Impaired long‐term potentiation–like cortical plasticity in presymptomatic genetic frontotemporal dementia

Neurophysiological biomarkers were assessed using a transcranial magnetic stimulation multiparadigm approach in 13 presymptomatic (n = 13 Granulin) and 14 symptomatic (n = 11 Granulin, n = 3 C9orf72) subjects with a pathogenic mutation for frontotemporal dementia (FTD). Intracortical facilitation and long‐term potentiation–like plasticity were impaired in presymptomatic carriers, compared to healthy controls, more than 15 years before expected symptom onset. In symptomatic carriers, a decrease in short‐interval intracortical inhibition, compared to presymptomatic carriers, was found. In conclusion, these biomarkers could provide the footprints of specific physiopathological processes in the development of this disease and possibly support the diagnosis of autosomal‐dominant FTD. Ann Neurol 2016;80:472–476     

Use of complementary and alternative therapies in outpatients with Parkinson's disease in Argentina

We interviewed 300 patients (54.7% male; mean age was 65.8 ± 9.5) attending the Movement Disorders Clinic at the Buenos Aires University Hospital to determine the prevalence of CATs use and their association with demographic, social, or disease‐specific characteristics among patients with Parkinson's disease (PD) in Buenos Aires, Argentina. We found that 25.7% of the PD patients interviewed (77/300) stated they had used CATs to improve their PD symptoms whereas 38.0% (114/300) had used some CATs without any relation to PD, at least once in life. At the moment of the interview, CATs prevalence use was 50.6% in the former group and 25.0% in the latter. The use of CATs was much more frequent among women and more common in the 50‐ to 69‐year age group. Friends and neighbors of the patients had most frequently recommended these therapies. No major association was observed between CATs use and the duration of the disease, side of initial involvement, PD phenotype, or the Hoehn and Yahr staging. Acupuncture, homeopathy, yoga, and therapeutic massage were the most widely used therapies. After the initiation of conventional treatment the use of massage, yoga, and acupuncture in patients using CATs to improve PD significantly increased. Neurologists should be aware and inquire about the use of CATs to rule out potentially harmful effects. © 2010 Movement Disorder Society     

Trophic cascade facilitates coral recruitment in a marine reserve

Reduced fishing pressure and weak predator-prey interactions within marine reserves can create trophic cascades that increase the number of grazing fishes and reduce the coverage of macroalgae on coral reefs. Here, we show that the impacts of reserves extend beyond trophic cascades and enhance the process of coral recruitment. Increased fish grazing, primarily driven by reduced fishing, was strongly negatively correlated with macroalgal cover and resulted in a 2-fold increase in the density of coral recruits within a Bahamian reef system. Our conclusions are robust because four alternative hypotheses that may generate a spurious correlation between grazing and coral recruitment were tested and rejected. Grazing appears to influence the density and community structure of coral recruits, but no detectable influence was found on the overall size-frequency distribution, community structure, or cover of corals. We interpret this absence of pattern in the adult coral community as symptomatic of the impact of a recent disturbance event that masks the recovery trajectories of individual reefs. Marine reserves are not a panacea for conservation but can facilitate the recovery of corals from disturbance and may help sustain the biodiversity of organisms that depend on a complex three-dimensional coral habitat.     

Natural variability in the HR-1 and HR-2 domains of HIV type 1 gp41 from different clades circulating in Italy

The human immunodeficiency virus type 1 (HIV-1) HR-1 and HR-2 gp41 regions were sequenced in a total of 228 plasma or peripheral blood mononuclear cell samples obtained from an equal number of enfuvirtide-naive subjects for pol genotypic resistance testing in clinical practice. Phylogenetic analysis of the env sequences indicated that 102 belonged to subtype B and 95 to non-B subtypes (31 CRF02_AG, 21 F1, 14 C, 11 A1/A2/A3, 9 CRF01_AE, 9 others) while the remaining 31 were unique recombinant forms. There was considerable variability in the consensus sequence of different clades, particularly in HR-2. The HR-1 amino acid region 36-45, containing all of the enfuvirtide resistance mutations so far characterized, was well conserved except for position 42 where serine and asparagine were unevenly distributed in different subtypes. Enfuvirtide resistance mutations were not present in any sample, reinforcing the expectation that enfuvirtide is effective against many different HIV-1 clades and recombinants. However, some of the mutations outside the amino acid 36-45 region and provisionally suggested to play a role in modulating resistance were detected in a minority of cases. Molecular epidemiological surveys coupled with long-term observation of in vivo response to enfuvirtide and future fusion inhibitors are required to clarify the clinical significance of gp41 natural variability.     

Recruitment to a physical activity intervention study in women at increased risk of breast cancer

Background  

Physical activity is being studied as a breast cancer prevention strategy. Women at risk of breast cancer report interest in lifestyle modification, but recruitment to randomized physical activity intervention studies is challenging.     

BODE Index and GOLD Staging as Predictors of 1-Year Exacerbation Risk in Chronic Obstructive Pulmonary Disease

BackgroundThe body mass index/airflow obstruction/dyspnea/exercise capacity (BODE) index and global initiative for chronic obstructive lung disease (GOLD) staging system are validated measures to define disease severity and to predict survival in chronic obstructive pulmonary disease (COPD). We aimed to investigate the influence of BODE classes (score: 0–2, 3–4, 5–7, and 7–10) and GOLD stages (I, II, III, and IV) on the moderate/severe exacerbation occurrence risk in a cohort of 120 mild/very severe stable patients with COPD.MethodsDemographics, clinical evaluation, spirometry, peripheral oxygen saturation, body composition, 6-minute walking distance, dyspnea, and quality of life measurements were obtained at baseline. Patients were followed up for 1 year or until death, and information on exacerbation was collected.ResultsThe median annual exacerbation rate was 0.8. Logistic regression showed that the relationship between the risk for moderate/severe exacerbations during a 1-year follow-up for the GOLD stage was odds ratio: 2.01;95% confidence interval: 1.39–2.98 and for the BODE index was odds ratio: 2.08; 95% confidence interval: 1.27–3.61. The area under the receiver-operator curve to predict exacerbation during the 1-year follow-up was 0.69 for the GOLD stage and 0.62 for the BODE index. Adjusted multiple logistic regression selected only older age and lower peripheral oxygen saturation as risk factors for COPD exacerbation in the 1-year follow-up.ConclusionsIn summary, our study shows that unidimensional GOLD classification and multidimensional BODE index staging systems seem to have similar clinical utility in predicting exacerbation in ambulatory COPD patients with COPD. However, variables not included in both systems seem to be the main predictors of the exacerbation risk.     

Neuroacanthocytosis and carbamazepine responsive paroxysmal dyskinesias

Neuroacanthocytosis (NA) comprises a genetically heterogeneous group of disorders characterized by dysfunction of the erythrocyte membrane, presenting with acanthocytes and several neurological manifestations. We report the case of a 42-year-old woman with NA who in addition had episodes consistent with paroxysmal dyskinesias. She was diagnosed with NA featuring mild chorea, weakness of the right lower extremity and myoclonic jerks. However, one year after onset she presented attacks of paroxysmal abnormal movements, consistent with paroxysmal kinesigenic dyskinesias. Carbamazepine markedly reduced the frequency and severity of the attacks. Our case illustrates that paroxysmal dyskinesias can be a hitherto unrecognized manifestation of neuroacanthocytosis responsive to carbamazepine.     

Strength training recommendations for the young athlete

In recent years there has been a significant increase in the number of youth participating in organized and competitive sports. Recent studies have supported the participation of preadolescent athletes in strength training to improve health and performance in sports. This article presents the most recent data available to help youth develop a safe and effective strength training program. Variables, such as the recommended rate of progression, the number of sets and repetitions an athlete should perform on each exercise, and how often an athlete needs to workout to avoid loss of strength achieved during a period of strength training are presented.     

1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines: a series of potent and selective dopamine D(3) receptor antagonists

The discovery of new highly potent and selective dopamine D3 receptor antagonists has recently permitted characterization of the role of the dopamine D3 receptor in a wide range of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine-seeking behavior in the rat, reduces oral operant alcohol self-administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.