Visual function in breast-fed term infants weaned to formula with or without long-chain polyunsaturates at 4 to 6 months: a randomized clinical trial

OBJECTIVE: Breast-fed infants receive docosahexaenoic acid (DHA) and arachidonic acid (ARA) in their diet. Upon weaning, infants lose this dietary source of long-chain polyunsaturates because many commercial formulas do not contain these important constituents for neural membrane biogenesis. We evaluated the benefits of postweaning dietary supplementation of DHA + ARA on visual maturation. STUDY DESIGN: Healthy term infants (n = 61) were breast-fed to 4 to 6 months, then were randomly assigned to commercial formula or formula supplemented with DHA (0.36%) + ARA (0.72%). Measurements of red blood cell (RBC) fatty acids, visually evoked potential (VEP) acuity, and stereoacuity were done before and after weaning. RESULTS: At 1 year of age, RBC-DHA in the commercial formula-fed group was reduced by 50% from the weaning level, whereas there was a 24% increase in the DHA + ARA-supplemented group. The primary outcome measure, VEP acuity, was significantly more mature in supplemented infants at 1 year of age. Elevated RBC-DHA levels were associated with more mature VEP acuity. There were no significant diet-related differences in stereoacuity. CONCLUSIONS: These data extend through the first year of life the critical period in which a dietary supply of DHA and ARA can contribute in optimizing visual development in term infants.     

Muscle strength, volume and activation following 12-month resistance training in 70-year-old males

In elderly males muscle plantar flexor maximal voluntary contraction (MVC) torque normalised to muscle volume (MVC/VOL) is reduced compared to young males as a result of incomplete muscle activation in the elderly. The aim of the present study was to determine the influence of a 12-month resistance training programme on muscle volume, strength, MVC/VOL, agonist activation and antagonist coactivation of the plantarfexors in elderly males. Thirteen elderly males aged 70 years and over (range 70–82 years), completed a 12-month whole body resistance-training programme (TRN), training three times a week. Another eight males (range 18–30 years), who maintained their habitual physical activity for the same 12-month period as the TRN group acted as controls (CTRL). Isometric plantarflexor maximal voluntary contraction (MVC) torque increased in the TRN group by 20% (P<0.01), from 113.1±22.0 Nm to 141.5±19.2 Nm. Triceps surae volume (TS VOL) assessed using MRI, increased by 12%, from 796.3±78.9 cm³ to 916.8±144.4 cm³ . PF activation, measured using supramaximal double twitch interpolation, increased from 83.6±11.0% pre training, to 92.1±7.6% post training (P<0.05). Dorsiflexion MVC and antagonist coactivation (assessed using surface electromyography) did not change with training. Plantarflexor MVC torque normalized for triceps surae muscle volume (MVC/VOL) was 142.6±32.4 kN m^–2 before training and 157.0± 27.9 kN m^–2 after training (a non-significant increase of 8%). No significant change in any measurement was observed in the CTRL group. This study has shown that the gain in muscle strength in response to long-term (12-month) training in older men is mostly accounted for by an increased muscle volume and activation.     

Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes

Background

Asthma is a chronic respiratory disease whose genetic basis has been explored for over two decades, most recently via genome-wide association studies. We sought to find asthma-susceptibility variants by using probands from a single population in both family-based and case-control association designs.

Methods

We used probands from the Childhood Asthma Management Program (CAMP) in two primary genome-wide association study designs: (1) probands were combined with publicly available population controls in a case-control design, and (2) probands and their parents were used in a family-based design. We followed a two-stage replication process utilizing three independent populations to validate our primary findings.

Results

We found that single nucleotide polymorphisms with similar case-control and family-based association results were more likely to replicate in the independent populations, than those with the smallest p-values in either the case-control or family-based design alone. The single nucleotide polymorphism that showed the strongest evidence for association to asthma was rs17572584, which replicated in 2/3 independent populations with an overall p-value among replication populations of 3.5E-05. This variant is near a gene that encodes an enzyme that has been implicated to act coordinately with modulators of Th2 cell differentiation and is expressed in human lung.

Conclusions

Our results suggest that using probands from family-based studies in case-control designs, and combining results of both family-based and case-control approaches, may be a way to augment our ability to find SNPs associated with asthma and other complex diseases.     

Associations of osseous abnormalities in Neurofibromatosis 1

The characteristic sites of Neurofibromatosis 1-associated osseous manifestations are the long bones (usually the tibia and fibula), vertebrae and sphenoid wing. Although these focal bony lesions may cause profound clinical consequences, a minority of people with NF1 are affected. However, most people with NF1 are shorter than expected for their age, gender and family. The pathogenesis of NF1 focal osteopathy and its relationship, if any, to short stature are unknown. We examined associations between the occurrence of various osseous lesions in 3377 NF1 probands from the Children's Tumor Foundation NF International Database. Using logistic regression analysis among 260 NF1 probands who had undergone radiological examination of both the spine and skull, we found associations between the occurrence of sphenoid wing and long bone osteopathy (conditional odds ratio [OR] = 6.1; 95% confidence interval [CI] = 1.7-22.3; P = 0.006) and between sphenoid wing and vertebral osteopathy (OR = 16.9; 95% CI = 5.3-53.3; P < 0.001) after adjusting for age and gender. Similar findings were observed from all 3377 NF1 probands using a multivariate probit regression model. In a separate analysis, we found lower age- and gender-standardized height in patients who had characteristic vertebral or sphenoid wing lesions than in people who did not (P < 0.05). We found no relationship between height and tibial osteopathy. We conclude that some people with NF1 are more likely to develop osseous manifestations than others and speculate that there may be a common pathogenetic mechanism responsible for the development of osseous abnormalities and that of the vertebrae and long bones.     

Gastrocnemius specific force is increased in elderly males following a 12-month physical training programme

The aim of the present investigation was to determine whether muscle force per physiological cross sectional area (PCSA) of the lateral gastrocnemius (GL) of elderly males increased following a 12-month physical training programme. Eleven elderly males were assigned to a 12-month training programme (TRN mean age 72.7 ± 3.3 years, mean ± SD) and eight elderly males were allocated to a control group (CTRL, 73.9 ± 4.0 years) who maintained their habitual physical activity levels. In vivo measurements of muscle architecture, muscle volume (VOL), achilles tendon moment arm length and plantarflexor torque were used to estimate GL PCSA (VOL/fascicle length) and specific force (GL fascicle force/GL PCSA). Maximal GL fascicle force was calculated accounting for agonist muscle activation and antagonist co-activation. Following training GL fascicle force increased by 31% (P < 0.01), which was not entirely accounted for by a 17% increase in PCSA (from 27.2 ± 5.9 to 31.8 ± 6.2 cm², P < 0.05). Specific force increased significantly from 8.9 ± 1.9 to 11.2 ± 3.0 N cm⁻² (P < 0.05). Pennation angle, but not fascicle length, increased by 12% with training (P < 0.05). The CTRL group showed no change in muscle size, strength or architecture over the 12-month period. In conclusion, with the level of agonist and antagonist muscle activity accounted for a 12-month strength training programme resulted in an increase in both PCSA and specific force in elderly males.     

Mutations in the RP1 gene causing autosomal dominant retinitis pigmentosa.

Retinitis pigmentosa is a genetically heterogeneous form of retinal degeneration that affects approximately 1 in 3500 people worldwide. Recently we identified the gene responsible for the RP1 form of autosomal dominant retinitis pigmentosa (adRP) at 8q11-12 and found two different nonsense mutations in three families previously mapped to 8q. The RP1 gene is an unusually large protein, 2156 amino acids in length, but is comprised of four exons only. To determine the frequency and range of mutations in RP1 we screened probands from 56 large adRP families for mutations in the entire gene. After preliminary results indicated that mutations seem to cluster in a 442 nucleotide segment of exon 4, an additional 194 probands with adRP and 409 probands with other degenerative retinal diseases were tested for mutations in this region alone. We identified eight different disease-causing mutations in 17 of the 250 adRP probands tested. All of these mutations are either nonsense or frameshift mutations and lead to a severely truncated protein. Two of the eight different mutations, Arg677X and a 5 bp deletion of nucleotides 2280-2284, were reported previously, while the remaining six mutations are novel. We also identified two rare missense changes in two other families, one new polymorphic amino acid substitution, one silent substitution and a rare variant in the 5'-untranslated region that is not associated with disease. Based on this study, mutations in RP1 appear to cause at least 7% (17/250) of adRP. The 5 bp deletion of nucleotides 2280-2284 and the Arg677X nonsense mutation account for 59% (10/17) of these mutations. Further studies will determine whether missense changes in the RP1 gene are associated with disease, whether mutations in other regions of RP1 can cause forms of retinal disease other than adRP and whether the background variation in either the mutated or wild-type RP1 allele plays a role in the disease phenotype.     

Growth in North American white children with neurofibromatosis 1 (NF1)

OBJECTIVE—To analyse the distributions of and generate growth charts for stature and occipitofrontal circumference (OFC) in neurofibromatosis 1 (NF1) patients.
DESIGN—Cross sectional database survey.
SETTING—The National Neurofibromatosis Foundation International Database (NFDB) includes clinical information on NF1 patients from 14 participating centres in North America.
SUBJECTS—A total of 569 white, North American, NF1 patients, 55% female and 45% male.
MAIN OUTCOME MEASURES—Stature and OFC measurements of NF1 patients were compared to age and sex matched population norms using z score standardisation and centile curves.
RESULTS—The distributions of stature and OFC are shifted and unimodal among NF1 patients; 13% of patients have short stature (2 standard deviations below the population mean) and 24% have macrocephaly (OFC 2 standard deviations above the population mean).
CONCLUSIONS—Alterations of stature and OFC are not limited to NF1 patients with frank short stature or macrocephaly.


Keywords: neurofibromatosis 1; stature; occipitofrontal circumference; macrocephaly     

Observations on the distribution and control of Salmonella in commercial duck hatcheries in the UK

Salmonella infection causes a significant number of cases of gastroenteritis and more serious illnesses in people in the UK and EU. The serovars Salmonella Enteritidis and Salmonella Typhimurium are most frequently associated with foodborne illness in Europe. Whilst control programmes exist to monitor these serovars in the chicken and turkey sectors, no regulatory programme is currently in place for the duck sector. A voluntary industry scheme (Duck Assurance Scheme) was launched in the UK in 2010. Hatcheries act as focal points of Salmonella contamination, in particular if Salmonella-contaminated eggs from positive breeding farms enter the hatchery. Five duck hatcheries were visited in this study and four were positive for Salmonella. S. Typhimurium DT8 and S. Indiana were isolated from hatchery 1 and S. Typhimurium DT41 and S. Senftenberg were isolated from hatchery 3. S. Kottbus, S. Bovismorbificans and S. Senftenberg were isolated from hatchery 2 and S. Kedougou was isolated from hatchery 4. Advice on the control/elimination of Salmonella was provided at each visit and a longitudinal study was undertaken to monitor its effectiveness. Extensive sampling was carried out in the hatcheries visited and the tray wash area and waste/external areas had the highest probability of being contaminated. The hatcher area was also found to be a primary focus of contamination. Improvements of farm and hatchery biosecurity standards have resulted in a reduction of hatchery contamination in this study and in previous investigations. Hatcheries 1 and 5 were cleared of Salmonella, demonstrating that elimination of Salmonella contamination from duck hatcheries is achievable.     

Novel mutations in the thymidine kinase and DNA polymerase genes of acyclovir and foscarnet resistant herpes simplex viruses infecting an immunocompromised patient.

BACKGROUND: Mutations in the thymidine kinase (TK) and DNA polymerase (pol) genes of herpes simplex virus (HSV) may confer resistance to antiviral drugs, particularly in the context of immunosuppression induced by infection with the human immunodeficiency virus (HIV). OBJECTIVES: To characterise the HSV type 2 (HSV-2) TK and DNA pol genes in an immunocompromised patient with clinical resistance to both acyclovir and foscarnet. STUDY DESIGN: The TK and DNA pol genes of isolates obtained over a 2-year period from an AIDS patient with severe genital herpes infection were characterised both phenotypically and genotypically. RESULTS: HSV strains that were acyclovir resistant/foscarnet sensitive, acyclovir sensitive/foscarnet sensitive and acyclovir resistant/foscarnet resistant were isolated during this time. The TK gene of all the acyclovir resistant isolates contained a large 969 bp deletion which extended into a downstream untranslated region. The foscarnet resistance was associated with an S725G mutation in a conserved region (region II) of the herpesvirus DNA pol gene. CONCLUSIONS: Clinical and virological suppression of the infection was not always associated with subsequent reactivation with wild-type virus. Mutations of the nature we describe have not previously been reported occurring simultaneously in HSV strains isolated from patients treated with acyclovir and foscarnet.