Splenic abscess is a serious complication associated with infective endocarditis. There is still contradicting evidence regarding the optimal treatment pathway including timing of valve intervention ...and the approach for managing splenic foci.
We present a case of a hybrid staged approach in which we successfully performed a laparoscopic splenectomy following percutaneous abscess drainage and a delayed aortic valve replacement.
A multidisciplinary teamwork is fundamental in providing optimal care for patients with distant complications associated with infective endocarditis. Our hybrid approach seems safe and feasible.
The large and increasing burden of stroke in Latin American countries, and the need to meet the UN and WHO requirements for reducing the burden from non-communicable disorders (including stroke), ...brought together stroke experts and representatives of the Ministries of Health of 13 Latin American countries for the 1st Latin American Stroke Ministerial meeting in Gramado, Brazil, to discuss the problem and identify ways of cooperating to reduce the burden of stroke in the region. Discussions were focused on the regional and country-specific activities associated with stroke prevention and treatment, including public stroke awareness, prevention strategies, delivery and organisation of care, clinical practice gaps, and unmet needs. The meeting culminated with the adoption of the special Gramado Declaration, signed by all Ministerial officials who attended the meeting. With agreed priorities for stroke prevention, treatment, and research, an opportunity now exists to translate this Declaration into an action plan to reduce the burden of stroke.
According to the United Nations’ latest forecast, the world population will reach 8.5 billion people by 2030. This rapid population growth imposes severe requirements in food production to meet ...demand. Moreover, the rise of temperatures and climate changes are also adversely affecting food supplies. In this paper, we design a scalable IoT-based monitoring system with prediction capabilities for agricultural applications. It provides an effective four-layered architecture that consist of sensing, networking, processing, and applications with low deployment and management costs. Hence, to demonstrate its feasibility, the proposed IoT system was constructed, experimentally tested, and validated by monitoring the temperature and humidity of a commercial-size greenhouse in Mexico for six months. Additionally, we integrated a data-driven predictive model for greenhouse microclimate conditions. Temperature predictions were accurately performed 24-hour in advance within an error of 1 °C. The obtained results confirm that the proposed IoT framework would facilitate farmers to monitor crops and enable productivity gains by increasing the level of technology progressively.
•An IoT monitoring approach was designed to help farmers increase efficiency.•The IoT framework was successfully validated in a tomato greenhouse for six months.•The solution incorporates a data-driven predictive model for microclimate conditions.•Temperature predictions were performed 24-hour in advance within an error of 1 °C.•An effective IoT sensor coverage strategy is proposed based on the packing density theory.
Intermittent Access (IntA) cocaine self‐administration is a protocol suggested to better simulate human addictive behavior due to the intermittent pattern of drug administration. IntA is also known ...to produce incentive salience and psychomotor sensitization. It is documented that IntA produces a neurochemical sensitization of the mesolimbic dopamine (DA) system by increasing both release and uptake of DA. The ventral tegmental area (VTA) DA neurons display a prominent mixed cation current conductance known as the hyperpolarization‐activated cyclic nucleotide current, or Ih. Neural processes such as resting membrane potential, firing frequency modulation, and synaptic integration are influenced by the Ih. Previous results from our laboratory demonstrated that Ih amplitude and membrane capacitance of putative VTA DA neurons are significantly reduced after cocaine sensitization. This Ihand capacitance reduction resulted in an increased temporal summation, mean depolarization and excitatory postsynaptic potential (EPSP) amplitude, all related to an enhanced neuronal excitability state. It is not known how IntA alters the intrinsic properties of VTA DA cells. Since the cocaine sensitization model involves experimenter administered drug injections (non‐contingent) it is important to determine if electrophysiological changes in VTA DA cells are present when drugs are self‐administered (contingent). In the present study we explored if synaptic integration, membrane capacitance and cell activity alterations are present after exposure to cocaine IntA. Our hypothesis is that IntA enhances synaptic integration and neuronal excitability of VTA DA cells. Whole‐cell patch‐clamp technique in rat brain slices was used to inject a 33‐Hz train of 5 αEPSCs (α = 5 ms; Imax = 50) into the soma of putative VTA DA neurons when clamped at ‐70 mV and analyze the effects of cocaine IntA, and passive cocaine infusions (yoked controls) on synaptic integration. Increasing depolarizing current injections were used to evaluate how neurons respond to a depolarizing stimulus. Our results demonstrate that an IntA protocol, but not passive cocaine infusions, produces a significant increase in the number of APs (P<0.05). Temporal summation was increased at depolarized potentials in the IntA group and Yoked controls (P<0.0001). These results suggests that neuronal activity regulation is dependent on associative learning to drug cues. The findings also suggest that enhanced synaptic integration could possibly be a cocaine‐induced pharmacological effect.
The ventral tegmental area (VTA) plays an important role in reward and motivational processes involved in drug addiction. Previous studies have shown that alpha1-adrenoreceptors (α1-AR) are primarily ...found pre-synaptically at this area. We hypothesized that GABA released onto VTA-dopamine (DA) cells is modulated by pre-synaptic α1-AR. Recordings were obtained from putative VTA-DA cells of male Sprague–Dawley rats (28–50 days postnatal) using whole-cell voltage clamp technique. Phenylephrine (10 μM; α1-AR agonist) decreased the amplitude of GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) evoked by electrical stimulation of afferent fibers (n = 7; p < 0.05). Prazosin (1 μM, α1-AR antagonist), blocked this effect. Paired-pulse ratios were increased by phenylephrine application (n = 13; p < 0.05) indicating a presynaptic site of action. Spontaneous IPSCs frequency but not amplitude, were decreased in the presence of phenylephrine (n = 7; p < 0.05). However, frequency or amplitude of miniature IPSCs were not changed (n = 9; p > 0.05). Phenylephrine in low Ca2+ (1 mM) medium decreased IPSC amplitude (n = 7; p < 0.05). Chelerythrine (a protein kinase C inhibitor) blocked the α1-AR action on IPSC amplitude (n = 6; p < 0.05). Phenylephrine failed to decrease IPSCs amplitude in the presence of paxilline, a BK channel blocker (n = 7; p < 0.05). Taken together, these results demonstrate that α1-ARs at presynaptic terminals can modulate GABA release onto VTA-DA cells. Drug-induced changes in α1-AR could contribute to the modifications occurring in the VTA during the addiction process.
This article is part of the Special Issue entitled ‘GABAergic Signaling in Health and Disease’.
•α1-ARs activation at the presynaptic site decreases GABA release onto putative DA cells within VTA.•Presynaptic α1-ARs activation modulates GABAergic inputs that affect VTA DA neurons excitability.•α1-ARs effect might be heterosynaptically localized at GABAergic fibers terminating onto VTA-DA neurons.
The hyperpolarization-activated cation current (Ih) is a determinant of intrinsic excitability in various cells, including dopaminergic neurons (DA) of the ventral tegmental area (VTA). In contrast ...to other cellular conductances, Ih is activated by hyperpolarization negative to -55 mV and activating Ih produces a time-dependent depolarizing current. Our laboratory demonstrated that cocaine sensitization, a chronic cocaine behavioral model, significantly reduces Ih amplitude in VTA DA neurons. Despite this reduction in Ih, the spontaneous firing of VTA DA cells after cocaine sensitization remained similar to control groups. Although the role of Ih in controlling VTA DA excitability is still poorly understood, our hypothesis is that Ih reduction could play a role of a homeostatic controller compensating for cocaine-induced change in excitability. Using in vivo single-unit extracellular electrophysiology in isoflurane anesthetized rats, we explored the contribution of Ih on spontaneous firing patterns of VTA DA neurons. A key feature of spontaneous excitability is bursting activity; bursting is defined as trains of two or more spikes occurring within a short interval and followed by a prolonged period of inactivity. Burst activity increases the reliability of information transfer. To elucidate the contribution of Ih to spontaneous firing patterns of VTA DA neurons, we locally infused an Ih blocker (ZD 7288, 8.3 μM) and evaluated its effect. Ih blockade significantly reduced firing rate, bursting frequency, and percent of spikes within a burst. In addition, Ih blockade significantly reduced acute cocaine-induced spontaneous firing rate, bursting frequency, and percent of spikes within a burst. Using whole-cell patch-clamp, we determine the progressive reduction of Ih after acute and chronic cocaine administration (15 mg/k.g intraperitoneally). Our data show a significant reduction (~25%) in Ih amplitude after 24 but not 2 h of acute cocaine administration. These results suggest that a progressive reduction of Ih could serve as a homeostatic regulator of cocaine-induced spontaneous firing patterns related to VTA DA excitability.
•Ih blockade diminishes VTA DA neuronal spontaneous firing activity.•Ih inhibition after acute cocaine administration increases the interspike interval.•Ih reduction can oppose cocaine enhanced VTA DA cell's excitability.
The ventral tegmental area (VTA) plays an important role in the reward and motivational processes that facilitate the development of drug addiction. Presynaptic α1-AR activation modulates glutamate ...and Gamma-aminobutyric acid (GABA) release. This work elucidates the role of VTA presynaptic α1-ARs and their modulation on glutamatergic and GABAergic neurotransmission during cocaine sensitization. Excitatory and inhibitory currents (EPSCs and IPSCs) measured by a whole cell voltage clamp show that α1-ARs activation increases EPSCs amplitude after 1 day of cocaine treatment but not after 5 days of cocaine injections. The absence of a pharmacological response to an α1-ARs agonist highlights the desensitization of the receptor after repeated cocaine administration. The desensitization of α1-ARs persists after a 7-day withdrawal period. In contrast, the modulation of α1-ARs on GABA neurotransmission, shown by decreases in IPSCs' amplitude, is not affected by acute or chronic cocaine injections. Taken together, these data suggest that α1-ARs may enhance DA neuronal excitability after repeated cocaine administration through the reduction of GABA inhibition onto VTA dopamine (DA) neurons even in the absence of α1-ARs' function on glutamate release and protein kinase C (PKC) activation. α1-AR modulatory changes in cocaine sensitization increase our knowledge of the role of the noradrenergic system in cocaine addiction and may provide possible avenues for therapeutics.
Midbrain dopamine neurons communicate signals of reward anticipation and attribution of salience. This capacity is distorted in heroin or cocaine abuse or in conditions such as human mania. A shared ...characteristic among rodent models of these behavioral disorders is that dopamine neurons in these animals acquired a small size and manifest an augmented spontaneous and burst activity. The biophysical mechanism underlying this increased excitation is currently unknown, but is believed to primarily follow from a substantial drop in K+ conductance secondary to morphology reduction. This work uses a dopamine neuron mathematical model to show, surprisingly, that under size diminution a reduction in K+ conductance is an adaptation that attempts to decrease cell excitability. The homeostatic response that preserves the intrinsic activity is the conservation of the ion channel density for each conductance; a result that is analytically demonstrated and challenges the experimentalist tendency to reduce intrinsic excitation to K+ conductance expression level. Another unexpected mechanism that buffers the raise in intrinsic activity is the presence of the ether‐a‐go‐go‐related gen K+ channel since its activation is illustrated to increase with size reduction. Computational experiments finally demonstrate that size attenuation results in the paradoxical enhancement of afferent‐driven bursting as a reduced temporal summation indexed correlates with improved depolarization. This work illustrates, on the whole, that experimentation in the absence of mathematical models may lead to the erroneous interpretation of the counterintuitive aspects of empirical data.
This article uses computational and analytical methods to illustrate that a reduction in potassium conductance, under cell size diminution, dampens the expected rise in intrinsic cell spiking and not the opposite. We demonstrate that the neuronal firing rate and spike waveform are, in effect, insensitive to changes in cell size as long as the number of channels per unit of membrane area is preserved. This work illustrates, on the whole, that experimentation in the absence of sound mathematical models may lead to an erroneous interpretation of reality.
The progressive escalation of psychomotor responses that results from repeated cocaine administration is termed sensitization. This phenomenon alters the intrinsic properties of dopamine (DA) neurons ...from the ventral tegmental area (VTA), leading to enhanced dopaminergic transmission in the mesocorticolimbic network. The mechanisms underlying this augmented excitation are nonetheless poorly understood. DA neurons display the hyperpolarization-activated, nonselective cation current, dubbed I
We recently demonstrated that I
and membrane capacitance are substantially reduced in VTA DA cells from cocaine-sensitized rats. The present study shows that 7 days of cocaine withdrawal did not normalize I
and capacitance. In cells from cocaine-sensitized animals, the amplitude of excitatory synaptic potentials, at -70 mV, was ∼39% larger in contrast to controls. Raise and decay phases of the synaptic signal were faster under cocaine, a result associated with a reduced membrane time constant. Synaptic summation was paradoxically elevated by cocaine exposure, as it consisted of a significantly reduced summation indexed but a considerably increased depolarization. These effects are at least a consequence of the reduced capacitance. I
attenuation is unlikely to explain such observations, since at -70 mV, no statistical differences exist in I
or input resistance. The neuronal shrinkage associated with a diminished capacitance may help to understand two fundamental elements of drug addiction: incentive sensitization and negative emotional states. A reduced cell size may lead to substantial enhancement of cue-triggered bursting, which underlies drug craving and reward anticipation, whereas it could also result in DA depletion, as smaller neurons might express low levels of tyrosine hydroxylase.
This work uses a new approach that directly extracts important biophysical parameters from alpha function-evoked synaptic potentials. Two of these parameters are the cell membrane capacitance (C
) and rate at any time point of the synaptic waveform. The use of such methodology shows that cocaine sensitization reduces C
and increases the speed of synaptic signaling. Paradoxically, although synaptic potentials show a faster decay under cocaine their temporal summation is substantially elevated.
The hyperpolarization-activated cation current (I
) is a determinant of intrinsic excitability in various cells, including dopaminergic neurons (DA) of the ventral tegmental area (VTA). In contrast ...to other cellular conductances, I
is activated by hyperpolarization negative to -55 mV and activating I
produces a time-dependent depolarizing current. Our laboratory demonstrated that cocaine sensitization, a chronic cocaine behavioral model, significantly reduces I
amplitude in VTA DA neurons. Despite this reduction in I
, the spontaneous firing of VTA DA cells after cocaine sensitization remained similar to control groups. Although the role of I
in controlling VTA DA excitability is still poorly understood, our hypothesis is that I
reduction could play a role of a homeostatic controller compensating for cocaine-induced change in excitability. Using in vivo single-unit extracellular electrophysiology in isoflurane anesthetized rats, we explored the contribution of I
on spontaneous firing patterns of VTA DA neurons. A key feature of spontaneous excitability is bursting activity; bursting is defined as trains of two or more spikes occurring within a short interval and followed by a prolonged period of inactivity. Burst activity increases the reliability of information transfer. To elucidate the contribution of I
to spontaneous firing patterns of VTA DA neurons, we locally infused an I
blocker (ZD 7288, 8.3 μM) and evaluated its effect. I
blockade significantly reduced firing rate, bursting frequency, and percent of spikes within a burst. In addition, I
blockade significantly reduced acute cocaine-induced spontaneous firing rate, bursting frequency, and percent of spikes within a burst. Using whole-cell patch-clamp, we determine the progressive reduction of I
after acute and chronic cocaine administration (15 mg/k.g intraperitoneally). Our data show a significant reduction (~25%) in I
amplitude after 24 but not 2 h of acute cocaine administration. These results suggest that a progressive reduction of I
could serve as a homeostatic regulator of cocaine-induced spontaneous firing patterns related to VTA DA excitability.
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