Distribution of acid hydrolases in subcellular fractions of proliferating vs non-proliferating fibroblasts.
We have employed colloidal silica (Percoll) density-gradient subcellular fractionation technique to examine the distribution of lysosomal hydrolases between intermediate vesicles (primary lysosomes) and secondary lysosomes in contact-inhibited non-proliferating vs proliferating chicken embryo fibroblasts. We find that the activities of lysosomal specific enzymes from both phases of growth are distributed within two peaks; however, the relative amounts differ markedly. In normal, non-proliferating cells approx. 60% of the total activities of cathepsin B, beta-mannosidase, alpha-fucosidase, beta-galactosidase and hexosaminidase is recovered in the heavier density fraction corresponding to secondary lysosomes, while less than 9% of the enzyme activities are recovered in the light-density peak. With transformed cells, between 16 and 22% of activity for these enzymes are recovered in the lighter density intermediate vesicle fraction, when less than 40% of the enzyme activities recovered in the heavy density fraction. beta-Glucuronidase distribution was different from that of the above enzymes. First, a more even distribution between the two lysosomal fractions was found with non-proliferating normal cells (33% in heavy-density fraction and 21% in light-density fraction), whereas more than 40% of the total enzyme activity was recovered in the lighter density fraction from transformed cells. Also, the amount of cathepsin B contained in the vesicle fractions is increased severalfold relative to that of contact-inhibited normal cells. However, the apparent differences in enzyme distribution between confluent normal and transformed cells are not found when vesicles are prepared from subconfluent, actively proliferating cultures. We have also compared the Percoll density gradient patterns of membrane vesicles from proliferating and non-proliferating human fibroblasts, since most earlier studies utilized this system. Again, we find that the majority of beta-hexosaminidase activity (41%) of contact-inhibited, confluent cells is recovered in the heavier density fraction with less than 15% in the lighter density fraction. Also, the distribution of beta-hexosaminidase between the heavy density and light density vesicle fractions is altered in homogenates from exponentially growing cells, being 22% and 26% respectively. We conclude that the distribution of lysosomal hydrolases between the two vesicle populations is growth-phase dependent and is markedly heterogeneous in proliferating cells.


Mandibular reconstruction using induced membranes with autologous cancellous bone graft and HA-betaTCP: animal model study and preliminary results in patients.
Providing an acceptable quality of life for patients after reconstruction of mandibular segmental defects is challenging because the surgical techniques available have limitations. The authors evaluated two-stage mandibular reconstruction in rabbits and provide preliminary results in humans. 21 rabbits underwent bilateral segmental mandibulectomy and the defect was filled with methylmethacrylate. The methylmethacrylate was removed after 4 weeks and an iliac autograft performed on the right-hand side and an autogenous graft with hydroxyapatite and triphasic calcium phosphate (HA-betaTCP) on the left-hand side. Four patients with severe mandibular osteoradionecrosis underwent a two-stage reconstruction. No clinical or paraclinical complications were noted. Hematoxylin-eosin-saffron staining revealed an induced membrane lining the cavity of all samples with dense vascularity. Decalcified, undecalcified and histomorphometric analysis showed new bone formation in the biomaterial and the autograft. Calcium uptake was higher inside the new cortical bone, notably at sites with HA-betaTCP. CT scans at 6 months showed that two patients had a favorable outcome with cortico-cancellous bone. Microscopic and immunochemical analysis confirmed the experimental data. This study demonstrates the feasibility of mandibular reconstruction using the induced membranes technique. This technique is efficient, and the results would be better in non-irradiated patients with good general health.


One-Pot synthesis of photochromic naphthopyrans in the solid state
p-TsOH-catalyzed condensation reactions of 1,1-diaryl-2-propyn-1-ol (1) and 2-naphthol (2) in the solid state gave 3, 3-diaryl-3H-naphtho[2,1-b]pyran (6) via Claisen rearrangement. Similar reactions of 1 with 2,6- (7) and 2,7-dihydroxynaphthalenes (8) afforded naphthodipyrane derivatives 9 and 10, respectively. Bis-naphthopyran derivatives 12 were also obtained by the reaction of 1,1,6,6-tetraaryl-2,5-hexadiyn-1,6-diol (11) and 2-naphthol (2) in the solid state.


A new emulsion method to synthesize well-defined mesoporous particles.
A new emulsion method for preparing ordered mesoporous materials with polymer PEG as the swelling agent has been explored in the present work. The synthesis conditions including the chain length and the PEG concentration, the duration of aging, the kind of emulsion, and the time when the swelling agents were added to the reaction system are discussed. The results show that with the advantage of the emulsion method, the nucleation and growth were controlled very well. The nicely spherical particles produced by the emulsion method were more uniform and less prone to agglomerate than those produced through the hydrothermal method. When different MW PEG were added as swelling agents, the pore size changed little: it was centered around 4 nm and had a narrow distribution. When different concentrations of PEG were applied, BET surface area, pore size, and pore volume changed. To summarize, in the formation of mesoporous materials, polymers such as PEG can not only control the pore size from 3 to 70 nm through variation of concentration, but also regulate the structures and improve the morphology of particles by the chain length of polymers. By adjusting the time of addition of the swelling agents, a poroshell mesoporous material was prepared. This method is particularly important for those applications that strictly require particle uniformity, such as chromatography separation.


The impact of curriculum-based suicide prevention programs for teenagers: an 18-month follow-up.
In a long-term follow-up of a study designed to assess the impact of school-based suicide prevention curricula on high school students, a group of 174 students from two high schools who were exposed to a prevention program were compared with a group of 207 control students from two additional high schools who were not exposed to the curriculum. A questionnaire, designed to measure the effects of the prevention program on actual help-seeking behaviors and suicide morbidity during the follow-up period, was administered 18 months after delivery of the program. The study failed to find convincing evidence of any program effect.


Totally thoracoscopic surgery and troubleshooting for bleeding in non-small cell lung cancer.
Although accumulating data support the feasibility and efficacy of video-assisted thoracic surgery anatomic resection, few studies have reported on intraoperative complications, such as vessel injury. The purpose of this study was to evaluate intraoperative vessel injury and to analyze troubleshooting. Twenty-six of 557 patients with non-small cell lung cancer who underwent thoracoscopic anatomic lung resection were identified as having intraoperative vessel injury between January 2004 and December 2011. The injured portion, devices used, recovery approach, and hemostatic procedure were analyzed. The perioperative outcomes in patients with and without vessel injury were compared. The most commonly used devices were ultrasonic coagulation shears in 9 cases, followed by scissors in 5 and an endostapler in 4. Seventeen of the 26 cases were injured at the branches of the pulmonary artery, and the others were at major vessels. Half of the patients were converted to thoracotomy, and 6 were treated by minithoracotomy. Hemostatic procedures were primary closure in 17 and sealant in 7. The perioperative outcomes, including operative time and blood loss, were significantly different between the two groups, but duration of chest tube drainage, length of hospital stay, and morbidity rate were not. No mortality was identified in the patients with vessel injury. Video-assisted thoracic surgery anatomic resection was feasible and safe, regardless of the intraoperative vessel injury. Although surgeons should pay attention to avoid unexpected bleeding, the magnitude of injury and effectual step-by-step management should lead to a safe operation.


Chemical composition of the edible flowers, pansy (Viola wittrockiana) and snapdragon (Antirrhinum majus) as new sources of bioactive compounds.
The nutritional composition - including total and individual phenolic compounds, carotenoids, and the antioxidant capacity - of two commercially available edible flowers, pansy and snapdragon, was studied. The edible flowers did not differ in their carbohydrates, fat, or ash contents, or in total energy, but pansy had higher values of moisture, protein, and total dietary fiber than snapdragon. Phenolic compounds were more abundant in pansy than in snapdragon, and flavonoids were the major compounds, followed by anthocyanins. The phenolic profile of pansy included flavonols, such as quercetin and isorhamnetin glycosides, flavones, such as apigenin glycosides, and anthocyanins, such as cyanidin and delphinidin glycosides; in snapdragon it included flavonol glycosides (e.g. quercetin and kaempferol glycosides) and anthocyanins, such as cyanidin and pelargonidin glycosides. The contents of total carotenoids were 146 and 29 µg/mg for pansy and snapdragon, respectively, and lutein was the dominant compound.


Tryptophanamide formation by Escherichia coli tryptophanyl-tRNA synthetase.
When tryptophanyl-tRNA synthetase from Escherichia coli is allowed to react with L-tryptophan and ATP-Mg in the presence of inorganic pyrophosphatase, the fluorescence change of the reaction mixture reveals three or four sequential processes, depending on the buffer used. Quenched-flow and stopped-flow experiments show that the first two processes, which occur in the 0.001-1.0-s time scale, can be correlated to the formation of two moles of tryptophanyl-adenylate per mole of dimeric enzyme. These two processes are reversible by adding PPi, as seen in the fluorimeter. The third process leads to a reaction product that can no longer reform ATP after addition of PPi and that represents tryptophanyl-ATP ester, as demonstrated by thin-layer chromatography. This compound has been previously shown to be formed by tryptophanyl-tRNA synthetase from E. coli [K. H. Muench (1969) Biochemistry 8, 4872-4879]. Its formation is accompanied by a fluorescence decrease which reaches a minimum in about 30 min. The nature of the fourth process depends on the reaction conditions employed. In sodium bicarbonate or potassium phosphate buffer, the fourth process corresponds to the non-enzymatic hydrolysis of tryptophanyl-ATP ester. This spontaneous hydrolysis competes with formation of the ester and limits its concentration. Eventually, the progressive exhaustion of ATP brings the fluorescence intensity of the reaction mixture back to its initial value. In contrast, in ammonium bicarbonate buffer the previous third process is no longer visible, as evidenced by the absence of a fluorescence decrease beyond the fast initial quenching linked to the formation of tryptophanyl-adenylate. Instead, a fluorescence increase is observed. However, unlike the fourth process seen in sodium bicarbonate buffer, the fluorescence increase in ammonium bicarbonate is much larger than the initial fluorescence decrease linked to adenylate formation, the final fluorescence greatly surpassing the starting fluorescence signal. The reaction product of this process is tryptophanamide, as evidenced by high-performance liquid chromatography. Tryptophanamide formation is faster than that of tryptophanyl-ATP ester and is enzyme-catalyzed with a Km of 1 mM for ammonia and a rate constant of 5.7 min-1 at pH 8.3, 25 degrees C. The affinity of tryptophanamide for the protein is too weak to allow the formation of a significant concentration of enzyme-product complex. Tryptophanamide is therefore released in the reaction medium and its concentration reaches that of the limiting substrate.


Applications of corneal topography and tomography: a review.
Corneal imaging is essential for diagnosing and management of a wide variety of ocular diseases. Corneal topography is used to characterize the shape of the cornea, specifically, the anterior surface of the cornea. Most corneal topographical systems are based on Placido disc that analyse rings that are reflected off the corneal surface. The posterior corneal surface cannot be characterized using Placido disc technology. Imaging of the posterior corneal surface is useful for diagnosis of corneal ectasia. Unlike corneal topographers, tomographers generate a three-dimensional recreation of the anterior segment and provide information about the corneal thickness. Scheimpflug imaging is one of the most commonly used techniques for corneal tomography. The cross-sectional images generated by a rotating Scheimpflug camera are used to locate the anterior and posterior corneal surfaces. The clinical uses of corneal topography include, diagnosis of corneal ectasia, assessment of corneal astigmatism, and refractive surgery planning. This review will discuss the applications of corneal topography and tomography in clinical practice.


Genetic variation of 15 autosomal STR loci in a population sample from Poland.
Fifteen autosomal STR loci included in AmpFlSTR NGM kit were analyzed in 154 unrelated individuals from Poland. This multiplex kit enables simultaneous amplification of 10 standard STR loci included in AmpFlSTR SGM Plus kit (D3S1358, vWA, D16S539, D2S1338, D8S1179, D19S433, TH01, FGA, D21S11 and D18S51) and five new mini- and midi-STR loci (D10S1248, D22S1045, D2S441, D1S1656 and D12S391). Population study was conducted to evaluate usefulness of the loci (especially the five new microsatellite systems) in forensic genetic identification examinations. All 15 markers were found to be in Hardy-Weinberg equilibrium. The combined probability of match for the 15 studied STR loci was 3.998 x 10(-19). The same parameter calculated for five new microsatellite loci equaled 8.83 x 10(-7). Discrimination power was particularly high in case of D1S1656 (0.975) and D12S391 (0.972) STR loci.


Size matters: influence of the size of nanoparticles on their interactions with ligands immobilized on the solid surface.
The correlation between the size of biotinylated nanoparticles and their affinity in relation to interactions with the solid surface was investigated. The silica particles with a diameter of 50-200 nm containing amino groups on the surface were labeled with different quantities of biotin. The affinity properties of biotinylated nanoparticles were studied using a Biacore 3000 instrument equipped with a streptavidin-coated sensor chip (SA chip). It was shown that the increase in the particle size from 50 to 200 nm reduced the affinity (K(D)) of biotin-streptavidin interactions from 1.2 x 10(-12) to 1.2 x 10(-10) M. It was found that the particles with higher concentrations of immobilized biotin on particle surfaces demonstrated stronger binding with streptavidin.


[Ru(NHC)(xantphos)(CO)H(2)] complexes: intramolecular C-H activation and applications in C-C bond formation.
Treatment of [Ru(PPh3)(xantphos)(CO)H2] (1) with the N-heterocyclic carbenes (NHCs) IEt2Me2 (1,3-diethyl-4,5-dimethylimidazol-2-ylidene), IiPr2Me2 (1,3-diisopropyl-4,5-dimethylimidazol-2-ylidene) and IMes (1,3-dimesitylimidazol-2-ylidene) at elevated temperature affords the C-H activated carbene complexes [Ru(NHC)(xantphos)(CO)H] (2-4). In contrast, ICy (1,3-dicyclohexylimidazol-2-ylidene) reacts with 1 to give the substitution product [Ru(ICy)(xantphos)(CO)H2] (6), which can be converted into the C-H activated species [Ru(ICy)(xantphos)(CO)H] (7) upon thermolysis in the presence of H2CCHSiMe3. Addition of H2 to 2 yields [Ru(IEt2Me2)(xantphos)(CO)H2] (5), while H2 reacts with 7 to reform 6. Complexes 2-4 and 7 catalyse the Knoevenagel reaction of PhCH2OH with tBuC(O)CH2CN, although they prove to be somewhat less active than the phosphine complex 1.


Spindle cell pseudotumor of the brain associated with Mycobacterium haemophilum and Mycobacterium simiae mixed infection in a patient with AIDS: the first case report.
Spindle cell pseudotumors may occur due to mycobacterial infection, especially in immunocompromised hosts including those with AIDS. They have been reported from many body sites; the lymph nodes are predominantly involved, most frequently associated with Mycobacterium avium complex infection. To the best of our knowledge, Mycobacterium-associated spindle cell pseudotumors have not been previously described in the brain stem and in association with mixed mycobacterial infection. We describe a man with AIDS who presented with right hemiparesis and truncal ataxia. Magnetic resonance imaging revealed enhancing nodular lesions at the cerebral peduncle and medulla. A mycobacterial spindle cell pseudotumor was diagnosed on surgical specimens. Blood and brain tissue cultures grew Mycobacterium haemophilum and Mycobacterium simiae. To our knowledge, this is the first case of spindle cell pseudotumor of the brain associated with M. haemophilum and M. simiae mixed infection.


Healthy and safe school environment, Part I: Results from the School Health Policies and Programs Study 2006.
Policies set at the state, district, and school levels can support and enhance a healthy and safe school environment. The Centers for Disease Control and Prevention conducts the School Health Policies and Programs Study every 6 years. In 2006, computer-assisted telephone interviews or self-administered mail questionnaires were completed by state education agency personnel in all 50 states plus the District of Columbia and among a nationally representative sample of school districts (n=461). Computer-assisted personal interviews were conducted with personnel in a nationally representative sample of elementary, middle, and high schools (n=1025). Most districts had adopted a policy on the inspection and maintenance of school facilities and equipment, and most schools had inspected and provided appropriate maintenance for each type of school facility and equipment during the 12 months preceding the study. Nearly all districts and schools had a comprehensive crisis preparedness, response, and recovery plan. Nearly all districts and schools prohibited tobacco, alcohol, and illegal drug use; fighting; weapons use; and weapon possession; but when students broke rules related to those behaviors, punitive measures were taken more often than provision of supportive services. Most schools did not reschedule outdoor activities to avoid times when the sun was at peak intensity, nor did they encourage the use of sunscreen before going outside. To provide students with a truly healthy and safe school environment in which learning can take place, more schools need to promote a positive school climate and reduce violence, injuries, and the use of tobacco, alcohol, and other substances. States and districts need to continue to provide policy and technical assistance in support of school efforts.


Plasma soluble Fas ligand concentration: decrease in elderly men and increase in patients with gastric carcinoma.
Fas ligand (FasL), which induces apoptosis against Fas-expressing cells, has been found to be expressed on various cell types including cancer cells. Membrane-bound FasL is cleaved to release soluble FasL (sFasL). Although serum or plasma sFasL concentration has been reported to increase in various diseases, sFasL concentration in healthy normal persons has not been fully studied. There have been few reports on sFasL concentrations in patients with carcinomas. We measured plasma sFasL concentrations using an enzyme-linked immunosorbent assay in 155 healthy volunteers (70 males and 85 females with an average age of 41.5+/-15.4) and 112 patients with gastric carcinoma (76 males and 36 females with an average age of 62.3+/-11.5). A significant negative correlation existed between age and plasma sFasL concentration in healthy volunteers. sFasL concentrations in males were significantly lower than those in females. Plasma sFasL levels were significantly higher in patients with gastric carcinoma than in healthy volunteers when male subjects aged 50 or older were analyzed, although no significant difference existed between the groups in the age bracket of 35 to 49. Male patients aged 50 or older with stage 1B or 2 tumors showed significantly higher plasma sFasL concentrations than those with stage 1A tumors or those with stage 3 or 4 tumors. In conclusion, age- and gender-matched controls should be used when plasma sFasL concentration is investigated. The origin and physiological or clinical significance of plasma sFasL in healthy volunteers and gastric cancer patients remain to be clarified.


The gene cluster of aureocyclicin 4185: the first cyclic bacteriocin of Staphylococcus aureus.
Staphylococcus aureus 4185 was previously shown to produce at least two bacteriocins. One of them is encoded by pRJ101. To detect the bacteriocin-encoding gene cluster, an ~9160 kb region of pRJ101 was sequenced. In silico analyses identified 10 genes (aclX, aclB, aclI, aclT, aclC, aclD, aclA, aclF, aclG and aclH) that might be involved in the production of a novel cyclic bacteriocin named aureocyclicin 4185. The organization of these genes was quite similar to that of the gene cluster responsible for carnocyclin A production and immunity. Four putative proteins encoded by these genes (AclT, AclC, AclD and AclA) also exhibited similarity to proteins encoded by cyclic bacteriocin gene clusters. Mutants derived from insertion of Tn917-lac into aclC, aclF, aclH and aclX were affected in bacteriocin production and growth. AclX is a 205 aa putative protein not encoded by the gene clusters of other cyclic bacteriocins. AclX exhibits 50 % similarity to a permease and has five putative membrane-spanning domains. Transcription analyses suggested that aclX is part of the aureocyclicin 4185 gene cluster, encoding a protein required for bacteriocin production. The aclA gene is the structural gene of aureocyclicin 4185, which shows 65 % similarity to garvicin ML. AclA is proposed to be cleaved off, generating a mature peptide with a predicted Mr of 5607 Da (60 aa). By homology modelling, AclA presents four α-helices, like carnocyclin A. AclA could not be found at detectable levels in the culture supernatant of a strain carrying only pRJ101. To our knowledge, this is the first report of a cyclic bacteriocin gene cluster in the genus Staphylococcus.


Multicentric reticulohistiocytosis: contrasting presentations in 2 Hispanic patients.
Multicentric reticulohistiocytosis (MR) is a rare debilitating disease that involves the skin and joints. It most commonly affects white individuals but has been reported in other ethnic groups including black individuals, Native Americans, and Asians. The Hispanic population is largely underrepresented in the epidemiology of MR. We describe 2 Hispanic patients with contrasting presentations of MR. Prompt recognition of MR is essential to expedite treatment and prevent potentially disabling sequelae of undiagnosed disease; however, diagnosis can be challenging due to the wide range of clinical presentations of MR as well as variable laboratory findings, especially in patients with skin of color. Our case reports underscore this phenomenon and demonstrate the importance of considering MR in all ethnic groups, including Hispanic patients.


Effect of anterior mandibular positioning on obstructive sleep apnea.
This prospective case report series utilized an anterior mandibular positioning (AMP) device on obstructive sleep apnea (OSA) patients and evaluated the changes in the respiratory disturbance index (RDI) and subjective overall satisfaction with the treatment. The RDI was based on all-night polysomnographic studies performed before and after approximately 4 months of appliance use. Overall satisfaction with the treatment was rated using a Likert scale (0 to 10) after 6, 18, and 36 months of AMP device use. Although only 15 of the 24 subjects agreed to undergo post-appliance polysomnograms, 14 of the 15 subjects showed a clear decrease in the RDI. The effect on the other subjects is unknown, but even if the 9 subjects without polysomnograms had no change in the RDI from the AMP device, a minimum rate of 58% of the subjects (14 of 24) would have substantially improved the RDI at the 3-month time point. Of the 24 subjects, 2 subjects claimed no immediate benefit and stopped using the device, 4 subjects were lost to followup, 1 subject lost weight and stopped using the device, 1 subject had mandibular advancement surgery after using the appliance for a period of time, and 3 stopped using the appliance because of persistent temporomandibular pain problems. The remaining 12 of the 23 (52%) original subjects were still using the appliance successfully at 36 months. One subject died of non-apnea-related causes before the 18-month follow-up time point. The 16 subjects who responded at 36 months reported a mean overall satisfaction with treatment of 6.9 +/- 3.3 on a scale of 10.


Evidence-based medicine and its role in plastic surgery.
In an era in which evidence-based medicine (EBM) has become an intricate aspect of the practice and advancement of the field of medicine, plastic surgery must aim to sustain its role as a pioneer division. It is critical that plastic surgeons understand the significance of EBM and, more importantly, its application to everyday practice. We aimed to review a comprehensive systemic approach to gather high-quality data that help support clinical decision making and assist in determining best available treatment. In addition, we provide evidence supporting the role of EBM in the field of plastic surgery.


Impaired biliary excretion of acetaminophen glucuronide in the isolated perfused rat liver after acute phenobarbital treatment and in vivo phenobarbital pretreatment.
The influence of phenobarbital (PB) on the hepatobiliary disposition of acetaminophen (APAP), acetaminophen glucuronide (AG) and acetaminophen sulfate (AS) was examined in the recirculating isolated perfused rat liver (IPL). PB was administered as a 5-mumol bolus to the IPL (acute) or in vivo (75 mg/kg/day, i.p., x 5 days), followed by a 48-hr washout, before addition of an APAP (66-mumol) bolus to the IPL. Acute PB administration to the IPL did not affect the total hepatic clearance of APAP or the formation clearance to AG and AS. The rate constant for the biliary excretion of AG and the percentage of the dose recovered in bile as AG were decreased significantly after the acute PB dose. In vivo PB pretreatment induced significantly the UDP-glucuronyltransferases (i.e., an increase in APAP clearance, the formation clearance to AG and in the estimate of the AG formation rate constant). The estimate of the AG sinusoidal egress rate constant after in vivo PB pretreatment also was increased significantly. The AG biliary excretion rate constant and the percentage of the dose recovered in bile as AG were decreased approximately 5-fold after in vivo PB pretreatment, similar to values obtained after acute PB administration. PB was detected only after acute PB administration, whereas unconjugated p-hydroxyphenobarbital was not detected after either treatment. These data indicate that neither PB itself nor an induction effect related to in vivo PB pretreatment are required directly to impair hepatobiliary disposition.


Managing vaginal mesh exposure/erosions.
To review the known causes, presentation, and management of synthetic mesh exposure and other healing abnormalities associated with transvaginal implantation for pelvic organ prolapse. The recent restriction of mesh used in urogynecology to type 1 monofilament/macroporous mesh has led to recognizable patterns of healing abnormality development. Excision of exposed or contracted mesh segments usually leads to symptom resolution. There are various surgical techniques recognized to reduce the risk of exposure development. Pain, when associated with mesh use, may be more challenging to manage and may persist in a small percentage of patients. Surgeons should be aware of recently recognized risk factors for exposure development and carefully select patients for mesh implantation based on risk:benefit assessment. The use of synthetic mesh implanted transvaginally for urogynecologic indications is associated with recognized risks, including exposure (approximately 10%) and contraction which can usually be managed successfully with local estrogen, in-office trimming, or surgical excision of the exposed or contracted segment.


Role for cyclooxygenase 2 in the development and maintenance of neuropathic pain and spinal glial activation.
Lines of evidence have indicated that cyclooxygenase 2 plays a role in the pathophysiology of neuropathic pain. However, the site and mechanism of its action are still unclear. Spinal glia has also been reported to mediate pathologic pain states. The authors evaluated the effect of continuous intrathecal or systemic cyclooxygenase-2 inhibitor on the development and maintenance of neuropathic pain and glial activation in a spinal nerve ligation model of rats. Continuous intrathecal infusion of meloxicam (32 or 320 mug . kg . day) or saline was started immediately after L5-L6 spinal nerve ligation. Mechanical allodynia and thermal hyperalgesia were evaluated on days 4 and 7 postoperatively. Spinal astrocytic activation was evaluated with glial fibrially acidic protein immunoreactivity on day 7. In other groups of rats, continuous intrathecal meloxicam was started 7 days after spinal nerve ligation, and effects on established neuropathic pain and glial activation were evaluated. Last, effects of continuous systemic meloxicam (16 mg . kg . day) on existing neuropathic pain and glial activation were examined. Intrathecal meloxicam prevented the development of mechanical allodynia and thermal hyperalgesia induced by spinal nerve ligation. It also inhibited spinal glial activation responses. In contrast, when started 7 days after the nerve ligation, intrathecal meloxicam did not reverse established neuropathic pain and glial activation. Systemic meloxicam started 7 days after ligation partially reversed neuropathic behaviors but not glial activation. Spinal cyclooxygenase 2 mediates the development but not the maintenance of neuropathic pain and glial activation in rats. Peripheral cyclooxygenase 2 plays a part in the maintenance of neuropathic pain.


Patients with chronic pain.
Preoperative evaluation of patients with chronic pain is important because it may lead to multidisciplinary preoperative treatment of patients' pain and a multimodal analgesia plan for effective pain control. Preoperative multidisciplinary management of chronic pain and comorbid conditions, such as depression, anxiety, deconditioning, and opioid tolerance, can improve patient satisfaction and surgical recovery. Multimodal analgesia using pharmacologic and nonpharmacologic strategies shifts the burden of analgesia away from simply increasing opioid dosing. In more complicated chronic pain patients, multidisciplinary treatment, including pain psychology, physical therapy, judicious medication management, and minimally invasive interventions by pain specialists, can improve patients' satisfaction and surgical outcome.


Protective effect of taurine on myocardial antioxidant status in isoprenaline-induced myocardial infarction in rats.
We have examined the protective effect of taurine on the myocardial antioxidant defense system in isoprenaline (isoproterenol)-induced myocardial infarction in rats, an animal model of myocardial infarction in man. Levels of diagnostic marker enzymes in plasma, lipid peroxides and reduced glutathione, and the activity of glutathione-dependent antioxidant enzymes and anti-peroxidative enzymes in the heart tissue were determined. Intraperitoneal administration of taurine significantly prevented the isoprenaline-induced increases in the levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatine phosphokinase in the plasma of rats. Taurine exerted an antioxidant effect against isoprenaline-induced myocardial infarction by preventing the accumulation of lipid peroxides and by maintaining the level of reduced glutathione and the activity of glutathione peroxidase, glutathione-S-transferase, catalase and superoxide dismutase at near normality. The results indicated that the cardioprotective potential of taurine was probably due to the increase of the activity of the free radical enzymes, or to a counteraction of free radicals by its antioxidant nature, or to a strengthening of myocardial membrane by its membrane stabilizing property.


Haemorheological changes in African breast cancer patients.
Several studies have indicated the existence of thrombo-embolic complications in cancer patients and that this could be associated with changes in heamorheological parameters. Packed cell volume (PCV), heamoglobin (Hb), relative plasma viscosity (RPV) and plasma Fibrinogen concentration (PFC) were measured in 50 healthy control women, 50 age-matched women with breast cancer, and 10 women with histophathologically proven benign breast tumour. There were significant differences between the controls and breast cancer patients in all the parameters measured (p < 0.05). However, patients with cancer have significantly higher RPV and PFC (P < 0.001) respectively than controls. There was significant mean difference between pre and post mastectomy in fibrinogen concentration (p < 0.05) and this was observed over the 5-week study period. Since increased fibrinogen may give rise to increase fibrin formation which has been asserted as an independent cardiovascular risk factor for thromb-oembolic complications, African patients with breast cancer may well be predisposed to thrombotic complications during illness. The theological assessment may offer valuable benefit for the management and early diagnosis of breast cancer in African women.


Shared mechanisms underlying the location-, word- and arrow-based Simon effects.
A left or right keypress response to a relevant stimulus attribute (e.g., color) is faster when irrelevant left or right stimulus-location information corresponds with the correct response than when it does not. This phenomenon, known as the Simon effect, is obtained not only for physical locations, but also location words "left" and "right" and left- or right-pointing arrows. However, these location-, word-, and arrow-based Simon effects show different patterns in the reaction-time (RT) distributions, as evident in delta plots. In the present study, we employed procedures, analysis of survival curves and divergence point analysis, which have not previously been applied to the Simon effect, to investigate differences in time course of these various Simon effects in more detail. Also, we examined whether the diffusion model for conflict tasks (DMC), which assumes that automatic activation of task-irrelevant information occurs in a pulse-like function, can capture not only features of the RT distributions for the location-based Simon effect, to which it has been fit previously, but also features of the word- and arrow-based Simon effects, to which it has not. Results showed different survival curves and earliest, maximum, and latest divergence points for the three Simon effects, but DMC was able to capture the basic features of the RT distributions reflected by delta plot and survival curves for all effects. The results imply that the location-, word-, and arrow-based Simon effects have shared mechanisms, although they have different RT distributions.


Survival of Salmonella Typhi and Shigella dysenteriae in dehydrated infant formula.
Powdered infant formula has previously been linked to the transmission of various bacterial pathogens in infants resulting in life-threatening disease and death. Survival studies of 2 common foodborne pathogens, Salmonella enterica serovar Typhi and Shigella dysenteriae, in powdered infant formula have not been previously studied despite the potentially devastating consequences from ingestion of these organisms, particularly by newborns, in case of a natural or deliberate contamination event. Therefore, to better predict the risk of S. Typhi and S. dysenteriae infection from consumption of infant formula, the present study was undertaken to determine survival of these microorganisms in dry infant formula under varying atmospheric conditions. A 2-strain cocktail of S. Typhi and a 3-strain cocktail of S. dysenteriae were stored for up to 12 wk in dehydrated infant formula in an ambient air or nitrogen atmosphere. Viable counts of S. Typhi at 12 wk in infant formula revealed a 2.9- and 1.69-log decrease in ambient air and nitrogen atmosphere, respectively. Viable counts of S. dysenteriae at 12 wk in infant formula revealed a 0.81- and 0.42-log decrease in ambient air and nitrogen atmosphere, respectively. These results show that S. Typhi and S. dysenteriae can remain viable for prolonged periods of time in powdered infant formula, and the presence of nitrogen enhances survival. Our goal in this work was to study the survival of S. Typhi and S. dysenteriae in dehydrated storage conditions in infant formula. This interest is partially generated by the possibility of using these 2 microorganisms to deliberately contaminate the food supply. The outcome of this study will help us to have a better idea how to respond and react to the risk of deliberate food contamination.


[Quantitative description of the process of radiation inactivation of cells. VIII. Microdosimetry in the analysis of the reproductive death of eukaryotic cells].
The microdosimetric approach permits to model the first physical stage of radiation damage developing of multistage model of radiation effect. It describes stochastics of absorbed energy distribution among and inside sensitive cell volumes. The analysis of radiobiological effect becoming more complete and adequate. The limits of application of valuable microdosimetric values to characterizing both the quality and quantity of radiation affecting the cells is considered. The aspects of the theory of dual action of radiation well compare with those of the cytogenetic model linking the reproductive cell death with asymmetrical chromosome exchanges.


[Experimental evidence on the role of different types unsaturated fats in the diet on ageing].
Nutrition has been largely related to the physiological ageing process. Several nutrients, such as certain types of dietary fat and various antioxidants have been shown to have positive effects on age-related diseases. The type of dietary fat affects mitochondrial structure and function, as well as its susceptibility to oxidative stress, all factors involved in ageing. The present review aims to summarise the studies conducted by our research group in the past 10 years, using virgin olive oil, sunflower oil, or fish oil as a source of unsaturated fat diet relative to a rat model of ageing.


Chromatin domains and the interchromatin compartment form structurally defined and functionally interacting nuclear networks.
In spite of strong evidence that the nucleus is a highly organized organelle, a consensus on basic principles of the global nuclear architecture has not so far been achieved. The chromosome territory-interchromatin compartment (CT-IC) model postulates an IC which expands between chromatin domains both in the interior and the periphery of CT. Other models, however, dispute the existence of the IC and claim that numerous chromatin loops expand between and within CTs. The present study was undertaken to resolve these conflicting views. (1) We demonstrate that most chromatin exists in the form of higher-order chromatin domains with a compaction level at least 10 times above the level of extended 30 nm chromatin fibers. A similar compaction level was obtained in a detailed analysis of a particularly gene-dense chromosome region on HSA 11, which often expanded from its CT as a finger-like chromatin protrusion. (2) We further applied an approach which allows the experimental manipulation of both chromatin condensation and the width of IC channels in a fully reversible manner. These experiments, together with electron microscopic observations, demonstrate the existence of the IC as a dynamic, structurally distinct nuclear compartment, which is functionally linked with the chromatin compartment.


The role of the Wnt signalling pathway in colorectal tumorigenesis.
Colorectal cancer (CRC) is the second largest cause of cancer-related deaths in Western countries. CRC arises from the colorectal epithelium as a result of the accumulation of genetic alterations in defined oncogenes and tumour suppressor genes. Mutations in the tumour suppressor APC (adenomatous polyposis coli) genes occur early in the development of CRC and lead to the stabilization of the Wnt pathway component beta-catenin and to the constitutive activation of Wnt signalling. Stabilizing mutations of beta-catenin can also lead to its accumulation, qualifying beta-catenin as a proto-oncogene. Here I will summarize the biochemical interactions occurring in Wnt signalling and describe how alterations in Wnt pathway components lead to CRC.


Plant phenology and global climate change: Current progresses and challenges.
Plant phenology, the annually recurring sequence of plant developmental stages, is important for plant functioning and ecosystem services and their biophysical and biogeochemical feedbacks to the climate system. Plant phenology depends on temperature, and the current rapid climate change has revived interest in understanding and modeling the responses of plant phenology to the warming trend and the consequences thereof for ecosystems. Here, we review recent progresses in plant phenology and its interactions with climate change. Focusing on the start (leaf unfolding) and end (leaf coloring) of plant growing seasons, we show that the recent rapid expansion in ground- and remote sensing- based phenology data acquisition has been highly beneficial and has supported major advances in plant phenology research. Studies using multiple data sources and methods generally agree on the trends of advanced leaf unfolding and delayed leaf coloring due to climate change, yet these trends appear to have decelerated or even reversed in recent years. Our understanding of the mechanisms underlying the plant phenology responses to climate warming is still limited. The interactions between multiple drivers complicate the modeling and prediction of plant phenology changes. Furthermore, changes in plant phenology have important implications for ecosystem carbon cycles and ecosystem feedbacks to climate, yet the quantification of such impacts remains challenging. We suggest that future studies should primarily focus on using new observation tools to improve the understanding of tropical plant phenology, on improving process-based phenology modeling, and on the scaling of phenology from species to landscape-level.


Establishment of a primary human sarcoma model in athymic nude mice.
Improvement of soft tissue sarcoma patient outcome requires well-characterized animal models in which to evaluate novel therapeutic options. Xenograft sarcoma models are frequently used, but commonly with established cell lines rather than with primary human sarcoma cells. The objective of the present study was to establish a reproducible xenograft model of primary human soft tissue sarcoma in athymic nude mice. Primary soft tissue sarcoma cells from four resected human sarcomas were isolated, cultured until the third passage and injected subcutaneously into athymic nude mice. The sarcoma xenograft was further analyzed by histological and immunohistochemical staining. In two out of four sarcomas tumor growth could successfully be established leading to solid tumors of up to 540 mm(3) volume. Histological and immunohistochemical staining confirmed the mouse xenograft as identical sarcoma compared with the original patient's tissue. In the present study a reproducible xenograft model of primary human soft tissue sarcoma in athymic nude mice was established. This animal model is of great interest for the study of sarcomogenesis and therapy.


The role of Clostridium septicum in paraneoplastic sepsis.
Clostridium septicum infections are rare but often associated with serious if not fatal outcomes. Clostridium septicum infection does not appear to be associated with a single specific defect in cellular or humoral immunity. It has been associated with multiple medical problems, including but not limited to leukemia, malignancy of the bowel, other solid tumors, cyclic neutropenia with enterocolitis, diabetes mellitus, and severe arteriosclerosis. Most cases of C septicum are associated with malignancy, and mortality approaches 100% if care is not rendered within 12 to 24 hours. To evaluate outcomes of patients with C septicum bacteremia, whether treated medically or surgically or both, and to note associated conditions. Retrospective evaluation of patients found to have C septicum bacteremia in the past 6 years. Two teaching hospitals, Brooke Army Medical Center (250 beds) and Wilford Hall Medical Center (292 beds), were the source of our patients. All patients found to have C septicum bacteremia during hospitalization or postmortem examination were included in the study. There were no exclusion criteria. Mortality associated with C septicum infection. In our case series, mortality was 33%, which is slightly lower than reported in prior studies (43%-70%). Presumptive identification based on Gram stain, awareness of C septicum infection as a paraneoplastic syndrome, and prompt, clear communication between laboratory personnel and clinicians are necessary for early diagnosis of C septicum infection. Early institution of antibiotic therapy improves prognosis.


Vasoactive intestinal peptide-mediated Th17 differentiation: an expanding spectrum of vasoactive intestinal peptide effects in immunity and autoimmunity.
Interactions between neural and immune effector pathways serve a vital role in mammalian defenses against foreign pathogens and toxins. The immune system initiates processes leading to the release of diverse mediators and cytokines that recruit neural and endocrine involvement in immunity. Inversely, transmitters released from nerves innervating immune organs regulate the development and functions of the immune cells. Vasoactive intestinal peptide (VIP) is the quantitatively and functionally most prominent immunoregulatory neuropeptide that participates in local tissue immune responses by potently affecting T cell and macrophage migration, proliferation, and cytokine production. T cells, macrophages, and mast cells express the VIP G protein-coupled receptors (GPCR) VPAC(1) and VPAC(2) that transduce the effects of VIP on immunity. The VIP-VPAC axes also are coupled to abnormal T cell functions in different autoimmune conditions. Recently, it has been shown that VIP also enhances the differentiation of distinctive type of proinflammatory Th17 cells by a VPAC(1)-dependent mechanism. This unique VIP-VPAC(1) signaling in Th17 cell differentiation expands our understanding of VIP immune functions, provides new insights into the immune roles of individual VPAC receptors, and offers meaningful possibilities for improving therapeutic potential of VIP in immune disorders.


Assessing neuromuscular disease with multifrequency electrical impedance myography.
Electrical impedance myography (EIM) is a noninvasive technique for neuromuscular assessment in which low-intensity alternating current is applied to a muscle and the consequent surface voltage patterns are evaluated. Previous work using a single frequency of 50 kHZ has demonstrated quantitative correlation of EIM parameters with disease status. In this investigation we examined the use of multifrequency EIM, studying a prototypical neurogenic disease (amyotrophic lateral sclerosis, ALS) and myopathic disorder (inflammatory myopathy, IM). Eleven ALS patients, 7 IM patients, and 46 normal subjects participated in the study. Although disease-specific patterns were not identified such that IM could be differentiated from ALS, impedance vs. frequency patterns for diseased subjects differed substantially from those of the age-matched normal subjects, with the greatest alterations occurring in the most severe cases. Multifrequency EIM may be well-suited to serve as an easily applied technique to assess disease severity in a variety of neuromuscular conditions.


Molecular polymorphism of head acetylcholinesterase from adult houseflies (Musca domestica L.).
Acetylcholinesterase (AChE) from housefly heads was purified by affinity chromatography. Three different native forms were separated by electrophoresis on polyacrylamide gradient gels. Two hydrophilic forms presented apparent molecular weights of 75,000 (AChE1) and 150,000 (AChE2). A third component (AChE3) had a migration that depended on the nature and concentration of detergents. In the presence of sodium deoxycholate in the gel, AChE3 showed an apparent molecular weight very close to that of AChE2. Among the three forms, AChE3 was the only one found in purified membranes. The relationships among the various forms were investigated using reduction with 2-mercaptoethanol or proteolytic treatments. Such digestion converted purified AChE3 into AChE2 and AChE1, and reduction of AChE3 and AChE2 by 2-mercaptoethanol gave AChE1, in both cases with a significant loss of activity. These data indicate that the three forms of purified AChE may be classified as an active hydrophilic monomeric unit (G1) plus hydrophilic and amphiphilic dimers. These two components were termed G2s and G2m, where "s" refers to soluble and "m" to membrane bound.


Spectroscopic characterization and modeling of quadrupolar charge-transfer dyes with bulky substituents.
Joint experimental and theoretical work is presented on two quadrupolar D-π-A-π-D chromophores characterized by the same bulky donor (D) group and two different central cores. The first chromophore, a newly synthesized species with a malononitrile-based acceptor (A) group, has a V-shaped structure that makes its absorption spectrum very broad, covering most of the visible region. The second chromophore has a squaraine-based core and therefore a linear structure, as also evinced from its absorption spectra. Both chromophores show an anomalous red shift of the absorption band upon increasing solvent polarity, a feature that is ascribed to the large, bulky structure of the molecules. For these molecules, the basic description of polar solvation in terms of a uniform reaction field fails. Indeed, a simple extension of the model to account for two independent reaction fields associated with the two molecular arms quantitatively reproduces the observed linear absorption and fluorescence as well as fluorescence anisotropy spectra, fully rationalizing their nontrivial dependence on solvent polarity. The model derived from the analysis of linear spectra is adopted to predict nonlinear spectra and specifically hyper-Rayleigh scattering and two-photon absorption spectra. In polar solvents, the V-shaped chromophore is predicted to have a large HRS response in a wide spectral region (approximately 600-1300 nm). Anomalously large and largely solvent-dependent HRS responses for the linear chromophores are ascribed to symmetry lowering induced by polar solvation and amplified in this bulky system by the presence of two reaction fields.


Use of alpha-naphthyl acetate esterase staining to identify T lymphocytes in cattle.
Peripheral blood lymphocytes (PBL), lymph nodes, and/or spleens from clinically normal cattle were examined for cytochemical staining of alpha-naphthyl acetate esterase (ANAE). Two types of positive-staining patterns in ANAE staining resulted. By a combination of ANAE staining and latex-ingesting test, diffuse ANAE-positive cells were considered as mononuclear phagocytic cells. Using erythrocyte rosettes, erythrocyte antibody complement rosettes, nylon-wool column technique, surface immunoglobulin (SIg) staining, and the ANAE staining technique, granular ANAE-positive lymphocytes were shown to be T lymphocytes. The frequency of T and B lymphocytes in PBL, spleens, and lymph nodes of clinically normal cattle was measured, using ANAE staining and SIg staining. In PBL, 47.7% were ANAE-positive and 26.9% were SIg-positive; in spleens, 22.4% were ANAE-positive and 53.7% were SIg-positive; and in lymph nodes, 38.5% were ANAE-positive and 28.3% were SIg-positive. The frequencies of T and B lymphocytes in PBL, spleens, and/or lymph nodes from cattle with enzootic bovine leukosis (EBL) and cattle with persistent lymphocytosis and in tumor cells from cattle with EBL were measured. When compared with those of clinically normal cattle, PBL, spleens, and lymph nodes of cattle with EBL and the PBL of cattle with persistent lymphocytosis contained numerous SIg-positive cells and few ANAE-positive cells. Tumor cells from cattle with EBL contained 7.3% ANAE-positive and 78.0% SIg-positive cells.


Communicating-occluding junction complexes in the alveolar epithelium. A freeze-fracture study.
Because studies differ as to the presence of communicating (gap) junctions in the alveolar epithelium, lung tissue from several mammalian species (man, dog, rabbit, rat, and mouse) was studied with the freeze-fracture method to clarify this problem. Communicating junctions were found between pneumonocytes in each species examined. They were always located within the meshes of or closely attached to the occluding junctions, forming communicating-occluding junction complexes. It is assumed that the communicating junctions between pneumonocytes serve mainly for metabolic coupling. The particular location of communicating junctions within the meshes of the occluding junction may be related to an additional mechanical function.


Structure of the Pds5-Scc1 Complex and Implications for Cohesin Function.
Sister chromatid cohesion is a fundamental prerequisite to faithful genome segregation. Cohesion is precisely regulated by accessory factors that modulate the stability with which the cohesin complex embraces chromosomes. One of these factors, Pds5, engages cohesin through Scc1 and is both a facilitator of cohesion, and, conversely also mediates the release of cohesin from chromatin. We present here the crystal structure of a complex between budding yeast Pds5 and Scc1, thus elucidating the molecular basis of Pds5 function. Pds5 forms an elongated HEAT repeat that binds to Scc1 via a conserved surface patch. We demonstrate that the integrity of the Pds5-Scc1 interface is indispensable for the recruitment of Pds5 to cohesin, and that its abrogation results in loss of sister chromatid cohesion and cell viability.


Complexity of the mouse gut T cell immune system: identification of two distinct natural killer T cell intraepithelial lineages.
Gut thymo-dependent (CD8 alpha + beta + or CD4+) or -independent (CD8 alpha + beta -) intraepithelial lymphocytes (IEL) mediate cytotoxicity following T cell receptor (TCR)-CD3 signaling, but only TCR gamma delta + and alpha beta + thymo-independent IEL show cytotoxicity of natural killer (NK) and antibody-dependent cell-mediated cytotoxicity types. Moreover, TCR alpha beta + and gamma delta + thymo-independent IEL express NK receptors, and may therefore be referred to as NK-TIEL. NK-TIEL cytotoxicity is mediated through perforin, Fas, or both pathways. In contrast to that of other NK cells, this cytotoxicity is not negatively regulated by signals delivered through the recognition of major histocompatibility complex class I molecules. Thus, gut IEL include T cell subsets with unique specificities and functions, ontogenically distinct from other T cell lineages, which may increase the antigenic repertoire diversity of the immune system participating in the defense of the epithelial barrier.


Accelerated clearance of uninfected red cells from Plasmodium berghei-infected mouse blood in normal mice.
51Cr-labelled uninfected cells, separated from Plasmodium berghei-infected mouse blood using the fluorescence-activated cell sorter, were cleared more rapidly than normal mouse erythrocytes after intravenous injection into normal mice.


[Advance directives in clinical practice : Living will, healthcare power of attorney and care directive].
In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.


A performance test for boar taint compounds in live boars.
Genetically reducing boar taint using low-taint lines is considered the most sustainable and economic long-term alternative to surgical castration of male pigs. Owing to the high heritability of the main boar taint components (androstenone, skatole and indole), breeding is an excellent tool for reducing the number of tainted carcasses. To incorporate boar taint into breeding programmes, standardized performance testing is required. The objective of this study was to develop and formally present a performance test for the main boar taint compounds on live breeding candidates. First, a standardized performance test for boar taint was established. A biopsy device was developed to extract small tissue samples (200 to 300 mg) from breeding candidates. Quantification of boar taint components from these small samples using specialized chemical extraction methods proved accurate and repeatable (r = 0.938). Following establishment of the method, biopsy samples of 516 live boars (100 to 130 kg live weight) were collected in the second step. Various mixed linear models were tested for each boar taint compound; models were ranked in terms of their information content. Pedigree information of 2245 ancestors of biopsied animals was included, and genetic parameters were estimated using univariate and multivariate models. Androstenone (in μg/g liquid fat (LF): mean = 0.578, σ = 0.527), skatole (in μg/g LF: mean = 0.033, σ = 0.002) and indole (in μg/g LF: mean = 0.032, σ = 0.002) levels obtained by biopsy were plausible. Heritability estimates for androstenone calculated with univariate (0.453) and multivariate (0.452) analyses were comparable to those in the literature. Heritabilities for skatole (0.495) and indole (0.550) were higher than that for androstenone. Genetic and phenotypic correlations were similar to those published previously. Our results show that data on boar taint compounds from small adipose samples obtained by biopsy provide similar genetic parameters as that described in the literature for larger samples and are therefore a reliable performance test for boar taint in live breeding candidates.


Outcome of Cesarean scar pregnancy managed expectantly: systematic review and meta-analysis.
To explore the outcome in women managed expectantly following the diagnosis of Cesarean scar pregnancy (CSP). An electronic search of MEDLINE, EMBASE and ClinicalTrials.gov databases was performed utilizing combinations of relevant medical subject headings for 'Cesarean scar pregnancy' and 'outcome'. Reference lists of relevant articles and reviews were hand-searched for additional reports. Observed outcomes included: severe first-trimester vaginal bleeding; clinical symptoms (abdominal pain, vaginal bleeding) requiring treatment; uncomplicated miscarriage; complicated miscarriage requiring intervention; first- or second-trimester uterine rupture or hysterectomy; third-trimester bleeding, uterine rupture or hysterectomy; maternal death; incidence of abnormally invasive placenta (AIP); prevalence of placenta percreta; ultrasound signs suggestive of AIP; and live birth. Meta-analyses of proportions using a random-effects model were used to combine data. Cases were stratified based on the presence or absence of embryonic/fetal heart activity at the time of diagnosis. A total of 17 studies (69 cases of CSP managed expectantly, 52 with and 17 without embryonic/fetal heart beat) were included. In women with CSP and embryonic/fetal heart activity, 13.0% (95% CI, 3.8-26.7%) experienced an uncomplicated miscarriage, while 20.0% (95% CI, 7.1-37.4%) required medical intervention. Uterine rupture during the first or second trimester of pregnancy occurred in 9.9% (95% CI, 2.9-20.4%) of cases, while hysterectomy was required in 15.2% (95% CI, 3.6-32.8%) of all cases. Forty (76.9% (95% CI, 65.4-86.5%)) women progressed to the third trimester of pregnancy, of whom 39.2% (95% CI, 15.4-66.2%) experienced severe bleeding. Finally, 74.8% (95% CI, 52.0-92.1%) had a surgical or pathological diagnosis of AIP at delivery and around two-thirds (69.7% (95% CI, 42.8-90.1%)) of them had placenta percreta. In women with CSP but no embryonic/fetal cardiac activity, an uncomplicated miscarriage occurred in 69.1% (95% CI, 47.4-87.1%) of cases, while surgical or medical intervention during or immediately after miscarriage was required in 30.9% (95% CI, 12.9-52.6%). Uterine rupture during the first trimester of pregnancy occurred in 13.4% (95% CI, 2.7-30.3%) of cases, but hysterectomy was not required in any case. CSP with positive embryonic/fetal heart activity managed expectantly is associated with a high burden of maternal morbidity including severe hemorrhage, early uterine rupture, hysterectomy and severe AIP. Despite this, a significant proportion of pregnancies complicated by CSP may progress to, or close to, term, thus questioning whether termination of pregnancy should be the only therapeutic option offered to these women. Expectant management of CSP with no cardiac activity may be a reasonable option in view of the low likelihood of maternal complications requiring intervention, although close surveillance is advisable to avoid adverse maternal outcome. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.


Selective decrease of small sensory neurons in lumbar dorsal root ganglia labeled with horseradish peroxidase after ND:YAG laser irradiation of the tibial nerve in the rat.
Recent electrophysiological evidence indicates that Q-switched Nd:YAG laser irradiation might have selective effects on neural impulse transmission in small slow conducting sensory nerve fibers as compared to large diameter afferents. In an attempt to clarify the ultimate fate of sensory neurons after laser application to their peripheral axons, we have used horseradish peroxidase (HRP) as a cell marker to retrogradely label sensory neurons innervating the distal hindlimb in the rat. Pulsed Nd:YAG laser light was applied to the tibial nerve at pulse energies of 70 or 80 mJ/pulse for 5 min in experimental rats. Seven days later HRP was applied to the left (laser-treated) and to the contralateral (untreated) tibial nerve proximal to the site of laser irradiation. In control animals the numbers of HRP-labeled dorsal root ganglion cells were not significantly different between the right and the left side. In contrast, after previous laser irradiation labeling was always less on the laser-treated side (2183 +/- 513 cells, mean +/- SEM) as compared to the untreated side (3937 +/- 225). Analysis of the dimensions of labeled cells suggested that the reduction of labeled cells on the laser-treated side was mainly due to a deficit in small sensory neurons. Since the conduction velocity of nerve fibers is related to the size of their somata, our histological data imply that laser light selectively affects retrograde transport mechanisms for HRP in slow conducting sensory nerve fibers.


Preoperative Risk Factors and Complication Rates in Facelift: Analysis of 11,300 Patients.
Facelift (rhytidectomy) is a prominent technique for facial rejuvenation with 126 713 performed in the United States in 2014. Current literature on facelift complications is inconclusive and derives from retrospective studies. This study reports the incidence and risk factors of major complications following facelift in a large, prospective, multi-center database. It compares complications of facelifts done alone or in combination with other cosmetic surgical procedures. A prospective cohort of patients undergoing facelift between 2008 and 2013 was identified from the CosmetAssure database. Primary outcome was occurrence of major complications, defined as complications requiring emergency room (ER) visit, hospital admission, or reoperation within 30 days of the procedure. Univariate and multivariate analysis evaluated risk factors including age, gender, BMI, smoking, diabetes, combined procedures, and type of surgical facility. Of the 129 007 patients enrolled in CosmetAssure, 11 300 (8.8%) underwent facelifts. Facelift cohort had more males (8.8%), diabetics (2.7%), elderly (mean age 59.2 years) and obese (38.5%) induviduals, but fewer smokers (4.8%). Combined procedures accounted for 57.4% of facelifts. Facelifts had a 1.8% complication rate, similar to the rate of 2% associated to other cosmetic surgeries. Hematoma (1.1%) and infection (0.3%) were most common. Combined procedures had up to 3.7% complication rate compared to 1.5% in facelifts alone. Male gender (relative risk 3.9) and type of facility (relative risk 2.6) were independent predictors of hematoma. Combined procedures (relative risk 3.5) and BMI ≥ 25 (relative risk 2.8) increased infection risk. Rhytidectomy is a very safe procedure in the hands of board-certified plastic surgeons. Hematoma and infection are the most common major complications. Male gender, BMI ≥ 25, and combined procedures are independent risk factors. LEVEL OF EVIDENCE 2: Risk.


Haemodialysis-associated thrombocytopenia: interactions among the immune system, membranes and sterilisation methods.
We present a case of a 47-year-old man with severe thrombocytopenia. The differential diagnosis for thrombocytopenia is wide. The assessment includes an evaluation for falsely low platelet counts (pseudothrombocytopenia), immune-mediated platelet destruction, bone marrow dysfunction, or increased consumption and sequestration. After extensive and systematic workup, we found a relationship of his thrombocytopenia with haemodialysis. Although not widely recognised by clinicians, partly due to an incomplete understanding of its pathophysiology, haemodialysis is also a potential cause of thrombocytopenia. His platelet counts completely normalised after the substitution of his haemodialysis membrane. We concluded that our patient had haemodialysis-induced thrombocytopenia, most likely secondary to electron-beam sterilisation.


Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.
The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment.


Isolation and characterization of glycogen synthase in Dictyostelium discoideum.
We have partially purified the protein and isolated the glcS gene for glycogen synthase in Dictyostelium. glcS mRNA is present throughout development and is the product of a single gene coding for 775 amino acids, with a predicted molecular mass of 87 kD. The sequence is highly similar to glycogen synthase from human muscle, yeast, and rat liver, diverging significantly only at the amino and carboxy termini. Phosphorylation and UDPG binding sites are conserved, with K(m) values for UDPG being comparable to those determined for other organisms, but in vitro phosphorylation failing to convert between the G6P-dependent (D) and -independent (I) forms. Enzyme activity is relatively constant throughout the life cycle: the I form of the enzyme isolates with the soluble fraction in amoebae, switches to the D form, becomes pellet-associated during early development, and finally reverts during late development to the I form, which again localizes to the soluble fraction. Deletion analysis of the promoter reveals a GC-rich element which, when deleted, abolishes expression of glcS.


Listeners' perceptions of the personality of male alaryngeal speakers.
Currently, there is limited information on listeners' perceptions of an individual with a laryngectomy. The purpose of this study is to determine whether listeners have different impressions of a laryngectomized speaker's personality based on mode of alaryngeal speech. Fifty-one listeners were presented with a reading passage produced by three male, alaryngeal speakers. Listeners were instructed to rate each speaker's personality and overall speech on a seven-point scale. Results showed that listeners' perceptions of personality were not affected by mode of alaryngeal speech, although listener's perceptions of overall speech were shown to be significantly affected by mode. Results, however, should be interpreted with caution due to small sample size and limited speaker representation. A portion of this information was previously presented at the American Speech Language and Hearing Association (ASHA) Annual Convention, Chicago, IL, November 13-15, 2003.


Prolonged latency of preterm premature rupture of membranes and risk of neonatal sepsis.
Preterm premature rupture of membranes (PPROM) is associated with inflammation and infection, and it may involve the loss of a barrier to ascending infection from the vagina, and it is possible that prolonged PPROM could be an independent risk factor for neonatal sepsis. The objective of the study was to determine whether prolonged latency after PPROM is associated with an increased risk of neonatal sepsis. This secondary analysis of the randomized controlled trial of magnesium sulfate for the prevention of cerebral palsy evaluated whether the time interval between diagnosis of PPROM and delivery was associated with an increased risk of neonatal sepsis. Latency time was categorized by weeks of latency (0 weeks to ≥ 4 weeks). The primary outcome was confirmed neonatal sepsis. Logistic regression was used to control for confounders. A total of 1596 patients with PPROM were analyzed, of whom 1390 had a < 4-week interval and 206 had an interval of ≥ 4 weeks. Confirmed neonatal sepsis occurred in 15.5% of patients in the cohort. In the univariate analysis, patients in the prolonged PPROM group were less likely to have neonatal sepsis (6.8% vs 17.2%, relative risk, 0.40 95% confidence interval, 0.24-0.66). This relationship was retained in the multivariable model; patients with prolonged PPROM ≥ 4 weeks had an adjusted odds ratio of 0.21 (95% confidence interval, 0.10-0.41) for neonatal sepsis. Neonatal sepsis was also significantly associated with earlier gestational age at rupture of membranes. Prolonged exposure to an intrauterine environment of PPROM does not increase the risk of neonatal sepsis; prolonged PPROM ≥ 4 weeks was associated with decreased risk of neonatal sepsis.


From the gallows to the grave - investigating the cause of death of seven skeletons from Renaissance Odense.
In 1982, archaeologists recovered seven skeletons at the site of Søndergade, OBM8230 in Odense, Denmark. The skeletons were isolated burials outside of cemetery context. This article examines the osteological and historical data of these seven skeletons and their burial location with the aim of examining the circumstances of their deaths. The chronological dating of the skeletons suggests that the seven individuals were buried around or after the Lutheran Reformation (AD 1536) up until the middle of the 17th century. From historical evidence, we can place the skeletons outside the western city gate, which is also where the wheel and gallows were located in Renaissance Odense. Based on the burial location and position in the grave of these skeletons, we hypothesize that the seven individuals were executed criminals. The results of the skeletal analysis show that all were young males. Two of the individuals have osteological evidence of decapitation. The remaining five individuals were most likely hanged based on historical and archaeological evidence, possibly for the crime of theft (Secher 1929). The historical, archeological and osteological analyses of these seven skeletons support the hypothesis that being buried in unconsecrated ground was a punishment in the form of expulsion of the community in death as the law indicates, rather than the absolution of the criminal's sins in life.


A review of ALK-rearranged renal cell carcinomas with a focus on clinical and pathobiological aspects.
ALK-rearranged renal cell carcinoma (ALK-RCC) has been recently proposed and incorporated into the recent World Health Organisation Classification of renal tumours as a provisional entity. In this article, we review ALK-RCC with a focus on clinical and pathobiological aspects. Seventeen cases have been described to date. ALK-RCC accounts for less than 1% of all renal tumours. The age of patients ranges from 6 to 61 years with a mean age of 29.6 years. Grossly, the tumour forms were ill-demarcated or well demarcated solid mass in the renal medulla. Histologically, RCC with VCL-ALK translocation resembles renal medullary carcinoma and mucinous cribriform pattern, signet-ring cell pattern and solid rhabdoid pattern are often observed in RCC with non-VCL-ALK fusion. Immunohistochemically, ALK protein diffusely expresses and TFE3 is often expressed. ALK gene can fuse to VCL, TPM3, EML4, HOOK1 or STRN gene. A break-apart fluorescence in situ hybridisation study is clinically available for the practice of definite diagnosis. ALK inhibitor therapy will provide great benefit for patients with advanced stage of ALK-RCC in the near future.


Human homolog of patched, a candidate gene for the basal cell nevus syndrome.
The basal cell nevus syndrome (BCNS) is characterized by developmental abnormalities and by the postnatal occurrence of cancers, especially basal cell carcinomas (BCCs), the most common human cancer. Heritable mutations in BCNS patients and a somatic mutation in a sporadic BCC were identified in a human homolog of the Drosophila patched (ptc) gene. The ptc gene encodes a transmembrane protein that in Drosophila acts in opposition to the Hedgehog signaling protein, controlling cell fates, patterning, and growth in numerous tissues. The human PTC gene appears to be crucial for proper embryonic development and for tumor suppression.


Comparison of fuel value and combustion characteristics of two different RDF samples.
Generation of Municipal Solid Waste (MSW) tends to increase with the growing population and economic development of the society; therefore, establishing environmentally sustainable waste management strategies is crucial. In this sense, waste to energy strategies have come into prominence since they increase the resource efficiency and replace the fossil fuels with renewable energy sources by enabling material and energy recovery instead of landfill disposal of the wastes. Refuse Derived Fuel (RDF), which is an alternative fuel produced from energy-rich Municipal Solid Waste (MSW) materials diverted from landfills, is one of the waste to energy strategies gaining more and more attention. This study aims to investigate the thermal characteristics and co-combustion efficiency of two RDF samples in Turkey. Proximate, ultimate and thermogravimetric analyses (TGA) were conducted on these samples. Furthermore, elemental compositions of ash from RDF samples were determined by X-Ray Fluorescence (XRF) analysis. The RDF samples were combusted alone and co-combusted in mixtures with coal and petroleum coke in a lab scale reactor at certain percentages on energy basis (3%, 5%, 10%, 20% and 30%) where co-combustion processes and efficiencies were investigated. It was found that the calorific values of RDF samples on dry basis were close to that of coal and a little lower compared to petroleum coke used in this study. Furthermore, the analysis indicated that when RDF in the mixture was higher than 10%, the CO concentration in the flue gas increased and so the combustion efficiency decreased; furthermore, the combustion characteristics changed from char combustion to volatile combustion. However, RDF addition to the fuel mixtures decreased the SO2 emission and did not change the NOx profiles. Also, XRF analysis showed that the slagging and fouling potential of RDF combustion was a function of RDF portion in fuel blend. When the RDF was combusted alone, the slagging and fouling indices of its ash were found to be higher than the limit values producing slagging and fouling.


Management of extremity soft tissue sarcomas with limb-sparing surgery and postoperative irradiation: do total dose, overall treatment time, and the surgery-radiotherapy interval impact on local control?
To evaluate potential prognostic factors in the treatment of extremity soft tissue sarcomas that may influence local control, distant metastases, and overall survival. Sixty-seven patients with extremity soft tissue sarcomas were treated with curative intent by limb-sparing surgery and postoperative radiation therapy at the Fox Chase Cancer Center or the Hospital of the University of Pennsylvania, between October 1970 and March 1991. Follow-up ranged from 4-218 months. The median external beam dose was 60.4 Gy. In 13 patients, interstitial brachytherapy was used as a component of treatment. The 5-year local control rate for all patients was 87%. The 5-year local control rate for patients who received < or = 62.5 Gy was 78% compared to 95% for patients who received > 62.5 Gy had larger tumors (p = 0.008) and a higher percentage of Grade 3 tumors and positive margins than patients who received < or = 62.5 Gy. The 5-year local control rate for patients with negative or close margins was 100% vs. 56% in patients with positive margins (p = 0.002). Cox proportional hazards regression analysis was performed using the following variables as covariates: tumor dose, overall treatment time, interval from surgery to initiation of radiation therapy, margin status, grade, and tumor size. Total dose (p = 0.04) and margin status (p = 0.02) were found to significantly influence local control. Only tumor size significantly influenced distant metastasis (p = 0.01) or survival (p = 0.03). Postoperative radiation therapy doses > 62.5 Gy were noted to significantly improve local control in patients with extremity soft tissue sarcomas. This is the first analysis in the literature to demonstrate the independent influence of total dose on local control of extremity soft tissue sarcomas treated with adjuvant postoperative irradiation.


White matter perivascular spaces are related to cortical superficial siderosis in cerebral amyloid angiopathy.
We set out to investigate whether MRI-visible centrum semiovale perivascular spaces (CSO-PVS), a potential biomarker of impaired interstitial fluid drainage in sporadic cerebral amyloid angiopathy, is associated with cortical superficial siderosis (cSS), reflecting recurrent hemorrhage from severe leptomeningeal and superficial cortical vascular amyloid. Retrospective multicenter cohort study of possible/probable cerebral amyloid angiopathy according to the Boston criteria. PVS were rated in basal ganglia and CSO (CSO-PVS) on axial T2-weighted sequences, using a validated 4-point visual rating scale and were classified as high (score>2) or low degree (score≤2) for prespecified analyses. Independent risk factors for high CSO-PVS degree were investigated in logistic regression. The final cohort consisted of 138 cerebral amyloid angiopathy patients (mean age, 71.8 years; 95% confidence interval, 70.2-73.4 years; 52.2% men). High CSO-PVS degree was present in 61.2% of cases. The prevalence of any cSS, and disseminated cSS (involving >3 sulci), was higher in patients with high versus low CSO-PVS degree (for any cSS 45.9% versus 13.5%; P<0.00005; for disseminated cSS 31.8% versus 0%; P<0.00005). In multivariable logistic regression analysis, cSS presence (odds ratio, 4.78; 95% confidence interval, 1.64-13.87; P=0.004) was an independent predictors of high CSO-PVS degree. We found no associations between basal ganglia PVS and cSS. High degree of CSO-PVS is highly prevalent in sporadic cerebral amyloid angiopathy and is related to cSS. Our findings suggest that severe leptomeningeal and cortical vascular amyloid (causing cSS) is related to impaired interstitial fluid drainage from cerebral white matter, although determining the causal direction of this relationship requires prospective studies.


How to estimate the size of the donor liver.
Of readily available methods to estimate the donor liver size, measurement of the body circumference at the xiphoid level (xiphoid measure) appeared to be the most accurate in the present prospective study of 60 donors and 57 recipients (r = 0.64, P = 0.0001). The estimated liver volume could be calculated using the equation: bloodless liver volume (1) = 1.44 x xiphoid measure (m). The difference between donor and recipient xiphoid measures was significantly higher in slowly recovering patients than in those recovering uneventfully (7 +/- 7 cm vs. - 5 +/- 8 cm, P < 0.001). The bloodless donor liver volume measured by water displacement averaged 1249 +/- 230 ml and had increased by 3 weeks posttransplant by 64 +/- 28% as determined using computed tomography. The volume of the liver graft seemed to adapt to the recipient as it correlated positively with body weight (r = 0.64, P < 0.01) and negatively with the age of the recipient (r = -0.42, P < 0.01). The liver graft volume seemed to increase less markedly in patients with a slow recovery than in those with an uncomplicated recovery (37% +/- 15% vs. 68% +/- 24%, P < 0.001). We conclude that a simple measurement of the body circumference at the xiphoid level can be used to estimate the donor liver volume. A gross mismatch of this parameter between the donor and the recipient seems to increase the risk of graft dysfunction. We also found that the change in the liver graft volume is influenced by the recipient's age and body weight.


Canine herpesvirus-1 (CHV-1): clinical, serological and virological patterns in breeding colonies.
Canine herpesvirus-1 (CHV-1) is presumed to be enzootic in the dog population and is associated with reproductive disorders and neonatal mortality. To advise dog breeders towards an effective management of CHV-1 infected colonies, 27 breeding bitches were studied during one reproductive cycle in field conditions: the effect of cycle stage, kennel size, initial antibody titre, mating and gestation on serologic and viral excretion patterns was evaluated, while the association between reproductive disorders and CHV-1 antibody titres and viral excretion was also analysed. All initially seronegative bitches seroconverted, while 40% of the initially seropositive bitches became seronegative at one or two occasions. No difference in antibody patterns was observed between mated and unmated bitches. Of the mated bitches, 46% experienced infertility, foetal resorption or mummification. No difference in antibody patterns was observed depending on the occurrence of reproductive disorders even if a decrease in antibody titres during early or late-di-oestrus was often present. Significantly higher titres were observed at all cycle stages in large kennels. None of the vaginal and nasal samples or buffy coats tested positive for CHV-1 DNA. The mixed image of clinical and sub-clinical carriage in this study demonstrated CHV-1 has a complex and difficult to predict clinical behavior. Preventive management with vaccination of reproducing bitches in kennels with reproductive disorders should therefore be advised.


Characterization of an atypical NOR site polymorphism in brown trout (Salmo trutta) with Ag- and CMA3-staining, and fluorescent in situ hybridization.
We have analyzed by Ag- and CMA3-staining, and rDNA fluorescent in situ hybridization an unusual NOR site polymorphism in a population of Salmo trutta from Mino basin (Northwestern Spain). A multichromosomal Ag-NOR distribution largely different from standard individuals both in the number and position of Ag-NORs, as well as in the pattern of activity, was revealed. Atypical Ag-NORs consist of rDNA genes, as evidenced by rDNA FISH, and are capable of constituting their own nucleolus. In spite of the large number of available NORs per individual, the mean number of Ag-NOR per cell was less than 3 in most individuals, which suggests a regulation mechanism to adjust the ribosomal production. The new rDNA clusters detected seem to be stably integrated, however, some characteristics of the NOR pattern observed suggest that this polymorphism is an unstable phenomenon.


The impact of sexual assault history and relationship context on appraisal of and responses to acquaintance sexual assault risk.
Although a major predictor of sexual victimization is previous victimization, the mechanism underlying this effect is not well understood. Sexual assault history's impact on appraisal of and responses to sexual assault risk was examined in an experimental analog study. Intimacy with perpetrator was also examined as a potential contributor to appraisal and responses. Young women varying in sexual assault history were randomly assigned to receive a scenario in which type of perpetrator was manipulated (someone just met, friend, date, boyfriend). Respondents appraised the man's actions as sexual interest or assault and indicated intentions to respond (resistance and nonresistance). Sexual assault history did not directly influence appraisal or intended responses but had modest indirect effects on resistance via sexual assertiveness. The primary influence on appraisal and responses was perpetrator intimacy. Women facing advances within a more intimate relationship were less likely to appraise those advances as threatening and less likely to resist.


Association of the C-type lectin-like domain family-16A (CLEC16A) gene polymorphisms with acute coronary syndrome in Mexican patients.
The CLEC16A gene has an important role in the immune activation and regulation inflammatory. This gene encodes to C-type lectin domain that is involved in the recognition of DAMPS. The aim of this study was assess the CLEC16A gene polymorphisms in the risk of developing ACS in a group of patients. Four rs12708716, rs12917716, rs6498142 and rs9925481 (positions 146529 A>G, 155804 G>C, 47905 C>G and 64135 C>T, respectively) single nucleotide polymorphisms of CLEC16A gene were analyzed by TaqMan assays in a group of 452 patients with ACS and 456 healthy controls. The analysis was performed on the total group of individuals and then in groups of men and women separately. Under co-dominant model adjusted by cardiovascular risk factors the rs12708716 (146529 A>G) and rs12917716 (155804 G>C) polymorphisms were significantly associated with decrease risk of ACS in men (OR=0.16, PCo-dom=0.027 and OR=0.37, PCo-dom=0.016, respectively). In summary, our data suggests that two polymorphisms of the CLEC16A gene play an important role in the developing of ACS in men.


ABC transporters and the blood-brain barrier.
The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) form a very effective barrier to the free diffusion of many polar solutes into the brain. Many metabolites that are polar have their brain entry facilitated by specific inwardly-directed transport mechanisms. In general the more lipid soluble a molecule or drug is, the more readily it will tend to partition into brain tissue. However, a very significant number of lipid soluble molecules, among them many useful therapeutic drugs have lower brain permeability than would be predicted from a determination of their lipid solubility. These molecules are substrates for the ABC efflux transporters which are present in the BBB and BCSB and the activity of these transporters very efficiently removes the drug from the CNS, thus limiting brain uptake. P-glycoprotein (Pgp) was the first of these ABC transporters to be described, followed by the multidrug resistance-associated proteins (MRP) and more recently breast cancer resistance protein (BCRP). All are expressed in the BBB and BCSFB and combine to reduce the brain penetration of many drugs. This phenomenon of "multidrug resistance" is a major hurdle when it comes to the delivery of therapeutics to the brain, not to mention the problem of cancer chemotherapy in general. Therefore, the development of strategies for bypassing the influence of these ABC transporters and for the design of effective drugs that are not substrates and the development of inhibitors for the ABC transporters becomes a high imperative for the pharmaceutical industry.


Purification and properties of carbonic anhydrase from salmon erythrocytes.
Carbonic anhydrase (CA) from erythrocytes of the pink salmon, Onchorhyncus gorbushka, was purified using chloroform-ethanol extraction and Sephadex G-75 gel filtration. A single, high specific-activity CA isozyme having a molecular weight of 29,000 was found. The enzyme sedimented as a single boundary at a sedimentation velocity of 2.9S. Amino acid analysis revealed a composition similar to other submammalian CAs with the exception that the cysteine content was low (1 mol cysteine/mol enzyme). Like other submammalian CAs, the presence of a sulfhydryl reducing agent was required to maintain full activity and to prevent structural changes in the enzyme.


Single-Fractionated Stereotactic Radiosurgery for Intracranial Meningioma in Elderly Patients: 25-Year Experience at a Single Institution.
Stereotactic radiosurgery (SRS) has been accepted as a therapeutic option for intracranial meningiomas; however, the detailed data on outcomes in elderly patients remain unclear. To delineate the efficacy of SRS for meningiomas in elderly patients. The outcomes of 67 patients aged ≥65 yr who underwent SRS for benign intracranial meningioma (World Health Organization grade I) between 1990 and 2014 at our institution were retrospectively analyzed. The median age was 71 yr (range, 65-83 yr), and the mean and median follow-up were 62 and 52 mo (range, 7-195 mo), respectively. Tumor margins were irradiated with a median dose of 16 Gy, and the median tumor volume was 4.9 cm3 (range, 0.7-22.9 cm3). Actuarial local tumor control rates at 3, 5, and 10 yr after SRS were 92%, 86%, and 72%, respectively. Previous surgery and parasagittal/falcine location were statistically significant predictive factors for failed tumor control. Mild or moderate adverse events were noted in 9 patients. No severe adverse event was observed. A higher margin dose was significantly associated with adverse events by univariate analysis. SRS is one of the standard therapies for meningiomas in elderly patients, providing both favorable tumor control and a low risk of adverse events under minimum invasiveness.


Comparison of post-tonsillectomy pain with two different types of bipolar forceps: low temperature quantum molecular resonance device versus high temperature conventional electrocautery.
The low temperature device did not show any advantages over the conventional high temperature electrocautery in terms of the postoperative pain, operation time, and complications in pediatric tonsillectomy. To compare post-tonsillectomy pain following the use of two different instruments with the same bipolar forceps techniques: low temperature quantum molecular resonance (QMR) device versus conventional high temperature electrocautery. Pediatric patients admitted from July 2008 through January 2009 were included. The participants underwent bilateral tonsillectomy; one side by the QMR device and the other by the bipolar electrocautery. The sides for each instrument were counterbalanced by the order of presentation. The postoperative pain was measured using the faces pain rating scale. In all, 33 patients with a mean age of 7.6 years were enrolled. The postoperative pain, operation time, and complications in 33 sides dissected by the electrocautery and 33 sides by the QMR device were compared. The average operation times with each device were not statistically different. The mean ratings of the perception of pain related to each instrument were not different on operation day and postoperative day 1, day 4, and day 7 (p = 0.133, 0.057, 0.625, and 1.0, respectively). There was no postoperative complication in any of the patients.


Gossypol toxicity and detoxification in Helicoverpa armigera and Heliothis virescens.
Gossypol is a polyphenolic secondary metabolite produced by cotton plants, which is toxic to many organisms. Gossypol's aldehyde groups are especially reactive, forming Schiff bases with amino acids of proteins and cross-linking them, inhibiting enzyme activities and contributing to toxicity. Very little is known about gossypol's mode of action and its detoxification in cotton-feeding insects that can tolerate certain concentrations of this compound. Here, we tested the toxicity of gossypol and a gossypol derivative lacking free aldehyde groups (SB-gossypol) toward Helicoverpa armigera and Heliothis virescens, two important pests on cotton plants. Larval feeding studies with these two species on artificial diet supplemented with gossypol or SB-gossypol revealed no detectable toxicity of gossypol, when the aldehyde groups were absent. A cytochrome P450 enzyme, CYP6AE14, is upregulated in H. armigera feeding on gossypol, and has been claimed to directly detoxify gossypol. However, using in vitro assays with heterologously expressed CYP6AE14, no metabolites of gossypol were detected, and further studies suggest that gossypol is not a direct substrate of CYP6AE14. Furthermore, larvae feeding on many other plant toxins also upregulate CYP6AE14. Our data demonstrate that the aldehyde groups are critical for the toxicity of gossypol when ingested by H. armigera and H. virescens larvae, and suggest that CYP6AE14 is not directly involved in gossypol metabolism, but may play a role in the general stress response of H. armigera larvae toward plant toxins.


Voriconazole MICs are predictive for the outcome of experimental disseminated scedosporiosis.
Scedosporiosis is associated with a mortality rate of up to 90% in patients suffering from disseminated infections. Recommended first-line treatment is voriconazole, but epidemiological cut-off values and clinical breakpoints have not been determined. To correlate voriconazole treatment response in mice suffering from disseminated scedosporiosis with MIC values determined using CLSI broth microdilution, Etest (bioMérieux) and disc diffusion. Voriconazole MICs for 31 Scedosporium apiospermum strains were determined using CLSI broth microdilution, Etest and disc diffusion. Groups of mice were challenged intravenously with 1 out of 16 S. apiospermum strains (voriconazole CLSI broth microdilution MIC range: 0.125-8.0 mg/L) and treated with 40 mg/kg voriconazole orally by gavage once daily. Efficacy of voriconazole was evaluated by a statistically significant ( P < 0.05) reduction in fungal burden in brain. A categorical agreement of 90.4% was reached for CLSI broth microdilution and disc diffusion and of 93.6% for CLSI broth microdilution and Etest. Correlation of CLSI MICs and in vivo outcome was good, as mice challenged with strains with an MIC ≤2 mg/L responded to voriconazole therapy in 92.3% and those challenged with strains with an MIC ≥4 mg/L responded to voriconazole therapy in 33.3%. CLSI broth microdilution and Etest deliver comparable results that enable a prediction of in vivo outcome. Our results suggest that voriconazole is able to reduce fungal burden in the brain of 92.3% of all mice challenged with strains with voriconazole CLSI MICs ≤2 mg/L, while mice challenged with strains with CLSI MICs ≥4 mg/L showed limited response to voriconazole treatment.