Real-Time Cardiac Beat Detection and Heart Rate Monitoring from Combined Seismocardiography and Gyrocardiography.

Cardiography is an indispensable element of health care. However, the accessibility of at-home cardiac monitoring is limited by device complexity, accuracy, and cost. We have developed a real-time algorithm for heart rate monitoring and beat detection implemented in a custom-built, affordable system. These measurements were processed from seismocardiography (SCG) and gyrocardiography (GCG) signals recorded at the sternum, with concurrent electrocardiography (ECG) used as a reference. Our system demonstrated the feasibility of non-invasive electro-mechanical cardiac monitoring on supine, stationary subjects at a cost of $100, and with the SCG-GCG and ECG algorithms decoupled as standalone measurements. Testing was performed on 25 subjects in the supine position when relaxed, and when recovering from physical exercise, to record 23,984 cardiac cycles at heart rates in the range of 36-140 bpm. The correlation between the two measurements had r2 coefficients of 0.9783 and 0.9982 for normal (averaged) and instantaneous (beat identification) heart rates, respectively. At a sampling frequency of 250 Hz, the average computational time required was 0.088 s per measurement cycle, indicating the maximum refresh rate. A combined SCG and GCG measurement was found to improve accuracy due to fundamentally different noise rejection criteria in the mutually orthogonal signals. The speed, accuracy, and simplicity of our system validated its potential as a real-time, non-invasive, and affordable solution for outpatient cardiac monitoring in situations with negligible motion artifact.

Double-Stranded Biotinylated Donor Enhances Homology-Directed Repair in Combination with Cas9 Monoavidin in Mammalian Cells.

Homology-directed repair (HDR) induced by site specific DNA double-strand breaks with CRISPR-Cas9 is a precision gene editing approach that occurs at low frequency in comparison to indel forming non-homologous end joining (NHEJ). In order to obtain high HDR percentages in mammalian cells, we engineered a Cas9 protein fused to a monoavidin domain to bind biotinylated donor DNA. In addition, we used the cationic polymer, polyethylenimine, to deliver Cas9-donor DNA complexes into cells. Improved HDR percentages of up to 90% in three loci tested (CXCR4, EMX1, and TLR) in standard HEK293T cells were observed. Our results suggest that donor DNA biotinylation and Cas9-donor conjugation in addition to delivery influence HDR efficiency.

Real time plasmonic qPCR: how fast is ultra-fast? 30 cycles in 54 seconds.

Polymerase Chain Reaction (PCR) is a critical tool for biological research investigators but recently it also has been making a significant impact in clinical, veterinary and agricultural applications. Plasmonic PCR, which employs the very efficient heat transfer of optically irradiated metallic nanoparticles, is a simple and powerful methodology to drive PCR reactions. The scalability of next generation plasmonic PCR technology will introduce various forms of PCR applications ranging from small footprint portable point of care diagnostic devices to large footprint central laboratory multiplexing devices. In a significant advance, we have introduced a real time plasmonic PCR and explored the ability of ultra-fast cycling compatible with both label-free and fluorescence-based monitoring of amplicon production. Furthermore, plasmonic PCR has been substantially optimized to now deliver a 30 cycle PCR in 54 seconds, with a detectable product. The advances described here will have an immediate impact on the further development of the use of plasmonic PCR playing a critical role in rapid point of care diagnostics.

Prostate-specific membrane antigen-directed nanoparticle targeting for extreme nearfield ablation of prostate cancer cells.

Almost all biological therapeutic interventions cannot overcome neoplastic heterogeneity. Physical ablation therapy is immune to tumor heterogeneity, but nearby tissue damage is the limiting factor in delivering lethal doses. Multi-walled carbon nanotubes offer a number of unique properties: chemical stability, photonic properties including efficient light absorption, thermal conductivity, and extensive surface area availability for covalent chemical ligation. When combined together with a targeting moiety such as an antibody or small molecule, one can deliver highly localized temperature increases and cause extensive cellular damage. We have functionalized multi-walled carbon nanotubes by conjugating an antibody against prostate-specific membrane antigen. In our in vitro studies using prostate-specific membrane antigen-positive LNCaP prostate cancer cells, we have effectively demonstrated cell ablation of >80% with a single 30-s exposure to a 2.7-W, 532-nm laser for the first time without bulk heating. We also confirmed the specificity and selectivity of prostate-specific membrane antigen targeting by assessing prostate-specific membrane antigen-null PC3 cell lines under the same conditions (<10% cell ablation). This suggests that we can achieve an extreme nearfield cell ablation effect, thus restricting potential tissue damage when transferred to in vivo clinical applications. Developing this new platform will introduce novel approaches toward current therapeutic modalities and will usher in a new age of effective cancer treatment squarely addressing tumoral heterogeneity.

Correction: Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells.

[This corrects the article DOI: 10.1371/journal.pone.0149723.].

Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells.

BACKGROUND: The incidence of papillary thyroid carcinoma (PTC) has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid) act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches. METHODS: Thyroid Stimulating Hormone Receptor (TSHR) was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin) were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm) was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining. RESULTS: TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:α-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls. CONCLUSION: A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam radiation or chemotherapy, with fewer side effects and improved quality of life.

Design and analysis of a spectro-angular surface plasmon resonance biosensor operating in the visible spectrum.

Surface plasmon resonance (SPR) sensing is one of the most widely used methods to implement biosensing due to its sensitivity and capacity for label-free detection. Whilst most commercial SPR sensors operate in the angular regime, it has recently been shown that an increase in sensitivity and a greater robustness against noise can be achieved by measuring the reflectivity when varying both the angle and wavelength simultaneously, in a so-called spectro-angular SPR biosensor. A single value decomposition method is used to project the two-dimensional spectro-angular reflection signal onto a basis set and allow the image obtained from an unknown refractive index sample to be compared very accurately with a pre-calculated reference set. Herein we demonstrate that a previously reported system operated in the near infra-red has a lower detection limit when operating in the visible spectrum due to the improved spatial resolution and numerical precision of the image sensor. The SPR biosensor presented here has an experimental detection limit of 9.8 × 10(-7) refractive index unit. To validate the system as a biosensor, we also performed the detection of synthetic RNA from pathogenic Legionella pneumophila with the developed biosensing platform.

Coexistence of malignant struma ovarii and cervical papillary thyroid carcinoma.

CONTEXT: Struma ovarii is an uncommon monodermal teratoma in which thyroid tissue is the predominant element. Malignant transformation of struma ovarii is an even rarer occurrence. CASE PRESENTATION: We describe a 42-year-old woman who underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for a symptomatic left pelvic mass. Histology revealed malignant struma ovarii with classical papillary thyroid carcinoma expression. Ultrasonography of the cervical neck showed thyroid micronodules and a dominant 1-cm nodule in the left thyroid lobe. As the ovarian tumor was large, the patient underwent a total thyroidectomy with the intention of administering ¹³¹I therapy in an adjuvant setting. Histology of the cervical thyroid gland revealed bilateral multifocal papillary thyroid carcinoma with extrathyroidal extension and perithyroidal lymph node metastasis. METHODS: Morphological (microscopy), immunohistochemical (Hector Battifora mesothelial cell 1, cytokeratin-19, galectin-3), and molecular (BRAF V600E, RAS, RET-PTC) characteristics and clonality analysis of the cervical thyroid and ovarian tumors were explored to distinguish them as separate malignancies. RESULTS: The thyroid-type tumors from the cervical gland and ovary were discordant in terms of tissue histology and level of cytokeratin-19 expression. The clinical features and tumor profile results supported the independent existence of these two embryologically related, although topographically distinct, malignancies. CONCLUSION: Our findings provided support for synchronous, albeit distinct, primary tumors in the ovary and cervical thyroid. "Field cancerization" and early genomic instability may explain multifocality in all thyroid-type tissue. In this regard, patients with malignant struma ovarii should undergo imaging of their thyroid gland for coexisting disease and thyroidectomy recommended for suspected malignancy or in preparation for radioiodine therapy.

Demonstration of a plasmonic thermocycler for the amplification of human androgen receptor DNA.

A plasmonic heating method for the polymerase chain reaction is demonstrated by the amplification of a section of the human androgen receptor gene. The thermocycler has a simple low-cost design, demonstrates excellent temperature stability and represents the first practical demonstration of plasmonic thermocycling.

Dynamical thermal effects in InGaAsP microtubes at telecom wavelengths.

We report on the observation of a dynamical thermal effect in InGaAsP microtubes at telecom wavelengths. The microtubes are fabricated by releasing a strained semiconductor bilayer and are picked up by abruptly tapered optical fibers for subsequent coupling with adiabatically tapered optical fibers. As a result of absorption by InAs quantum dots embedded in the tube structure, these microtubes show dynamical thermal effects at wavelengths around 1525 nm and 1578 nm, while they are passive at longer wavelengths near 1634 nm. The photon absorption induced thermal effect is visualized by generating a pair of microbottles. The dynamical thermal effect can be avoided or exploited for passive or active applications by utilizing appropriate resonance wavelengths.

Analysis of surface plasmon spectro-angular reflectance spectrum: real-time measurement, resolution limits, and applications to biosensing.

A surface plasmon biosensing technique based on real-time measurement of the spectro-angular reflectance spectrum of a gold surface is presented. A significant improvement in refractive index resolution and drift compensation has been achieved for the spectro-angular technique to demonstrate a biosensing platform that is, in addition, applicable to plasmonic bandgap measurements. Instrumental improvements are detailed and constants for the model bovine serum albumin (BSA):oxacillin bioassay are presented.

Genetic signs of connectivity in Primula vulgaris (Primulaceae) in a hedgerow network landscape.

The effects of landscape configuration on the genetic connectivity of the heterostylous species Primula vulgaris Huds. (Primulaceae) were studied using AFLP markers. Isolation by distance pattern was shown by spatial autocorrelation analysis; moreover, hedgerow network distances were found to contribute less than Euclidian distances to spatial genetic structure. Pollen flow is probably the main factor shaping the spatial genetic structure rather than seed dispersal, which is limited in this myrmecochorous species. Detailed analysis on the genetic similarity between neighborhoods and differentiation rates showed that density of hedgerow networks impede gene flow. We therefore concluded that a high degree of habitat contiguity does not necessarily promote genetic connectivity.

Active and passive dispersal of an invading land snail in Mediterranean France.

1. Land snail dispersal abilities are considered poor; however, the current invasion of the French Mediterranean region by Xeropicta derbentina (Krynicki 1836), as well as the past invasions of this region by several other species, seems to contradict this view. 2. Using a multilevel approach, from individual experimentation to landscape analysis, the dispersal abilities and mechanisms allowing the passive dispersal of X. derbentina are studied. 3. The colonization of Provence occurred by stratified diffusion, where short-range active dispersal occurs side by side with long-range passive dispersal. 4. Active dispersal is not as limited as previously thought. In the field, the capture-mark-recapture method recorded a maximum distance covered of 42 m in 6 months within a radius of 38 m from the original release point. 5. Temperature and humidity, and therefore the time of year, influence the main type of dispersal. Dispersal is active during wet periods and essentially passive in dry and hot months. 6. Heat avoidance behaviour is one of the mechanisms allowing passive dispersal. 7. Passive dispersal via human activities is the main determinant of X. derbentina distribution within the landscape. In comparison to other species, X. derbentina is found more often in the vicinity of a communication route. 8. These results show that land snails can cover large distances in a lifetime. The potential for active and passive dispersal described in this paper enables X. derbentina to be a successful invasive species and explains the rapid spread and current distribution of this species.

Spatio-temporal growth dynamics of a subAlpine Pinus uncinata stand in the French Alps.

Natural forests are characterised by a high level of both spatial and temporal heterogeneity. The major processes involved in the creation and maintenance of forest heterogeneity in temperate climates are small-sized canopy disturbances. The resulting openings also modify the growth conditions for the remaining trees. The analysis of tree growth responses using dendrochronological techniques allows the reconstruction of the time sequence of the disturbances. The radial growth analysis is coupled here with both a spatial analysis and a demographic analysis of the forest structure. The age classes are temporally organised in cohorts and spatially distributed in spatial aggregates. The analysis of the most documented disturbance event allowed us to determine the size of the disturbance response patch (between 0.036 and 0.073 ha) and the duration of the disturbance (six years). We considered that this small-scale disturbance event may have been caused by the fall of a single tree and has freed the surrounding trees of its competition.

Psicosis exógenas agudas / Acute exogenous psychosis

Se describen los diferentes tipos de reacción exógena aguda descritos por Karl Bonhöffer. Entre ellas se analizan la obnubilación simple; el estado crespucular; el delirio agudo; la alucinosis; el estado epileptoide angustioso y la amencia. A los anteriores se agregan las llamadas formas de transcurso tales como el síndrome hiperestésico emocional y el síndrome de Korsakow En la revisión se describen los tipos de presentación clínica; la evolución y el tratamiento de las diversas formas de reacción exógena aguda, señalando además algunas consideraciones aportadas por Bleuler. En lo que respecta a tratamiento se señalan el aspecto etiológico (supresión de la causa desencadenante; infecciosa, metabólica, tumoral, etc) y el sintomático. Este último incluye medidas generales y empleo de agentes farmacológicos tales como benzodiazepinas (si no hay agitación) y neurolépticos (thorazine y haloperidol) cuando se trata de pacientes agitados

Tratamiento del síndrome de privación alcohólica / Treatment of the alcoholic withdrawal syndrome

En el tratamiento del síndrome de privación alcohólica es fundamental la aplicación de medidas generales tales como luz suave, ambiente silenciosos, observación continua del paciente además de restrición en la administración parenteral de medicamentos. La implementación de dichas medidas disminuye las necesidades de tranquilizantes. Las benzodiazepinas son las drogas más efectivas en el tratamiento del síndrome de privación alcohólica. La dosis se deben ir diminuyendo durante la evolución del síndrome con el fin de evitar las sobredosis. El uso de tiamina es primordial para evitar la aparición de la enfermedad de Wernicke-Korsakoff. La pesquisa y tratamiento precoz de las complicaciones tienen gran importancia en la evolución y pronóstico del síndrome de privación alcohólica