Video game training enhances cognitive control in older adults.

Cognitive control is defined by a set of neural processes that allow us to interact with our complex environment in a goal-directed manner. Humans regularly challenge these control processes when attempting to simultaneously accomplish multiple goals (multitasking), generating interference as the result of fundamental information processing limitations. It is clear that multitasking behaviour has become ubiquitous in today's technologically dense world, and substantial evidence has accrued regarding multitasking difficulties and cognitive control deficits in our ageing population. Here we show that multitasking performance, as assessed with a custom-designed three-dimensional video game (NeuroRacer), exhibits a linear age-related decline from 20 to 79 years of age. By playing an adaptive version of NeuroRacer in multitasking training mode, older adults (60 to 85 years old) reduced multitasking costs compared to both an active control group and a no-contact control group, attaining levels beyond those achieved by untrained 20-year-old participants, with gains persisting for 6 months. Furthermore, age-related deficits in neural signatures of cognitive control, as measured with electroencephalography, were remediated by multitasking training (enhanced midline frontal theta power and frontal-posterior theta coherence). Critically, this training resulted in performance benefits that extended to untrained cognitive control abilities (enhanced sustained attention and working memory), with an increase in midline frontal theta power predicting the training-induced boost in sustained attention and preservation of multitasking improvement 6 months later. These findings highlight the robust plasticity of the prefrontal cognitive control system in the ageing brain, and provide the first evidence, to our knowledge, of how a custom-designed video game can be used to assess cognitive abilities across the lifespan, evaluate underlying neural mechanisms, and serve as a powerful tool for cognitive enhancement.

Magnesium-ibogaine therapy in veterans with traumatic brain injuries.

Traumatic brain injury (TBI) is a leading cause of disability. Sequelae can include functional impairments and psychiatric syndromes such as post-traumatic stress disorder (PTSD), depression and anxiety. Special Operations Forces (SOF) veterans (SOVs) may be at an elevated risk for these complications, leading some to seek underexplored treatment alternatives such as the oneirogen ibogaine, a plant-derived compound known to interact with multiple neurotransmitter systems that has been studied primarily as a treatment for substance use disorders. Ibogaine has been associated with instances of fatal cardiac arrhythmia, but coadministration of magnesium may mitigate this concern. In the present study, we report a prospective observational study of the Magnesium-Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), provided together with complementary treatment modalities, in 30 male SOVs with predominantly mild TBI. We assessed changes in the World Health Organization Disability Assessment Schedule from baseline to immediately (primary outcome) and 1 month (secondary outcome) after treatment. Additional secondary outcomes included changes in PTSD (Clinician-Administered PTSD Scale for DSM-5), depression (Montgomery-Åsberg Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale). MISTIC resulted in significant improvements in functioning both immediately (Pcorrected < 0.001, Cohen's d = 0.74) and 1 month (Pcorrected < 0.001, d = 2.20) after treatment and in PTSD (Pcorrected < 0.001, d = 2.54), depression (Pcorrected < 0.001, d = 2.80) and anxiety (Pcorrected < 0.001, d = 2.13) at 1 month after treatment. There were no unexpected or serious adverse events. Controlled clinical trials to assess safety and efficacy are needed to validate these initial open-label findings. ClinicalTrials.gov registration: NCT04313712 .

Influence of socioeconomic factors on litigation in surgery: Addressing the gap in malpractice literature.

The practice of medicine is occasionally volatile and increasingly litigious. Within the specialities, plastic surgery has a high risk, with negative outcomes seen as dissatisfaction, as compared to actual physical harm. To date, most research has focused on potential triggers for litigation, such as poor communication and perceived behavioural deficiencies among physicians. Few studies have addressed patient characteristics or socioeconomic factors. The 'Influence of Socio-Economic Factors on Attitudes Towards Surgery' questionnaire was designed to reflect these goals. It was distributed for a 12-month period to patients in an Emergency Department waiting room. Three hundred twelve completed questionnaires were submitted for analysis. Within the study population, we identified certain socioeconomic trends among those with a low threshold to pursue litigation. Patients with a low threshold to sue were more likely to be male, aged 25-55 years, currently unemployed, without dependents and divorced. However, these parameters did not reach statistical significance. Although these characteristics are interesting, they cannot reliably identify or predict those with a low threshold for litigation. For now, the clinical focus should remain on careful adherence to best practice in an effort to reduce the risk of potential litigation.

Characterizing cognitive control abilities in children with 16p11.2 deletion using adaptive 'video game' technology: a pilot study.

Assessing cognitive abilities in children is challenging for two primary reasons: lack of testing engagement can lead to low testing sensitivity and inherent performance variability. Here we sought to explore whether an engaging, adaptive digital cognitive platform built to look and feel like a video game would reliably measure attention-based abilities in children with and without neurodevelopmental disabilities related to a known genetic condition, 16p11.2 deletion. We assessed 20 children with 16p11.2 deletion, a genetic variation implicated in attention deficit/hyperactivity disorder and autism, as well as 16 siblings without the deletion and 75 neurotypical age-matched children. Deletion carriers showed significantly slower response times and greater response variability when compared with all non-carriers; by comparison, traditional non-adaptive selective attention assessments were unable to discriminate group differences. This phenotypic characterization highlights the potential power of administering tools that integrate adaptive psychophysical mechanics into video-game-style mechanics to achieve robust, reliable measurements.

Biodistribution of an oncolytic adenovirus after intracranial injection in permissive animals: a comparative study of Syrian hamsters and cotton rats.

Conditionally replicative adenoviruses (CRAds) are often evaluated in mice; however, normal and cancerous mouse tissues are poorly permissive for human CRAds. As the cotton rat (CR) is a semipermissive animal and the Syrian hamster (SH) is a fully permissive model for adenoviral replication, we compared them in a single study following intracranial (i.c.) injection of a novel glioma-targeting CRAd. Viral genomic copies were quantified by real-time PCR in brain, blood, liver and lung. The studies were corroborated by immunohistochemical, serological and immunological assays. CR had a multiple log higher susceptibility for adenoviral infection than SH. A similar amount of genomic copies of CRAd-Survivin-pk7 and human adenovirus serotype 5 (AdWT) was found in the brain of CR and in all organs from SH. In blood and lung of CR, AdWT had more genomic copies than CRAd-Survivin-pk7 in some of the time points studied. Viral antigens were confirmed in brain slices, an elevation of serum transaminases was observed in both models, and an increase in anti-adenoviral antibodies was detected in SH sera. In conclusion, CR represents a sensitive model for studying biodistribution of CRAds after i.c. delivery, allowing for the detection of differences in the replication of CRAd-Survivin-pk7 and AdWT that were not evident in SH.

Eficacia de la terapia restrictiva sobre funcionalidad de la extremidad superior en niños de 3 a 8 años con parálisis cerebral hemiparética: un ensayo clínico experimental / Efficacy of constraint-induced movement therapy on upper limb function in children with hemiparetic cerebral palsy from 3 to 8 years old. A pilot randomized clinical trial

Introducción: Los niños con hemiparesia presentan disminución de habilidades motrices y funcionales de la extremidad afectada, con escasa integración de ésta en actividades cotidianas; la terapia restrictiva ha sido escasamente estudiada en la realidad nacional. Objetivo: Evaluar eficacia de terapia restrictiva con yeso y terapia restrictiva más infiltración de onabotulinumtoxinA (Botox®), en funcionalidad de extremidad superior parética, en niños de 3-8 años de edad, con hemiparesia y compromiso funcional leve o moderado del Instituto Teletón Valparaíso-Chile. Método: Estudio experimental, controlado, aleatorio, simple ciego en 42 pacientes con consentimiento informado. Se distribuyen en tres grupos: sólo terapia convencional (control); con terapia convencional más restricción de extremidad indemne con yeso y terapia convencional con restricción de extremidad indemne con yeso más infiltración de onabotulinumtoxinA. Concluyen el estudio 29 niños, sometidos a tratamiento durante 6 semanas, con 3 sesiones semanales de 45 min cada una. Un terapeuta ocupacional ciego al grupo de pertenencia del paciente, evalúa calidad de movimiento (prueba Quest), actividades de la vida diaria (WeeFIM) y posicionamiento del pulgar (prueba House) al inicio, final del tratamiento y seguimiento en 3 meses. Resultados: Dentro de los grupos experimentales, las medianas de las pruebas WeeFIM y Quest, disminuyen al término del tratamiento y al seguimiento en relación al momento basal. La prueba House no cambia durante el proceso. No se registran diferencias significativas respecto del grupo control. Conclusión: No se comprueba mejoría de funcionalidad motriz de la extremidad superior parética y nivel de independencia en las AVD, con terapia restrictiva y adicionada con onabotulinumtoxina .

Introduction: Children with hemiparetic cerebral palsy show decreased motor and functional skills of their paretic extremity, along with scarce integration of it in daily activities. Constraint-induced movement therapy has been scantily studied in our country. Objective: To assess the effectiveness of plaster constraint-induced movement therapy alone and plaster constraint-induced movement therapy plus a onabotulinumtoxinA (Botox®) infiltration, on paretic upper limb function, in children from 3 to 8 years old, with hemiparetic cerebral palsy, and mild or moderate functional impairment, all patients at Valparaíso’s Teleton Institute in Chile. Method: An experimental, controlled, randomized and simple blind clinical trial was conducted with 42 patients who were distributed into three groups: only conventional therapy (control); conventional therapy with plaster constraint of undamaged upper extremity; and conventional therapy with plaster constraint of undamaged upper extremity plus a onabotulinum toxin A (Botox) infiltration.The protocol was completed by 29 children who participated during 6 weeks of treatment, with three 45 minutes sessions each week. A blind occupational therapist assessed quality of movement (QUEST), daily live activities (WEE FIM) and position of thumb at onset and end of treatment; and at 3 months follow-up. Results: WEE FIM and QUEST median scores for the experimental groups declined by the end of treatment and at follow-up, when compared to baseline measures. HOUSE test results showed no improvement either. No differences between control and experimental groups were observed. Conclusion: Motor functionality improvement of hemiparetic upper extremity and level of independence in daily activities, was not demonstrated for plaster constraint induced movement therapy alone or with infiltration of onabotulinumtoxinA (Botox).

Change in prescribing patterns of general practitioners in Italy before and after the Reform Drug Act. A case study of changes in the city of Turin.

As of 1 January 1994, the introduction of a new classification of the drugs to be reimbursed by the National Health Service was approved by the Italian parliament in order to limit expenditure on pharmaceutical agents. This has set off a 'cultural revolution', unprecedented in Italy. The criteria that inspired the expert group charged with attributing drugs to different classes (Class A: essential, free of charge drugs; Class B: drugs to be paid for 50% by the patient; Class C: drugs to be paid entirely by the patient) were principally scientific rather than merely economic or administrative. Expectedly, the creation of Class C (drugs not reimbursed by the National Health Service on account of their insufficiently proven clinical effectiveness, or their unfavourable cost/benefit ratio with respect to therapeutically equivalent agents) has provoked remarkable changes in general practitioners' prescription options, particularly given the fact that many of these drugs were among the most prescribed in Italy. A database including the prescriptions of about 940 general practitioners, dispensed through the 280 community pharmacies of the city of Turin, has been analysed for a comparative sample of time periods in 1993 and 1994, in order to quantify the changes that occurred and to qualify them with respect to more relevant therapeutic groups and sentinel drugs.