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Ocular Surface (OS) somatosensory innervation detects external stimuli producing perceptions, such as pain or dryness, the most relevant symptoms in many OS pathologies. Nevertheless, little is known about the central nervous system circuits involved in these perceptions, and how they integrate multimodal inputs in general. Here, we aim to describe the thalamic and cortical activity in response to OS stimulation of different modalities. Electrophysiological extracellular recordings in anaesthetized rats were used to record neural activity, while saline drops at different temperatures were applied to stimulate the OS. Neurons were recorded in the ophthalmic branch of the trigeminal ganglion (TG, 49 units), the thalamic VPM-POm nuclei representing the face (Th, 69 units) and the primary somatosensory cortex (S1, 101 units). The precise locations for Th and S1 neurons receiving OS information are reported here for the first time. Interestingly, all recorded nuclei encode modality both at the single neuron and population levels, with noxious stimulation producing a qualitatively different activity profile from other modalities. Moreover, neurons responding to new combinations of stimulus modalities not present in the peripheral TG subsequently appear in Th and S1, being organized in space through the formation of clusters. Besides, neurons that present higher multimodality display higher spontaneous activity. These results constitute the first anatomical and functional characterization of the thalamocortical representation of the OS. Furthermore, they provide insight into how information from different modalities gets integrated from the peripheral nervous system into the complex cortical networks of the brain. KEY POINTS: Anatomical location of thalamic and cortical ocular surface representation. Thalamic and cortical neuronal responses to multimodal stimulation of the ocular surface. Increasing functional complexity along trigeminal neuroaxis. Proposal of a new perspe

[Background]: The vasculature function is mainly regulated by the autonomic nervous system. Importantly, the sensory-motor nervous system also innervates peripheral vessels and has the capacity to modulate vascular tone. Here we investigated the effects of electrical stimulation of a mixed nerve trunk on blood flow in deep arteries and muscle perfusion. Our hypothesis is that stimulation of a mixed nerve can modify blood flow., [Methods]: Twenty-nine healthy participants were included into a randomized-crossover and blinded clinical trial. Each subject received a placebo and two percutaneous peripheral nerve stimulation (pPNS) protocols on the median nerve: Pain Threshold continuous Low Frequency (PT-cLF) and Sensory Threshold burst High Frequency (ST-bHF). Blood flow was then assessed bilaterally using Power Doppler Ultrasonography at the main arteries of the arm, and blood perfusion at the forearm muscles. Afterwards, blood flow was quantified using a semi-automatized software, freely shared here., [Results]: Placebo, consisting in needle insertion, produced an immediate and generalized reduction on peak systolic velocity in all arteries. Although nerve stimulation produced mainly no effects, some significant differences were found: both protocols increased the relative perfusion area of the forearm muscles, the ST-bHF protocol prevented the reduction in peak systolic velocity and TAMEAN of the radial artery produced by the control protocol and PT-cLF produced a TAMEAN reduction of the ulnar artery., [Conclusions]: Therefore, the arterial blood flow in the arm is mainly impervious to the electrical stimulation of the median nerve, composed by autonomic and sensory-motor axons, although it produces mild modifications in the forearm muscles perfusion.

El presente Trabajo Fin de Grado consiste en una propuesta didáctica para llevar a cabo en el curso de 3º de ESO. El principal objetivo es plantear una propuesta de intervención para abordar la prevención del sobrepeso y la obesidad desde la educación física. Dicha propuesta consta de 12 sesiones con las que se pretende formar a estudiantes y familias acerca del sobrepeso y/u obesidad y concienciar al alumnado sobre la prevención de la obesidad. Igualmente se busca mejorar la autoestima de aquellos estudiantes que tengan problemas de sobrepeso u obesidad y mostrarles ejemplos de cómo pueden integrar la actividad física en su día día, de una forma lúdica y realizando las adaptaciones necesarias según sus necesidades. La Educación Física en el mejor vehículo para trabajar situaciones de este tipo y fomentar los hábitos saludables entre los más jóvenes. Desde los centros educativos se han de priorizar iniciativas como el proyecto anual que aquí se presenta.

Objetivos: Si el dolor es una sensación (relacionado con perturbaciones corporales) o una percepción (relacionado con las diferentes evaluaciones del paciente) es una pregunta que, en principio, la Fisioterapia no tiene la responsabilidad de responder, como tampoco lo es resolver el problema de la consciencia. Sin embargo, el dolor es un fenómeno consciente y esto tiene unas implicaciones científicas y clínicas importantes que no podemos seguir soslayando durante más tiempo, ni en la consulta ni en el laboratorio. Nos preguntamos entonces qué luz puede arrojar el estudio de las Teorías de la Consciencia y del dolor para aproximarnos al problema real del paciente con dolor de una manera rigurosa y ética. Métodos: Se realizó una revisión crítica de la neurociencia de la consciencia y del dolor y de la filosofía de la mente y del dolor, tomando la estructura del superventas Being You: A new science of consciousness (Seth, 2021), en relación con el marco teórico de la Fisioterapia y su aplicación en la práctica clínica y la investigación. Resultados: La HOT se relaciona con el evaluativismo y la Educación en Neurociencia del Dolor. El imperativismo y la Teoría Corporal guardan relación con la GNWT. Desde la IIT se propone un marco de tipo pluralista para disolver las aporías y paradojas que se presentan en el campo del dolor, así como para delimitar el alcance de nuestras intervenciones. Conclusiones: Con el cuerpo de conocimiento actual, científico y filosófico, no se puede estudiar seriamente el dolor dejando de lado sistemáticamente el asunto de la consciencia. Las Teorías de la Consciencia, desde una perspectiva pluralista, pueden arrojar luz sobre problemas acuciantes en el campo, tanto a nivel clínico como investigador. Quizá no para obtener respuestas, pero sin duda para ayudar plantear las preguntas correctas.

Peripheral sensory neurons are fundamental for stimulus detection, but many of their properties remain poorly understood (Velasco et al., 2022). One of these is the marked instability of the resting membrane potential recorded in such neurons, known as Membrane Potential Instabilities (MPIs). MPIs are enhanced in pain states, but their functional significance and molecular bases remain largely unknown. Here, we addressed this using whole-cell current-clamp recordings in primary cultured mouse trigeminal (TG) neurons. MPI detection and morphological analyses were performed semi-automatically, using custom-made scripts. We found that 82.2% of small diameter neurons recorded displayed MPI activity in the shape of Membrane Potential Transients (MPTs), spontaneously or upon depolarizing current injection. The frequency, amplitude and rates of upstroke and repolarization of MPTs were increased by membrane depolarization. Morphological analyses of the MPTs and of the initial depolarizing phase of action potentials (Aps) revealed that larger and faster MPTs precede AP firing. This was confirmed by a regression analysis showing that the maximal rate of depolarization and amplitude of the MPTs strongly predict subsequent AP firing, following a Boltzmann dependency. MPT activity was enhanced by the application of heat, cold, capsaicin and menthol, via their depolarizing effect on the resting membrane potential. MPT activity was reduced by blocking TTX-resistant, but not TTX-sensitive voltage-gated Na+ channels. Accordingly, MPTs were also reduced in neurons isolated from NaV1.8 and NaV1.9 knockout mice. We hereby identify, for the first time, the molecular determinants of the trigger of MPTs and demonstrate a causal relationship between MPTs and AP firing upon exogenous stimulation of sensory neurons. These findings unveil MPTs as crucial regulators of peripheral sensory processing, with possible implications in pathological conditions featuring altered activities of TTX-resis

The role of TRPA1 in the thermosensitivity of the corneal cold thermoreceptor nerve endings was studied in young and aged mice. The contribution of the TRPA1-dependent activity to basal tearing and thermally-evoked blink was also explored. The corneal cold thermoreceptors' activity was recorded extracellularly in young (5-month-old) and aged (18-month-old) C57BL/6WT (WT) and TRPA1-/- knockout (TRPA1-KO) mice at basal temperature (34 °C) and during cooling (15 °C) and heating (45 °C) ramps. The blink response to cold and heat stimulation of the ocular surface and the basal tearing rate were also measured in young animals using orbicularis oculi muscle electromyography (OOemg) and phenol red threads, respectively. The background activity at 34 °C and the cooling- and heating-evoked responses of the cold thermoreceptors were similar in WT and TRPA1-KO animals, no matter the age. Similar to the aged WT mice, in the young and aged TRPA1-KO mice, most of the cold thermoreceptors presented low frequency background activity, a low cooling threshold, and a sluggish response to heating. The amplitude and duration of the OOemg signals correlated with the magnitude of the induced thermal change in the WT but not in the TRPA1-KO mice. The basal tearing was similar in the TRPA1-KO and WT mice. The electrophysiological data suggest that the TRPA1-dependent nerve activity, which declines with age, contributes to detecting the warming of the ocular surface and also to integrating the thermally-evoked reflex blink.

[Background]: Electrical stimulation of skin afferents can induce somatosensory plasticity in humans. Nevertheless, it is unknown if this is possible to do through percutaneous stimulation of a peripheral nerve, which will allow for regional anaesthesia interventions. Furthermore, potentiation protocols applied over mainly non-nociceptive fibres inhibit nociception in rodents, but this has not been tested in humans., [Objective]: To determine whether a protocol aiming to depress the nociceptive circuit and another aiming to potentiate non-nociceptive circuits produce regional hypoalgesia and changes in motor function, applied through percutaneous peripheral nerve stimulation (pPNS), and to assess which of them is more promising for pain relief, immediately and 24 h after the intervention., [Methods]: PT-cLF protocol aims to depress the nociceptive pathway through Pain Threshold, continuous Low Frequency stimulation and ST-bHF aims to produce potentiation of the non-nociceptive pathway, through Sensory Threshold burst stimulation at High Frequency. All subjects (n = 29) went through both protocols and a control condition in a randomized and blinded crossover design., [Results]: Compared to control, ST-bHF induced distal hypoalgesia, towards electrical (p = 0.04) and mechanical stimuli (p = 0.02) and produced mechanical hypoesthesia (p = 0.02). Contrarily, hypoalgesia was not observed after PT-cLF (p > 0.05) but increased electrical motor threshold (p = 0.04), reduced motor recruitment (p = 0.03), and the subjects reported feeling reduced strength (p < 0.01)., [Conclusion]: This works provides evidence that is possible to induce antinociceptive plasticity in a wide territory using pPNS. Moreover, it demonstrates for the first time in humans that a protocol aiming to produce long-term potentiation applied predominantly over non-nociceptive afferents induces hypoesthesia and hypoalgesia.

Peripheral sensory neurons transduce physicochemical stimuli affecting somatic tissues into the firing of action potentials that are conveyed to the central nervous system. This results in conscious perception, adaptation, and survival, but alterations of the firing patterns can result in pain and hypersensitivity conditions. Thus, understanding the molecular mechanisms underlying action potential firing in peripheral sensory neurons is essential in sensory biology and pathophysiology. Over the past 30 years, it has been consistently reported that these cells can display membrane potential instabilities (MPIs), in the form of subthreshold membrane potential oscillations or depolarizing spontaneous fluctuations. However, research on this subject remains sparse, without a clear conductive thread to be followed. To address this, we here provide a synthesis of the description, molecular bases, mathematical models, physiological roles, and pathophysiological implications of MPIs in peripheral sensory neurons. Membrane potential instabilities have been reported in trigeminal, dorsal root, and Mes-V ganglia, where they are believed to support repetitive firing. They are proposed to have roles also in intercellular communication, ectopic firing, and responses to tonic and slow natural stimuli. We highlight how MPIs are of great interest for the study of sensory transduction physiology and how they may represent therapeutic targets for many pathological conditions, such as acute and chronic pain, itch, and altered sensory perceptions. We identify future research directions, including the elucidation of the underlying molecular determinants and modulation mechanisms, their relation to the encoding of natural stimuli and their implication in pain and hypersensitivity conditions.

“Nasal hyperreactivity” is a key feature in various phenotypes of upper airway diseases, whereby reactions of the nasal epithelium to diverse chemical and physical stimuli are exacerbated. In this review, we illustrate how nasal hyperreactivity can result from at least three types of mechanisms: (1) impaired barrier function, (2) hypersensitivity to external and endogenous stimuli, and (3) potentiation of efferent systems. We describe the known molecular basis of hyperreactivity related to the functional impairment of epithelial cells and somatosensory innervation, and indicate that the thermal, chemical, and mechanical sensors determining hyperreactivity in humans remain to be identified. We delineate research directions that may provide new insights into nasal hyperreactivity associated with rhinitis/rhinosinusitis pathophysiology and therapeutics. The elucidation of the molecular mechanisms underlying nasal hyperreactivity is essential for the treatment of rhinitis according to the precepts of precision medicine.

The class IIa histone deacetylases (HDACs) have pivotal roles in the development of different tissues. Of this family, Schwann cells express Hdac4, 5, and 7 but not Hdac9. Here, we show that a transcription factor regulated genetic compensatory mechanism within this family of proteins, blocks negative regulators of myelination ensuring peripheral nerve developmental myelination and remyelination after injury. Thus, when Hdac4 and 5 are knocked-out from Schwann cells in mice, a JUN-dependent mechanism induces the compensatory overexpression of Hdac7 permitting, although with a delay, the formation of the myelin sheath. When Hdac4, 5, and 7 are simultaneously removed, the myocyte-specific enhancer-factor d (MEF2D) binds to the promoter and induces the de novo expression of Hdac9, and although several melanocytic lineage genes are misexpressed and Remak bundle structure is disrupted, myelination proceeds after a long delay. Thus, our data unveil a finely tuned compensatory mechanism within the class IIa Hdac family, coordinated by distinct transcription factors, that guarantees the ability of Schwann cells to myelinate during development and remyelinate after nerve injury.

The purpose of this double-blinded randomized controlled trial was to investigate whether percutaneous electrolysis (PE) is able to activate endogenous pain modulation and whether its effects are dependent on the dosage of the galvanic current. A total of 54 asymptomatic subjects aged 18–40 years were randomized into three groups, receiving a single ultrasound-guided PE intervention that consisted of a needle insertion on the lateral epicondyle tendon: sham (without electrical current), low-intensity (0.3 mA, 90 s), and high-intensity (three pulses of 3 mA, 3 s). Widespread pressure pain thresholds (PPT), conditioned pain modulation (CPM), and temporal summation (TS) were assessed in the elbow, shoulder, and leg before and immediately after the intervention. Both high and low intensity PE protocols produced an increase in PPT in the shoulder compared to sham (p = 0.031 and p = 0.027). The sham group presented a significant decrease in the CPM (p = 0.006), and this finding was prevented in PE groups (p = 0.043 and p = 0.025). In addition, high-intensity PE decreased TS respect to sham in the elbow (p = 0.047) and both PE groups reduced TS in the leg (p = 0.036 and p = 0.020) without significant differences compared to sham (p = 0.512). Consequently, a single PE intervention modulated pain processing in local and widespread areas, implying an endogenous pain modulation. The pain processing effect was independent of the dosage administrated.

Corneal cold nerve endings are crucial structures in the maintenance of the ocular surface due to their ability to detect cold and humidity changes, thereby regulating cold-evoked blink reflex and tearing flow. However, despite their physiological relevance, their functional organization remains poorly understood. Optopharmacological agents allow modulation of neural activity acting on native ion channels without requiring exogenous gene expression. Amongst them, photo-isomerizable small molecules (photoswitches) have been shown to confer light-sensitivity to a variety of neurons at the central nervous system (1). Nevertheless, there is no direct evidence on whether photoswitches can modulate electrical activity of neural structures located far away from the neuron cell body, such as peripheral nerve terminals. Here, we show that DENAQ, a photochromic potassium channel blocker, enters guinea-pig corneal cold sensory nerve endings primarily through P2X channels. Subsequently, DENAQ produces a robust decrease in spontaneous nerve terminal activity and sensitizes cold-evoked responses of the cold thermoreceptors upon light irradiation. Moreover, DENAQ photo-modulates electrical activity of the orbicularis oculi muscle associated with cold-evoked blink reflex in rats. Small molecules acting as chemical photoswitches may be potentially useful as drugs for patients with corneal ectopic nerve activity, such as in dry- eye and ocular neuropathic pain.

[Objective]: To systematically review the literature on the use of the transcranial static magnetic stimulation (tSMS) technique in humans and animals, its effects on different areas of the central nervous system (CNS), its influence on neural excitability and on the subject’s behavior, and its biological effects and future possibilities. All static magnetic field applications that can be considered to have a physiologically similar effect have been reviewed., [Methods]: We searched studies using key terms in NCBI PubMed, Scopus, PEDro, SciELO, Cochrane, and links to publications (inception to September 2019). Three reviewers independently selected the studies, extracted data, and assessed the methodological quality of the studies using the recommendations described in the Cochrane Handbook for Systematic Reviews of Interventions, PRISMA guidelines., [Results]: We analyzed 27 studies. The reviewed literature suggests that the use of these magnetic fields has an inhibitory effect on different areas of the CNS, such as motor, somatosensory, and visual cortex, cerebellum, and spinal cord. Regarding subject’s behavior, the different effects of tSMS appear to be transient and dependent on the stimulated area, such as loss of visual discrimination or improvement of somatosensory perception. In addition, the technique has some therapeutic utility, specifically in pathologies with cortical hyperexcitability., [Conclusions]: These results suggest that tSMS may be a promising tool to modulate cerebral excitability in a safe and non-invasive way. Further investigations could give a better explanation of its precise mechanisms of action and applications.

Perfluorohexyloctane (F6H8) eyedrops have been recently introduced in Europe as a product to treat dry eye disease, based on its ability to reduce tear film instability in Meibomian gland dysfunction and evaporative dry eye disease, although its mechanism of action is still unknown. In the present pilot study, we evaluated the effects of the ocular instillation of a single drop of commercial F6H8 eyedrops in 20 healthy humans (9 women/11 men), measuring: (a) Corneal surface temperature (CST) from infrared video images; (b) tear volume using phenol red threads; (c) blinking frequency; and (d) ocular surface sensations (cold, dryness, pricking, foreign body, burning, itching, gritty, eye fatigue, watering eyes, and light-evoked discomfort sensations; scored using 10 cm Visual Analog Scales), before and 5–60 min after F6H8 or saline treatment. CST decreased and tearing and blinking frequency increased significantly after F6H8 but not after saline solution. When applied unilaterally, CST decreased only in the F6H8-treated eye. No sensations were evoked after F6H8 or saline. The corneal surface temperature reduction produced by topical F6H8 does not evoke conscious ocular sensations but is sufficient to increase the activity of corneal cold thermoreceptors, leading to an increased reflex lacrimation and blinking that may relieve dry eye condition thus reducing ocular discomfort and pain.

Transcranial direct current stimulation (tDCS) has been investigated as a way of improving motor learning. Our purpose was to explore the reversal bilateral tDCS effects on manual dexterity training, during five days, with the retention component measured after 5 days to determine whether somatosensory effects were produced. In this randomized, triple-blind clinical trial, 28 healthy subjects (14 women) were recruited and randomized into tDCS and placebo groups, although only 23 participants (13 women) finished the complete protocol. Participants received the real or placebo treatment during five consecutive days, while performing a motor dexterity training program of 20 min. The motor dexterity and the sensitivity of the hand were assessed pre- and post-day 1, post 5 days of training, and 5 days after training concluded. Training improved motor dexterity, but tDCS only produced a tendency to improve retention. The intervention did not produce changes in the somatosensory variables assessed. Thus, reversal bi-tDCS had no effects during motor learning on healthy subjects, but it could favor the retention of the motor skills acquired. These results do not support the cooperative inter-hemispheric model.

Percutaneous electrolysis consists of the application of a galvanic electrical current throughout an acupuncture needle. It has been previously hypothesized that needling procedures’ neurophysiological effects may be related to endogenous pain modulation (EPM). This protocol study describes the design of a double-blind (participant, assessor) randomized controlled trial with the aim to investigate whether percutaneous electrolysis is able to enhance EPM and whether the effect is different between two applications depending on the dosage of the galvanic electrical current. Seventy-two asymptomatic subjects not reporting the presence of pain symptoms the previous 6 months before the study, aged 18–40 years, are randomized into one of four groups: a control group who does not receive any intervention, a needling group who receives a needling intervention without electrical current, a low-intensity percutaneous electrolysis group (0.3 mA × 90 s), and a high-intensity percutaneous electrolysis group (three bouts of 3 mA × 3 s). Needling intervention consists of ultrasound-guided insertion of the needle on the common extensor tendon of the lateral epicondyle. The primary outcome is conditioned pain modulation (CPM), and secondary outcomes include widespread pressure pain sensitivity (pressure pain thresholds (PPT) over the lateral epicondyle, the cervical spine, and the tibialis anterior muscle) and temporal summation (TS). We expected that percutaneous electrolysis would have a greater influence on CPM than an isolated needling procedure and no intervention. In addition, we also postulated that there might be differences in outcome measures depending on the intensity of the electrical current during the percutaneous electrolysis application. This study makes a new contribution to the field of neurophysiological effects of percutaneous electrolysis and needling interventions.

The evolution of communication technologies has allowed a change in the development and application of rights within democracy, in this way the right to information has become fundamental in social networks by allowing people to have more elements to broadcast an informed suffrage, likewise increases the spaces for penetration and dissemination of content to political figures to reach a larger population. However, social networks generate a large amount of false news, this alters the right to information since inaccurate data is distributed that affects the true content of law that is to inform and deteriorates democracy by allowing citizens not to carry out an evaluation objective of your political choices, La evolución de las tecnologías de comunicación ha permitido un cambio en el desarrollo y aplicación de los derechos dentro de la democracia, de esta forma el derecho a la información se ha vuelto fundamental en las redes sociales al permitir a las personas tener mayores elementos para emitir un sufragio informado, así mismo incrementa los espacios de penetración y divulgación de contenido a los personajes políticos para llegar a más población. Sin embargo, las redes sociales generan una gran cantidad de noticias falsas, esto altera el derecho a la información ya que se distribuyen datos inexactos que afectan el verdadero contenido de derecho que es informar y deterioran la democracia al permitir que la ciudadanía no realice una evaluación objetiva de sus opciones políticas.

Livers from donation after circulatory death (DCD) donors are an increasingly more common source of organs for transplantation. While there are few high-level studies in the field of DCD liver transplantation, clinical practice has undergone progressive changes during the past decade, in particular due to mounting use of postmortem normothermic regional perfusion (NRP). In Spain, uncontrolled DCD has been performed since the late 1980s/early 1990s, while controlled DCD was implemented nationally in 2012. Since 2012, the rise in DCD liver transplant activity in Spain has been considerable, and the great majority of DCD livers transplanted in Spain today are recovered with NRP. A panel of the Spanish Liver Transplantation Society was convened in 2018 to evaluate current evidence and accumulated experience in DCD liver transplantation, in particular addressing issues related to DCD liver evaluation, acceptance criteria, and recovery as well as recipient selection and postoperative management. This panel has created a series of consensus statements for the standard of practice in Spain and has published these statements with the hope they might help guide other groups interested in implementing new forms of DCD liver transplantation and/or introducing NRP into their clinical practices.

Livers from donation after circulatory death (DCD) donors are an increasingly more common source of organs for transplantation. While there are few high-level studies in the field of DCD liver transplantation, clinical practice has undergone progressive changes during the past decade, in particular due to mounting use of postmortem normothermic regional perfusion (NRP). In Spain, uncontrolled DCD has been performed since the late 1980s/early 1990s, while controlled DCD was implemented nationally in 2012. Since 2012, the rise in DCD liver transplant activity in Spain has been considerable, and the great majority of DCD livers transplanted in Spain today are recovered with NRP. A panel of the Spanish Liver Transplantation Society was convened in 2018 to evaluate current evidence and accumulated experience in DCD liver transplantation, in particular addressing issues related to DCD liver evaluation, acceptance criteria, and recovery as well as recipient selection and postoperative management. This panel has created a series of consensus statements for the standard of practice in Spain and has published these statements with the hope they might help guide other groups interested in implementing new forms of DCD liver transplantation and/or introducing NRP into their clinical practices.

Livers from donation after circulatory death (DCD) donors are an increasingly more common source of organs for transplantation. While there are few high-level studies in the field of DCD liver transplantation, clinical practice has undergone progressive changes during the past decade, in particular due to mounting use of postmortem normothermic regional perfusion (NRP). In Spain, uncontrolled DCD has been performed since the late 1980s/early 1990s, while controlled DCD was implemented nationally in 2012. Since 2012, the rise in DCD liver transplant activity in Spain has been considerable, and the great majority of DCD livers transplanted in Spain today are recovered with NRP. A panel of the Spanish Liver Transplantation Society was convened in 2018 to evaluate current evidence and accumulated experience in DCD liver transplantation, in particular addressing issues related to DCD liver evaluation, acceptance criteria, and recovery as well as recipient selection and postoperative management. This panel has created a series of consensus statements for the standard of practice in Spain and has published these statements with the hope they might help guide other groups interested in implementing new forms of DCD liver transplantation and/or introducing NRP into their clinical practices.

[Purpose]: In retinas lacking photoreceptors, photoisomerizable small molecules (photoswitches) enter retinal ganglion cells, thus modulating their electrical activity by acting on native Kv and HCN ion channels and conferring them sensitivity to a particular light wavelength. The aim of the present study was to explore the effect of the synthetic photoswitch DENAQ on the electrical activity of peripheral nerve terminals of trigeminal sensory neurons innervating the cornea of the guinea pig, and to define the mechanisms used by DENAQ to enter into the nerve endings., [Methods]: Nerve terminal impulse activity of cold terminals was recorded in excised guinea-pig corneas pre-incubated with DENAQ (2µM-2mM); a set of corneas were incubated with either a P2X or TRPV1 channel antagonist before incubation with DENAQ. Non-incubated corneas served as control. Spontaneous activity (SA) of cold thermoreceptors at 34oC was recorded under dim light. Then a light stimulating protocol consisting of 5 light pulses (460 nm, 125 mW/cm2, 15s-duration) applied at 15s intervals was applied to define the photoswitching effect of DENAQ on SA. Presence of P2X and TRPV1 channels in corneal cold nerves was ascertained by immunohistochemistry., [Results]: SA of corneal cold nerve endings was reduced after pre-incubation with DENAQ compared with control (3.1±0.5 imps/s vs 7.6±0.8 imp/s, 200µM DENAQ vs control respectively, p<0.001). In addition, SA was further reduced by 50% during the 460nm light-on periods (p<0.001). This photoswitching effect of DENAQ was dose-dependent. Illumination with 460 nm light did not affect SA in control corneas. Photoswitching effect of DENAQ was abolished by pre-treatment with non-selective P2X antagonists (suramine, TNT-ATP) and selective P2X3 antagonist purotoxin 1 but not by selective P2X7 antagonist A740003 nor by TRPV1 blocker capsazepine. A fraction of TRPM8+ cold nerves was positive for P2X3 receptor. TRPV1 was also functional in part of corneal cold terminals., [Conclusions]: The non-membrane permeable photoswitch DENAQ enters to corneal cold sensory nerve endings preferentially through ATP-gated P2X cation channels, mainly P2X3. Once inside, DENAQ photoisomerization to cis configuration when exposed to 460 nm blue light hyperpolarizes the nerve terminal and decreases significantly the spontaneous activity of corneal cold thermoreceptors, opening a new approach to treat ocular pain and dry eye.

Hard models for particle interactions have played a crucial role in the understanding of the structure of condensed matter. In particular, they help to explain the formation of oriented phases in liquids made of anisotropic molecules or colloidal particles and continue to be of great interest in the formulation of theories for liquids in bulk, near interfaces and in biophysical environments. Hard models of anisotropic particles give rise to complex phase diagrams, including uniaxial and biaxial nematic phases, discotic phases and spatially ordered phases such as smectic, columnar or crystal. Also, their mixtures exhibit additional interesting behaviours where demixing competes with orientational order. Here we review the different models of hard particles used in the theory of bulk anisotropic liquids, leaving aside interfacial properties and discuss the associated theoretical approaches and computer simulations, focusing on applications in equilibrium situations. The latter include one-component bulk fluids, mixtures and polydisperse fluids, both in two and three dimensions, and emphasis is put on liquid-crystal phase transitions and complex phase behaviour in general.

Este trabajo va a representar el final del Máster en Profesor de Educación Secundaria Obligatoria de Bachillerato, formación profesional y enseñanza de idiomas en la especialidad de Biología y Geología. El objetivo del presente trabajo es desarrollar la unidad didáctica “Dinámica de ecosistemas” correspondiente al 4º curso de Educación Secundaria Obligatoria, de la asignatura Biología y Geología., Máster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idiomas

Este trabajo va a representar el final del Máster en Profesor de Educación Secundaria Obligatoria de Bachillerato, formación profesional y enseñanza de idiomas en la especialidad de Biología y Geología. El objetivo del presente trabajo es desarrollar la unidad didáctica “Dinámica de ecosistemas” correspondiente al 4º curso de Educación Secundaria Obligatoria, de la asignatura Biología y Geología., Máster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idiomas

Este trabajo va a representar el final del Máster en Profesor de Educación Secundaria Obligatoria de Bachillerato, formación profesional y enseñanza de idiomas en la especialidad de Biología y Geología. El objetivo del presente trabajo es desarrollar la unidad didáctica “Dinámica de ecosistemas” correspondiente al 4º curso de Educación Secundaria Obligatoria, de la asignatura Biología y Geología., Máster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idiomas

Este trabajo va a representar el final del Máster en Profesor de Educación Secundaria Obligatoria de Bachillerato, formación profesional y enseñanza de idiomas en la especialidad de Biología y Geología. El objetivo del presente trabajo es desarrollar la unidad didáctica “Dinámica de ecosistemas” correspondiente al 4º curso de Educación Secundaria Obligatoria, de la asignatura Biología y Geología., Máster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idiomas

Este trabajo va a representar el final del Máster en Profesor de Educación Secundaria Obligatoria de Bachillerato, formación profesional y enseñanza de idiomas en la especialidad de Biología y Geología. El objetivo del presente trabajo es desarrollar la unidad didáctica “Dinámica de ecosistemas” correspondiente al 4º curso de Educación Secundaria Obligatoria, de la asignatura Biología y Geología., Máster en Profesor de Educación Secundaria Obligatoria y Bachillerato, Formación Profesional y Enseñanzas de Idiomas

Two-dimensional nematics possess peculiar properties that have been studied recently using computer simulation and various theoretical models. Here we review our own contribution to the field using density-functional theory, and present some preliminary simulation results on confined two-dimensional nematics. First we discuss the possible stable bulk phases and phase diagrams and the relation between phases and particle geometry. We then explore the adsorption properties on a single substrate and the confinement effects that arise when the fluid is confined between parallel walls. Next, confinement in circular cavities is presented; this geometry allows us to measure some properties of the simplest defects that arise in two-dimensional nematics. Finally, preliminary Monte Carlo simulation results of confined nematics in circular geometry are shown. © 2012 Elsevier B.V.

We discuss the Lebwohl-Lasher model of nematic liquid crystals in a confined geometry, using Monte Carlo simulation and mean-field theory. A film of material is sandwiched between two planar, parallel plates that couple to the adjacent spins via a surface strength s . We consider the cases where the favored alignments at the two walls are the same (symmetric cell) or different (asymmetric cell). In the latter case, we demonstrate the existence of a single phase transition in the slab for all values of the cell thickness. This transition has been observed before in the regime of narrow cells, where the two structures involved correspond to different arrangements of the nematic director. By studying wider cells, we show that the transition is in fact the usual isotropic-to-nematic (capillary) transition under confinement in the case of antagonistic surface forces. We show results for a wide range of values of film thickness and discuss the phenomenology using a mean-field model.

Fission of many prokaryotes as well as some eukaryotic organelles depends on the self-assembly of the FtsZ protein into a membrane-associated ring structure early in the division process. Different components of the machinery are then sequentially recruited. Although the assembly order has been established, the molecular interactions and the understanding of the force-generating mechanism of this dividing machinery have remained elusive. It is desirable to develop simple reconstituted systems that attempt to reproduce, at least partially, some of the stages of the process. High-resolution studies of Escherichia coli FtsZ filaments’ structure and dynamics on mica have allowed the identification of relevant interactions between filaments that suggest a mechanism by which the polymers could generate force on the membrane. Reconstituting the membrane-anchoring protein ZipA on E. coli lipid membrane on surfaces is now providing information on how the membrane attachment regulates FtsZ polymer dynamics and indicates the important role played by the lipid composition of the membrane

FtsZ is a bacterial protein that forms filaments that play an essential role in midcell constriction during the process of cell division. The shape of individual filaments of different lengths imaged with atomic force microscopy was modeled considering the protein monomers as beads in a chain and a few parameters to represent their effective interactions. The flexural rigidity and persistence length of the filaments were estimated. This latter value was comparable to the filament length, implying that these biological polymers are halfway between the perfectly stiff linear aggregate whose shapes are fully controlled by the angle between the monomers and highly flexible polymers whose shapes follow a random walk model. The lateral interactions between adjacent filaments, also estimated in the modeling, were found to play an essential role in determining the final shape and kinetics of the coiled structures found in longer polymers. The estimated parameters were used to model the behavior of the polymers also on a cylindrical surface. This analysis points to the formation of helical structures that suggest a mechanism for force generation and amplification through the development of FtsZ spirals at the midcell division point

A recent theoretical article provided a mechanical explanation for the formation of cytoskeletal rings and helices in bacteria assuming that these shapes arise, at least in part, from the interaction of the inherent mechanical properties of the protein polymers and the constraints imposed by the curved cell membrane (Andrews, S., and A. P. Arkin. 2007. Biophys. J. 93:1872–1884). Due to the lack of experimental data regarding the bending rigidity and preferential bond angles of bacterial polymers, the authors explored their model over wide ranges of preferred curvature values. In this letter, we present the shape diagram of the FtsZ bacterial polymer on a curved surface but now including recent experimental data on the in vitro formed FtsZ polymers. The lateral interactions between filaments observed experimentally change qualitatively the shape diagram and indicate that the formation of rings over spirals is more energetically favored than estimated in the above-mentioned article. In recent years, it has become evident that the bacterial cell contains a large number of organized elements that fit within the wide concept of cytoskeleton used in eukaryotes: stable or dynamic polymers of filamentous nature with long-range order that can assemble, disassemble, and redistribute rapidly within the cell in response to signals that regulate cellular functions [1.] and [2.]. Some of these polymers are bound to the inside of the cell membrane, forming rings or helices [3.], [4.], [5.] and [6.], and they can serve different functions that go from helping define the cell morphology (7); locating the cell division site (2); to forming a ring that contracts during cell division [8.] and [9.]. A recent theoretical analysis (10) characterizes the shape of the membrane-bound polymers with a sequence of turning angles (see Fig. 1 D). The energy was taken as a sum of independent contributions for each bond along the filament, assuming quadratic dependence of the bond energy with the d

Using density-functional theory, we have analyzed the phase behavior of binary mixtures of hard rods of different lengths and diameters. Previous studies have shown a strong tendency of smectic phases of these mixtures to segregate and, in some circumstances, to form microsegregated phases. Our focus in the present work is on the formation of columnar phases which some studies, under some approximations, have shown to become thermodynamically stable prior to crystallization. Specifically we focus on the relative stability between smectic and columnar phases, a question not fully addressed in previous work. Our analysis is based on two complementary perspectives: on the one hand, an extended Onsager theory, which includes the full orientational degrees of freedom but with spatial and orientational correlations being treated in an approximate manner; on the other hand, we formulate a Zwanzig approximation of fundamental-measure theory on hard parallelepipeds, whereby orientations are restricted to be only along three mutually orthogonal axes, but correlations are faithfully represented. In the latter case novel, complete phase diagrams containing regions of stability of liquid-crystalline phases are calculated. Our findings indicate that the restricted-orientation approximation enhances the stability of columnar phases so as to preempt smectic order completely while, in the framework of the extended Onsager model, with full orientational degrees of freedom taken into account, columnar phases may preempt a large region of smectic stability in some mixtures, but some smectic order still persists.

Using a version of density-functional theory which combines Onsager approximation and fundamental-measure theory for spatially nonuniform phases, we have studied the phase diagram of freely rotating hard rectangles and hard discorectangles. We find profound differences in the phase behavior of these models, which can be attributed to their different packing properties. Interestingly, bimodal orientational distribution functions are found in the nematic phase of hard rectangles, which cause a certain degree of biaxial order, albeit metastable with respect to spatially ordered phases. This feature is absent in discorectangles, which always show unimodal behavior. This result may be relevant in the light of recent experimental results which have confirmed the existence of biaxial phases. We expect that some perturbation of the particle shapes (either a certain degree of polydispersity or even bimodal dispersity in the aspect ratios) may actually destabilize spatially ordered phases thereby stabilizing the biaxial phase.

We have recently proposed [Phys. Rev. Lett. 87, 166101 (2001)] that any isotropic fluid should exhibit surface layering at its liquid–vapor interface above the triple temperature provided that the system has a low triple temperature. In this article we present an extensive study of systems with different isotropic pair interactions, some of which present a very low triple temperature. We have confirmed that surface layering is a general characteristic of very cold liquids, independent of the specific shape of the potential, and that only pair potentials presenting a low triple-point temperature do exhibit surface oscillations; in other cases layering is preempted by solidification. Finally, we study the damping of surface oscillations due to capillary waves and conclude that for any model pair potential the temperature threshold below which layering would be observed for the typical experimental transverse sampling sizes is 15% of the critical temperature.

We use a generalized van der Waals molecular theory to study a model substrate-nematic interface in the regime of complete wetting and in a situation of competing interactions at the interface. The analysis shows that an anchoring transition between states with planar and homeotropic director configuration may play the role of a prewetting transition, and that reentrant anchoring must generally occur. As a result one expects complete wetting in a finite temperature range. The study provides a general context within which anchoring and wetting phenomena can be related

We use a generalized van der Waals molecular theory to study a model substrate-nematic interface in the regime of complete wetting and in a situation of competing interactions at the interface. The analysis shows that an anchoring transition between states with planar and homeotropic director configuration may play the role of a prewetting transition, and that reentrant anchoring must generally occur. As a result one expects complete wetting in a finite temperature range. The study provides a general context within which anchoring and wetting phenomena can be related

We use a generalized van der Waals molecular theory to study a model substrate-nematic interface in the regime of complete wetting and in a situation of competing interactions at the interface. The analysis shows that an anchoring transition between states with planar and homeotropic director configuration may play the role of a prewetting transition, and that reentrant anchoring must generally occur. As a result one expects complete wetting in a finite temperature range. The study provides a general context within which anchoring and wetting phenomena can be related

We use a generalized van der Waals molecular theory to study a model substrate-nematic interface in the regime of complete wetting and in a situation of competing interactions at the interface. The analysis shows that an anchoring transition between states with planar and homeotropic director configuration may play the role of a prewetting transition, and that reentrant anchoring must generally occur. As a result one expects complete wetting in a finite temperature range. The study provides a general context within which anchoring and wetting phenomena can be related

We use a generalized van der Waals molecular theory to study a model substrate-nematic interface in the regime of complete wetting and in a situation of competing interactions at the interface. The analysis shows that an anchoring transition between states with planar and homeotropic director configuration may play the role of a prewetting transition, and that reentrant anchoring must generally occur. As a result one expects complete wetting in a finite temperature range. The study provides a general context within which anchoring and wetting phenomena can be related

Esta Tesis Doctoral surge a partir de una experiencia de cooperación sanitaria efectuada entre marzo de 1989 y marzo de 1991 en un Hospital rural del Chad, el Hospital de Beboro, perteneciente a la Iglesia Católica y apoyado por diversas Organizaciones No Gubernamentales, principalmente Medicus Mundi España, INTERMON (España) y CEBEMO (Holanda). El disfuncionamiento organizativo y la inadecuada calidad de la prestación de los servicios tanto a nivel del Hospital de Beboro como de los otros servicios de salud de la Subprefectura Administrativa donde se encontraba situado, condujo a estudiar los problemas y las causas de tal situación con la finalidad de iniciar un proceso de cambio organizativo. Dos factores matizaban la manera de abordar los problemas y las soluciones del Hospital: 1) el trabajo in situ, frente a una situación real y práctica; 2) la evidencia cada vez mayor, constatada en la experiencia y la literatura, de que un enfoque unilateral, simplista y teórico de cualquier problema del Tercer Mundo, conduce a visiones reduccionistas que son cuestionables a raíz de los resultados prácticos de una gran mayoría de acciones de desarrollo. Ello conducía a intentar abordar nuestro trabajo y nuestro análisis con un enfoque global (y en cierta manera multidisciplinario), en el que los problemas y las soluciones se contemplaran en estrecha interrelación con el contexto histórico, político, económico y cultural, todo ello teñido de un espíritu de promoción humana. Con ello pretendía estudiar la aplicación práctica de un modelo conceptual de enfoque de salud que en la mayoría de ocasiones se quedan en mera letra impresa, a lo sumo en declaraciones de intenciones de los organismos que promueven la salud en el Tercer Mundo. La salud de la población que el Hospital de Beboro atendía presentaba graves problemas que exigía soluciones a largo plazo actuando sobre todo la compleja interrelación de factores que determinan el estado de salud: biológicos, ambientales, etc. Entr