Human language, as well as birdsong, relies on the ability to arrange vocal elements in novel sequences. However, little is known about the ontogenetic origin of this capacity. We tracked the development of vocal combinatorial capacity in three species of vocal learners, combining an experimental approach in zebra finches with an analysis of natural development of vocal transitions in Bengalese finches and pre-lingual human infants and found a common, stepwise pattern of acquiring vocal transitions across species. In our first study, juvenile zebra finches were trained to perform one song and then the training target was altered, prompting the birds to swap syllable order, or insert a new syllable into a string. All birds solved these permutation tasks in a series of steps, gradually approximating the target sequence by acquiring novel pair-wise syllable transitions, sometimes too slowly to fully accomplish the task. Similarly, in the more complex songs of Bengalese finches, branching points and bidirectional transitions in song-syntax were acquired in a stepwise manner, starting from a more restrictive set of vocal transitions. The babbling of pre-lingual human infants revealed a similar developmental pattern: instead of a single developmental shift from reduplicated to variegated babbling (i.e., from repetitive to diverse sequences), we observed multiple shifts, where each novel syllable type slowly acquired a diversity of pair-wise transitions, asynchronously over development. Collectively, these results point to a common generative process that is conserved across species, suggesting that the long-noted gap between perceptual versus motor combinatorial capabilities in human infants1 may arise from the challenges in constructing new pair-wise transitions.
Numerous options exist for the treatment of Dupuytren’s contracture. This study describes the technique and early results of partial fasciectomy through a mini-incision approach as an additional treatment option for Dupuytren’s disease.
This procedure involves the excision of diseased Dupuytren’s tissue with the use of multiple 1 cm transverse incisions. Patient demographics, digit involvement, the number of incisions required to release each digit, and complications were recorded for all patients. Range of motion data was obtained from a subgroup of patients that had at least 6 months of follow-up. A paired t test was used to compare preoperative and postoperative contracture.
Sixty-seven patients underwent 75 procedures that involved 119 digits. The mean patient age at the time of surgery was 63 years (range, 33–95 years). A total of 32 digits (47 joints) were available for range of motion analysis. After a mean of 2.2 years following surgery, metacarpophalangeal joint contractures maintained correction (34° preoperatively, 19° postoperatively, p = 0.008). After a mean postoperative duration of 2.0 years, proximal interphalangeal joint contractures trended worse than preoperative levels (39° preoperatively, 45° postoperatively, p = 0.319). There was one major complication, which consisted of a nerve laceration that was identified and repaired intraoperatively.
Partial fasciectomy through the described mini-incision approach provides an additional surgical option for patients who desire a less invasive surgical procedure than traditional fascietomy. Although this procedure is safe and effective at achieving immediate cord release, maintenance of correction for proximal interphalangeal joint contractures remains problematic.
Dupuytren’s contracture; Minimally invasive; Fasciectomy
Carpal tunnel syndrome (CTS) is the most common compressive neuropathy affecting the upper extremity, yet evidence-based guidelines for its diagnosis and treatment are lacking. We set out to expose any potential discrepancies in CTS practice attitudes based on surgeon’s academic background, residency training, clinical experience, and other factors.
This was an online survey-based study. Members of the American Association for Hand Surgery (AAHS) were sent an electronic mail request (n = 817). The online questionnaire consisted of 12 questions that queried surgeons’ approaches to the diagnosis as well as operative and non-operative management of carpal tunnel syndrome.
One hundred twenty-three surgeons responded to the survey (15.1 %). The locations of surgical practices varied within the United States and beyond. Most respondents were either orthopedic or plastic surgeons. With respect to practice duration, 15.4 % had been in practice for 5 years or less, 30.9 % of the respondents had been in practice between 6 and 15 years, 30.9 % had been in practice between 16 and 25 years, and 26.8 % had been in practice for more than 25 years. The most notable interspecialty differences were related to the use of operative antibiotics and the surgical approach. Plastic surgeons were less likely to recommend antibiotic use during surgery and more likely to utilize an open extensile approach during surgical release. Younger surgeons were more likely to employ a mini-open approach for carpal tunnel release.
We conclude that background training and generational differences contribute to the varied approaches observed in the diagnosis and management of CTS.
Carpal tunnel syndrome; Surgeon attitudes; Questionnaire; Survey
Epilepsy is a common chronic neurological disease. One of its characteristics is that it can bring severe stigma for patients. At the same time as controlling the epileptic seizures, taking appropriate measures to reduce the stigma of epilepsy is an important aspect of any comprehensive intervention strategy. We examined the views of 106 participants of different target groups, including patients with epilepsy (PWE), their family members, neighbors, teachers, employers, community administrators, doctors and nurses, using one to one in-depth interviews and group discussions. The discussions covered the following aspects related to epilepsy: the participants’ understanding of epilepsy, the patients’ own perception of epilepsy, the attitudes of surrounding people, the social and cultural environment, the social support available to them, and government regulations and policies. We found that the stigma of epilepsy is a very negative self-feeling from the patients’ perspective. Many complex and diverse factors determine its formation and severity. The stigma of epilepsy, in a particular social and cultural context, can be demonstrated in the internalized, interpersonal and institutional levels. Hence, we suggest that effective measures to alleviate stigma should be based on ways of eliminating factors which cause institutional stigma. Additionally, depending on the specific circumstances of PWE, a personalized approach to eliminate factors which cause internalized and interpersonal stigma needs to be adopted. Only by addressing impacting factors at each of these three levels, can the stigma of PWE in China be alleviated or even eliminated.
Coral reefs are damaged by natural disturbances and local and global anthropogenic stresses. As stresses intensify, so do debates about whether reefs will recover after significant damage. True headway in this debate requires documented temporal trajectories for coral assemblages subjected to various combinations of stresses; therefore, we report relevant changes in coral assemblages at Little Cayman Island. Between 1999 and 2012, spatiotemporal patterns in cover, densities of juveniles and size structure of assemblages were documented inside and outside marine protected areas using transects, quadrats and measurements of maximum diameters. Over five years, bleaching and disease caused live cover to decrease from 26% to 14%, with full recovery seven years later. Juvenile densities varied, reaching a maximum in 2010. Both patterns were consistent within and outside protected areas. In addition, dominant coral species persisted within and outside protected areas although their size frequency distributions varied temporally and spatially. The health of the coral assemblage and the similarity of responses across levels of protection suggested that negligible anthropogenic disturbance at the local scale was a key factor underlying the observed resilience.
qnr genes were discovered on plasmids by their ability to reduce quinolone susceptibility, but homologs can be found in the genomes of at least 92 Gram-negative, Gram-positive, and strictly anaerobic bacterial species. The related pentapeptide repeat protein-encoding mfpA gene is present in the genome of at least 19 species of Mycobacterium and 10 other Actinobacteria species. The native function of these genes is not yet known.
PX-478 is a potent small-molecule inhibitor of HIF-1α. In preclinical studies, it had antitumor activity against various solid tumors in subcutaneous xenografts but had no measurable activity against a non-small cell lung cancer (NSCLC) xenograft. To determine the effectiveness of PX-478 against lung tumors, we investigated HIF-1α expression in several lung cancer cell lines, both in vitro and in vivo, and treated orthotopic mouse models of human lung cancer with PX-478.
Cells from two human lung adenocarcinoma cell models (PC14-PE6 and NCI-H441) or two human small cell lung cancer (SCLC) models (NCI-H187 and NCI-N417) were injected into the left lungs of nude mice and were randomized 16 to 18 days after injection with daily oral treatment with PX-478 or vehicle for 5 days.
In the PC14-PE6 NSCLC model, treatment with 20 mg/kg PX-478 significantly reduced the median primary lung tumor volume by 87% (p = 0.005) compared with the vehicle-treated group. PX-478 treatment also markedly reduced mediastinal metastasis and prolonged survival. Similar results were obtained in a second NSCLC model. In SCLC models, PX-478 was even more effective. In the NCI-H187 model, the median primary lung tumor volume was reduced by 99% (p = 0.0001). The median survival duration was increased by 132%. In the NCI-N417 model, the median primary lung tumor volume was reduced by 97% (p = 0.008).
We demonstrated that the PX-478, HIF-1α inhibitor, had significant antitumor activity against two orthotopic models of lung adenocarcinomas and two models of SCLC. These results suggest the inclusion of lung cancer patients in phase I clinical trials of PX-478.
Hypoxia; HIF-1α; PX-478; Orthotopic model; Lung cancer
Ozone exposure causes airway hyperreactivity and increases hospitalizations resulting from pulmonary complications. Ozone reacts with the epithelial lining fluid and airway epithelium to produce reactive oxygen species and lipid peroxidation products, which then activate cell signaling pathways, including the mitogen activated protein kinase (MAPK) pathway. Both p38 and c-Jun NH2 terminal kinase (JNK) are MAPK family members that are activated by cellular stress and inflammation. To test the contribution of both p38 and JNK MAPK to ozone-induced airway hyperreactivity, guinea pigs were pretreated with dual p38 and JNK MAPK inhibitors (30 mg/kg, ip) 60 minutes before exposure to 2 ppm ozone or filtered air for 4 hours. One day later airway reactivity was measured in anesthetized animals. Ozone caused airway hyperreactivity one day post-exposure, and blocking p38 and JNK MAPK completely prevented ozone-induced airway hyperreactivity. Blocking p38 and JNK MAPK also suppressed parasympathetic nerve activity in air exposed animals, suggesting p38 and JNK MAPK contribute to acetylcholine release by airway parasympathetic nerves. Ozone inhibited neuronal M2 muscarinic receptors and blocking both p38 and JNK prevented M2 receptor dysfunction. Neutrophil influx into bronchoalveolar lavage was not affected by MAPK inhibitors. Thus p38 and JNK MAPK mediate ozone-induced airway hyperreactivity through multiple mechanisms including prevention of neuronal M2 receptor dysfunction.
Objective. To adapt and evaluate the psychometric properties of the Brazilian version of the SCHFI v 6.2. Methods. With the approval of the original author, we conducted a complete cross-cultural adaptation of the instrument (translation, synthesis, back translation, synthesis of back translation, expert committee review, and pretesting). The adapted version was named Brazilian version of the self-care of heart failure index v 6.2. The psychometric properties assessed were face validity and content validity (by expert committee review), construct validity (convergent validity and confirmatory factor analysis), and reliability. Results. Face validity and content validity were indicative of semantic, idiomatic, experimental, and conceptual equivalence. Convergent validity was demonstrated by a significant though moderate correlation (r = −0.51) on comparison with equivalent question scores of the previously validated Brazilian European heart failure self-care behavior scale. Confirmatory factor analysis supported the original three-factor model as having the best fit, although similar results were obtained for inadequate fit indices. The reliability of the instrument, as expressed by Cronbach's alpha, was 0.40, 0.82, and 0.93 for the self-care maintenance, self-care management, and self-care confidence scales, respectively. Conclusion. The SCHFI v 6.2 was successfully adapted for use in Brazil. Nevertheless, further studies should be carried out to improve its psychometric properties.
Impairments in the ability to recollect specific details of personally experienced events are one of the main cognitive changes associated with aging. Cognitive training can improve older adults’ recollection. However, little is currently known regarding the neural correlates of these training-related changes in recollection. Prior research suggests that the hippocampus plays a central role in supporting recollection in young and older adults, and that age-related changes in hippocampal function may lead to age-related changes in recollection. The present study investigated whether cognitive training-related increases in older adults’ recollection are associated with changes in their hippocampal activity during memory retrieval. Older adults’ hippocampal activity during retrieval was examined before and after they were trained to use semantic encoding strategies to intentionally encode words. Training-related changes in recollection were positively correlated with training-related changes in activity for old words in the hippocampus bilaterally. Positive correlations were also found between training-related changes in activity in prefrontal and left lateral temporal regions associated with self-initiated semantic strategy use during encoding and training-related changes in right hippocampal activity associated with recollection during retrieval. These results suggest that cognitive training-related improvements in older adults’ recollection can be supported by changes in their hippocampal activity during retrieval. They also suggest that age differences in cognitive processes engaged during encoding are a significant contributor to age differences in recollection during retrieval.
aging; encoding strategy; fMRI; hippocampus; memory retrieval
We used Laser Doppler Fluximetry (LDF) to define "normal" endothelial function in a large cohort of healthy children and adolescents and to evaluate skin microcirculation in paediatric patients with type 1 diabetes mellitus.
LDF was performed in 102 healthy children (12.8 ± 3.3 years of age; 48 male) and 68 patients (12.9 ± 3.3 years of age; 33 male). Duration of disease was 5.0 ± 3.97 years. Each participant sequentially underwent three stimulation protocols (localized thermal hyperaemia with localized warming to maximum 40°C, iontophoretic delivery of pilocarpine hydrochloride (PCH) and sodium nitroprusside (SNP)). The maximum relative increase in skin blood flow and the total relative response, i.e. the area under the curve (AUC) to each stimulus (AUCheat, AUCPCH, AUCSNP) was determined. In addition, the area of a right-angled triangle summarizing the time to and the amplitude of the first peak, which represents the axon reflex mediated neurogenic vasodilation (ARR) was calculated.
In healthy controls, AUCheat, AUCPCH, AUCSNP, and ARR turned out to be independent of sex, age, and anthropometric values. Per parameter the 10th percentile generated from data of healthy controls was used as the lower threshold to define normal endothelial function. Diabetic patients showed significantly reduced vasodilatative response to either physical or pharmacological stimulation with SNP, whereas the response to PCH was comparable in both cohorts. In patients compared to controls i) a significantly higher frequency of impaired vasodilatation in response to heat and SNP was noted and ii) vascular response was classified as pathological in more than one of the parameters with significantly higher frequency.
Skin microvascular endothelial dysfunction is already present in about 25% of paediatric type 1 diabetic patients suffering from type 1 diabetes for at least one year. Future studies are needed to assess the predictive value of endothelial dysfunction in the development of long-term (cardio)vascular comorbidity in these patients.
Children; Laser Doppler Fluximetry; Skin microcirculation; Type 1 diabetes mellitus
Proximal row carpectomy (PRC) combined with distal radius hemiarthroplasty is a relatively novel procedure that rivals total wrist arthrodesis and offers a new surgical treatment option for select patients with painful, end-stage wrist disease. We present our early experience with this procedure. A retrospective chart review was conducted for nonrheumatoid patients diagnosed with wrist arthritis and subsequently treated with wrist hemiarthroplasty combined with PRC. The minimum follow-up duration was 12 months. Preoperative and postoperative flexion, extension, and grip strength were recorded. Postoperative radiographic findings were assessed. The Patient-Rated Wrist Evaluation (PRWE) questionnaire was administered to gauge postoperative pain and function. The records of 10 patients were reviewed. The mean age was 64 years and the mean postoperative follow-up duration was 19 months. Postoperative flexion, extension, and grip strength were all found to be less than the preoperative levels. The mean postoperative PRWE score for pain and function were 26 and 23, respectively. The complications were diverse and occurred at a relatively high rate. PRC combined with distal radius hemiarthroplasty is a novel procedure that offers a potential surgical option for the treatment of wrist arthritis in select patients. Our early experience has lead us to modify our technique with regard to the implant material, and at this stage, the surgical technique and the most appropriate implant may require further optimization. The level of evidence for this study is IV (therapeutic).
wrist arthritis; hemiarthroplasty; proximal row carpectomy; wrist; motion preserving surgery
Snake bite is one of the most neglected public health issues in poor rural communities worldwide. In addition to the clinical effects of envenoming, treatment with antivenom frequently causes serious adverse reactions, including hypersensitivity reactions (including anaphylaxis) and pyrogenic reactions. We aimed to investigate the immune responses to Sri Lankan snake envenoming (predominantly by Russell's viper) and antivenom treatment.
Plasma concentrations of Interleukin (IL)-6, IL-10, tumor necrosis factor α (TNFα), soluble TNF receptor I (sTNFRI), anaphylatoxins (C3a, C4a, C5a; markers of complement activation), mast cell tryptase (MCT), and histamine were measured in 120 Sri Lankan snakebite victims, both before and after treatment with antivenom. Immune mediator concentrations were correlated with envenoming features and the severity of antivenom-induced reactions including anaphylaxis. Envenoming was associated with complement activation and increased cytokine concentrations prior to antivenom administration, which correlated with non-specific systemic symptoms of envenoming but not with coagulopathy or neurotoxicity. Typical hypersensitivity reactions to antivenom occurred in 77/120 patients (64%), satisfying criteria for a diagnosis of anaphylaxis in 57/120 (48%). Pyrogenic reactions were observed in 32/120 patients (27%). All patients had further elevations in cytokine concentrations, but not complement activation, after the administration of antivenom, whether a reaction was noted to occur or not. Patients with anaphylaxis had significantly elevated concentrations of MCT and histamine.
We have demonstrated that Sri Lankan snake envenoming is characterized by significant complement activation and release of inflammatory mediators. Antivenom treatment further enhances the release of inflammatory mediators in all patients, with anaphylactic reactions characterised by high levels of mast cell degranulation but not further complement activation. Anaphylaxis is probably triggered by non allergen-specific activation of mast cells and may be related to the quality of available antivenom preparations, as well as a priming effect from the immune response to the venom itself.
Snakebites cause life-threatening symptoms including uncontrolled bleeding and paralysis. The body's immune responses to snake venom may contribute to the severity of these symptoms but have not been well characterized in humans. Treatment with antivenom is potentially lifesaving, but also carries risk, as severe allergic reactions (anaphylaxis) are common. Anaphylaxis occurs when mast cells, triggered by either allergen-specific antibodies, other immunological mechanisms, or non-immune mechanisms, release mediators that cause skin rashes, shortness of breath and, in severe cases, life-threatening hypotension and/or hypoxia. We have studied 120 snakebite victims in Sri Lanka, both before and after treatment with antivenom. Our results have shown snakebite triggers activation of the complement cascade (an important part of the body's innate immune defence) and production of proinflammatory mediators. In addition, we have demonstrated a quite astonishing level of immune activation after antivenom treatment in virtually every person treated, regardless of whether they had a reaction to the antivenom. Half of the patients treated experienced anaphylaxis, with clear evidence of mast cell activation. Anaphylaxis to antivenom is unlikely to be triggered by allergen-specific antibodies, as patients had not been previously exposed to antivenom, but may be related to the quality of available antivenom preparations, as well as a priming effect from the immune response to the venom itself.
Host antibacterial responses include mechanisms that kill bacteria, but also those that protect or tolerize the host to potentially damaging antibacterial effects. We determined that Chitinase 3-like-1 (Chi3l1), a conserved prototypic chitinase-like protein, is induced by Streptococcus pneumoniae and plays central roles in promoting bacterial clearance and mediating host tolerance. S. pneumoniae-infected Chi3l1 null mice exhibit exaggerated lung injury, inflammation and hemorrhage, more frequent bacterial dissemination, decreased bacterial clearance, and enhanced mortality compared to controls. Chi3l1 augments macrophage bacterial killing by inhibiting caspase-1-dependent macrophage pyroptosis and augments host tolerance by controlling inflammasome activation, ATP accumulation, expression of ATP receptor P2×7R, and production of thymic stromal lymphopoietin and type 1, type 2, and type 17 cytokines. These data demonstrate that Chi3l1 is induced during infection, where it promotes bacterial clearance while simultaneously augmenting host tolerance, and that these roles likely contributed to the retention of Chi3l1 over species and evolutionary time.
Poorly controlled acute and chronic pain can increase morbidity, impair quality of life and prolong disability. Over 80 percent of post surgical patients report moderate to severe uncontrolled postoperative pain. Over-reliance on potent opioid agonists can lead to several opioid related side effects such as gastrointestinal intolerability, respiratory depression and cognitive impairment. A recently approved dual acting central analgesic tapentadol may offer improved tolerability over traditional opioid agonists while having multimodal opioid and nonopioid analgesic benefits. Tapentadol, classified by the US Food and Drug Administration as a class 2 opioid, is currently marketed in the United States as immediate release (IR) NUCYNTA® for moderate to severe acute pain in tablets of 50 mg, 75 mg, and 100 mg, and as extended release (ER) NUCYNTA ER® for the treatment of chronic moderate to severe pain in tablets of 50 mg, 100 mg, 150 mg, 200 mg, and 250 mg. Tapentadol is a low affinity mu opioid receptor agonist and a norepinephrine reuptake inhibitor. Tapentadol has no active metabolites and this property makes it useful in patients with hepatic and renal failure. Clinical trials with tapentadol IR showed that there was improved gastrointestinal tolerability and similar pain relief as compared to oxycodone IR. Tapentadol ER allows for twice daily dosing. Clinical trials showed that tapentadol ER could effectively relieve moderate to severe chronic pain and was associated with significantly fewer gastrointestinal adverse effects as compared to oxycodone controlled release. Tapentadol ER is indicated and has Food and Drug Administration approval for the treatment of chronic painful diabetic neuropathy. The most common side effects of tapentadol are nausea (30%), vomiting (18%), dizziness (24%), and somnolence (15%). Tapentadol, due to its potential synergistic effects on norepinephrine levels, is contraindicated in patients who have taken monoamine oxidase inhibitors within the last 14 days. Caution has to be exercised with the use of tapentadol IR and tapentadol ER in the presence of other central nervous system depressants such as neuroleptics, opioids, illicit drugs, muscle relaxants, sedatives, and anxiolytics.
tapentadol immediate release; tapentadol extended release; diabetic neuropathy; acute pain; chronic pain
Human rhinovirus (HRV) species C (HRV-C) have been associated with frequent and severe acute lower respiratory infections and asthma in hospitalized children. The prevalence of HRV-C among healthy children and whether this varies with ethnicity is unknown.
to describe the prevalence of HRV species and their associations with demographic, environmental and socioeconomic factors in healthy aboriginal and non-aboriginal children.
respiratory viruses and bacteria were identified in 1006 nasopharyngeal aspirates collected from a cohort of 79 aboriginal and 88 non-aboriginal Western Australian children before 2 years of age. HRV-positive nasopharyngeal aspirates were typed for HRV species and genotypes. Longitudinal growth models incorporating generalized estimating equations were used to investigate associations between HRV species and potential risk factors.
Of the 159 typed specimens, we identified 83 (52.2%) human rhinovirus species a (HrV-A), 26 (16.4%), human rhinovirus species B and 50 (31.4%) HrV-C. HRV-C was associated with upper respiratory symptoms in aboriginal (odds ratio, 3.77; 95% confidence interval:1.05–13.55) and non-aboriginal children (odds ratio, 5.85; 95% confidence interval: 2.33–14.66). HRV-A and HRV-C were associated with carriage of respiratory bacteria. In aboriginal children, HRV-A was more common in the summer and in those whose mothers were employed prior to delivery. In non-aboriginal children, day-care attendance and exclusive breast-feeding at age 6–8 weeks were associated with detection of HRV-A, and gestational smoking with detection of HRV-C.
Factors associated with the presence of HRV differ between aboriginal and non-aboriginal children. In contrast to HRV-A, HRV-C is associated with upper respiratory symptoms suggesting that HRV-C is likely to be implicated in respiratory illness.
human rhinovirus; aboriginal; bacterial association; environmental risk factors; upper respiratory symptoms; seasonality
Fetal growth is an important risk factor for infant morbidity and mortality. In turn, socioeconomic status is a key predictor of fetal growth; however, other sociodemographic factors and environmental effects may also be important. This study modelled geographic variation in poor fetal growth after accounting for socioeconomic status, with a fixed effect for socioeconomic status and a combination of spatially-correlated and spatially-uncorrelated random effects. The dataset comprised 88,246 liveborn singletons, aggregated within suburbs in Perth, Western Australia. Low socioeconomic status was strongly associated with an increased risk of poor fetal growth. An increase in geographic variation of poor fetal growth from 1999–2001 (interquartile odds ratio among suburbs = 1.20) to 2004–2006 (interquartile odds ratio = 1.40) indicated a widening risk disparity by socioeconomic status. Low levels of residual spatial patterns strengthen the case for targeting policies and practices in areas of low socioeconomic status for improved outcomes. This study indicates an alarming increase in geographic inequalities in poor fetal growth in Perth which warrants further research into the specific aspects of socioeconomic status that act as risk factors.
poor fetal growth; socioeconomic status; conditional autoregression; spatial variation
Men who have sex with men (MSM), especially MSM of color, are disproportionately impacted by HIV/AIDS compared to heterosexuals and Caucasians. Nonetheless, fewer sexual and ethnic minorities participate in prevention interventions for people with HIV. We consider recruitment for Positive Connections, a randomized controlled trial comparing unsafe sex prevention interventions primarily for HIV-positive (HIV+) MSM in six US epicenters. One community-based organization (CBO) in each city recruited adult MSM, particularly men of color and HIV+. Recruitment methods included on-line and print advertising, outreach events, health professionals, and social networks. Data on demographics, HIV status, and recruitment method were collected at registration. We tested for differences in registration proportions and attendance rates by recruitment strategy, stratified on race/ethnicity and serostatus. Of the 1,119 registrants, 889 attended the intervention. The sample comprised 41% African American, 18% Latino/Hispanic, and 77% HIV+. Friend referral was reported by the greatest proportion of registrants, particularly among African American (33%) and HIV+ men (25%). Print advertising yielded the largest proportions of non-Hispanic white (27%) and HIV-negative registrants (25%). Registrants recruited on-line were the least likely to attend (45% versus 69% average); this effect was strongest among Latino/Hispanic (27% attendance) and non-Hispanic white men (36%). Retention during the follow-up period did not differ by serostatus, race/ ethnicity, or recruitment method. Differential attendance and retention according to recruitment strategy, serostatus, and racial/ethnic group can inform planning for intervention sample size goals.
Recruitment; Men who have sex with men (MSM); HIV-positive; Minorities
Although defined by the presence of recurrent seizures, epilepsy can be so much more and can include a very wide range of difficulties in cognition, psychiatric status, and social adaptive functioning. These psychosocial complications of epilepsy have a long history, generating calls for action by national commissions, public health agencies, and special action groups which are briefly summarized here. Next, a brief overview of the prevalence of psychosocial complications of epilepsy in population-based and other non-selected studies is presented. Finally, focusing on the onset and development of psychosocial difficulties, the following points are stressed:
1) neurobiological factors likely contribute to psychosocial problems in a major way, but currently this contribution is poorly understood, and 2) while neurobiological factors may prove important, they operate in a social setting, and therefore a full accounting of the etiology, treatment and prevention of psychosocial problems in epilepsy will require an integrated biopsychosocial model and lifespan perspective.
Nonindigenous apple snails, Pomacea maculata (formerly Pomacea insularum), are currently spreading rapidly through the southeastern United States. This mollusk serves as an intermediate host of the rat lungworm parasite (Angiostrongylus cantonensis), which can cause eosinophilic meningitis in humans who consume infected mollusks. A PCR-based detection assay was used to test nonindigenous apple snails for the rat lungworm parasite in Louisiana, Texas, Mississippi, and Florida. Only apple snails obtained from the New Orleans, Louisiana, area tested positive for the parasite. These results provide the first evidence that Angiostrongylus cantonensis does occur in nonindigenous apple snails in the southeastern United States. Additionally, Angiostrongylus cantonensis was identified in the terrestrial species Achatina fulica in Miami, Florida, indicating that rat lungworm is now established in Florida as well as Louisiana. Although the study suggests that the rat lungworm is not widespread in the Gulf States region, the infected snail population could still pose a risk to human health and facilitate the spread of the parasite to new areas.
Angiostrongylus cantonensis; Apple snail; Invasive species; Parastrongylus cantonensis; Pomacea; Rat lungworm
Some solid tumors have reduced posttranscriptional RNA editing by adenosine deaminase acting on RNA (ADAR) enzymes, but the functional significance of this alteration has been unclear. Here, we found the primary RNA-editing enzyme ADAR1 is frequently reduced in metastatic melanomas. In situ analysis of melanoma samples using progression tissue microarrays indicated a substantial downregulation of ADAR1 during the metastatic transition. Further, ADAR1 knockdown altered cell morphology, promoted in vitro proliferation, and markedly enhanced the tumorigenicity in vivo. A comparative whole genome expression microarray analysis revealed that ADAR1 controls the expression of more than 100 microRNAs (miRNAs) that regulate many genes associated with the observed phenotypes. Importantly, we discovered that ADAR1 fundamentally regulates miRNA processing in an RNA binding–dependent, yet RNA editing–independent manner by regulating Dicer expression at the translational level via let-7. In addition, ADAR1 formed a complex with DGCR8 that was mutually exclusive with the DGCR8-Drosha complex that processes pri-miRNAs in the nucleus. We found that cancer cells silence ADAR1 by overexpressing miR-17 and miR-432, which both directly target the ADAR1 transcript. We further demonstrated that the genes encoding miR-17 and miR-432 are frequently amplified in melanoma and that aberrant hypomethylation of the imprinted DLK1-DIO3 region in chromosome 14 can also drive miR-432 overexpression.
Lean mass is associated with bone mineral density (BMD) in athletes, attributable to the anabolic pull of muscle on bone. Fat mass is also important, and subcutaneous fat positively and visceral fat negatively correlates with BMD in obese adolescents. The contribution of regional body composition to low BMD in amenorrheic athletes (AA) has not been elucidated. We hypothesized that in adolescent athletes (runners), BMD is associated positively with total fat (surrogate for subcutaneous fat) and lean mass, and inversely with percent trunk fat and trunk-to-extremity fat ratio (surrogates for visceral fat).
Subjects and methods
We examined BMD and body composition using dual energy X-ray absorptiometry (DXA) in 21 AA and 19 eumenorrheic athletes (EA) (12–18 years) (runners). We report total hip and height-adjusted BMD [lumbar bone mineral apparent density (LBMAD) and whole body bone mineral content/height (WBBMC/Ht)].
AA had lower BMD than EA. Lean mass was less strongly associated with hip BMD in AA than EA; fat mass was positively associated with LBMAD in EA. Percent trunk fat and trunk-to-extremity fat ratio were inversely associated with lumbar and WB measures in AA. In a regression model, lean and fat mass were positively, and percent trunk fat and trunk-to-extremity fat ratio negatively associated with LBMAD and WBBMC/Ht for all athletes, even after controlling for serum estradiol.
DXA surrogates for visceral fat are inversely associated with bone density in athletes.
athletes; body composition; bone density; fat mass; lean mass; regional fat; trunk fat
Glioblastomas (GBM), the most common and aggressive malignant astrocytic tumors, contain a small subpopulation of cancer stem cells (GSCs) that are implicated in therapeutic resistance and tumor recurrence. Here, we study the expression and function of miR-137, a putative suppressor miRNA, in GBM and GSCs. We found that the expression of miR-137 was significantly lower in GBM and GSCs compared to normal brains and neural stem cells (NSCs) and that the miR-137 promoter was hypermethylated in the GBM specimens. The expression of miR-137 was increased in differentiated NSCs and GSCs and overexpression of miR-137 promoted the neural differentiation of both cell types. Moreover, pre-miR-137 significantly decreased the self-renewal of GSCs and the stem cell markers Oct4, Nanog, Sox2 and Shh. We identified RTVP-1 as a novel target of miR-137 in GSCs; transfection of the cells with miR-137 decreased the expression of RTVP-1 and the luciferase activity of RTVP-1 3'-UTR reporter plasmid. Furthermore, overexpression of RTVP-1 plasmid lacking its 3'-UTR abrogated the inhibitory effect of miR-137 on the self-renewal of GSCs. Silencing of RTVP-1 decreased the self-renewal of GSCs and the expression of CXCR4 and overexpression of CXCR4 abrogated the inhibitory effect of RTVP-1 silencing on GSC self-renewal. These results demonstrate that miR-137 is downregulated in GBM probably due to promoter hypermethylation. miR-137 inhibits GSC self-renewal and promotes their differentiation by targeting RTVP-1 which downregulates CXCR4. Thus, miR-137 and RTVP-1 are attractive therapeutic targets for the eradication of GSCs and for the treatment of GBM.
Glioma stem cells; self renewal; miR-137; RTVP-1; CXCR4
Center-surround antagonistic receptive fields (CSARFs) are building blocks for spatial vision and contrast perception. Retinal horizontal cells (HCs) are the first lateral elements along the visual pathway, and are thought to contribute to receptive field surrounds of higher order neurons. Primate HC receptive fields have not been found to change with light, and dopaminergic modulation has not been investigated. Recording intracellularly from HCs in dark-adapted macaque retina, we found that H1-HCs had large receptive fields (λ = 1,158 ± 137 μm) that were reduced by background light (–45%), gap junction closure (–53%), and D1 dopamine receptor activation (–48%). Tracer coupling was modulated in a correlative manner, suggesting that coupling resistance plays a dominant role in receptive field formation under low light conditions. The D1 antagonist SCH23390 increased the size of receptive fields (+13%), suggesting tonic dopamine release in the dark. Because light elevates dopamine release in primate retina, our results support a dopaminergic role in post-receptoral light adaptation by decreasing HC receptive field diameters, which influences the center-surround receptive field organization of higher-order neurons and thereby spatial contrast sensitivity.
horizontal cell; tracer coupling; retina; dopamine; center surround; electrophysiology
Prior research suggests that older adults are less likely than young adults to use effective learning strategies during intentional encoding. This functional magnetic resonance imaging (fMRI) study investigated whether training older adults to use semantic encoding strategies can increase their self-initiated use of these strategies and improve their recognition memory. The effects of training on older adults' brain activity during intentional encoding were also examined. Training increased older adults' self-initiated semantic encoding strategy use and eliminated pretraining age differences in recognition memory following intentional encoding. Training also increased older adults' brain activity in the medial superior frontal gyrus, right precentral gyrus, and left caudate during intentional encoding. In addition, older adults' training-related changes in recognition memory were strongly correlated with training-related changes in brain activity in prefrontal and left lateral temporal regions associated with semantic processing and self-initiated verbal encoding strategy use in young adults. These neuroimaging results demonstrate that semantic encoding strategy training can alter older adults' brain activity patterns during intentional encoding and suggest that young and older adults may use the same network of brain regions to support self-initiated use of verbal encoding strategies.
aging; cognitive training; fMRI; intentional encoding; prefrontal cortex