Neurodevelopmental outcome of fetal isolated ventricular asymmetry without dilation: a cohort study.

OBJECTIVE: Fetal isolated ventricular asymmetry (IVA) is a relatively common finding in pregnancy, but data regarding its effect on neurodevelopmental outcome are scarce and founded principally on ultrasound-based studies. The purpose of this study was to assess the neurodevelopmental outcome of IVA cases in a magnetic resonance imaging (MRI)-based study. METHODS: Cases referred for fetal brain MRI as part of the assessment of IVA without ventriculomegaly (lateral ventricular atrial diameter ≤ 10 mm), identified during routine ultrasound examination, were assessed for possible inclusion. Asymmetry was defined as a difference in width of ≥ 2 mm between the two lateral ventricles. Forty-three cases were included in the study group and compared with a control group of 94 normal cases without IVA. Children were assessed at ages 13-74 months using the Vineland-II Adaptive Behavior Scales (VABS-II). RESULTS: VABS-II scores were within normal range. There was no significant difference in composite VABS-II score between the study and control groups (106.5 vs 108.0; P = 0.454). VABS-II scores did not differ between the groups when matched for gender and age at VABS-II interview (109.6 in study group vs 107.8 in control group; P = 0.690). CONCLUSION: In cases of IVA without ventriculomegaly on MRI, neurodevelopmental test scores were normal and did not differ from cases without IVA. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Consumption of ultra-processed food products and its effects on children's lipid profiles: a longitudinal study.

BACKGROUND AND AIMS: Cardiovascular disease development is related to known risk factors (such as diet and blood lipids) that begin in childhood. Among dietary factors, the consumption of ultra-processing products has received attention. This study investigated whether children's consumption of processed and ultra-processing products at preschool age predicted an increase in lipid concentrations from preschool to school age. METHODS AND RESULTS: Cohort study conducted with 345 children of low socioeconomic status from São Leopoldo, Brazil, aged 3-4 years and 7-8 years. Blood tests were done to measure lipid profile. Dietary data were collected through 24-h recalls and the children's processed and ultra-processing product intake was assessed. Linear regression analysis was used to assess the relationship between processed and ultra-processed product intake at 3-4 years on changes in lipid concentrations from preschool to school age. The percentage of daily energy provided by processed and ultra-processed products was 42.6 ± 8.5 at preschool age and 49.2 ± 9.5 at school age, on average. In terms of energy intake, the main products consumed were breads, savoury snacks, cookies, candy and other sweets in both age groups. Ultra-processed product consumption at preschool age was a predictor of a higher increase in total cholesterol (ß = 0.430; P = 0.046) and LDL cholesterol (ß = 0.369; P = 0.047) from preschool to school age. CONCLUSION: Our data suggest that early ultra-processed product consumption played a role in altering lipoprotein profiles in children from a low-income community in Brazil. These results are important to understanding the role of food processing and the early dietary determinants of cardiovascular disease.

Immediate and extended effects of abrasion on stratum corneum natural moisturizing factor.

BACKGROUND: Natural moisturizing factor (NMF), principally comprised of hygroscopic amino acids and derivatives that absorb moisture from the surrounding environment, serves as the primary humectant of the stratum corneum (SC). Acute barrier disruption has been shown to differentially affect the concentration of NMF in the SC. This study measured the recovery kinetics of NMF after mechanical damage of the SC, which is not well understood. METHODS: The study population included 20 healthy female volunteers (18-72-year old) with no history of dermatological disorders. Transepidermal water loss (TEWL), erythema, and SC water and NMF were measured at all sites before abrasion, 30 min following abrasion, and 1-3, 6, 8, and 10 days following abrasion. Measurements obtained from the abraded site were compared with those obtained from an untreated site. RESULTS: As expected, both TEWL and erythema increased significantly with abrasion. Erythema and TEWL values remained higher at the abraded site for 2 and 6 days, respectively, after abrasion. No changes in NMF component levels in the SC were observed at 30 min after abrasion. One day following abrasion, reduced levels of glycine, histidine pH4, trans-urocanic acid (tUca) pH4, and tUca pH8 were observed. In addition, a significantly lower level of serine was observed at the abraded site 2 and 6 days following abrasion. Within 8 days after abrasion, these components returned to levels comparable to those observed in untreated skin. Throughout the study, no differences were observed in the level of water in the SC. CONCLUSION: These results demonstrate that acute barrier disruption induced by mechanical abrasion has relatively little impact on biochemical events responsible for NMF generation. Though reductions in certain NMF components were observed, abrasion had no measureable effect on SC water content over the duration of the study. This implies that the reduced NMF components may not contribute substantially to water retention in the SC. The reduced components belong to a group of NMF molecules thought to be principally derived through degradation of S-100 proteins in the epidermis. NMF components measured in this study that are derived from sweat and/or urea cycling were not impacted. These data imply that while abrasion elicits clinical signs of barrier disruption within the SC, effects on its biochemical constituents and ability to retain water are relatively minor.

Immediate and extended effects of sodium lauryl sulphate exposure on stratum corneum natural moisturizing factor.

OBJECTIVES: Natural moisturizing factor (NMF) serves as the primary humectant of the stratum corneum (SC), principally comprised of hygroscopic amino acids and derivatives that absorb moisture. Barrier disruption has been shown to differentially affect the levels of specific NMF components, though the kinetics of NMF component restoration following disruption have not been examined. Here, we investigated the impact of barrier disruption caused by surfactant exposure on a subset of NMF components immediately following exposure and out to 10 days post-exposure. METHODS: Volunteers wore patches containing either 1% w/v sodium lauryl sulphate (SLS) or distilled water on their forearms for 24 h. Measurements of transepidermal water loss, erythema, SC water content and a subset of SC NMF and lipid components were obtained at both sites before treatment, the day of patch removal, and 1, 2, 3, 6, and 10 days following treatment. RESULTS: Most measured NMF components decreased in response to SLS exposure. Exceptions were increases in lactate, ornithine and urea, and no difference in proline levels. In the days following exposure, reduced levels of several NMF components continued at the SLS site; however, all measured NMF components demonstrated equivalence to the vehicle control within 10 days. Histidine pH 7, lactate, ornithine and urea were the first to achieve levels equivalent to the vehicle control site, normalizing within 1 day after patch removal. CONCLUSION: Results imply that NMF components derived from sweat and urea cycling are least impacted by SLS exposure whereas NMF components derived from degradation of filaggrin and/or other S-100 proteins are most impacted. This implies the restoration of the processes responsible for S-100 protein processing into free amino acids takes several days to return to normal. Further examination of the enzymes involved in S-100 protein processing following barrier disruption would provide insight into the pathway(s) for NMF restoration during SC recovery.

Graft Choice in Pancreatectomy with Vascular Resection: Equivalent Safety in Selected Patients.

BACKGROUND: Pancreatic cancer is the third leading cause of cancer related death in the US, with surgical resection being the only option for long term survival. The ability to manage vascular involvement has expanded the pool of patients who are able to undergo resection with curative intent. However, not all vascular involvement can be detected pre-operatively. We investigated patterns of vascular resection and methods of repair or reconstruction METHODS: Single center retrospective review of adult patients undergoing pancreatectomy with vascular involvement at a tertiary care referral hospital between 2010-2022. Our primary endpoint was graft thrombosis within 90 days. RESULTS: 147 patients were included in the study. 21.8% of whom were not suspected of having vascular involvement pre-operatively. 68% of patients required vascular reconstruction (68%) with the remaining 32% undergoing repair (either primary repair or patch angioplasty). The majority undergoing reconstruction underwent primary end to end anastomosis (63%), with 19 patients requiring autogenous interposition grafts and 16 patients requiring Cryovein® interposition grafts. Univariate analysis found no clinical or technical predictors of early or 90 day thrombosis, including graft choice. 30 and 90 day mortality occurred in 1 and 7 patients respectively. CONCLUSION: Pancreatectomy with vascular resection can be performed with low mortality in carefully selected patients. Unsuspected vascular involvement is relatively common (1 in 5). If autologous graft is not readily available, Cryovein® is a safe alternative with similar perioperative outcomes.

Characterization of diamond and organic scintillation detectors utilizing radiation sources for continuous plasma operation.

This paper provides a comprehensive study of neutron calibration methodologies, specifically highlighting the capabilities for n-γ discrimination in diamond and EJ-309, and stilbene scintillation detectors. The calibration process detailed in this study includes pulse height analysis and pulse shape discrimination, relying on the analysis of charge deposition resulting from both γ and neutron interactions. Utilizing 60Co and 252Cf radiation sources, the energy spectra of these sources are obtained. The characterized detectors were used in ST40 experiments and allowed acquiring neutron signal during a plasma shot with good agreement among diamond and scintillation detectors. Then, the diamond detector was cross-calibrated against indium activation foils placed at the same location in proximity to the ST40 during plasma shots: both detectors measured a neutron flux of ≈106 cm-2 s-1 at ≈1 m distance from the tokamak center, and the discrepancy between the diamond detector and the activation foils is ≈25%.

Attosecond-pump attosecond-probe x-ray spectroscopy of liquid water.

Attosecond-pump/attosecond-probe experiments have long been sought as the most straightforward method for observing electron dynamics in real time. Although there has been much success with overlapped near-infrared femtosecond and extreme ultraviolet attosecond pulses combined with theory, true attosecond-pump/attosecond-probe experiments have been limited. We used a synchronized attosecond x-ray pulse pair from an x-ray free-electron laser to study the electronic response to valence ionization in liquid water through all x-ray attosecond transient absorption spectroscopy (AX-ATAS). Our analysis showed that the AX-ATAS response is confined to the subfemtosecond timescale, eliminating any hydrogen atom motion and demonstrating experimentally that the 1b1 splitting in the x-ray emission spectrum is related to dynamics and is not evidence of two structural motifs in ambient liquid water.

Hierarchical radial and polar organisation of chromosomes in human sperm.

It is well established that chromosomes occupy distinct positions within the interphase nuclei, conferring a potential functional implication to the genome. In addition, alterations in the nuclear organisation patterns have been associated with disease phenotypes (e.g. cancer or laminopathies). The human sperm is the smallest cell in the body with specific DNA packaging and the mission of delivering the paternal genome to the oocyte during fertilisation. Studies of nuclear organisation in the sperm have postulated nonrandom chromosome position and have proposed a chromocentre model with the centromeres facing toward the interior and the telomeres toward the periphery of the nucleus. Most studies have assessed the nuclear address in the sperm longitudinally predominantly using centromeric or telomeric probes and to a lesser extent with whole chromosome paints. To date, studies investigating the radial organisation of human sperm have been limited. The purpose of this study was to utilise whole chromosome paints for six clinically important chromosomes (18, 19, 21, 22, X, and Y) to investigate nuclear address by assessing their radial and longitudinal nuclear organisation. A total of 10,800 sperm were analysed in nine normozoospermic individuals. The results have shown nonrandom chromosome position for all chromosomes using both methods of analysis. We present novel radial and polar analysis of chromosome territory localization within the human sperm nucleus. Specifically, a hierarchical organisation was observed radially with chromosomes organised from the interior to the periphery (chromosomes 22, 21, Y, X, 19, and 18 respectively) and polar organisation from the sperm head to tail (chromosomes X, 19, Y, 22, 21, and 18, respectively). We provide evidence of defined nuclear organisation in the human sperm and discuss the function of organisation and potential possible clinical ramifications of these results in regards to male infertility and early human development.

The KSHV ORF20 Protein Interacts with the Viral Processivity Factor ORF59 and Promotes Viral Reactivation.

Upon Kaposi's Sarcoma-associated herpesvirus (KSHV) lytic reactivation, rapid and widespread amplification of viral DNA (vDNA) triggers significant nuclear reorganization. As part of this striking shift in nuclear architecture, viral replication compartments are formed as sites of lytic vDNA production along with remarkable spatial remodeling and the relocalization of cellular and viral proteins. These viral replication compartments house several lytic gene products that coordinate viral gene expression, vDNA replication, and nucleocapsid assembly. The viral proteins and mechanisms that regulate this overhaul of the nuclear landscape during KSHV replication remain largely unknown. KSHV's ORF20 is a widely conserved lytic gene among all herpesviruses, suggesting it may have a fundamental contribution to the progression of herpesviral infection. Here, we utilized a promiscuous biotin ligase proximity labeling method to identify the proximal interactome of ORF20, which includes several replication-associated viral proteins, one of which is ORF59, the KSHV DNA processivity factor. Using coimmunoprecipitation and immunofluorescence assays, we confirmed the interaction between ORF20 and ORF59 and tracked the localization of both proteins to KSHV replication compartments. To further characterize the function of ORF20, we generated an ORF20-deficient KSHV and compared its replicative fitness to that of wild-type virus. Virion production was significantly diminished in the ORF20-deficient virus as observed by supernatant transfer assays. Additionally, we tied this defect in viable virion formation to a reduction in viral late gene expression. Lastly, we observed an overall reduction in vDNA replication in the ORF20-deficient virus, implying a key role for ORF20 in the regulation of lytic replication. Taken together, these results capture the essential role of KSHV ORF20 in progressing viral lytic infection by regulating vDNA replication alongside other crucial lytic proteins within KSHV replication compartments. IMPORTANCE Kaposi's Sarcoma-associated herpesvirus (KSHV) is a herpesvirus that induces lifelong infection, and as such, its lytic replication is carefully controlled to allow for efficient dissemination from its long-term reservoir and for the spread of the virus to new hosts. Viral DNA replication involves many host and viral proteins, coordinating both in time and space to successfully progress through the viral life cycle. Yet, this process is still not fully understood. We investigated the role of the poorly characterized viral protein ORF20, and through proximity labeling, we found that ORF20 interacts with ORF59 in replication compartments and affects DNA replication and subsequent steps of the late viral life cycle. Collectively, these results provide insights into the possible contribution of ORF20 to the complex lytic DNA replication process and suggest that this highly conserved protein may be an important modulator of this key viral mechanism.

Correlation between 2D and 3D Fetal Brain MRI Biometry and Neurodevelopmental Outcomes in Fetuses with Suspected Microcephaly and Macrocephaly.

BACKGROUND AND PURPOSE: Definitions of fetal microcephaly and macrocephaly are debatable. A better understanding of their long-term prognoses would help guide parental education and counseling. This study aimed to explore the correlation between 2D and 3D fetal brain MR imaging biometry results and the long-term neurodevelopmental outcomes. MATERIALS AND METHODS: This analysis is a historical cohort study. Fetal brain biometry was measured on 2D and 3D MR imaging using a volumetric MR imaging semiautomated algorithm. We measured and assessed the following brain structures: the supratentorial brain volume and cerebellar volume and cerebellar volume/supratentorial brain volume ratio, in addition to commonly used 2D brain MR imaging biometric variables, including occipitofrontal diameter, biparietal diameter, and transcerebellar diameter. Microcephaly was defined as ≤ 3rd percentile; and macrocephaly, as ≥ 97th percentile, corresponding to -2 SDs and +2 SDs. The neurodevelopmental outcome of this study cohort was evaluated using the Vineland-II Adaptive Behavior Scales, and the measurements were correlated to the Vineland standard scores. RESULTS: A total of 70 fetuses were included. No significant correlation was observed between the Vineland scores and either the supratentorial brain volume, cerebellar volume, or supratentorial brain volume/cerebellar volume ratio in 3D or 2D MR imaging measurements, after correction for multiple comparisons. No differences were found among fetuses with macrocephaly, normocephaly, or microcephaly regarding the median Vineland standard scores. CONCLUSIONS: Provided there is normal brain structure on MR imaging, the developmental milestone achievements in early years are unrelated to 2D and 3D fetal brain MR imaging biometry, in the range of measurements depicted in this study.

Visualization of Mad2 dynamics at kinetochores, along spindle fibers, and at spindle poles in living cells.

The spindle checkpoint prevents errors in chromosome segregation by inhibiting anaphase onset until all chromosomes have aligned at the spindle equator through attachment of their sister kinetochores to microtubules from opposite spindle poles. A key checkpoint component is the mitotic arrest-deficient protein 2 (Mad2), which localizes to unattached kinetochores and inhibits activation of the anaphase-promoting complex (APC) through an interaction with Cdc20. Recent studies have suggested a catalytic model for kinetochore function where unattached kinetochores provide sites for assembling and releasing Mad2-Cdc20 complexes, which sequester Cdc20 and prevent it from activating the APC. To test this model, we examined Mad2 dynamics in living PtK1 cells that were either injected with fluorescently labeled Alexa 488-XMad2 or transfected with GFP-hMAD2. Real-time, digital imaging revealed fluorescent Mad2 localized to unattached kinetochores, spindle poles, and spindle fibers depending on the stage of mitosis. FRAP measurements showed that Mad2 is a transient component of unattached kinetochores, as predicted by the catalytic model, with a t(1/2) of approximately 24-28 s. Cells entered anaphase approximately 10 min after Mad2 was no longer detectable on the kinetochores of the last chromosome to congress to the metaphase plate. Several observations indicate that Mad2 binding sites are translocated from kinetochores to spindle poles along microtubules. First, Mad2 that bound to sites on a kinetochore was dynamically stretched in both directions upon microtubule interactions, and Mad2 particles moved from kinetochores toward the poles. Second, spindle fiber and pole fluorescence disappeared upon Mad2 disappearance at the kinetochores. Third, ATP depletion resulted in microtubule-dependent depletion of Mad2 fluorescence at kinetochores and increased fluorescence at spindle poles. Finally, in normal cells, the half-life of Mad2 turnover at poles, 23 s, was similar to kinetochores. Thus, kinetochore-derived sites along spindle fibers and at spindle poles may also catalyze Mad2 inhibitory complex formation.

A phosphatidylinositol 4,5-bisphosphate-sensitive casein kinase I alpha associates with synaptic vesicles and phosphorylates a subset of vesicle proteins.

In interphase cells, alpha-casein kinase I (alpha-CKI) is found associated with cytosolic vesicular structures, the centrosome, and within the nucleus. To identify the specific vesicular structures with which alpha-CKI is associated, established cell lines and primary rat neurons were immunofluorescently labeled with an antibody raised to alpha-CKI. In nonneuronal cells, alpha-CKI colocalizes with vesicular structures which align with microtubules and are partially coincident with both Golgi and endoplasmic reticulum markers. In neurons, alpha-CKI colocalizes with synaptic vesicle markers. When synaptic vesicles were purified from rat brain, they were highly enriched in a CKI, based on activity and immunoreactivity. The synaptic vesicle-associated CKI is an extrinsic kinase and was eluted from synaptic vesicles and purified. This purified CKI has properties most similar to alpha-CKI. When the activities of casein kinase I or II were specifically inhibited on isolated synaptic vesicles, CKI was shown to phosphorylate a specific subset of vesicle proteins, one of which was identified as the synaptic vesicle-specific protein SV2. As with alpha-CKI, the synaptic vesicle CKI is inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2). However, synthesis of PIP2 was detected only in plasma membrane-containing fractions. Therefore, PIP2 may spatially regulate CKI. Since PIP2 synthesis is required for secretion, this inhibition of CKI may be important for the regulation of secretion.

Cytoplasmic dynein/dynactin drives kinetochore protein transport to the spindle poles and has a role in mitotic spindle checkpoint inactivation.

We discovered that many proteins located in the kinetochore outer domain, but not the inner core, are depleted from kinetochores and accumulate at spindle poles when ATP production is suppressed in PtK1 cells, and that microtubule depolymerization inhibits this process. These proteins include the microtubule motors CENP-E and cytoplasmic dynein, and proteins involved with the mitotic spindle checkpoint, Mad2, Bub1R, and the 3F3/2 phosphoantigen. Depletion of these components did not disrupt kinetochore outer domain structure or alter metaphase kinetochore microtubule number. Inhibition of dynein/dynactin activity by microinjection in prometaphase with purified p50 "dynamitin" protein or concentrated 70.1 anti-dynein antibody blocked outer domain protein transport to the spindle poles, prevented Mad2 depletion from kinetochores despite normal kinetochore microtubule numbers, reduced metaphase kinetochore tension by 40%, and induced a mitotic block at metaphase. Dynein/dynactin inhibition did not block chromosome congression to the spindle equator in prometaphase, or segregation to the poles in anaphase when the spindle checkpoint was inactivated by microinjection with Mad2 antibodies. Thus, a major function of dynein/dynactin in mitosis is in a kinetochore disassembly pathway that contributes to inactivation of the spindle checkpoint.

Metal mutagens and carcinogens affect RNA synthesis rates in a distinct manner.

Five metal salts (lead, cadmium, cobalt, copper, and manganese),which are mutagenic or carcinogenic, decreasing the fidelity of DNA synthesis in vitro, stimulated chain initiation of RNA synthesis at concentrations that inhibited overall RNA synthesis. In contrast, other metal salts (zinc, magnesium, lithium, sodium,and potassium) not in this category inhibited chain initiation of RNA synthesis at concentrations that inhibited overall RNA synthesis.

Muscle and movement representations in the primary motor cortex.

What aspects of movement are represented in the primary motor cortex (M1): relatively low-level parameters like muscle force, or more abstract parameters like handpath? To examine this issue, the activity of neurons in M1 was recorded in a monkey trained to perform a task that dissociates three major variables of wrist movement: muscle activity, direction of movement at the wrist joint, and direction of movement in space. A substantial group of neurons in M1 (28 out of 88) displayed changes in activity that were muscle-like. Unexpectedly, an even larger group of neurons in M1 (44 out of 88) displayed changes in activity that were related to the direction of wrist movement in space independent of the pattern of muscle activity that generated the movement. Thus, both "muscles" and "movements" appear to be strongly represented in M1.

Studying the effect of pH variation on the incorporation of the antipsychotic drug clozapine into dyed and non-dyed hair samples using micro-attenuated total reflection spectroscopy.

Antipsychotic drugs are among the mostly widely used medications and are usually taken for prolonged periods of time. Due to its accumulation and trapping of drugs, hair can provide a useful indication of long-term exposure. Of interest also is what if any changes in the structural components of hair occur as a result of the drug binding process. Micro-attenuated total reflection (ATR) spectroscopy is able to examine the structural changes of hair samples by the application of sufficient pressure and without microtoming the hair (A. Koçak and S. L. Berets, Appl. Spectrosc. 62, 803 (2008)). In this investigation, we examined changes resulting from exposure of dyed and undyed hair to external clozapine as a function of the pH of the exposing solution. Single samples from different individuals and in one case from different regions of the scalp from the same individual were analyzed. The results demonstrated that pH related differences exist between drug-exposed dyed and non-dyed samples.

Volumetric MRI Study of the Brain in Fetuses with Intrauterine Cytomegalovirus Infection and Its Correlation to Neurodevelopmental Outcome.

BACKGROUND AND PURPOSE: In recent years, effort has been made to study 3D biometry as a method for fetal brain assessment. In this study, we aimed to compare brain volumes of fetuses with cytomegalovirus infection and noninfected controls. Also, we wanted to assess whether there is a correlation to their neurodevelopmental outcome as observed after several years. MATERIALS AND METHODS: A retrospective cohort study examined MR imaging brain scans of 42 fetuses (at 30-34 weeks' gestational age) that were diagnosed with intrauterine cytomegalovirus infection. Volumetric measurements of 6 structures were assessed using a semiautomated designated program and were compared with a control group of 50 fetuses. Data collected included prenatal history and MR imaging and sonographic and neurodevelopmental follow-up. RESULTS: We found that all brain volumes measured were smaller in the cytomegalovirus-infected group and that there was a correlation between smaller cerebellar volume and lower Vineland II Adaptive Behavior Scales questionnaire scores, especially in the fields of daily living and communication skills. CONCLUSIONS: In this study, we found that brain volumes are affected by intrauterine cytomegalovirus infection and that it has a developmental prognostic meaning. Such information, which should be supported by further research, may help clinicians further analyze imaging data to treat and make a better assessment of these fetuses.

Growth, tolerance, and DHA and ARA status of healthy term infants receiving formula with two different ARA concentrations: Double-blind, randomized, controlled trial.

Circulating docosahexaenoic acid (DHA) and arachidonic acid (ARA) in total red blood cells (RBC) are considered indicators of fatty acid status. In this study, healthy term infants received study formula through 120 days of age. All study formulas had 17 mg DHA/100 kcal. Investigational formulas had 1) 25 g ARA/100 kcal and no added prebiotic blend (ARA-25; n = 29) or 2) 34 mg ARA/100 kcal and a prebiotic blend (1:1 ratio; 4 g/L) of polydextrose and galactooligosaccharides (PDX/GOS; n = 20). The control formula had 34 mg ARA/100 kcal and no added prebiotic blend (Control: n = 31). Fatty acids in total RBCs and plasma phospholipids (PPLs) at 120 days and buccal epithelial PLs at 14 and 120 days of age were assessed by capillary column gas chromatography. The calculated 90% confidence interval (CI) of each investigational formula relative to the Control for total RBC ARA (ARA-25: 93-105%; PDX/GOS: 96-110%) and total RBC DHA (ARA-25: 95-113%; PDX/GOS: 94-113%) fell within the pre-specified equivalence limit (85-118%), establishing study formula equivalence with respect to ARA and DHA. At day 120, total RBC and buccal epithelia PL ARA (µg/ml) were not significantly correlated (r = 0.041; p = 0.732); correlation in total RBC and buccal epithelia PL DHA was low, albeit significant (r = 0.324; p = 0.006). Consequently, buccal epithelial may not provide a suitable substitute for RBC when assessing fatty acid status and availability. The present RBC data suggest availability of DHA for central nervous system development and function is equivalent among infants receiving formulas that had 34 or 25 mg/100 kcal ARA and 17 mg/100 kcal DHA.

Direction of action is represented in the ventral premotor cortex.

The ventral premotor area (PMv) is a major source of input to the primary motor cortex (M1). To examine the potential hierarchical processing between these motor areas, we recorded the activity of PMv neurons in a monkey trained to perform wrist movements in different directions with the wrist in three different postures. The task dissociated three major variables of wrist movement: muscle activity, direction of joint movement and direction of movement in space. Many PMv neurons were directionally tuned. Nearly all of these neurons (61/65, 94%) were 'extrinsic-like'; they seemed to encode the direction of movement in space independent of forearm posture. These results are strikingly different from results from M1 of the same animal, and suggest that intracortical processing between PMv and M1 may contribute to a sensorimotor transformation between extrinsic and intrinsic coordinate frames.

Immune Function in Critically Ill Dogs.

BACKGROUND: People with critical illness (CI) commonly develop various forms of immune dysfunction, however, there is limited information concerning immune dysfunction in dogs with CI. HYPOTHESIS: The immune response in CI dogs differs from that of healthy dogs. ANIMALS: Immunologic variables were compared between 14 dogs with CI, defined as APPLEfast score of >20 points, admitted to the University of Missouri Veterinary Health Center Small Animal Clinic Intensive Care Unit and healthy controls (n = 15). METHODS: Cohort study evaluating constitutive and lipopolysaccharide (LPS)-stimulated TNF-α, IL-6, and IL-10 production, phagocytosis of opsonized E. coli and respiratory burst capacity after opsonized E. coli or phorbol 12-myristate 13-acetate (PMA) stimulation, peripheral blood lymphocyte phenotype, and monocyte expressions of HLA-DR and TLR-4. RESULTS: Lipopolysaccharide-stimulated leukocyte TNF-α (median, Q1, Q3; CI, 49, 49, 120; control, 655, 446, 1174 pg/mL; P = < 0.001), IL-6 (median, Q1, Q3; CI, 49, 49, 64; control, 100, 49, 166 pg/mL; P = 0.029), and IL-10 (CI, 49, 49, 56; control, 96, 49, 203 pg/mL; P = 0.014) production and both E. coli (median, Q1, Q3; CI, 60.5, 43, 88.5; control, 86.6, 81, 89.2%; P = 0.047) and PMA (CI, 40, 11.7, 70; control, 93, 83, 97.6%; P = < 0.001)-stimulated respiratory burst capacity significantly decreased in CI dogs. Percentage of monocytes expressing TLR-4 greater in the CI dogs (median, Q1, Q3; CI, 46.9, 24.3, 64.2; control, 16.4, 9.4, 26.2%; P = 0.005). CONCLUSION: These findings suggest dogs with CI develop immune system alterations that result in reduced respiratory burst function and cytokine production despite upregulation of TLR-4.