Follicular fluid and serum metabolites in Holstein cows are predictive of genetic merit for fertility.

The aims of the present study were to: (1) characterise the metabolome of follicular fluid and serum in dairy cows with similar genetic merit for milk production but with extremes of good (Fert+) or poor (Fert-) genetic merit for fertility; and (2) identify potential biomarkers of dairy cow fertility. Follicular fluid from the first wave dominant follicle and serum were collected on Day 7 of the oestrous cycle. The most pronounced effect of genotype was noted in the serum, where the abundance of total polyunsaturated fatty acids and n-6 polyunsaturated fatty acids was greater in Fert+ cows, and the abundance of total saturated fatty acids was greater in Fert- cows. The abundance of nine fatty acids (arachidic acid, heneicosanoic acid, myristic acid, behenic acid, myristoleic acid, heptadecenoic acid, cis-11-eicosanoic acid, nervonic acid and γ-linolenic acid) in follicular fluid was affected by genotype. Concentrations of cysteine, leucine, ornithine, proline and tyrosine in follicular fluid, and asparagine, creatinine, cysteine, methionine, proline and valine in serum, were also affected by genotype. Receiver operating characteristic curve analysis indicated that the follicular fluid and serum fatty acids and follicular fluid amino acids that were significantly affected by genotype were highly predictive of fertility genotype.

Suture fixation of an Akin osteotomy: A cost effective and clinically reliable technique.

BACKGROUND: The Akin osteotomy is commonly performed as an adjunct to osteotomies of the first metatarsal for the correction of hallux valgus such as the scarf or chevron osteotomies. The Akin osteotomy is indicated for the correction of a hallux valgus interphalangeus and can be used supplementary in any first metatarsal osteotomy for a hallux valgus. Various techniques have been described for fixation of the osteotomy. Most commonly the osteotomy is held and fixed with metalwork consisting of either a staple [2,3], a screw [4,5] or wiring [6,7]. While these techniques have been shown to be effective they are not without complications. They may require the use of additional instrumentation and in particular there is a described incidence of subsequent implant removal due to irritation of surrounding tissues and migration of the implanted metalwork [8-12]. Suture fixation of osteotomies in the foot has previously been described [14,15]. This offers a cost effective method with reliable results without the risk of implant complication. METHOD: In this study we report the outcomes of a large series performed by a single surgeon and compare them to a similar series of Akin osteotomies performed by a different surgeon at the same institute using the staple technique. RESULTS: The results demonstrate no significant difference in outcome between the two series and a significant cost saving with the use of the suture fixation. CONCLUSIONS: As a result of the study, we advocate the use of suture fixation of Akin osteotomy as a cost effective and reliable alternative to other forms of fixation.

Metabolic profiling of human follicular fluid identifies potential biomarkers of oocyte developmental competence.

The use of metabolomic based techniques to aid oocyte and embryo selection has gained attention in recent years. Previous work from our laboratory has demonstrated that the (1)H NMR-based metabolic profile of follicular fluid correlates with oocyte developmental potential. Patients undergoing IVF at the Merrion Fertility Clinic had follicular fluid collected at the time of oocyte retrieval. The fatty acid composition of follicular fluid from follicles where oocytes fertilised and developed into multi-cell embryos (n=15) and from oocytes that fertilised normally but failed to cleave (n=9) (cleaved vs non-cleaved) was compared. Statistical analysis was performed on the data using univariate and multivariate techniques. Analysis of the fatty acid composition revealed that there were nine fatty acids significantly different between follicular fluid from the cleaved and the non-cleaved sample groups. Of particular interest were the higher concentration of total saturated (P=0.03) and the lower concentration of total polyunsaturated fatty acids in the non-cleaved sample group (P=0.001). Random forest classification models were used to predict successful cleavage in follicular fluid samples producing models with errors rates of <10%. Receiver operating characteristic analysis demonstrated that the model had good predictability with an area under the curve of 0.96. The panel of fatty acid biomarkers identified in this study indicates that the fatty acid composition of follicular fluid may be more predictive in comparison to other previously identified biomarkers. Following validation in a larger cohort, these biomarkers may have the potential to be used in fertility clinics to aid the selection of oocytes in the future.

The role of metabolomics in determination of new dietary biomarkers.

Traditional methods for the assessment of dietary intake are prone to error; in order to improve and enhance these methods increasing interest in the identification of dietary biomarkers has materialised. Metabolomics has emerged as a key tool in the area of dietary biomarker discovery and to date the use of metabolomics has identified a number of putative biomarkers. Applications to identify novel biomarkers of intake have in general taken three approaches: (1) specific acute intervention studies to identify specific biomarkers of intake; (2) searching for biomarkers in cohort studies by correlating to self-reported intake of a specific food/food group(s); (3) analysing dietary patterns in conjunction with metabolomic profiles to identify biomarkers and nutritypes. A number of analytical technologies are employed in metabolomics as currently there is no single technique capable of measuring the entire metabolome. These approaches each have their own advantages and disadvantages. The present review will provide an overview of current technologies and applications of metabolomics in the determination of new dietary biomarkers. In addition, it will address some of the current challenges in the field and future outlooks.

Evaluation of ensemble Monte Carlo variable selection for identification of metabolite markers on NMR data.

The aim of this study was to investigate the potential of the recently developed ensemble Monte Carlo Variable Selection (EMCVS) method to identify the relevant portions of high resolution 1H NMR spectra as a metabolite fingerprinting tool and compare to a widely used method (Variable importance on projection (VIP)) and recently proposed variable selected methods i.e. selectivity ratio (SR) and significance multivariate correlation (sMC). As case studies two quantitative publicly available datasets: wine samples, urine samples of rats, and an experiment on mushroom (Agaricus bisporus) were examined. EMCVS outperformed the three other variable selection methods in most cases, selecting fewer chemical shifts and leading to improved classification of mushrooms and prediction of onion by-products intake and wine components. These fewer chemical shift regions facilitate the interpretation of the NMR spectra, fingerprinting and identification of metabolite markers.

Relationship between in vitro sperm functional assessments, seminal plasma composition, and field fertility after AI with either non-sorted or sex-sorted bull semen.

The hypothesis of this study was that different in vitro parameters are required to predict the in vivo fertility of non-sorted (NS) and sex-sorted (SS) semen. Thus, the aim was to correlate in vitro bull sperm functional parameters (experiment 1) and seminal plasma composition (experiment 2) with pregnancy rates using 2 cohorts of bulls (NS and SS). Experiment 1: ejaculates from each bull (n = 3 ejaculates per bull; n = 6 bulls for both NS and SS) were assessed for motility, thermal stress tolerance and morphology using microscopy, and viability, osmotic resistance, mitochondrial membrane potential, and acrosome integrity using flow cytometry. Fertilizing ability was assessed using IVF. Experiment 2: ejaculates (n = 3 per bull; n = 8 and 6 bulls for NS and SS, respectively) were collected, seminal plasma harvested and frozen and later analyzed for amino acid and fatty acid composition using gas chromatography mass spectrometry. In the NS cohort of bulls, there was no correlation between pregnancy rate and any of the sperm functional parameters assessed. However, within the SS cohort, motility and viability were correlated with pregnancy rate (r = 0.84 and 0.80, respectively; P < 0.05). There was no correlation between IVF outcome and pregnancy rate in either the SS or NS cohort of bulls. In the NS cohort of bulls, concentrations of the amino acid isoleucine and the fatty acid tricosylic acid (C23:0) were correlated with pregnancy rate (r = 0.80 and 0.74, respectively; P < 0.05). Within the SS cohort of bulls, the amino acid glutamic acid and the fatty acid arachidic acid (C20:0) were correlated with pregnancy rate (r = 0.84 and 0.82, respectively; P < 0.05). In conclusion, this study suggests that different in vitro markers of fertility are required to predict the fertility of NS and SS sperm.

Identification of a plasma signature of psychotic disorder in children and adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.

The identification of an early biomarker of psychotic disorder is important as early treatment is associated with improved patient outcome. Metabolomic and lipidomic approaches in combination with multivariate statistical analysis were applied to identify plasma alterations in children (age 11) (38 cases vs 67 controls) and adolescents (age 18) (36 cases vs 117 controls) preceeding or coincident with the development of psychotic disorder (PD) at age 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC). Overall, 179 lipids were identified at age 11, with 32 found to be significantly altered between the control and PD groups. Following correction for multiple comparisons, 8 of these lipids remained significant (lysophosphatidlycholines (LPCs) LPC(18:1), LPC(18:2), LPC(20:3); phosphatidlycholines (PCs) PC(32:2; PC(34:2), PC(36:4), PC(0-34-3) and sphingomyelin (SM) SM(d18:1/24:0)), all of which were elevated in the PD group. At age 18, 23 lipids were significantly different between the control and PD groups, although none remained significant following correction for multiple comparisons. In conclusion, the findings indicate that the lipidome is altered in the blood during childhood, long before the development of psychotic disorder. LPCs in particular are elevated in those who develop PD, indicating inflammatory abnormalities and altered phospholipid metabolism. These findings were not found at age 18, suggesting there may be ongoing alterations in the pathophysiological processes from prodrome to onset of PD.

Subdural hematomas in infants with benign enlargement of the subarachnoid spaces are not pathognomonic for child abuse.

BACKGROUND AND PURPOSE: Patients who have benign enlargement of the subarachnoid spaces (BESS) have long been suspected of having an increased propensity for subdural hematomas either spontaneously or as a result of accidental injury. Subdural hematomas in infants are often equated with nonaccidental trauma (NAT). A better understanding of the clinical and imaging characteristics of subdural hematomas that occur either spontaneously or as a result of accidental trauma may help distinguish this group of patients from those who suffer subdural hematomas as a result of NAT. The purpose of this study is to describe the clinical and imaging characteristics of subdural hematomas that occur either spontaneously or as a result of accidental injury in infants with BESS. METHODS: We conducted a retrospective review of all patients with BESS complicated by subdural hematomas evaluated at a single institution from 1998 to 2004. Data concerning the patient's clinical presentation, physical findings, imaging, and management are described. RESULTS: During the study period, 7 patients with BESS complicated by subdural hematoma were identified. Their mean age at identification of the subdural hematoma was 7.4 months of age. In 5 cases, there was no recognized trauma before identification of the subdural hematoma. In 3 cases, baseline CT or MR imaging was available, showing prominent subarachnoid spaces without any evidence of subdural hemorrhage. CONCLUSION: Although suspicious for NAT, subdural hematomas can occur in children either spontaneously or as a result of accidental trauma. Caution must be exercised when investigating for NAT based on the sole presence of subdural hematomas, especially in children who are otherwise well and who have BESS.

An Irish outbreak of New Delhi metallo-ß-lactamase (NDM)-1 carbapenemase-producing Enterobacteriaceae: increasing but unrecognized prevalence.

BACKGROUND: Carbapenemase-producing Enterobacteriaceae (CPE) may cause healthcare-associated infections with high mortality rates. New Delhi metallo-ß-lactamase-1 (NDM-1) is among the most recently discovered carbapenemases. AIM: To report the first outbreak of NDM-1 CPE in Ireland, including microbiological and epidemiological characteristics, and assessing the impact of infection prevention and control measures. METHODS: This was a retrospective microbiological and epidemiological review. Cases were defined as patients with a CPE-positive culture. Contacts were designated as roommates or ward mates. FINDINGS: This outbreak involved 10 patients with a median age of 71 years (range: 45-90), located in three separate but affiliated healthcare facilities. One patient was infected (the index case); the nine others were colonized. Nine NDM-1-producing Klebsiella pneumoniae, an NDM-1-producing Escherichia coli and a K. pneumoniae carbapenemase (KPC)-producing Enterobacter cloacae were detected between week 24, 2014 and week 37, 2014. Pulsed-field gel electrophoresis demonstrated similarity. NDM-1-positive isolates were meropenem resistant with minimum inhibitory concentrations (MICs) ranging from 12 to 32 µg/mL. All were tigecycline susceptible (MICs ≤1 µg/mL). One isolate was colistin resistant (MIC 4.0 µg/mL; mcr-1 gene not detected). In 2015, four further NDM-1 isolates were detected. CONCLUSION: The successful management of this outbreak was achieved via the prompt implementation of enhanced infection prevention and control practices to prevent transmission. These patients did not have a history of travel outside of Ireland, but several had frequent hospitalizations in Ireland, raising concerns regarding the possibility of increasing but unrecognized prevalence of NDM-1 and potential decline in value of travel history as a marker of colonization risk.

Effects of insulation on the temperature within farrowing huts and the weaning weights of piglets reared on a commercial outdoor pig unit.

The air temperatures inside uninsulated and insulated huts were recorded on an outdoor pig unit in the south of England between September 1997 and September 1998, and the herd's production parameters were also recorded. During the summer the temperatures inside some of the uninsulated huts exceeded 45 degrees C, but the temperatures inside the insulated huts were lower and fluctuated less. Despite the high temperatures, the weaning weight of piglets reared in the uninsulated huts were often higher than those of the piglets reared in the insulated huts, possibly as a result of the higher mortality of small piglets in the uninsulated huts, especially during the winter. The weaning weights of the piglets were higher during the summer.

Targeting colon cancer cell NF-κB promotes an anti-tumour M1-like macrophage phenotype and inhibits peritoneal metastasis.

In a model of peritoneal metastasis in immune-competent mice, we show that nuclear factor (NF)-κB inhibition in CT26 colon cancer cells prevents metastasis. NF-κB inhibition, by stable overexpression of IκB-α super-repressor, induced differential polarization of co-cultured macrophages to an M1-like anti-tumour phenotype in vitro. NF-κB-deficient cancer cell-conditioned media (CT26/IκB-α SR) induced interleukin (IL)-12 and nitric oxide (NO) synthase (inducible NO synthase (iNOS)) expression in macrophages. Control cell (CT26/EV) conditioned media induced high levels of IL-10 and arginase in macrophages. In vivo, this effect translated to reduction in metastasis in mice injected with CT26/ IκB-α SR cells and was positively associated with increased CD8(+)CD44(+)CD62L(-) and CD4(+)CD44(+)CD62L(-) effector T cells. Furthermore, inhibition of NF-κB activity induced high levels of NO in infiltrating immune cells and decreases in matrix metalloproteinase-9 expression, simultaneous with increases in tissue inhibitor of metalloproteinases 1 and 2 within tumours. CT26/IκB-α SR tumours displayed increased pro-inflammatory gene expression, low levels of angiogenesis and extensive intratumoral apoptosis, consistent with the presence of an anti-tumour macrophage phenotype. Macrophage depletion reduced tumour size in CT26/EV-injected animals and increased tumour size in CT26/IκB-α SR cells compared with untreated tumours. Our data demonstrate, for the first time, that an important implication of targeting tumour cell NF-κB is skewing of macrophage polarization to an anti-tumour phenotype. This knowledge offers novel therapeutic opportunities for anticancer treatment.

Incidence, management and outcomes of the first cfr-mediated linezolid-resistant Staphylococcus epidermidis outbreak in a tertiary referral centre in the Republic of Ireland.

AIM: To report the first Irish outbreak of cfr-mediated linezolid-resistant Staphylococcus epidermidis. METHODS: Linezolid-resistant S. epidermidis isolated at University Hospital Limerick from four blood cultures, one wound and four screening swabs (from nine patients) between April and June 2013 were characterized by pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST) and staphylococcal cassette chromosome (SCCmec) typing. Antibiotic susceptibilities were determined according to the guidelines of the British Society for Antimicrobial Chemotherapy. The outbreak was controlled through prohibiting prescription and use of linezolid, adherence to infection prevention and control practices, enhanced environmental cleaning, isolation of affected patients, and hospital-wide education programmes. FINDINGS: PFGE showed that all nine isolates represented a single clonal strain. MLST showed that they belonged to ST2, and SCCmec typing showed that they encoded a variant of SCCmecIII. All nine isolates were cfr positive, and eight isolates were positive for the G2576T 23S rRNA mutation commonly associated with linezolid resistance. Isolates exhibited multiple antibiotic resistances (i.e. linezolid, gentamicin, methicillin, clindamycin, ciprofloxacin, fusidic acid and rifampicin). The adopted infection prevention intervention was effective, and the outbreak was limited to the affected intensive care unit. CONCLUSIONS: This is the first documented outbreak of cfr-mediated linezolid-resistant S. epidermidis in the Republic of Ireland. Despite this, and due to existing outbreak management protocols, the responsible micro-organism and source were identified efficiently. However, it became apparent that staff knowledge of antimicrobial susceptibilities and appropriate hygiene practices were suboptimal at the time of the outbreak, and that educational interventions (and re-inforcement) are necessary to avoid occurrence of antimicrobial resistance and outbreaks such as reported here.

Septo-optic dysplasia plus: a spectrum of malformations of cortical development.

The authors describe three children with septo-optic dysplasia (SOD)-plus: SOD and an associated malformation of cortical development. All three children had developmental delay, and two of the children had significant associated motor deficits. The associated cortical malformations with SOD include a spectrum of disorders of neuronal organization, not limited, as previously described, to schizencephaly. SOD-plus should be suspected in children with SOD and developmental delay.

Congenital bilateral perisylvian polymicrogyria presenting as congenital hemiplegia.

We report three children with pure congenital hemiplegia found to have congenital bilateral perisylvian polymicrogyria (CBPP). None of our patients had the seizures, oromotor dysfunction, or cognitive impairment usually associated with CBPP. CBPP may be more common and heterogeneous than previously thought, is easily recognized by MRI, and should be included in the differential diagnosis of the young child presenting with congenital hemiplegia.

Increased yields of IL-2 in media conditioned by MLA 144 cells.

The gibbon leukaemia cell line MLA 144 produces IL-2 constitutively, and has been used as a source of IL-2 for the in vitro growth of T cells from a range of species. We have tried to increase the amount of IL-2 present in conditioned medium produced by this cell line, by manipulating the growth conditions and using compounds known to increase IL-2 production in other cell lines. We found that conditioned media containing a higher amount of IL-2 could be obtained from 72 h cultures of MLA 144 cells originally seeded at 4 X 10(5) cells/ml in DMEM containing 10% FBS and supplemented with 2-ME at 5 X 10(-5) M and PMA at 10 ng/ml.

Knobloch syndrome involving midline scalp defect of the frontal region.

We report on a 4-year-old boy with Knobloch syndrome. He has vitreoretinal degeneration, high myopia, cataract, telecanthus, hypertelorism, and a high-arched palate. He also has a defect of the anterior midline scalp with involvement of the frontal bone as documented by a computed tomography (CT) scan. The brain was normal on CT scan and magnetic resonance imaging. We present a review of the 23 published cases with this syndrome. Our patient illustrates the importance of investigating for underlying ocular and central nervous system pathology whenever midline scalp defects are present.

Computed tomography of intracranial gangliogliomas.

Thirteen patients with pathologically proven gangliogliomas were studied radiographically. The computed tomographic (CT) features of these 13 lesions and the other 35 cases in the literature were analyzed. Although the CT appearance of gangliogliomas was varied, certain characteristics were noted. The most common location was in the cerebral hemispheres, most often the temporal lobe. At least part of the tumor was low density in 71% of the unenhanced CT examinations. There were focal calcifications in 35% and enhancement with contrast material in 50%.

Duplicated odontoid process: plain radiographic and CT appearance of a rare congenital anomaly of the cervical spine.

We describe a duplication of the odontoid process in a 6-year-old patient that included a partially fused midline ossicle on the anterior arch of C-1, fusion of the anterior lip of the foramen magnum and the arch of C-1, and an incomplete bony posterior arch of C-1.

Traumatic aneurysm from shaken baby syndrome: case report.

OBJECTIVE AND IMPORTANCE: We present a 6-week-old infant who developed a traumatic aneurysm from clearly documented shaken baby syndrome. Despite the theoretical similarity in the mechanism of such injuries, this is the first aneurysm reported that resulted from such a cause. The infant is also the youngest reported patient to have suffered from a traumatic aneurysm. CLINICAL PRESENTATION: Police records documented shaking of the child as well as direct impact on the child's head. Three weeks later, the patient developed an intracerebral hemorrhage, which was revealed by angiography to have resulted from a pericallosal artery aneurysm. TECHNIQUE: The aneurysm was totally resected through a porencephalic cyst, which had developed secondary to ischemic injury to the brain. CONCLUSION: The temporal course, as well as the location of this traumatic aneurysm, is similar to that in older patients.

Neonatal intracranial hemorrhage. A clinical and serial computerized tomographic study.

Forty-six neonates with intracranial hemorrhage were classified into three groups on the basis of the major computerized tomography (CT) scan findings: Group I consisted of 24 cases of subarachnoid hemorrhage, Group II 20 cases of intracerebral and/or intraventricular hemorrhage, and Group III two cases of subdural hemorrhage. The initial scans in Group I showed blood in the interhemispheric fissure and the supratentorial recess. Sixty percent had an associated hypodensity in the frontal and/or parietal areas, thought to be an indication of ischemia. Changes in the configuration of the ventricular system were infrequent. Initial scans in Group II showed hematomas as follows: one in the brain stem, five in the basal ganglia, 10 in the temporal lobes, and 11 in the ventricles. In 70% of these cases, changes in the configuration of the ventricular system were seen, including compression of a lateral ventricle by mass effect, ventricular dilatation with blood, and obstructive hydrocephalus. Subarachnoid blood was an associated finding in 55% of cases, and focal and diffuse cerebral edema in 40%. Scans in both Group III patients initially showed a mass effect from a subdural clot. In all, 30 patients had one or more follow-up CT scans, and 13 of these were scanned at regular intervals. None of the Group I patients developed hydrocephalus, but 85% of Group II patients with intraventricular blood extending from an intracerebral hemorrhage had this complication. A seizure disorder occurred in 31% of Group I patients and 20% of Group II patients, where it was seen exclusively in those with an intralobar hematoma. A major motor disturbance occurred in 16% of patients; their Ct scans showed evidence of brain destruction involving enlargement of a lateral ventricle, porencephaly, or focal atrophy. Computerized tomography is a useful adjunct to the diagnosis, management, and follow-up study of neonatal intracranial hemorrhage, and correlates well with the clinical findings.