Pharmacology and Therapeutic Potential of Benzothiazole Analogues for Cocaine Use Disorder.

Pharmacological targeting of the dopamine D4 receptor (D4R)─expressed in brain regions that control cognition, attention, and decision-making─could be useful for several neuropsychiatric disorders including substance use disorders (SUDs). This study focused on the synthesis and evaluation of a novel series of benzothiazole analogues designed to target D4R. We identified several compounds with high D4R binding affinity (Ki ≤ 6.9 nM) and >91-fold selectivity over other D2-like receptors (D2R, D3R) with diverse partial agonist and antagonist profiles. Novel analogue 16f is a potent low-efficacy D4R partial agonist, metabolically stable in rat and human liver microsomes, and has excellent brain penetration in rats (AUCbrain/plasma > 3). 16f (5-30 mg/kg, i.p.) dose-dependently decreased iv cocaine self-administration in rats, consistent with previous results produced by D4R-selective antagonists. Off-target antagonism of 5-HT2A or 5-HT2B may also contribute to these effects. Results with 16f support further efforts to target D4R in SUD treatment.

Randomized, controlled clinical trial of the DIALIVE liver dialysis device versus standard of care in patients with acute-on- chronic liver failure.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is characterized by severe systemic inflammation, multi-organ failure and high mortality rates. Its treatment is an urgent unmet need. DIALIVE is a novel liver dialysis device that aims to exchange dysfunctional albumin and remove damage- and pathogen-associated molecular patterns. This first-in-man randomized-controlled trial was performed with the primary aim of assessing the safety of DIALIVE in patients with ACLF, with secondary aims of evaluating its clinical effects, device performance and effect on pathophysiologically relevant biomarkers. METHODS: Thirty-two patients with alcohol-related ACLF were included. Patients were treated with DIALIVE for up to 5 days and end points were assessed at Day 10. Safety was assessed in all patients (n = 32). The secondary aims were assessed in a pre-specified subgroup that had at least three treatment sessions with DIALIVE (n = 30). RESULTS: There were no significant differences in 28-day mortality or occurrence of serious adverse events between the groups. Significant reduction in the severity of endotoxemia and improvement in albumin function was observed in the DIALIVE group, which translated into a significant reduction in the CLIF-C (Chronic Liver Failure consortium) organ failure (p = 0.018) and CLIF-C ACLF scores (p = 0.042) at Day 10. Time to resolution of ACLF was significantly faster in DIALIVE group (p = 0.036). Biomarkers of systemic inflammation such as IL-8 (p = 0.006), cell death [cytokeratin-18: M30 (p = 0.005) and M65 (p = 0.029)], endothelial function [asymmetric dimethylarginine (p = 0.002)] and, ligands for Toll-like receptor 4 (p = 0.030) and inflammasome (p = 0.002) improved significantly in the DIALIVE group. CONCLUSIONS: These data indicate that DIALIVE appears to be safe and impacts positively on prognostic scores and pathophysiologically relevant biomarkers in patients with ACLF. Larger, adequately powered studies are warranted to further confirm its safety and efficacy. IMPACT AND IMPLICATIONS: This is the first-in-man clinical trial which tested DIALIVE, a novel liver dialysis device for the treatment of cirrhosis and acute-on-chronic liver failure, a condition associated with severe inflammation, organ failures and a high risk of death. The study met the primary endpoint, confirming the safety of the DIALIVE system. Additionally, DIALIVE reduced inflammation and improved clinical parameters. However, it did not reduce mortality in this small study and further larger clinical trials are required to re-confirm its safety and to evaluate efficacy. CLINICAL TRIAL NUMBER: NCT03065699.

Pregnant woman from southern Peru with rabies infection who delivered a healthy baby.

Rabies in pregnancy is rare with a high mortality. We report a pregnant woman who developed urban rabies from the bite of an infected dog. An emergency Cesarean section was performed at 31 weeks of gestation, and a premature baby was delivered who survived and did not develop rabies. The mother, however, suffered a rapid clinical deterioration and was admitted to intensive care where a Milwaukee protocol was followed. The patient survived 19 months but developed severe neurological sequelae secondary to rabies encephalitis and finally died of respiratory failure.

Control del hábito en la mordida abierta / Control of the habit in the open bite

Se presenta un dispositivo diseñado con el obje-tivo de impedir la interposición lingual en un caso con una severa mordida abierta esqueletal, re-suelta con tratamiento ortodóncico no quirúrgico. La terapéutica se complementa con la extracción de los cuatro segundos molares permanentes, con el objetivo tanto de resolver la discrepancia dentoalveolar, como la anomalía basal.

It is presented a device designed with the purpose of preventing tongue interposition in a severe skeletal open bite case, resolved by non-surgical orthodontic treatment. All four second permanent molars extraction complements the therapeutics, with the objective of solving both the dentoalveolar discrepancy as well as the basal anomaly.

Viability of anastomoses with coupler in extra-intracranial bypass: cadaveric study.

BACKGROUND: The time required to perform an anastomosis in extra-intracranial bypass is approximately 20 to 60 minutes. The search for alternative methods to reduce the ischemic time remains vital. OBJECTIVE: To evaluate Coupler anastomosis for extra-intracranial bypass in cadavers. METHODS: In 8 fresh adult cadavers, the saphenous vein and radial artery were used as donor vessels. The superficial temporal and the extracranial internal and external carotid arteries were dissected. A wide craniotomy with a sylvian fissure opening was performed, exposing the middle cerebral and supraclinoid internal carotid arteries. The Coupler devices were tested in all 8 cadavers. The diameter of the donor and recipient vessels as well as the time required to perform the anastomosis were measured. Bypass permeability was evaluated by injecting saline solution under pressure, checking for leaks. RESULTS: The anastomoses were successfully performed in all specimens. The size of the head of the fitting Coupler required the performance of a wide craniotomy (6 × 6 cm) and a wide opening of the sylvian fissure. The time required to perform each anastomosis ranged from 4 to 7 minutes, being easier with the radial artery than with the saphenous vein. CONCLUSION: Coupler devices are helpful to perform the anastomoses, because they significantly reduce ischemia time. Their use is easier at the M1 segment, just before the bifurcation and after takeoff of the lenticulostriate arteries, and in the M2 segment. It would be advisable to have a smaller coupling system, allowing maneuverability in the deeper areas where space is limited.

[National consensus of diagnosis and treatment of non-small cell lung cancer]. / Consenso nacional de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas.

Mexican specialists in oncology, oncologic surgery, thoracic surgery, pneumology, pathology, molecular biology, anesthesiology, algology, psychology, nutrition, and rehabilitation (all of them experts in lung cancer treatment) in order to develop the National Consensus on Lung Cancer. The consensus has been developed as an answer to the need of updated Mexican guidelines for the optimal treatment of the disease, as well as to the requirements that such guidelines be established by multidisciplinary panel, depicting the current attention given to cancer lung cases in Mexico. Thus, this paper analyses the epidemiological review, screening, diagnosis, staging, pathology, translational medicine, and the suitable therapies for early, locally advanced, and metastatic disease in the first, second, and third lines of management, as well as rehabilitation and palliative measures.

Diagnóstico tardío de la aspiración de un cuerpo extraño / Delayed diagnosis of foreign body aspiration

Introducción. La aspiración de cuerpos extraños es un problema común en el paciente pediátrico y representa una causa importante de morbilidad y mortalidad. En Estados Unidos se considera la causa de 7% de las muertes accidentales de niños de entre 1 y 3 años de edad. La presentación clínica requiere de un alto grado de sospecha diagnóstica por el médico, sobre todo cuando el antecedente del evento de atragantamiento no es claro en la historia clínica debido a que la exploración física y los hallazgos radiológicos son inespecíficos en la mayoría de las ocasiones. Caso clínico. Se presenta el caso de un adolescente de 14 años que, a pesar de tener el antecedente de la aspiración de un cuerpo extraño, no se le dio importancia y sus síntomas se confundieron con otras entidades. Recibió diversos tratamientos pero sus síntomas se mantuvieron por un año. Fue remitido a la Unidad de Neumología Pediátrica Fernando Katz del Instituto Nacional de Enfermedades Respiratorias donde se realizó el estudio broncoscópico y la extracción del cuerpo extraño del bronquio intermedio. Conclusiones. El diagnóstico tardío ocasiona problemas respiratorios que van desde la obstrucción de las vías aéreas (que pone en riesgo la vida) hasta síntomas respiratorios crónicos como sibilancias e infecciones recurrentes de las vías respiratorias. Es común también que estos síntomas se confundan con otras entidades patológicas como el asma, el reflujo gastroesofágico y la disfunción laríngea.

Background. Aspiration of foreign bodies in the central airway is a common problem in the pediatric population, representing a major cause of morbidity and mortality in our country. In the U.S., foreign body aspiration is the cause for 7% of accidental deaths in children between 1 and 3 years of age. Clinical diagnosis requires a high degree of suspicion in the medical history especially when the choking event is unclear in the clinical history because physical examination and radiological findings have a low sensitivity. Case report. We present the case of a 14-year-old male with a history of foreign body aspiration. The patient's symptoms were given little importance. A 1-year delay in diagnosis occurred due to symptoms mimicking other pathologies. The patient was referred to the Pediatric Pulmonology Unit "Fernando Katz" of the National Institute of Respiratory Diseases where bronchoscopic exploration was performed with removal of foreign body (plastic object) from the intermediary bronchus. Conclusions. Delayed diagnosis causes respiratory problems ranging from life-threatining airway obstruction to chronic respiratory symptoms such as wheezing and recurrent respiratory infections. It has been shown that these symptoms can be confused with other pathologies such as asthma.

Endoscopic endonasal clipping of a ruptured vertebral-posterior inferior cerebellar artery aneurysm: technical case report.

BACKGROUND AND IMPORTANCE: Aneurysms arising from the vertebral and posterior inferior cerebellar artery complex account for only 0.5 to 3% of all aneurysms. Surgery for these aneurysms is technically challenging because of the deep location and intimate relation with the medulla and lower cranial nerves. The authors report the case of a patient with a right vertebral-posterior inferior cerebellar artery complex (VA-PICA) aneurysm that was successfully clipped via an extended endoscopic endonasal transclival approach. CLINICAL PRESENTATION: A 74-year-old woman with the sudden onset of severe headache, nausea, and vomiting was admitted to our hospital. A computed tomography (CT) of the brain revealed diffuse subarachnoid hemorrhage associated with intraventricular hemorrhage and incipient hydrocephalus. Cerebral angiography revealed a 1.2-mm aneurysm arising at the origin of the right PICA. The aneurysm was considered unsuitable for selective coil embolization, so neck clipping was performed. With the use of an extended endoscopic endonasal transclival approach, the aneurysm was accurately reached endoscopically and successfully clipped from the parent artery. The patient was discharged neurologically intact. CONCLUSION: To the best of the authors' knowledge, this is the first report of a successfully treated VA-PICA ruptured aneurysm using a pure endoscopic endonasal transclival approach. Endoscopic surgery may be added to the armamentarium of procedures for the treatment of posterior circulation aneurysms.

Intervención familiar sobre la conducta suicida en la policlínica “Manuel Piti Fajardo año 2002 / Family intervention on suicidal behaviour at Manuel Piti Fajardo Policlinic 2002

Se realizó un estudio de intervención para precisar la eficacia de una estrategia de intervención familiar en la atención de individuos con intentos suicidas, de edad mayor o igual a 18 años en la Policlínica “Manuel Pity Fajardo” del municipio las Tunas, la muestra estuvo constituida por 25 individuos. Se realizaron acciones de salud sobre el individuo: tratamiento de las enfermedades físicas y mentales subyacentes a través de psicofármacos y psicoterapia breve. La familia: se mejoró el funcionamiento mediante la psicoterapia de familia. A los resultados se le realizaron pruebas de significación estadísticas (Test de Análisis de Proporciones). Con la intervención se reajustaron los factores desencadenantes de la conducta suicida, modificación de actitudes respecto al conflicto (76 por ciento). El funcionamiento familiar mejoró significativamente (Test de Percepción de funcionamiento familiar). La evolución de los pacientes dispensarizados fue favorable en el 88(AU)