Early neonatal inflammation affects adult pain reactivity and anxiety related traits in mice: genetic background counts

Protracted or recurrent pain and inflammation in the early neonatal period may cause long-lasting changes in central neural function. However, more research is necessary to better characterize the long-term behavioral sequelae of such exposure in the neonatal period. Objectives: (1) to study whether timing of postnatal exposure to persistent inflammation alters responsiveness to thermal pain in the adult animal; (2) to assess whether animals experiencing early postnatal chronic inflammation display altered anxiety related behavior; (3) to study the importance of genetic background. Newborn mice (outbred strain, CD1 and F1 hybrid strain, B6C3F1) received an injection of Complete Freund's Adjuvant (CFA) or saline on either postnatal day 1 or 14 (PND1; PND14) into the left hind paw. Pain to radiant heat and anxiety were examined in 12-week-old adult animals. Adult baseline PWL was significantly decreased in CD1 mice exposed to CFA on PND 1 and 14 as compared to their saline treated counterparts. B6C3F1 mice exposed to CFA on PND14 showed markedly reduced baseline PWL compared to the PND14 saline group. Persistent inflammation experienced by B6C3F1 mice on PND1 failed to affect baseline adult thermal responsiveness. Adult mice, CD1 and B6C3F1, displayed low anxiety traits only if they had been exposed to persistent inflammation on PND1 and not on PND14. Our research suggests a role for genetic background in modulating long-term behavioral consequences of neonatal persistent inflammation: the data support the hypothesis that pain experienced very early in life differentially affects adult behavioral and emotional responsiveness in outbred (CD1) and hybrid mice (B6C3F1).     

Gesture development: a review for clinical and research practices.

The aim of this article is to provide clinicians and researchers a comprehensive overview of the development and functions of gesture in childhood and in select populations with developmental language impairments. Of significance is the growing body of evidence that gesture enhances, not hinders, language development. In both normal and impaired populations, gesture and language development parallel each other and share underlying symbolic abilities. Gesture serves several functions, including those of communication, compensation, and transition to spoken language. In clinical practice, gesture may play a valuable role in diagnosis, prognosis, goal selection, and intervention for children with language impairments. Where available, supporting evidence is presented. Needs for additional research on gesture are also highlighted.     

Novel therapeutic targets

Neurological Sciences - The need for novel therapeutic strategies for the treatment of migraine and other primary headaches is well recognised. Although the underlying mechanism(s) and the...     

Co‐occurring medical conditions in adults with Down syndrome: A systematic review toward the development of health care guidelines. Part II

Adults with Down syndrome (DS) represent a unique population who are in need of clinical guidelines to address their medical care. Many of these conditions are of public health importance with the potential to develop screening recommendations to improve clinical care for this population. Our workgroup previously identified and prioritized co‐occurring medical conditions in adults with DS. In this study, we again performed detailed literature searches on an additional six medical conditions of clinical importance. A series of key questions (KQ) were formulated a priori to guide the literature search strategy. Our KQs focused on disease prevalence, severity, risk‐factors, methodologies for screening/evaluation, impact on morbidity, and potential costs/benefits. The available evidence was extracted, evaluated and graded on quality. The number of participants and the design of clinical studies varied by condition and were often inadequate for answering most of the KQ. Based upon our review, we provide a summary of the findings on hip dysplasia, menopause, acquired cardiac valve disease, type 2 diabetes mellitus, hematologic disorders, and dysphagia. Minimal evidence demonstrates significant gaps in our clinical knowledge that compromises clinical decision‐making and management of these medically complex individuals. The creation of evidence‐based clinical guidance for this population will not be possible until these gaps are addressed.     

Autistic-spectrum disorders in Down syndrome: further delineation and distinction from other behavioral abnormalities.

The present study extends our previous work characterizing the behavioral features of autistic-spectrum disorder (ASD) in Down syndrome (DS) using the Aberrant Behavior Checklist (ABC) and Autism Behavior Checklist (AutBehav). We examined which specific behaviors distinguished the behavioral phenotype of DS + ASD from other aberrant behavior disorders in DS, by determining the relative contribution of ABC and AutBehav subscales and items to the diagnosis of ASD. A total of 127 subjects (aged 2-24 years; mean age: 8.4 years; approximately 70% male), comprising: a cohort of 64 children and adolescents with DS and co-morbid ASD (DS + ASD), 19 with DS and stereotypic movement disorder (DS + SMD), 18 with DS and disruptive behaviors (DS + DB), and 26 with DS and no co-morbid behavior disorders (DS + none) were examined using the aforementioned measures of aberrant behavior. We found that subjects with DS + ASD showed the most severe aberrant behavior, especially stereotypy compared to DS + none and lethargy/social withdrawal and relating problems compared to DS + SMD. Specifically, relatively simple stereotypic behavior differentiated DS + ASD from DS + DB, whereas odd/bizarre stereotypic and anxious behavior characterized DS + ASD relative to DS + SMD and DS + none. Additionally, in a subset of subjects with DS + ASD and anxiety, social withdrawal was particularly pronounced. Overall, our findings indicate that a diagnosis of DS + ASD represents a distinctive set of aberrant behaviors marked by characteristic odd/bizarre stereotypic behavior, anxiety, and social withdrawal.     

Surgical management of subfoveal neovascularization in children.

OBJECTIVE: To report the authors' clinical experience with submacular surgery for subfoveal membranes in children and to evaluate the histopathologic findings of membranes in children with various etiologies of choroidal neovascularization. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Twelve eyes of 12 consecutive children with subfoveal choroidal neovascularization treated by vitrectomy and excision of the choroidal neovascular complex. INTERVENTION: Vitrectomy, excision of the choroidal neovascular complex, and air-fluid exchange. MAIN OUTCOME MEASURES: Visual acuity and recurrence of choroidal neovascular membrane. RESULTS: Preoperative visual acuities ranged from 20/60 to 20/800 (median, 20/300). Postoperative visual acuities ranged from 20/25 to 20/400 (median, 20/80) after an average follow-up of 20 months (range, 7-62 months). Ten of 12 eyes improved from immediate preoperative visual acuity, and four eyes developed recurrence of neovascular membranes over a mean follow-up of 18 months. Histopathologic examination of six excised membranes showed that the most common components of the membranes were retinal pigment epithelium, fibrocytes, vascular endothelium, and collagen. CONCLUSION: Selected eyes of children with subfoveal neovascular membranes and no evidence of membrane regression may benefit from submacular surgery. The histopathologic findings were similar to adult choroidal neovascularization not associated with age-related macular degeneration.     

Transpupillary thermotherapy in the management of circumscribed choroidal hemangioma

PURPOSE: To report a case of circumscribed choroidal hemangioma effectively managed with transpupillary thermotherapy. METHOD: A 53-year-old man affected by extramacular circumscribed choroidal hemangioma had sustained a decline in visual acuity caused by subretinal fluid exudation into the macular area. Multiple attempts at treatment with scatter photocoagulation over the surface of the lesion for several years had been unsuccessful in reducing tumor-related exudation. The patient was examined on referral and underwent a single session of treatment employing transpupillary thermotherapy. The course of the lesion after treatment was documented with fundus photography and ultrasonography. RESULT: Complete atrophy of the choroidal hemangioma with resorption of subretinal fluid was documented over the 6 months after transpupillary thermotherapy, with improvement in visual acuity. CONCLUSION: Transpupillary thermotherapy is an effective alternative to conventional scatter photocoagulation or radiation therapy for precise ablation of circumscribed choroidal hemangioma.     

Renal functional reserve: its significance in normal and salt depletion conditions.

The aim of this study was the evaluation, in healthy subjects, of the renal functional reserve (RFR), that is, the GFR increase induced by a combined infusion of amino acids (AA) and dopamine (D), in conditions of extracellular volume depletion caused by diuretic administration. In particular, this study was undertaken: a) to evaluate whether and to which extent, AA + D can reverse the functional GFR impairment induced by salt depletion, without volume restoration; b) to study whether any relationship may be found between the GFR in normal condition (the so-called "resting" GFR), and/or the renal functional reserve and the GFR impairment induced by salt depletion, in order to understand the role of both "resting" GFR and RFR in the degree of renal dysfunction induced by salt depletion. In control conditions the i.v. infusion of AA + D significantly increased RPF (+ 41% vs. baseline period) with a mean absolute increase of 211 ml/min. A similar pattern was observed in GFR behavior (+31.5% with 34 ml/min of mean absolute increase). A significant inverse exponential relationship was observed between GFR before AA + D i.v. infusion ("resting" GFR) and renal functional reserve (P less than 0.05), suggesting that, in normal conditions, these inversely related parameters may widely vary according to the tone of the glomerular arterioles. Following salt depletion, we observed a variable degree of GFR impairment. Both GFR and RPF were significantly decreased (-25.9%, P less than 0.05 and -29%, P less than 0.05, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)