Cyclosporin is safe and effective in severe atopic dermatitis of childhood. Report of three cases.
Severe atopic dermatitis causes major impairment in the life of both children and their parents. Generally, symptoms can be controlled with emollients, topical steroids, antibiotics, antihistaminic but some patients remain intensely ill and may require treatment with systemic steroids and so on. Cyclosporin has been found to be effective in a variety of inflammatory skin disorders since it reduces the number of activated T-cells expressing interleukin 2 (IL-2) receptors. In order to monitor the safety and clinical efficacy of therapy and days of remission we performed Cyclosporin on 3 children with severe atopic dermatitis, refractory to all traditional therapies. Cyclosporin suspension at dosage of 5 mg/kg daily, in 2 doses for 8 weeks has been used. Cyclosporin blood levels, liver and kidney function, blood pressure and some immunological parameters (eosinophils, IgE, IL-2 receptors) were monitored. All patients showed a marked clinical improvement with reduction of pruritus, erythema, papules, vesciculation, excoriation, scaly crusts and lichenification. No clinical or haematological side effects were demonstrated. The soluble IL-2 receptor concentration decreased even after 8 weeks of treatment in all 3 patients, regardless of IgE levels (case 1: low IgE level; case 2: very high IgE level) as in several others T-cell mediated non IgE-related skin disease. The authors suggest that courses of 8 weeks seem effective and safe as well as longer time in producing early remission with the advantage of a low cumulative exposure to the drug. The main question is whether a prolonged remission will permain as well as continuous therapy. This study underscores the potential value of systemic administration of this powerful immuno-suppressive agent in the treatment of many cases of severe atopic dermatitis working regardless of the IgE values. Although 3 cases report does not justify any definitive conclusion however it does a contribute to understand the heterogeneity of atopic dermatitis and it adds information to its current treatment guidelines.


Fluid mechanics aspects of magnetic drug targeting.
Experiments and numerical simulations using a flow phantom for magnetic drug targeting have been undertaken. The flow phantom is a half y-branched tube configuration where the main tube represents an artery from which a tumour-supplying artery, which is simulated by the side branch of the flow phantom, branches off. In the experiments a quantification of the amount of magnetic particles targeted towards the branch by a magnetic field applied via a permanent magnet is achieved by impedance measurement using sensor coils. Measuring the targeting efficiency, i.e. the relative amount of particles targeted to the side branch, for different field configurations one obtains targeting maps which combine the targeting efficiency with the magnetic force densities in characteristic points in the flow phantom. It could be shown that targeting efficiency depends strongly on the magnetic field configuration. A corresponding numerical model has been set up, which allows the simulation of targeting efficiency for variable field configuration. With this simulation good agreement of targeting efficiency with experimental data has been found. Thus, the basis has been laid for future calculations of optimal field configurations in clinical applications of magnetic drug targeting. Moreover, the numerical model allows the variation of additional parameters of the drug targeting process and thus an estimation of the influence, e.g. of the fluid properties on the targeting efficiency. Corresponding calculations have shown that the non-Newtonian behaviour of the fluid will significantly influence the targeting process, an aspect which has to be taken into account, especially recalling the fact that the viscosity of magnetic suspensions depends strongly on the magnetic field strength and the mechanical load.


Effect of acetyl-L-carnitine treatment on the density of muscarinic receptors in the brain of methylazoxymethanol-microencephalic rats.
The effect of methylazoxymethanol (MAM), administered on the 15th gestational day, on the density and pattern of muscarinic cholinergic receptors in some brain areas was assessed using combined radioreceptor binding and autoradiographic techniques. The effect of 15 days' treatment with acetyl-L-carnitine on the same parameter was also assessed. The density of muscarinic cholinergic receptors was found to be increased in the brain of MAM-microencephalic rats. Acetyl-L-carnitine administration caused a significant reduction in the density of receptors under study. A possible role of acetyl-L-carnitine in restoring central cholinergic neurotransmission is discussed.


Transilluminated powered phlebectomy: a clinical report.
Twenty-one patients with varicose vein incompetence of the legs have been treated with the TriVex system (Smith & Nephew, Andover, MA, USA). The technique is designed for treatment of local varicosities to provide a good cosmetic result (remaining varicosities and pigmentation) and less morbidity (pain and loss of work days). These parameters showed good results with few remaining varicosities and pigmentations. Reasonable number of days out of work and moderate pain. Eighteen of the 21 patients had an overall good outcome with no complaints.


Critical role of c-jun (NH2) terminal kinase in paracetamol- induced acute liver failure.
Acute hepatic failure secondary to paracetamol poisoning is associated with high mortality. C-jun (NH2) terminal kinase (JNK) is a member of the mitogen-activated protein kinase family and is a key intracellular signalling molecule involved in controlling the fate of cells. To examine the role of JNK in paracetamol-induced acute liver failure (ALF). A previously developed mouse model of paracetamol poisoning was used to examine the role of JNK in paracetamol-induced ALF. Paracetamol-induced hepatic JNK activation both in human and murine paracetamol hepatotoxicity and in our murine model preceded the onset of hepatocyte death. JNK inhibition in vivo (using two JNK inhibitors with different mechanisms of action) markedly reduced mortality in murine paracetamol hepatotoxicity, with a significant reduction in hepatic necrosis and apoptosis. In addition, delayed administration of the JNK inhibitor was more effective than N-acetylcysteine after paracetamol poisoning in mice. JNK inhibition was not protective in acute carbon tetrachloride-mediated or anti-Fas antibody-mediated hepatic injury, suggesting specificity for the role of JNK in paracetamol hepatotoxicity. Furthermore, disruption of the JNK1 or JNK2 genes did not protect against paracetamol-induced hepatic damage. Pharmacological JNK inhibition had no effect on paracetamol metabolism, but markedly inhibited hepatic tumour necrosis foctor alpha (TNF alpha) production after paracetamol poisoning. These data demonstrated a central role for JNK in the pathogenesis of paracetamol-induced liver failure, thereby identifying JNK as an important therapeutic target in the treatment of paracetamol hepatotoxicity.


Nosocomial Mycobacterium tuberculosis transmission among healthcare students in a high incidence region, in Vitória, State of Espírito Santo.
This open comparative study for evaluating hypersensitivity to tuberculin among medical students (n=441), nursing students (n=178) and economics students (n=230) in Vitória, State of Espírito Santo, had the aim of assessing whether the prevalence of positive tuberculin tests among healthcare students could be used as a sentinel event for nosocomial transmission in localities with high endemicity. There was a significant change in the frequency of purified protein derivative reactivity in the nursing students (20.3%) and medical students (18.4%), in comparison with the economics students (6%) (p <0.001). As expected, the medical and nursing students had more knowledge about tuberculosis than did the economics students (p <0.001). Our data suggest that the incidence of Mycobacterium tuberculosis infection among nursing and medical students in our region, which has high endemicity of tuberculosis, does not differ from what is found in low-incidence countries. These data reinforce the need for implementing biosafety programs for this target population.


HIF1α/VEGF Feedback Loop Contributes to 5-Fluorouracil Resistance.
5-Fluorouracil (5-Fu) is one of the basic drugs in colorectal cancer (CRC) chemotherapy, and its efficacy is mainly limited by the acquisition of drug resistance. However, the underlying mechanisms remain unclear. In this study, hypoxia inducible factor 1α (HIF1α) was screened for high expression in 5-Fu resistant HCT115 cells, which displayed epithelial-mesenchymal transition (EMT) phenotype. Suppression of HIF1α reversed EMT phenotype, reduced glucose transporter 1 (Glut1) expression, a key molecule mediated drug resistance. Moreover, we unveiled that vascular endothelial growth factor (VEGF) was regulated by HIF1α and mediated HIF1α-maintained malignant phenotype of 5-Fu resistant cells. Further studies verified that AKT/GSK3β signaling was activated in resistant cells and controlled HIF1α expression. Interestingly, we demonstrated that VEGF could feedback up-regulate HIF1α via AKT/GSK3β signaling. Clinically, HIF1α and VEGF were high expressed and associated with survival and prognosis in CRC patients. In conclusion, our findings proposed that HIF1α/VEGF feedback loop contributed to 5-Fu resistance, which might be potential therapeutic targets.


Vancomycin administration in continuous ambulatory peritoneal dialysis: the risk of ototoxicity.
A prospective study was undertaken in 16 patients with chronic renal failure on continuous ambulatory peritoneal dialysis, with 22 episodes of peritonitis treated with vancomycin, a known ototoxic agent. Twelve patients had one episode each, and four had recurrent peritonitis. Each treatment course consisted of two infusions of vancomycin (30 mg/kg body weight) in 2 L of peritoneal dialysate administered at 6-day intervals. Serum vancomycin analyzed by enzyme immunoassay showed a mean trough level of 11.00 microg/ml on day 6 and mean serum levels of 33.8 and 38.6 microg/ml about 12 hours after administration on days 1 and 7, respectively. Similar levels, well within the therapeutic range, were encountered with repeated vancomycin therapy for recurrent episodes of peritonitis, suggesting that no changes occurred in the pharmacokinetic profile of the drug. Pure-tone audiometry, electronystagmography, and clinical assessment performed during each course of treatment showed no evidence of ototoxicity even on repeated courses of vancomycin therapy. The results suggest that vancomycin therapy when given in appropriate concentrations as a single therapeutic agent is both effective and safe. We believe, however, that vancomycin administered in combination with an aminoglycoside may produce ototoxic effects that may be greatly aggravated, possibly because of synergism.


Oleoylethanolamide Alleviates Hepatic Ischemia-Reperfusion Injury via Inhibiting Endoplasmic Reticulum Stress-Associated Apoptosis.
Liver ischemia/reperfusion (I/R) injury is a primary complication in major liver surgery. Our previous study about proteome profiling has revealed that the PPAR signaling cascade was significantly upregulated during liver ischemia/reperfusion. To elucidate the potential mechanisms of PPARα involved in I/R injury, we used oleoylethanolamide (OEA), the peroxisome proliferator-activated receptor alpha (PPARα) agonist, in this study. We demonstrated a protective role of OEA on liver I/R injury by using a mouse model of partial warm ischemia-reperfusion and hypoxia-reoxygenation model of hepatocytes. These effects were caused by ameliorating liver damage, decreasing the level of serum ALT and AST, and reducing the apoptosis of hepatocytes. Furthermore, a mechanistic study revealed that OEA regulated endoplasmic reticulum (ER) stress by activating PPARα, thereby reducing ER stress-associated apoptosis to attenuate liver I/R injury. Briefly, these data first proposed that OEA-mediated PPARα activation could be an effective therapy against hepatic ischemia/reperfusion injury.


Role of alpha smooth muscle actin in odontogenic differentiation of dental pulp stem cells.
Pulpotomy is an effective treatment for retaining vital pulp after pulp exposure caused by caries removal and/or trauma. The expression of alpha smooth muscle actin (α-SMA) is increased during the wound-healing process, and α-SMA-positive fibroblasts accelerate tissue repair. However, it remains largely unknown whether α-SMA-positive fibroblasts influence pulpal repair. In this study, we established an experimental rat pulpotomy model and found that the expression of α-SMA was increased in dental pulp after pulpotomy relative to that in normal dental pulp. In vitro results showed that the expression of α-SMA was increased during the induction of odontogenic differentiation in dental pulp stem cells (DPSCs) compared with untreated DPSCs. Moreover, α-SMA overexpression promoted the odontogenic differentiation of DPSCs via increasing mitochondrial function. Mechanistically, α-SMA overexpression activated the mammalian target of rapamycin (mTOR) signaling pathway. Inhibition of the mTOR signaling pathway by rapamycin decreased the mitochondrial function in α-SMA-overexpressing DPSCs and suppressed the odontogenic differentiation of DPSCs. Furthermore, we found that α-SMA overexpression increased the secretion of transforming growth factor beta-1 (TGF-β1). In sum, our present study demonstrates a novel mechanism by which α-SMA promotes odontogenic differentiation of DPSCs by increasing mitochondrial respiratory activity via the mTOR signaling pathway.


Urinary Retention in Surgical Patients.
Urinary retention is an important and potentially avoidable postoperative complication. Identifying risk factors for retention is important given expedient bladder decompression is important for long-term outcomes. Age, benign prostatic hyperplasia, and lower urinary tract symptoms are patient factors that predispose to retention. Surgery-related factors include operative time, intravenous fluid administration, type of anesthesia, and procedure type. The mainstay for treatment in the acute setting is Foley catheter placement. Starting alpha-blockers in men is also indicated as they increase voiding trial success. Long-term solutions for chronic retention include a variety of surgeries, with transurethral prostatectomy as the gold standard.


The Political Constitution of the United States of Mexico (CPEUM) dates from February 5, 1917. It recognizes that all people will enjoy the guarantees granted by the Constitution, which may not be restricted or suspended, except in some cases and under the conditions that it herself establishes.On the centenary of the promulgation of its Magna Carta, Mexico is experiencing a deep economic, political, social and governmental crisis, and the consequent loss of access to fundamental human rights to survive.Among the effects of this situation, 44 million people are in the age of preparing to enter the labor market and sustain the Mexican economy for the next four decades. However, their economic situation prevents them from having the resources required to access adequate food, pay educational expenses and enter the labor market.This reality makes it essential to explore the possible causes that have originated these circumstances and propose viable alternatives that alleviate – in the medium term – the immense deficiencies of the Mexicans and recover the hope that there will be possibilities of a lasting life.


Vital and Clinical Signs Gathered Within the First Minutes After a Motorcycle Accident on a Racetrack: an Observational Study.
Little is known about vital signs during the very first minutes after an accident. This study aimed to describe the vital signs of motorcycle riders shortly after racetrack crashes and examine the clinical value of these data for the prehospital clinical assessments. A retrospective observational cohort based on data from medical records on 104 motorcycle accidents at a racetrack in Sweden, covering the season of 2019 (May 01 until September 17), was conducted. Both race and practice runs were included. In addition, data from the Swedish Trauma Registry were used for patients referred to the hospital. Kruskal-Wallis test and linear regression were calculated in addition to descriptive statistics. In all, 30 riders (29%) were considered injured. Sixteen riders (15%) were referred to the hospital, and of these, five patients (5% of all riders) had suffered serious injuries. Aside from a decreased level of consciousness, no single vital sign or kinematic component observed within the early minutes after a crash was a strong clinical indicator of the occurrence of injuries. However, weak links were found between highsider or collision crashes and the occurrence of injuries. Except for a decreased level of consciousness, this study indicates that the clinical value of early measured vital signs might be limited for the pre-hospital clinical assessment in the motorsport environment. Also, an adjustment of general trauma triage protocols might be considered for settings such as racetracks. Using the context with medical professionals at the victim's side within a few minutes after an accident, that is common in motorsport, offers unique possibilities to increase our understanding of clinical signs and trauma in the early state after an accident.


Cefepime Therapy for Monomicrobial Enterobacter cloacae Bacteremia: Unfavorable Outcomes in Patients Infected by Cefepime-Susceptible Dose-Dependent Isolates.
A new category of cefepime susceptibility, susceptible dose dependent (SDD), for Enterobacteriaceae, has been suggested to maximize its clinical use. However, clinical evidence supporting such a therapeutic strategy is limited. A retrospective study of 305 adults with monomicrobial Enterobacter cloacae bacteremia at a medical center from 2008 to 2012 was conducted. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) to assess therapeutic effectiveness. The 30-day crude mortality rate is the primary endpoint, and clinical prognostic factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem therapy, there were no significant differences in terms of age, sex, comorbidity, source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%; P = 0.7) among those treated with cefepime (n = 72) or a carbapenem (n = 72). In the multivariate analysis, the presence of critical illness, rapidly fatal underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and cefepime-SDD (cefepime MIC, 4 to 8 μg/ml) isolates was independently associated with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with definitive cefepime therapy had a higher mortality rate than those treated with a carbapenem (5/7 [71.4%], versus 2/11 [18.2%]; P = 0.045). Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy.


[Influence of Type D Personality on Adherence to Treatment in Cardiac Patients].
of the study was to examine relationship between behavioral type D and adherence to therapy in cardiological patients. Patients (n=308, 63 [20.5%] women and 245 [79.5%] men, mean age 59+/-4 years) with stable ischemic heart disease and arterial hypertension were divided into 2 groups: with (n=84) and without (n=224) type D. Psychological status was assessed using type D scale-14 (DS-14) questionnaire, adherence to treatment - with the help of S.V. Davydov method and the Morisky-Green test. Patients with compared with those without type D personality more often had indicators of lower adherence to treatment (48 vs 39%, <0.05). Indicators of higher adherence were found more often in the group without type D personality (11 vs 19%, p<0.003). Indicators of lower compliance were independently associated with type D personality (odds ratio 3.21, p=0.02). Patients with type D personality have lower adherence to therapy. This can be a link between type D behavior and unfavorable prognosis in patients with cardiovascular diseases.


Potential Involvement of Calcineurin in Regulating the State of Differentiation and Apoptosis of HL-60 Cells During Methylprednisolone-Treatment.
To evaluate the role of calcineurin (protein phosphatase type 2B, PP2B) in methylprednisolone-induced differentiation and apoptosis of leukaemic cells, we have investigated the induction of apoptosis, calcineurin specific protein phosphatase activity and expression of regulatory and catalytic subunits of calcineurin and calmodulin after induction of HL-60 leukaemic cells with methylprednisolone. The cells underwent differentiation and apoptosis within 72 hours time period after methylprednisolone added to cell culture media. Before apoptosis occurred, the specific calcineurin enzyme activity revealed gradual increase during the differentiation process. However, immunoblots of catalytic and regulatory subunits of calcineurin showed no amplification in the amount of these cellular signaling mediators during methylprednisolone-induced differentiation and apoptosis but calmodulin expression gradually increased during the process. Significant increase in the specific calcineurin enzyme activity during differentiation and apoptosis might be crucial to the posttranslational modifications of calcineurin during methylprednisolone-induced differentiation.


Robotic Surgery: A Narrative Review.
In general surgery, the use of robotic and laparoscopic methods has increased. Robotic surgery that requires the least incision has advanced over the years in a short period of time, benefitting both the patient and the surgeon. According to this, robotic platforms and tools are now being used and improved more commonly in general surgery. In a quickly growing and dynamic environment of research and development, the goal of this review is to explore the present and emerging surgical robotic technologies. Future progress in robotics will focus primarily on more durable haptic systems that would provide tactile and kinesthetic input, miniaturisation and micro-robotics, better visual feedback with higher fidelity detail and magnification, and autonomous robots. It is recommended to develop a structured training course with benchmarks for success and evidence-based training strategies. This usually includes a step-by-step progression starting with observation, case aid in programming and manipulation of surgical instruments, learning the basics of robotics in a dry and wet lab setting, attaining non-technical skills on an individual and team level, and monitored modular console training, accompanied by autonomous practice. Prior to independent practice, basic robotics skills and procedural activities must be performed safely and effectively as part of robotic surgical training. It is advised to create a systematic training programme with performance indicators and research-based instructional techniques.


Rice ethylene-response AP2/ERF factor OsEATB restricts internode elongation by down-regulating a gibberellin biosynthetic gene.
Plant height is a decisive factor in plant architecture. Rice (Oryza sativa) plants have the potential for rapid internodal elongation, which determines plant height. A large body of physiological research has shown that ethylene and gibberellin are involved in this process. The APETALA2 (AP2)/Ethylene-Responsive Element Binding Factor (ERF) family of transcriptional factors is only present in the plant kingdom. This family has various developmental and physiological functions. A rice AP2/ERF gene, OsEATB (for ERF protein associated with tillering and panicle branching) was cloned from indica rice variety 9311. Bioinformatic analysis suggested that this ERF has a potential new function. Ectopic expression of OsEATB showed that the cross talk between ethylene and gibberellin, which is mediated by OsEATB, might underlie differences in rice internode elongation. Analyses of gene expression demonstrated that OsEATB restricts ethylene-induced enhancement of gibberellin responsiveness during the internode elongation process by down-regulating the gibberellin biosynthetic gene, ent-kaurene synthase A. Plant height is negatively correlated with tiller number, and higher yields are typically obtained from dwarf crops. OsEATB reduces rice plant height and panicle length at maturity, promoting the branching potential of both tillers and spikelets. These are useful traits for breeding high-yielding crops.


Dual function of active constituents from bark of Ficus racemosa L in wound healing.
Different parts including the latex of Ficus racemosa L. has been used as a medicine for wound healing in the Ayurveda and in the indigenous system of medicine in Sri Lanka. This plant has been evaluated for its wound healing potential using animal models. The aim of this study was to obtain an insight into the wound healing process and identify the potential wound healing active substance/s present in F. racemosa L. bark using scratch wound assay (SWA) as the in-vitro assay method. Stem bark extracts of F. racemosa were evaluated using scratch wound assay (SWA) on Baby Hamster Kidney (BHK 21) and Madin-Darby Canine Kidney (MDCK) cell lines and Kirby Bauer disc diffusion assay on common bacteria and fungi for cell migration enhancing ability and antimicrobial activity respectively. Dichloromethane and hexanes extracts which showed cell migration enhancement activity on SWA were subjected to bioactivity directed fractionation using column chromatography followed by preparative thin layer chromatography to identify the compounds responsible for the cell migration enhancement activity. Dichloromethane and hexanes extracts showed cell migration enhancement activity on both cell lines, while EtOAc and MeOH extracts showed antibacterial activity against Staphylococcus and Bacillus species and antifungal activity against Saccharomyces spp. and Candida albicans. Lupeol (1) and β-sitosterol (2) were isolated as the potential wound healing active compounds which exhibited significant cell migration enhancement activity on BHK 21 and MDCK cell lines (> 80%) in par with the positive control, asiaticoside at a concentration of 25 μM. The optimum concentration of each compound required for the maximum wound healing has been determined as 30 μM and 35 μM for 1 and 2 respectively on both cell lines. It is also established that lupeol acetate (3) isolated from the hexanes extract act as a pro-drug by undergoing hydrolysis into lupeol in the vicinity of cells. Different chemical constituents present in stem bark of Ficus racemosa L show enhancement of cell migration (which corresponds to the cell proliferation) as well as antimicrobial activity. This dual action of F. racemosa stem bark provides scientific support for its traditional use in wound healing.


Impact of ligand deformation on the P,T-violation effects in the YbOH molecule.
Ytterbium monohydroxide is a promising molecule in the search for new physics. It is well known that levels of opposite parity, separated by energy split, the so-called l-doublets, define the experimental electric field strength required for molecule polarization. In addition, in our previous paper [Phys. Rev. A 105, L050801 (2022)], we have shown that the value of l-doubling directly influences the sensitivity of linear triatomic molecules toward the P,T-odd effects. In our work [J. Chem. Phys. 155, 164301 (2021)], we have calculated the value of l-doubling for YbOH molecules with the approximation of fixed O-H bond length. Taking the importance of this property into account, in the present study, we consider the additional degree of freedom corresponding to ligand (OH) deformation.


Reciprocal Inuit and Western research training: facilitating research capacity and community agency in Arctic research partnerships.
Engaging community partners to work as co-researchers and research assistants for research involving Inuit communities or regions helps to ensure the equitable recognition of community and researcher priorities, mutual trust and respect, participation by local participants, inclusion of local knowledge and local uptake of research findings. However, research knowledge still in development among community members has been described as a barrier to effective Arctic community research partnerships. This paper describes two 3-day, cross-cultural research training workshops held in the Nunavut communities of Arviat and Iqaluit during Spring 2017. The purpose was to encourage reciprocity as a basis for research training that incorporates both Western and Inuit approaches and that emphasises relationship building to benefit both Inuit and non-Inuit research communities. A review of participant responses to the workshops suggests value in using an integrated Western-Inuit framework of educational objectives to guide the training. Responses suggest the workshops helped improve understanding of research practices and ethics rooted in different traditions for participants interested in assisting with or conducting research in Canada's Arctic communities.


Tumor Suppressor WWOX and p53 Alterations and Drug Resistance in Glioblastomas.
Tumor suppressor p53 are frequently mutated in glioblastomas (GBMs) and appears to contribute, in part, to resistance to temozolomide (TMZ) and therapeutic drugs. WW domain-containing oxidoreductase WWOX (FOR or WOX1) is a proapoptotic protein and is considered as a tumor suppressor. Loss of WWOX gene expression is frequently seen in malignant cancer cells due to promoter hypermethylation, genetic alterations, and translational blockade. Intriguingly, ectopic expression of wild type WWOX preferentially induces apoptosis in human glioblastoma cells harboring mutant p53. WWOX is known to physically bind and stabilize wild type p53. Here, we provide an overview for the updated knowledge in p53 and WWOX, and postulate potential scenarios that wild type and mutant p53, or isoforms, modulate the apoptotic function of WWOX. We propose that triggering WWOX activation by therapeutic drugs under p53 functional deficiency is needed to overcome TMZ resistance and induce GBM cell death.


The too-long anterior process and osteochondral lesion of the talus: Is there an anatomical predisposition? A case-control study on 135 feet.
The too-long anterior process (TLAP) increases mechanical stress on the hindfoot and could lead to osteochondral lesions of the talus (OLT) by localized hyper-pressure. The purpose of this study is to investigate an association between TLAP and OLT in children. This is a retrospective, multicenter, case-control study conducted between 2010 and 2020. The OLT group was compared to a control group (CoG). TLAP is characterized by a distance between the anteromedial process of the calcaneus and the navicular bone (CN) of< 5 mm. Forty-three feets were included in the OLT group and 92 in the CoG. The OLT group had a lower CN distance on CT than the CoG, a median of 2.8 mm versus 3.75 mm (p = 0.002); 86% of patients (37 feet/43) in the OLT group had a CN distance of< 5 mm (OR=3.0 [1.1; 9.5], p = 0.023) compared to 67% in the CoG. The OLT group had an increased risk of developing TLAP compared to the CoG. III.


Impaired effects of interleukin-1 beta on fever and thermogenesis in genetically obese rats.
Interleukin-1 beta (IL-1 beta) is an endogenous peptide which induced fever (1.8 degrees C rise in colonic temperature) when injected interacerebroventricularly (i.c.v., 80ng human recombinant IL-1 beta) into conscious lean rats. IL-1 beta also stimulated resting oxygen consumption (VO2) by 38 percent, in vitro thermogenic activity (mitochondrial GDP binding) of brown adipose tissue (BAT) by almost two-fold, and blood flow to brown fat (assessed from the distribution of radiolabelled microspheres) by nine-fold in lean animals. Genetically obese Zucker rats showed only small increases in temperature (0.5 degrees C), VO2 (15 percent) and blood flow to BAT (less than two-fold), and no change in GDP binding, but exhibited normal thermogenic responses to i.c.v. injection of corticotrophin releasing factor (GRF). The results indicate that the obese Zucker is insensitive to the central effects of interleukin; this may explain the reduced febrile responses to endotoxin which have previously been reported.


Novel Adjuvant Based on the Pore-Forming Protein Sticholysin II Encapsulated into Liposomes Effectively Enhances the Antigen-Specific CTL-Mediated Immune Response.
Vaccine strategies to enhance CD8+ CTL responses remain a current challenge because they should overcome the plasmatic and endosomal membranes for favoring exogenous Ag access to the cytosol of APCs. As a way to avoid this hurdle, sticholysin (St) II, a pore-forming protein from the Caribbean Sea anemone Stichodactyla helianthus, was encapsulated with OVA into liposomes (Lp/OVA/StII) to assess their efficacy to induce a CTL response. OVA-specific CD8+ T cells transferred to mice immunized with Lp/OVA/StII experienced a greater expansion than when the recipients were injected with the vesicles without St, mostly exhibiting a memory phenotype. Consequently, Lp/OVA/StII induced a more potent effector function, as shown by CTLs, in vivo assays. Furthermore, treatment of E.G7-OVA tumor-bearing mice with Lp/OVA/StII significantly reduced tumor growth being more noticeable in the preventive assay. The contribution of CD4+ and CD8+ T cells to CTL and antitumor activity, respectively, was elucidated. Interestingly, the irreversibly inactive variant of the StI mutant StI W111C, encapsulated with OVA into Lp, elicited a similar OVA-specific CTL response to that observed with Lp/OVA/StII or vesicles encapsulating recombinant StI or the reversibly inactive StI W111C dimer. These findings suggest the relative independence between StII pore-forming activity and its immunomodulatory properties. In addition, StII-induced in vitro maturation of dendritic cells might be supporting these properties. These results are the first evidence, to our knowledge, that StII, a pore-forming protein from a marine eukaryotic organism, encapsulated into Lp functions as an adjuvant to induce a robust specific CTL response.


An expanded set of amino acid analogs for the ribosomal translation of unnatural peptides.
The application of in vitro translation to the synthesis of unnatural peptides may allow the production of extremely large libraries of highly modified peptides, which are a potential source of lead compounds in the search for new pharmaceutical agents. The specificity of the translation apparatus, however, limits the diversity of unnatural amino acids that can be incorporated into peptides by ribosomal translation. We have previously shown that over 90 unnatural amino acids can be enzymatically loaded onto tRNA. We have now used a competition assay to assess the efficiency of tRNA-aminoacylation of these analogs. We have also used a series of peptide translation assays to measure the efficiency with which these analogs are incorporated into peptides. The translation apparatus tolerates most side chain derivatives, a few alpha,alpha disubstituted, N-methyl and alpha-hydroxy derivatives, but no beta-amino acids. We show that over 50 unnatural amino acids can be incorporated into peptides by ribosomal translation. Using a set of analogs that are efficiently charged and translated we were able to prepare individual peptides containing up to 13 different unnatural amino acids. Our results demonstrate that a diverse array of unnatural building blocks can be translationally incorporated into peptides. These building blocks provide new opportunities for in vitro selections with highly modified drug-like peptides.


Methanol causes posteriorization of cervical vertebrae in mice.
Inhalation of methanol by pregnant mice before gestation day nine (gd 9) produces fetal skeletal alterations, principally in the cervical region. The appearance of these defects suggests homeotic shifts in segment identity, patterning, or both. To explore this possibility, detailed morphological analyses of the effects of methanol on fetal skeletal development were done. Pregnant mice were gavaged with 0, 4.0, or 5.0 g/kg methanol (MeOH) split in two doses on gd 7, the most sensitive day for induction of skeletal alterations with methanol. Dams were killed on gd 18 and the fetuses were counted, weighed, and examined externally. Fetuses were double stained with alcian blue and alizarin red for examination of cartilaginous and ossified vertebral and rib characteristics, and in selected fetuses cervical vertebrae were disarticulated for more detailed analysis. Observations indicative of methanol-induced homeotic transformations were as follows: [tabular data: see abstract volume] Examination of disarticulated vertebrae revealed foramina and other distinguishing characteristics on vertebrae anterior to those on which they normally appear. These results demonstrate that maternal methanol exposure can alter segment patterning in the developing mouse embryo, producing posteriorization of cervical vertebrae.


NEUTRAL GENETIC DIVERSITY IN A METAPOPULATION WITH RECURRENT LOCAL EXTINCTION AND RECOLONIZATION.
Many species exist as metapopulations in balance between local population extinction and recolonization, processes that may strongly affect the distribution of neutral genetic diversity within demes and in the metapopulation as a whole. In this paper we use both the infinite-alleles and the infinite-sites models to reframe Slatkin's propagulepool and migrant-pool models in terms of mean within-deme and among-deme genetic diversity; the infinite-sites model is particularly relevant to DNA sequence data. Population turnover causes a major reduction in neutral genetic diversity within demes, πS , and in the metapopulation as a whole, πt . This effect is particularly strong for propagulepool colonization, in which colonists are drawn from a single extant deme. Because metapopulation dynamics affect both within-deme and total metapopulation diversity similarly, comparisons between species with different ecologies on the basis of ratios such as FST are difficult to interpret and absolute measures of divergence between populations should be used as well. Although the value of FST in a metapopulation with local extinction depends strongly on the mode of colonization, this has almost no effect on the numerator of the FST ratio, πt - πS , so that FST is influenced mainly by the effect of the colonization mode on the denominator (πt ). Our results also indicate that it is inappropriate to use measures of average within-deme diversity in species with population turnover to estimate the scaled mutation rate, θ, because extinction can greatly reduce πS . Finally, we discuss the effect of population turnover on the effective size of a metapopulation.


Reverse Binding Mode of Phosphotyrosine Peptides with SH2 Protein.
Discerning the different interaction states during dynamic protein-ligand binding is difficult. Here we apply site-specific cysteine-α-chloroacetyl cross-linking to scrutinize the binding between the Src homology 2 (SH2) domain and phosphotyrosine (pY) peptides, a highly dynamic interaction that is a key to cellular signal transduction. From a model SH2 protein to a set of representative SH2 domains, we showed here that a proximity-induced cysteine-α-chloroacetyl reaction cross-linked two spatially adjacent chemical groups as a result of the binding interaction, and reciprocally, the information about the interaction states can be deduced from the cross-linked products. To our surprise, we found SH2 domains can adopt a reverse binding mode with "single-pronged", "two-pronged", and "half" pY peptides. This finding was further supported by a set of 500 ns molecular dynamics simulations. This serendipitous finding defies the canonical theory of SH2 binding, suggests a possible answer about the source of the versatility of SH2 signaling, and sets a model for other protein binding interactions.


Theoretical study on an intriguing excited-state proton transfer process induced by weakened intramolecular hydrogen bonds.
In the present work, we have systematically investigated the dual hydrogen-bonded system 2Z,2'Z-3,3'-(4,4'-methylenebis(4,1-phenylene)bis(azanediyl)bis(1,3-diphenylprop-2-en-1-one)) (abbreviated as L) utilizing quantum chemistry methods, in which the excited-state intramolecular proton transfer (ESIPT) does not conform to the usual stereotype but proceeds along the weakened intramolecular hydrogen bonds (IHBs). Two primary configurations were confirmed to coexist in the ground state (i.e., anti-L and syn-L) by calculating the Boltzmann distribution in three different solvents. Based on the cardinal geometrical parameters involved in IHBs and the interaction region indicator (IRI) isosurface, it can be revealed that the dual IHBs of L were both weakened upon photoexcitation, not least the N1-H2⋯O3 IHB was utterly destroyed in the excited state. The proton-transfer process of anti and syn in three solvents with different polarities has been analyzed by constructing S0- and S1-state potential energy surfaces (PESs). It can be concluded that only the single proton transfer behavior along N1-H2⋯O3 occurs in the S1 state, and the corresponding energy barrier is gradually enlarged with increasing solvent polarity. To further expound the weakened IHB-induced ESIPT mechanism, the scanned PESs connecting the transition state (TS) structures and the initial forms indicate that the ESIPT process is infeasible without the appropriate structural torsion. Our work not only unveils the extraordinary ESIPT process of L, but also complements the results obtained from previous experiments.


Infant digestion physiology and the relevance of in vitro biochemical models to test infant formula lipid digestion.
Lipids play an important role in the diet of preterm and term infants providing a key energy source and essential lipid components for development. While a lot is known about adult lipid digestion, our understanding of infant digestion physiology is still incomplete, the greatest gap being on the biochemistry of the small intestine, particularly the activity and relative importance of the various lipases active in the intestine. The literature has been reviewed to identify the characteristics of lipid digestion of preterm and term infants, but also to better understand the physiology of the infant gastrointestinal tract compared to adults that impacts the absorption of lipids. The main differences are a higher gastric pH, submicellar bile salt concentration, a far more important role of gastric lipases as well as differences at the level of the intestinal barrier. Importantly, the consequences of improper in vitro replication of gastric digestions conditions (pH and lipase specificity) are demonstrated using examples from the most recent of studies. It is true that some animal models could be adapted to study infant lipid digestion physiology, however the ethical relevance of such models is questionable, hence the development of accurate in vitro models is a must. In vitro models that combine up to date knowledge of digestion biochemistry with intestinal cells in culture are the best choice to replicate digestion and absorption in infant population, this would allow the adaptation of infant formula for a better digestion and absorption of dietary lipids by preterm and term infants.


Enzyme inhibition kinetics and molecular interactions of patatin peptides with angiotensin I-converting enzyme and renin.
In this work, the inhibitory effects of potato patatin-derived peptides Trp-Gly (WG) and Pro-Arg-Tyr (PRY) on angiotensin I-converting enzyme (ACE) and renin activities were investigated using kinetics, intrinsic fluorescence and molecular docking. The results indicated that PRY was a more potent ACE- and renin-inhibitory peptide than WG. Enzyme inhibition kinetics showed that WG and PRY inhibited ACE activity through mixed-type and competitive modes, respectively. The inhibitory mechanism of WG and PRY towards renin was determined to be mixed-type. PRY exhibited stronger affinity towards ACE and renin molecules, when compared to WG as determined by intrinsic fluorescence intensity. Molecular docking data confirmed that the higher inhibitory potency of PRY might be attributed to formation of more hydrogen bonds with the enzyme's active site or non-active sites that distorted the configuration necessary for catalysis.


Evaluation of four different systems for extraction of RNA from stool suspensions using MS-2 coliphage as an exogenous control for RT-PCR inhibition.
Knowing when, and to what extent co-extracted inhibitors interfere with molecular RNA diagnostic assays is of utmost importance. The QIAamp Viral RNA Mini Kit (A); MagNA Pure LC2.0 Automatic extractor (B); KingFisher (C); and NucliSENS EasyMag (D) RNA extraction systems were evaluated for extraction efficiency and co-purification of inhibitors from stool suspensions. Real-Time Reverse Transcriptase Polymerase Chain Reaction (rRT-PCR) of MS-2 coliphage spiked into each system's lysis buffer served as an external control for both. Cycle thresholds (Cts) of the MS2 were determined for RNA extracted from stool suspensions containing unknown (n = 93) or varying amounts of inhibitors (n = 92). Stool suspensions from the latter group were also used to determine whether MS-2 and enterovirus rRT-PCR inhibitions were correlated. Specifically 23 RNA extracts from stool suspensions were spiked with enterovirus RNA after extraction and 13 of these stool suspension were spiked with intact enterovirus before extraction. MS2 rRT-PCR inhibition varied for RNAs extracted by the different systems. Inhibition was noted in 12 (13.0%), 26 (28.3%), 7 (7.6%), and 7 (7.6%) of the first 93 RNA extracts, and 58 (63.0%), 55 (59.8%), 37 (40.2%) and 30 (32.6%) of the second 92 extracts for A, B, C, and D, respectively. Furthermore, enterovirus rRT-PCR inhibition correlated with MS2 rRT-PCR inhibition for added enterovirus RNA or virus particles. In conclusion, rRT-PCR for MS-2 RNA is a good predictor of inhibition of enterovirus RNA extracted from stool suspensions. EasyMag performed the best, however all four extraction methods were suitable provided that external controls identified problematic samples.


Prolonged stimulation of μ-opioid receptors produces β-arrestin-2-mediated heterologous desensitization of α(2)-adrenoceptor function in locus ceruleus neurons.
Prolonged agonist stimulation of the μ-opioid receptor (MOR) initiates receptor regulatory events that rapidly attenuate receptor-mediated signaling (homologous desensitization). Emerging evidence suggests that persistent MOR stimulation can also reduce responsiveness of effectors to other G-protein-coupled receptors, termed heterologous desensitization. However, the mechanisms by which heterologous desensitization is triggered by MOR stimulation are unclear. This study used whole-cell patch-clamp recordings of ligand activated G-protein-activated inwardly rectifying potassium channel currents in mouse brain slices containing locus ceruleus (LC) neurons to determine the effects of prolonged stimulation of MOR on α(2)-adrenoceptor (α(2)-AR) function. The results show distinct and sequential development of homologous and heterologous desensitization during persistent stimulation of MOR in LC neurons with Met(5)-enkephalin (ME). ME stimulation of MOR promoted rapid homologous desensitization that reached a steady state after 5 min and partially recovered over 30 min. Longer stimulation of MOR (10 min) induced heterologous desensitization of α(2)-AR function that exhibited slower recovery than homologous desensitization. Heterologous (but not homologous) desensitization required β-arrestin-2 (βarr-2) because it was nearly abolished in βarr-2-knockout (ko) mice. Heterologous (but not homologous) desensitization was also prevented by inhibition of ERK1/2 and c-Src signaling in wild-type (wt) mouse LC neurons. Heterologous desensitization may be physiologically relevant during exposure to high doses of opioids because α(2)-AR-mediated slow inhibitory postsynaptic currents were depressed in wt but not βarr-2 ko LC neurons after prolonged exposure to opioids. Together, these findings demonstrate a novel mechanism by which βarr-2 can regulate postsynaptic responsiveness to neurotransmitter release.


Differential light threshold in automated static perimetry. Factors influencing short-term fluctuation.
The scatter of the differential light threshold observed during a single visual field test is called the short-term fluctuation. A number of factors that may influence the magnitude of the short-term fluctuation were studied. The main factor was the level of the differential light sensitivity itself, followed by the rate of false responses in the catch trials. The pupil size was only notable in patients with glaucoma, while age as well as the mean reaction time did not appear to be notable. The short-term fluctuation is not dependent on the location in the visual field up to 27 degrees of eccentricity degrees tested in normal subjects and patients suspected of having glaucoma, but there is a slight tendency in patients with glaucoma for a larger short-term fluctuation in the upper half of the visual field.


Hormetic mechanisms of anti-aging and rejuvenating effects of repeated mild heat stress on human fibroblasts in vitro.
The phenomenon of hormesis is represented by mild stress-induced stimulation of maintenance and repair pathways, resulting in beneficial effects for cells and organisms. We have reported that repeated mild heat stress (RMHS) has anti-aging hormetic effects on growth and various cellular and biochemical characteristics of human skin fibroblasts undergoing aging in vitro. These effects of RMHS include the maintenance of the stress protein profile, reduction in the accumulation of oxidatively and glycoxidatively damaged proteins, stimulation of the activities of the proteasome and its 11S activator, improvement in cellular resistance to ethanol, hydrogen peroxide, and ultraviolet rays, and increased antioxidative activity of the cells. We have also reported that RMHS prolongs the lifespan of Drosophila. Others have reported anti-aging and life prolonging effects of a wide variety of so-called stressors, such as pro-oxidants, aldehydes, calorie restriction, irradiation, heat shock, and hypergravity. Although molecular mechanisms of hormesis are yet to be elucidated, there are indications that relatively small hormetic effects become biologically amplified, resulting in significant improvement of cellular and organic functions and survival. Hormesis, therefore, can be an effective approach for modulating aging, for preventing or delaying the onset of age-related diseases, and for improving the quality of life in old age.


Comparison of the effects produced by headgear and pendulum appliances followed by fixed orthodontic treatment.
This study compared the effects produced by two different molar distalizers, namely cervical headgear (CHG) and the intraoral pendulum appliance, associated with fixed orthodontic appliances. The headgear group comprised 30 patients (19 females, 11 males), with an initial age of 13.07 years [standard deviation (SD) = 1.3], treated with CHG and fixed orthodontic appliances for a mean period of 3.28 years, and the pendulum group 22 patients (15 females, 7 males), with initial age of 13.75 years (SD = 1.86), treated with the pendulum appliance followed by fixed orthodontic appliances for a mean period of 4.12 years. Lateral cephalograms were taken at the start (T1) and on completion (T2) of orthodontic treatment. The pendulum and CHG groups were similar as to initial age, severity of the Class II malocclusion, gender distribution, initial cephalometric characteristics, and initial and final treatment priority index (TPI). Only treatment time was not similar between the groups, with a need for annualization for data for the pendulum group. The data were compared with independent t-tests. There was significantly greater restriction of maxillary forward growth and improvement of the skeletal maxillomandibular relationship in the CHG group (P < 0.05). The maxillary molars were more mesially tipped and extruded and the mandibular molars more uprighted in the CHG group compared with the pendulum group (P < 0.05). There was more labial tipping of the mandibular incisors and greater overbite reduction in the pendulum group. The pendulum appliance produced only dentoalveolar effects, different from the CHG appliance, which restricted maxillary forward displacement, thus improving the skeletal maxillomandibular relationship.


[Application of capillary electrophoresis in analysis of intact mammalian cells].
Cell is the basic structural and functional unit of human body. The research of cells' structure, function and behavior is very important. Capillary electrophoresis (CE) is a powerful tool for the separation and analysis, the application of which in cell analysis has progressed significantly. In this paper, the developments of CE applied in the intact mammalian cell analysis are reviewed, which consist of cell population and single cell analysis. The erythrocyte, boar sperm, HeLa cells, SH-SY5Y cells, Caco-2 cells, K562 cells and rat cerebellar granule cells are involved in this review. The methods and conditions for the intact mammalian cell analysis are summarized. In addition, the problems caused by the breakage, aggregation, sedimentation, adsorption and electrophoretic heterogeneity of the cell in the intact mammalian cell analysis by CE are discussed, and the corresponding solutions are introduced. Also, the future research trends are presented. Forty nine papers in all are reviewed.


Evaluation of long-term daily administration of oral low-dose etoposide in elderly patients with relapsing or refractory non-Hodgkin's lymphoma.
Etoposide produces reversible inhibition of topoisomerase II, leading to cleavage of DNA, and thereby has an antitumor effect. This mechanism suggests that the longer treatment is continued, the greater the antitumor effect will be. In the present study, both therapeutic and adverse effects of long-term treatment with low-dose oral etoposide were studied in 29 patients aged > or = 65 years with non-Hodgkin's lymphoma (NHL) for whom standard chemotherapy was not effective or refractory. These patients received etoposide at a dose of 50 mg/d for as long as possible. Treatment was continued until white blood cell count decreased to < or = 2,000/microL or the platelet count decreased to < or = 5 x 10(4)/microL. According to the World Health Organization (WHO) criteria of therapeutic effects, 6 (20.7%) of the 29 patients achieved complete remission and 13 patients (44.8%) had partial remission, for a response rate of 65.5%. Adverse effects of > or = grade 3 included leukopenia in 24 patients (82.8%) and anemia in 7 (24.1%). Granulocyte colony-stimulating factor (G-CSF) was given in combination with etoposide to eight patients because of leukopenia (granulocyte count < or = 1,000/microL). In view of the excellent subjective tolerance, low incidence of serious adverse effects, and good activity, single agent oral etoposide given continuously over prolonged periods represents a useful treatment for elderly patients with NHL.


Awake, long-term intranasal insulin treatment does not affect object memory, odor discrimination, or reversal learning in mice.
Intranasal insulin delivery is currently being used in clinical trials to test for improvement in human memory and cognition, and in particular, for lessening memory loss attributed to neurodegenerative diseases. Studies have reported the effects of short-term intranasal insulin treatment on various behaviors, but less have examined long-term effects. The olfactory bulb contains the highest density of insulin receptors in conjunction with the highest level of insulin transport within the brain. Previous research from our laboratory has demonstrated that acute insulin intranasal delivery (IND) enhanced both short- and long-term memory as well as increased two-odor discrimination in a two-choice paradigm. Herein, we investigated the behavioral and physiological effects of chronic insulin IND. Adult, male C57BL6/J mice were intranasally treated with 5μg/μl of insulin twice daily for 30 and 60days. Metabolic assessment indicated no change in body weight, caloric intake, or energy expenditure following chronic insulin IND, but an increase in the frequency of meal bouts selectively in the dark cycle. Unlike acute insulin IND, which has been shown to cause enhanced performance in odor habituation/dishabituation and two-odor discrimination tasks in mice, chronic insulin IND did not enhance olfactometry-based odorant discrimination or olfactory reversal learning. In an object memory recognition task, insulin IND-treated mice did not perform differently than controls, regardless of task duration. Biochemical analyses of the olfactory bulb revealed a modest 1.3 fold increase in IR kinase phosphorylation but no significant increase in Kv1.3 phosphorylation. Substrate phosphorylation of IR kinase downstream effectors (MAPK/ERK and Akt signaling) proved to be highly variable. These data indicate that chronic administration of insulin IND in mice fails to enhance olfactory ability, object memory recognition, or a majority of systems physiology metabolic factors - as reported to elicit a modulatory effect with acute administration. This leads to two alternative interpretations regarding long-term insulin IND in mice: 1) It causes an initial stage of insulin resistance to dampen the behaviors that would normally be modulated under acute insulin IND, but ability to clear a glucose challenge is still retained, or 2) There is a lack of behavioral modulation at high concentration of insulin attributed to the twice daily intervals of hyperinsulinemia caused by insulin IND administration without any insulin resistance, per se.


Application of classification tree and logistic regression for the management and health intervention plans in a community-based study.
A community-based aboriginal study was conducted and analysed to explore the application of classification tree and logistic regression. A total of 1066 aboriginal residents in Yilan County were screened during 2003-2004. The independent variables include demographic characteristics, physical examinations, geographic location, health behaviours, dietary habits and family hereditary diseases history. Risk factors of cardiovascular diseases were selected as the dependent variables in further analysis. The completion rate for heath interview is 88.9%. The classification tree results find that if body mass index is higher than 25.72 kg m(-2) and the age is above 51 years, the predicted probability for number of cardiovascular risk factors > or =3 is 73.6% and the population is 322. If body mass index is higher than 26.35 kg m(-2) and geographical latitude of the village is lower than 24 degrees 22.8', the predicted probability for number of cardiovascular risk factors > or =4 is 60.8% and the population is 74. As the logistic regression results indicate that body mass index, drinking habit and menopause are the top three significant independent variables. The classification tree model specifically shows the discrimination paths and interactions between the risk groups. The logistic regression model presents and analyses the statistical independent factors of cardiovascular risks. Applying both models to specific situations will provide a different angle for the design and management of future health intervention plans after community-based study.


The association between total energy intake and early mortality: data from the Malmö Diet and Cancer Study.
In animal studies, low energy intake (EI) has been associated with a longer lifespan. We examine whether EI is an independent risk factor for prospective all-cause mortality, cardiovascular and cancer mortality in humans. Population-based, prospective cohort study. The Malmö Diet and Cancer Study is a population-based prospective cohort study. A total of 28 098 individuals, mean age 58.2 years, completed questionnaires on diet and life-style and attended a physical examination during 1991-96. Information on mortality was acquired from national registries during a mean follow-up time of 6.6 years. Subjects were categorized by quartiles of total EI. The first quartile was used as a reference point in estimating multivariate relative risks (RR; 95% CI, Cox's regression model). Adjustments were made for confounding by age and various life-style factors. The lowest total mortality was observed for women in the third quartile (RR: 0.74; CI: 0.57-0.96) and for men in the second and third quartiles (RR: 0.85; CI: 0.69-1.04 and RR: 0.85; CI: 0.69-1.04 respectively). Similar U-shaped patterns were observed for cardiovascular mortality amongst women and cancer mortality amongst men. A statistically significant trend (P = 0.029) towards lower cardiovascular mortality from the first to the fourth quartile was observed for men. Low caloric consumers did, on average, not have lower mortality than average or high caloric consumers. Generally, individuals approximately meeting national recommendations for total EI had the lowest mortality. For men, high caloric intake was associated with lower cardiovascular mortality.


Intermittent local prophylaxis against recurrent vaginal candidosis.
Women with recurrent vaginal candidosis were treated until the infection cleared and were then given one clotrimazole 500 mg vaginal tablet a month or an identical placebo as prophylaxis. Of 21 women who received placebo, 16 developed symptoms or signs within three months, compared with nine of 17 women given active treatment. Women who relapsed were treated and then given active prophylaxis once a month. Of 30 women given such treatment, 13 relapsed within three months. Women who relapsed were treated and then given two clotrimazole 500 mg vaginal tablets a month. Of 17 women given prophylaxis twice a month, four developed symptoms or signs within three months, but 10 remained clear for 12 months. No appreciable difference was seen in the incidence of mycological recurrence between the different regimens; within three months over half the women in all treatment groups had become recolonised.


Comparative study of perturbative methods for computing electron transfer tunneling matrix elements with a nonorthogonal basis set.
The authors consider the problem of computing tunneling matrix elements for bridge-mediated electron transfer reactions using the Lowdin [J. Math. Phys. 3, 969 (1962); J. Mol. Spectrosc. 13, 326 (1964)] projection-iteration technique with a nonorthogonal basis set. They compare the convergence properties of two different Lowdin projections, one containing the overlap matrix S and the other containing the inverse S-1 in the projected Hamiltonian. It was suggested in the literature that the projected Hamiltonian with S-1 has better convergence properties compared to the projected Hamiltonian with S. The authors test this proposal using a simple analytical model, and ab initio Hartree-Fock calculations on different molecules with several types of basis sets. Their calculations show that, for Gaussian-type basis sets, the projected Hamiltonian containing S has the best convergence properties, especially for diffuse basis sets and in the strong coupling limit. The limit of diffuse basis sets is relevant to tunneling matrix element calculations involving excited states and anionic electron transfer.


Effects of bifenthrin on Daphnia magna during chronic toxicity test and the recovery test.
The acute and chronic toxic effects of bifenthrin on Daphnia magna were studied. The results showed that 24 h-EC50, 48 h-LC50 and 96 h-LC50 of bifenthrin on D. magna were 3.24, 12.40 and 1.40 microg/L respectively. And the LOEC and NOEC of bifenthrin were 0.02 and 0.004 microg/L respectively. The recovery test of bifenthrin on Daphnia magna was presented. Daphnia magna (F0 generation) were exposed during 21 d to different bifenthrin concentrations. Offspring (animals from the first and third brood: F1 (1st) and F1 (3rd), respectively) were transferred to a free pesticide medium during a 21 d recovery period. In this recovery study, survival, growth, reproduction (mean total young per female, onset of reproduction and number broods per female) and the intrinsic rate of natural increase (r) were assessed as parameters. Reproduction such as number of young per female as well as length was still reduced in F1 (1st) generation daphnids from parentals (F0) exposed to the bifenthrin. However F, (3rd) individuals from parentals exposed to pesticide concentrations were able to restore reproduction when a recovery period of 21 d was allowed, but the length of F, (3rd) from parentals exposed to the 0.5 and 0.75 microg/L bifenthrin concentration was still significantly effected (P < 0.05).


Determinant Factors of the Direct Medical Costs Associated with Genotype 1 Hepatitis C Infection in Treatment-Experienced Patients.
Limited evidence is available on predictors of medical resource utilization (MRU) and related direct costs, especially in treatment-experienced patients infected with genotype 1 hepatitis C virus (HCV). This study aimed at investigating patient and treatment characteristics that predict MRU and related non-drug costs in treatment-experienced patients with chronic hepatitis C (CHC) treated with simeprevir (SMV) or telapravir (TVR) in combination with pegylated interferon and ribavirin (PegIFN/R). A total of 709 patients who completed the 72-week ATTAIN trial were included in the study. Cost data were analysed from the UK NHS perspective. Descriptive statistics and regression analyses were used to determine patterns and predictors of total MRU-related costs associated with SMV/PegIFN/R and TVR/PegIFN/R. Independent predictors for total MRU-related costs were age, region and the following interaction terms: (1) gender × F3-F4 METAVIR score × baseline viral load (BLVL), (2) body mass index (BMI) × F3-F4 METAVIR score × prior response to PegIFN/R and (3) gender × achievement of SVR at 12 weeks (SVR12) × BLVL. A F3-F4 METAVIR score was a stronger predictor of total MRU-related costs than SVR12. Predictors of adverse events included older age, female gender, low BMI, TVR/PegIFN/R and SVR12. Wilcoxon rank sum test revealed comparable total MRU-related costs between SMV/PegIFN/R and TVR/PegIFN/R. To the best of our knowledge, this study is the first to describe the relationship between commonly admitted predictors of MRU-related costs and their joint effect on total MRU-related costs in treatment-experienced patients with CHC. The identified predictors of MRU-related costs suggest that significant treatment costs can be avoided by starting treatment early before the disease progresses. Furthermore, adverse events seem to be the most important factor to take into consideration for the choice of treatment, especially when therapeutic options are associated with similar levels of medical resource utilization and associated costs.


[The value of synthetic MRI in differential diagnosis of benign and malignant breast lesions].
Objective: To explore the diagnostic value of synthetic magnetic resonance imaging (syMRI) quantitative parameters for benign and malignant breast lesions. Methods: From September 2018 to March 2019, a total of 43 cases of breast lesions which were confirmed by surgery and pathology in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled in this study. All patients underwent syMRI sequence scans before and after enhancement except for conventional T2WI, DWI, and enhancement scans. GE AW4.7 workstation was used to generate syMRI parameter maps (T1, T2, proton density mappings), and ITK-SNAP software was used to delineate the volume of interest. The T1, T2, PD values before and after dynamic contrast enhanced (DCE) were obtained, and the change values of each parameter were calculated. Meanwhile, the apparent diffusion coefficient (ADC) and time intensity curve (TIC) of the lesions were measured. The differences of each parameter value were compared between benign and malignant breast lesions, and the receiver operating characteristic (ROC) curve was used to analyze the diagnostic performance of each parameter. Results: Among the 43 enrolled cases, 13 were benign and 30 were malignant. Among the syMRI parameters, the pre-enhancement parameters including T1pre (median 1 663.07 ms), T2pre (median 103.33 ms), post-enhancement parameters ΔT1 (median 1 022.68 ms) and ΔT2 (median 27.67 ms) of benign group, significantly higher than those of the malignant group (the medians were 1 141.74, 92.53, 664.95, and 16.19 ms, respectively, P<0.05). The ADC value of the benign group (median 1.66×10(-3)mm(2)/s) was significantly higher than that of the malignant group (median 1.00×10(-3)mm(2)/s, P<0.05). The benign group included 6 cases of TIC curve type Ⅰ, 5 cases of type Ⅱ, and 2 cases of type Ⅲ. The malignant group included 2 cases of TIC curve type Ⅰ, 17 cases of type Ⅱ, and 11 cases of type Ⅲ. The difference between the two groups was statistically significant (P<0.05). The area under the ROC curve (AUC) of T1pre before DCE was 0.869, higher than 0.806 of ADC and 0.697 of TIC. When the best cut-off value of 1 282.94 ms was chosen, the sensitivity and specificity of diagnosis were 76.9% and 93.3%, respectively. The combination of T1pre and T2pre can further improve the diagnostic performance (AUC=0.908). Conclusions: Among the syMRI quantitative parameters, T1pre, T2pre, ΔT1 and ΔT2 have good value for the differential diagnosis of benign and malignant breast lesions. T1pre has the best diagnostic performance, and the combination of T1pre and T2pre can further improve the diagnostic performance.


Novel Fluorine Boron Hybrid Complex as Potential Antiproliferative Drugs on Colorectal Cancer Cell Line.
Colorectal Cancer (CRC) is one of the most common types of cancer in both sexes; it is considered to be the third leading death factor among other types of cancer. This study aimed to examine the cytotoxicity of a new fluorine boron hybrid complex [L(BF2)2] on human colorectal adenocarcinoma cell line (HT-29), based on the potency of the half-metal based complexes to initiate apoptosis. Based on this data, the impact of it in different concentrations on HT-29 cancerous cells was determined by apoptosis (ELISA, DNA fragmentation laddering, AO/EB staining), cytotoxicity (MTT) and genotoxicity (comet assay). We also calculated the cellular Oxidative Stress Index (OSI) by measuring the Total Antioxidant Status (TAS) and Total Oxidant Status (TOS). Firstly, [L(BF2)2] was examined in view of cytotoxic effect in seven various cell lines (HELA, DU-145, PC3, DLD-1, ECC, PNT1-A and HT-29), and then it was found that the applied complex had a mighty antiproliferative action on HT-29 cells. Thus, the most effective IC50 value turned out to be 26.49 µM in HT-29 cell line. The present study found a tremendous efficacy of [L(BF2)2] on HT-29 cells, especially in terms of damage to cancer cells' DNA, and consequently caused a series of reactions leading to programmed cell death. The results suggest that the [L(BF2)2] as a novel fluorine boron hybrid complex can induce the apoptosis of HT-29 colorectal cancerous cell line and is a possible candidate for future cancer studies.


Cimetidine treatment in acute experimental pancreatitis.
The effects of cimetidine on acute experimental pancreatitis was studied in the rat. Acute pancreatitis was induced in a highly standardized manner, using transduodenal injection of sodiumtaurodeoxycholate and trypsin, into the bile-pancreatic duct. Subcutaneous injections of 32 mg/kg body weight of cimetidine every 8 h did not influence the severity of pancreatitis as evaluated on basis of mortality, macroscopic evaluation, S amylase and amylase activity in ascites or amylase and lipase activity within pancreatic tissue. When, however, the dose of cimetidine was increased tenfold, a significantly increased mortality rate was observed as compared to normal rats given either dose of cimetidine and to pancreatitic rats given the low dose of the drug. Our study does not justify the use of cimetidine in acute pancreatitis.


Factors affecting adherence to evidence-based guidelines in the treatment of URI, sinusitis, and pharyngitis.
Sinus infections, sore throats, and upper respiratory tract infections (URI) are common reasons patients seek medical care. Well-established treatment guidelines exist for prescribing antibiotics in these clinical scenarios, but are not often followed. The objective of this study is to determine practice patterns related to prescribing antibiotics for sinusitis, URI, and pharyngitis. The main hypothesis is that attending physicians improve their adherence to antibiotic guidelines with a learner present. A retrospective cohort study was performed on patients treated for URI, sinusitis, and pharyngitis at an ambulatory faculty practice. The use of relevant ICD-9 codes from January 1, 2008 to January 30, 2012 resulted in 1,548 patient encounters which were reviewed for guideline adherence. Univariate analysis and multivariate logistic regression was performed for each outcome variable to determine if they influence antibiotic adherence. Variables studied were physician, presence of a learner, BMI, age, gender, day of the week, month, diabetes, immunosuppression, and COPD. Multivariate analysis showed the statistically significant variables were age (p=0.038) for pharyngitis and provider (p=0.013) for URI. There were no significant findings for sinusitis. Guideline adherence was 24% in patients with pharyngitis, 42% in acute sinusitis, 79% in URI, and 57% overall. Guideline adherence varies depending on the treating physician and decreases when treating younger patients with pharyngitis. The presence of a learner did not improve prescribing habits. The reason for these findings remain unclear, but considerations for improvement could include following antibiotic adherence as a quality measure, giving patients handouts educating them about the impact of overprescribing antibiotics, and further education amongst faculty and residents about adhering to nationally recognized guidelines.


Characterization of an antigenically distinct porcine rotavirus.
A porcine virus with rotavirus morphology, which was antigenically unrelated to previously described rotaviruses, is described. Particles with an outer capsid layer measured 75 nm and those lacking the outer layer were 63 nm in diameter. Particles which resembled cores were also identified. The virus was shown to be antigenically distinct from other rotaviruses as judged by immunofluorescence and immune electron microscopy, and it failed to protect piglets from challenge with porcine rotavirus. Analysis of the genome indicated that it was composed of 11 segments of double-stranded RNA with the same overall size range as other rotaviruses but with an unusual segment pattern.


A concise update on prostate pathology.
Prostate carcinoma is the most common non-cutaneous malignancy in men in developed countries and the incidence has been steadily rising in the developing countries. Active research in recent years has led to tremendous progress in our understanding of the biology and genetics, and marked improvement in diagnosis and treatment of prostate cancer. Gleason grading has remained as the cornerstone for management of patients with prostate cancer. However, the grading system has continuously evolving since its inception in response to changes in the clinical practice of diagnosis and treatment of prostate cancer. The modification of Gleason grading system implemented by the International Society of Urological Pathology in 2005 has profoundly changed the way prostate cancer is graded and consequently how patients are managed. Several prostate cancer histological types with distinct clinical and pathological features have been rediscovered or redefined. Finally, elucidations of the molecular and genetic mechanism helps not only better understand the pathogenesis of prostate cancer, but also identify biomarkers for improved diagnosis, risk stratification and clinical management. This article briefly reviews the most recent advances in the Gleason grading system, new histological types and molecular genetics of prostate cancer.


Selective N7 Alkylation of 7-Azaindazoles.
A general and mild procedure for alkylation of 7-azaindazoles at the N7 position using alkyl halides in butanone is reported, which requires no additives such as acids or bases. The scope of the reaction regarding substituents on 7-azaindazoles and the alkyl electrophiles is presented.


Quinapril improves endothelial function in postmenopausal hypertensive patients.
Hypertension is one of the main cardiovascular risk factors, and it may be responsible for the excess morbidity and mortality in postmenopausal women. Endothelium-dependent dilation of conduit arteries is reduced in women after menopause, as shown by the reduced flow-mediated dilation (FMD) of the brachial artery. The aim of this study was to evaluate changes in FMD during and following a 6-month-long treatment with increasing doses (10, 20 and 40 mg) of quinapril in hypertensive postmenopausal patients. A multicenter, open-label, non-comparative, baseline control study in 61 postmenopausal outpatients. The mean baseline FMD (% +/- SD) of the 53 patients in the intent-to-treat population (patients with at least one FMD evaluation) was 2.83 +/- 1.24%; FMD of the 51 subjects on 10 mg quinapril daily was 5.58 +/- 2.179%; FMD of the 52 patients on 20 mg quinapril was 7.06 +/- 2.31%, and FMD of the 53 subjects on 40 mg daily was 8.07 +/- 2.57% (p < 0.001 for each dose, compared to baseline). Ourresults confirmed that quinapril improves endothelial function at all examined doses as measured by FMD. Modulation of the renin-angiotensin system may act as a target for reducing cardiovascular risk in postmenopausal hypertensive women.


Attitudes scale toward cancer-related cognitive changes - an initial Colombian validation.
The aim of this study was to develop an initial valid tool to measure attitudes toward cancer-related cognitive changes. After revising the literature, three main dimensions were hypothesized. Eight judges were contacted to obtain content validity evidence. A robust Exploratory Factor Analysis (EFA) was performed via a parallel analysis with an Unweighted Least Squares (ULS) estimator and polychoric correlations. The results were crossed with sociodemographic variables to find possible statistical differences and estimate the size effect. Analysis was performed in the software Factor and the statistical package R. A sample of 374 participants was obtained, involving oncology patients, their caregivers, and people from the general community. A statistical fit was found in two dimensions: Awareness and Judgments [root mean squared error of approximation (RMSEA) = 0.042, standardized root mean square residual (SRMR) = 0.02, comparative fit index (CFI) = 0.99, Tucker-Lewis index (TLI) = 0.98] with a moderate correlation between them (r = 0.612). Optimal reliability indices were obtained for the total scale and its dimensions. No real statistical difference was found between sociodemographic variables; the interpretation norms were established via the quartiles. The first attempt to measure the construct of interest was developed with two primary validity evidence based on the content and its internal structure. This instrument could help strengthen the prevention of cancer-related cognitive changes. More research is needed to adhere more valid evidence to the scale.


Measurements of the in vivo synthesis of thromboxane and prostacyclin in humans.
Our studies on the urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha in humans strongly indicate that these metabolites are good indicators of the in vivo synthesis of TxA2 and PGI2. Our finding that physical exercise increases PGI2 synthesis was of particular importance for the design of adequate studies on the effects of various drugs on the in vivo formation of PGI2. The rapid recovery (within 3-4 h) of PGI2 formation found following administration of 1.0 g of aspirin together with the long-lasting inhibition of TxA2, suggests that in the prophylaxis of thromboembolic events an intermittent dosage of 0.5 g of aspirin every third day should be a better alternative than daily low or high doses of aspirin. The increased TxA2 formation found in patients with acute myocardial infarction, deep vein thrombosis and in patients following insertion of synthetic surfaces into the circulation, is very likely a reflection of an increased activation of platelets. The increased TxA2 synthesis may cause further platelet activation, vasoconstriction and activation of the coagulation system. Thus, theoretically, inhibition of TxA2 could diminish platelet activation and reduce the risk of thrombotic complications. It is well known that the interaction between platelets and the vessel wall plays an important role in haemostasis and in the development of thrombosis. On the basis of its biological properties, PGI2 may play a local haemostatic role in the regulation of this interaction. Our studies of myocardial infarction and deep vein thrombosis clearly demonstrate the involvement of PGI2 in those diseases.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification and isolation of genes involved in poly(beta-hydroxybutyrate) biosynthesis in Azospirillum brasilense and characterization of a phbC mutant.
Like many other prokaryotes, rhizobacteria of the genus Azospirillum produce high levels of poly(beta-hydroxybutyrate) (PHB) under suboptimal growth conditions. Utilization of PHB by bacteria under stress has been proposed as a mechanism that favors their compatible establishment in competitive environments, thus showing great potential for the improvement of bacterial inoculants for plants and soils. The three genes that are considered to be essential in the PHB biosynthetic pathway, phbA (beta-ketothiolase), phbB (acetoacetyl coenzyme A reductase), and phbC (PHB synthase), were identified in Azospirillum brasilense strain Sp7, cloned, and sequenced. The phbA, -B, and -C genes were found to be linked together and located on the chromosome. An A. brasilense phbC mutant was obtained by insertion of a kanamycin resistance cassette within the phbC gene. No PHB production was detected in this mutant. The capability of the wild-type strain to endure starvation conditions was higher than that of the mutant strain. However, motility, cell aggregation, root adhesion, and exopolysaccharide (EPS) and capsular polysaccharide (CPS) production were higher in the phbC mutant strain than in the wild type.


Clinical outcome and quantitative evaluation of periprosthetic bone-remodeling of an uncemented femoral component with taper design. A prospective study.
The rationale of uncemented taper stems is based on fixation in the proximal portion of the femoral diaphysis, a self-locking principle, and a low modulus of elasticity. The aim of this study was to evaluate a collarless femoral component designed to be a three-dimensional taper for press-fit insertion with regard to clinical outcome, efficacy of fixation, incidence of osteolysis, and periprosthetic bone-remodeling. The first 48 consecutive patients (50 hips) with osteoarthritis who had had primary total hip arthroplasty using the Cerafit Multicone stem and the Cerafit Triradius-M press-fit cup with alumina-alumina pairing (Ceraver Osteal, Paris, France) were followed-up for a mean of 2.3 years (2 to 2.5 years). The mean age of patients at index operations was 52.5 years. Current criteria were used for clinical and radiological assessment. Quantitative evaluation of periprosthetic bone-remodeling was prospectively assessed using computed tomography. Clinical and radiological follow-up was obtained in all hips. Forty-nine hips (98%) were clinically rated good or excellent, one hip (2%) was rated fair, owing to a persisting limp. The mean preoperative Harris Hip Score was rated 62, and it has improved to 93.5 at the time of follow-up. One hip (2%) had marked postoperative thigh pain. This pain had disappeared at 3-month follow-up. All stems showed radiological signs of stable fixation by bone ingrowth. No stem required revision. Thirty-four hips (68%) had either no change in femoral bone density or only patchy loss of bone density isolated to Gruen zones 1 and 7. Sixteen hips (32%) had some reduction of bone density isolated to zone 1. Radiolucencies without progression were found in zones 1 and 7 in 3 hips (6%), and in zone 1 alone in 3 other hips (6%). A slight cortical hypertrophy was seen in 3 hips (6%). Twenty-three hips (46%) developed radiographic appearance of bone apposition at the stem tip as partial pedestal (19 hips) and as complete pedestal (4 hips). No signs of cup loosening were detected at follow-up. Twenty-four patients (25 hips) were eligible for computed tomography. The mean decrease of the overall bone mineral density in the metaphyseal portion of the femur one year after insertion of the stem was rated 15.4%, and the mean decrease of the cortical bone mineral density was rated 17.2%. On the other hand, a mean decrease of the cortical bone mineral density of less than 5% was observed in the diaphyseal portion of the femur around the implant. The clinical and radiological results of the Cerafit Multicone stem at a mean follow-up of 2.3 years are very promising and do not contrast with those achieved using other uncemented stems with tapered design. Furthermore, results of quantitative evaluation of periprosthetic bone-remodeling were considered satisfactory favourably with others reported in the literature using stems inserted without cemented.


Increase of intravascular blood volume in Ischaemic heart disease.
Circulating blood volume, cardiac index, heart rate, and ejection rate were measured in patients with angina pectoris. The controls and the patients were divided in sub-groups of those under 45 and over 45 years of age. The investigation was carried out using the isotope method. A significant difference was observed in the value of intravascular blood volume at rest between the controls and patients with ischaemic heart disease unrelated to anginal attack. The blood volume was 5.6 litre in the control group and 6.4 litre in patients with ischaemic heart disease. Exercise tests produced further increases during attack in the blood volume of angina patients. A significant increase of blood volume after moderate exercise was also observed in patients under 45 with ischaemic heart disease but without angina. It is suggested that the increase of intravascular blood volume plays a part in the pathogenesis of angina pectoris.


Specneuzhenide Ameliorate Complete Freund Adjuvant Induced Arthritis in Rats: Involvement of NF-κB and HO-1/Nrf-2 Pathway.
Rheumatoid arthritis (RA) is growing autoimmune and inflammatory disease that occur due to self-destruction of immune response inducing joint deformity and bone erosion. During the arthritis inducing the swelling, pain and inflammation in around the joint and other body organs due to injury of tendons and ligaments. Specneuzhenide (SZ) already proved antioxidant and anti-inflammatory effect against the various diseases. In this experimental study, we scrutinized the anti-arthritic effect of SZ against the complete freund adjuvant (CFA) induced arthritic in rats. Subcutaneously injection of CFA was injected into the subplantar region of the left hind paw for induction the arthritis and rats were divided into different groups and rats received the oral administration of SZ (5, 10 and 15 mg/kg) for 28 days. The body weight, paw swelling arthritic score mRNA expression and biochemical parameters were determined at regular time interval. CFA induced arthritic rats treated with SZ significantly (p < 0.001) enhanced the body weight and decreased the paw swelling, arthritic index and organ (spleen and thymus) index, respectively. SZ treated rats significantly (p < 0.001) decreased the hepatic parameter such as SGPT, SGOT and ALP, anti-CII IgG levels (IgG1 and IgG2A) and inflammatory parameters (COX-2 and PGE2). SZ treated rats significantly (p < 0.001) suppressed the level of MDA and increased the level of GSH, SOD and CAT. SZ treated rats suppressed the inflammatory cytokines such as TNF-α, Il-1β, IL-2, IL-6, IL-16, IL-17 and increased the level of IL-10, TGF-β. SZ treated rats significantly (p < 0.001) suppressed the mRNA expression of Nrf2, HO-1 and NF-κB. On the basis of result, we can say that specneuzhenide protective effect against CFA induced arthritis in rats via alteration of HO-1/Nrf-2 pathway.


Eight-year blood pressure change in middle-aged men: relationship to multiple nutrients.
Relationships of nutrients, alcohol intake, and change in weight to change in blood pressure over 8 years in 1714 employed middle-aged men from the Chicago Western Electric Study were explored. At first and second annual examinations, 2 in-depth interviews were performed to assess usual intake of foods and beverages during the preceding 28 days. Annual follow-up data through examination year 9 were used to determine change in weight and blood pressure. Averages of nutrients from 2 interviews were related to annual blood pressure change from baseline by use of the Generalized Estimating Equation, with control for confounders. In analyses of dietary variables considered individually, total and animal protein; total, saturated, monounsaturated, and polyunsaturated fatty acids; cholesterol; Keys dietary lipid score; calcium; alcohol; and average annual change in weight were positively and significantly related to average annual change in systolic pressure; vegetable protein, total carbohydrate, beta-carotene, and an antioxidant vitamin score based on vitamin C and beta-carotene were inversely and significantly related to average annual change in systolic pressure. In analyses of combinations of dietary factors, cholesterol, Keys score, and alcohol were positively related to change in systolic pressure (eg, Z-scores 2.21, 2.05, and 2.50); vegetable protein and antioxidant index were inversely related to change in systolic and diastolic pressure. Change in weight was directly related to change in systolic and diastolic pressure. These findings support the concept that multiple macro- and micronutrients, alcohol intake, and calorie imbalance relate prospectively to blood pressure change.


[Verapamil and betamimetics].
The authors review the studies which have been conducted on combination therapy with verapamil and beta-mimetics. This form of treatment does not appear to be wise or effective in clinical practice and should be rejected because the risks far outweigh the purely subjective benefits.


How worrisome is testicular microlithiasis?
Anecdotal reports of men developing testicular cancer after previous identification of microcalcifications on ultrasound generated significant concern in the literature about the relationship of testicular microlithiasis and testis cancer. Until 2001 little prospective data were available on the prevalence or natural history of testicular microlithiasis in the healthy male population. Testicular microlithiasis is present in 5.6% of the male population between 17 and 35 years of age (14.1% in African Americans), far more common than testicular cancer (7:100,000). The majority of men with testicular microlithiasis will not develop testicular cancer. Previously recommended surveillance regimens using ultrasound, tumor markers or testicular biopsy are too costly and do not offer an improved outcome over testicular self-examination. Testicular microlithiasis is common and while microcalcifications do exist in roughly 50% of germ cell tumors the majority of men with testicular microlithiasis will not develop testicular cancer. Increased emphasis on testicular examination is the recommended follow up for men identified with testicular microlithiasis.


Asymmetric catalytic emulsion polymerization in chiral micelles.
Achiral substituted acetylene monomers undergo aqueous catalytic emulsion asymmetric polymerizations in chiral micelles consisting of SDS and amino acid, providing optically active helical polymer emulsions. The asymmetric polymerizations lead to one-handed helical polymers, which are the origin of the optical activity of polymer emulsions.


Leiomyoma of the kidney--report of two cases.
Renal leimyoma is an uncommon benign tumour, which pose a challenging diagnostic and therapeutic problem. When multiple (leiomyomatosis) they are preoperatively mistaken for malignant tumors. We herein-present one case of renal leiomyomatois developing in a 50 year old male, which was clinically diagnosed as renal cell carcinoma and one case of renal leiomyoma in a 37 year old male.


Transcription and evolutionary dynamics of the centromeric satellite repeat CentO in rice.
Satellite DNA is a major component of centromeric heterochromatin in most multicellular eukaryotes, where it is typically organized into megabase-sized tandem arrays. It has recently been demonstrated that small interfering RNAs (siRNAs) processed from centromeric satellite repeats can be involved in epigenetic chromatin modifications which appear to underpin centromere function. However, the structural organization and evolution of the centromeric satellite DNA is still poorly understood. We analyzed the centromeric satellite repeat arrays from rice chromosomes 1 and 8 and identified higher order structures and local homogenization of the CentO repeats in these 2 centromeres. We also cloned the CentO repeats from the CENH3-associated nucleosomes by a chromatin immunoprecipitation (ChIP)-based method. Sequence variability analysis of the ChIPed CentO repeats revealed a single variable domain within the repeat. We detected transcripts derived from both strands of the CentO repeats. The CentO transcripts are processed into siRNA, suggesting a potential role of this satellite repeat family in epigenetic chromatin modification.


A radiographic recall evaluation of 894 endodontic cases treated in a dental school setting.
A radiographic recall evaluation of 894 endodontic cases treated by dental students at the University of Oklahoma College of Dentistry was conducted by faculty. The purpose of this study was to determine the success of standardized nonsurgical endodontic treatments by using radiographic techniques of determination and to compare the results to similar studies at other dental schools. Cases were labeled as successful, acceptable, questionable, and failing. Observations included time since treatment, age, gender, and tooth type. The combined percentage of successful and acceptable cases was 91.05%. Differences in percentage of success among recall time intervals were statistically significant (p < 0.01), as were the percentages of success between tooth types treated (p < 0.05). Success rate was not affected by age or gender (p > 0.05). The overall rate of successful and acceptable cases in this study was found to compare favorably with those from recall studies conducted at other dental schools.


Lack of association between polymorphisms of the dopamine receptor D4 and dopamine transporter genes and personality traits in a Korean population.
Human personality traits have a considerable genetic component. Cloninger et al. were the first to postulate that certain personality traits, such as novelty seeking, are related to the dopamine neurotransmitter system. In this study, we investigated the associations between dopamine receptor D4 (DRD4) exon III and dopamine transporter (DAT1) polymorphisms and personality traits. The DRD4 and DAT1 gene polymorphisms were genotyped in 214 healthy Korean subjects, whose personality traits were assessed with the Temperament and Character Inventory (TCI). There were no significant differences between scores of TCI temperament dimensions (novelty seeking, harm avoidance, reward dependence, and persistence) and DRD4 gene polymorphism. The DAT1 gene polymorphisms also showed no significant association with any of the temperament subscales of the TCI. These data suggest that DRD4 and DAT1 gene polymorphism may not associated with personality traits in a Korean population.


New drug-strategies to tackle viral-host interactions for the treatment of influenza virus infections.
The influenza virus (IV) is a highly contagious virus causing seasonal global outbreaks affecting annually up to 20% of the world's population and leading to 250,000-500,000 deaths worldwide. Current vaccines have variable effectiveness, and, in particular during a pandemic outbreak, they are probably not available in the amounts needed to protect the world population. Therefore we need effective small molecule drugs to combat an IV infection and that can be produced, in case of pandemic, rapidly and in large quantities. Unfortunately, natural occurring IV becomes more and more resistant to current anti-IV drugs. And thus, there is an urgent need for development of alternative agents with new mechanisms of action. This review provides an overview of the pharmacology and effectiveness of new anti-IV agents, focusing on inhibition mechanisms directed against virus-host interactions.