Aerobic Fitness and the Brain: Increased N-Acetyl-Aspartate and Choline Concentrations in Endurance-Trained Middle-Aged Adults

Engagement in regular aerobic exercise is associated with cognitive benefits, but information on the mechanisms governing these changes in humans is limited. The goal of the current study was to compare neurometabolite concentrations relating to cellular metabolism, structure, and viability in endurance-trained and sedentary middle-aged adults. Twenty-eight endurance-trained and 27 sedentary adults, aged 40–65 years, underwent general health assessment, cardiorespiratory fitness measurement, neuropsychological testing, and proton magnetic resonance spectroscopy (¹H MRS). ¹H MRS was used to examine N-acetyl-aspartate (NAA), creatine (Cr), myo-inositol (mI), choline (Cho), and glutamate (Glu) concentrations in frontal and occipitoparietal grey matter. Group differences in concentrations of NAA, Cho, mI, and Glu, calculated as ratios over Cr, were explored using ANOVA. There were no significant differences in global cognitive function, memory, and executive function performance between the groups. In comparison to sedentary adults, the endurance-trained group displayed significantly higher NAA/Cr in the frontal grey matter (F(1, 53) = 5.367, p = 0.024) and higher Cho/Cr in the occipitoparietal grey matter (F(1, 53) = 5.138, p = 0.028). Within our middle-aged sample, endurance-trained adults demonstrated higher levels of NAA/Cr in the frontal grey matter and higher Cho/Cr in the occipitoparietal grey matter. Higher levels of NAA may indicate greater neuronal integrity and higher cerebral metabolic efficiency in association with cardiorespiratory fitness, whereas increased Cho may represent increased phospholipid levels secondary to neural plasticity.     

Molecular Characterization of Enterotoxigenic Escherichia coli Isolates Recovered from Children with Diarrhea during a 4-Year Period (2007 to 2010) in Bolivia

Enterotoxigenic Escherichia coli (ETEC) is an important cause of childhood diarrhea. This study aimed to characterize ETEC strains isolated from Bolivian children aged <5 years according to enterotoxin profile, colonization factors (CFs), suggested virulence genes, and severity of disease. A total of 299 ETEC isolates recovered from children with diarrhea and 55 ETEC isolates from children without diarrhea (controls) were isolated over a period of 4 years. Strains expressing heat-labile toxin (LT) or heat-stable toxin (ST) alone were about equally common and twice as common as ETEC producing both toxins (20%). ETEC strains expressing human ST (STh) were more common in children aged <2 years, while ETEC strains expressing LT plus STh (LT/STh) were more frequent in 2- to 5-year-old children. Severity of disease was not related to the toxin profile of the strains. CF-positive isolates were more frequently identified in diarrheal samples than in control samples (P = 0.02). The most common CFs were CFA/I and CS14. CFA/I ETEC strains were more frequent in children aged <2 years than CS1+CS3 isolates and CS14 isolates, which were more prevalent in 2- to 5-year-old children. The presence of suggested ETEC virulence genes (clyA, eatA, tia, tibC, leoA, and east-1) was not associated with disease. However, east-1 was associated with LT/STh strains (P < 0.001), eatA with STh strains (P < 0.001), and tia with LT/STh strains (P < 0.001). A minor seasonal peak of ETEC infections was identified in May during the cold-dry season and coincided with the peak of rotavirus infections; this pattern is unusual for ETEC and may be important for vaccination strategies in Bolivia.     

Tau‐positive nuclear indentations in P301S tauopathy mice

Increased incidence of neuronal nuclear indentations is a well‐known feature of the striatum of Huntington's disease (HD) brains and, in Alzheimer's disease (AD), neuronal nuclear indentations have recently been reported to correlate with neurotoxicity caused by improper cytoskeletal/nucleoskeletal coupling. Initial detection of rod‐shaped tau immunostaining in nuclei of cortical and striatal neurons of HD brains and in hippocampal neurons of early Braak stage AD led us to coin the term “tau nuclear rods (TNRs).” Although TNRs traverse nuclear space, they in fact occupy narrow cytoplasmic extensions that fill indentations of the nuclear envelope and we will here refer to this histological hallmark as Tau‐immunopositive nuclear indentations (TNIs). We reasoned that TNI formation is likely secondary to tau alterations as TNI detection in HD correlates with an increase in total tau, particularly of the isoforms with four tubulin binding repeats (4R‐tau). Here we analyze transgenic mice that overexpress human 4R‐tau with a frontotemporal lobar degeneration‐tau point mutation (P301S mice) to explore whether tau alteration is sufficient for TNI formation. Immunohistochemistry with various tau antibodies, immunoelectron microscopy and double tau‐immunofluorescence/DAPI‐nuclear counterstaining confirmed that excess 4R‐tau in P301S mice is sufficient for the detection of abundant TNIs that fill nuclear indentations. Interestingly, this does not correlate with an increase in the number of nuclear indentations, thus suggesting that excess total tau or an isoform imbalance in favor of 4R‐tau facilitates tau detection inside preexisting nuclear indentations but does not induce formation of the latter. In summary, here we demonstrate that tau alteration is sufficient for TNI detection and our results suggest that the neuropathological finding of TNIs becomes a possible indicator of increased total tau and/or increased 4R/3R‐tau ratio in the affected neurons apart from being an efficient way to monitor pathology‐associated nuclear indentations.     

Adenosine A2A receptors are up-regulated in Pick's disease frontal cortex

Adenosine A2A receptors (A2AR) are highly expressed in striatum. However, they are also present in extrastriatal structures. A2AR were studied in post-mortem human frontal cortex from Pick's disease (PiD) and age-matched non-demented controls by radioligand binding assays, Western-blotting, real-time PCR and adenylyl cyclase activity determination. Saturation binding assay using [3H]ZM 241385, a selective A2A antagonist, as radioligand revealed a significant increase in total adenosine A2AR numbers (Bmax) in frontal cortex from PiD samples (191% of control Bmax), suggesting up-regulation of this receptor. A significant increase in the level of A2AR was also detected by Western-blotting. Furthermore, expression of mRNA coding A2AR determined by quantitative real-time PCR was enhanced. In agreement, stimulation of adenylyl cyclase by CGS 21680, a selective A2A receptor agonist, was significantly strengthened. Up-regulation of A2B receptors and their corresponding mRNA was also observed. These results show that A2A adenosine receptor/adenylyl cyclase transduction pathway is up-regulated and sensitized in frontal cortex brain from PiD.     

Birth weight charts for gestational age in 63 620 healthy infants born in Peruvian public hospitals at low and at high altitude

Aim: To construct distribution curves for birth weight, length and head circumference using a large sample of infants born at low (150 m) and high (3000–4400 m) altitude.
Methods: Cross-sectional analysis of a perinatal database. All live singleton deliveries from public hospitals during 2001–2006 (gestational age from 26 to 42 weeks) with no history of perinatal deaths or smoking and no current obstetric complications (n = 63 620) were included. Fractional polynomial regression models were used to smooth curves for each gestational age.
Results: Mean and median birth weight differences between those born at low and high altitudes reached statistical significance after 35 and 33 weeks, respectively. Values of the 10th percentile were higher at low altitude from 36 weeks, whereas values at the 90th percentile were different from 34 weeks. In the Peruvian growth curves, birth weight was greater at each gestational age than in the curves derived by Lubchenco.
Conclusion: Altitude affects growth patterns; these growth standards will provide useful references for the care of the newborn in highland populations. In addition, the data have implications for the antepartum management of pregnant patients undergoing sonographic evaluation of fetal weight in whom new definitions of what represents small or large for gestational age in utero can result in differences in time or mode of delivery.     

The association between human papillomavirus deoxyribonucleic acid status and the results of cytologic rescreening tests in young, sexually active women.

We examined the utility of cytologic rescreening tests in women who had positive test results for human papillomavirus deoxyribonucleic acid but who were diagnosed as having benign conditions at cytologic testing. One hundred twenty-five Papanicolaou smears from women who were screened for human papillomavirus deoxyribonucleic acid were sent routinely to a private laboratory for diagnoses. These slides were then reviewed independently by two pathologists who were blinded to the human papillomavirus deoxyribonucleic acid results. The effects of cytologic rescreening in cases of both positive and negative human papillomavirus deoxyribonucleic acid were assessed by calculating z scores. Cervical intraepithelial neoplasia was diagnosed in 40% by pathologist A and in 20% by pathologist B of the human papillomavirus-positive subjects compared with none diagnosed by the private cytology laboratory (z = 3.09, p less than 0.005 and z = 1.98, p less than 0.05, respectively). No significant differences were found in the human papillomavirus-negative group. We conclude that cytologic rescreening in human papillomavirus deoxyribonucleic acid-positive women who were initially diagnosed as having benign cytologic results will yield a significant proportion of cases of cervical intraepithelial neoplasia.     

Implementing a syphilis elimination and importation control strategy in a low-incidence urban area: San Diego County, California, 1997-1998

OBJECTIVES: This study assessed a strategy designed to contain imported cases of syphilis and prevent reestablishment of ongoing transmission. METHODS: Reported syphilis cases during an endemic period (1990-1992) and an elimination period (1997-1998) were compared in San Diego, Calif. The elimination strategy, which focuses on rapid reporting of infectious syphilis cases by clinicians, prompt partner and sexual network management, outreach to marginalized populations, and implementation of an outbreak containment plan, was evaluated. RESULTS: Infectious syphilis incidence rates declined from 18.3 per 100,000 in 1998 to 1.0 per 100,000 in 1998. Of the 46 cases involving probable infection during 1997-1998, 19 (41%) were imported, mostly (79%) from Mexico. Outbreak containment procedures were implemented successfully for 2 small clusters. Outreach workers provided sexually transmitted disease information to a large number of individuals; however, no cases of infectious syphilis were identified, suggesting that syphilis transmission was not occurring among marginalized groups. CONCLUSIONS: This syphilis elimination and importation control strategy will require monitoring and adjustments. Controlling syphilis along the US-Mexico border is a necessary component of syphilis elimination in the United States.