Cholinergic Polarization of Human Macrophages.

Macrophages serve as vital defenders, protecting the body by exhibiting remarkable cellular adaptability in response to invading pathogens and various stimuli. These cells express nicotinic acetylcholine receptors, with the α7-nAChR being extensively studied due to its involvement in activating the cholinergic anti-inflammatory pathway. Activation of this pathway plays a crucial role in suppressing macrophages' production of proinflammatory cytokines, thus mitigating excessive inflammation and maintaining host homeostasis. Macrophage polarization, which occurs in response to specific pathogens or insults, is a process that has received limited attention concerning the activation of the cholinergic anti-inflammatory pathway and the contributions of the α7-nAChR in this context. This review aims to present evidence highlighting how the cholinergic constituents in macrophages, led by the α7-nAChR, facilitate the polarization of macrophages towards anti-inflammatory phenotypes. Additionally, we explore the influence of viral infections on macrophage inflammatory phenotypes, taking into account cholinergic mechanisms. We also review the current understanding of macrophage polarization in response to these infections. Finally, we provide insights into the relatively unexplored partial duplication of the α7-nAChR, known as dup α7, which is emerging as a significant factor in macrophage polarization and inflammation scenarios.

Left Atrial Myxoma With Aortic Insufficiency Leading to Cerebrovascular Accident.

Primary cardiac tumors are extremely rare and can lead to significant neurologic symptoms if not diagnosed and treated appropriately. Cardiac myxomas represent the most common subtype of cardiac tumors and are typically located on the left side of the heart and, when diagnosed appropriately with echocardiography, are typically treated with surgical excision. Simultaneous presentation of myxoma and valvular insufficiency is rare and under-documented. This is a rare case of a patient with a left atrial myxoma and aortic insufficiency leading to cerebrovascular symptoms.

Optimizing the Production of gp145, an HIV-1 Envelope Glycoprotein Vaccine Candidate and Its Encapsulation in Guanosine Microparticles.

We have developed a pipeline to express, purify, and characterize HIV envelope protein (Env) gp145 from Chinese hamster ovary cells, to accelerate the production of a promising vaccine candidate. First in shake flasks, then in bioreactors, we optimized the growth conditions. By adjusting the pH to 6.8, we increased expression levels to 101 mg/L in a 50 L bioreactor, nearly twice the previously reported titer value. A battery of analytical methods was developed in accordance with current good manufacturing practices to ensure a quality biopharmaceutical. Imaged capillary isoelectric focusing verified proper glycosylation of gp145; dynamic light scattering confirmed the trimeric arrangement; and bio-layer interferometry and circular dichroism analysis demonstrated native-like properties (i.e., antibody binding and secondary structure). MALDI-TOF mass spectrometry was used as a multi-attribute platform for accurate mass determination, glycans analysis, and protein identification. Our robust analysis demonstrates that our gp145 product is very similar to a reference standard and emphasizes the importance of accurate characterization of a highly heterogeneous immunogen for the development of an effective vaccine. Finally, we present a novel guanosine microparticle with gp145 encapsulated and displayed on its surface. The unique properties of our gp145 microparticle make it amenable to use in future preclinical and clinical trials.

Staphylococcus lugdunensis Endophthalmitis Following Intravitreal Anti-vascular Endothelial Growth Factor Injections.

Staphylococcus lugdunensis is a rare causative organism of endophthalmitis following intravitreal injections. It presents an aggressive disease course with potentially devastating outcomes. In this case, the patient presented late with a severely painful, red eye with a reduced visual acuity from 6/18 to light perception following bilateral intravitreal injections of anti-vascular endothelial growth factor. Strict adherence to the bilateral intravitreal injection protocol meant prevention of infection in the right eye. Intravitreal vancomycin was administered without delay and an emergency vitreous biopsy was performed, confirming S. lugdunensis as the causative organism. An intense course of oral and topical steroids was chosen due to the aggressiveness of this organism. Early vitreo-retinal opinion was sought but the patient was deemed not suitable for vitrectomy due to initial improvements in visual acuity to hand movements. The patient showed improvements in the visual acuity to 1/60, and remains on a weaning regime of oral and topical steroids with no further complications.

Neurotizaciones para la flexión del codo en lesiones traumáticas del plexo braquial / Nerve transfers for elbow flexion in traumatic brachial plexus injuries

Objetivo: Evaluar los resultados de diferentes neurotizaciones utilizadas para la flexión del codo en pacientes con lesión traumática del plexo braquial. materiales y métodos: Entre abril de 2012 y enero de 2019, se operaron 13 pacientes (12 hombres) con lesión traumática del plexo braquial, 5 con parálisis totales sin recuperación, 4 con parálisis totales que recuperaron el tronco inferior parcialmente y 4 con parálisis altas. Las neurotizaciones para la flexión del codo fueron: 3 nervios intercostales con injerto sural a nervio musculocutáneo o su(s) rama(s) motora(s) (4 pacientes), 3 nervios intercostales a nervio musculocutáneo sin injerto (3 pacientes), nervio espinal accesorio a ramas motoras del nervio musculocutáneo con injerto sural (2 pacientes), fascículos del nervio cubital a rama motora del bíceps (3 pacientes) y fascículos del nervio cubital y fascículos del nervio mediano a ramas motoras del bíceps y braquial anterior (3 pacientes). Se evaluaron la fuerza de flexión del codo (M0-M5), el dolor con la escala analógica visual y se utilizó el puntaje DASH. El seguimiento promedio fue de 50 meses. Resultados: La fuerza de flexión del codo fue M5 (1 paciente), M4 (7 pacientes), M3 (1 paciente), M2 (1 paciente) y M1 (2 pacientes). El puntaje DASH promedio fue de 54,1 antes de la cirugía y 29,5 en el posoperatorio. El puntaje de dolor preoperatorio fue de 7 y de 0,9 posoperatorio. No hubo complicaciones. Conclusiones: Las neurotizaciones lograron resultados satisfactorios en la reconstrucción de la flexión activa del codo en pacientes con lesión del plexo braquial. Nivel de Evidencia: IV Serie de casos

Objective: To evaluate the results of different nerve transfers used for elbow flexion in patients with traumatic brachial plexus injury. Materials and methods: Between April 2012 and January 2019, 13 patients (12 men) with traumatic brachial plexus injury underwent surgery. 5 patients had total paralysis and did not recover, 4 had total paralysis and partially recovered the lower trunk, and 4 had high paralysis. The nerve transfers performed for elbow flexion were: 3 intercostal nerves with a sural graft to the musculocutaneous nerve or its motor branch(es) (4 patients), 3 intercostal nerves to the musculocutaneous nerve without graft (3 patients), the accessory spinal nerve to motor branches of the musculocutaneous nerve with sural graft (2 patients), fascicles of the ulnar nerve to the motor branch of the biceps (3 patients) and fascicles of the ulnar nerve and fascicles of the median nerve to the motor branches of the biceps and anterior brachialis (3 patients). We assessed elbow flexion strength (M0-M5), pain on the visual analog scale, and DASH score. The average follow-up was 50 months. Results: Elbow flexion strength was M5 (1 patient), M4 (7 patients), M3 (1 patient), M2 (1 patient), and M1 (2 patients). The mean DASH score was 54.1 before surgery and 29.5 postoperatively. The preoperative pain score was 7 and 0.9 postoperatively. There were no complications. Conclusions: Nerve transfers achieved satisfactory outcomes for active elbow flexion reconstruction in patients with brachial plexus injury. Level of Evidence: IV Case report

Resección de osteoma osteoide vertebral asistida por planificación 3D. Presentación de un caso / Resection of spinal osteoid osteoma assisted by 3D planning. Case report

La localización vertebral de una lesión compatible con un osteoma osteoide requiere, muchas veces, su resección en bloque mar-ginal mediante cirugía. El objetivo de este artículo es informar sobre el uso de la tecnología en impresión 3D para desarrollar guías de corte y así lograr una resección segura y completa de un osteoma osteoide de L1. Presentamos a un varón de 13 años, operado de un osteoma osteoide de L1 y detallamos la planificación preoperatoria con asistencia de la tecnología 3D, la técnica quirúrgica mediante guías de corte impresas y un modelo real de la columna lumbar y el control posoperatorio. Conclusiones: Ante la indicación de cirugía para una lesión compatible con osteoma osteoide en la columna debe decidirse entre la posibilidad de resección intralesional abierta o percutánea y la resección marginal en bloque. Para localizar la lesión durante la cirugía, se utilizan diferentes métodos. En nuestro Servicio, estamos utilizando la tecnología 3D para la planificación preoperatoria de múltiples enfermedades traumatológicas agudas y las secuelas. Esto nos permite una mayor precisión y seguridad en la identificación de los márgenes de resección intraoperatoria, reduciendo, al mínimo, la extracción de tejidos sanos y evitando la inestabilidad posoperatoria. Nivel de Evidencia: IV

The vertebral location of a lesion compatible with an osteoid osteoma often requires a marginal en bloc resection. Our objective is to present the use of 3D printing technology for the development of specific cutting guides that achieve a safe and complete resection of an L1 osteoid osteoma. We present the case of a 13-year-old male who underwent surgery for an L1 osteoid osteoma, de-tailing the preoperative planning assisted by 3D technology, the surgical technique using 3D printed cutting guides, a real model of the lumbar spine, and the postoperative control. Conclusion: Before the surgical indication of a lesion compatible with an osteoid osteoma in the spine, we must decide between the possibility of an open intralesional resection or percutaneous and marginal en bloc resection. Different methods can be used for the intraoperative location of the lesion. In our department, we use 3D technology for preoperative planning of multiple acute and post-traumatic pathologies. This allows us to be precise and safe in the identification of intraoperative resection margins, minimizing the removal of healthy tissues and avoiding postoperative instability. Level of Evidence: IV

Pursuing High-Resolution Structures of Nicotinic Acetylcholine Receptors: Lessons Learned from Five Decades.

Since their discovery, nicotinic acetylcholine receptors (nAChRs) have been extensively studied to understand their function, as well as the consequence of alterations leading to disease states. Importantly, these receptors represent pharmacological targets to treat a number of neurological and neurodegenerative disorders. Nevertheless, their therapeutic value has been limited by the absence of high-resolution structures that allow for the design of more specific and effective drugs. This article offers a comprehensive review of five decades of research pursuing high-resolution structures of nAChRs. We provide a historical perspective, from initial structural studies to the most recent X-ray and cryogenic electron microscopy (Cryo-EM) nAChR structures. We also discuss the most relevant structural features that emerged from these studies, as well as perspectives in the field.

A reversed phase HPLC method for the quantification of HIV gp145 glycoprotein levels from cell culture supernatants.

A reversed phase high performance liquid chromatography (RP-HPLC) method was developed for the quantitative determination of recombinant HIV-1 gp145 produced in CHO-K1 cells, as measured directly from culture supernatants. Samples were diluted in 50% D-PBS and 50% PowerCHO-2 (PC2) spent medium, and resolved on a Zorbax 300SB-C8 Rapid Resolution (2.1 × 50 mm, 3.5 µm) column, fitted with a C8 guard column (Zorbax 300SB-C8, 2.1 × 12.5 mm, 5 µm), using 0.1% TFA and 2% n-propanol in LC-MS water as mobile phase A and 0.1% TFA, 70% isopropanol, and 20% acetonitrile in LC-MS water as mobile phase B. The column temperature was 80 °C, the flow rate was 0.4 mL/min and the absorbance was monitored at 280 nm. The procedures and capabilities of the method were evaluated against the criteria for linearity, limit of detection (LOD), accuracy, repeatability, and robustness as defined by the International Conference on Harmonization (ICH) 2005 Q2(R1) guidelines. Two different variants of the HIV-1 envelope protein (Env), CO6980v0c22 gp145 and SF162 gp140, were analyzed and their retention times were found to be different. The method showed good linearity (R2 = 0.9996), a lower LOD of 2.4 µg/mL, and an average recovery of 101%. The analysis includes measurements of accuracy, inter-user precision, and robustness. Overall, we present a RP-HPLC method that could be applied for the quantitation of cell culture titers for this and other variants of HIV Env following ICH guidelines.

Luxofracturas radiocarpianas: evaluación retrospectiva de una serie de casos / Radiocarpal fracture-dislocation. Retrospective evaluation of a case series

Introducción: Las luxofracturas radiocarpianas consisten en la pérdida total de contacto entre las superficies articulares de la primera fila del carpo y del radio. Se producen por traumatismos de alta energía. El objetivo de este estudio fue evaluar retrospectivamente una serie de casos para comparar la incidencia de estas lesiones, el manejo terapéutico y los resultados funcionales con la bibliografía publicada por centros de referencia en esta enfermedad. Materiales y métodos: Entre febrero de 2018 y junio de 2020, se evaluó, en forma retrospectiva, a pacientes con luxofractura radiocarpiana, clasificada en tipos I y II según Dumontier. Criterios de inclusión: hombres y mujeres >18 años con luxofractura radiocarpiana cerrada o abierta y un seguimiento mínimo de 3 meses. Se llevó a cabo un seguimiento clínico/por imágenes mediante radiografías, el cuestionario DASH, la escala de muñeca modificada de la Clínica Mayo, la escala analógica visual para dolor y el PSQ-18. Resultados: Se evaluó a 8 pacientes con 9 lesiones, y un seguimiento promedio de 8 meses. Las luxaciones eran 4 tipo I y 5 tipo II. Todos fueron operados. Según valores finales, hubo 2 resultados excelentes, 6 buenos/aceptables y uno pobre. Conclusión: El mejor método para el tratamiento definitivo es quirúrgico. La correcta clasificación y el estudio de la enfermedad tienen un rol fundamental en la toma de decisiones terapéuticas. Nivel de Evidencia: IV

Introduction: Radiocarpal fracture-dislocations consist of the total loss of contact between the articular surfaces of the first row of the carpus and the radius. They are caused by high-energy trauma. The purpose of the work is to retrospectively evaluate a series of cases to compare the incidence of these lesions, their therapeutic management and functional outcomes with the literature published by reference centers in this pathology. Materials and methods: Between February 2018 and June 2020 we retrospectively evaluated patients with radiocarpal fracture-dislocations, which were classified into groups I and II according to Dumontier. Inclusion criteria: males and females over 18 years of age with closed or open radiocarpal fracture-dislocations with a minimum follow-up of 3 months. A clinical/imaging follow-up was carried out using radiographs, the DASH questionnaire (Disabilities of the Arm, Shoulder and Hand), Modified Mayo Wrist Score, visual analog scale (VAS) and Patient Satisfaction Questionnaire Short Form (PSQ-18). Results: Eight patients with nine lesions with an average follow-up of 8 months were evaluated. Lesions were grouped into type I (4) and type II (5). All were surgically operated. According to the final values, outcomes were excellent in two cases, good/acceptable in six, and poor in one. Conclusion: We believe that the best method for definitive treatment is surgical. The correct classification and study of the pathology will play a fundamental role in making therapeutic decisions. Level of Evidence: IV

A recombinant gp145 Env glycoprotein from HIV-1 expressed in two different cell lines: Effects on glycosylation and antigenicity.

The envelope glycoprotein (Env) of the human immunodeficiency virus (HIV), has been the primary target for the development of a protective vaccine against infection. The extensive N-linked glycosylation on Env is an important consideration as it may affect efficacy, stability, and expression yields. The expression host has been shown to influence the extent and type of glycosylation that decorates the protein target. Here, we report the glycosylation profile of the candidate subtype C immunogen CO6980v0c22 gp145, which is currently in Phase I clinical trials, produced in two different host cells: CHO-K1 and Expi293F. The amino acid sequence for both glycoproteins was confirmed to be identical by peptide mass fingerprinting. However, the isoelectric point of the proteins differed; 4.5-5.5 and 6.0-7.0 for gp145 produced in CHO-K1 and Expi293F, respectively. These differences in pI were eliminated by enzymatic treatment with sialidase, indicating a large difference in the incorporation of sialic acid between hosts. This dramatic difference in the number of sialylated glycans between hosts was confirmed by analysis of PNGase F-released glycans using MALDI-ToF MS. These differences in glycosylation, however, did not greatly translate into differences in antibody recognition. Biosensor assays showed that gp145 produced in CHO-K1 had similar affinity toward the broadly neutralizing antibodies, 2G12 and PG16, as the gp145 produced in Expi293F. Additionally, both immunogens showed the same reactivity against plasma of HIV-infected patients. Taken together, these results support the notion that there are sizeable differences in the glycosylation of Env depending on the expression host. How these differences translate to vaccine efficacy remains unknown.

Nicotinic Acetylcholine Receptors in HIV: Possible Roles During HAND and Inflammation.

Infection with the human immunodeficiency virus (HIV) remains a threat to global health. Since its discovery, many efforts have been directed at understanding the mechanisms and consequences of infection. Although there have been substantial advances since the advent of antiretroviral therapy, there are still complications that significantly compromise the health of infected patients, particularly, chronic inflammation and HIV-associated neurocognitive disorders (HAND). In this review, a new perspective is addressed in the field of HIV, where the alpha7 nicotinic acetylcholine receptor (α7-nAChR) is the protagonist. We comprehensively discuss the available evidence implicating α7-nAChRs in the context of HIV and provide possible explanations about its role in HAND and inflammation in both the central nervous system and the periphery.

The Cholinergic Anti-Inflammatory Response and the Role of Macrophages in HIV-Induced Inflammation.

Macrophages are phagocytic immune cells that protect the body from foreign invaders and actively support the immune response by releasing anti- and proinflammatory cytokines. A seminal finding revolutionized the way macrophages are seen. The expression of the neuronal alpha7 nicotinic acetylcholine receptor (α7-nAChR) in macrophages led to the establishment of the cholinergic anti-inflammatory response (CAR) in which the activation of this receptor inactivates macrophage production of proinflammatory cytokines. This novel neuroimmune response soon began to emerge as a potential target to counteract inflammation during illness and infection states. Human immunodeficiency virus (HIV)-infected individuals suffer from chronic inflammation that persists even under antiretroviral therapy. Despite the CAR's importance, few studies involving macrophages have been performed in the HIV field. Evidence demonstrates that monocyte-derived macrophages (MDMs) recovered from HIV-infected individuals are upregulated for α7-nAChR. Moreover, in vitro studies demonstrate that addition of an HIV viral constituent, gp120IIIB, to uninfected MDMs also upregulates the α7-nAChR. Importantly, contrary to what was expected, activation of upregulated α7-nAChRs in macrophages does not reduce inflammation, suggesting a CAR disruption. Although it is reasonable to consider this receptor as a pharmacological target, additional studies are necessary since its activity seems to differ from that observed in neurons.

The alpha7-nicotinic receptor contributes to gp120-induced neurotoxicity: implications in HIV-associated neurocognitive disorders.

Currently, there are no specific therapies to treat HIV-1 associated neurocognitive disorders (HAND). The HIV-1 envelope, gp120, induces neuropathological changes similar to those in HAND patients; furthermore, it triggers an upregulation of the α7-nicotinic acetylcholine receptor (α7-nAChR), facilitating intracellular calcium overload and neuronal cell death. Using a gp120IIIB-transgenic mouse (gp120-tgm) model, we demonstrate that α7-nAChRs are upregulated on striatal neurons. Activation of α7-nAChRs leads to an increase in both intracellular calcium and percentage of apoptotic cells, which can be abrogated by antagonizing the receptor, suggesting a role for α7-nAChRs in gp120-induced neurotoxicity. Moreover, we demonstrate for the first time that gp120-tgm have learning deficiencies on a striatum-dependent behavioral task. They also show locomotor deficiencies, which improved with α7-nAChR antagonists, further supporting a role for this receptor in gp120-induced neurotoxicity. Together, these results uncover a new mechanism through which gp120-induced modulation of α7-nAChRs in the striatum can contribute to HAND development.

A Panel of Slow-Channel Syndrome Mice Reveals a Unique Locomotor Behavioral Signature.

Muscle nicotinic acetylcholine receptor (nAChR) mutations can lead to altered channel kinetics and neuromuscular junction degeneration, a neurodegenerative disorder collectively known as slow-channel syndrome (SCS). A multivariate analysis using running wheels was used to generate activity profiles for a variety of SCS models, uncovering unique locomotor patterns for the different nAChR mutants. Particularly, the αL251T and ɛL269F mutations exhibit decreased event distance, duration, and velocity over a period of 24 hours. Our approach suggests a robust relationship between the pathophysiology of SCS and locomotor activity.

Implementation Issues of Adaptive Energy Detection in Heterogeneous Wireless Networks.

Spectrum sensing (SS) enables the coexistence of non-coordinated heterogeneous wireless systems operating in the same band. Due to its computational simplicity, energy detection (ED) technique has been widespread employed in SS applications; nonetheless, the conventional ED may be unreliable under environmental impairments, justifying the use of ED-based variants. Assessing ED algorithms from theoretical and simulation viewpoints relies on several assumptions and simplifications which, eventually, lead to conclusions that do not necessarily meet the requirements imposed by real propagation environments. This work addresses those problems by dealing with practical implementation issues of adaptive least mean square (LMS)-based ED algorithms. The paper proposes a new adaptive ED algorithm that uses a variable step-size guaranteeing the LMS convergence in time-varying environments. Several implementation guidelines are provided and, additionally, an empirical assessment and validation with a software defined radio-based hardware is carried out. Experimental results show good performance in terms of probabilities of detection ( P d > 0 . 9 ) and false alarm ( P f ∼ 0 . 05 ) in a range of low signal-to-noise ratios around [ - 4 , 1 ] dB, in both single-node and cooperative modes. The proposed sensing methodology enables a seamless monitoring of the radio electromagnetic spectrum in order to provide band occupancy information for an efficient usage among several wireless communications systems.

Expression of CHRFAM7A and CHRNA7 in neuronal cells and postmortem brain of HIV-infected patients: considerations for HIV-associated neurocognitive disorder.

Despite the recent advances in antiretroviral therapy, human immunodeficiency virus type 1 (HIV-1) remains a global health threat. HIV-1 affects the central nervous system by releasing viral proteins that trigger neuronal death and neuroinflammation, and promotes alterations known as HIV-associated neurocognitive disorders (HAND). This disorder is not fully understood, and no specific treatments are available. Recently, we demonstrated that the HIV-1 envelope protein gp120IIIB induces a functional upregulation of the α7-nicotinic acetylcholine receptor (α7) in neuronal cells. Furthermore, this upregulation promotes cell death that can be abrogated with receptor antagonists, suggesting that α7 may play an important role in the development of HAND. The partial duplication of the gene coding for the α7, known as CHRFAM7A, negatively regulates α7 expression but its role in HIV infection has not been studied. Hence, we studied both CHRNA7 and CHRFAM7A regulation patterns in various gp120IIIB in vitro conditions. In addition, we measured CHRNA7 and CHRFAM7A expression levels in postmortem brain samples from patients suffering from different stages of HAND. Our results demonstrate the induction of CHRNA7 expression accompanied by a significant downregulation of CHRFAM7A in neuronal cells when exposed to pathophysiological concentrations of gp120IIIB. Our results suggest a dysregulation of CHRFAM7A and CHRNA7 expressions in the basal ganglia from postmortem brain samples of HIV+ subjects and expand the current knowledge about the consequences of HIV infection in the brain.

Activation of the Macrophage α7 Nicotinic Acetylcholine Receptor and Control of Inflammation.

Inflammatory responses to stimuli are essential body defenses against foreign threats. However, uncontrolled inflammation may result in serious health problems, which can be life-threatening. The α7 nicotinic acetylcholine receptor, a ligand-gated ion channel expressed in the nervous and immune systems, has an essential role in the control of inflammation. Activation of the macrophage α7 receptor by acetylcholine, nicotine, or other agonists, selectively inhibits production of pro-inflammatory cytokines while leaving anti-inflammatory cytokines undisturbed. The neural control of this regulation pathway was discovered recently and it was named the cholinergic anti-inflammatory pathway (CAP). When afferent vagus nerve terminals are activated by cytokines or other pro-inflammatory stimuli, the message travels through the afferent vagus nerve, resulting in action potentials traveling down efferent vagus nerve fibers in a process that eventually leads to macrophage α7 activation by acetylcholine and inhibition of pro-inflammatory cytokines production. The mechanism by which activation of α7 in macrophages regulates pro-inflammatory responses is subject of intense research, and important insights have thus been made. The results suggest that activation of the macrophage α7 controls inflammation by inhibiting NF-κB nuclear translocation, and activating the JAK2/STAT3 pathway among other suggested pathways. While the α7 is well characterized as a ligand-gated ion channel in neurons, whole-cell patch clamp experiments suggest that α7's ion channel activity, defined as the translocation of ions across the membrane in response to ligands, is absent in leukocytes, and therefore, ion channel activity is generally assumed not to be required for the operation of the CAP. In this perspective, we briefly review macrophage α7 activation as it relates to the control of inflammation, and broaden the current view by providing single-channel currents as evidence that the α7 expressed in macrophages retains its ion translocation activity despite the absence of whole-cell currents. Whether this ion-translocating activity is relevant for the proper operation of the CAP or other important physiological processes remains obscure.

The α7-nicotinic receptor is upregulated in immune cells from HIV-seropositive women: consequences to the cholinergic anti-inflammatory response.

Antiretroviral therapy partially restores the immune system and markedly increases life expectancy of HIV-infected patients. However, antiretroviral therapy does not restore full health. These patients suffer from poorly understood chronic inflammation that causes a number of AIDS and non-AIDS complications. Here we show that chronic inflammation in HIV+ patients may be due to the disruption of the cholinergic anti-inflammatory pathway by HIV envelope protein gp120IIIB. Our results demonstrate that HIV gp120IIIB induces α7 nicotinic acetylcholine receptor (α7) upregulation and a paradoxical proinflammatory phenotype in macrophages, as activation of the upregulated α7 is no longer capable of inhibiting the release of proinflammatory cytokines. Our results demonstrate that disruption of the cholinergic-mediated anti-inflammatory response can result from an HIV protein. Collectively, these findings suggest that HIV tampering with a natural strategy to control inflammation could contribute to a crucial, unresolved problem of HIV infection: chronic inflammation.

Potential medication errors associated with computer prescriber order entry.

INTRODUCTION: To assess the frequency of medication errors (ME) induced or enhanced by computerized physician order entry (CPOE). Error type, drug classes involved, specialty, patient outcome and system failures were also evaluated. METHODS: Observational quantitative study in a large tertiary care medical center over March 2012 3 years after CPOE implementation. Pharmacists detected ME associated with CPOE (those that wouldn't have occurred if the clinician had prescribed manually) and unassociated in pharmacological treatments in inpatients of 13 specialties (421 beds). Main outcome measured were ME associated and unassociated with CPOE. RESULTS: We found 714 ME with 85.857 drug prescriptions (a 0.8 % error rate, 95 % CI 0.6-0.7). Percentage of error associated with CPOE was 77.7 %. The main types of error related to CPOE were wrong medication selection (20.9 %) and improper data placement (20.3 %). Failures with medications prescribed in primary care, unavailable in the hospital pharmacy, were involved in 21.6 % of all ME. Errors involving surgical specialties were double those involving medical specialties (1.2 vs. 0.6 %). Most ME associated with CPOE were potential errors (90 %). During the study system failures occurred four times. CONCLUSIONS: The use of CPOE minimises the occurrence of medication errors, however, they still occur. Most errors are associated with the CPOE technology. We therefore face a new challenge in the prevention of ME that require a change in strategy for patient safety. Continued training of prescribers, standardization of the electronic prescription programs and integration between computer applications in hospitals and with primary care should be a priority.