Development of cyclic gamma-MSH analogues with selective hMC3R agonist and hMC3R/hMC5R antagonist activities.

A series of cyclic lactam analogues of gamma-MSH (H-Tyr1-Val2-Met3-Gly4-His5-Phe6-Arg7-Trp8-Asp9-Arg10-Phe11-Gly12-OH) with a bulky hydrophobic residue in the direct proximity to the pharmacophore (Xaa-D-Phe/D-Nal(2')-Arg-Trp) were designed and synthesized by solid-phase methods. A variety of amino acids with a broad range of hydrophobic/hydrophilic properties was introduced in position 5 to further explore their complementary role in receptor selectivity. Biological evaluation of these peptides revealed several analogues with potent hMC3R agonist and hMC3R/hMC5R antagonist activities, and good receptor selectivity.

Leucodysplasia, microcephaly, cerebral malformation (LMC): a novel recessive disorder linked to 2p16.

We report three related and one unrelated child with an apparently novel neurodevelopmental disorder. The clinical course was very similar in all the four patients: congenital microcephaly with severe failure of post-natal brain growth, neonatal onset of intractable seizures associated with lack of developmental progression and death within the first 3 years of life. The appearance on cerebral neuroimaging was almost identical, with simplified gyration associated with a non-thickened cortex, severe hypoplasia of the corpus callosum, a small flattened brain stem, and specific cystic lesions in the white matter around the temporal and occipital horns.

Forced eruption: review and case reports.

When developing a diagnosis and prognosis for a compromised anterior tooth, dentists often deem these teeth to be nonrestorable or hopeless without exploring some of the less common options for saving the tooth. This article reviews literature concerning forced eruption as a treatment alternative, discusses treatment planning considerations, and presents two cases in which forced eruption was used. The first case involves a deeply fractured central incisor; the second case deals with a periodontally involved central incisor that was used to prepare its own extraction site for implant placement.

Canine epilepsy: what can we learn from human seizure disorders?

Epilepsy is a common neurological disorder in both dogs and humans. It is refractory to therapy in approximately one-third of canine patients, and even with the advent of new antiepileptic drugs for humans, appropriate treatment options in dogs remain limited. The pathogenesis and pathophysiology of epilepsy is being studied extensively in both human patients and rodent models of experimental epilepsy at the cellular and molecular level, but very little is known about the aetiologies of epilepsies in dogs.

Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.

Background: Sotos syndrome is characterised by learning difficulties, overgrowth, and a typical facial appearance. Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos.

Analysis of L -shell line spectra with 50-ps time resolution from Mo X -pinch plasmas.

Mo wire X pinches typically emit several x-ray bursts from a bright spot near the crossing of the X -pinch wires. Streak camera images of L -shell line emission from Mo wire X pinches have been analyzed using a non-local thermodynamic equilibrium (NLTE) collisional-radiative atomic kinetics model, providing temperature and density profiles with approximately 50 ps time resolution over the approximately 350 ps x-ray bursts. In conjunction with nonspectroscopic measurements, the analysis is used to propose a picture of the dynamic evolution of the X -pinch plasma.

Faculty members acceptance of web-based education.

Objective: To assess the effect of the WebCLS project on clinical laboratory science (CLS) faculty members including improvement of participating CLS educators' skills in designing, developing, delivering, and evaluating interactive, Web-based instructional programs.

Design: A survey was developed that included 24 statements related to respondents' perceptions of how their participation in the project: a) improved their course development skills, b) developed their evaluation skills, and c) affected them personally. Four open-ended questions asked the respondents to comment on the project's effect on their traditional course development skills, plans for future usage of WebCLS-produced course materials, the most beneficial outcomes of their participation, any problems that participation in the project caused them, and any unexpected positive or negative outcomes that could be attributed to their participation.

Biochemical indices of vascular function, glucose metabolism and oxidative stress in horses with equine Cushing's disease.

Reasons For Performing Study: The mechanisms underlying the increased risk of laminitis in horses with equine Cushing's disease (ECD) are poorly understood.

Hypothesis: That abnormalities in glucose homeostasis, similar to those which cause microvascular dysfunction in human diabetics, contribute to development of laminitis in horses with ECD.

Methods: Thirty-one aged horses were divided into 3 groups based on clinical signs and dexamethasone suppression testing (DST).

Delineation of Cohen syndrome following a large-scale genotype-phenotype screen.

Cohen syndrome is an autosomal recessive condition associated with developmental delay, facial dysmorphism, pigmentary retinopathy, and neutropenia. The pleiotropic phenotype, combined with insufficient clinical data, often leads to an erroneous diagnosis and has led to confusion in the literature. Here, we report the results of a comprehensive genotype-phenotype study on the largest cohort of patients with Cohen syndrome assembled to date.

Plasticity of GABA(B) receptor-mediated heterosynaptic interactions at mossy fibers after status epilepticus.

Several neurotransmitters, including GABA acting at presynaptic GABA(B) receptors, modulate glutamate release at synapses between hippocampal mossy fibers and CA3 pyramidal neurons. This phenomenon gates excitation of the hippocampus and may therefore prevent limbic seizure propagation. Here we report that status epilepticus, triggered by either perforant path stimulation or pilocarpine administration, was followed 24 hr later by a loss of GABA(B) receptor-mediated heterosynaptic depression among populations of mossy fibers.

Ophthalmic lesions in 83 geriatric horses and ponies.

Ophthalmic lesions were detected in 67 of 83 horses and ponies aged 15 years or more. Degeneration of the vitreous, followed by senile retinopathy, were the most common lesions and both of them became more common with advancing age, although few of the owners reported disturbances of vision in their animals.

Cohen syndrome is caused by mutations in a novel gene, COH1, encoding a transmembrane protein with a presumed role in vesicle-mediated sorting and intracellular protein transport.

Cohen syndrome is an uncommon autosomal recessive disorder whose diagnosis is based on the clinical picture of nonprogressive psychomotor retardation and microcephaly, characteristic facial features, retinal dystrophy, and intermittent neutropenia. We have refined the critical region on chromosome 8q22 by haplotype analysis, and we report the characterization of a novel gene, COH1, that is mutated in patients with Cohen syndrome. The longest transcript (14,093 bp) is widely expressed and is transcribed from 62 exons that span a genomic region of approximately 864 kb.

Neuropsychological assessment of a group of UK patients with Cohen syndrome.

Cohen syndrome is a rare autosomal recessive syndrome with a distinctive clinical phenotype that includes mental retardation and a characteristic sociable disposition. Variability in the level of learning disability and the behavioural phenotype is seen in the published literature. In a cohort of Finnish Cohen syndrome patients, severe mental retardation and non-maladaptive behaviour were described.

Diagnostic criteria, clinical characteristics, and natural history of Cohen syndrome.

Cohen syndrome is a rare, recessively inherited condition associated with facial dysmorphism, developmental delay, and visual disability. A delay in making the diagnosis commonly occurs, contributed to by the lack of a definitive molecular test and the clinical variability of published case reports. A specific clinical phenotype has been delineated in a homogeneous cohort of Finnish Cohen syndrome patients, but the applicability of their diagnostic criteria to non-Finnish patients has been debated.

The ophthalmic findings in Cohen syndrome.

Aim: Cohen syndrome is an uncommon autosomal recessive condition comprising a characteristic facial appearance, mental retardation, benign neutropenia, and retinal dystrophy. This study aimed to identify patients with Cohen syndrome from across the United Kingdom in order to define the variability of ophthalmic manifestations.

Methods: Ophthalmic assessment was undertaken and past ophthalmic records reviewed in 22 patients with classic features of Cohen syndrome.

High energy density z-pinch plasma conditions with picosecond time resolution.

Using an X-pinch configuration, we have determined that micropinches produced by exploding-wire z pinches can have densities approaching solid density and temperatures of 0.5-1.8 keV, depending upon the wire material used.

Urinary cortisol:creatinine ratios in healthy horses and horses with hyperadrenocorticism and non-adrenal disease.

Urinary cortisol and creatinine concentrations, and the cortisol:creatinine ratio were compared between 12 healthy horses (group 1), 13 horses with Cushing's disease (group 2), and eight horses with dysautonomia syndrome (equine grass sickness) (group 3). The mean (sd) urinary cortisol concentrations were 112 (55.7), 250 (357) and 864 (526) nmol/litre in groups 1, 2 and 3, respectively; the mean (sd) urinary creatinine concentrations were 18.