Comparative evaluation of supplemental zilpaterol hydrochloride sources on growth performance, dietary energetics and carcass characteristics of finishing lambs.

OBJECTIVE: We compare the effects of three different approved sources of supplemental zilpaterol on growth-performance responses and carcass characteristics of finishing lambs. METHODS: Twenty four Pelibuey×Katahdin lambs (46.75±2.43 kg) were used in a 33-day feeding trial. Lambs were fed a dry rolled corn-based finishing diet. Treatments consisted of the non-supplemental basal diet (Control) versus the basal diet supplemented with 125 mg zilpaterol/kg of diet (as fed basis) from three commercial sources marketed in Mexico: Zilmax (ZIL), Grofactor, and Zipamix. RESULTS: Compared to controls, zilpaterol (ZH) supplementation did not affect dry matter intake (DMI), but increased carcass adjusted daily weight gain (ADG, 36.7%), gain efficiency (34.2%), and dietary net energy (26.0%), and decreased (23.4%) the ratio of observed:expected DMI. Compared to controls, supplemental ZH increased hot carcass weight (6.4%), dressing percentage (3.2%), m. longissimus thoracis (LM) area (15.6%), and shoulder muscle:fat ratio (28.7%), but decreased kidney-pelvic-heart fat, and fat thickness. Supplemental ZH increased 10.9% and 14.3% whole cut weight of loin and leg, respectively, and the proportion (as percentage of cold carcass weight) of leg (4.3%). These increases were reflected in greater forequarter and hindquarter weights. Lambs fed ZH increased (4.6%) empty body weight (EBW) and reduced (14.7%) liver/spleen weight (as g/kg EBW). Likewise, ZH supplementation tended (p = 0.08) to lower (8.9%) visceral fat. Growth performance, energetic efficiency, hot carcass weight, dressing percentage, LM area and whole cuts were not different across supplemental ZH sources. However, compared with non-supplemented controls, only ZIL appreciably decreased carcass fat distribution, including fat thickness, percentage kidney pelvic and heart fat, shoulder fat, and visceral fat. CONCLUSION: Supplemental ZH increases ADG, gain efficiency, carcass dressing percentage, and LM area. The magnitude of these responses was similar among ZH sources. Nevertheless, compared with non-supplemented controls, only ZIL appreciably decreases carcass fat. The basis for this is uncertain, but indicative that some practical differences in zilpaterol bio-equivalency may exist across commercial sources tested.

Molecular profiling and feasibility using a comprehensive hybrid capture panel on a consecutive series of non-small-cell lung cancer patients from a single centre.

BACKGROUND: Targeted next-generation sequencing (NGS) is recommended to screen actionable genomic alterations (GAs) in patients with non-small-cell lung cancer (NSCLC). We determined the feasibility to detect actionable GAs using TruSight™ Oncology 500 (TSO500) in 200 consecutive patients with NSCLC. MATERIALS AND METHODS: DNA and RNA were sequenced on an Illumina® NextSeq 550 instrument and processed using the TSO500 Docker pipeline. Clinical actionability was defined within the molecular tumour board following European Society for Medical Oncology (ESMO) guidelines for oncogene-addicted NSCLC. Overall survival (OS) was estimated as per the presence of druggable GAs and treatment with targeted therapy. RESULTS: Most patients were males (69.5%) and former or current smokers (86.5%). Median age was 64 years. The most common histological type and tumour stage were lung adenocarcinoma (81%) and stage IV (64%), respectively. Sequencing was feasible in most patients (93.5%) and actionable GAs were found in 26.5% of patients. A high concordance was observed between single-gene testing and TSO500 NGS panel. Patients harbouring druggable GAs and receiving targeted therapy achieved longer OS compared to patients without druggable GAs. Conversely, patients with druggable GAs not receiving targeted therapy had a trend toward shorter OS compared with driver-negative patients. CONCLUSIONS: Hybrid capture sequencing using TSO500 panel is feasible to analyse clinical samples from patients with NSCLC and is an efficient tool for screening actionable GAs.

Ni doped Fe3O4 magnetic nanoparticles.

In this work, the effect of nickel doping on the structural and magnetic properties of Fe3O4 nanoparticles is analysed. Ni(x)Fe(3-x)O4 nanoparticles (x = 0, 0.04, 0.06 and 0.11) were obtained by chemical co-precipitation method, starting from a mixture of FeCl2 x 4H2O and Ni(AcO)2 x 4H2O salts. The analysis of the structure and composition of the synthesized nanoparticles confirms their nanometer size (main sizes around 10 nm) and the inclusion of the Ni atoms in the characteristic spinel structure of the magnetite Fe3O4 phase. In order to characterize in detail the structure of the samples, X-ray absorption (XANES) measurements were performed on the Ni and Fe K-edges. The results indicate the oxidation of the Ni atoms to the 2+ state and the location of the Ni2+ cations in the Fe2+ octahedral sites. With respect to the magnetic properties, the samples display the characteristic superparamagnetic behaviour, with anhysteretic magnetic response at room temperature. The estimated magnetic moment confirms the partial substitution of the Fe2+ cations by Ni2+ atoms in the octahedral sites of the spinel structure.

Antibacterial spectrum of cefiderocol.

Cefiderocol, a siderophore catechol cephalosporin, recently introduced in the market has been developed to enhance the in vitro activity of extended spectrum cephalosporins and to avoid resistance mechanisms affecting cephalosporins and carbapenems. The in vitro study of cefiderocol in the laboratory requires iron depleted media when MIC values are determined by broth microdilution. Disk diffusion presents good correlation with MIC values. In surveillance studies and in clinical trials it has been demonstrated excellent activity against Gram-negatives, including carbapenemase producers and non-fermenters such as Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia. Few cefiderocol resistant isolates have been found in surveillance studies. Resistance mechanisms are not directly associated with porin deficiency and or efflux pumps. On the contrary, they are related with gene mutations affecting iron transporters, AmpC mutations in the omega loop and with certain beta-lactamases such us KPC-variants determining also ceftazidime-avibactam resistance, certain infrequent extended-spectrum betalactamases (PER, BEL) and metallo-beta-lactamases (certain NDM variants and SPM enzyme).

A C-terminal deletion in Corynebacterium glutamicum homoserine dehydrogenase abolishes allosteric inhibition by L-threonine.

In Escherichia coli, Bacillus subtilis and Corynebacterium glutamicum, homoserine dehydrogenase (HD), the enzyme after the branch point of the threonine/methionine and lysine biosynthetic pathways, is allosterically inhibited by L-threonine. To investigate the regulation of the C. glutamicum HD enzyme by L-threonine, the structural gene, hom, was mutated by UV irradiation of whole cells to obtain a deregulated allele, homdr. L-Threonine inhibits the wild-type (wt) enzyme with a Ki of 0.16 mM. The deregulated enzyme remains 80% active in the presence of 50 mM L-threonine. The homdr gene mutant was isolated and cloned in E. coli. In a C. glutamicum wt host background, but not in E. coli, the cloned homdr gene is genetically unstable. The cloned homdr gene is overexpressed tenfold in C. glutamicum and is active in the presence of over 60 mM L-threonine. Sequence analysis revealed that the homdr mutation is a single nucleotide (G1964) deletion in codon 429 within the hom reading frame. The resulting frame-shift mutation radically alters the structure of the C terminus, resulting in ten amino acid (aa) changes and a deletion of the last 7 aa relative to the wt protein. These observations suggest that the C terminus may be associated with the L-threonine allosteric response. The homdr mutation is unstable and probably deleterious to the cell. This may explain why only one mutation was obtained despite repeated mutagenesis.

Metabolic and cardiovascular effects of a progressive exercise test in patients with chronic fatigue syndrome.

PURPOSE: To evaluate the aerobic power (as maximum volume of oxygen consumed [VO2 max]) of women with chronic fatigue syndrome (CFS). PATIENTS AND METHODS: Twenty-one women with CFS and 22 sedentary healthy controls (CON) were studied at the CFS Cooperative Research Center Exercise Laboratory at the VA Medical Center, East Orange, New Jersey. Performance was measured on an incremental treadmill protocol walking to exhaustion. Expired gases were analyzed by a metabolic system, heart rate was recorded continuously, and ratings of perceived exertion (RPE) were taken at each workload. The groups were divided into those who achieved VO2 max (CFS-MAX and CON-MAX) and those who stopped at a submaximal level (CFS-NOMAX and CON-NOMAX) by using standard criteria. RESULTS: Seventeen CON and 10 CFS subjects achieved VO2 max. The VO2 max (mL/kg/min) of the CFS-MAX (28.1 +/- 5.1) was lower than that of the CON-MAX (32.1 +/- 4.3, P = 0.05). The CFS-MAX achieved 98 +/- 11% of predicted VO2 max. The CFS group had a higher RPE at the same absolute workloads as controls (P < 0.01) but not the same relative workloads. CONCLUSION: Compared with normal controls, women with CFS have an aerobic power indicating a low normal fitness level with no indication of cardiopulmonary abnormality. Our CFS group could withstand a maximal treadmill exercise test without a major exacerbation in either fatigue or other symptoms of their illness.

Baroreceptor modulation of active cutaneous vasodilation during dynamic exercise in humans.

The hypothesis that baroreceptor unloading during dynamic limits cutaneous vasodilation by withdrawal of active vasodilator activity was tested in seven human subjects. Increases in forearm skin blood flow (laser-Doppler velocimetry) at skin sites with (control) and without alpha-adrenergic vasoconstrictor activity (vasodilator only) and in arterial blood pressure (noninvasive) were measured and used to calculate cutaneous vascular conductance (CVC). Subjects performed two similar dynamic exercise (119 +/- 8 W) protocols with and without baroreceptor unloading induced by application of -40 mmHg lower body negative pressure (LBNP). The LBNP condition was reversed (i.e., either removed or applied) after 15 min while exercise continued for an additional 15 min. During exercise without LBNP, the increase in body core temperature (esophageal temperature) required to elicit active cutaneous vasodilation averaged 0.25 +/- 0.08 and 0.31 +/- 0.10 degrees C (SE) at control and vasodilator-only skin sites, respectively, and increased to 0.44 +/- 0.10 and 0.50 +/- 0.10 degrees C (P < 0.05 compared with without LBNP) during exercise with LBNP. During exercise baroreceptor unloading delayed the onset of cutaneous vasodilation and limited peak CVC at vasodilator-only skin sites. These data support the hypothesis that during exercise baroreceptor unloading modulates active cutaneous vasodilation.

A non-hemorrhagic manifestation of vasa previa: a clinicopathologic case report.

BACKGROUND: The rare entity of vasa previa occurs when fetal vessels lying between the amniotic and chorionic membranes cross the cervical os. This report presents a case that was associated with vessel compression and concomitant adverse effects on fetal hemodynamics. CASE: A 23-year-old nulliparous woman at 36 weeks' gestation developed persistent, progressive severe variable decelerations several hours after spontaneous rupture of the membranes, resulting in a decision to perform a cesarean. At delivery, fetal vessels were noted in the membranes near the cervical os, leading into a marginally inserted cord. The decelerations were attributed to compression of the unprotected umbilical arteries by the fetal head. CONCLUSION: Vasa previa often results in fetal death and may be associated with fetal hemorrhage, but lack of bleeding does not exclude the existence of vasa previa. Altered fetal hemodynamics from varying degrees of vessel compression by the presenting part during labor may result in hypoxia and acidosis. A high index of suspicion is necessary to make the diagnosis and institute proper, timely management.

Intraligamentary pregnancy.

Intraligamentary pregnancy, although rare, tests the physician's acumen in diagnostic and therapeutic skills. Two cases illustrating this entity are presented, the first involves an 18-week fetus, the second a partial hydatidiform mole. Although their presentation and pathogenesis may be indistinguishable, their clinical course and management is different. To the best of our knowledge, this is the first reported case of an intraligamentary pregnancy involving a partial hydatidiform mole.

Caudal regression syndrome: etiopathogenesis, prenatal diagnosis, and perinatal management.

Caudal regression syndrome represents a continuum of congenital malformations ranging from agenesis of the lumbosacral spine to the most severe cases of sirenomelia with lower extremities fusion and major visceral anomalies. The etiology of this syndrome is not well known. Maternal diabetes, genetic predisposition, and vascular hypoperfusion have been suggested as possible causative factors. The degree of associated anomalies usually parallels the severity of the primary defect. Ultrasonography is the diagnostic tool of choice revealing the absent distal vertebrae of the fetal spine. Amnioinfusion and magnetic resonance imaging (MRI) are of help in better evaluation of the fetal anatomy in cases with oligohydramnios. Perinatal management depends mainly on gestational age at diagnosis and severity of the lesion. It should include genetic counseling and serial sonography to assess interval growth and amniotic fluid volume. Surviving infants have usually a normal mental function and they require extensive urologic and orthopedic assistance. Their long-term morbidity consists mostly of neurogenic bladder dysfunction resulting in progressive renal damage and disabling neuromuscular deficits of the lower extremities. Neurosurgical and orthopedic intervention with physical rehabilitation is indicated to improve the quality of their lives.

Periodontal treatment needs in 12-16-yr-old children from Santo Domingo.

The purpose of this study was to determine the periodontal treatment needs, using the CPITN, in 12-16 yr-old children from private and public schools from Santo Domingo, Dominican Republic. A total of 1080 children was studied (540 in private schools and 540 in public schools). More children from private schools were seen without signs of periodontal disease than in public schools. More children from private schools showed no need for treatment. There was no statistical difference between children from private and public schools regarding the treatment need categories I and III. However, for the treatment need II category (oral hygiene-scaling), the children from public schools showed a slight increase in need over the private schoolchildren. Combining private and public schools, 12.9% of the 1080 children examined needed no treatment, 5.9% needed treatment I, 80.8% needed treatment II, and 0.4% needed treatment III.

Cardiopulmonary arrest in pregnancy: the role of caesarean section in the resuscitative protocol.

A 36-year-old black multipara at 32 weeks gestation was referred with apparent peripartal cardiomyopathy. Upon arrival, she was found to be in pulmonary edema; and shortly thereafter developed cardiopulmonary arrest. She failed to respond to initial attempts at cardiopulmonary resuscitation but subsequently responded after Caesarean section and pericardiocentesis. This case exemplifies the unique aspects of performing cardiopulmonary resuscitation on a gravid female in the latter part of pregnancy and that Caesarean section should be considered an integral part of the resuscitative protocol when standard protocols fail.

Spontaneous resolution of an isolated unilateral fetal pleural effusion: a case report.

Isolated pleural effusion is rare and occurs when varying degrees of fluid surround the fetal lung without concomitant hydrops. This article reports a case in which spontaneous resolution of an isolated fetal pleural effusion occurred four weeks following the third trimester sonographic diagnosis, without any morbidity or mortality to the fetus or neonate. The diagnosis and possible complications associated with fetal pleural effusions are also discussed, as well as a proposal for management when confronted with this entity.

In vitro response of pre-osteoblastic cells to laser microgrooved PEEK.

Polyetheretherketone (PEEK) is currently being used in implants as an alternative to titanium, due to its mechanical properties, cytocompatibility and inertness. Several studies have demonstrated that certain patterning on the implants promotes the oriented cell growth of osteoblasts, favouring the formation of bone tissue. This patterning improves the implant's osteointegration in the bone and its mechanical stability. Therefore, the objective of this work is to micro-structure PEEK by laser radiation and to carry out an exhaustive study of the orientation of pre-osteoblast cells that grow on this material. Parallel microgrooves were obtained using an ArF excimer laser coupled with a mask projection unit with distances of 25, 50, 75 and 100 µm between grooves. The cell growth on these PEEK surfaces was studied, in order to compare the effect of different distances between grooves on the biological response of MC3T3-E1 pre-osteoblastic cells. Preferential cell orientation was observed for all studied distances, which was more pronounced in the 25 and 50 µm ones.

Aspirin triggered-lipoxin A4 reduces the adhesion of human polymorphonuclear neutrophils to endothelial cells initiated by preeclamptic plasma.

INTRODUCTION: Preeclampsia is a disorder of pregnancy, characterized by hypertension and proteinuria after 20 weeks of gestation. Here, we evaluated the role of aspirin triggered-lipoxin A(4) (ATL, 15-epi-LXA(4)) on the modulation of the adhesion of human polymorphonuclear neutrophils (PMN) to endothelial cells initiated by preeclamptic plasma. MATERIALS AND METHODS: Plasma from preeclamptic, normotensive pregnant, and non-pregnant women were analyzed for factors involved in regulating angiogenesis, inflammation and lipid peroxidation. Plasma from preeclamptic women was added to human umbilical vein endothelial cells, and the adhesion of PMN (incubated with or without ATL) to cells was evaluated. RESULTS: Preeclampsia was associated with some augmented anti-angiogenic, oxidative and pro-inflammatory markers, as well as increasing human PMN-endothelial cell adhesion. This cell adhesion was reduced when human PMN were incubated with ATL prior to addition to endothelial monolayers. DISCUSSIONS AND CONCLUSIONS: Our results are the starting point for further research on the efficacy and rational use of aspirin in preeclampsia.

Molecular imaging of phosphorylation events for drug development.

PURPOSE: Protein phosphorylation mediated by protein kinases controls numerous cellular processes. A genetically encoded, generalizable split firefly luciferase (FL)-assisted complementation system was developed for noninvasive monitoring phosphorylation events and efficacies of kinase inhibitors in cell culture and in small living subjects by optical bioluminescence imaging. PROCEDURES: An Akt sensor (AST) was constructed to monitor Akt phosphorylation and the effect of different PI-3K and Akt inhibitors. Specificity of AST was determined using a non-phosphorylable mutant sensor containing an alanine substitution (ASA). RESULTS: The PI-3K inhibitor LY294002 and Akt kinase inhibitor perifosine led to temporal- and dose-dependent increases in complemented FL activities in 293T human kidney cancer cells stably expressing AST (293T/AST) but not in 293T/ASA cells. Inhibition of endogenous Akt phosphorylation and kinase activities by perifosine also correlated with increase in complemented FL activities in 293T/AST cells but not in 293T/ASA cells. Treatment of nude mice bearing 293T/AST xenografts with perifosine led to a 2-fold increase in complemented FL activities compared to that of 293T/ASA xenografts. Our system was used to screen a small chemical library for novel modulators of Akt kinase activity. CONCLUSION: This generalizable approach for noninvasive monitoring of phosphorylation events will accelerate the discovery and validation of novel kinase inhibitors and modulators of phosphorylation events.

Ornithine transcarbamylase deficiency in pregnancy.

Women heterozygous for mutations at the ornithine transcarbamylase (OTC) locus may be at risk for hyperammonaemia and its untoward effects including coma and death in the postpartum period. We present the case of a pregnant woman heterozygous for OTC deficiency (McKusick 311250) whose past medical history was significant for two prior pregnancies complicated by postpartum hyperammonaemic coma. In the index pregnancy, increased levels of serum ammonium were noted during labour. Postpartum hyperammonaemia was averted by administration of oral sodium benzoate. Our experience demonstrates that in women at risk, perilous hyperammonaemia can be prevented through appropriate medical management.

Cardiovascular regulation in multiple sclerosis.

Traditional assessments of autonomic nervous system function have depended on invasive and complex procedures. Vagal power, which is the respiratory component of heart rate variability (HRV) is an alternative and non-invasive measure for indexing autonomic nervous control of the heart. In the current study, 18 multiple sclerosis (MS) and 20 healthy subjects matched with respect to age, education and intelligence served as subjects. The MS group showed significantly lower vagal power during natural and paced breathing than healthy subjects. Importantly, heart rate did not differ between the two groups. If MS patients exhibit abnormalities in mechanisms mediating cardiac parasympathetic control, the impact on quality of life and vulnerability to adverse cardiac events need to be further evaluated. The results of this study may have implications with respect to the feasibility of using HRV as both a diagnostic and prognostic tool for evaluating parasympathetic nervous system dysfunction and in providing valuable information for developing more effective treatment and rehabilitation strategies.