Rotatable microfluidic device for simultaneous study of bilateral chemosensory neurons in Caenorhabditis elegans

The nematode Caenorhabditis elegans is a leading model system in genetics, development and neurobiology; its transparent body and small size make it particularly suitable for fluorescent imaging of cells and neurons within microfluidic setups. Simultaneously recording activity in bilaterally symmetric cells has proved difficult in C. elegans because the worm enters the chip and is then immobilised when it is lying on one side of the body. We developed a side-view rotatable microfluidic device that allows us to image a pair of bilateral neurons in a single focal plane of an epi-fluorescence microscope. We demonstrated the utility of the device by recording the responses of immobilised worms to controlled stimuli, focusing on the responses of two classes of head sensory neurons to changes in NaCl concentration. The results indicate that responses of ASE left and right and ASH left and right sensory neurons are stochastic. Simultaneous recordings of ASH left and right neurons tend to synchronise, pointing to a role of gap junctional connectivity. The anatomy of the C. elegans nerve ring makes this microfluidic approach ideally suited for the study of spatially extended pairs of neurons or larger neuronal circuits that lie within a limited depth of field

A population-based study of 92 clinically recognised risk factors for heart failure: co-occurrence, prognosis and preventive potential

BACKGROUND: Primary prevention strategies for heart failure(HF) have had limited success, possibly due to a wide range of underlying risk factors(RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. OBJECTIVE: To estimate evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF. METHODS: We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170 885 individuals aged ≥30 years with incident HF from 1997-2017, using linked primary and secondary care UK electronic health records(EHR) and rule-based phenotypes(ICD-10, Read Version 2, OPCS-4 procedure and medication codes) for each of 92 RFs. RESULTS: Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective RCT-based interventions for HF prevention(RCT-HF), and 6 for CVD prevention, but not HF(RCT-CVD), and the remainder had no RCT-based preventive interventions(RCT-0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5 years prior to HF diagnosis, 44.3% had ≥4 RFs. By RCT evidence, the most common RCT-HF RFs were hypertension(48.5%), stable angina(34.9%), unstable angina(16.8%), myocardial infarction(15.8%), and diabetes(15.1%); RCT-CVD RFs were smoking(46.4%) and obesity(29.9%); and RCT-0 RFs were atrial arrhythmias(17.2%), cancer(16.5%),), heavy alcohol intake(14.9%). Mortality at 1 year varied across all 91 factors(lowest: pregnancy-related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs. 15.6% had either no RF or only RCT-0 RFs. CONCLUSION: 1 in 6 individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co-occurrence and the need for trials tackling multiple RFs

Serum amyloid A primes microglia for ATP-dependent interleukin-1\u3b2 release

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves production of acute-phase proteins, including serum amyloid A (SAA). Interleukin-1\u3b2 (IL-1\u3b2), a master regulator of neuroinflammation produced by activated inflammatory cells of the myeloid lineage, in particular microglia, plays a key role in the pathogenesis of acute and chronic diseases of the peripheral nervous system and CNS. IL-1\u3b2 release is promoted by ATP acting at the purinergic P2X7 receptor (P2X7R) in cells primed with toll-like receptor (TLR) ligands

Light-Cone Quantization and Hadron Structure

In this talk, I review the use of the light-cone Fock expansion as a tractable and consistent description of relativistic many-body systems and bound states in quantum field theory and as a frame-independent representation of the physics of the QCD parton model. Nonperturbative methods for computing the spectrum and LC wavefunctions are briefly discussed. The light-cone Fock state representation of hadrons also describes quantum fluctuations containing intrinsic gluons, strangeness, and charm, and, in the case of nuclei, "hidden color". Fock state components of hadrons with small transverse size, such as those which dominate hard exclusive reactions, have small color dipole moments and thus diminished hadronic interactions; i.e., "color transparency". The use of light-cone Fock methods to compute loop amplitudes is illustrated by the example of the electron anomalous moment in QED. In other applications, such as the computation of the axial, magnetic, and quadrupole moments of light nuclei, the QCD relativistic Fock state description provides new insights which go well beyond the usual assumptions of traditional hadronic and nuclear physics.Comment: LaTex 36 pages, 3 figures. To obtain a copy, send e-mail to [email protected]

Dolor posoperatorio en craneotomía

In the postoperative period, 47% to 75% of the patients report some degree of pain. This study aimed to evaluate pain in the pre and postoperative period of patients submitted to craniotomy. This prospective research was carried out at the neurosurgery unit of a large Brazilian hospital. For a quantitative evaluation of pain, the verbal numeric 0 - 10 rating scale was used. Forty patients with a mean age of 36 years were evaluated. In the preoperative period, 34 (85%) patients indicated headache as the main cause of pain. In the postoperative period, 37 (93%) patients complained of pain while three (7%) reported absence of pain. Pain peaks were observed on the 2nd postoperative day, when 12 (32%) of the patients reported severe pain and 10 (27%) moderate pain. Absence of severe pain occurred after the 8th postoperative day. It was concluded that protocols of analgesia in craniotomy are needed, such as training nurses to better evaluate and handle pain.En el periodo postoperatorio, entre el 47% y el 75% de los pacientes relatan algún grado de dolor. Los objetivos de este trabajo fueron evaluar el dolor en el pre y postoperatorio de pacientes sometidos a craneotomía. Este estudio prospectivo fue realizado en la unidad de neurocirugía del Hospital São Paulo, Brasil. Para una evaluación cuantitativa del dolor se utilizó la escala numérica verbal graduada de 0 a 10. Fueron evaluados 40 pacientes con edad mediana de 36 años. En el preoperatorio 34 (85%) pacientes, reportaran cefalea como la principal causa del dolor. En el postoperatorio, 37 (93%) pacientes se quejaron de dolor, mientras 3 (7%) pacientes indicaron ausencia de dolor. El pico de dolor fue observado en el segundo día postoperatorio, cuando 12 (32%) pacientes reportaron dolor grave y 10 (27%) moderado. La ausencia de dolor grave ocurrió después del 8º día postoperatorio. Se concluyó que son necesarios protocolos de analgesia en craneotomía, tales como el entrenamiento de enfermeros para mejor evaluar y manejar el dolor.No pós-operatório, 47 a 75% dos pacientes relatam algum grau de dor. O objetivo deste trabalho foi avaliar a dor no pré e pós-operatório de pacientes submetidos a craniotomia. Estudo prospectivo, realizado na unidade de neurocirurgia do Hospital São Paulo. Para avaliação quantitativa de dor, foi utilizada a escala numérica verbal, graduada de 0 a 10. Foram avaliados 40 pacientes, com idade mediana de 36 anos. No pré-operatório, 34 (85%) pacientes relataram cefaléia como a principal causa de dor. No pós-operatório, 37 (93%) pacientes queixaram-se de dor e 3 (7%) pacientes referiram ausência de dor. O pico da dor foi observado no 2º pós-operatório, quando 16 (40%) dos pacientes referiram dor intensa e 11 (28%) queixaram-se de dor moderada. Ausência de dor intensa ocorreu após 6º pós-operatório. Concluí-se que há necessidade de protocolos de analgesia em craniotomia, como treinamento para os enfermeiros para melhor avaliação e manejo da dor.Hospital Israelita Albert EinsteinUniversidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

Inclusive double-quarkonium production at the Large Hadron Collider

Based on the nonrelativistic QCD (NRQCD) factorization formalism, we investigate inclusive productions of two spin-triplet S-wave quarkonia pp->2J/psi+X, 2Upsilon+X, and J/psi+Upsilon+X at the CERN Large Hadron Collider. The total production rates integrated over the rapidity (y) and transverse-momentum (p_T) ranges |y|<2.4 and p_T<50 GGeV are predicted to be sigma[pp->2J/psi+X] = 22 (35) nb, sigma[pp->2Upsilon+X] = 24 (49) pb, and sigma[pp->J/psi+Upsilon+X] = 7 (13) pb at the center-of-momentum energy sqrt{s} = 7 (14) TeV. In order to provide predictions that can be useful in both small- and large-p_T regions, we do not employ the fragmentation approximation and we include the spin-triplet S-wave color-singlet and color-octet channels for each quarkonium final state at leading order in the strong coupling. The p_T distributions of pp->2J/psi+X and 2Upsilon+X in the low-p_T region are dominated by the color-singlet contributions. At leading order in the strong coupling, the color-singlet channel is absent for pp->J/psi+Upsilon+X. Therefore, the process pp->J/psi+Upsilon+X may provide a useful probe to the color-octet mechanism of NRQCD.Comment: 26 pages, 7 figures, 3 tables, version published in JHE

Expression and Differential Responsiveness of Central Nervous System Glial Cell Populations to the Acute Phase Protein Serum Amyloid A

Acute-phase response is a systemic reaction to environmental/inflammatory insults and involves hepatic production of acute-phase proteins, including serum amyloid A (SAA). Extrahepatically, SAA immunoreactivity is found in axonal myelin sheaths of cortex in Alzheimer's disease and multiple sclerosis (MS), although its cellular origin is unclear. We examined the responses of cultured rat cortical astrocytes, microglia and oligodendrocyte precursor cells (OPCs) to master pro-inflammatory cytokine tumour necrosis factor (TNF)-\u3b1 and lipopolysaccaride (LPS). TNF-\u3b1 time-dependently increased Saa1 (but not Saa3) mRNA expression in purified microglia, enriched astrocytes, and OPCs (as did LPS for microglia and astrocytes). Astrocytes depleted of microglia were markedly less responsive to TNF-\u3b1 and LPS, even after re-addition of microglia. Microglia and enriched astrocytes showed complementary Saa1 expression profiles following TNF-\u3b1 or LPS challenge, being higher in microglia with TNF-\u3b1 and higher in astrocytes with LPS. Recombinant human apo-SAA stimulated production of both inflammatory mediators and its own mRNA in microglia and enriched, but not microglia-depleted astrocytes. Co-ultramicronized palmitoylethanolamide/luteolin, an established anti-inflammatory/neuroprotective agent, reduced Saa1 expression in OPCs subjected to TNF-\u3b1 treatment. These last data, together with past findings suggest that co-ultramicronized palmitoylethanolamide/luteolin may be a novel approach in the treatment of inflammatory demyelinating disorders like MS

Peroxisome Proliferator-Activated Receptor alpha (PPAR alpha) down-regulation in cystic fibrosis lymphocytes

Background: PPARs exhibit anti-inflammatory capacities and are potential modulators of the inflammatory response. We hypothesized that their expression and/or function may be altered in cystic fibrosis (CF), a disorder characterized by an excessive host inflammatory response. Methods: PPARα, β and γ mRNA levels were measured in peripheral blood cells of CF patients and healthy subjects via RT-PCR. PPARα protein expression and subcellular localization was determined via western blot and immunofluorescence, respectively. The activity of PPARα was analyzed by gel shift assay. Results: In lymphocytes, the expression of PPARα mRNA, but not of PPARβ, was reduced (-37%; p < 0.002) in CF patients compared with healthy persons and was therefore further analyzed. A similar reduction of PPARα was observed at protein level (-26%; p < 0.05). The transcription factor was mainly expressed in the cytosol of lymphocytes, with low expression in the nucleus. Moreover, DNA binding activity of the transcription factor was 36% less in lymphocytes of patients (p < 0.01). For PPARα and PPARβ mRNA expression in monocytes and neutrophils, no significant differences were observed between CF patients and healthy persons. In all cells, PPARγ mRNA levels were below the detection limit. Conclusion: Lymphocytes are important regulators of the inflammatory response by releasing cytokines and antibodies. The diminished lymphocytic expression and activity of PPARα may therefore contribute to the inflammatory processes that are observed in CF

Negative pressure characteristics of an evaporating meniscus at nanoscale

This study aims at understanding the characteristics of negative liquid pressures at the nanoscale using molecular dynamics simulation. A nano-meniscus is formed by placing liquid argon on a platinum wall between two nano-channels filled with the same liquid. Evaporation is simulated in the meniscus by increasing the temperature of the platinum wall for two different cases. Non-evaporating films are obtained at the center of the meniscus. The liquid film in the non-evaporating and adjacent regions is found to be under high absolute negative pressures. Cavitation cannot occur in these regions as the capillary height is smaller than the critical cavitation radius. Factors which determine the critical film thickness for rupture are discussed. Thus, high negative liquid pressures can be stable at the nanoscale, and utilized to create passive pumping devices as well as significantly enhance heat transfer rates