Face-specific identification impairments following sight-providing treatment may be alleviated by an initial period of low visual acuity.

Identifying faces requires configural processing of visual information. We previously proposed that the poor visual acuity experienced by newborns in their first year of life lays the groundwork for such configural processing by forcing integration over larger spatial fields. This hypothesis predicts that children treated for congenital cataracts late in life will exhibit persistent impairments in face- but not object-identification, because they begin their visual journey with higher than newborn acuity. This would not be the case for patients whose pretreatment condition has allowed for initial low acuity vision, like that of a newborn. Here, we test this prediction by assessing the development of facial identification skill in three groups: patients treated for congenital cataracts whose pretreatment visual acuity was worse than that of a newborn, patients whose pretreatment acuity was better than that of a newborn, and age-matched controls. We find that while both patient groups show significant gains in object-identification, the emergence of face identification is determined by pretreatment acuity: patients with pre-operative acuity worse than a newborn did not show any improvements on face-identification tasks despite years of visual experience, whereas those with pretreatment acuity comparable to a newborn improved on both the object- and face-identification tasks. These findings not only answer our research question but also provide new insights into the role of early visual acuity in facial identification development. We discuss these results in the context of both typical and atypical visual development.

DNA methylation signatures in cord blood associated with birthweight are enriched for dmCpGs previously associated with maternal hypertension or pre-eclampsia, smoking and folic acid intake.

Many epidemiological studies have linked low birthweight to an increased risk of non-communicable diseases (NCDs) in later life, with epigenetic proceseses suggested as an underlying mechanism. Here, we sought to identify neonatal methylation changes associated with birthweight, at the individual CpG and genomic regional level, and whether the birthweight-associated methylation signatures were associated with specific maternal factors. Using the Illumina Human Methylation EPIC array, we assessed DNA methylation in the cord blood of 557 and 483 infants from the UK Pregnancies Better Eating and Activity Trial and Southampton Women's Survey, respectively. Adjusting for gestational age and other covariates, an epigenome-wide association study identified 2911 (FDR≤0.05) and 236 (Bonferroni corrected p ≤ 6.45×10-8) differentially methylated CpGs (dmCpGs), and 1230 differentially methylated regions (DMRs) (Stouffer ≤0.05) associated with birthweight. The top birthweight-associated dmCpG was located within the Homeobox Telomere-Binding Protein 1 (HMBOX1) gene with a 195 g (95%CI: -241, -149 g) decrease in birthweight per 10% increase in methylation, while the top DMR was located within the promoter of corticotropin-releasing hormone-binding protein (CRHBP). Furthermore, the birthweight-related dmCpGs were enriched for dmCpGs previously associated with gestational hypertension/pre-eclampsia (14.51%, p = 1.37×10-255), maternal smoking (7.71%, p = 1.50 x 10-57) and maternal plasma folate levels during pregnancy (0.33%, p = 0.029). The identification of birthweight-associated methylation markers, particularly those connected to specific pregnancy complications and exposures, may provide insights into the developmental pathways that affect birthweight and suggest surrogate markers to identify adverse prenatal exposures for stratifying for individuals at risk of later NCDs.

A simpler definition of major depressive disorder.

BACKGROUND: The DSM-IV symptom criteria for major depressive disorder (MDD) are somewhat lengthy, with many studies showing that treatment providers have difficulty recalling all nine symptoms. Moreover, the criteria include somatic symptoms that are difficult to apply in patients with medical illnesses. In a previous report, we developed a briefer definition of MDD that was composed of the mood and cognitive symptoms of the DSM-IV criteria, and found high levels of agreement between the simplified and full DSM-IV definitions. The goal of the present study was to replicate these findings in another large sample of psychiatric out-patients and to extend the findings to other patient samples. METHOD: We interviewed 1100 psychiatric out-patients and 210 pathological gamblers presenting for treatment and 1200 candidates for bariatric surgery. All patients were interviewed by a diagnostic rater who administered a semi-structured interview. We inquired about all symptoms of depression for all patients. RESULTS: In all three samples high levels of agreement were found between the DSM-IV and the simpler definition of MDD. Summing across all 2510 patients, the level of agreement between the two definitions was 95.5% and the kappa coefficient was 0.87. CONCLUSIONS: After eliminating the four somatic criteria from the DSM-IV definition of MDD, a high level of concordance was found between this simpler definition and the original DSM-IV classification. This new definition offers two advantages over the current DSM-IV definition--it is briefer and it is easier to apply with medically ill patients because it is free of somatic symptoms.

Economic evaluation of a randomized clinical trial of haemodilution with cell salvage in aortic surgery.

BACKGROUND: This study evaluated the costs of acute normovolaemic haemodilution (ANH) and intraoperative cell salvage (ICS) versus homologous blood transfusion in aortic surgery in a prospective multicentre randomized trial. METHODS: One hundred and forty-five patients were randomized either to standard transfusion practice (homologous) or to a combination of ANH and ICS (autologous). Costs for each inpatient admission were identified. Cell salvage costs were assigned on the assumption that 50 operations were done each year employing a trained cell salvage operator. The results were analysed statistically using bias-corrected bootstrap analysis. RESULTS: Patients who had transfusion of homologous blood received some 251 units and those having a homologous transfusion received 103 units (P = 0.008). There was no difference in morbidity, mortality and duration of hospital stay. Transfusion-related mean costs were similar at 340 UK pounds for patients having a homologous transfusion and 357 UK pounds for those receiving autologous blood (mean difference 17 UK pounds (95 per cent confidence interval [c.i.]--184 UK pounds to 174 UK pounds); P not significant). There was also no significant difference in mean overall costs: 5859 UK pounds for homologous and 5384 UK pounds for autologous transfusion (mean difference--475 UK pounds (95 per cent c.i.--2231 UK pounds to 1342 UK pounds)). Sensitivity analysis showed that costs remained similar for 20 and 150 operations per annum. Exclusion of a dedicated cell salvage operator reduced autologous transfusion costs but did not have a significant impact on overall cost. CONCLUSION: Autologous transfusion is cost neutral in aortic surgery even when surgical activity is low.

The influence of homologous blood transfusion on immunity and clinical outcome in aortic surgery.

OBJECTIVES: To evaluate the influence of homologous blood transfusion on immune responses and post-operative morbidity in aortic surgery. DESIGN: Analysis of the effects of homologous blood transfusion in 128 patients in a prospective randomised trial evaluating homologous and autologous blood transfusion in aortic surgery. MATERIALS AND METHODS: Blood sampled before and at five times after surgery was assayed for C-reactive protein (CRP), neutrophil elastase, TNF-alpha and IL-6. Transfusions, morbidity and mortality were recorded; factors associated with poor outcome were identified by logistic regression. RESULTS: homologous transfusion during surgery was required in 32 patients and precipitated an increase in neutrophil elastase (p=0.008) and TNF-alpha (p=0.015) but not IL-6 and CRP. Elastase peaked early in transfused patients at 41.27 (13.92-52.11) Deltang/ml by 2 h compared to a peak of 21.51 (10.64-31.13) Deltang/ml by 24 h in those who were not transfused. TNF-alpha peaked at 1.2 (0-4.33) Deltapg/ml by wound closure in transfused patients and at -0.1 (-2.05-2.52) Deltapg/ml by 2 h without transfusion. Intra-operative homologous transfusion was associated with increased mortality (p=0.01) and prolonged intensive care stay (p=0.03). Mortality increased with age (p=0.003) and was inversely related to the CRP peak (p=0.007). Prolonged surgery predicted post-operative complications (p=0.025). CONCLUSION: Homologous transfusion increased the inflammatory response to aortic surgery and was associated with mortality.

Molecular regulation of tongue and craniofacial muscle differentiation.

The molecular regulation of muscle development is tightly controlled at three distinct stages of the process: determination, differentiation, and maturation. Developmentally, specific populations of myoblasts exhibit distinct molecular phenotypes that begin to limit the ultimate characteristics of the muscle fibers. The expression of the myogenic regulatory factor family of the transcription process plays a key role in muscle development and, ultimately, in the subset of contractile genes expressed in a specific muscle. Craniofacial muscles have distinct functional requirements and associated molecular phenotypes that distinguish them from other skeletal muscles. The general principles of muscle molecular differentiation with specific reference to craniofacial muscles, such as the tongue, are discussed in this review.

Expression of myogenic regulatory factors during the development of mouse tongue striated muscle.

While the role of myogenic regulatory factors (MRFs) in skeletal myogenesis has been well evaluated in limb and trunk muscles, very little is known about their role in tongue myogenesis. Here the expression of MRF mRNA in mouse tongue muscle was examined during development from embryonic day (E)11 to birth and compared them with that in hind-limb muscle. Desmin, muscle creatine kinase and troponin C mRNAs were used as markers for myoblast determination, myotubule formation and myofibre maturation, respectively. The mRNA quantities were determined by competitive reverse transcriptase-polymerase chain reaction. The expression profile of desmin mRNA indicated that myoblast determination occurred before E11 in both the tongue and hind-limb muscles; the profile of muscle creatine kinase and troponin C mRNAs indicated that myotubule formation and myofibre maturation began between E11 and 13 in both tongue and hind-limb muscles, but ended 2 days earlier in the tongue than in the hind limb. Expression of myoD and myogenin mRNAs began at E11, increased, and showed peak values earlier in the tongue muscle (E13) than in the hind-limb muscle (E15). Expression of MRF4 mRNA appeared earlier in the tongue (E13) than in the hind-limb muscle (E15) and increased in both muscles after that. These results suggest that myotubule formation and myofibre maturation in the tongue muscle progress faster than in the hind-limb muscle, a result of earlier expression of myoD, myogenin, and MRF4 in response to earlier functional demands such as suckling immediately after birth.

Embryonic, fetal, and neonatal tongue myoblasts exhibit molecular heterogeneity in vitro.

Variable gene expression patterns have been shown to exist between embryonic, fetal, and neonatal lineages of limb skeletal myoblasts in vitro and in vivo. In this study, we examined the molecular phenotype of embryonic, fetal, and neonatal tongue myoblasts in primary culture for comparison with in vivo developmental tongue myoblasts. Myogenic regulatory factor (MRF) and myosin heavy chain (MHC) gene expression were determined in culture during both growth and differentiation conditions by PCR, immunoblotting, and immunohistochemistry. Unlike their in vivo tongue myoblast equivalents, developmental tongue myoblast cultures featured the expression of MyoD when kept in growth conditions. Differentiation conditions in vitro induced myogenic tongue lineages to maintain characteristics of their in vivo morphologic and contractile gene phenotype. Both in vivo and in vitro, embryonic tongue lineages predominantly expressed MHC-embryonic isoforms, while fetal and neonatal tongue lineages predominantly expressed fast and perinatal isoforms of contractile genes. A notable difference from the in vivo condition that was observed in differentiated tongue myotubes in vitro was the presence of the MHC-slow protein. It was previously demonstrated that MHC-slow protein was undetectable during the in vivo development of the tongue musculature despite the abundance of slow isoform transcripts. The present characterization of primary tongue myogenic cultures indicates that murine myoblast heterogeneity exists primarily between developmental lineages at the level of contractile gene expression. Outside their native surroundings, developmental myogenic tongue populations are unable to recapitulate the determination and differentiation molecular profiles that occur in vivo.

Vascular surgical society of great britain and ireland: autologous transfusion reduces blood transfusion requirements in aortic surgery

BACKGROUND: Elective aortic surgery is associated with a blood loss that warrants a routine blood crossmatch of 4-6 units. Autologous transfusion strategies to reduce blood requirements were evaluated in a pilot study involving six hospitals in the North West. METHODS: Eighty patients undergoing elective aortic surgery were randomized to either autologous (a combination of acute normovolaemic haemodilution and intraoperative cell salvage) or homologous transfusion. The transfusion trigger, in the absence of pressing clinical need, was 8 g dl-1 haemoglobin for both groups. RESULTS: Randomization achieved two groups well matched for age, aneurysm or occlusive surgery, aspirin intake, estimated blood volume, preoperative haemoglobin and aneurysm size. In the 'best' hospitals (n = 49) mean(s.d.) blood loss (630(49) ml) was significantly lower (P < 0.01) than that in the 'worst' hospitals (1077(110) ml, n = 31) and fewer patients required transfusion (nine of 42 versus 15 of 30; P < 0.05). No significant differences were found between homologous and autologous groups for all variables measured in the 'best' hospitals. In the 'worst' hospitals blood requirements were significantly higher (P < 0.05) for the homologous group (800(112) ml) compared with the autologous group (489(65) ml), although blood loss was similar (1239(195) versus 915(92) ml respectively). CONCLUSION: Autologous transfusion techniques significantly reduced homologous blood requirements in aortic surgery where blood loss exceeded 800 ml.

Murine tongue muscle displays a distinct developmental profile of MRF and contractile gene expression.

Few studies have addressed the molecular differences that exist between muscles of the body and those of the craniofacial apparatus. In this study, we characterize the molecular events associated with determination and differentiation of the tongue musculature. We assess the expression of myogenic regulatory factors as well as the developmentally regulated myosin heavy chain, (MHC), genes which serve as markers of differentiation. These results suggest that tongue and limb muscle form by distinct molecular pathways. The myoblasts that contribute to the formation of the tongue preferentially express Myf-5 during myoblast determination rather than MyoD. Subsequently, isolated regions of myogenin expression mark the differentiation of first, the small primary myofibers and later, the larger secondary myofibers. Analysis of differentiation markers demonstrates that the tongue muscle also assumes a unique profile of MHC expression as compared to that of the muscles of the body. Unlike the myoblasts of the developing limb, which express embryonic and neonatal forms of MHC and later express MHC-slow, the tongue myoblasts co-express MHC-embryonic, MHC-slow and MHC-fast isoforms from gestational age E12. Proteins for MHC embryonic and MHC fast isoforms are detected almost simultaneously. Interestingly, MHC-slow transcripts do not appear to be translated into a detectable MHC slow protein at any developmental stage assayed. These results provide further evidence to suggest that skeletal tongue muscle represents a myoblast lineage that develops differently than the limb.

Differential expression of troponin C genes during tongue myogenesis.

Determination of muscle fiber type is related to the developmental stage of the tissue. Ordinarily the final distribution of fast and slow fibers in a muscle is determined postnatally. Tongue muscle, however, is composed solely of fast-twitch fibers that express only troponin C fast mRNA and fast (type II) myosin heavy chain (MHC) proteins in both the adult and the one-day-old mouse. The fiber-type determination of this muscle was examined during fetal development. Both troponin C fast and slow mRNAs were expressed at initial stages of tongue development at embryonic day 18. However, by embryonic day 16 the troponin C fast transcripts predominated. AT 17 days of embryonic development, TnC fast mRNA was 10 times more abundant than TnC slow, and at 18 days of development the TnC slow mRNA was barely detectable. The tongue muscle myotubes expressed fast, slow, and embryonic MHC isoforms during early embryonic development. At 18 days of gestation, the MHC isoform expressed by the majority of the myotubes was the fast isoform, whereas the slow isoform was present in very few fibers. RT-PCR analysis of the MHC transcripts present throughout tongue development demonstrated expression of the mdms or type IIx MHC in both late fetal and postnatal stages of development. In contrast, the type I/beta slow MHC mRNA was undetectable in the postnatal and adult tongue. The absence of TnC and MHC slow-isoform mRNAs in the newborn mouse tongue suggests that slow isoform genes become dominantly repressed with the TnC-F and MHC type IIx genes remaining transcriptionally active, giving rise to an unusually homogeneous fast-twitch phenotype. The tongue muscle fibers acquire their specific adult-type fiber characteristics during fetal development rather than postnatally.

Direct DNA injection into mouse tongue muscle for analysis of promoter function in vivo.

The striated muscle of the tongue provides a readily accessible site for the introduction of DNA expression vectors. Parameters were established to use the striated muscle of the tongue as a model system for the examination of gene expression following the direct injection of DNA constructs bearing gene promoter sequences controlling the expression of reporter genes. Plasmid expression vectors were used that contained either constitutive or muscle-specific promoters directing the transcription of reporter genes. Chloramphenicol acetyltransferase (CAT), luciferase, and beta-galactosidase (lacZ) were used as the reporter genes to detect the promoter-specific expression of the injected DNA. The expression of the injected plasmids was directly correlated with the mass of injected DNA and the time of incubation following the injection. Maximal levels of reporter gene expression were observed seven days after the injection, and the expression was maintained for more than two months following injection. Simultaneous injection of two individual expression vectors bearing either CAT or luciferase reporter genes resulted in a dose-dependent level of expression for each of the plasmids. The linearity of the coexpression provided a means to normalize DNA uptake and analyze promoter efficiency. The troponin C-fast enhancer linked to its own promoter directed significantly more CAT expression than an enhancerless SV40 promoter-CAT plasmid, demonstrating that different promoter strengths could be determined in the mouse tongue muscle in vivo. This model system represents a convenient means to approach the functional analysis of muscle gene promoters in vivo.