A scientific milestone that has tremendously impacted the cardiac research field has been the discovery and establishment of human-induced pluripotent stem cells (hiPSC). Key to this discovery has been uncovering a viable path in generating human patient and disease-specific cardiac cells to dynamically model and study human cardiac diseases in an in vitro setting. Recent studies have demonstrated that hiPSC-derived cardiomyocytes can be used to model and recapitulate various known disease features in hearts of patient donors harboring genetic-based cardiac diseases. Experimental drugs have also been tested in this setting and shown to alleviate disease phenotypes in hiPSC-derived cardiomyocytes, further paving the way for therapeutic interventions for cardiac disease. Here, we review state-of-the-art methods to generate high-quality hiPSC and differentiate them towards cardiomyocytes as well as the full range of genetic-based cardiac diseases, which have been modeled using hiPSC. We also provide future perspectives on exploiting the potential of hiPSC to compliment existing studies and gain new insights into the mechanisms underlying cardiac disease.

BACKGROUND

Leptin may play a role in mediating obesity-related hypertension. However, its effects on the vasculature and blood pressure (BP) remain poorly defined in humans.

METHODS

In the first study, we performed a short-term, placebo-controlled, randomized, double-blind, cross-over experiment investigating the actions of recombinant human leptin (r-metHuLeptin) in 15 nonobese adults. To compliment the acute study, we retrospectively analyzed available BP results from a previously performed 85-day, placebo-controlled, randomized, double-blind, parallel weight-loss study using r-metHuLeptin in 284 obese adults.

RESULTS

In the acute study, conduit artery endothelial function determined by brachial flow-mediated dilatation (FMD) increased 2 hours following 0.2 mg . Kg(1) subcutaneously (SC) of r-metHuLeptin versus placebo (+3.3% versus -2.8%, P = .02). BP remained unchanged 4 hours after injections. In the retrospective analysis of the weight loss study data, 10 mg every day before noon (QAM), 10 mg every day after noon (QPM), or 10 mg twice a day (BID) SC of r-metHuLeptin was found to not alter the degree of weight loss (-3.2 +/- 3.7 versus -2.9 +/- 3.2 Kg, P = .54), change in systolic (-1.6 + 12.9 versus -2.0 +/- 13.9 mmHg, P = .85) and diastolic BP (-0.2 +/- 8.7 versus -1.5 +/- 8.6, P = .30), as well as heart rate (-1.4 +/- 10.7 versus -1.4 +/- 10.4 beats/min, P = .98) compared to placebo.

CONCLUSIONS

In our acute study, marked hyperleptinemia rapidly enhanced endothelial function and did not alter BP. The available data from a longer-term study in healthy obese adults did not demonstrate a significant effect of hyperleptinemia upon BP. These combined findings do not support a direct role for leptin in linking obesity to hypertension, however more studies are required to corroborate these observations.

A cross-sectional study was conducted to investigate the seroprevalence of brucellosis and identify risk factors in exotic and cross bred cattle in Ethiopia. A total of 2334 cattle from 273 farms were tested serially for Brucella antibodies using the Rose Bengal Plate Test (RBPT) and the Compliment Fixation Test (CFT). The overall animal level seroprevalence was 1.9% (95% CI: 1.2, 2.6), with urban and peri-urban dairy 2.4% (95% CI: 1.4, 3.4), commercial 1.5% (95% CI: 0.5, 2.5) and breeding farms 1.5% (95% CI: 0.2, 3.2). The overall farm level prevalence was 10.6% (95% CI: 6.9, 14.3), with 8.6% (95% CI: 4.8, 12.4) in urban and peri-urban dairy followed by 16.9% (95% CI: 7.3, 26.6) in commercial and 20.0% (95% CI: 0.0, 59.4) in breeding farms. At individual animal level, purchased cows and adult age groups were observed to associate with Brucella seropositivity while presence of small ruminants on the farm was the only factor associated with increased risk of herd level Brucella infection. The lack of association between reproductive disorders and Brucella seroprevalence suggest that other causes largely outweigh as causes of the aforesaid disorder in studied production systems and demands an investigation. Finally, the need for isolation and characterization of circulating Brucella spp. and institution of regulatory measures to reinforce farm biosecurity was suggested.

Two mentally retarded boys with autism and one mentally retarded girl with Down syndrome were taught to initiate and play a ball game with an adult confederate. The program targeted both nonverbal responses related to the actual execution of the ball game as well as verbal responses for play initiation and providing compliments for the confederate's behavior. Training sessions provided ample practice in all aspects of the game from initiation to termination through use of brief play cycles. Instruction was provided using a combination of physical and verbal prompts as well as reinforcement and time-out. All three children learned the game and by the study's completion executed multiple play cycles each session. The implications of combining play and social skills training in programming for developmentally handicapped children are discussed.

As novel and drug-resistant bacterial strains continue to present an emerging health threat, the development of new antibacterial agents is critical. This includes making improvements to existing antibacterial scaffolds as well as identifying novel ones. The aim of this study is to apply a Bayesian classification QSAR approach to rapidly screen chemical libraries for compounds predicted to have antibacterial activity. Toward this end we assembled a data set of 317 known antibacterial compounds as well as a second data set of diverse, well-validated, non-antibacterial compounds from 215 PubChem Bioassays against various bacterial species. We constructed a Bayesian classification model using structural fingerprints and physicochemical property descriptors and achieved an accuracy of 84% and precision of 86% on an independent test set in identifying antibacterial compounds. To demonstrate the practical applicability of the model in virtual screening, we screened an independent data set of ~200k compounds. The results show that the model can screen top hits of PubChem Bioassay actives with accuracy up to ~76%, representing a 1.5-2-fold enrichment. The top screened hits represented a mixture of both known antibacterial scaffolds as well as novel scaffolds. Our study suggests that a well-validated Bayesian classification QSAR approach could compliment other screening approaches in identifying novel and promising hits. The data sets used in constructing and validating this model have been made publicly available.

We report significantly decreased white matter protein levels in the nucleus accumbens in an adult mouse model of chronic cocaine abuse. Previous studies from human cocaine abuse patients show disruption of white matter and myelin loss, thus supporting our observations. Understanding the neuropathological mechanisms for white matter disruption in cocaine abuse patients is complicated by polydrug use and other comorbid factors, hindering the development of effective therapeutic strategies to ameliorate damage or compliment rehabilitation programs. In this context, our data further demonstrate that cocaine-induced loss of white matter proteins is absent in mice treated with the β-lactam antibiotic, ceftriaxone, during cocaine withdrawal. Other studies report that ceftriaxone, a glutamate transporter subtype-1 activator, is neuroprotective in murine models of multiple sclerosis, thereby demonstrating potential therapeutic properties for diseases with white matter loss. Cocaine-induced white matter abnormalities likely contribute to the cognitive, motor, and psychological deficits commonly afflicting cocaine abusers, yet the underlying mechanisms responsible for these changes remain unknown. Our observations describe an adult animal model for the study of cocaine-induced myelin loss for the first time, and highlight a potential pharmacological intervention to ameliorate cocaine-induced white matter loss.

Increasing evidence indicates that an important consequence of protein posttranslational modification (PTM) is the creation of a high affinity binding site for the selective interaction with a PTM-specific binding protein (BP). This PTM-mediated interaction is typically required for downstream signaling propagation and corresponding biological responses. Because the vast majority of mammalian proteins contain PTMs, there is an immediate need to discover and characterize previously undescribed PTMBPs. To this end, we developed and validated an innovative in vivo approach called mammalian tethered catalysis (MTeC). By using methylated histones and methyl-specific histone binding proteins as the proof-of-principle, we determined that the new MTeC approach can compliment existing in vitro binding methods, and can also provide unique in vivo insights into PTM-dependent interactions. For example, we confirmed previous in vitro findings that endogenous HP1 preferentially binds H3K9me3. However, in contrast to recent in vitro observations, MTeC revealed that the tandem tudor domain-containing proteins, JMJD2A and 53BP1, display no preferential H4K20 methyl-selectivity in vivo. Last, by using MTeC in an unbiased manner to identify H3K9 methyl-specific PTMBPs, we determined that endogenous G9a binds methylated H3K9 in vivo. Further use of MTeC to characterize this interaction revealed that G9a selectively binds H3K9me1 in vivo, but not H3K9me2, contrary to recent in vitro findings. Although this study focused solely on methylated histones, we demonstrate how the innovative MTeC approach could be used to identify and characterize any PTMBP that binds any PTM on any protein in vivo.

Cell based models of coagulation (CBM) have provided mechanistic insight into numerous hematological issues for nearly two decades. This review discusses another coagulation model system--the clot lifespan model (CLSM)--that has been designed to compliment the CBM-based approach to elucidating the mechanisms responsible for a variety of hemostatic disorders/phenomena. The CLSM is a thrombelastograph-based approach that utilizes a standardized clotting stimulus (e.g., celite, tissue factor) and a fibrinolytic stimulus (e.g., tissue type plasminogen activator) to assess clot growth and disintegration via changes in clot resistance. The CLSM utilizes parametric, elastic modulus-based parameters to document these phenomena. The CLSM has recently been employed to discern the effects of protamine and hydroxyethyl starch on key fibrinolytic-antifibrinolytic protein interactions, as well as demonstrating differences in fibrinolytic kinetics dependent on whether contact pathway proteins or tissue factor is used to initiate coagulation. The CLSM is presently being utilized to investigate the effects of ventricular assist device placement on fibrinolysis, and it is anticipated that this model system will be employed in both basic science and clinical investigations in the future.

In closed-loop systems, sensor feedback delays may have disastrous implications for performance and stability. Flies have evolved multiple specializations to reduce this latency, but the fastest feedback during flight involves a delay that is still significant on the timescale of body dynamics. We explored the effect of sensor delay on flight stability and performance for yaw turns using a dynamically scaled robotic model of the fruitfly, Drosophila. The robot was equipped with a real-time feedback system that performed active turns in response to measured torque about the functional yaw axis. We performed system response experiments for a proportional controller in yaw velocity for a range of feedback delays, similar in dimensionless timescale to those experienced by a fly. The results show a fundamental trade-off between sensor delay and permissible feedback gain, and suggest that fast mechanosensory feedback in flies, and most probably in other insects, provide a source of active damping which compliments that contributed by passive effects. Presented in the context of these findings, a control architecture whereby a haltere-mediated inner-loop proportional controller provides damping for slower visually mediated feedback is consistent with tethered-flight measurements, free-flight observations and engineering design principles.

BACKGROUND

Gene expression microarray and other multiplex data hold promise for addressing the challenges of cellular complexity, refined diagnoses and the discovery of well-targeted treatments. A new approach to the construction and quantification of transcriptional regulatory networks (TRNs) is presented that integrates gene expression microarray data and cell modeling through information theory. Given a partial TRN and time series data, a probability density is constructed that is a functional of the time course of transcription factor (TF) thermodynamic activities at the site of gene control, and is a function of mRNA degradation and transcription rate coefficients, and equilibrium constants for TF/gene binding.

RESULTS

Our approach yields more physicochemical information that compliments the results of network structure delineation methods, and thereby can serve as an element of a comprehensive TRN discovery/quantification system. The most probable TF time courses and values of the aforementioned parameters are obtained by maximizing the probability obtained through entropy maximization. Observed time delays between mRNA expression and activity are accounted for implicitly since the time course of the activity of a TF is coupled by probability functional maximization, and is not assumed to be proportional to expression level of the mRNA type that translates into the TF. This allows one to investigate post-translational and TF activation mechanisms of gene regulation. Accuracy and robustness of the method are evaluated. A kinetic formulation is used to facilitate the analysis of phenomena with a strongly dynamical character while a physically-motivated regularization of the TF time course is found to overcome difficulties due to omnipresent noise and data sparsity that plague other methods of gene expression data analysis. An application to Escherichia coli is presented.

CONCLUSIONS

Multiplex time series data can be used for the construction of the network of cellular processes and the calibration of the associated physicochemical parameters. We have demonstrated these concepts in the context of gene regulation understood through the analysis of gene expression microarray time series data. Casting the approach in a probabilistic framework has allowed us to address the uncertainties in gene expression microarray data. Our approach was found to be robust to error in the gene expression microarray data and mistakes in a proposed TRN.

BACKGROUND

Most neonatal deaths in developing countries are caused by infections, birth asphyxia and prematurity. Even though most of these deaths occur at home, newborns admitted to hospital neonatal units have a high risk of contracting fatal multi-drug resistant infections.

OBJECTIVE

To compare the type of bacteria and the pattern of antimicrobial susceptibility of organisms causing neonatal infections in 2001/02 with 1991/92 in the same neonatal unit.

METHODS

We reviewed the hospital records of newborns admitted to the neonatal unit in 2001/02 that had positive blood cultures and compared the findings with similar work done 1991/92.

METHODS

Neonatal Unit, Korle Bu Teaching Hospital, Ghana.

RESULTS

Gram negative organisms (predominantly Enterobacter, Klebsiella and Acinetobacter) remained the predominant cause of neonatal infection. There was a reduction in the proportion of gram negative bacteraemia [70.9% in 1991/92 vs. 54.2% in 2001/02 (p<0.001)] due to the increased prevalence of coagulase negative staphylococcus (31.9% in 2001/02 vs. 0% in 1991/92) as a cause of neonatal bacteraemia ten years later. In 1991/92 as 2001/02 all bacterial isolates showed less than 40% susceptibility to ampicillin. The susceptibility of Klebsiella and Enterobacter to commonly used aminoglycosides and cephalosporins had decreased from over 80% in 1991/92 to less than 35% in 2001/02.

CONCLUSIONS

Bacterial causes of neonatal infections change over time and antimicrobial resistance is a major cause for concern in neonatal units in resource-poor hospitals. Improving infection control practices and instituting systems to monitor antimicrobial use and resistance will compliment community efforts to reduce neonatal mortality.

There is a growing awareness that if we are to achieve the ambitious goal of malaria elimination, we must compliment indoor-based vector control interventions (such as bednets and indoor spraying) with outdoor-based interventions such as larval source management (LSM). The effectiveness of LSM is limited by our capacity to identify and map mosquito aquatic habitats. This study provides a proof of concept for the use of a low-cost (< $1000) drone (DJI Phantom) for mapping water bodies in seven sites across Zanzibar including natural water bodies, irrigated and non-irrigated rice paddies, peri-urban and urban locations.

With flying times of less than 30 min for each site, high-resolution (7 cm) georeferenced images were successfully generated for each of the seven sites, covering areas up to 30 ha. Water bodies were readily identifiable in the imagery, as well as ancillary information for planning LSM activities (access routes to water bodies by road and foot) and public health management (e.g. identification of drinking water sources, mapping individual households and the nature of their construction).

The drone-based surveys carried out in this study provide a low-cost and flexible solution to mapping water bodies for operational dissemination of LSM initiatives in mosquito vector-borne disease elimination campaigns. Generated orthomosaics can also be used to provide vital information for other public health planning activities.

Facial disfigurement can be a consequence of treatment for oral or oropharyngeal cancer. Patients' concerns about appearance and the impact this has on quality of life are very important, but are often not recognised in a busy outpatient clinic. We aimed to assess concerns about appearance using the University of Washington Quality of Life questionnaire version 4 (UW-QoL) and the Patient Concerns Inventory (PCI), a self-administered questionnaire that allows patients to choose what they would like to discuss in their consultation. Prospective data were collected from 204 patients who attended routine follow-up clinics from August 2007 to mid-July 2009. Fifty-seven percent were male, 68% had cancer of the oral cavity, 78% had clinical T1-T2 tumours, 19% had node positive tumours, 44% had had radiotherapy since diagnosis, and 48% had had free-flap reconstructive surgery. They all completed the questionnaires using touch-screen computer technology at 454 clinic appointments. Appearance was raised on the inventory at 9% (42/454) of clinics, and at 10% (47/454) it was indicated as a serious problem on the UW-QoL questionnaire. Concerns about appearance were raised on the inventory or were shown to be a serious problem on the UW-QoL in 14% (64/454) of patients. The main factors associated with those who reported concerns about appearance were age (younger patients), sex (female), T stage (III and IV), and site (oropharynx). Patients who choose concerns about appearance for discussion on the UW-QoL questionnaire and not on the PCI risk being missed if only the PCI is completed. Both tools compliment the screening of patients who have problems with facial disfigurement; failure to identify them can have serious clinical and psychosocial implications.

We have earlier reported pluripotent, very small embryonic-like stem cells (VSELs) and slightly bigger endometrial stem cells (EnSCs) in adult mouse uterus and their regulation by gonadotropin and steroid hormones. VSELs can differentiate into cells of all three lineages in vitro; however, they neither expand readily in vitro nor compliment a developing embryo. In the present study, a robust protocol is described to enrich uterine stem/progenitor cells along with their characterization and variation across estrus cycle. After enzymatic digestion of adult mouse uterus, single-cell suspension obtained was spun at 1000 rpm (250 g) to pellet majority of cells. Stem cells remain buoyant at this speed and were pelleted by spinning supernatant at 3000 rpm (1000 g). Spherical, darkly stained VSELs (2-6 μm) with high nucleo-cytoplasmic ratio and EnSCs (> 6 μm) expressed OCT-4, NANOG, SSEA-1, SCA-1, and c-KIT. OCT-4-positive cells co-expressed SSEA-1, ERα, ERβ, PR, and FSHR. Transcripts specific for pluripotent state (Oct-4, Oct-4a, Sox-2, Nanog), primordial germ cells (Stella, Fragilis), and receptors for pituitary and steroid hormones (ERα, ERβ, PR, FSHR 1 and 3) were studied by RT-PCR in 3000 rpm pellet. Cell pellet collected at 3000 rpm showed 10-fold enrichment of VSELs (2-6 μm, viable cells with surface phenotype of LIN-CD45-SCA-1+) by flow cytometry and upregulation of pluripotent transcripts by qRT-PCR compared with 1000 rpm pellet. VSELs were maximal during estrus and metestrus phases of estrus cycle. To conclude, VSELs/EnSCs can be enriched from adult uterus using the strategy described here, vary in numbers across estrus cycle, and are vulnerable to endocrine disruption as they express steroid receptors.

Keywords: EnSCs; Endometrium; Epithelial cells; Myometrium; Pluripotent; Stem cells; Uterus; VSELs.

OBJECTIVE

Detection of faecal gluten immunogenic peptides (GIP) is a biomarker of recent gluten consumption. GIP levels can be used to monitor gluten intake and compliment clinical methods to evaluate compliance to gluten-free diet (GFD). In the present study, recent gluten intake was measured by GIP in children with coeliac disease (CD) and compared to routine clinical measures to evaluate GFD compliance.

METHODS

GIP was measured in 90 samples from 63 CD children (44 previously and 19 newly diagnosed with follow-up samples at 6 and 12 months on GFD). Compliance to GFD was evaluated based on clinical assessment, tissue transglutaminase (tTG) levels, and Biagi score.

RESULTS

GIP was detectable in 16% of patients with previous CD diagnosis on GFD. Body mass index z score (P = 0.774), height z score (P = 0.723), haemoglobin concentration (P = 0.233), age (P = 0.448), sex (P = 0.734), or disease duration (P = 0.488) did not differ between those with detectable and nondetectable GIP. In newly diagnosed patients, on gluten-containing diet, GIP was detectable in 95% of them. Following GFD initiation, GIP decreased (P < 0.001); 17% and 27% had detectable levels at 6 and 12 months, respectively. Compared to GIP, the Biagi score, tTG, and clinical assessment presented sensitivity of 17%, 42%, and 17%, respectively. Likewise, GIP was detectable in 16%, 16%, and 14% of patients evaluated as GFD compliant according to the Biagi score, tTG, and clinical assessment, respectively. A combination of methods did not improve identification of patients who were noncompliant.

CONCLUSIONS

Inclusion of faecal GIP measurements is likely to improve identification of GFD recent noncompliance in CD management and could be incorporated into current follow-up strategies.

Sumoylation is essential for progression through mitosis, but the specific protein targets and functions remain poorly understood. In this study, we used chromosome spreads to more precisely define the localization of SUMO-2/3 (small ubiquitin-related modifier) to the inner centromere and protein scaffold of mitotic chromosomes. We also developed methods to immunopurify proteins modified by endogenous, untagged SUMO-2/3 from mitotic chromosomes. Using these methods, we identified 149 chromosome-associated SUMO-2/3 substrates by nLC-ESI-MS/MS. Approximately one-third of the identified proteins have reported functions in mitosis. Consistent with SUMO-2/3 immunolocalization, we identified known centromere- and kinetochore-associated proteins, as well as chromosome scaffold associated proteins. Notably, >30 proteins involved in chromatin modification or remodeling were identified. Our results provide insights into the roles of sumoylation as a regulator of chromatin structure and other diverse processes in mitosis. Furthermore, our purification and fractionation methodologies represent an important compliment to existing approaches to identify sumoylated proteins using exogenously expressed and tagged SUMOs.

We previously showed that otx2 regulates Xenopus cement gland formation in the ectoderm. Here, we show that otx2 is sufficient to direct anterior neural gene expression, and that its activity is required for cement gland and anterior neural determination. otx2 activity at midgastrula activates anterior and prevents expression of posterior and ventral gene expression in whole embryos and ectodermal explants. These data suggest that part of the mechanism by which otx2 promotes anterior determination involves repression of posterior and ventral fates. A dominant negative otx2-engrailed repressor fusion protein (otx2-En) ablates endogenous cement gland formation, and inhibits expression of the mid/hindbrain boundary marker engrailed-2. Ectoderm expressing otx2-En is not able to respond to signals from the mesoderm to form cement gland, and is impaired in its ability to form anterior neural tissue. These results compliment analyses in otx2 mutant mice, indicating a role for otx2 in the ectoderm during anterior neural patterning.

Muscle density is a risk factor for fractures in older adults; however, its association with falls is not well described. After adjusting for biologically relevant confounding factors, a unit decrease in muscle density was associated with a 17 % increase in odds of reporting a fall, independent of functional mobility.

Falls are the leading cause of injury, disability, and fractures in older adults. Low muscle density (i.e., caused by muscle adiposity) and functional mobility have been identified as risk factors for incident disability and fractures in older adults; however, it is not known if these are also independently associated with falls. The purpose of this study was to explore the associations of muscle density and functional mobility with fall status.

Cross-sectional observational study of 183 men and women aged 60-98 years. Descriptive data, including a 12-month fall recall, Timed Up and Go (TUG) test performance, lower leg muscle area, and density. Odds ratio (OR) of being a faller were calculated, adjusted for age, sex, body mass index, general health status, diabetes, and comorbidities.

Every mg/cm(3) increase in muscle density (mean 70.2, SD 2.6 mg/cm(3)) independently reduced the odds of being a faller by 19 % (OR 0.81 [95 % CI 0.67 to 0.97]), and every 1 s longer TUG test time (mean 9.8, SD 2.6 s) independently increased the odds by 17 % (OR 1.17 [95 % CI 1.01 to 1.37]). When both muscle density and TUG test time were included in the same model, only age (OR 0.93 [95 % CI 0.87 to 0.99]) and muscle density (OR 0.83 [95 % CI 0.69 to 0.99]) were independently associated with fall status.

Muscle density was associated with fall status, independent of functional mobility. Muscle density may compliment functional mobility tests as a biometric outcome for assessing fall risk in well-functioning older adults.

OBJECTIVE

Recent studies have provided a better understanding of the molecular mechanisms responsible for hemolytic uremic syndromes. In this review, we summarize biochemical and genetic data that may lead to new clinical approaches.

RESULTS

The structures and modes of action of Shiga toxins have been deciphered. Patients with non-Shiga-like toxin hemolytic uremic syndrome have been found to carry mutations in three genes that encode for regulators of the complement system (factor H, membrane cofactor protein, and factor I).

CONCLUSIONS

Shiga-like toxin-1 and Shiga-like toxin-2 regulate genes that encode for chemokines, cytokines, cell adhesion molecules, and transcription factors involved in immune response and apoptosis. Mutations in factor H, membrane cofactor protein and factor I have recently been identified. Reduced expression of compliment regulators might prevent restriction of complement deposition on glomerular endothelial cells, leading to microvascular cell damage and tissue injury. Shiga-like toxin hemolytic uremic syndrome in children has a favorable prognosis in 90% of cases; kidney transplantation shows a good graft survival rate (80%) in children who progress to end stage renal disease. As for non-Shiga-like toxin hemolytic uremic syndrome, treatment with plasma infusion or exchange has been used with controversial effects. Kidney transplantation is not recommended in those patients with mutations in factor H and factor I; however, a kidney transplant corrects membrane cofactor protein dysfunction. These findings vividly underscore the clinical heterogeneity of outcomes depending upon the nature of the underlying cause of the disease.

This paper presents Respondent-Driven Sampling (RDS) as a viable method of sampling and analyzing social networks with survey data. RDS is a network based sampling and analysis method that provides a middle ground compliment to ego-centric and saturated methods of social network analysis. The method provides survey data, similar to ego-centric approaches, on individuals who are connected by behaviorally documented ties, allowing for macro-level analysis of network structure, similar to that supported by saturated approaches. Using racial interaction of university undergraduates as an empirical example, the paper examines whether and to what extent racial diversity at the institutional level is reflected as racial integration at the interpersonal level by testing hypotheses regarding the quantity and quality of cross-race friendships. The primary goal of this article, however, is to introduce RDS to the network community and to stimulate further research toward the goal of expanding the analytical capacity of RDS. Advantages, limitations, and areas for future research to network analysis using RDS are discussed.

The lateral organization of lipid components within membranes is usually investigated with fluorescence microscopy, which, though highly sensitive, introduces bulky fluorophores that might alter the behavior of the components they label. Secondary ion mass spectroscopy performed with a NanoSIMS 50 instrument also provides high lateral resolution and sensitivity, and many species can be observed in parallel without the use of bulky labels. A tightly focused beam (approximately 100 nm) of Cs ions is scanned across a sample, and up to five of the resulting small negative secondary ions can be simultaneously analyzed by a high-resolution mass spectrometer. Thin layers of (15)N- and (19)F-labeled proteins were microcontact-printed on an oxidized silicon substrate and imaged using the NanoSIMS 50, demonstrating the sensitivity and selectivity of this approach. Supported lipid bilayers were assembled on an oxidized silicon substrate, then flash-frozen and freeze-dried to preserve their lateral organization. Lipid bilayers were analyzed with the NanoSIMS 50, where the identity of each specific lipid was determined through detection of its unique secondary ions, including (12)C(1)H(-), (12)C(2)H(-), (13)C(-), (12)C(14)N(-), and (12)C(15)N(-). Steps toward obtaining quantitative composition analysis of lipid membranes that varied spatially in isotopic composition are presented. This approach has the potential to provide a composition-specific analysis of membrane organization that compliments other imaging modalities.

An accurate diagnosis of aeroallergen sensitization is pivotal to clinical practice and research. Given the recent technological advances in analyzing serum allergen-specific IgE, the question of which testing method, skin or serum testing, is superior in diagnosing allergic sensitization must be readdressed, as well as their value in predicting clinical disease. This review article provides a detailed summary of recent studies addressing these questions. Conclusively, most studies show substantial discordance between serum-specific IgE and skin testing results, suggesting that the two testing methods compliment each other and cannot be used interchangeably. On average, using only one testing method may misdiagnose every fourth allergically sensitized patient as non-sensitized. In addition, depending on the allergen tested, skin prick testing and serum-specific IgE testing appear to be the methods of choice in predicting outcomes of experimental allergen challenge, while intradermal testing is less contributory.

OBJECTIVE

COPD is a condition with systemic effects of which peripheral muscle dysfunction is a prominent contributor to exercise limitation, health related quality of life (HRQoL) impairment, and is an independent predictor of morbidity and mortality. Pulmonary rehabilitation (PR) is a successful strategy to improve exercise tolerance and HRQoL through the improvement of muscle function in patients with stable COPD or early after severe exacerbations of COPD (SECOPD). However, muscle function further deteriorates during SECOPD before early PR programmes commence. We aimed to investigate the feasibility and efficacy of quadriceps neuromuscular electrical stimulation (NMES) applied during a SECOPD to prevent muscle function deterioration.

METHODS

We have conducted a pilot study in eleven COPD patients (FEV(1) 41.3 ± 5.6 % pred) admitted to hospital with a SECOPD. We randomly allocated one leg to receive NMES (once a day for 14 days) with the other leg as a control (non-stimulated leg). We measured the change in quadriceps maximal voluntary contraction (ΔQMVC) as the main outcome.

RESULTS

Mean quadriceps muscle strength decreased in control legs (ΔQMVC -2.9 ± 5.3 N, p = ns) but increased in the stimulated legs (ΔQMVC 19.2 ± 6.1 N, p < 0.01). The difference in ΔQMVC between groups was statistically significant (p < 0.05). The effect of NMES was directly related to the stimulation intensity (∑mA) applied throughout the 14 sessions (r = 0.76, p < 0.01). All patients tolerated NMES without any side effects.

CONCLUSIONS

NMES is a feasible and effective treatment to prevent quadriceps muscle strength derangement during severe exacerbations of COPD and may be used to compliment early post-exacerbation pulmonary rehabilitation.

There is no entirely satisfactory way to monitor nerve root integrity during spinal surgery. In particular, standard free-running electromyography carries a high false-positive rate and some false-negative rate of injury. Stimulated electromyography to direct root stimulation can only be done intermittently, and roots are often inaccessible. This article reviews to what extent muscle motor evoked potential (MEP) monitoring might help. It presents background considerations, describes MEP methodology, and summarizes relevant experimental animal and clinical studies. Based on current evidence, root compromise can cause myotomal MEP deterioration that in some cases may be reversible. However, because of radicular overlap, limited sampling, confounding factors, and response variability, the effects range from no appreciable change to variable degrees of amplitude reduction to disappearance and some false-positive and false-negative results should be expected. For root monitoring, multichannel MEP recordings should span adjacent myotomes and avoid mixed myotome derivations. Only amplitude reduction warning criteria have been studied, but no percentage cutoff consensus has emerged, and this approach is troubled by response variability. There is some evidence that MEPs might reduce false electromyographic results. In conclusion, muscle MEPs could compliment electromyography but seem unlikely to completely solve the problem of nerve root monitoring.