Scale‐free functional brain dynamics during recovery from sport‐related concussion

Studies using blood‐oxygenation‐level‐dependent functional magnetic resonance imaging (BOLD fMRI) have characterized how the resting brain is affected by concussion. The literature to date, however, has largely focused on measuring changes in the spatial organization of functional brain networks. In the present study, changes in the temporal dynamics of BOLD signals are examined throughout concussion recovery using scaling (or fractal) analysis. Imaging data were collected for 228 university‐level athletes, 61 with concussion and 167 athletic controls. Concussed athletes were scanned at the acute phase of injury (1–7 days postinjury), the subacute phase (8–14 days postinjury), medical clearance to return to sport (RTS), 1 month post‐RTS and 1 year post‐RTS. The wavelet leader multifractal approach was used to assess scaling ( c₁ ) and multifractal ( c₂ ) behavior. Significant longitudinal changes were identified for c₁ , which was lowest at acute injury, became significantly elevated at RTS, and returned near control levels by 1 year post‐RTS. No longitudinal changes were identified for c₂ . Secondary analyses showed that clinical measures of acute symptom severity and time to RTP were related to longitudinal changes in c₁ . Athletes with both higher symptoms and prolonged recovery had elevated c₁ values at RTS, while athletes with higher symptoms but rapid recovery had reduced c₁ at acute injury. This study provides the first evidence for long‐term recovery of BOLD scale‐free brain dynamics after a concussion.     

Vesiculobullous Hailey-Hailey disease: Successful treatment with oral retinoids

A 56-year-old male presented with a pruritic, generalized vesiculobullous eruption. His past history revealed classical symptoms of limited Hailey-Hailey disease for 34 years. Clinically, vesicles, bullae and occasional pustules were present and multiple biopsies confirmed this to be an unusual presentation of Hailey-Hailey disease. Various therapeutic modalities including topical and oral antibiotics, oral prednisone and dapsone failed to achieve sustained remission. Treatment with lowdose oral etretinate (25 mg daily) produced marked clinical improvement with complete suppression of new vesicle formation after 6 weeks.     

Dubin-Johnson综合征1例

Dubin-Johnson综合征是一种先天性非溶血性黄疸,在临床中较罕见,需与其他原因所导致的黄疸相鉴别.本文报告了我院1例Dubin- Johnson综合征的诊治情况,有助于加深对该病的认识.     

Phagocytic efficiency of monocytes and macrophages obtained from Sydney blood bank cohort members infected with an attenuated strain of HIV-1

Defective function of monocyte-derived macrophages contributes to HIV-1 pathogenesis. We found that phagocytosis of the opportunistic pathogens Mycobacterium avium complex and Toxoplasma gondii was impaired in monocytes obtained from individuals infected with wild-type strains of HIV-1 but generally not in monocytes collected over a 6-year period from Sydney Blood Bank Cohort (SBBC) members infected with nef/long terminal repeats (LTR) region-defective strains of HIV-1. However, longitudinal analysis of phagocytosis in 1 SBBC member, C54, showed the development of defective engulfment of opportunistic pathogens at the most recent time points, coincident with the development of further molecular deletions in the nef/LTR region. Another SBBC member, C98, underwent bronchoscopy, which provided material to examine phagocytic signaling in alveolar macrophages. In contrast to normal phagocytic efficiency of C98's monocytes (over a 6-year period), defective signaling events during FcgammaR-mediated phagocytosis by C98's alveolar macrophages were observed. High basal phosphorylation within HIV-infected macrophages correlated with colocalization of tyrosine-phosphorylated proteins with HIV-1 p24 antigen rather than around the phagocytic targets as observed in uninfected cells. Thus, although phagocytic efficiency appears to be generally unimpaired in monocytes from SBBC members, evidence of impairment in recent samples from 1 SBBC member, coincident with further genetic changes within the virus, and abnormal phagocytic signaling in alveolar macrophages from another SBBC member may herald loss of attenuation of those strains.     

自体骨髓干细胞移植治疗失代偿期肝硬化

选择36例失代偿期肝硬化患者,年龄37～59岁,患者在无菌条件下,从髂后上棘抽取骨髓100～200mL,在体外分离纯化骨髓干细胞后,局部麻醉下经股动脉插管经肝动脉将分离的骨髓干细胞移植于肝脏。自移植后12周,25例(69.4%)患者谷丙转氨酶逐渐降低,由平均(2788.56±357.90)nkat/L降至(1077.05±440.25)nkat/L;22例(61.1%)患者总胆红素逐渐下降,由平均(151.47±25.77)μmol/L降至(69.93±18.86)μmol/L;27例(75%)患者白蛋白逐渐升高,由平均(25.17±11.79)g/L升至(30.87±12.17)g/L。在干细胞移植后凝血酶原活动度逐渐上升,由术前平均(25.89±12.67)%上升至术后12周的(50.39±19.38)%,患者凝血机制明显改善。移植后大多数患者身体状况有明显的改善;移植后12周腹水减轻的19例(52.7%),食欲改善的28例(77.7%),体力好转20例(58.3%),腹胀减轻17例(47.2%),36例干细胞移植患者未出现严重并发症。     

Cellular Mechanisms of Renin Release

ABSTRACT

The renin-angiotensin system plays a central role in salt and water balance and in the regulation of arterial blood pressure. The level of activity of this system is determined primarily by the rate at which the granulated juxtaglomerular cells (JG cells) secrete renin into the blood. Physiologically, renin secretory rate is controlled by a number of first messengers: afferent arteriolar transmural pressure or some function of it, such as stretch (the baroreceptor mechanism); solute transport in the macula densa segment of the nephron (the macula densa mechanism); catecholamines released from the renal nerves and the adrenal medulla (the β-adrenergic mechanism); extracellular concentrations of many organic and inorganic substances including angiotensin II, vasopressin, K, and Mg (1-3). In addition to these physiological first messengers, a number of pharmacological agents affect renin secretion (3).

It is an accepted principle of cellular biology that first messengers act by affecting the intracellular concentrations of only a few second messengers. The evidence that intracellular free ionic calcium, cyclic AMP, and cyclic GMP are second messengers in renin secretion has been reviewed in detail recently (4-9). These reviews are cited extensively, since space limitations precluded citing all the original literature.     

A Randomized Clinical Trial of the Building on Family Strengths Program: An Education Program for Parents of Children with Chronic Health Conditions

To test the 6-month efficacy of an inclusive non-diagnosis-specific, 7-session parent education curriculum on five pre-specified outcomes. A randomized clinical trial with 100 parents having children 2–11 years with a variety of chronic conditions was conducted. The 7-session curriculum, Building on Family Strengths (BFS), was created by an interdisciplinary pediatric team as a derivative of a successful adult chronic disease self-Management program distributed by Stanford University Patient and Education Research Center. Despite no differences at baseline, intervention participants had higher scores on self-efficacy to manage the child’s condition (p = 0.049), coping with childhood chronic illness (p < 0.001), parent–child shared management of the condition (p = 0.097), family quality of life (p = 0.010), and, lower scores on a measure of depressive symptoms (p = 0.046) at the 6-month end-point. Average effect-sizes were modest across outcomes (7–11 % improvement) with intervention participants having baseline scores in the least favorable quartile improving the most (12–41 %). This research provides evidence that the BFS curriculum can yield significant improvements across five important outcomes for parents of children with various chronic conditions. Parent education programs should be offered especially to parents of children with chronic health conditions, regardless of the type of condition, who lack adequate support. These programs can help parents cope with and manage their children’s chronic conditions more effectively.     

Prenatal diagnosis of aniridia

OBJECTIVE: To use molecular genetic techniques to prenatally screen for aniridia. DESIGN: Case report. METHODS: DNA was extracted from cultured fibroblasts obtained through amniocentesis. Two mutation detection methods, Ava1 restriction digestion and single-strand conformational polymorphism electrophoresis, were used to screen the PAX6 gene. MAIN OUTCOME MEASURES: The results from the amniocentesis sample were compared with DNA obtained from the affected father, firstborn infant, and unaffected mother to determine whether the fetus carried the PAX6 mutation. RESULTS: DNA from the fetus demonstrated the same banding pattern as the affected father and firstborn infant. CONCLUSIONS: The fetus carried the mutated PAX6 allele and was predicted to develop aniridia. This was later confirmed when the child was born. This case report illustrates an important use of genetic mutation screening in the clinical setting.     

Genetic screening in a large family with juvenile onset primary open angle glaucoma

AIMS: A number of genetic loci have been implicated in the pathogenesis of primary open angle glaucoma (POAG). The aim of this study was to identify the genetic cause of POAG in a large Scottish family and, if possible, offer genetic screening and advice to family members. METHODS: Family members were examined to determine their disease status. Base excision sequence scanning was carried out in order to test for the presence of a POAG causing mutation at known genetic loci. Direct DNA sequencing was performed in order to determine the mutation sequence. RESULTS: All family members of known affected disease status and two family members of unknown disease status were found to have a mutation in the TIGR gene. The mutation resulted in the substitution of a glycine residue with an arginine residue at codon 252 (Gly252Arg). No other sequence variations were present in any members of the family. CONCLUSION: The Gly252Arg mutation in the TIGR gene results in the development of POAG in this family. It was possible to identify younger, currently unaffected, members of the family who carry the mutation and who are therefore at a very high risk of developing POAG themselves. This is the first demonstration that Gly252Arg can be a disease causing mutation rather than a benign polymorphism. The possible pathogenic mechanisms and wider implications of the mutation are considered.