WM damage in the notable case of Phineas P. Gage, in whom a “tamping iron” was accidentally shot through his skull and brain, resulting in profound behavioral changes. The specific effects of this injury on Mr. Gage's WM connectivity have not previously been considered in detail. Using computed tomography (CT) image data of the Gage skull in conjunction with modern anatomical MRI and diffusion imaging data obtained in contemporary right handed male subjects (aged 25–36), we computationally simulate the passage of the iron through the skull on the basis of reported and observed skull fiducial landmarks and assess the extent of cortical gray matter (GM) and WM damage. Specifically, we find that while considerable damage was, indeed, localized to the left frontal cortex, the impact on measures of network connectedness between directly affected and other brain areas was profound, widespread, and a probable contributor to both the reported acute as well as long-term behavioral changes. Yet, while significantly affecting several likely network hubs, damage to Mr. Gage's WM network may not have been more severe than expected from that of a similarly sized “average” brain lesion. These results provide new insight into the remarkable brain injury experienced by this noteworthy patient