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1.  Midsagittal Anatomy of Lumbar Lordosis in Adult Egyptians: MRI Study 
Anatomy Research International  2014;2014:370852.
Despite the increasing recognition of the functional and clinical importance of lumbar lordosis, little is known about its description, particularly in Egypt. At the same time, magnetic resonance imaging (MRI) has been introduced as a noninvasive diagnostic technique. The aim of this study was to investigate the anatomy of the lumbar lordosis using midsagittal MRIs. Normal lumbar spine MRIs obtained from 93 individuals (46 males, 47 females; 25–57 years old) were evaluated retrospectively. The lumbar spine curvature and its segments “vertebrae and discs” were described and measured. The lumbar lordosis angle (LLA) was larger in females than in males. Its mean values increased by age. The lumbar height (LH) was longer in males than in females. At the same time, the lumbar breadth (LB) was higher in females than in males. Lumbar index (LI = LB/LH × 100) showed significant gender differences (P < 0.0001). Lordosis was formed by wedging of intervertebral discs and bodies of lower lumbar vertebrae. In conclusion, MRI might clearly reveal the anatomy of the lumbar lordosis. Use of LI in association with LLA could be useful in evaluation of lumbar lordosis.
PMCID: PMC4151604  PMID: 25210630
2.  Novel Synthesis Method of Micronized Ti-Zeolite Na-A and Cytotoxic Activity of Its Silver Exchanged Form 
The core-shell method is used as a novel synthetic process of micronized Ti-Zeolite Na-A which involves calcination at 700°C of coated Egyptian Kaolin with titanium tetrachloride in acidic medium as the first step. The produced Ti-coated metakaolinite is subjected to microwave irradiation at low temperature of 80°C for 2 h. The prepared micronized Ti-containing Zeolites-A (Ti-Z-A) is characterized by FTIR, XRF, XRD, SEM, and EDS elemental analysis. Ag-exchanged form of Ti-Z-Ag is also prepared and characterized. The Wt% of silver exchanged onto the Ti-Zeolite structure was determined by atomic absorption spectra. The in vitro cytotoxic activity of Ti-Z-Ag against human hepatocellular carcinoma cell line (HePG2), colon cell line carcinoma (HCT116), lung carcinoma cell line (A549), and human Caucasian breast adenocarcinoma (MCF7) is reported. The results were promising and revealed that the exchanged Ag form of micronized Ti-Zeolite-A can be used as novel antitumor drug.
PMCID: PMC4332468
3.  Synthesis, Docking and Biological Activities of Novel Hybrids Celecoxib and Anthraquinone Analogs as Potent Cytotoxic Agents 
Herein, novel hybrid compounds of celecoxib and 2-aminoanthraquinone derivatives have been synthesized using condensation reactions of celecoxib with 2-aminoanthraquinone derivatives or 2-aminoanthraquinon with celecoxib derivatives. Celecoxib was reacted with different acid chlorides, 2-chloroethylisocyanate and bis (2-chloroethyl) amine hydrochloride. These intermediates were then reacted with 2-aminoanthraquinone. Also the same different acid chlorides and 2-chloroethylisocyanate were reacted with 2-aminoanthraquinone and the resulting intermediates were reacted with celecoxib to give isomers for the previous compounds. The antitumor activities against hepatic carcinoma tumor cell line (HEPG2) have been investigated in vitro, and all these compounds showed promising activities, especially compound 3c, 7, and 12. Flexible docking studies involving AutoDock 4.2 was investigated to identify the potential binding affinities and the mode of interaction of the hybrid compounds into two protein tyrosine kinases namely, SRC (Pp60v-src) and platelet-derived growth factor receptor, PDGFR (c-Kit). The compounds in this study have a preferential affinity for the c-Kit PDGFR PTK over the non-receptor tyrosine kinase SRC (Pp60v-src).
PMCID: PMC4284725  PMID: 25490139
antitumor; anthraquinone; celecoxib; HEPG2; docking; protein kinase activities
4.  Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: A review 
Journal of Advanced Research  2014;6(1):17-33.
Graphical abstract
Natural products are structurally and biologically interesting metabolites, but they have been isolated in minute amounts. The syntheses of such natural products help in obtaining them in bulk amounts. The recognition of microbial biotransformation as important manufacturing tool has increased in chemical and pharmaceutical industries. In recent years, microbial transformation is increasing significantly from limited interest into highly active area in green chemistry including preparation of pharmaceutical products. This is the first review published on the usage of microbial biocatalysts for some natural product classes and natural product drugs.
PMCID: PMC4293675
Natural products; Biotransformation; Microbial biocatalysts; Pharmaceutical products
5.  Crystal structure of 4-meth­oxy­quinazoline 
The title compound, C9H8N2O, is almost planar, with the C atom of the meth­oxy group deviating from the mean plane of the quinazoline ring system (r.m.s. deviation = 0.011 Å) by 0.068 (4) Å. In the crystal, mol­ecules form π–π stacks parallel to the b-axis direction [centroid–centroid separation = 3.5140 (18) Å], leading to a herringbone packing arrangement.
PMCID: PMC4257374  PMID: 25553044
crystal structure; 4-meth­oxy­quinazoline; quinazoline derivatives; π–π stacks; herringbone packing
6.  Iatrogenic Biliary Injuries: Multidisciplinary Management in a Major Tertiary Referral Center 
HPB Surgery  2014;2014:575136.
Background. Iatrogenic biliary injuries are considered as the most serious complications during cholecystectomy. Better outcomes of such injuries have been shown in cases managed in a specialized center. Objective. To evaluate biliary injuries management in major referral hepatobiliary center. Patients & Methods. Four hundred seventy-two consecutive patients with postcholecystectomy biliary injuries were managed with multidisciplinary team (hepatobiliary surgeon, gastroenterologist, and radiologist) at major Hepatobiliary Center in Egypt over 10-year period using endoscopy in 232 patients, percutaneous techniques in 42 patients, and surgery in 198 patients. Results. Endoscopy was very successful initial treatment of 232 patients (49%) with mild/moderate biliary leakage (68%) and biliary stricture (47%) with increased success by addition of percutaneous (Rendezvous technique) in 18 patients (3.8%). However, surgery was needed in 198 patients (42%) for major duct transection, ligation, major leakage, and massive stricture. Surgery was urgent in 62 patients and elective in 136 patients. Hepaticojejunostomy was done in most of cases with transanastomotic stents. There was one mortality after surgery due to biliary sepsis and postoperative stricture in 3 cases (1.5%) treated with percutaneous dilation and stenting. Conclusion. Management of biliary injuries was much better with multidisciplinary care team with initial minimal invasive technique to major surgery in major complex injury encouraging early referral to highly specialized hepatobiliary center.
PMCID: PMC4243137  PMID: 25435672
7.  Optimized CGenFF force-field parameters for acylphosphate and N-phosphonosulfonimidoyl functional groups 
Journal of molecular modeling  2013;19(11):5075-5087.
We report an optimized set of CGenFF parameters that can be used to model small molecules containing acylphosphate and N-phosphonosulfonimidoyl functional groups in combination with the CHARMM force field. Standard CGenFF procedures were followed to obtain bonded interaction parameters, which were validated by geometry optimizations, comparison to the results of calculations at the MP2/6-31+G(d) level of theory, and molecular dynamics simulations. In addition, partial atomic charges were assigned so that the energy of hydrogen bonding of the model compounds with water was correctly reproduced. The availability of these parameters will facilitate computational studies of enzymes that generate acyladenylate intermediates during catalytic turnover. In addition, given that the N-phosphonosulfonimidoyl moiety is a stable transition state analog for the reaction of ammonia with an acyladenylate, the parameters developed in this study should find use in efforts to develop novel and potent inhibitors of various glutamine-dependent amidotransferases that have been validated as drug targets. Topology and parameter files for the model compounds used in this study, which can be combined with other CGenFF parameters in computational studies of more complicated acylphosphates and N-phosphonosulfonimidates are made available.
PMCID: PMC3904551  PMID: 24085536
CGenFF; Parameters; Acylphosphates; Sulfoximines; N-Phosphonosulfonimidates; Force Field; Drug Discovery
8.  Consistent Beneficial Effects of Killer Cell Immunoglobulin-Like Receptor 2DL3 and Group 1 Human Leukocyte Antigen-C Following Exposure to Hepatitis C Virus 
Hepatology (Baltimore, Md.)  2010;51(4):1168-1175.
Natural killer cells are a key component in the immune control of viral infections. Their functions are controlled by inhibitory receptors for major histocompatability complex (MHC) class I, including the killer cell immunoglobulin-like receptors (KIR). KIR2DL3 in combination with its cognate human leukocyte antigen (HLA)-C ligand has been shown to be associated with spontaneous resolution of viremia following hepatitis C virus (HCV) infection. In order to determine if this gene combination is advantageous across all potential outcomes following HCV exposure, we studied individuals with apparent resistance to HCV infection who remain seronegative and aviremic despite long-term injection drug use and also individuals chronically infected with HCV who successfully clear HCV with treatment. Homozygosity for KIR2DL3 in combination with group 1 HLA-C allotypes was more frequent in exposed seronegative aviremic individuals as compared to those with chronic HCV (25.0% versus 9.7%, P = 0.003, odds ratio [OR] = 3.1, 95% confidence interval [CI] = 1.3-7.1) in a model similar to that found for those spontaneously resolving HCV. In individuals undergoing treatment for HCV, those with KIR2DL3 and group 1 HLA-C were more likely to make a sustained virological response (SVR) (P = 0.013, OR = 2.3, 95% CI = 1.1-4.5). KIR and HLA-C protection in both treatment response and spontaneously resolving HCV was validated at the allelic level, in which KIR2DL3-HLA-Cw*03 was associated with SVR (P = 0.004, OR = 3.4, 95% CI = 1.5-8.7) and KIR2DL3/KIR2DL3-HLA-Cw*03 was associated with spontaneous resolution of HCV infection (P = 0.01, OR = 2.3, 95% CI = 1.2-4.4).
KIR and HLA-C genes are consistently beneficial determinants in the outcome of HCV infection. This advantage extends to the allelic level for both gene families.
PMCID: PMC4202114  PMID: 20077564
9.  Crystal structure of 2-[4-(methyl­sulfan­yl)quinazolin-2-yl]-1-phenyl­ethanol 
In the mol­ecule of the title compound, C17H16N2OS, the almost planar methyl­sulfanylquinazoline group [the methyl C atom deviates by 0.032 (2) Å from the plane through the ring system] forms an inter­planar angle of 76.26 (4)° with the plane of the phenyl group. An intra­molecular O—H⋯N hydrogen bond is present between the quinazoline and hy­droxy groups. In the crystal, mol­ecules are stacked along the b-axis direction.
PMCID: PMC4257174  PMID: 25484694
crystal structure; 4-(methyl­sulfan­yl)quinazoline derivative; hydrogen bonding
10.  Crystal structure of 4,4-dibutyl-2-phenyl-3,4-di­hydro­quinazoline 
In the title compound, C22H28N2, the dihedral angle between the planes of the phenyl ring and the di­hydro­quinazoline ring system (r.m.s. deviation = 0.030 Å) is 24.95 (7)° and both n-butane chains assume all-trans conformations. In the crystal, N—H⋯N hydrogen bonds link the mol­ecules into C(4) chains propagating in the [001] direction.
PMCID: PMC4257218  PMID: 25484693
crystal structure; quinazoline; hydrogen bonding
11.  Amalgamation of procalcitonin, C-reactive protein, and sequential organ failure scoring system in predicting sepsis survival 
The clinical value of inflammatory biomarkers is still questionable.
Aim of the Work:
The aim of this study is to compare the clinical informative value of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentration in the early detection of sepsis, as well as relating these biomarkers to other scoring systems.
Patients and Methods:
A total of 138 patients were enrolled in our study. All were subjected to PCT, CRP, and sequential organ failure assessment (SOFA) scores daily for 7 days (starting from admission day). Blood samples were collected before starting antibiotics, with 28 days follow-up and patients were assigned to three groups: Group I: SOFA 2-7, Group II: SOFA 8-10, and Group III: SOFA ≥11.
Underlying clinical diagnosis revealed pneumonia in 72 patients, urinary tract infections in eight, bloodstream infection in four, and other infections in 23, while infection could not be traced in 25 patients. The mean PCT was 3 ng/ml (95% confidence interval [CI]: 1-4), 12 ng/ml (95% CI: 9.1-14), and 19 ng/ml (95% CI: 16.3-22.3) in Groups I, II, and III, respectively, with a statistically significant difference in the mean PCT level among the three groups (P < 0.0001). On the other hand, CRP mean level did not significantly differentiate between the groups (147.1 mg/L in Group II, which was even higher than the level of Group III, 138.4 mg/L).
PCT seems to do better than CRP in predicting the SOFA groups, giving its patronage display over a wide spectrum of insults.
PMCID: PMC4258970
Acute physiology and chronic health evaluation II score; C-reactive protein; procalcitonin; sepsis; sequential organ failure assessment
12.  Crystal structure of 4-(2,2-di­methyl­propanamido)­pyridin-3-yl N,N-diiso­propyl­dithio­carbamate 
In the title compound, C17H27N3OS2, the amide group is approximately coplanar with the pyridine ring [dihedral angle = 1.6 (1)°], whereas the di­thio­carbamate group is nearly perpendicular to the pyridine ring [dihedral angle = 76.7 (1)°]. In the crystal, pairs of weak C—H⋯O hydrogen bonds link the mol­ecules into inversion dimers.
PMCID: PMC4186077  PMID: 25309230
crystal structure; di­thio­carbamate; pyridine derivatives; hydrogen bonding
13.  Blake's pouch cyst and Werdnig-Hoffmann disease: Report of a new association and review of the literature 
Surgical Neurology International  2014;5(Suppl 4):S282-S288.
We report a case of a neonate with proximal spinal muscular atrophy (SMA) type 1 (also known as Werdnig-Hoffmann disease or severe infantile acute SMA) associated with a Blake's pouch cyst; a malformation that is currently classified within the spectrum of Dandy-Walker complex. The association of the two conditions has not been previously reported in the English literature. A comprehensive review of the pertinent literature is presented.
Case Description:
A male neonate was noted to have paucity of movement of the four limbs with difficulty of breathing and poor feeding soon after birth. Respiratory distress with tachypnea, necessitated endotracheal intubation and mechanical ventilation. Pregnancy was uneventful except for decreased fetal movements reported by the mother during the third trimester. Neurological examination revealed generalized hypotonia with decreased muscle power of all limbs, nonelicitable deep tendon jerks, and occasional tongue fasciculations. Molecular genetic evaluation revealed a homozygous deletion of both exons 7 and 8 of the survival motor neuron 1 (SMN1) gene, and exon 5 of the neuronal apoptosis inhibitory protein (NAIP) gene on the long arm of chromosome 5 consistent with Werdnig-Hoffmann disease (SMA type 1). At the age of 5 months, a full anterior fontanelle and abnormal increase of the occipito-frontal circumference were noted. Computed tomographic (CT) scan and magnetic resonance imaging (MRI) of the brain revealed a tetraventricular hydrocephalus and features of Blake's pouch cyst of the fourth ventricle.
This case represents a previously unreported association of Blake's pouch cyst and SMA type 1.
PMCID: PMC4163908  PMID: 25225621
Blake's Pouch Cyst; Dandy–Walker complex; spinal muscular atrophy; Werdnig-Hoffmann disease
14.  Crystal structure of 2-tert-butyl-1,3-thia­zolo[4,5-b]pyridine 
The title compound, C10H12N2S, does not contain any strong hydrogen-bond donors but two long C—H⋯N contacts are observed in the crystal structure, with the most linear inter­action linking mol­ecules along [010]. The ellipsoids of the tert-butyl group indicate large librational motion.
PMCID: PMC4186112  PMID: 25309261
crystal structure; C—H⋯N contacts; 1,3-thia­zolo[4,5-b]pyridine
15.  Crystal structure of 2-ethyl­quinazoline-4(3H)-thione 
In the title compound, C10H10N2S, all non-H atoms are almost coplanar [maximum deviation = 0.103 (1) Å]. In the crystal, N—H⋯S inter­actions form R 2 2(8) rings linking pairs of mol­ecules related by inversion. The mol­ecular pairs are stacked along [100]. A herringbone arrangement of pairs in the [010] direction forms layers parallel to (010).
PMCID: PMC4186129  PMID: 25309275
crystal structure; N—H⋯S inter­actions; quinazoline-4(3H)-thione; hydrogen-bonded dimers; herringbone arrangement
16.  Crystal structure of 4-methyl­sulfanyl-2-phenyl­quinazoline 
In the title compound, C15H12N2S, the methylthioquinazoline group is planar with the methyl C displaced by only 0.116 (3) Å from the plane of the quinazoline moiety. The dihedral angle between the phenyl ring and the quinazoline ring system is 13.95 (5)°. In the crystal, each molecule is linked by π–π stacking between to two adjacent inversion-related molecules. On one side, the inverted quinazoline groups interact with a centroid–centroid distance of 3.7105 (9) Å. On the other side, the quinazoline group interacts with the pyrimidine and phenyl rings of the second neighbour with centroid–centroid distances of 3.5287 (8) and 3.8601 (9) Å, respectively.
PMCID: PMC4158504  PMID: 25249928
crystal structure; methylthioquinazoline; π–π stacking
17.  Analysis of Oxidative Stress Status, Catalase and Catechol-O-Methyltransferase Polymorphisms in Egyptian Vitiligo Patients 
PLoS ONE  2014;9(6):e99286.
Vitiligo is the most common depigmentation disorder of the skin. Oxidative stress is implicated as one of the probable events involved in vitiligo pathogenesis possibly contributing to melanocyte destruction. Evidence indicates that certain genes including those involved in oxidative stress and melanin synthesis are crucial for development of vitiligo. This study evaluates the oxidative stress status, the role of catalase (CAT) and catechol-O-Methyltransferase (COMT) gene polymorphisms in the etiology of generalized vitiligo in Egyptians. Total antioxidant capacity (TAC) and malondialdehyde (MDA) levels as well as CAT exon 9 T/C and COMT 158 G/A polymorphisms were determined in 89 patients and 90 age and sex-matched controls. Our results showed significantly lower TAC along with higher MDA levels in vitiligo patients compared with controls. Meanwhile, genotype and allele distributions of CAT and COMT polymorphisms in cases were not significantly different from those of controls. Moreover, we found no association between both polymorphisms and vitiligo susceptibility. In conclusion, the enhanced oxidative stress with the lack of association between CAT and COMT polymorphisms and susceptibility to vitiligo in our patients suggest that mutations in other genes related to the oxidative pathway might contribute to the etiology of generalized vitiligo in Egyptian population.
PMCID: PMC4051781  PMID: 24915010
18.  1-(2-Bromo-4-chloro­phen­yl)-3,3-di­methyl­thio­urea 
In the title compound, C9H10BrClN2S, the di­methyl­thio­urea group is twisted from the benzene ring plane by 54.38 (6)°. In the crystal, the amino groups are involved in the formation of N—H⋯S hydrogen bonds, which link the mol­ecules into chains along [010]. Weak C—H⋯Cl inter­actions further link these chains into layers parallel to the ab plane.
PMCID: PMC4051011  PMID: 24940276
19.  Comparative study of Y-split recession versus bilateral medial rectus recession for surgical management of infantile esotropia 
This prospective study compares the results of bilateral medial rectus recession versus (vs) Y-split recession of medial recti techniques for surgical management of essential infantile esotropia.
Patients and methods
Thirty patients were included in this study and had preoperative infantile esotropia with large angles (ie, >30 prism diopters [PD]). Patients were divided into Group A, which underwent bilateral medial rectus (BMR) recession and Group B, which underwent bilateral Y-split recession of medial recti muscles. All patients were subjected to complete ophthalmologic examination and met the criteria for inclusion in this study. The degrees of BMR recessions performed ranged from 6.0–7.5 mm. All operations were performed under general anesthesia. Follow-up visits were conducted at 1 and 2 weeks, and 1, 3, and 6 months postoperatively. Rates of reoperation for residual esotropia and consecutive exotropia were determined.
The patients’ preoperative angles of deviation ranged from 30–80 PD. Group A consumed 57% less operative time than Group B. Immediately postoperatively, the Y-splitting technique showed satisfactory results (ie, orthotropic or residual angles ≤15 PD) in 73% of patients vs 67% only for the BMR recession patients. By the end of six months of follow up; 13% of the BMR technique patients vs 27% of the Y-splitting technique patients showed negative change of PD but without reoperation.
Our results suggest that, although the Y-splitting technique is more difficult and time consuming, both procedures are effective and have shown comparable results for the correction of horizontal deviation ≤70 PD.
PMCID: PMC4043800  PMID: 24920880
BMR recession; Y-splitting technique; torque reduction; oculomotor pathology; strabismus; faden operation
20.  Computed tomographic evaluation of C5 root exit foramen in patients with cervical spondylotic myelopathy 
Surgical Neurology International  2014;5(Suppl 3):S59-S61.
Narrowing of the intervertebral foramen for C5 root and a larger superior articular process in myelopathic patients with postlaminoplasty motor dominant C5 radiculopathy has been reported. We investigated whether the C4-5 foraminal dimensions and surface area in patients with cervical spondylotic myelopathy are universally smaller than the intervertebral foramina at other cervical levels.
The study population consisted of 44 consecutive patients (sex: 24 males and 20 females), averaging 55.7 years of age (range 42-84) years who presented with clinical features suggestive of cervical spondylotic myelopathy. Using computed tomography (CT) imaging, we prospectively compared height, transverse diameter, and surface area of the C4-5 foramen to those of C3-4, C5-6 and C6-7 foramina of the same side in the whole study population as well as in male and female patients.
In the whole study population at C4-5 intervertebral foramen the mean foraminal height was 8.37 ± 1.3 mm on the right and 8.85 ± 1.16 mm on the left; and the mean foraminal transverse diameter on the right was 4.97 ± 1.35 mm and 5.14 ± 1.16 mm on the left. No statistically significant difference was found between the measurements in the whole study population at various levels, between or within male and female patient groups.
C4-5 intervertebral foramen is not uniformly smaller in patients with cervical spondylotic myelopathy.
PMCID: PMC4023000  PMID: 24843812
C5 root; cervical; foramen; intervertebral; myelopathy; spondylosis
21.  New Terpenes from the Egyptian Soft Coral Sarcophyton ehrenbergi 
Marine Drugs  2014;12(4):1977-1986.
Chemical investigations of the Egyptian soft coral Sarcophyton ehrenbergi have led to the isolation of compounds 1–3 as well as the previously reported marine cembranoid diterpene sarcophine (4). Structures were elucidated by comprehensive NMR and HRMS experimentation. Isolated compounds were in vitro assayed for cytotoxic activity against human hepatocarcinoma (HepG2) and breast adenocarcinoma (MCF-7) cell lines.
PMCID: PMC4012453  PMID: 24699113
Sarcophyton ehrenbergi; soft coral; terpenes; cembranoids; sesquiterpenes; cytotoxic activity
22.  2-Ethyl-3-[(R)-2-phenyl­butanamido]­quinazolin-4(3H)-one monohydrate 
In the title compound, C20H21N3O2·H2O (EQR·H2O), the quinazoline ring system forms dihedral angles of 53.1 (1) and 85.6 (1)° with the phenyl ring and the amide link, respectively. In the crystal, O—H⋯O hydrogen bonds link two EQR and two water mol­ecules into a centrosymmetric R 4 4(18) ring motif. N—H⋯O hydrogen bonds further link these hydrogen-bonded fragments into columns extending in [010].
PMCID: PMC3998561  PMID: 24826166
23.  Cysteine- rich secretory protein 3 (CRISP3), ERG and PTEN define a molecular subtype of prostate cancer with implication to patients’ prognosis 
Cysteine- rich secretory protein 3 (CRISP3) prognostic significance in prostate cancer (PCA) has generated mixed result. Herein, we investigated and independently validated CRISP3 expression in relation to ERG and PTEN genomic aberrations and clinical outcome. CRISP3 protein expression was examined by immunohistochemistry using a cohort of patients with localized PCA (n = 215) and castration resistant PCA (CRPC) (n = 46). The Memorial Sloan Kettering (MSKCC) and Swedish cohorts were used for prognostic validation. Results showed, CRISP3 protein intensity to be significantly associated with neoplastic epithelium, being highest in CRPC vs. benign prostate tissue (p < 0.0001), but was not related to Gleason score (GS). CRISP3 mRNA was significantly associated with higher GS (p = 0.022 in MSKCC, p = 1.1e-4 in Swedish). Significant association between CRISP3 expression and clinical outcome was documented at the mRNA but not the protein expression levels. CRISP3 mRNA expression was related to biochemical recurrence in the MSKCC (p = 0.038) and lethal disease in the Swedish cohort (p = 0.0086) and retained its prognostic value in the subgroup of patients with GS 6 & 7. Furthermore, CRISP3 protein and mRNA expression was significantly associated with positive ERG status and with PTEN deletions. Functional biology analysis documented phenylalanine metabolism as the most significant pathway governing high CRISP3 and ERG expression in this subtype of PCA. In conclusion, the combined status of CRISP3, ERG and PTEN define a molecular subtype of PCA with poorest and lethal outcome. Assessing their combined value may be of added value in stratifying patients into different prognostic groups and identify those with poorest clinical outcome.
PMCID: PMC3975646  PMID: 24606912
CRISP3; ERG; PTEN; Biological pathways; Prostate cancer; Poorest outcome; Molecular subtypes
24.  2,2-Dimethyl-N-(4-methyl­pyridin-2-yl)propanamide 
In the title compound, C11H16N2O, the dihedral angle between the mean plane of the 4-methypyridine group and the plane of the amide link is 16.7 (1)°, and there is a short intra­molecular C—H⋯O contact. Hydrogen bonding (N—H⋯O) between amide groups forms chains parallel to the b axis. Pairs of methyl­pyridine groups from mol­ecules in adjacent chains are parallel but there is minimal π–π inter­action.
PMCID: PMC3998503  PMID: 24765040
25.  Delayed surgical debridement in pediatric open fractures: a systematic review and meta-analysis 
Open fractures are considered orthopedic emergencies that are traditionally treated with surgical debridement within 6 h of injury to prevent infection. However, this proclaimed “6-h rule” is arbitrary and not based on rigorous scientific evidence. The aim of our study was to systematically review the literature that compares late (>6 h from the time of injury) to early (<6 h from the time of injury) surgical debridement of pediatric open fractures.
We searched several databases from 1946 to 2013 for any observational or experimental studies that evaluated late and early surgical debridement of pediatric open fractures. We performed a meta-analysis using a random effects model to pool odds ratios for a comparison of infection rates between children undergoing late versus early surgical debridement. We also investigated the infection rates in upper- and lower-limb pediatric open fractures. Descriptive, quantitative, and qualitative data were extracted.
Of the 12 articles identified, three studies (retrospective cohort studies) were eligible for the meta-analysis, encompassing a total of 714 open fractures. The pooled odds ratio (OR = 0.79) for infection between late and early surgical debridement was in favor of late surgical debridement but was not statistically significant (95 % CI 0.32, 1.99; p = 0.38, I2 = 0 %). No significant difference in infection rate was detected between pediatric open fractures in the upper and lower limbs according to the time threshold in the included studies (OR = 0.72, 95 % CI 0.29, 1.82; p = 0.40, I2 = 0 %).
The cumulative evidence does not, at present, indicate an association between late surgical debridement and higher infection rates in pediatric open fractures. However, initial expedient surgical debridement of open fractures in children should always remain the rule. Thus, multi-center randomized controlled trials or prospective cohort studies will be able to answer this question with more certainty and a higher level of evidence.
Level of evidence
Level III.
PMCID: PMC3965772  PMID: 24554129
Open fracture; Children; Debridement; Meta-analysis; Systematic review

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