Calcium channel modulation as a target in chronic pain control

Neuropathic pain remains poorly treated for large numbers of patients and little progress has been made in developing novel classes of analgesics. To redress this issue, ziconotide (PrialtTM ) was developed and approved as a first in class synthetic version of ω-conotoxin MVIIA, a Cav 2.2 peptide blocker. Unfortunately, the impracticalities of intrathecal delivery, low therapeutic index and severe neurological side effects associated with ziconotide has restricted its use to exceptional circumstances. Ziconotide exhibits no state or use dependent block of Cav 2.2 channels; activation state dependent blockers were hypothesised to circumvent the side effects of state independent blockers by selectively targeting high frequency firing of nociceptive neurones in chronic pain states, thus alleviating aberrant pain but not affecting normal sensory transduction. Unfortunately, numerous drugs, including state dependent calcium channel blockers, have displayed efficacy in pre-clinical models but have subsequently disappointed in clinical trials. In recent years, it has become more widely acknowledged that trans-aetiological sensory profiles exist amongst chronic pain patients, and may indicate similar underlying mechanisms and drug sensitivities. Heterogeneity amongst patients, a reliance on stimulus evoked endpoints in pre-clinical studies and a failure to utilise translatable endpoints has likely contributed to negative clinical trial results. We provide an overview of how electrophysiological and operant based assays provide insight into sensory and affective aspects of pain in animal models, and how these may relate to chronic pain patients in order to improve bench-to-bedside translation of calcium channel modulators

¿Y dónde quedó el reactivo limitante? Algunas preconcepciones sobre reactivo limitante detectadas en alumnos de licenciatura

El trabajo que se presenta forma parte de un proyecto de investigación educativa cuyo énfasis se centra en conocer algunos factores importantes que interfieren la comprensión de la reacción química. En este caso abordamos las preconcepciones, sobre el reactivo limitante, de un grupo piloto de alumnos de licenciatura de la Facultad de Química (UNAM). Se presenta el análisis de las respuestas después de aplicar un cuestionario de opción múltiple, en el que se solicitaba la justificación de la opción elegida así como de las entrevistas realizadas

Frequency-shift vs phase-shift characterization of in-liquid quartz crystal microbalance applications

The improvement of sensitivity in quartz crystal microbalance (QCM) applications has been addressed in the last decades by increasing the sensor fundamental frequency, following the increment of the frequencymass sensitivity with the square of frequency predicted by Sauerbrey. However, this sensitivity improvement has not been completely transferred in terms of resolution. The decrease of frequency stability due to the increase of the phase noise, particularly in oscillators, made impossible to reach the expected resolution. A new concept of sensor characterization at constant frequency has been recently proposed. The validation of the new concept is presented in this work. An immunosensor application for the detection of a low molecular weight contaminant, the insecticide carbaryl, has been chosen for the validation. An, in principle, improved version of a balanced-bridge oscillator is validated for its use in liquids, and applied for the frequency shift characterization of the QCM immunosensor application. The classical frequency shift characterization is compared with the new phase-shift characterization concept and system proposed. © 2011 American Institute of Physics.The authors are grateful to the Spanish Ministry of Science and Technology for the financial support to this research under contract reference AGL2009-13511, and to the company Advanced Wave Sensors S. L. (www.awsensors.com) for the help provided in the development of some parts of this work.Montagut Ferizzola, YJ.; García Narbón, JV.; Jiménez Jiménez, Y.; March Iborra, MDC.; Montoya Baides, Á.; Arnau Vives, A. (2011). Frequency-shift vs phase-shift characterization of in-liquid quartz crystal microbalance applications. Review of Scientific Instruments. 82(6):1-14. https://doi.org/10.1063/1.3598340S114826Sauerbrey, G. (1959). 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Some new concepts on factors influencing the operational frequency of liquid-immersed quartz microbalances. Sensors and Actuators A: Physical, 30(3), 197-202. doi:10.1016/0924-4247(92)80120-rWessendorf, K. O. (s. f.). The Lever oscillator for use in high resistance resonator applications. 1993 IEEE International Frequency Control Symposium. doi:10.1109/freq.1993.367466Borngraber, R., Schroder, J., Lucklum, R., & Hauptmann, P. (2002). Is an oscillator-based measurement adequate in a liquid environment? IEEE Transactions on Ultrasonics, Ferroelectrics and Frequency Control, 49(9), 1254-1259. doi:10.1109/tuffc.2002.1041542Ehahoun, H., Gabrielli, C., Keddam, M., Perrot, H., & Rousseau, P. (2002). Performances and Limits of a Parallel Oscillator for Electrochemical Quartz Crystal Microbalances. Analytical Chemistry, 74(5), 1119-1127. doi:10.1021/ac010883sMartin, S. J., Spates, J. J., Wessendorf, K. O., Schneider, T. W., & Huber, R. J. (1997). Resonator/Oscillator Response to Liquid Loading. Analytical Chemistry, 69(11), 2050-2054. doi:10.1021/ac961194xFerrari, V., Marioli, D., & Taroni, A. (2001). Improving the accuracy and operating range of quartz microbalance sensors by a purposely designed oscillator circuit. IEEE Transactions on Instrumentation and Measurement, 50(5), 1119-1122. doi:10.1109/19.963169Arnau, A., Sogorb, T., & Jiménez, Y. (2002). Circuit for continuous motional series resonant frequency and motional resistance monitoring of quartz crystal resonators by parallel capacitance compensation. Review of Scientific Instruments, 73(7), 2724-2737. doi:10.1063/1.1484254Jakoby, B., Art, G., & Bastemeijer, J. (2005). Novel analog readout electronics for microacoustic thickness shear-mode sensors. IEEE Sensors Journal, 5(5), 1106-1111. doi:10.1109/jsen.2005.844330Ferrari, M., Ferrari, V., Marioli, D., Taroni, A., Suman, M., & Dalcanale, E. (2006). In-Liquid Sensing of Chemical Compounds by QCM Sensors Coupled With High-Accuracy ACC Oscillator. IEEE Transactions on Instrumentation and Measurement, 55(3), 828-834. doi:10.1109/tim.2006.873792Ferrari, M., Ferrari, V., & Kanazawa, K. K. (2008). Dual-harmonic oscillator for quartz crystal resonator sensors. Sensors and Actuators A: Physical, 145-146, 131-138. doi:10.1016/j.sna.2007.10.087Riesch, C., & Jakoby, B. (2007). Novel Readout Electronics for Thickness Shear-Mode Liquid Sensors Compensating for Spurious Conductivity and Capacitances. IEEE Sensors Journal, 7(3), 464-469. doi:10.1109/jsen.2007.891931Arnau, A., García, J. V., Jimenez, Y., Ferrari, V., & Ferrari, M. (2008). Improved electronic interfaces forAT-cut quartz crystal microbalance sensors under variable damping and parallel capacitance conditions. Review of Scientific Instruments, 79(7), 075110. doi:10.1063/1.2960571Barnes, C. (1991). Development of quartz crystal oscillators for under-liquid sensing. Sensors and Actuators A: Physical, 29(1), 59-69. doi:10.1016/0924-4247(91)80032-kAuge, J., Hauptmann, P., Eichelbaum, F., & Rösler, S. (1994). Quartz crystal microbalance sensor in liquids. Sensors and Actuators B: Chemical, 19(1-3), 518-522. doi:10.1016/0925-4005(93)00983-6Auge, J., Hauptmann, P., Hartmann, J., Rösler, S., & Lucklum, R. (1995). New design for QCM sensors in liquids. Sensors and Actuators B: Chemical, 24(1-3), 43-48. doi:10.1016/0925-4005(95)85010-4Chagnard, C., Gilbert, P., Watkins, A. N., Beeler, T., & Paul, D. W. (1996). An electronic oscillator with automatic gain control: EQCM applications. Sensors and Actuators B: Chemical, 32(2), 129-136. doi:10.1016/0925-4005(96)80121-3Rodriguez-Pardo, L., Fariña, J., Gabrielli, C., Perrot, H., & Brendel, R. (2004). Resolution in quartz crystal oscillator circuits for high sensitivity microbalance sensors in damping media. Sensors and Actuators B: Chemical, 103(1-2), 318-324. doi:10.1016/j.snb.2004.04.060Rodriguez-Pardo, L., Fariña, J., Gabrielli, C., Perrot, H., & Brendel, R. (2006). Quartz crystal oscillator circuit for high resolution microgravimetric sensors in fluids. Electronics Letters, 42(18), 1065. doi:10.1049/el:20061854Wessendorf, K. O. (s. f.). The active-bridge oscillator for use with liquid loaded QCM sensors. Proceedings of the 2001 IEEE International Frequncy Control Symposium and PDA Exhibition (Cat. No.01CH37218). doi:10.1109/freq.2001.956260E. Benes, M. Schmid, M. Gröschl, P. Berlinger, H. Nowotny, and K. C. Harms, Proceedings of the Joint Meeting of the European Frequency and Time Forum and the IEEE International Frequency Control Symposium, Vol. 2, p. 1023–1026 (1999).J. Rabe, S. Büttgenbach, B. Zimmermann, and P. Hauptmann, 2000 IEEE/EIA International Frequency Control Symposium and Exhibition, pp. 106–112 (2000).Uttenthaler, E., Schräml, M., Mandel, J., & Drost, S. (2001). Ultrasensitive quartz crystal microbalance sensors for detection of M13-Phages in liquids. Biosensors and Bioelectronics, 16(9-12), 735-743. doi:10.1016/s0956-5663(01)00220-2Zimmermann, B., Lucklum, R., Hauptmann, P., Rabe, J., & Büttgenbach, S. (2001). Electrical characterisation of high-frequency thickness-shear-mode resonators by impedance analysis. Sensors and Actuators B: Chemical, 76(1-3), 47-57. doi:10.1016/s0925-4005(01)00567-6Sagmeister, B. P., Graz, I. M., Schwödiauer, R., Gruber, H., & Bauer, S. (2009). User-friendly, miniature biosensor flow cell for fragile high fundamental frequency quartz crystal resonators. Biosensors and Bioelectronics, 24(8), 2643-2648. doi:10.1016/j.bios.2009.01.023Bustabad, E. A., Rose, D., Arnau, A., Garcia, G., Rodriguez-Pardo, L., Farina, J., … Lazerges, M. (2009). A biosensor for detection of DNA sequences based on a 50MHz QCM electronic oscillator circuit. 2009 IEEE Sensors. doi:10.1109/icsens.2009.5398346Arnau, A., Montagut, Y., García, J. V., & Jiménez, Y. (2009). A different point of view on the sensitivity of quartz crystal microbalance sensors. Measurement Science and Technology, 20(12), 124004. doi:10.1088/0957-0233/20/12/124004Martin, S. J., Granstaff, V. E., & Frye, G. C. (1991). Characterization of a quartz crystal microbalance with simultaneous mass and liquid loading. Analytical Chemistry, 63(20), 2272-2281. doi:10.1021/ac00020a015Keiji Kanazawa, K., & Gordon, J. G. (1985). The oscillation frequency of a quartz resonator in contact with liquid. Analytica Chimica Acta, 175, 99-105. doi:10.1016/s0003-2670(00)82721-xPax, M., Rieger, J., Eibl, R. H., Thielemann, C., & Johannsmann, D. (2005). Measurements of fast fluctuations of viscoelastic properties with the quartz crystal microbalance. The Analyst, 130(11), 1474. doi:10.1039/b504302fMontrose, M. I. (1998). EMC and the Printed Circuit Board. doi:10.1002/047172310xA. Montoya, A. Ocampo, and C. March, inPiezoelectric Transducers and Applications, edited by A. 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Concepciones alternativas, equilibrio químico y cambio conceptual

Considerando los resultados obtenidos en un examen diagnóstico aplicado durante 3 semestres en la asignatura de Química Analítica I, insertada en el 4º semestre de las licenciaturas de química que se imparten en la Facultad de Química, se detectó la necesidad de lograr un verdadero cambio conceptual en los temas de: equilibrio químico, cálculo de la constante, principio de LeChatelier y reacción reversible. Los alumnos que van a cursar Química Analítica I, ya acreditaron las asignaturas de Química General I y II y Química Inorgánica. Con base en el análisis de ese examen, las autoras planeamos, un taller con alumnos, para analizar y reflexionar acerca de las concepciones alternativas que prevalecen para esos conceptos. Se presentan los resultados obtenidos con este grupo de alumnos

Love Mode Surface Acoustic Wave and High Fundamental Frequency Quartz Crystal Microbalance immunosensors for the detection of carbaryl pesticide

[EN] In this work we determined the Sensitivity (estimated as the I50 value) and Limit of Detection (LOD) for the immunodetection of carbaryl pesticide with two different types of acoustic wave sensors: High Fundamental Frequency Quartz Crystal Microbalance (HFF-QCM) and Love Mode Surface Acoustic Wave (LM-SAW). Results were compared with others previously reported using different sensors and techniques, like traditional QCM, Surface Plasmon Resonance (SPR) and Enzyme-Linked ImmunoSorbent Assay (ELISA). We used the AWS-A10 research platform (AWSensors, Spain) to perform the experiments. We obtained I50 values of 0.31 μg/L and 0.66 μg/L, and LODs of 0.09 μg/L and 0.14 μg/L, for 120 MHz LM-SAW and 100 MHz HFF-QCM devices, respectively. Both the sensitivities and LODs of the immunosensors improved previously reported SPR and QCM results by one and two orders of magnitude, respectively, and reached those of ELISA.The authors acknowledge: the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (ERDF) for their financing support through the grant of the INNPACTO 2012 project (DETECTA IPT-2012-0154-300000) and J.V. García's Fellowship, ref. AP2007-03745 of the FPU (Formación de Profesorado Universitario) program; the Mexican Consejo Nacional de Ciencia y Tecnología (CONACyT) for M.I. Rocha-Gaso's PhD CONACyT Fellowship.García Narbón, JV.; Rocha, M.; March Iborra, MDC.; García, P.; Francis, LA.; Montoya Baides, Á.; Arnau Vives, A.... (2014). Love Mode Surface Acoustic Wave and High Fundamental Frequency Quartz Crystal Microbalance immunosensors for the detection of carbaryl pesticide. Procedia Engineering. 87:759-762. https://doi.org/10.1016/j.proeng.2014.11.649S7597628

Patients' views and experiences of live supervised tele-exercise classes following bariatric surgery during the COVID-19 pandemic: The BARI-LIFESTYLE qualitative study

The BARI-LIFESTYLE trial is a randomized controlled trial evaluating the efficacy of a post-surgery nutritional and behavioural tele-counselling, and supervised exercise programme to maximize the health benefits of bariatric surgery. Due to the coronavirus disease 2019 (COVID-19) pandemic, the in-person supervised exercise component had to be converted to remote tele-exercise. However, patients' acceptability of this method of exercise provision is unknown. Between 3 and 6 months following bariatric surgery, 13 adults participated in weekly, structured, 60-min supervised exercise classes delivered via Zoom by a trained exercise therapist. A total of 12 participants (n = 8 female), with a mean age of 46.3 (range 33–63) years, who had undergone either sleeve gastrectomy (n = 8) or Roux-en-Y gastric bypass (n = 4) surgery, participated in one-to-one semi-structured interviews following the tele-exercise classes. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Participants described how the tele-exercise classes helped them to cope with the changes to their lives brought about by the COVID-19 pandemic. Participants found the tele-exercise schedule, content and intensity to be acceptable, and were satisfied with the privacy, security and safety of the technology and classes. Professional supervision and guidance from an exercise therapist were described as central to the tele-exercise provision. Importantly, participation in the tele-exercise provided physical, emotional and social benefits. Few participants reported barriers to participation. Overall, the tele-exercise classes were deemed acceptable and compared favourably to in-person exercise classes

Phase I/II study of DHA–paclitaxel in combination with carboplatin in patients with advanced malignant solid tumours

DHA–paclitaxel is a conjugate of paclitaxel and the fatty acid, docosahexaenoic acid. Preclinical studies have demonstrated increased activity, relative to paclitaxel, with the potential for an improved therapeutic ratio. We conducted a phase I study to determine the maximum tolerated doses of DHA–paclitaxel and carboplatin when administered in combination. Two cohorts of patients were treated: carboplatin AUC 5 with DHA–paclitaxel 660 mg m-2 and carboplatin AUC 5 with DHA–paclitaxel 880 mg m-2. Both drugs were given on day 1 every 21 days. A total of 15 patients were enrolled with a median age of 59 years (range 33–71). All patients had advanced cancer refractory to standard treatment, performance status 0–2 and were without major organ dysfunction. A total of 54 cycles of treatment were delivered. No dose-limiting toxicity (DLT) was seen in the first cohort of three patients. In an expanded second cohort, neutropenia was the main DLT, occurring in the first cycle of treatment in five of 12 patients: three of these patients and one additional patient also experienced dose-limiting grade 3 transient rises in liver transaminases. No alopecia was seen and one patient developed clinically significant neuropathy. One partial response was seen in a patient with advanced adenocarcinoma of the oesophago-gastric junction and 12 patients had stable disease with a median time to progression of 184 days (range 60–506 days). The recommended phase II dose in pretreated patients is Carboplatin AUC 5 and DHA–paclitaxel 660 mg m-2 given every 21 days. Further studies with Carboplatin AUC 5 and DHA-paclitaxel 880 mg m-2, given every 28 days, are warranted in chemo-naive patients

Patients' views and experiences of live supervised tele-exercise classes following bariatric surgery during the COVID-19 pandemic: The BARI-LIFESTYLE qualitative study.

The BARI-LIFESTYLE trial is a randomized controlled trial evaluating the efficacy of a post-surgery nutritional and behavioural tele-counselling, and supervised exercise programme to maximize the health benefits of bariatric surgery. Due to the coronavirus disease 2019 (COVID-19) pandemic, the in-person supervised exercise component had to be converted to remote tele-exercise. However, patients' acceptability of this method of exercise provision is unknown. Between 3 and 6 months following bariatric surgery, 13 adults participated in weekly, structured, 60-min supervised exercise classes delivered via Zoom by a trained exercise therapist. A total of 12 participants (n = 8 female), with a mean age of 46.3 (range 33-63) years, who had undergone either sleeve gastrectomy (n = 8) or Roux-en-Y gastric bypass (n = 4) surgery, participated in one-to-one semi-structured interviews following the tele-exercise classes. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Participants described how the tele-exercise classes helped them to cope with the changes to their lives brought about by the COVID-19 pandemic. Participants found the tele-exercise schedule, content and intensity to be acceptable, and were satisfied with the privacy, security and safety of the technology and classes. Professional supervision and guidance from an exercise therapist were described as central to the tele-exercise provision. Importantly, participation in the tele-exercise provided physical, emotional and social benefits. Few participants reported barriers to participation. Overall, the tele-exercise classes were deemed acceptable and compared favourably to in-person exercise classes

Early embryonic exposure of freshwater gastropods to pharmaceutical 5α-reductase inhibitors results in a surprising open-coiled “banana-shaped” shell

National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), https://www.nc3rs.org.uk/ grant ‘The Snail Assay as an Alternative to the Rodent Hershberger Assay for Detecting Androgens and Anti-androgens’ G0900802/1

Impact of nutritional-behavioral and supervised exercise intervention following bariatric surgery: The BARI-LIFESTYLE randomized controlled trial

Objective: The study's aim was to investigate the impact of a 12-month adjunctive lifestyle intervention on weight loss and health outcomes after bariatric surgery.// Methods: A total of 153 participants (78.4% females; mean [SD], age 44.2 [10.6] years; BMI 42.4 [5.7] kg/m2) were randomized to intervention (n = 79) and control (n = 74). The BARI-LIFESTYLE program combined 17 nutritional-behavioral tele-counseling sessions plus once-weekly supervised exercise for 12 weeks. The primary outcome was percentage weight loss at 6 months post surgery. Secondary outcomes included body composition, physical activity levels, physical function and strength, health-related quality of life, depressive symptomatology, and comorbidities.// Results: Longitudinal analysis of the entire cohort showed significant reductions in body weight, fat mass, fat-free mass, and bone mineral density at the total hip, femoral neck, and lumbar spine (all p  0.05). There was no significant difference in the primary outcome between the intervention versus control (20.4% vs. 21.2%; mean difference = −0.8%; 95% CI: −2.8 to 1.1; p > 0.05) and no between-group differences in secondary outcomes.// Conclusions: An adjunctive lifestyle program implemented immediately after surgery had no favorable impact upon weight loss and health outcomes