The Acute Effects of Multiple Doses of Methamphetamine on Locomotor Activity and Anxiety-Like Behavior in Adolescent and Adult Mice

Methamphetamine (MA) is a highly addictive psychomotor stimulant drug. Research has shown that the acute effects of MA can be modulated by age, although previous findings from our lab do not find age differences in the effects of MA. Relatively little research has examined the effects of adolescent MA exposure; thus, it is important to understand how MA affects adolescent behavior and brain function compared to adults. In order to better understand the age differences in the effects of acute MA exposure, this research examined the effects of MA exposure on locomotor and anxiety-like behavior and plasma corticosterone levels in adolescent and adult C57BL/6 J mice. Mice were exposed to saline, 2 mg/kg MA, or 4 mg/kg MA and behavior was measured in the open field test. Immediately following behavioral testing, serum was collected, and plasma corticosterone levels were measured. MA-exposed mice showed increased locomotor activity and anxiety-like behavior compared to saline controls, regardless of age and dose of MA. However, adolescent mice showed the greatest locomotor response to the high dose of MA (4 mg/kg), whereas the adult mice showed the greatest locomotor response to the low dose of MA (2 mg/kg). There were no differences in stereotyped behavior between the adolescent and adult mice exposed to the low dose of MA (2 mg/kg) and the high dose of MA (4 mg/kg). There was no effect of MA exposure on plasma corticosterone levels. These data suggest age modulates the locomotor response to MA and further research is warranted to determine the developmental neurobiological mechanism underlying the dose-response age differences in the response to acute MA exposure

Experiencias de practicantes: Una mirada reflexiva sobre la propia formación.

El presente trabajo tiene el objeto de compartir nuestra experiencia de formación en el marco del desarrollo de las prácticas profesionales como practicantes e integrantes del equipo de Praxis IV “Práctica docente” y del Proyecto de Extensión “Intercambio y formación entre universidad e instituciones educativas: la formación de formadores como responsabilidad conjunta”. La propuesta es organizada por los equipos docentes de los Profesorados en Educación (Educación Inicial, Educación Especial y Ciencias de la Educación), y la participación de los docentes co-formadores de las instituciones educativas del medio que todos los años reciben practicantes/residentes en sus aulas. Este espacio también convoca a los/las estudiantes de estas carreras, que están desarrollando sus prácticas docentes en dichas instituciones. Pretendiendo así superar la distancia cada vez mayor entre universidad y escuelas, siendo el propósito fundamental potenciar la interacción, convergencia y cooperación profesional entre ambos espacios educativos. En este sentido es que se plantea la conformación de un grupo de trabajo heterogéneo, que permita dar respuestas a múltiples situaciones que se suceden de forma diferente en la cotidianeidad educativa, ya que la realidad interna de las aulas es un complejo entramado difícilmente explicable. Desde aquí se busca generar herramientas (teóricas y prácticas), que sirvan de apoyo al docente co-formador para comprometerse con la tarea de seguimiento y formación de los futuros profesores en los espacios de práctica profesional. Para quienes participamos en calidad de estudiantes-practicantes de la carrera de Ciencias de la Educación, esta experiencia ha constituido un valioso aporte ya que, al ser este espacio conformado por múltiples actores, nos ha permitido enriquecer nuestro marco referencial para reflexionar las propias vivencias. La participación en el proyecto constituye un espacio central en la formación desde y para la práctica, particularmente en la formación de formadores, el acompañamiento a docentes noveles y la capacitación de docentes en ejercicio. Llevándonos a reflexionar sobre las experiencias áulicas y vehiculizar su comprensión, la construcción conjunta de conocimiento y favorecer procesos de comunicación e intercambio que faciliten un vínculo de compromiso diferente con el acto pedagógico

Novel mutations in human and mouse SCN4A implicate AMPK in myotonia and periodic paralysis

Mutations in the skeletal muscle channel (SCN4A), encoding the Nav1.4 voltage-gated sodium channel, are causative of a variety of muscle channelopathies, including non-dystrophic myotonias and periodic paralysis. The effects of many of these mutations on channel function have been characterized both in vitro and in vivo. However, little is known about the consequences of SCN4A mutations downstream from their impact on the electrophysiology of the Nav1.4 channel. Here we report the discovery of a novel SCN4A mutation (c.1762A>G; p.I588V) in a patient with myotonia and periodic paralysis, located within the S1 segment of the second domain of the Nav1.4 channel. Using N-ethyl-N-nitrosourea mutagenesis, we generated and characterized a mouse model (named draggen), carrying the equivalent point mutation (c.1744A>G; p.I582V) to that found in the patient with periodic paralysis and myotonia. Draggen mice have myotonia and suffer from intermittent hind-limb immobility attacks. In-depth characterization of draggen mice uncovered novel systemic metabolic abnormalities in Scn4a mouse models and provided novel insights into disease mechanisms. We discovered metabolic alterations leading to lean mice, as well as abnormal AMP-activated protein kinase activation, which were associated with the immobility attacks and may provide a novel potential therapeutic target

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Developmental Methamphetamine Exposure Results in Short- and Long-Term Alterations in HPA Axis-Associated Proteins

Developmental exposure to methamphetamine (MA) causes long-term behavioral and cognitive deficits. One pathway through which MA might induce these deficits is by elevating glucocorticoid levels. Glucocorticoid overexposure during brain development can lead to long-term disruptions in the hypothalamic-pituitary-adrenal (HPA) axis. These disruptions affect the regulation of stress responses and may contribute to behavioral and cognitive deficits reported following developmental MA exposure. Furthermore, alterations in proteins associated with the HPA axis, including vasopressin, oxytocin, and glucocorticoid receptors (GR), are correlated with disruptions in mood and cognition. We therefore hypothesized that early MA exposure will result in short- and long-term alterations in the expression of HPA axis-associated proteins. Male mice were treated with MA (5 mg/kg daily) or Saline from postnatal day (P) 11–20. At P20 and P90, mice were perfused and their brains processed for vasopressin, oxytocin, and GR-immunoreactivity within HPA axis-associated regions. At P20, there was a significant decrease in the number of vasopressin-immunoreactive cells and area occupied by vasopressin-immunoreactiviy in the paraventricular nucleus (PVN) of MA-treated mice, but no difference in oxytocin-immunoreactivity in the PVN, or GR-immunoreactivity in the hippocampus or PVN. In the central nucleus of the amygdala, area occupied by GR-immunoreactivity was decreased by MA. At P90, the number of vasopressin-immunoreactive cells was still decreased, but the area occupied by vasopressin-immunoreactivity no longer differed from Saline controls. No effects of MA were found on oxytocin or GR-immunoreactivity at P90. Thus developmental MA exposure has short- and long-term effects on vasopressin-immunoreactivity and short-term effects on GR-immunoreactivity

Beyond methamphetamine: Documenting the implementation of the Matrix model of substance use treatment for opioid users in a South African setting

INTRODUCTION: The Matrix model of substance use treatment has been evaluated extensively in the United States as an effective treatment for methamphetamine use disorders. Since 2007, the Matrix model has been implemented in Cape Town, South Africa, where one in four treatment-seeking individuals are primarily opioid rather than stimulant users. Yet, there has been limited data on the application of the Matrix model for other types of substance use disorders in a resource-limited setting. METHODS: We compared primary opioid and primary methamphetamine users seeking treatment at the first certified Matrix model substance use treatment site in Cape Town, South Africa from 2009–2014 (n=1,863) on engagement in treatment, an important early predictor of later substance use treatment outcomes, and urine-verified abstinence at treatment exit. RESULTS: Compared to primary opioid users, primary methamphetamine users had over 50% greater odds of initiating treatment (defined as attending at least one treatment session following intake; OR=1.55; 95%CI: 1.24–1.94), and 4.5 times greater odds of engaging in treatment (i.e., attending at least four treatment sessions; OR=4.48; 95%CI: 2.27–8.84). There were no significant differences in rates of urine-verified abstinence at treatment exit. CONCLUSIONS: Results suggest primary opioid users may experience additional barriers to treatment initiation and engagement with Matrix model substance use treatment, yet those who enter treatment are equally as likely compared to primary methamphetamine users to be abstinent at treatment exit. Findings highlight the need for additional strategies to optimize treatment initiation and engagement among primary opioid users in this setting, for instance by integrating medication-assisted treatment (e.g., methadone)

Methicillin-Resistant Staphylococcus aureus USA300 Latin American Variant in Patients Undergoing Hemodialysis and HIV Infected in a Hospital in Bogotá, Colombia.

We aimed to determine the prevalence of MRSA colonization and examine the molecular characteristics of colonizing isolates in patients receiving hemodialysis and HIV-infected in a Colombian hospital. Patients on hemodialysis and HIV-infected were prospectively followed between July 2011 and June 2012 in Bogota, Colombia. Nasal and axillary swabs were obtained and cultured. Colonizing S. aureus isolates were identified by standard and molecular techniques. Molecular typing was performed by using pulse-field gel electrophoresis and evaluating the presence of lukF-PV/lukS-PV by PCR. A total of 29% (n = 82) of HIV-infected and 45.5% (n = 15) of patients on hemodialysis exhibited S. aureus colonization. MSSA/MRSA colonization was observed in 28% and 3.6% of the HIV patients, respectively and in 42.4% and 13.3% of the hemodialysis patients, respectively. Staphylococcal cassette chromosome mec typing showed that four MRSA isolates harbored the type IV cassette, and one type I. In the hemodialysis group, two MRSA isolates were classified as belonging to the USA300-LV genetic lineage. Conversely, in the HIV infected group, no colonizing isolates belonging to the USA300-Latin American Variant (UDA300-LV) lineage were identified. Colonizing isolates recovered from the HIV-infected group belonged to the prevalent hospital-associated clones circulating in Latin America (Chilean [n = 1] and Pediatric [n = 2]). The prevalence of MRSA colonization in the study groups was 3.6% (HIV) and 13.3% (hemodialysis). Surveillance programs should be implemented in this group of patients in order to understand the dynamics of colonization and infection in high-risk patients

Distinct Clinical Presentations and Outcomes of Hospitalized Adults with the SARS-CoV-2 Infection Occurring during the Omicron Variant Surge

The COVID-19 Omicron variant has imposed a tremendous burden on healthcare services. We characterized the types of the Omicron variant-associated hospitalizations and their associations with clinical outcomes. Consecutive adults hospitalized with COVID-19 during the Omicron variant surge period of 1–14 January 2022, were classified into one of three groups based on their clinical presentations on admission: Group 1—primary COVID-19; Group 2—extrapulmonary manifestations of COVID-19; and Group 3—incidental COVID-19. Of the 500 patients who were hospitalized, 51.4% fell into Group 1, 16.4% into Group 2, and 32.2% into Group 3. The patients in Groups 1 and 2 were older, with higher proportions of comorbidities than patients in Group 3. The Group 1 patients had the highest mortality rate (15.6%), followed by Group 2 (8.5%), and Group 3 (0.6%), with adjusted odds ratios (OR) of 22.65 (95% confidence interval [CI], 2.75–239.46; p = 0.004) and 10.95 (95% CI, 1.02–117.28; p = 0.048), respectively, compared to Group 3. Those in Group 1 showed a greater utilization of intensive care services (15.9%), followed by Group 2 (10.9%), and Group 3 (2.5%), with adjusted ORs of 7.95 (95% CI, 2.52–25.08; p p = 0.017), respectively, compared to Group 3. The patients in Groups 1 and 2 had longer hospitalization stays than the patients in Group 3 (p p = 0.002, respectively). Older age (≥65 years) was an independent factor associated with longer hospital stays (OR = 1.72, 95% CI, 1.07–2.77). These findings can help hospitals prioritize patient care and service planning for future SARS-CoV-2 variants