Mandibulofacial dysostosis, severe lower eyelid coloboma, cleft palate, and alopecia: A new distinct form of mandibulofacial dysostosis or a severe form of Johnson-McMillin syndrome?

We describe a patient with a phenotype characterized by mandibulofacial dysostosis with severe lower eyelid coloboma, cleft palate, abnormal ears, alopecia, delayed eruption and crowded teeth, and sensorioneural hearing loss. The karyotype and the screening for mutations in the coding region of TCOF1 gene were normal. The clinical signs of our case overlap the new mandibulofacial dysostosis described by Stevenson et al.

Antitrypanosomal and antileishmanial activities of novel N-alkyl-(1-phenylsubstituted-beta-carboline)-3-carboxamides.

A series of 1-phenylsubstituted beta-carbolines containing an N-butylcarboxamide group at C-3 of beta-carboline nucleus were synthesized and evaluated in vitro against epimastigote form of Trypanosoma cruzi and promastigote form of Leishmania amazonensis. Among all compounds tested, two derivatives (2b and 2d) presented potent activity against both parasites. The most active derivative 2b showed also the higher selectivity index ratio (SI) for L.

Energy expenditure, lipid profile, oxidative stress, and cardiac energy metabolism after growth hormone treatment in obese young rats.

Obesity is rampant in modern society and growth hormone (GH) could be useful as adjunct therapy to reduce the obesity-induced cardiovascular damage. To investigate GH effects on obesity, initially 32 male Wistar rats were divided into two groups (n=16): control (C) was fed standard-chow and water and hypercaloric (H) was fed hypercaloric chow and 30% sucrose in its drinking water. After 45 days, both C and H groups were divided into two subgroups (n=8): C+PL was fed standard-chow, water and received saline subcutaneously; C+GH was fed standard-chow, water, and received 2 mg/kg/day GH subcutaneously; H+PL was fed hypercaloric diet, 30% sucrose in its drinking water, and received saline subcutaneously; and H+GH was fed hypercaloric diet, 30% sucrose in its drinking water, and received GH subcutaneously.

Enhanced visual acuity and image perception following correction of highly aberrated eyes using an adaptive optics visual simulator.

Purpose: To evaluate the changes in visual acuity and visual perception generated by correcting higher order aberrations in highly aberrated eyes using a large-stroke adaptive optics visual simulator.

Methods: A crx1 Adaptive Optics Visual Simulator (Imagine Eyes) was used to correct and modify the wavefront aberrations in 12 keratoconic eyes and 8 symptomatic postoperative refractive surgery (LASIK) eyes. After measuring ocular aberrations, the device was programmed to compensate for the eye's wavefront error from the second order to the fifth order (6-mm pupil).

Saethre-Chotzen syndrome, Pro136His TWIST mutation, hearing loss, and external and middle ear structural anomalies: report on a Brazilian family.

Objective: To describe the clinical, speech, hearing, and imaging findings in three members of a Brazilian family with Saethre-Chotzen syndrome (SCS) who presented some unusual characteristics within the spectrum of the syndrome.

Design: Clinical evaluation was performed by a multidisciplinary team. Direct sequencing of the polymerase chain reaction-amplified coding region of the TWIST1 gene, routine and electrophysiological hearing evaluation, speech evaluation, and imaging studies through computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed.

Energy expenditure and oxygen consumption as novel biomarkers of obesity-induced cardiac disease in rats.

The purpose of the present study was to determine calorimetric parameters to predict obesity adverse effects on oxidative stress and cardiac energy metabolism. Male Wistar 24 rats were divided into three groups (n = 8): given standard chow and water (C), receiving standard chow and 30% sucrose in its drinking water (S), and given sucrose-rich diet and water (SRD). After 45 days, both S and SRD rats had obesity, serum oxidative stress, and dyslipidemic profile, but the body weight gain and feed efficiency (FE) were higher in SRD than in S, whereas the obesity-related oxidative stress, myocardial triacylglycerol accumulation, and enhanced cardiac lactate dehydrogenase (LDH) activity were higher in S than in SRD rats.

Alcoholism and alcohol abstinence: N-acetylcysteine to improve energy expenditure, myocardial oxidative stress, and energy metabolism in alcoholic heart disease.

Alcoholism has been associated with a wide range of pathologic conditions, including alcoholic heart disease (AHD). Because AHD may be associated with oxidative stress, antioxidant compounds, such as N-acetylcysteine (NAC) could be useful to control the damage done by alcohol (ethanol) consumption. To investigate the NAC effects on alcoholism and alcohol abstinence, initially, 30 male Wistar rats were divided into two groups: (C, N=6) given standard chow and water; (E, N=24) receiving standard chow and aqueous ethanol solution in semi-voluntary research.

Calculation of intraocular lens power using Orbscan II quantitative area topography after corneal refractive surgery.

Purpose: To present the prospective application of the Orbscan II central 2-mm total-mean corneal power obtained by quantitative area topography in intraocular lens (IOL) calculation after refractive surgery.

Methods: Calculated and achieved refraction and the difference between them were studied in 77 eyes of 61 patients with previous radial keratotomy (RK), RK and additional surgeries, myopic LASIK, myopic photorefractive keratectomy (PRK), or hyperopic LASIK who underwent phacoemulsification without complications in 3 eye centers. All IOL calculations used the average from the central 2-mm Orbscan II total-mean power of maps centered on the pupil without the use of previous refractive data.

3D Topology Preserving Flows for Viewpoint-Based Cortical Unfolding.

We present a variational method for unfolding of the cortex based on a user-chosen point of view as an alternative to more traditional global flattening methods, which incur more distortion around the region of interest. Our approach involves three novel contributions. The first is an energy function and its corresponding gradient flow to measure the average visibility of a region of interest of a surface with respect to a given viewpoint.

PCBs and DDE in tree swallow (Tachycineta bicolor) eggs and nestlings from an estuarine PCB superfund site, New Bedford Harbor, MA, U.S.A.

While breeding tree swallows (Tachycineta bicolor) have been used as biomonitors for freshwater sites, we report the first use of this species to assess contaminant bioaccumulation from estuarine breeding grounds into these aerial insectivores. Eggs and nestlings were collected from nest boxes in a polychlorinated biphenyl (PCB) contaminated estuary, the New Bedford Harbor Superfund site (NBH, Massachusetts, USA), and a reference salt marsh, Fox Hill (FH, Jamestown, Rhode Island, USA). Sediments, eggs, and nestlings were compared on a ng g(-1) wet weight basis for total PCBs and DDE (1,1-bis-(4-chlorophenyl)-2,2-dichloroethene), metabolite of DDT (1,1,1-trichloro-2,2-bis-(p-chlorophenyl)ethane).

Expanding depth of focus by modifying higher-order aberrations induced by an adaptive optics visual simulator.

Purpose: To evaluate the impact of higher-order aberrations on depth of focus using an adaptive optics visual simulator.

Setting: Refractive Surgery Department, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Methods: An adaptive optics simulator was used to optically introduce individual aberrations in eyes of subjects with a 6.

JAK2(V617F) mutation in myelodysplastic syndrome (MDS) with del(5q) arises in genetically discordant clones.

The 2008 World Health Organization (WHO) proposed revision of the classification of MDS recognizes a deletion (5q) subtype with mutation of Janus kinase-2 (JAK2(V617F)). We investigated the clonal origin of this gene mutation in a patient with del(5q) MDS presenting with thrombocytosis and normal hemoglobin. Analysis of colony forming units-granulocyte-monocyte (CFU-GM) and erythropoietin-independent growth of bone marrow (BM) and peripheral blood (PB) burst forming units-erythroid (BFU-E) showed that del(5q) and JAK2(V617F) existed in progenitors derived from independent clones.

A critical role for phosphatase haplodeficiency in the selective suppression of deletion 5q MDS by lenalidomide.

Lenalidomide is the first karyotype-selective therapeutic approved for the treatment of myelodysplastic syndromes (MDS) owing to high rates of erythroid and cytogenetic response in patients with chromosome 5q deletion [del(5q)]. Although haploinsufficiency for the RPS14 gene and others encoded within the common deleted region (CDR) have been implicated in the pathogenesis of the del(5q) phenotype, the molecular basis of the karyotype specificity of lenalidomide remains unexplained. We focused our analysis on possible haplodeficient enzymatic targets encoded within the CDR that play key roles in cell-cycle regulation.

Incidence of rainbow glare after laser in situ keratomileusis flap creation with a 60 kHz femtosecond laser.

Purpose: To report the incidence of and factors associated with rainbow glare after laser in situ keratomileusis (LASIK) flap creation with a 60 kHz femtosecond laser.

Setting: Department of Refractive Surgery, Cleveland Clinic Cole Eye Institute, Cleveland, Ohio, USA.

Methods: Consecutive patients having LASIK by the same surgeon were questioned during postoperative examinations or by telephone about postoperative rainbow glare (radiating colors around a white light at night).

Central and peripheral corneal thickness measured with optical coherence tomography, Scheimpflug imaging, and ultrasound pachymetry in normal, keratoconus-suspect, and post-laser in situ keratomileusis eyes.

Purpose: To compare central (CCT) and peripheral corneal thickness (PCT) using Scheimpflug imaging (Pentacam), high-speed optical coherence tomography (Visante OCT), and ultrasound (US) pachymetry (Sonogage Corneo-Gage Plus) in normal, keratoconus-suspect, and post-laser in situ keratomileusis (LASIK) eyes.

Setting: Department of Refractive Surgery, Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Methods: The CCT and PCT were retrospectively measured using US pachymetry, Scheimpflug imaging, and high-speed OCT from January 2006 to March 2008.

Thresholds for interface haze formation after thin-flap femtosecond laser in situ keratomileusis for myopia.

Purpose: To evaluate the risk factors for interface haze formation after thin-flap femtosecond laser--laser in situ keratomileusis (LASIK).

Design: Prospective case series.

Methods: One hundred and ninety-nine consecutive eyes that underwent femtosecond laser LASIK with a LADAR 4000 excimer laser (Alcon Laboratories, Fort Worth, Texas, USA), were analyzed from January 1 to April 30, 2008.

Resveratrol toxicity: effects on risk factors for atherosclerosis and hepatic oxidative stress in standard and high-fat diets.

The beneficial action of moderate wine consumption is increasingly being attributed to resveratrol (trans-3,4',5-trihydroxystilbene). To test the safety of resveratrol use as a dietary supplement, 24 male Wistar rats were initially divided into three groups: (C, n=6) was given standard chow and water; (R, n=6) received standard chow and 6 mg/l resveratrol in its drinking water (1mg/kg/day), and (HFD, n=12) received high-fat diet and water. In order to more appropriately study the effects of resveratrol on high-fat diet, after 30 days of treatments, HFD-rats were divided into two subgroups (n=6/group):(HFD) remained receiving high-fat diet and water; (HFD-R) given high-fat diet and 6 mg/l resveratrol in its drinking water (1mg/kg/day).

Protein-drug interaction studies for development of drugs against Plasmodium falciparum.

The study of protein-drug interaction is of pivotal importance to understand the structural features essential for ligand affinity. The explosion of information about protein structures has paved the way to develop structure-based virtual screening approaches. Parasitic protein kinases have been pointed out as potential targets for antiparasitic development.

Genomic databases and the search of protein targets for protozoan parasites.

The development of databases devoted to biological information opened the possibility to integrate, query and analyze biological data obtained from several sources that otherwise would be scattered through the web. Several issues arise in the handling of biological information, mainly due to the diversity of biological subject matter and the complexity of biological approaches towards phenomena of the living world. The integration of genomic data, three-dimensional structures of proteins, biological activity, and drugs availability allows a system approach to the study of the biology.

N-acetylcysteine an allium plant compound improves high-sucrose diet-induced obesity and related effects.

This study was designed to determine whether N-acetylcysteine (NAC, C(5)H(9)-NO(3)S), a compound from Allium species may be used as a complementary therapeutic agent, to inhibit high-sucrose induced-obesity and its effects on glucose tolerance, in vivo low-density lipoprotein (LDL)-oxidation and serum oxidative stress in rats. Initially, 24 male Wistar rats were divided into two groups: controls receiving standard chow (C, n = 6) and those receiving high-sucrose diet (HS, n = 18). After 22 days, (HS) group was divided into three groups (n = 6/group); (HS-HS) continued to eat high-sucrose diet and water; (HS-N) continued to eat high-sucrose diet and received 2 mg l(-1)-NAC in its drinking water; (HS-CN) changing high-sucrose to standard chow and receiving 2 mg l(-1)-NAC in its drinking water.

N-acetylcysteine in high-sucrose diet-induced obesity: energy expenditure and metabolic shifting for cardiac health.

To study the effects of N-acetylcysteine (NAC, C(5)H(9)-NO(3)S) on high-sucrose diet-induced obesity and its effects on energy metabolism and cardiac oxidative stress, male Wistar 24 rats were divided into four groups (n=6): (C) given standard chow and water; (N) receiving standard chow and 2g/l N-acetylcysteine in its drinking water; (HS) given standard chow and 30% sucrose in its drinking water, and (HS-N) receiving standard chow, 30% sucrose and N-acetylcysteine in its drinking water. After 30 days of the treatment, obesity was evidenced in HS rats from enhanced body weight, respiratory quotient, hypertriglyceridemia. As well depressed resting metabolic rate, and oxygen consumption per surface area.

Comparative study of riboflavin-UVA cross-linking and "flash-linking" using surface wave elastometry.

Purpose: To investigate comparative stiffness values in porcine corneas after standard cross-linking and a new, rapid method of cross-linking (flash-linking) using surface wave elastometry.

Methods: Ten porcine eyes were treated using an ultraviolet A (UVA) double diode light source with a wavelength of 370 nm and delivering an irradiance of 4.2 mW/cm2 at a distance of 1.

Fibroblast growth factor 2 restrains Ras-driven proliferation of malignant cells by triggering RhoA-mediated senescence.

Fibroblast growth factor 2 (FGF2) is considered to be a bona fide oncogenic factor, although results from our group and others call this into question. Here, we report that exogenous recombinant FGF2 irreversibly inhibits proliferation by inducing senescence in Ras-dependent malignant mouse cells, but not in immortalized nontumorigenic cell lines. We report the following findings in K-Ras-dependent malignant Y1 adrenocortical cells and H-Ras V12-transformed BALB-3T3 fibroblasts: (a) FGF2 inhibits clonal growth and tumor onset in nude and immunocompetent BALB/c mice, (b) FGF2 irreversibly blocks the cell cycle, and (c) FGF2 induces the senescence-associated beta-galactosidase with no accompanying signs of apoptosis or necrosis.

Method for optimizing topography-guided ablation of highly aberrated eyes with the ALLEGRETTO WAVE excimer laser.

Purpose: To evaluate the clinical outcomes of custom topographic neutralizing technique in treating highly aberrated eyes using the WaveLight ALLEGRETTO WAVE Excimer Laser.

Methods: A retrospective consecutive case series of 67 eyes with decentered ablations and 48 eyes with symptomatic small optical zones after previous LASIK underwent topography-guided retreatment with the ALLEGRETTO WAVE. Sixteen keratoconus eyes underwent topographic neutralizing technique photorefractive keratectomy (PRK).