Effect of propranolol on the factors promoting bacterial translocation in cirrhotic rats with ascites.
Bacterial translocation appears to be an important mechanism in the pathogenesis of spontaneous infections in cirrhosis. Cirrhotic patients are commonly treated with beta-adrenoceptor blockers, but the impact of this treatment in the factors promoting bacterial translocation has not been investigated. This study was aimed at investigating in cirrhotic rats with ascites the effect of propranolol on intestinal bacterial load, transit, and permeability of the bowel and on the rate of bacterial translocation. Bacterial translocation to mesenteric lymph nodes and intestinal bacterial overgrowth, permeability (urinary excretion of (99m)Tc-diethylenetriaminepentaacetic acid [(99m)Tc-DTPA]), and transit (geometric center ratio of (51)Cr) were assessed in 29 rats with carbon tetrachloride (CCl(4)) cirrhosis and 20 controls. These variables were then measured in 12 placebo- and in 13 propranolol-treated ascitic cirrhotic rats. Bacterial translocation was present in 48% of the cirrhotic rats and in none of the controls. Cirrhotic rats with intestinal bacterial overgrowth had a significantly higher rate of translocation and slower intestinal transit than those without it. Among the 15 rats with overgrowth and a (99m)Tc-DTPA excretion greater than 10%, 15 had translocation and 2 had bacterial peritonitis. Only 1 of the 14 rats with either intestinal overgrowth or a (99m)Tc-DTPA excretion greater than 10% presented translocation. Compared with the placebo group, propranolol-treated animals had significantly lower portal pressure, faster intestinal transit, and lower rates of bacterial overgrowth and translocation. In ascitic cirrhotic rats, bacterial translocation results from intestinal overgrowth and severe damage to gut permeability. In this setting, intestinal overgrowth is associated with intestinal hypomotility. Propranolol accelerates the intestinal transit, decreasing the rates of bacterial overgrowth and translocation.


Analysis of single nucleotide polymorphisms of CRYGA and CRYGB genes in control population of western Indian origin.
Polymorphisms in gamma-crystallins ( CRYG ) can serve as markers for lens differentiation and eye disorders leading to cataract. Several investigators have reported the presence of sequence variations within crystallin genes, with or without apparent effects on the function of the proteins both in mice and humans. Delineation of these polymorphic sites may explain the differences observed in the susceptibility to cataract observed among various ethnic groups. An easier Restriction Fragment Length Polymorphism (RFLP)-based method has been used to detect the frequency of four single nucleotide polymorphisms (SNPs) in CRYGA / CRYGB genes in control subjects of western Indian origin. A total of 137 healthy volunteers from western India were studied. Examination was performed to exclude volunteers with any ocular defects. Polymerase chain reaction (PCR)-RFLP based method was developed for genotyping of G198A (Intron A), T196C (Exon 3) of CRYGA and T47C (Promoter), G449T (Exon 2) of CRYGB genes. The exonic SNPs in CRYGA and CRYGB were found to have an allele frequency 0.03 and 1.00 for ancestral allele respectively, while frequency of non-coding SNP in CRYGA was 0.72. Allele frequency of T90C of CRYGB varied significantly ( P = 0.02) among different age groups. An in-silico analysis reveals that this sequence variation in CRYGB promoter impacts the binding of two transcription factors, ACE2 (Member of CLB2 cluster) and Progesterone Receptor (PR) which may impact the expression of CRYGB gene. This study establishes baseline frequency data for four SNPs in CRYGA and CRYGB genes for future case control studies on the role of these SNPs in the genetic basis of cataract.


[Diagnostic Value of the Dual Source CT Dual Energy Pulmonary Perfusion Imaging for Pulmonary Embolism].
Objective To assess the diagnostic value of dual energy pulmonary perfusion imaging(DEPI)for pulmonary embolism.Methods The clinical data of 87 patients with suspected pulmonary embolism who had received DEPI between August 2017 and July 2018 in Jiaxing Second Hospital were retrospectively analyzed.With the findings of CT pulmonary angiography(CTPA)as the reference standard and with patients and pulmonary lobes as evaluation units,respectively,a diagnostic test was performed to calculate the diagnostic coincidence rate,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,positive likelihood ratio,negative likelihood ratio,and Kappa coefficient value for the diagnosis of DEPI and CTPA.Results The coincidence rate,sensitivity,specificity,positive predictive value,negative predictive value,Youden index,positive likelihood ratio,and negative likelihood ratio were 85.06%,88.41%,72.22%,92.42%,61.90%,0.61,3.18,and 0.16,respectively,when applying the patients as evaluation units.When the pulmonary lobes were invoked as evaluation units,the above-mentioned indexes were 89.57%,76.80%,96.82%,93.20%,88.02%,0.74,24.15,and 0.24,respectively.The diagnostic results of DEPI and CTPA had a good and excellent consistency,respectively(Kappa value=0.571,0.765).Conclusions DEPI has high accuracy,sensitivity,and specificity in the detection of pulmonary embolism.The combination of DEPI with CTPA can simultaneously obtain the anatomical structure and functional information images,greatly improving the diagnostic accuracy for pulmonary embolism.Thus,it can be used as the preferred examination for patients with clinically suspected pulmonary embolism.


Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent.
Isavuconazole is a new extended-spectrum triazole with activity against yeasts, molds, and dimorphic fungi. It is approved for the treatment of invasive aspergillosis and mucormycosis. Advantages of this triazole include the availability of a water-soluble intravenous formulation, excellent bioavailability of the oral formulation, and predictable pharmacokinetics in adults. A randomized, double-blind comparison clinical trial for treatment of invasive aspergillosis found that the efficacy of isavuconazole was noninferior to that of voriconazole. An open-label trial that studied primary as well as salvage therapy of invasive mucormycosis showed efficacy with isavuconazole that was similar to that reported for amphotericin B and posaconazole. In patients in these studies, as well as in normal volunteers, isavuconazole was well tolerated, appeared to have few serious adverse effects, and had fewer drug-drug interactions than those noted with voriconazole. As clinical experience increases, the role of this new triazole in the treatment of invasive fungal infections will be better defined.


Differential effects of elicitors on the viability of rice suspension cells.
We have compared the effects of two elicitors of defense-related processes on rice (Oryza sativa L.) suspension cells. Both chitosan and salicylic acid induced the accumulation of extracellular chitinase, thickening of the cell wall, and a variety of cytological changes in treated cells. Chitosan also induced the production of a brown pigment and cell death. Both of these effects depended on the availability of reactive oxygen species, because the damage was greatly reduced by either catalase or free-radical scavengers. Pretreating cells with salicylic acid also protected them from the cytotoxic effects of chitosan. This type of induced tolerance persisted when salicylic acid was removed and was not simply due to the release of extracellular substances, because salicylic acid-treated cells did not protect untreated cells from chitosan-induced death. Salicylic acid also stimulated the production of a 10-kilodalton subtilisin inhibitor that was not produced by chitosan-treated cells. Most of these changes are associated with the hypersensitive response of many plant species, including monocotyledons, and may serve as an in vitro model for investigating the biochemistry of some diseases.


The 41st Annual Meeting of the American Society of Clinical Oncology. Orlando, FL, USA, 13-17 May, 2005.
Nearly 29,000 scientists from all over the world gathered at the 41st Annual Meeting of the American Society of Clinical Oncology (ASCO). The programme included the presentation of new data encompassing all the fields of cancer research, including cancer prevention, treatment and biology. Special sessions were added to summarise and discuss achievements in the field of translational research on biologically targeted therapies. Rational drug design based on tumour biology and genetics represents a promising strategy to overcome the limitations of conventional chemotherapy. Increased knowledge in the field of molecular oncology, genetics and progress in technology are revolutionising tumour classification, prognostication, prediction and therapy. However, at present, for most of the diseases, improvements brought about by the newer therapies are small, although clinically meaningful. This review will briefly address some of the most interesting data presented at ASCO 2005.


A supramolecular hexameric ring from alumazene and methylsulfonate.
A dealkylsilylation reaction of alumazene [2,6-(i-Pr)2C6H3NAlMe]3 (1) with trimethylsilyl methylsulfonate in a 1:2 molar ratio in toluene afforded a supramolecular cyclic hexamer {Me[2,6-(i-Pr)2C6H3NAl]3(O3SMe)2}6 (2) composed of six intact alumazene rings and possessing two types of bridging sulfonate groups. Changing the reagent molar ratio to 1:3 caused the third sulfonate to partially substitute the last alumazene methyl group in an eta2 fashion and introduced a disorder in the crystal lattice.


Catalysis of covalent Lp(a) assembly: evidence for an extracellular enzyme activity that enhances disulfide bond formation.
The assembly of lipoprotein(a) (Lp(a)) particles occurs via a two-step mechanism in which noncovalent interactions between apolipoprotein(a) (apo(a)) and the apolipoproteinB-100 component of low density lipoprotein precede the formation of a single disulfide bond. Although we have previously demonstrated that the rate constant for the covalent step of Lp(a) assembly can be enhanced by altering the conformational status of apo(a), the resultant rates of covalent Lp(a) particle formation measured in vitro are relatively slow. The large excess of Lp(a) (over apo(a)) observed in vivo can be accounted for by a preferential clearance of apo(a) over Lp(a) and/or a sufficiently high rate of covalent Lp(a) assembly. In the present study, we report that cultured human hepatoma cells secrete an oxidase activity that dramatically enhances the rate of covalent Lp(a) assembly. This activity is likely possessed by a protein because it is heat-sensitive and is retained in the concentrate following ultrafiltration through a 5 kDa cutoff filter. However, a small molecule cofactor for the activity is suggested by the observation that the activity is lost upon dialysis. Plots of Lp(a) assembly rate versus input apo(a) concentration gave rectangular hyperbolae; the reaction displayed an unusual dependence on the concentration of apoB-100, with increasing concentrations of apoB-100 resulting in slower rates of Lp(a) assembly at low concentrations of apo(a), an effect that was alleviated by higher apo(a) concentrations. Interestingly, V(max(app))/K(m(app)) ratios were insensitive to apoB-100 concentration, which is diagnostic of a ping-pong reaction mechanism. In this way, the putative Lp(a) oxidase may be functionally analogous to protein disulfide isomerase, which exhibits a similar mechanism during the catalysis of disulfide bond formation during protein folding, although we have ruled out a role for this enzyme in Lp(a) assembly.


Enhanced Efficiency in Pediatric Interfacility Transport Through a Centralized Hospital System Communication Center.
Assess the implementation of a new centralized communication center and the effect on our institution's interfacility transport team's ability to respond to requests for patient transport. Retrospective review of data over 12 months prior to opening compared with 12 months after implementation of our centralized communication center. Quaternary academic pediatric hospital system with three campuses, a specialized transport team with expertise in pediatric, neonatal, and maternal-fetal critical care, and a new centralized hospital system communication center. All patients for whom transport to our hospital system was requested within the review period. Our hospital developed a multidisciplinary, centralized hub incorporating technology and integrated electronic tracking systems to coordinate real-time patient flow including intra- and interhospital transfers. One function of this center is to provide a communication center for critical care transports. Multiple new protocols and processes for transport were implemented upon opening. After implementation, total transports increased 60% (from 1,200 to >1,900 transports/yr). Team dispatch time decreased 40% from 57-34 minutes. Time from initiation of call to physician acceptance decreased 15% (median, 27-23 min). Over the same interval, there were 59% fewer lost transport opportunities. With this growth, our program was able to expand our transport program in scope and numbers. A centralized communication center for pediatric hospital patient flow that included specialized critical care patient transport has increased transport capacity and enhanced efficiency throughout our multicampus hospital system.


Effect of hemodialysis on the concentration of the seven tumor markers carcinoembryonic antigen, alpha-fetoprotein, squamous cell carcinoma-related antigen, neuron-specific enolase, CA 125, CA 19-9 and CA 15-3 in uremic patients.
The incidence of the 7 tumor markers carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), squamous cell carcinoma-related antigen (SCC), neuron-specific enolase (NSE), CA 125, CA 19-9 and CA 15-3 was studied before and after hemodialysis (HD) in 144 uremic patients who had no malignancies. Before HD, of all tumor markers, the mean concentration of SCC only exceeded the normal value. The positive rate was highest in SCC (95.1%), and that of CEA and NSE was 25.7 and 10.6%, respectively. However, AFP was within the normal range in all cases. Among CA antigens, the positive rate of CA 125 was 7.6%, of CA 19-9 was 6.3% and of CA 15-3 was 3.5%. After HD, the incidence as well as the mean concentration of all tumor markers increased. A parallel increment of total protein was observed after HD. The membrane filter used in HD appears to be insufficient to remove tumor marker proteins during HD. It is necessary to consider the clinical interpretation of elevated tumor markers in patients with uremia.


[Acquired haemophilia A].
A 74-year-old man developed a severe bleeding disorder on the basis of acquired Factor VIII (F VIII) inhibitor. Coagulation assays showed a prolonged activated partial thromboplastin time (APTT) with a normal prothrombin time (PT);F VIII level was 0.07 IU and F VIII inhibitor level 8.8 Bethesda units (BU). At least half the cases of acquired haemophilia A are associated with pregnancy, the postpartum period or an underlying malignancy or autoimmune disease. Haemorrhagic diathesis can be severe and life-threatening. Treatment of acute haemorrhages consists of human or porcine factor VIII concentrate, activated prothrombin complex concentrate (FEIBA) or recombinant factor VIIa, depending on the antibody titre. Immunosuppressive therapy is successful in at least 60% of the patients in making the inhibitor disappear. In patients with a spontaneous haemorrhagic diathesis, a thorough medical history should be taken, coagulation assays should be performed and a specialist should be consulted.


[Treatement of colorectal obstruction with self-expanding metallic stents under fluoroscopic guidance].
To prospectively evaluate fluoroscopic-assisted insertion of self-expanding metallic stents before surgery or for palliative treatment of soft tissue colorectal obstruction. Materials and methods. From January 1999 to October 2000, 18 consecutive patients with colorectal obstruction were included in the study. Treatment with self-expanding metallic stent was either the first line of treatment before surgery (n=8) (group I) or purely palliative (n=10) (group II). Colic stenosis was located proximal to the sigmoid in seven cases. Technical success was achieved in 83.3% of cases and colic decompression was observed after 48 hours in all patients with a stent. Thirty days mortality and stent related complications were respectively 0% and 37.5% for group I, and 20% and 50% for group II. All complications were minor except for one colic perforation by a guidewire. Stent insertion was effective and provided relief of colic obstruction in the majority of cases. Randomized studies would be necessary to demonstrate a definitive reduction in mortality and morbidity with this technique as compared to the classical surgical approach.


NF1 is a critical regulator of muscle development and metabolism.
There is emerging evidence for reduced muscle function in children with neurofibromatosis type 1 (NF1). We have examined three murine models featuring NF1 deficiency in muscle to study the effect on muscle function as well as any underlying pathophysiology. The Nf1(+/-) mouse exhibited no differences in overall weight, lean tissue mass, fiber size, muscle weakness as measured by grip strength or muscle atrophy-recovery with limb disuse, although this model lacks many other characteristic features of the human disease. Next, muscle-specific knockout mice (Nf1muscle(-/-)) were generated and they exhibited a failure to thrive leading to neonatal lethality. Intramyocellular lipid accumulations were observed by electron microscopy and Oil Red O staining. More mature muscle specimens lacking Nf1 expression taken from the limb-specific Nf1Prx1(-/-) conditional knockout line showed a 10-fold increase in muscle triglyceride content. Enzyme assays revealed a significant increase in the activities of oxidative metabolism enzymes in the Nf1Prx1(-/-) mice. Western analyses showed increases in the expression of fatty acid synthase and the hormone leptin, as well as decreased expression of a number of fatty acid transporters in this mouse line. These data support the hypothesis that NF1 is essential for normal muscle function and survival and are the first to suggest a direct link between NF1 and mitochondrial fatty acid metabolism.


Successfully navigating a career change.
Start your career evaluation by knowing yourself through self-assessment, so that you can "navigate" the career path most likely to match your wants, needs, strengths, and limitations. Evaluate your career options, and see how well they match those characteristics you have identified as important to you. When you take a new position, make a good first impression through your visual appearance, voice, and words. Learn the new workplace culture and politics to help you succeed. Use good personal management techniques for you, your workplace, and your life. Have a personal career plan so that you know the "harbor" where you want to be.


Transient Subclinical Hypothyroidism and Acute Suicidal Ideation Following Treatment with Escitalopram.
Thyroid function abnormalities after the use of selective serotonin reuptake inhibitors (SSRIs) have been reported in the extant literature, but the strength of this correlation is unclear and a commentary on its clinical significance is necessary. The one-week hospital course of a 16-year-old male presenting with worsening of major depressive disorder after the initiation of escitalopram was significant for the development of transient subclinical hypothyroidism (SCH). An analysis of the aberrant thyroid indices in the setting of escitalopram use was pursued. Data from previous studies suggesting similar events were reviewed in order to better characterize the nature of this association. The exact diagnostic criterion for SCH in the pediatric population has been undergoing reform and, based on the newer suggestions, our patient was assessed to have transient SCH. Thyroid hormone derangement following SSRI use has been reported in the past; however, the clinical implications of developing transient SCH in adolescent patients with major depression who are taking SSRIs is still unclear and not well understood at this time. The importance of having a better understanding of this potential interaction is marked by both the increased risk for suicidal ideation in the pediatric population with the use of SSRIs, as well as the confounding overlap of symptom presentation between hypothyroidism and major depressive disorder.


Inflammatory biomarkers are not useful for predicting prognosis in nursing and healthcare-associated pneumonia: A prospective, cohort study.
Whether inflammatory biomarkers including procalcitonin (PCT) and C-reactive protein (CRP) are useful for predicting prognosis in nursing and healthcare-associated pneumonia (NHCAP) is unknown. The aim of the present study was to investigate the utility of serial PCT and CRP measurements for predicting prognosis and treatment efficacy for hospitalized NHCAP patients. This prospective, observational, cohort study enrolled consecutive NHCAP patients hospitalized at Kurashiki Central Hospital from October 2010 to September 2017. PCT and CRP were measured twice, once on admission and again within 48-72 h after admission. The primary outcome was 30-day all-cause mortality, and the secondary outcome was initial treatment failure. A total of 299 patients were included. The 30-day mortality rate was 8.4% (25/299), and the initial treatment failure rate was 15.4% (46/299). On multivariate analysis, performance status [odds ratio (OR) (95% confidence interval (CI)): 2.25 (1.34-3.77), P = 0.002], temperature [OR (95%CI): 0.53 (0.32-0.88), P = 0.02], heart rate [OR (95%CI): 1.03 (1.01-1.06), P = 0.007], albumin [OR (95%CI): 0.42 (0.18-0.95), P = 0.04], and blood urea nitrogen [OR (95%CI): 1.02 (1.00-1.05), P = 0.04] were significant prognostic factors, and CRP D3 [OR (95%CI): 1.07 (1.02-1.11), P = 0.003] and PSI [OR (95%CI): 1.01 (1.00-1.02), P = 0.01] were the predictors of initial treatment failure. Consecutive measurements of PCT and CRP were not significant predictors of 30-day mortality. Inflammatory biomarkers including PCT and CRP were not useful for predicting prognosis and treatment efficacy in NHCAP patients. We should carefully evaluate the patients' vital signs and comorbidities when managing NHCAP patients.


[Not Available].
Congenital insensitivity to pain is a rare illness that can cause accidental external and internal injuries in children. When child abuse is suspected, the awareness of this illness can complicate any medicolegal interpretation of findings.Several components are needed to diagnose congenital insensitivity to pain: lack of sensitivity to pain since birth; involvement of the whole body; integrity of osteotendinous reflexes; and other sensitivity processes and negative paraclinical, including histological, examinations.This article describes the case of two siblings examined during an emergency legal procedure at the forensic medicine unit of the Grenobles University Hospital Centre in France. The medico-legal interpretation of facts and examinations must be conservative in case of legal complications and must follow an analysis of the child's and family's medicosocial problems since the child's birth. The family's socioeducational support and the communication of information on this illness should be a priority to avoid any misunderstanding and overrun in the child's management and monitoring.


Tip graft: a 20-year retrospective.
This paper chronicles a personal experience with nasal tip grafts over 20 years. In the first period (1968-1975), the original graft was designed for use in secondary rhinoplasty cases to obtain both projection of the tip and increased angulation at the columellar-lobular junction. The use was soon expanded to primary patients with inadequate tip projection. During the middle period (1975-1982), the applications for tip grafting were expanded to include many kinds of tip problems (both primary and secondary), cleft lip noses, and various ethnic noses, especially those with thick skin. The incidence of postoperative displacement and/or visibility of the graft was reduced as multiple grafts of solid, bruised, and crushed cartilage became routine. Ear cartilage was first used and ethmoid was abandoned as a primary graft. The incidence of infection was significantly reduced. The current period (1982-1991) is marked by refinements in technique and materials. Greater versatility with graft composition and materials makes possible a variety of tip configurations, custom-made for individual requirements.


Autoinhibition of Ethylene Formation in Nonripening Stages of the Fruit of Sycomore Fig (Ficus sycomorus L.).
Differences in the mechanism of ethylene emanation of Ficus sycomorus L. during various stages of the fruit development were investigated by enclosing the figs in jars. Two distinct patterns of ethylene emanation were found. Pattern a. in stages not capable of ripening, neither spontaneously nor as a result of physiological treatment (nonripening stages A and C), ethylene concentration in the jar increased linearly for a short time and then remained constant. Pattern b. in stages capable of ripening (ripening stages B, D, and E), the linear increase in ethylene concentration continued for the entire period of measurement. In nonripening stages, ethylene emanation stopped when ethylene concentration in the jar reached a constant value (0.6 mul/l at stage C). Aeration of the figs and the jar renewed ethylene emanation. CO(2) concentration in the jar never exceeded 0.5%. Treatment of stage C figs with 0.6 to 10 mul/l exogenous ethylene caused immediate and complete cessation of ethylene emanation whereas the same treatment did not cause any change in rate of ethylene emanation from figs at the ripening stages B and D. Gashing (wounding) of stage C figs temporarily changed the pattern of ethylene emanation from pattern a to pattern b.We concluded that in the nonripening stages ethylene acts as an autoinhibitor of its own production but this does not occur in the ripening stages.


An unusual case of penetrating intracranial injury due to scissors.
Craniocerebral penetrating non-missile injuries caused by metallic foreign bodies are uncommon events. Healthy 10 year-old boy applied to the hospital emergency service with his parents. Family members stated that the scissors have been stalled his head accidentally by his sister when they had played together. During physical examination the scissors located on left parietal region of the head was examined. There was no loss of consciousness and oriented with normal vital signs. Radiological investigation demonstrated a hyper dense foreign body (scissors) penetrating cranial cavity and ended before reaching posterior region of the left parietal lobe. To our knowledge, the presented was rare case of intracranial penetrating scissor, which was not removed until, injured, reached the hospital. Our goal was to discuss the rare case of penetrating non-missile foreign body cranial injury from medico legal aspect.


Does surgical experience have an effect on the success of retinal detachment surgery?
To examine the relationship between surgeon experience and success rates in retinal detachment surgery. Success rates during a follow-up of 11 months of 8 surgeons who performed in total 375 retinal detachment procedures ranging from 14 to 115 cases between December 1997 and January 2002 were correlated to the total number of vitreoretinal procedures ranging between 176 and 2,587. All patients received either scleral buckling or vitrectomy, and complicated cases were excluded. Mean primary anatomical success rates were 0.69 ± 0.14 for scleral buckling and 0.9 ± 0.05 for primary vitrectomy (P < 0.05). The primary anatomical success rates did not correlate to the number of vitreoretinal procedures. Seven of the eight surgeons showed an intraindividual learning effect with better success rates in the second versus the first half of the observed procedures. The learning effect was correlated to the total number of procedures with a higher effect in inexperienced surgeons. An intraindividual learning effect that was higher in inexperienced surgeons could be demonstrated. The learning effect was reduced by half after 500 vitreoretinal procedures while the primary anatomical success rates were not correlated to the number of vitreoretinal procedures.


[Expression of PTEN, p53 and P-glycoprotein in Non-small cell Lung Cancer and Their Predictive Values.].
Multiple drug resisting (MDR) phenotype is the sign of intrinsic or acquired resistance and is the key factor which leads to chemotherapy failure. It has been proven that PTEN, p53, P-gp expressions were related to drug resistance and prognosis of the patients with lung cancer. The aim of this study is to analyze the association of the expression of PTEN, p53, P-gp with postoperative survival in patients with non-small cell lung cancer (NSCLC), and to explore the relationship between the characteristics and drug resistance of NSCLC patients. A total of 61 patients with NSCLC were followed up. Immunohistochemical staining using polyclonal PTEN, p53 and P-gp antibody were performed on paraffinimbedded specimens from 61 patients with NSCLC and 20 specimens of tumor-surrounding normal lung tissue were used as control. The PTEN expression was significantly lower in NSCLC than in tumor-surrounding normal lung tissue and the expression of p53 and P-gp were in the opposite aspects (P<0.05). Expression of PTEN was positively related with histology, clinical stage, lymphatic metastasis, p53 expression was positively related with gender, lymphatic metastasis and the three kinds of protein expression were related with prognosis (P<0.05). The expression of PTEN was related with p53 expression (r=-0.282, P<0.05), but the expression of PTEN and p53 were not related with P-gp in NSCLC (P>0.05). To some extent, the expression level of PTEN, p53 and P-gp may predict the effect of radiotherapy, chemotherapy and prognosis of NSCLC.


Reconsidering Water Electrolysis: Producing Hydrogen at Cathodes Together with Selective Oxidation of n-Butylamine at Anodes.
Electrocatalysis for the oxygen evolution reaction (OER) is of great interest for improving the effectiveness of water splitting devices. Decreasing the anodic overpotential and simultaneously changing the anodic reaction selectively to produce valuable chemicals instead of O2 would be a major improvement of the overall cost efficiency. Some amines, when present in aqueous electrolytes, were recently shown to change the selectivity of the anodic process to generate H2 O2 rather than O2 on MnOx at pH 10. This results in unusually high apparent "anodic activities". In this work, industrially relevant OER catalysts, oxyhydroxides of cobalt (CoOx ), nickel-iron (NiFeOx ), and nickel (NiOx ) all show more pronounced effects. Moreover, as anodes they also selectively catalyzed the production of nbutyronitrile from n-butylamine at higher pH as an easily retrievable valuable product. The pH dependence of the activity was investigated at pH values closer those at which alkaline electrolyzers operate. The highest activities were observed for NiOx thin-film electrodes at pH 12 in the presence of 0.4 m n-butylammonium sulfate, without poisoning the active sites of Pt electrocatalysts at the hydrogen evolution electrode. 1 H NMR spectroscopy showed that n-butylamine is selectively oxidized to n-butyronitrile, an organic chemical with numerous applications. However, measurements using rotating ring-disk electrodes indicated that some H2 O2 is also generated at the surface of the oxide anodes.


Potassium currents in precursor cells isolated from the anterior subventricular zone of the neonatal rat forebrain.
The progenitor cells from the anterior part of the neonatal subventricular zone, the SVZa, are unusual in that, although they undergo division, they have a neuronal phenotype. To characterize the electrophysiological properties of the SVZa precursor cells, recordings were made of potassium and sodium currents from SVZa cells that were removed from postnatal day 0-1 rats and cultured for 1 day. The properties of the delayed rectifier and A-type potassium currents were described by classical Hodgkin and Huxley analyses of activation and inactivation. In addition, cells were assessed under current clamp for their ability to generate action potentials. The A-type potassium current (IK(A)) was completely inactivated at a holding potential of -50 mV. The remaining potassium current resembled the delayed rectifier current (IK(DR)) in that it was blocked by tetraethylammonium (TEA; IC50 4.1 mM) and activated and inactivated slowly compared with IK(A). The conductance-voltage (G-V) curve revealed that G increased continuously from 0.2 nS at -40 mV to a peak of 2.6 nS at +10 or +20 mV, and then decreased for voltages above +30 mV. Activation time constants were largest at -40 mV ( approximately 11 ms) and smallest at 100 mV ( approximately 1.5 ms). The properties of IK(A) were studied in the presence of 20 mM TEA, to block IK(DR), and from a holding potential of -15 mV, to inactivate both IK(DR) and IK(A). IK(A) was then allowed to recover from inactivation to negative potentials during 200- to 800-ms pulses. Recovery from inactivation was fastest at -130 mV ( approximately 21 ms) and slowest at -90 mV ( approximately 135 ms). Inactivation was voltage independent from -60 to +60 mV with a time constant of approximately 15 ms. At steady state, IK(A) was half inactivated at -90 mV. GK(A) increased from 0.2 nS at -60 mV to a peak of 2.4 nS at +40 mV. Finally, the activation time constants ranged from approximately 1.9 ms at -50 mV to 0.7 ms at +60 mV. The properties of IK(A) resembled those of IK(A) found in differentiating cerebellar granule neurons. Most SVZa cells had sodium currents (28/32 cells). However, in current clamp 11 of 12 cells were incapable of generating action potentials from voltages of -30 to -100 mV, suggesting that the available current densities were too low to support excitability.


Translational paradigms in scientific and clinical imaging of cardiac development.
Congenital heart defects (CHD) are the most prevalent congenital disease, with 45% of deaths resulting from a congenital defect due to a cardiac malformation. Clinically significant CHD permit survival upon birth, but may become immediately life threatening. Advances in surgical intervention have significantly reduced perinatal mortality, but the outcome for many malformations is bleak. Furthermore, patients living while tolerating a CHD often acquire additional complications due to the long-term systemic blood flow changes caused by even subtle anatomical abnormalities. Accurate diagnosis of defects during fetal development is critical for interventional planning and improving patient outcomes. Advances in quantitative, multidimensional imaging are necessary to uncover the basic scientific and clinically relevant morphogenetic changes and associated hemodynamic consequences influencing normal and abnormal heart development. Ultrasound is the most widely used clinical imaging technology for assessing fetal cardiac development. Ultrasound-based fetal assessment modalities include motion mode (M-mode), two dimensional (2D), and 3D/4D imaging. These datasets can be combined with computational fluid dynamics analysis to yield quantitative, volumetric, and physiological data. Additional imaging modalities, however, are available to study basic mechanisms of cardiogenesis, including optical coherence tomography, microcomputed tomography, and magnetic resonance imaging. Each imaging technology has its advantages and disadvantages regarding resolution, depth of penetration, soft tissue contrast considerations, and cost. In this review, we analyze the current clinical and scientific imaging technologies, research studies utilizing them, and appropriate animal models reflecting clinically relevant cardiogenesis and cardiac malformations. We conclude with discussing the translational impact and future opportunities for cardiovascular development imaging research.


Topology of the phenylalanine-specific permease of Escherichia coli.
The PheP protein is a high-affinity phenylalanine-specific permease of the bacterium Escherichia coli. A topological model based on sequence analysis of the putative protein in which PheP has 12 transmembrane segments with both N and C termini located in the cytoplasm had been proposed (J. Pi, P. J. Wookey, and A. J. Pittard, J. Bacteriol. 173:3622-3629, 1991). This topological model of PheP has been further examined by generating protein fusions with alkaline phosphatase. Twenty-five sandwich fusion proteins have been constructed by inserting the 'phoA gene at specific sites within the pheP gene. In general, the PhoA activities of the fusions support a PheP topology model consisting of 12 transmembrane segments with the N and C termini in the cytoplasm. However, alterations to the model, affecting spans III and VI, were indicated by this analysis and were supported by additional site-directed mutagenesis of some of the residues involved.


Active layer-incorporated, spectrally tuned Au/SiO2 core/shell nanorod-based light trapping for organic photovoltaics.
We demonstrate that incorporation of octadecyltrimethoxysilane (OTMS)-functionalized, spectrally tuned, gold/silica (Au/SiO2) core/shell nanospheres and nanorods into the active layer of an organic photovoltaic (OPV) device led to an increase in photoconversion efficiency (PCE). A silica shell layer was added onto Au core nanospheres and nanorods in order to provide an electrically insulating surface that does not interfere with carrier generation and transport inside the active layer. Functionalization of the Au/SiO2 core/shell nanoparticles with the OTMS organic ligand was then necessary to transfer the Au/SiO2 core/shell nanoparticles from an ethanol solution into an OPV polymer-compatible solvent, such as dichlorobenzene. The OTMS-functionalized Au/SiO2 core/shell nanorods and nanospheres were then incorporated into the active layers of two OPV polymer systems: a poly(3-hexylthiophene):[6,6]-phenyl-C61-butyric acid methyl ester (P3HT:PCB60M) OPV device and a poly[2,6-4,8-di(5-ethylhexylthienyl)benzo[1,2-b;3,4-b]dithiophene-alt-5-dibutyloctyl-3,6-bis(5-bromothiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4-dione] (PBDTT-DPP:PC60BM) OPV device. For the P3HT:PC60BM polymer with a band edge of ~700 nm, the addition of the core/shell nanorods with an aspect ratio (AR) of ~2.5 (extinction peak ~670 nm) resulted in a 7.1% improvement in PCE, while for the PBDTT-DPP:PC60BM polymer with a band edge of ~860 nm, the addition of core/shell nanorods with an AR of ~4 (extinction peak ~830 nm) resulted in a 14.4% improvement in PCE. The addition of Au/SiO2 core/shell nanospheres to the P3HT:PC60BM polymer resulted in a 2.7% improvement in PCE, while their addition to a PBDTT-DPP:PC60BM polymer resulted in a 9.1% improvement. The PCE and Jsc enhancements were consistent with external quantum efficiency (EQE) measurements, and the EQE enhancements spectrally matched the extinction spectra of Au/SiO2 nanospheres and nanorods in both OPV polymer systems.


Diagnostic utility of chest computerized tomography in the diagnosis of recurrence among sputum scarce and sputum negative previously treated pulmonary tuberculosis suspects.
The objective was to study the sensitivity, specificity, and diagnostic accuracy of various computed tomography (CT) chest findings in diagnosing recurrence among pulmonary tuberculosis (PTB) suspects. A prospective observational study was conducted in a tertiary care hospital in New Delhi. A total of 130 suspects with a past history of treatment for PTB, who presented with any of the symptoms suggestive of recurrence were included. Sputum-positive, HIV-positive patients, pregnant females, and patients aged <18 years were excluded. Patients underwent CT chest followed by bronchoalveolar lavage (BAL). A total of 62 patients were there in the final analysis. The median age of the patients with recurrent PTB was 27.5 years. Cough was the universal symptom in all these patients (>90%). Hemoptysis was the predominant symptom among patients with chronic pulmonary aspergillosis (66.6%). Necrotic mediastinal lymph nodes had good diagnostic accuracy of 88.71% with area under the curve of 0.806, P < 0.001 in diagnosing recurrent TB. BAL GeneXpert and mycobacteria growth indicator tube had good sensitivity (83.33% and 84.62%, respectively), specificity (100% for both), and excellent diagnostic accuracy (95.16% and 96.36%, respectively) for diagnosing recurrence in sputum negative and sputum scarce patient, (P < 0.001) when compared with composite reference standard. For culture-positive cases, BAL GeneXpert MTB/RIF had 100% sensitivity and 97.73% specificity in diagnosing recurrent PTB patients. The presence of mediastinal necrotic lymph node is the most accurate CT finding that can differentiate recurrent TB from post-TB sequelae. No other single chest CT scan finding had reliable diagnostic accuracy in comparison to microbiological tools in diagnosing recurrence among sputum negative or scarce previously treated PTB suspects.


Boundary effects on backscattering by a solid aluminum cylinder: experiment and finite element model comparisons (L).
Backscattering of sound by a solid aluminum cylinder was measured in the free field and with the cylinder near a flat surface. The target was suspended just below the surface of a water tank to simulate some aspects of backscattering when resting on the seabed. Measurements were compared with predictions made by an approximate hybrid approach based on multiple two-dimensional finite element calculations and the use of images. Many of the spectral features present in the tank data were present in the model. Comparing numerical model predictions with experimental data serves to build credibility for the modeling approach and can assist in developing insight into the underlying physical processes.


Effectiveness of Bromelain in the control of postoperative pain after periodontal surgery: A crossover randomized clinical trial.
This study aimed to compare the analgesic effects of Ibuprofen and bromelain after periodontal surgery. A double-blinded crossover clinical trial was conducted on 22 patients needing two crown lengthening surgeries without bone surgery or with limited bone surgery on two quadrants of the maxilla, with control and test sides. Each quadrant was randomly assigned to bromelain (500 GUD) or ibuprofen (400 mg). Immediately after the surgery and 6 hours after it, the first dose of the drugs was packaged in the same capsules in A and B. Postoperative pain was evaluated during the first 8 hours and on the following day using a visual analog scale (VAS). Using the VAS, the Ibuprofen group showed significantly lower mean pain scores than the bromelain group at 4 hours (P=0.047). In contrast, there were no significant differences between the two groups at 2, 6, 8, 10, 12, 24, and 48 hours (P>0.05). The effectiveness of bromelain for pain control following periodontal surgery was comparable to that of Ibuprofen. Therefore, bromelain can be an efficient replacement for ibuprofen in managing pain after periodontal surgery, especially in patients with gastric ulceration and increased bleeding tendency.


Phylogenetic and phylodynamic analyses of human metapneumovirus in Buenos Aires (Argentina) for a three-year period (2009-2011).
Human metapneumovirus, which belongs to the Paramyxoviridae family and has been classified as a member of the Pneumovirus genus, is genetically and clinically similar to other family members such as human respiratory syncytial virus. A total of 1146 nasopharyngeal aspirates from pediatric patients with moderate and severe acute lower respiratory tract infections, hospitalized at the Ricardo Gutierrez Childreńs Hospital (Buenos Aires, Argentina), were tested by real time RT-PCR for human metapneumovirus. Results showed that 168 (14.65%) were positive. Thirty-six of these 168 samples were randomly selected to characterize positive cases molecularly. The phylogenetic analysis of the sequences of the G and F genes showed that genotypes A2 and B2 cocirculated during 2009 and 2010 and that only genotype A2 circulated in 2011 in Argentina. Genotype A2 prevailed during the study period, a fact supported by a higher effective population size (Neτ) and higher diversity as compared to that of genotype B2 (10.9% (SE 1.3%) vs. 1.7% (SE 0.4%), respectively). The phylogeographic analysis of the G protein gene sequences showed that this virus has no geographical restrictions and can travel globally harbored in hosts. The selection pressure analysis of the F protein showed that although this protein has regions with polymorphisms, it has vast structural and functional constraints. In addition, the predicted B-linear epitopes and the sites recognized by previously described monoclonal antibodies were conserved in all Argentine sequences. This points out this protein as a potential candidate to be the target of future humanized antibodies or vaccines.


Asthma & COPD--IQPC's Second Conference.
The International Quality & Productivity Center's (IQPC) Second Asthma & COPD conference, held in Philadelphia, included topics covering new therapeutic developments in the field of asthma and COPD. This conference report highlights selected presentations on mAb treatments for asthma, including targeting IL-5, IL-13, IL-9 and TNFa, CCR3 inhibitors, histamine H4 receptor inhibition, novel mouse models of COPD and inhaled antisense asthma therapies. Investigational drugs discussed include mepolizumab (GlaxoSmithKline plc), benralizumab (BioWa Inc/Kyowa Hakko Kirin Co Ltd/MedImmune LLC), AMG-317 (Amgen Inc/Takeda Bio Development Center Ltd), TPI-ASM-8 (Pharmaxis Ltd) and AIR-645 (Altair Therapeutics Inc).


Poor graft outcome in recipients with de novo donor-specific anti-HLA antibodies after living related kidney transplantation.
Antibody-mediated rejection (AMR) is now widely recognized as a major problem in organ transplantation. This study was conducted to investigate the relationship between newly developing anti-HLA antibodies post-transplantation (de novo Abs) and the outcome of living related kidney transplantation (LRKT). The subjects included 87 patients who had received living donor kidney allografts at our institution. Panel reactive Ab assay (Flow-PRA) and graft biopsies were performed in all the recipients before and 6 months after the LRKT. The incidence of AMR, the donor specificity and time of appearance of the de novo Abs were retrospectively studied. Among the 87 LRKT recipients, 47 (54%) showed negative/negative (N/N) results, 15 (17%) showed positive/positive (P/P) results, 12 (14%) showed positive/negative results (P/N), and 13 (15%) showed negative/positive (N/P) results (de novo Abs) in the pre-/post-transplant Flow-PRA analysis. Among the 13 cases with de novo Abs, 5 (38%) had donor-specific Abs (DSA) and the remaining 8 (62%) had nondonor-specific Abs, as determined by LAB single antigen analysis. Eighty percent of the recipients with DSA showed evidence of AMR in the graft biopsies. The 5-year graft survival rate of the recipients with de novo Abs (N/P) was 69%, as compared with 96% in the N/N, 88% in the P/N and 93% in the P/P recipient groups (P = 0.009). LRKT recipients developing de novo Abs, especially those with DSA, showed a much higher incidence of AMR and a worse prognosis. Cautious monitoring for the appearance of anti-HLA Abs should be adopted after transplantation, even in patients without anti-HLA Abs prior to the transplantation.


Evolutionary relationships of human populations on a global scale.
Using gene frequency data for 29 polymorphic loci (121 alleles), we conducted a phylogenetic analysis of 26 representative populations from around the world by using the neighbor-joining (NJ) method. We also conducted a separate analysis of 15 populations by using data for 33 polymorphic loci. These analyses have shown that the first major split of the phylogenetic tree separates Africans from non-Africans and that this split occurs with a 100% bootstrap probability. The second split separates Caucasian populations from all other non-African populations, and this split is also supported by bootstrap tests. The third major split occurs between Native American populations and the Greater Asians that include East Asians (mongoloids), Pacific Islanders, and Australopapuans (native Australians and Papua New Guineans), but Australopapuans are genetically quite different from the rest of the Greater Asians. The second and third levels of population splitting are quite different from those of the phylogenetic tree obtained by Cavalli-Sforza et al. (1988), where Caucasians, Northeast Asians, and Ameridians from the Northeurasian supercluster and the rest of non-Africans form the Southeast Asian supercluster. One of the major factors that caused the difference between the two trees is that Cavalli-Sforza et al. used unweighted pair-group method with arithmetic mean (UPGMA) in phylogenetic inference, whereas we used the NJ method in which evolutionary rate is allowed to vary among different populations. Bootstrap tests have shown that the UPGMA tree receives poor statistical support whereas the NJ tree is well supported. Implications that the phylogenetic tree obtained has on the current controversy over the out-of-Africa and the multiregional theories of human origins are discussed.


Positive Association of Physical Activity with Both Objective and Perceived Measures of the Neighborhood Environment among Older Adults: The Aichi Workers' Cohort Study.
We examined the association between objective and perceived neighborhood characteristics and self-reported leisure-time physical activity (PA) in older Japanese residents living in areas ranging from metropolitan to rural in 2016. Objective measures used were walkability and the numbers of parks/green spaces and sports facilities within 500 or 1000 m of subjects' homes, calculated using geographic information systems. Subjective measures were the subjects' perceptions of their neighborhoods, assessed using a structured questionnaire. All variables were divided into three groups, and the lowest tertile was used as the reference. We assessed the location and frequency of strolling or brisk walking, moderate-intensity PA, and vigorous-intensity PA (sports) using a self-reported questionnaire and defined as performing a certain type of PA 3-4 times/week as a habit. Living in a neighborhood in the highest tertile for walkability and number of parks/green spaces as well as perception of having good access to recreational facilities, observing others exercising and the presence of walkable sidewalks was associated with walking and sports habits (multivariable odds ratios (ORs): 1.33-2.46, all p < 0.05). Interestingly, objective measures of PA-friendly environmental features were inversely associated with moderate-intensity PA habits, potentially because moderate-intensity PA consisted predominantly of gardening. In conclusion, living in an environment supportive of PA, whether objectively or subjectively measured, is related to leisure-time PA habits among older Japanese adults.


Nudging healthy food choices: a field experiment at the train station.
Recognizing the mindless nature of many food decisions, it has been suggested that attempts to increase healthy eating should not focus on convincing people what is 'right' but rather aim to adjust the environment such that people are automatically directed toward healthy choices. This study investigated a nudge aiming to promote healthy food choices in train station snack shops. The nudge involved a repositioning of food products: healthy foods were placed at the cash register desk, while keeping unhealthy products available elsewhere in the shop. Three snack shops were included: a control condition; a nudge condition repositioning healthy products and a nudge + disclosure condition employing the same nudge together with an explanatory sign. Next to examining its effectiveness during 1 week, the study assessed customers' acceptance of the nudge. Controlling for a baseline week, more healthy (but not fewer unhealthy) products were sold in both nudge conditions, with no difference between the nudge and the nudge + disclosure condition. A majority of customers reported positive attitudes toward the nudge. Repositioning healthy foods is a simple, effective and well-accepted nudge to increase healthy purchases. Moreover, disclosing its purpose does not impact on effectiveness.


Interleukin 35: Inhibitory regulator in monocyte-derived dendritic cell maturation and activation.
IL-35, a novel IL-12 family member, is a potent inhibitory cytokine predominantly produced by regulatory T and B lymphocytes that exerts optimal suppression in immune response. However, it remains unclear whether IL-35 plays an inhibitory role on human dendritic cells. In the present study, we focused on the possible immunosuppressive effect of IL-35 on the differentiation, maturation and function of monocyte-derived DCs (MoDCs). Addition of exogenous IL-35 was able to partially suppress MoDCs differentiation in vitro. Subsequently, LPS was used for the maturation of MoDCs and IL-35 was found to mainly restrain the maturation of MoDCs, characterized by the remarkable down-regulation of costimulatory molecules, CD83 and HLA-DR as well as a reduced production of pro-inflammatory cytokines (IL-12p70, IFN-γ, and TNF-α). Furthermore, IL-35-treated MoDCs exhibited strong inhibition in the proliferation of allogeneic CD4+/CD8+ T lymphocytes. Meanwhile, IL-35-treated MoDCs also suppressed the polarization of naïve CD4+ T lymphocytes towards Th1 phenotype and impaired CD8+ T cells allogeneic responses. And the foregoing suppression of MoDCs maturation and function by IL-35 might be due to the aberrant activation of STAT1/STAT3 and inhibition of p38 MAPK/NF-κB signaling pathway. Our results demonstrated for the first time that IL-35 played a critical role in modulating not only adaptive immune response, but also innate immune response. The inhibitory effect of IL-35 on MoDCs maturation and function may facilitate the development of promising therapeutic interventions in tumors and other diseases.


Effect of L-lysine and L-arginine on primary osteoblast cultures from normal and osteopenic rats.
A therapeutic role of amino acids L-lysine (Lys) and L-arginine (Arg) in osteoporosis and fracture healing was demonstrated previously by in vivo studies. In the present study, primary cultures of osteoblasts were used to investigate the effect of amino acids on gene expression (alkaline phosphatase activity, ALP; osteocalcin, OC; type I collagen), nitric oxide production (NO) and proliferation (MTT) of cells. Cells were isolated from the distal femurs of normal and osteopenic rats. Normal and osteopenic bone-derived cells were divided into four groups: control, Lys (0.587 mg/mL/d), Arg (0.625 mg/mL/d), and Lys + Arg (0.587 + 0.625 mg/mL/d). No evidence of differences between normal and osteopenic bone-derived cultures in basal conditions was observed. A significant (P = 0.002) increase of 10.4% in NO production was observed in normal bone-derived osteoblasts treated with Lys + Arg when compared to the control group at 7 days. At the same time, normal bone-derived osteoblasts treated with Arg and Lys + Arg showed significant increases in type I collagen synthesis of 25.3% and 28.4%, respectively, when compared to the control group. Osteopenic bone-derived osteoblasts showed significant (P = 0.002) increases of 27.6% in MTT and 28.7% in cell count at 48 hours when treated with Lys + Arg in comparison with the control group. At 7 days, NO production and type I collagen synthesis increased significantly (P< 0.005) both in osteopenic bone-derived osteoblasts treated with Arg (NO: 18.5%; type I collagen: 34.4%) and Lys + Arg (NO: 23.7%; type I collagen: 20.9%) compared to the control group. Finally, a significant (P = 0.025) decrease of 5.8% in OC level was observed in osteopenic bone-derived osteoblasts treated with Arg. Results suggest that the potential therapeutic effect of Lys and Arg on bone could be related, at least in part, to an improvement of NO production and type I collagen synthesis by osteoblasts both in normal and in osteopenic bone. In osteopenic bone-derived osteoblasts this synthetic phase is preceded by an initial increase of cell proliferation.


Isoform-specific effects of apolipoprotein E on cognitive performance in targeted-replacement mice overexpressing human APP.
The epsilon 4 allele of apolipoprotein E (apoE4) is the predominant genetic risk factor for late-onset Alzheimer's disease (AD) and is also implicated in cognitive deficits associated with normal aging. The biological mechanisms by which APOE genotype affects cognitive processes or AD pathogenesis remain unclear, but interactions of apoE with amyloid beta peptide (A beta) are thought to play an important role in mediating apoE's isoform-specific effects on brain function. Here, we investigated the potential isoform-dependent effects of apoE on behavioral and cognitive performance in human apoE3 and apoE4 targeted-replacement (TR) mice that also overexpress the human amyloid precursor protein (APP). Beginning at 6-7 months of age, female APP-Yac/apoE3-TR ('poE3') and APP-Yac/apoE4-TR ('poE4') mice were tested on a battery of tests to evaluate basic sensorimotor functioning, spatial working memory, spatial recognition, episodic-like memory and attentional processing. Compared with apoE3 mice, a generalized reduction in locomotor activity was observed in apoE4 mice. Moderate, but significant, cognitive impairments were also detected in apoE4 mice in the novel object-location preference task, the contextual fear conditioning test, and a two-choice visual discrimination/detection test, however spontaneous alternation performance in the Y-maze was spared. These results offer additional support for the negative impact of apoE4 on both memory and attention and further suggest that APP-Yac/apoE-TR mice provide a novel and useful model for investigating the role of apoE in mediating susceptibility to cognitive decline.


Astaxanthin Attenuates the Changes in the Expression of MicroRNAs Involved in the Activation of Hepatic Stellate Cells.
We previously demonstrated that astaxanthin (ASTX), a xanthophyll carotenoid, has an antifibrogenic effect in hepatic stellate cells (HSC), primarily responsible for the accumulation of extracellular matrix protein during the development of liver fibrosis. Studies have shown that microRNAs (miRNAs) are involved in HSC activation. Therefore, we analyzed the expression of 84 miRNAs using miRNA arrays in primary mouse quiescent HSC (qHSC) and activated HSC (aHSC) treated with/without ASTX during their activation. Compared with qHSC, the expression of 14 miRNAs and 23 miRNAs was increased and decreased by more than 2-fold, respectively, in aHSC. Among the 14 miRNAs increased in aHSC, the expression of miR-192-5p, miR-382-5p, and miR-874-3p was reduced by ASTX. In addition, ASTX increased the expression of miR-19a-3p, miR-19b-3p, and miR-101a-3p among 23 miRNAs decreased in aHSC. Moreover, we confirmed miR-382-5p expression was ~15-fold higher in aHSC than qHSC, and ASTX markedly inhibited the induction measured by quantitative real-time PCR. We identified that the expression of Baz1a and Zfp462 from the predicted miR-382-5p target genes was significantly reduced in aHSC while increased by ASTX treatment similar to the levels in qHSC. The roles of Baz1a and Zfp462 in HSC activation and the antifibrogenic effect of ASTX need to be further investigated.


[Multi-reasons, severe megaloblastic anaemia--description of two cases].
We report two cases of young patients (44 and 26 years old) with severe macrocytic, megaloblastic anaemia in course of Addison-Biermer's disease. In addition we found also other reasons of vitamin B12 deficiency. The one of them was chronic autoimmune thyroiditis and the second was, surely, Helicobacter pylori infection. The presented cases confirm the importance of spreading the diagnosis with antithyroid antibodies detection and Helicobacter pylori test in all patients with Addison-Biermer's diseaese.


Consumption of a dietary portfolio of cholesterol lowering foods improves blood lipids without affecting concentrations of fat soluble compounds.
Consumption of a cholesterol lowering dietary portfolio including plant sterols (PS), viscous fibre, soy proteins and nuts for 6 months improves blood lipid profile. Plant sterols reduce blood cholesterol by inhibiting intestinal cholesterol absorption and concerns have been raised whether PS consumption reduces fat soluble vitamin absorption. The objective was to determine effects of consumption of a cholesterol lowering dietary portfolio on circulating concentrations of PS and fat soluble vitamins. Using a parallel design study, 351 hyperlipidemic participants from 4 centres across Canada were randomized to 1 of 3 groups. Participants followed dietary advice with control or portfolio diet. Participants on routine and intensive portfolio involved 2 and 7 clinic visits, respectively, over 6 months. No changes in plasma concentrations of α and γ tocopherol, lutein, lycopene and retinol, but decreased β-carotene concentrations were observed with intensive (week 12: p = 0.045; week 24: p = 0.039) and routine (week 12: p = 0.031; week 24: p = 0.078) portfolio groups compared to control. However, cholesterol adjusted β-carotene and fat soluble compound concentrations were not different compared to control. Plasma PS concentrations were increased with intensive (campesterol:p = 0.012; β-sitosterol:p = 0.035) and routine (campesterol: p = 0.034; β-sitosterol: p = 0.080) portfolio groups compared to control. Plasma cholesterol-adjusted campesterol and β-sitosterol concentrations were negatively correlated (p < 0.001) with total and LDL-C levels. Results demonstrate that consuming a portfolio diet reduces serum total and LDL-C levels while increasing PS values, without altering fat soluble compounds concentrations. The extent of increments of PS with the current study are not deleterious and also maintaining optimum levels of fat soluble vitamins are of paramount necessity to maintain overall metabolism and health. Results indicate portfolio diet as one of the best options for CVD risk reduction. clinicaltrials.gov Identifier: NCT00438425.


The mechanism of loosening of cemented acetabular components in total hip arthroplasty. Analysis of specimens retrieved at autopsy.
Late aseptic loosening of cemented acetabular components is governed by the progressive, three-dimensional resorption of the bone immediately adjacent to the cement mantle. This process begins circumferentially at the intraarticular margin and progresses toward the dome of the implant. Evidence of bone resorption at the cement-bone interface was present even in the most well-fixed implants before the appearance of lucent lines on standard roentgenographic views. The mechanical stability of the implant was determined by the three-dimensional extent of bone resorption and membrane formation at the cement-bone interface. The leading edge of the membrane is a transition zone from regions of membrane interposition between the cement and the bone to regions of intimate cement-bone contact. Histologic analysis revealed that progressive bone resorption is fueled by small particles of high density polyethylene (HDP) migrating along the cement-bone interface and bone resorption occurs as a result of the macrophage inflammatory response to the particulate HDP. Evidence in support of a mechanical basis for failure of fixation was lacking. The mechanism of late aseptic loosening of a cemented acetabular component is therefore biologic in nature, not mechanical. This is exactly opposite to the mechanism of loosening on the femoral side of a cemented total hip replacement, which is mechanical in nature.


Presystolic mitral annular septal-lateral shortening is independent from left atrial and left ventricular contraction during acute volume depletion.
The mitral annulus (MA) is a dynamic structure that joins the left atrium (LA) and left ventricle (LV), but it is unknown whether MA motion is coupled to the LA or the LV or neither of the two. Since a well orchestrated coordination of LA, MA and LV septal-lateral (S-L) dynamics is essential for efficient valve closure, we assessed their functional coupling in an experimental ovine model. To assess the coupling under a wide range of physiological conditions, data were acquired in normal and acutely volume depleted hearts. In 10 sheep, radiopaque markers were placed in LA, MA and LV base (LVbase). Twelve weeks postoperatively, 4-D marker coordinates were obtained by stereo videofluoroscopy (60 frames/s) before (CTRL) and during acute inferior vena caval occlusion (VCO). Septal-lateral dimensions were calculated as distances between corresponding marker pairs in the LA, MA and LVbase 5 frames before end-diastole (ED-84 ms) and at end-diastole. Dynamics during late diastole are described as changes from ED-84 ms versus end-diastole. To study the functional coupling between LA, MA and LVbase we calculated slopes during late diastole from simple linear regressions on an animal-by-animal basis. During late diastole in CTRL, the LA and MA both shortened along the S-L dimension (32.9 +/- 6.6 mm vs 31.0 +/- 5.5 mm, p = 0.026 and 27.3 +/- 3.7 mm vs 24.6 +/- 4.1 mm, p = 0.005, respectively) whereas the LVbase lengthened (56.2 +/- 9.3 mm vs 57.3 +/- 9.3 mm, p = 0.012). VCO abolished septal-lateral dynamics of LA and LVbase during late diastole (27.8 +/- 4.3 mm vs 27.4 +/- 3.9 mm, p = 0.155 and 49.4 +/- 7.7 mm vs 49.5 +/- 7.5 mm, p = 0.752, respectively) while the MA still shortened (19.0 +/- 2.9 vs 18.0 +/- 2.8, p = 0.042). Under CTRL conditions LA dynamics were linearly dependent from MA dynamics (average coefficient 0.57, p = 0.001), suggesting that LA and MA are functionally coupled. With acute volume depletion, MA dynamics were linearly independent from both, LA and LV (average coefficient 0.28, p = 0.159 and 0.58, p = 0.192, respectively). Whereas MA and LA dynamics are coupled during late diastole in hearts with normal LV volumes, presystolic mitral annular septal-lateral shortening is independent from LA and LV dynamics with acute volume depletion. A better understanding of mitral annular dynamics and their functional coupling may help improve mitral valve repair strategies.


Production and characterization of monoclonal antibody to gentamicin.
Splenocytes from BALB/c mice immunized with a gentamicin-hemocyanin conjugate were fused with X63-Ag8.653 murine myeloma cells to produce hybridomas that secreted monoclonal antibody to gentamicin. Sixteen positive clones were obtained. The monoclonal antibody chosen for a gentamicin immunoassay has been characterized with respect to class, subclass, type of light chain, electrophoretic homogeneity, and binding affinity. Gentamicin monoclonal antibody purified from mouse ascites fluid was analyzed by immunoelectrophoresis, double immunodiffusion, enzyme-linked immunosorbent assay (ELISA), and polyacrylamide gel electrophoresis (PAGE). The results show that the antibody is an IgG2a (kappa). Two bands were detected when the purified antibody was electrophoresed on polyacrylamide gels: a major band and a less mobile minor component (5.6% of the major band). Both were IgG2a (kappa). The major band contained antibody which bound 2.1 moles of the substrate-labeled gentamicin derivative, beta-galactosyl-umbelliferone sisomicin, per mole of IgG, whereas one mole of the minor band bound only 0.095 moles of the substrate-labeled conjugate. The antibody has an affinity constant of 1.22 X 10(10) M-1.


Co-cyprindiol prescribing in a large, rural general practice in England.
To describe current co-cyprindiol prescribing in a large, rural general practice in England. To specifically investigate whether co-cyprindiol is prescribed within its license and Medicines and Healthcare products Regulatory Agency (MHRA) guidelines. To investigate the effect of a simple, low-cost intervention on the number and appropriateness of co-cyprindiol prescriptions. The computerised medical record system in a 17,435 patient general practice was examined to identify individuals prescribed co-cyprindiol. The medical records for each individual identified were examined to see if they satisfied the MHRA guidelines in co-cyprindiol use. Prescribers were then contacted and sent copies of the MHRA guideline. All patients were invited to attend for review. Prescriptions for co-cyprindiol were then re-audited. Co-cyprindiol comprised 3.4% of total combined oral contraceptive prescriptions. The most common indication was acne (69%). At baseline, the majority of prescriptions did not meet the MHRA guidelines. Prescriptions that did not meet guidelines tended to have been for longer (32 vs 19.5 months). After the intervention, the number of individuals prescribed co-cyprindiol fell (26 vs 12) and the number of prescriptions that met the guidelines increased (30.7% vs 75%). The largest change was a decrease in inappropriate prescriptions for acne. In this population, co-cyprindiol was rarely prescribed, though its use often contravened guidelines. Simple interventions can increase appropriateness of prescribing.


Incorporation of carbohydrate residues into peroxidase isoenzymes in horseradish roots.
Sliced root tissue of the horseradish plant (Armoracia rusticana), when incubated with mannose-U-(14)C, incorporated radioactivity into peroxidase isoenzymes. Over 90% of the radioactivity in the highly purified peroxidase isoenzymes was present in the neutral sugar residues of the molecule, i.e. fucose, arabinose, xylose, mannose. When the root slices were incubated simultaneously with leucine-4,5-(3)H and mannose-U-(14)C, cycloheximide strongly inhibited leucine incorporation into the peptide portion of peroxidase isoenzymes but had little effect on the incorporation of (14)C into the neutral sugars. These results indicated that synthesis of the peptide portion of peroxidase was completed before the monosaccharide residues were attached to the molecule. This temporal relationship between the synthesis of protein and the attachment of carbohydrate residues in the plant glycoprotein, horseradish peroxidase, appears to be similar to that reported for glycoprotein biosynthesis in many mammalian systems.


The costs and benefits of bone marrow transplantation.
The average direct costs of performing a bone marrow transplant (BMT), including the subsequent year, was found to be NZ$27,074 for 43 consecutive transplants. In 29 BMTs a full two year period of follow up was available and a quality of life analysis was carried out on these patients. It was calculated that 59 quality adjusted life years (QALYs) had been gained by the BMT procedure at the time of analysis. By combining these two analyses the cost of each QALY gained by BMT is NZ$13,272. The relatively low cost of BMT is partly due to the extremely low annual costs in second and subsequent years post BMT. In our patients this cost amounted to $195 per year. The costs and benefits of BMT compare very favourably with other complex medical procedures.


Evaluation of methods to detect circular RNAs from single-end RNA-sequencing data.
Circular RNA (circRNA), a class of RNA molecule with a loop structure, has recently attracted researchers due to its diverse biological functions and potential biomarkers of human diseases. Most of the current circRNA detection methods from RNA-sequencing (RNA-Seq) data utilize the mapping information of paired-end (PE) reads to eliminate false positives. However, much of the practical RNA-Seq data such as cross-linking immunoprecipitation sequencing (CLIP-Seq) data usually contain single-end (SE) reads. It is not clear how well these tools perform on SE RNA-Seq data. In this study, we present a systematic evaluation of six advanced RNA-based methods and two CLIP-Seq based methods for detecting circRNAs from SE RNA-Seq data. The performances of the methods are rigorously assessed based on precision, sensitivity, F1 score, and true discovery rate. We investigate the impacts of read length, false positive ratio, sequencing depth and PE mapping information on the performances of the methods using simulated SE RNA-Seq simulated datasets. The real datasets used in this study consist of four experimental RNA-Seq datasets with ≥100bp read length and 124 CLIP-Seq samples from 45 studies that contain mostly short-read (≤50bp) RNA-Seq data. The simulation study shows that the sensitivities of most of the methods can be improved by increasing either read length or sequencing depth, and that the levels of false positive rates significantly affect the precision of all methods. Furthermore, the PE mapping information can improve the method's precision but can not always guarantee the increase of F1 score. Overall, no method is dominant for all SE RNA-Seq data. The RNA-based methods perform better for the long-read datasets but are worse for the short-read datasets. In contrast, the CLIP-Seq based methods outperform the RNA-Seq based methods for all the short-read samples. Combining the results of these methods can significantly improve precision in the CLIP-Seq data. The results provide a systematic evaluation of circRNA detection methods on SE RNA-Seq data that would facilitate researchers' strategies in circRNA analysis.


KNOWLEDGE RELATED TO HIV/TB/HCV AMONG PRIMARY HEALTH CARE WORKERS AND THE INTEGRATED SCREENING IN KVEMO KARTLI REGION.
Integration of TB/HIV/HCV screening into primary health care has been implemented in Georgia since 2018. The aim of the program is to strengthen TB, HIV/HCV screening and early detection capabilities in the primary health care, as early detection and treatment are considered to be the most effective strategies to prevent these infections. The goal of the study was to evaluate and compare the baseline and follow-up knowledge about TB, HIV and HCV infectious among primary health care workers in Kvemo Kartli Region. The study instrument was a self-administered questionnaire. A total of 459 primary HCWs from Kvemo Kartli region were surveyed. The proportion of HCWs correctly knowing MDR TB definition increased from 34.6% to 82.8% and this difference was statistically significant (p<0.01). Nurses were less informed about HIV infection. Only 70.7% of them knew modes of HIV transmission, while 89.3% of physicians answered this question correctly (p<0.001). An assessment of knowledge among primary health care workers (PHC) providers is important, as they represent the first level of community contact with health care. The post-test after the training showed significant improvement in knowledge among trained HCWs. Follow-up knowledge and practice surveys are needed to understand the long-term impact of training on the rate screening referrals by PHC providers.


Multidisciplinary clinical management of paroxysmal nocturnal hemoglobinuria.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired disease caused by clonal expansion of one or more hematopoietic stem cell (HSC) lines due to a somatic mutation of the phosphatidylinositol glycan anchor (PIG-A) gene located on Xp22.1. PNH incidence is 1.5-2 cases per million of the population per year. PNH can affect multiple systems in the body and requires multidisciplinary clinical management. Patients can manifest with severe pancytopenia, life-threatening thrombosis affecting the hepatic, abdominal, cerebral, and subdermal veins, and high requirements for blood transfusion due to haemolytic anemia. PNH can also be associated with bone marrow failure. Advances in diagnostic techniques and a targeted therapeutic approach for PNH have emerged in the last two decades. Eculizumab, a promising humanized monoclonal antibody against C5, is the first approved therapy for PNH.


An Economic Analysis of the Pre-Deeming US Market for Nicotine Vaping Products.
Public health policies are often enacted without adequate consideration of the existing market structure or their impacts on that market structure. This paper provides context for the potential impact of regulations on nicotine vaping products (NVP) use by providing a structural analysis of competition in the US NVP market before FDA regulation. A literature review was conducted with the aim of providing a framework for analysis that: 1) defines the market; 2) evaluates market concentration; 3) identifies entry barriers; and 4) examines firm conduct. The NVP market includes retail, internet sellers and vape shops. Although conventional retail became more concentrated after the major cigarette companies entered the NVP market, the vape shop and internet sectors remain substantially less concentrated, producing an overall low market concentration, with few entry barriers and competitive behavior. The largely unregulated US NVP market has been highly competitive, with a high degree of innovation. However, new FDA deeming regulations as applied to NVPs could make it difficult for smaller companies to remain in the market and could discourage new companies and new product innovations from entering the market.


Enteral electrolytic solutions administered in continuous flow via naso-ruminal route in adult goats.
This study aimed to investigate the effects of maintenance enteral electrolytic solutions administered naso-ruminally in continuous flow in adult goats subjected to water and food restriction. Six adult non-pregnant and non-lactating female goats, aged between two and five years old, were used in a crossover (6 × 2) study. Solution 1 (SEE1) comprised: 4.5 g sodium chloride (NaCl); 1 g potassium chloride (KCl); 0.5 g magnesium chloride (MgCl); 1 g calcium chloride in 1,000 ml of water (measured osmolarity: 202 mOsm/l). Solution 2 (SEE2) comprised: 4.5 g of NaCl; 1 g of KCl; 0.5 g of MgCl; 2 g of calcium acetate in 1,000 ml of water (measured osmolarity: 212 mOsm/l). The solutions were administered naso-ruminally at a dose rate of 15 ml/kg/hr, for 12 hr. The animals were evaluated at times T-24, T0, T4, T8, T12, and T24. Both enteral electrolytic solutions were effective in expanding blood volume. SEE1 showed a low-intensity acidifying potential, while SEE2 showed behavior of a neutral enteral electrolytic solution.


Cardiac hydatid disease: report of two cases.
Cardiac involvement in hydatid disease is rare, occurring in less than 2% of cases of hydatid infection. It can occur as part of a widespread systemic infection or as an isolated event. It may be asymptomatic for a long period before presenting with a myriad of non-specific symptoms. Imaging plays an important role in the diagnosis, surgical planning and follow up of cases. Current treatment involves attempted surgical resection (cystopericystectomy) with long-term follow-up chemotherapy (Albendazole). Both the disease and its surgical treatment carry a high complication rate, including rupture leading to anaphylaxis and death.


Core knowledge.
Compex cognitive skills such as reading and calculation and complex cognitive achievements such as formal science and mathematics may depend on a set of building block systems that emerge early in human ontogeny and phylogeny. These core knowledge systems show characteristic limits of domain and task specificity: Each serves to represent a particular class of entities for a particular set of purposes. By combining representations from these systems, however, human cognition may achieve extraordinary flexibility. Studies of cognition in human infants and in nonhuman primates therefore may contribute to understanding unique features of human knowledge.


Sexually dimorphic expression of pituitary growth hormone-releasing factor receptor in the rat.
Secretion of growth hormone (GH) exhibits marked sexual dimorphism in the rat. To examine the underlying mechanism that involves hypothalamic GH-releasing factor (GRF), we determined pituitary GRF receptor mRNA levels in male and female rats and compared their in vitro abilities to release GRF, an endogenous ligand for GRF receptor. Female rats expressed GRF receptor mRNA at a level of only 15% (P < 0.001) of that of male rats. Female rats also showed a 33% lower (P < 0.01) ability to release GRF than male rats. These results indicate that the GRF secretion and action system of female rats is characterized by the combined reduction in GRF receptor expression and GRF-releasing capacity compared with that of male rats. This could explain the in vivo finding that spontaneous, GRF-triggered GH pulses are of much lower amplitude in the female than in the male rat.


Characteristics of three-dimensional prospectively isolated mouse bone marrow mesenchymal stem/stromal cell aggregates on nanoculture plates.
Three-dimensional (3-D) aggregate culturing is useful for investigating the functional properties of mesenchymal stem/stromal cells (MSCs). For 3-D MSC analysis, however, pre-expansion of MSCs with two-dimensional (2-D) monolayer culturing must first be performed, which might abolish their endogenous properties. To avoid the need for 2-D expansion, we used prospectively isolated mouse bone marrow (BM)-MSCs and examined the differences in the biological properties of 2-D and 3-D MSC cultures. The BM-MSCs self-assembled into aggregates on nanoculture plates (NCP) that have nanoimprinted patterns with a low-cellular binding texture. The 3-D MSCs proliferated at the same rate as 2-D-cultured cells by only diffusion culture and secreted higher levels of pro-angiogenic factors such as vascular endothelial growth factor and hepatocyte growth factor (HGF). Conditioned medium from 3-D MSC cultures promoted more capillary formation than that of 2-D MSCs in an in vitro tube formation assay. Matrigel-implanted 3-D MSC aggregates tended to induce angiogenesis in host mice. The 3-D culturing on NCP induced alpha-fetoprotein (AFP) expression in MSCs without the application of AFP- or endodermal-inducible factors, possibly via an HGF-autocrine mechanism, and maintained their differentiation ability for adipocytes, osteocytes, and chondrocytes. Prospectively isolated mouse BM-MSCs expressed low/negative stemness-related genes including Oct3/4, Nanog, and Sox2, which were not enhanced by NCP-based 3-D culturing, suggesting that some of these cells differentiate into meso-endodermal layer cells. Culturing of prospectively isolated MSCs on NCP in 3-D allows the analysis of the biological properties of more closely endogenous BM-MSCs and might contribute to tissue engineering and repair.


Serum alpha-fetoprotein: II. Clinical evaluation of two automated immunoassays for maternal serum screening.
A prospective clinical evaluation is reported for analysis of maternal serum alpha fetoprotein (s.AFP) testing by recently developed enzymeimmunoassay automated systems. The reference method for the study was a manual competitive binding radioimmunoassay which has been utilized by us in the Maternal Serum AFP Screening Program at the Medical University of South Carolina for the past five years. The patients were classified by weeks of gestation, 16 to 20. Mean concentrations of s.AFP increased with the increase in gestational week for each method; calculated multiples of median (MoM) values remained relatively constant regardless of the week of gestation. Mean and median concentrations of s.AFP measured by the radioimmunoassay and the coated tube enzymeimmunoassay methods showed close agreement, indicating the direct transferability of the methods for clinical purposes. The microparticle capture enzymeimmunoassay yielded higher results of s.AFP indicating the necessity for a correction if the method transfer is to be considered for sequential patient testing. (Multiples of median values for each method were uncorrected for maternal age, weight, or diabetes mellitus; lack of correction would not affect comparison of methods for clinical application.


Human cervical ripening is associated with an increase in cervical inducible nitric oxide synthase expression.
The mechanisms that ultimately regulate cervical ripening during parturition remain largely unknown. A possible role for nitric oxide (NO) has recently emerged; however, the expression of NO synthase (NOS) within the human cervix in the ripening process has not been investigated. The purpose of this study was to identify cell types in the human cervix that contain NOS isoforms and to examine changes in their expression during the ripening process and the nonpregnant state. Inducible NOS (iNOS) immunoreactivity was observed in the epithelial cells and stromal spindle cells in 17 of 20 biopsies from cervices obtained within 10 min postpartum, but in only 4 of 12 nonpregnant controls (p = 0.03). Endothelial NOS (eNOS) immunoreactivity was restricted to vascular endothelia in all sections, whereas neuronal NOS was not detectable. Inducible NOS activity in the postpartum group was 3.2 times that of the control group (p = 0.0005), whereas constitutive NOS activity remained unchanged in both groups (p = 0.222). Competitive reverse transcription-polymerase chain reaction revealed no differences in the expression of iNOS (p = 0.443) or eNOS mRNA (p = 0.409). The existence of iNOS in the human postpartum cervix suggests that increased production of NO, probably induced by cytokines, may be relevant to the process of natural cervical ripening in humans.


Antibody-induced modulation of H-2Kb antigens on mouse tumor cells in vitro.
Modulation of H-2Kb antigens on cells of a subline of the murine Lewis lung carcinoma was induced in vitro by a monoclonal antibody with specificity for H-2Kb antigens. High antibody concentrations resulted in a more spherical morphology of the cells, in a discrete loss of all antibody-antigen complexes within 4-6 hr, and in a corresponding maximal decrease in the total cellular antigen content 6-8 hr after antibody exposure. Restoration was complete within 2 hr after removal of the complexed antigen and occurred without any visible cap formation.


Why study plasticity in multiple traits? New hypotheses for how phenotypically plastic traits interact during development and selection.
Organisms can often respond adaptively to a change in their environment through phenotypic plasticity in multiple traits, a phenomenon termed as multivariate plasticity. These different plastic responses could interact and affect each other's development as well as selection on each other, but the causes and consequences of these interactions have received relatively little attention. Here, we propose a new conceptual framework for understanding how different plastic responses can affect each other's development and why organisms should have multiple plastic responses. A plastic change in one trait could alter the phenotype of a second plastic trait by changing either the cue received by the organism (cue-mediated effect) or the response to that cue (response-mediated effect). Multivariate plasticity could benefit the organism either because the plastic responses work better when expressed together (synergy) or because each response is more effective under different environmental circumstances (complementarity). We illustrate these hypotheses with case studies, focusing on interactions between behavior and morphology, plastic traits that differ in their reversibility. Future empirical and theoretical research should investigate the consequences of these interactions for additional factors important for the evolution of plasticity, such as the limits and costs of plasticity.


[Pyelo-ureteric amyloidosis].
The authors report a case of urinary tract amyloidosis in a 55-year-old woman with no particular medical history. In the light of this original case, the authors present a review of the pathophysiology, diagnosis, histology and treatment of this disease. A review of the literature confirms the rarity of this entity and its variable clinical expression. An aetiological work-up must always be performed, as amyloidosis can be the complication of numerous diseases.


FIAT control of osteoblast activity.
The basic domain-leucine zipper transcription factor activating transcription factor 4 (ATF4) regulates most functions of the osteoblast. It is therefore not surprising that its activity should be regulated through several mechanisms. Factor inhibiting ATF4-mediated transcription (FIAT) is a leucine zipper nuclear molecule lacking a basic domain for DNA binding that interacts with ATF4 to repress its transcriptional activity. FIAT expression was monitored in parallel with ATF4 during osteoblastogenesis. The mechanism of ATF4 repression by FIAT was investigated through structure-function analysis. The physiological significance of FIAT expression in osteoblasts was studied through silencing FIAT in osteoblasts by RNA interference, as well as through characterization of two genetic mouse models: FIAT transgenic mice which overexpress FIAT in osteoblasts, and FIAT knockout mice. Studies to date show that FIAT and ATF4 are co-expressed in osteoblasts, and that FIAT inhibition of matrix mineralization requires dimerization with ATF4 through the second leucine zipper. Furthermore, transgenic mice overexpressing FIAT exhibit osteopenia. The phenotype of FIAT knockout mice is still under evaluation but the salient aspects are discussed here. Taken together, the results accumulated to date support the hypothesis that FIAT is a transcriptional repressor that modulates osteoblast function.


A literature review of adolescence and cancer.
Cancer is a relatively rare phenomenon in adolescents and a traumatic experience which arouses feelings of anger, anxiety, fear and sadness. For the adolescent with cancer, there are missed opportunities, not only in daily life but also through lost social events such as dances or football games with friends. Adolescent cancer patients may understand the implications of the diagnosis of cancer but lack the personal resources or life event experience which could equip them to cope and make sense of the many potential problems which may accompany cancer. This paper reviews and explores the literature associated with the adolescent with cancer.


Altered Development of Mesencephalic Dopaminergic Neurons in SIDS: New Insights into Understanding Sudden Infant Death Pathogenesis.
Sudden infant death syndrome (SIDS) is defined as the unexpected sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation. The SIDS pathogenesis is still unknown; however, abnormalities in brain centers that control breathing and arousal from sleep, including dramatic changes in neurotransmitter levels, have been supposed in these deaths. This is the first study focusing on mesencephalic dopaminergic neurons, so far extensively studied only in animals and human neurological diseases, in SIDS. Dopaminergic structures in midbrain sections of a large series of sudden infant deaths (36 SIDS and 26 controls) were identified using polyclonal rabbit antibodies against tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, and the dopamine transporter, a membrane protein specifically expressed in dopaminergic cells. Dopamine-immunolabeled neurons were observed concentrated in two specific structures: the pars compacta of the substantia nigra and in the subnucleus medialis of the periaqueductal gray matter. Anatomical and functional degenerations of dopaminergic neurons in these regions were observed in most SIDS cases but never in controls. These results indicate that dopamine depletion, which is already known to be linked especially to Parkinson's disease, is strongly involved even in SIDS pathogenesis.


Effects of dibutyryl adenosine 3',5'-monophosphate, angiotensin II, and atrial natriuretic factor on phosphorylation of a 17,600-dalton protein in adrenal glomerulosa cells.
Rat adrenal glomerulosa cells were incubated with [32P]phosphate and (Bu)2AMP (dbcAMP), angiotensin II, and atrial natriuretic factor (ANF). Incorporation of [32P]phosphate into cellular proteins was analyzed by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. dbAMP stimulated phosphorylation of a 17.6K protein, while angiotensin II did not stimulate it. ANF did not affect the protein phosphorylation, whether the cells were in the basal state or stimulated by dbcAMP or angiotensin II. On the other hand, ANF markedly inhibited angiotensin II-stimulated aldosterone production, but only slightly inhibited dbcAMP-stimulated aldosterone. These results suggest that in rat adrenal glomerulosa cells phosphorylation of the 17.6K protein may have a relationship with the stimulatory effect of cAMP on aldosterone production; however, neither angiotensin II nor ANF affected the phosphorylation of this protein, and phosphorylation of the 17.6K protein is not an obligatory step in the regulation of aldosterone production.


The utility of human epididymal protein 4, cancer antigen 125, and risk for malignancy algorithm in ovarian cancer and endometriosis.
In women with pelvic mass, cancer antigen 125 (CA125) had not achieved satisfactory sensitivity and specificity in the detection of ovarian cancer, particularly in patients with underlying endometriosis. The aim of this study was to determine the diagnostic potential of human epididymal protein 4 (HE4), the combination of HE4+CA125, and the Risk of Ovarian Malignancy Algorithm (ROMA) for patients with pelvic mass, particularly in differentiating endometriosis from carcinoma. A prospective cross-sectional study was conducted at the Clinic for Gynecology and Obstetrics, Clinical Center of Serbia. Serum samples were obtained preoperatively from 108 women undergoing surgery for pelvic mass; 29 of them had ovarian carcinoma, and 79 had a nonmalignant ovarian disease (39 with benign tumor, 20 with endometriosis, 20 healthy controls). Sera were analyzed for the levels of HE4 and CA125 and were then compared with the final pathologic results. The diagnostic performance of HE4 and CA125 was estimated using receiver operating characteristic curve and area under the receiver operating characteristic curve. The level of HE4 and CA125 was significantly higher among the patients with malignant tumors, compared with patients with nonmalignant disease. At the predefined specificity of 95%, HE4 and CA125 showed sensitivity of 65.5% and 58.6%, respectively, whereas the combination of HE4+CA125 reached 68.9% at the same specificity. Importantly, the level of HE4 did not differ significantly between the patients with endometriosis and with other nonmalignant diseases (which was not the case with CA125). Risk of Ovarian Malignancy Algorithm classified 96% of benign premenopausal cases as at low risk for ovarian cancer. HE4 showed satisfactory capability of distinguishing endometriosis from ovarian cancer, which CA125 lacked. The Risk of Ovarian Malignancy Algorithm score proved to be useful in excluding malignant diagnosis in premenopausal women.


Diacerhein improves glucose tolerance and insulin sensitivity in mice on a high-fat diet.
Obesity and type 2 diabetes are characterized by insulin resistance, and the common basis of these events is a chronic and systemic inflammatory process marked by the activation of the c-Jun N-terminal kinase (JNK) and inhibitor-κB kinase (IKKβ)/nuclear factor-κB (NFκB) pathways, up-regulated cytokine synthesis, and endoplasmic reticulum dysfunction. The aim of this study was to evaluate the effects of diacerhein administration, an antiinflammatory drug that reduces the levels of inflammatory cytokines, on insulin sensitivity and signaling in diet-induced obese (DIO) mice. Swiss mice were fed with conventional chow (control group) or a high-fat diet (DIO group). Later, DIO mice were randomly subdivided into a new subgroup (DAR) that received 20 mg/kg diacerhein for 10 d. Western blotting was used to quantify the expression and phosphorylation of insulin receptor, insulin receptor substrate 1, and Akt and of inflammatory mediators that modulate insulin signaling in a negative manner (IKKβ, JNK, and inducible nitric oxide synthase). We show here, for the first time, that the administration of diacerhein in DIO mice improved endoplasmic reticulum stress, reduced JNK and IKKβ phosphorylation, and resulted in a marked improvement in fasting glucose, a decrease in macrophage infiltration in adipose tissue, and a reduced expression and activity of proinflammatory mediators accompanied by an improvement in the insulin signaling mainly in the liver and adipose tissue. Taken together, these results indicate that diacerhein treatment improves insulin sensitivity in obesity, mediated by the reversal of subclinical inflammation, and that this drug may be an alternative therapy for insulin resistance.


Characterization and functional analysis of a novel C1q-domain-containing protein in Japanese flounder (Paralichthys olivaceus).
The complement system is important in the innate immune response. C1q-domain-containing proteins have multiple functions and occur extensively in invertebrates and vertebrates. In this study, PoC1ql3 encoding a C1q-domain-containing protein in the Japanese flounder was identified. The 266-amino-acid polypeptide encoded, PoC1ql3, shares high sequence and structural similarity with orthologues in other fish and mammals. PoC1ql3 is abundantly expressed in the brain, but less in the blood, gills, and liver. Transcripts of PoC1ql3 were down-regulated in the spleen and liver 6-24 h after bacterial infection, but were significantly up-regulated after 48 h. Full-length PoC1ql3 (C1ql3-full) and its gC1q domain (C1ql3-part) were both exerted anti-Edwardsiella tarda activity. C1ql3-part bound to lipopolysaccharide and peptidoglycan, and exerted antibacterial effects against E. tarda in vivo, suggesting that C1ql3 functions as a pathogen-recognition receptor. Therefore, PoC1ql3 functions in the innate immune system, which would facilitate the investigation of the immune system in Japanese flounder.