Post-Concussion and Post-Traumatic Stress Symptoms after Pediatric Traumatic Brain Injury: Shared Vulnerability Factors?

Following pediatric traumatic brain injury (TBI), post-concussion symptoms (PCS) and post-traumatic stress symptoms (PTSS) occur commonly; however, it is unknown to what degree they overlap. The study examined PCS and PTSS persisting 7 weeks after injury in children and adolescents ages 8-15 years with TBI (n = 89) or extracranial injury (EI; n = 40) after vehicle collisions. TBI was divided into mild, complicated-mild/moderate, and severe groups. Parents retrospectively rated children\u27s pre-injury symptoms and behavior problems, and children completed self-report measures after injury. PCS and PTSS total scores were significantly correlated in TBI and EI groups, respectively, for child (rs = 0.75; rs = 0.44), and adolescent (rs = 0.61; rs = 0.67) cohorts. Generalized linear models examined whether injury type and severity, age, sex, and pre-injury symptom ratings predicted PCS and PTSS total scores and factor scores. Specific PCS and PTSS factor scores were elevated in different TBI severity groups, with most frequent problems following mild or severe TBI. PCS did not differ by age; however, girls had more emotional symptoms than boys. Only PTSS were predicted by pre-injury externalizing behavior. Significant age by sex interactions indicated that adolescent girls had more total, avoidance, and hyperarousal PTSS symptoms than younger girls or all boys. PCS and PTSS significantly overlapped in both TBI and EI groups, highlighting shared persistent symptoms after injury. Shared vulnerability factors included female sex, milder TBI, and poorer pre-injury adjustment. Older age was a unique vulnerability factor for PTSS. Psychological health interventions after injury should be customized to address comorbid symptoms

Estudio de la regeneración de nervio periférico a través de cámaras permeables de silicona con poros de 10 y 60 micras

Rat sciatic nerves were transected and intubated with a fourteen millimeter lengthsilicone chamber, with two 8 mm windows covered with either a 10 or 60 pm mesh. After six months, the animals were perfused with a glutaraldehyde and paraformaldehyde mixture and the regenerated nerve histology was evaluated at two levels within the chamber (3 mm and midlevel) and 5 mm distal to the chamber. The myelinated nerve fibers were counted and compared for al1 levels and treatments. We found a disorganized endoneurium at midchamber level. Distally, a very low myelinated nerve fibers count was registered. No significant differences were observed between 10 and 60 vm meshes. We conclude that 10 or 60 pm meshes do not control the massive invasion of the chamber by fibroblasts, leading to a highly disorganized regenerated nerve.Se entubó el nervio ciático de ratas, luego de un corte transverso, utilizando una cámara de silicona de 14 mm de largo que tenía dos ventanas de 8 mm de largo cubiertas con malla de 10 o 60 pm. Después de 6 meses, los animales se perfundieron con una mezcla de glutaraldehído y paraformaldehído, y se evaluó el aspecto microscópico de los nervios regenerados en dos niveles dentro de la cámara (3 mm y nivel medio) y 5 mm distal a ésta. Se contó el número de fibras mielínicas presentes en cada nivel y tratamiento, y se realizó una comparación entre ellos. Se encontró una importante desorganización del endoneurio a nivel medio de la cámara. Distalmente, los conteos de fibras mielínicas fueron muy bajos. No se observaron diferencias significativas entre los grupos con mallas de 10 y 60 pm. En conclusión, la presencia de poros de 10 o 60 pm no impide la entrada masiva de fibroblastos a la cámara, llevando a una marcada desorganización del nervio regenerado

A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Distribución de neuropéptidos en el tronco del encéfalo del hombre y del mono (saimiri sciureus): estudio inmunocitoquímico

[ES]Esta tesis doctoral está basada en una pormenorizada consulta bibliográfica, relacionada con los diferentes estudios en cuanto a la distribución de fibras y somas inmunomarcados con los diferentes neuropéptidos en el tronco del encéfalo del hombre y del mono ardilla (Saimiri sciureus), así como también de otras especies de mamíferos (rata, gato, perro y alpaca). Es importante indicar que el estudio de la distribución de neuropéptidos en el sistema nervioso central de mamíferos se remonta a los años ochenta, sin embargo actualmente se desconoce la distribución de numerosos neuropéptidos en el sistema nervioso central de primates (humanos y no humanos).[EN]This thesis is based on a detailed bibliographical, related to the different studies regarding the distribution of fibers and cell bodies immunolabeled with the different neuropeptides in the brain stem of man and squirrel monkey (Saimiri sciureus), as well as mammalian species (rat, cat, dog and alpaca). Importantly, the study of the distribution of neuropeptides in the mammalian central nervous system goes back to the eighties, however currently unknown distribution of many neuropeptides in the central nervous system of primates (human and nonhuman)

Neuropeptides in the human brainstem

The physiological importance of the brainstem has made it one of the most studied structures of the central nervous system of mammals (in- cluding human). This structure receives somatic and visceral inputs and its neurons send motor efferences by means of the cranial nerves, which innervate the head, neck and sensory organs, and it mediates in several actions such as movement, pain, cardiovascular, respiratory, salivary, sleep, vigil and sexual mechanisms. Most of these actions are mediated by neuroactive substances denominated neuropeptides, which are short amino acid chains widespread dis- tributed in the nervous system, that play a role in neurotransmission, neuro- modulation (paracrine and autocrine actions), and act as neurohormones. In- creased study of these substances has taken place since the 1980s to shed light on both their potential role and the way that they mediate in the organism’s different activities. Thus, our aim is a detailed review of available morphologic and physiologic data regarding some neuropeptides in the human brainstem. To such end, we will discuss aspects like: 1) the distribution of neuropeptides in the human brainstem; 2) their possible physiological actions in the human brainstem; 3) neuropeptide coexistences in the human brainstem; and 4) fu- ture research in neuropeptides in the human brainstem

Altered stress system reactivity after pediatric injury: Relation with post-traumatic stress symptoms.

Injury is the leading cause of death and disability in childhood. Injured children are at high risk for developing alterations in stress response systems and post-traumatic stress symptoms (PTSS) that may compromise long-term physical and psychological health. In a prospective, observational cohort study, we examined individual differences in, and correlates of, stress-reactivity of the hypothalamic-pituitary-adrenal axis (HPA; salivary cortisol) and autonomic nervous system (ANS; salivary alpha amylase, sAA) following pediatric injury. Participants were 8-15 years of age and hospitalized for traumatic brain injury (TBI; n=55; M age=13.9 yrs; 40 males) or extracranial injury (EI; n=29; M age 12.3 yrs, 20 males) following vehicular accidents. Six months post-injury, saliva was collected before and after the Trier Social Stress Test and later assayed for cortisol and sAA. Relative to a healthy non-injured comparison group (n=33; M age=12.5 yrs, 16 males), injured children (ages 8-12 years), but not adolescents (ages 13-15 yrs), had higher cortisol levels; regardless of age, injured participants showed dampened cortisol reactivity to social evaluative threat. Compared to participants with EI, children with TBI had elevated cortisol and adolescents had elevated sAA. With respect to PTSS, individual differences in sAA were negatively correlated with avoidance in the TBI group and positively correlated with emotional numbing within the EI group. Importantly, psychological and neurobiological sequelae were weakly related to injury severity. Given the high prevalence of pediatric injury, these sequelae affect many children and represent a significant public health concern. Consequently, surveillance of post-traumatic sequelae should include the full spectrum of injury severity. Monitoring the activity, reactivity, and regulation of biological systems sensitive to environmental insults may advance our understanding of individual differences in sequelae and adaptation following traumatic pediatric injury

Altered stress system reactivity after pediatric injury: Relation with post-traumatic stress symptoms

Injury is the leading cause of death and disability in childhood. Injured children are at high risk for developing alterations in stress response systems and post-traumatic stress symptoms (PTSS) that may compromise long-term physical and psychological health. In a prospective, observational cohort study, we examined individual differences in, and correlates of, stress-reactivity of the hypothalamic-pituitary-adrenal axis (HPA; salivary cortisol) and autonomic nervous system (ANS; salivary alpha amylase, sAA) following pediatric injury. Participants were 8-15 years of age and hospitalized for traumatic brain injury (TBI; n=55; M age=13.9 yrs; 40 males) or extracranial injury (EI; n=29; M age 12.3 yrs, 20 males) following vehicular accidents. Six months post-injury, saliva was collected before and after the Trier Social Stress Test and later assayed for cortisol and sAA. Relative to a healthy non-injured comparison group (n=33; M age=12.5 yrs, 16 males), injured children (ages 8-12 years), but not adolescents (ages 13-15 yrs), had higher cortisol levels; regardless of age, injured participants showed dampened cortisol reactivity to social evaluative threat. Compared to participants with EI, children with TBI had elevated cortisol and adolescents had elevated sAA. With respect to PTSS, individual differences in sAA were negatively correlated with avoidance in the TBI group and positively correlated with emotional numbing within the EI group. Importantly, psychological and neurobiological sequelae were weakly related to injury severity. Given the high prevalence of pediatric injury, these sequelae affect many children and represent a significant public health concern. Consequently, surveillance of post-traumatic sequelae should include the full spectrum of injury severity. Monitoring the activity, reactivity, and regulation of biological systems sensitive to environmental insults may advance our understanding of individual differences in sequelae and adaptation following traumatic pediatric injury