Older adults benefit from more widespread brain network integration during working memory.

Neuroimaging evidence suggests that the aging brain relies on a more distributed set of cortical regions than younger adults in order to maintain successful levels of performance during demanding cognitive tasks. However, it remains unclear how task demands give rise to this age-related expansion in cortical networks. To investigate this issue, functional magnetic resonance imaging was used to measure univariate activity, network connectivity, and cognitive performance in younger and older adults during a working memory (WM) task. Here, individuals performed a WM task in which they held letters online while reordering them alphabetically. WM load was titrated to obtain four individualized difficulty levels with different set sizes. Network integration-defined as the ratio of within-versus between-network connectivity-was linked to individual differences in WM capacity. The study yielded three main findings. First, as task difficulty increased, network integration decreased in younger adults, whereas it increased in older adults. Second, age-related increases in network integration were driven by increases in right hemisphere connectivity to both left and right cortical regions, a finding that helps to reconcile existing theories of compensatory recruitment in aging. Lastly, older adults with higher WM capacity demonstrated higher levels of network integration in the most difficult task condition. These results shed light on the mechanisms of age-related network reorganization by demonstrating that changes in network connectivity may act as an adaptive form of compensation, with older adults recruiting a more distributed cortical network as task demands increase.

Online repetitive transcranial magnetic stimulation during working memory in younger and older adults: A randomized within-subject comparison.

Working memory is the ability to perform mental operations on information that is stored in a flexible, limited capacity buffer. The ability to manipulate information in working memory is central to many aspects of human cognition, but also declines with healthy aging. Given the profound importance of such working memory manipulation abilities, there is a concerted effort towards developing approaches to improve them. The current study tested the capacity to enhance working memory manipulation with online repetitive transcranial magnetic stimulation in healthy young and older adults. Online high frequency (5Hz) repetitive transcranial magnetic stimulation was applied over the left dorsolateral prefrontal cortex to test the hypothesis that active repetitive transcranial magnetic stimulation would lead to significant improvements in memory recall accuracy compared to sham stimulation, and that these effects would be most pronounced in working memory manipulation conditions with the highest cognitive demand in both young and older adults. Repetitive transcranial magnetic stimulation was applied while participants were performing a delayed response alphabetization task with three individually-titrated levels of difficulty. The left dorsolateral prefrontal cortex was identified by combining electric field modeling to individualized functional magnetic resonance imaging activation maps and was targeted during the experiment using stereotactic neuronavigation with real-time robotic guidance, allowing optimal coil placement during the stimulation. As no accuracy differences were found between young and older adults, the results from both groups were collapsed. Subsequent analyses revealed that active stimulation significantly increased accuracy relative to sham stimulation, but only for the hardest condition. These results point towards further investigation of repetitive transcranial magnetic stimulation for memory enhancement focusing on high difficulty conditions as those most likely to exhibit benefits.

Complementary topology of maintenance and manipulation brain networks in working memory.

Working memory (WM) is assumed to consist of a process that sustains memory representations in an active state (maintenance) and a process that operates on these activated representations (manipulation). We examined evidence for two distinct, concurrent cognitive functions supporting maintenance and manipulation abilities by testing brain activity as participants performed a WM alphabetization task. Maintenance was investigated by varying the number of letters held in WM and manipulation by varying the number of moves required to sort the list alphabetically. We found that both maintenance and manipulation demand had significant effects on behavior that were associated with different cortical regions: maintenance was associated with bilateral prefrontal and left parietal cortex, and manipulation with right parietal activity, a link that is consistent with the role of parietal cortex in symbolic computations. Both structural and functional architecture of these systems suggested that these cognitive functions are supported by two dissociable brain networks. Critically, maintenance and manipulation functional networks became increasingly segregated with increasing demand, an effect that was positively associated with individual WM ability. These results provide evidence that network segregation may act as a protective mechanism to enable successful performance under increasing WM demand.

Injury risk due to collisions in Major League Baseball.

Purpose is to determine if Major League Baseball plays at risk for collisions have higher injury rates than typical base running plays. 2002-2011 Major League Baseball play data was obtained: non-force putouts by catcher at home plate (Catcher Tag Out), groundball force outs at 2(nd) base with less than 2 outs (Double Play Attempt), and the control play, outfield assisted non-force putouts of runners attempting to advance to 2(nd) or 3(rd) base (Outfield Assist 2(nd)/3(rd)). This list was cross-referenced with 2002-2011 disabled lists to see if an involved player went on the disabled list the day of or day after the play. An on-line search for each match determined if the injury was attributable to that play. Rate calculated per 1 000 plays, severity in days on disabled list. Injury rate and severity for Catcher Tag Out was 6.98 and 45.6 respectively, Double Play Attempt 0.42 and 41.3, Outfield Assist 2(nd/)3(rd) 1.56 and 47.0. Injury rate for Catcher Tag Out was higher (P = 0.03) than the control while Double Play Attempt trended lower (P = 0.05). There was no difference in severity. Catcher Tag Outs carry greater injury risk than typical base running plays. Major League Baseball should consider prohibiting base path collisions.

The effects of necrotic enteritis, aflatoxin B1, and virginiamycin on growth performance, necrotic enteritis lesion scores, and mortality in young broilers.

The effects of increasing aflatoxin B1 concentration (0, 0.75, 1.5 mg/kg) on broilers with or without necrotic enteritis or virginiamycin were determined. In the 23-d study, 22 male Cobb 500 chicks per pen were allotted to 12 treatments (3 × 2 × 2 factorial arrangement) with 8 replications. Intestines of 5 birds per pen were examined for lesions on d 21. Birds were allowed to consume feed and water ad libitum. Aflatoxin was included in the diets from d 0. All birds received a 10× dose of coccidiosis vaccine on d 10. Pens of birds where necrotic enteritis was being induced were on Clostridium perfringens pathogen (CPP) contaminated litter from d 0. Aflatoxin decreased gain and feed intake and resulted in poorer feed:gain, increased mortality, and higher lesion scores. Inducing necrotic enteritis increased lesion scores and decreased feed intake and gain. Adding virginiamycin to the diets improved gain, feed intake, feed conversion, and decreased mortality. There was a 3-way interaction (aflatoxin × virginiamycin × CPP) on gain; increasing aflatoxin decreased gain and the effects of CPP and virginiamycin were dependent on aflatoxin concentration. In the absence of aflatoxin virginiamycin increased gain but was unable to prevent the growth suppression caused by CPP. At 0.75 mg/kg of aflatoxin virginiamycin no longer increased growth in non-CPP challenged birds but was able to increase growth in CPP-challenged birds. At the 1.5 mg/kg of aflatoxin concentration, virginiamycin increased gain in non-CPP-challenged birds but challenging birds with CPP had no effect on gain. Virginiamycin improved overall feed conversion with the greatest improvement at 1.5 mg/kg (aflatoxin × virginiamycin, P < 0.05). Aflatoxin increased lesion scores in unchallenged birds but not in challenged birds (aflatoxin × CPP, P < 0.001). Aflatoxin and necrotic enteritis decrease broiler performance and interact to decrease weight gain, virginiamycin helps improve gain in challenged birds at 0.75 mg/kg of aflatoxin, but not at 1.5 mg/kg of aflatoxin.

Molecular mechanisms of pituitary organogenesis: In search of novel regulatory genes.

Defects in pituitary gland organogenesis are sometimes associated with congenital anomalies that affect head development. Lesions in transcription factors and signaling pathways explain some of these developmental syndromes. Basic research studies, including the characterization of genetically engineered mice, provide a mechanistic framework for understanding how mutations create the clinical characteristics observed in patients. Defects in BMP, WNT, Notch, and FGF signaling pathways affect induction and growth of the pituitary primordium and other organ systems partly by altering the balance between signaling pathways. The PITX and LHX transcription factor families influence pituitary and head development and are clinically relevant. A few later-acting transcription factors have pituitary-specific effects, including PROP1, POU1F1 (PIT1), and TPIT (TBX19), while others, such as NeuroD1 and NR5A1 (SF1), are syndromic, influencing development of other endocrine organs. We conducted a survey of genes transcribed in developing mouse pituitary to find candidates for cases of pituitary hormone deficiency of unknown etiology. We identified numerous transcription factors that are members of gene families with roles in syndromic or non-syndromic pituitary hormone deficiency. This collection is a rich source for future basic and clinical studies.

Variation in injury risk over the course of a two-day youth club soccer tournament.

Athletic injury risk in youth is known to be greater in organised sport, higher levels of competition, games, and tournaments, yet young athletes are often expected to participate in tournaments that involve multiple matches per day on consecutive days. In 2006 and 2008 injury rates were observed during a club youth soccer tournament that involved athletes aged 9-18 years playing three to four matches over two consecutive days, to determine if injury risk varied over the course of the event. The injury rate for day 1 was 7.91/1000 hours with a mean severity of 3.5 days missed versus a day 2 rate of 6.75 and severity of 2.3. The rate and severity for the first game in a day were 7.13 and 3.5 respectively compared to 7.9 and 2.5 for game 2. Further research is needed to determine if a high density match schedule increases injury risk for youth soccer players.

Broiler performance and carcass characteristics when fed diets containing lysine maize (LY038 or LY038 x MON 810), control, or conventional reference maize.

Lysine maize (Zea mays), LY038, was developed through the application of modern biotechnology to accumulate free Lys in the germ portion of maize grain and provide an alternative to direct addition of supplemental Lys to poultry diets. Maize LY038 x MON 810 was produced by conventional breeding of LY038 with MON 810, which provides the corn plant protection against feeding damage from the European corn borer. A 42-d broiler feeding study (10 pens of 10 male Cobb x Cobb 500 broilers/treatment) was conducted to compare the feeding value of grain from LY038 or LY038 x MON 810 to that of a conventional control (similar genetic background to the test maize) and 5 conventional maize hybrids. The LY038 and LY038 x MON 810 maize-based diets and control and conventional reference maize-based diets supplemented with l-Lys HCl were formulated to a Lys level below that required for optimal bird performance, whereas all other essential amino acids were present at levels, relative to Lys, above those required for optimal bird performance [1.05% and 0.90% total Lys (as-fed) for d 0 to 21 and d 21 to 42, respectively]. Total Lys level in control and reference maize-based diets without supplemental l-Lys HCl was formulated to be 0.079% lower than supplemented diets. Weight gain, feed efficiency, and carcass yield and composition of broilers fed diets containing LY038 or LY038 x MON 810 were not different (P > 0.05) from that of broilers fed l-Lys HCl-supplemented diets and were superior (P < or = 0.05) to that of broilers fed conventional maize diets without supplemental l-Lys HCl. Both broiler performance and carcass data demonstrate that the bioefficacy of the incremental Lys in LY038 or LY038 x MON 810 grain was not different from that of Lys in conventional maize diets supplemented with l-Lys HCl. Thus, LY038 and LY038 x MON 810 can be considered as wholesome as and more nutritious than conventional maize due to its higher-than-average Lys content.

Housing quality among North Carolina farmworker families.

Substandard housing poses risks for health and safety. Few studies have documented the housing conditions experienced by Latino farmworker families in the U.S. The purpose of this analysis is to assess the quality of housing occupied by farmworker families in eastern North Carolina and determine how individual and family characteristics are associated with housing quality. Interviews were completed in six North Carolina counties with 186 Latino farmworker households that included a child under the age of 18 to document respondent, household, and dwelling characteristics. Most households were crowded, with 69.4% having more than one person per room (excluding bathrooms and kitchens). Dwellings were often located adjacent to fields (46.0%), suffered from structural problems (e.g., 18.3% had roof leaks), and lacked facilities and appliances (e.g., 26.9% did not have a working oven). Most farmworker family dwellings did not meet the U.S. Department of Housing and Urban Development's minimum criteria for health and safety. Respondents in their thirties, who lived in North Carolina for less than five years, moved two or more times in the past year to follow crops, and lived in grower-provided housing had the poorest housing quality. These results demonstrate that North Carolina Latino farmworker families lack adequate housing. Further research is needed to evaluate farmworker housing conditions in all areas of the U.S., and to document the relationship of these housing conditions to health outcomes. The collaboration of researchers, advocates, policy makers, housing developers, health care providers, and educators is needed to improve the housing conditions of farmworker families.

Oral health and quality of life of migrant and seasonal farmworkers in North Carolina.

Oral health deficits can have a significant effect on workers' general health and their ability to carry out normal activities. Although farmworkers have been found to lack access to dental care, few studies have documented their oral health status or its impact on quality of life (QOL). This research (1) describes the oral health problems experienced and oral health care received by Latino farmworkers in North Carolina, and (2) explores the association between oral health and QOL. Data were collected using face-to-face interviews from a representative sample of 151 farmworkers; data included oral health-related QOL (OHIP-14) and general health-related QOL (SF-12 Health Survey). Workers reported a high number of unmet needs: 52% reported caries, and 33% reported missing teeth. Only 21% had received dental services in the past year, almost all in Mexico rather than the U.S. The dimensions of oral health-related QOL most impaired were psychological discomfort and physical pain caused by dental problems. Number of functional oral health problems was the strongest predictor of oral health-related QOL (p < 0.001) and physical health-related QOL (p < 0.05), but was unrelated to mental health-related QOL. These findings indicate that the high rate of unmet oral health needs is associated with poorer farmworker QOL. The consequences of suffering on-going dental pain for work performance, sleep, and nutritional status are unknown. Because national data indicate that fewer farmworkers are returning to their countries of origin, communities with large farmworker populations need to address their unmet needs for dental care.

A randomized trial of a brief intervention to increase fruit and vegetable intake: a replication study among callers to the CIS.

BACKGROUND: Results are reported from a large randomized trial designed to increase fruit and vegetable consumption among callers to the National Cancer Institute's Cancer Information Service (CIS) (n = 1,717). METHODS: CIS callers assigned to the intervention group (n = 861) received a brief proactive educational intervention over the telephone at the end of usual service, with two follow-up mailouts. Key educational messages and print material derived from the NCI 5 A Day for Better Health program were provided to intervention participants. Participants were interviewed by telephone at 4 weeks (n = 1,307), 4 months (n = 1,180), and 12 months for follow-up (n = 1,016). RESULTS: Results obtained from a single-item measure of fruit and vegetable consumption indicate a significant intervention effect of 0.88 servings per day at 4 weeks follow-up (P < 0.001), 0.63 servings per day at 4 months follow-up (P < 0.001), and 0.43 servings per day at 12 months follow-up (P < 0.001). Using a 7-item food frequency measure, an intervention effect of 0.63 servings per day was obtained at 4 weeks follow-up (P < 0.001), compared with 0.39 servings per day at 4 months follow-up (P = 0.002) and 0.44 servings per day at 12 months follow-up (P = 0.002). A 24-h recall assessment included in the 4-month interviews also yielded a significant intervention effect of 0.67 servings per day (P = 0.015). The vast majority of callers (90%) endorsed the strategy of providing 5 A Day information proactively within the CIS. CONCLUSIONS: This brief educational intervention was associated with higher levels of self-reported fruit and vegetable intake at both short- and long-term follow-up. Additional research is recommended to test this or a similar intervention in diverse populations.

Detecting symptoms of alcohol abuse in primary care settings.

BACKGROUND: Studies on alcohol abuse are frequently based on patients who meet minimum diagnostic criteria, thus ignoring patients with individual symptoms of harmful or hazardous use. Consequently, we are unable to characterize alcohol-abusing patients with sufficient clarity to effectively focus screening for primary prevention. OBJECTIVE: To determine the prevalence of harmful and hazardous use of alcohol, assess screening instruments for detecting alcohol abuse or dependence, and assess the impact of alcohol use on other diagnoses treated in outpatient settings. DESIGN: Survey (cross-sectional study). SETTING: Hospital-based outpatient clinic. PARTICIPANTS: Three hundred randomly selected adults (aged 18 years and older). MAIN OUTCOME MEASURE: Diagnosis of alcohol abuse or dependence based on the Diagnostic Interview Schedule (DIS). RESULTS: About 18% met DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) criteria of abuse or dependence while almost 50% had at least one symptom of harmful or hazardous use. The T-ACE questionnaire, a modified version of the CAGE questionnaire, was the most effective screening instrument for both men and women. Selected diagnoses, personal characteristics such as family history of alcohol abuse, and self-reported patterns of alcohol use could identify patients likely to meet diagnostic criteria. CONCLUSIONS: Many symptoms of substance use disorders are not adequately addressed in outpatient practice. Little is known about how alcohol use in varying quantities affects health care utilization and treatment of conditions commonly seen in outpatient medicine. Consequently, we lack a full appreciation of the burden of disease borne by alcohol use and have yet to achieve a universally accepted method of approaching primary and secondary prevention of alcohol-related problems.

Isolation of developmental mutants of the ascidian Ciona savignyi.

Ascidians have been used extensively as model animals for experimental embryology. We report here the results of a pilot study with the aim of developing genetic methods for the ascidian Ciona savignyi. The chemical mutagen N-ethyl-N-nitrosourea (ENU) was used to induce point mutations. F1 animals, produced by using sperm from ENU-treated animals to fertilize untreated eggs, were grown to reproductive age. Sperm and eggs collected from the hermaphrodite F1 adults were used to generate self-fertilized F2 broods, which were then screened for recessive, zygotically acting mutations. Animals carrying potential mutations were outcrossed to wild type to test for the heritability of the phenotypes. We report on a number of mutants isolated using this method, including several with abnormalities in tail and notochord development.

Building effective partnerships: a national evaluation of the Cancer Information Service outreach program. Part 2.

The Cancer Information Service's (CIS) nationally coordinated, regionally focused outreach program establishes partnerships with government, nonprofit, and private organizations to reach underserved and minority populations. A national random sample telephone survey, conducted with 867 partner organizations who had contact with the CIS in early 1996, assessed the types of CIS assistance used, satisfaction with and usefulness of these services, organizational characteristics, and the overall impact on partners' cancer-related programs. CIS partners provide programs for the medically underserved (79%) and specific racial and ethnic groups (72%) and address a range of cancer control issues. Partners use and highly value an array of CIS assistance. Over 90% are satisfied with the CIS services. Diffusion of accurate and science-based information, materials and resources is a key element of the outreach assistance. Two out of three partners are receiving late-breaking news and scientific information from the CIS and 86% are disseminating it to their constituents. The majority of those partners surveyed reported that they rely on the CIS to assist with their most important cancer programs. Sixty-eight percent of the partners rated the CIS assistance as important or very important to their cancer-related programs. These survey results indicate that the CIS outreach program provides key support to partners' cancer programs and has an impact on their efforts. The results support the effectiveness of a regionally based outreach program working in partnership with existing organizations at the state, county, and local level who are addressing the needs of underserved populations.

Treatment and clinical trials decisionmaking: the impact of the Cancer Information Service. Part 5.

The Cancer Information Service (CIS) provides accurate, up-to-date information to cancer patients, their families, the general public, and health professionals. In 1996, the CIS telephone service received 208,971 calls from people with questions about cancer treatments and clinical trials (total calls = 500,000). Cancer information specialists are trained and certified to access the PDQ database of treatment options and clinical trials, to translate medical information into understandable terms in order to help callers make treatment decisions, and to discuss clinical trials proactively. A telephone service user survey was conducted to assess the satisfaction and impact of the assistance and information provided to CIS callers. Almost half of the callers (46% of those calling for treatment information, 50% calling for clinical trial information) discussed the CIS information with a physician. Over half (55% treatment, 54% clinical trial) said the information helped them make a treatment decision. Twenty-four percent of treatment and 64% of clinical trial callers had enrolled in or had considered a clinical trial. Almost all (95%) were satisfied with information received from the CIS. The authors find that the CIS is fulfilling its role in disseminating information on cancer treatment and clinical trials through its telephone service. The CIS proactively educates treatment callers about clinical trials. However, the CIS needs to apply other strategies to reach medically underserved populations. Although most callers were able to understand the information, clinical trial callers found the information more difficult than did treatment callers. The CIS is working to simplify written clinical trial information.

Promoting cancer prevention and screening: the impact of the Cancer Information Service. Part 7.

Cancer Information Service (CIS) inquiries about cancer prevention and screening are an important opportunity to educate callers about primary or secondary cancer prevention, facilitate their decision-making, and, where appropriate, encourage action. An evaluation was conducted to assess whether these callers' information needs are being satisfied and to determine if the information provided facilitates decisionmaking and subsequent risk reduction actions. A random sample of 2,489 callers was surveyed during a 5-week period, 3 to 6 weeks after their initial call to CIS; prevention or screening was stated as the main reason for calling by 331 respondents. A series of questions was asked regarding level of satisfaction with CIS's performance and how helpful the information provided was in terms of feeling more knowledgeable, making decisions, and taking action. The vast majority of respondents were satisfied with the information received, found it to be helpful, felt more knowledgeable as a result, and would call CIS again with subsequent questions. Although demand characteristics are a possible source of bias, nearly three-quarters of the respondents reported subsequently discussing the information provided with someone else, and almost half sought additional information recommended by CIS. Nearly two-thirds of primary prevention respondents and about half of secondary prevention respondents indicated that they had taken some risk-reducing action subsequent to their interaction with CIS. The CIS is effectively satisfying the information needs of prevention and screening callers; information it is providing is effectively facilitating decisionmaking and stimulating callers to take action.

P2u purinoceptor regulation of mucin secretion in SPOC1 cells, a goblet cell line from the airways.

The SPOC1 cell, a novel goblet cell line derived from rat trachea, was tested for its ability to exhibit regulated mucin secretion in response to purinergic (P2) agonists. High-molecular mass glycoconjugates (HMMGs) purified by CsCl-density-gradient centrifugation had a buoyant density of 1.45 g/ml. The purified HMMG material exhibited a single major band with an apparent molecular mass of greater than 1000 kDa in SDS/ polyacrylamide gels stained with silver or blotted and stained with soya-bean agglutinin. [3H]HMMG was resistant to proteoglycan-degrading enzymes, but was susceptible to neuraminidase. The HMMG was approx. 91% carbohydrate by weight, and the glycosides were O-linked. The HMMG amino acid composition was enriched in Ser and Thr (sum 27%). Thus SPOC1-cell HMMG possess the characteristics of mucin. Mucin secretion by SPOC1 cells, grown on permeable supports and perfused luminally, was stimulated by ATP, UTP and adenosine 5'-[gamma-thio]triphosphate (100 microM) 4-5-fold over a baseline of 4 ng/min. The three dose-effect relations were nearly identical (K0.5 approximately 4 microM). SPOC1 cells grown on plastic and rat tracheal epithelial primary cells responded similarly to ATP and/or UTP. SPOC1 cells failed to respond to other purinergic agonists, either luminally or serosally, and consequently seem to possess an apical membrane P2u purinoceptor. SPOC1-cell total RNA was probed for P2u purinoceptor mRNA. Using conserved primers for both reverse transcriptase and PCR, a single band of the predicted size was observed, which had a nucleotide base sequence identical with the rat P2u purinoceptor mRNA. Thus SPOC1 cells secrete mucin under the control of a P2u purinoceptor; they should prove useful in dissecting the associated cellular regulatory pathways.

Selective kallikrein-kinin system activation in inbred rats differentially susceptible to granulomatous enterocolitis.

BACKGROUND & AIMS: Crohn's disease is characterized by unrestrained inflammation with a genetic component. Genetic susceptibility and activation of the kalli-krein-kinin (contact) system were investigated in experimental enterocolitis and extraintestinal inflammation induced by bacterial polymers. METHODS: Kinetics of inflammation in inbred Lewis and Buffalo rats injected subserosally with peptidoglycan-polysaccharide polymers were correlated with in vivo and in vitro activation of the contact system. RESULTS: Lewis rats had a biphasic course of enterocolitis. Acute inflammation peaked 1 day after injection, gradually decreasing until day 14 when intestinal inflammation spontaneously reactivated and persisted for 16 weeks, accompanied by arthritis, granulomatous hepatitis, anemia, and leukocytosis. Self-limited acute enterocolitis in Buffalo rats resolved by 24 days without extraintestinal involvement. Consumption of the precursor proteins prekalli-krein and high-molecular-weight kininogen indicated activation of the plasma contact system in Lewis rats and closely correlated with chronic intestinal inflammation. Contact system activation did not occur in Buffalo rats, even during acute inflammation. In vitro studies showed a decreased rate of kininogen cleavage in Buffalo plasma. CONCLUSIONS: Selective in vivo and in vitro activation of the contact system in susceptible Lewis rats suggests that this pathway is one determinant of genetic susceptibility to granulomatous enterocolitis and systemic complications.