T cell abnormalities in systemic lupus erythematosus.
Because of the consensus that T cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE), we explored the molecular basis of the defective function of SLE T cells for expression of signal transduction molecules, as well as surface structures such as adhesion molecules, by extensively testing peripheral blood T cells from SLE patients. Upregulated expression and function of adhesion molecules was observed in T cells from patients with active SLE who had specific clinical manifestations such as vasculitis, epithelitis and arthritis, but proximal signal transduction was defective. Comprehensive analysis to identify the molecules responsible for the defects showed the expression of the TCR zeta chain was attenuated, or absent in more than half of SLE patients. Moreover, the aberrant transcripts of the TCR zeta chain, including spliced variants lacking exon 7 and with a short 3' UTR, were detected in SLE T cells. Although attenuated expression of the TCR zeta chain is also observed in patients with cancers, infections and other autoimmune diseases, sustained attenuation of TCR zeta expression and aberrant transcripts are only observed in SLE. In this review we discuss the unique features of the TCR zeta defects in SLE.


The mouse iduronate sulfatase gene: identification of a novel transcript.
Complementary DNAs, cDNAs, coding for iduronate sulfatase (IDS, E.C.220.127.116.11) have been isolated and characterized in man and mouse. The murine cDNA (MTA16) was highly homologous to the human counterpart. By screening the same mouse thymus cDNA library another cDNA (MTA13) was isolated: it is 1831 bp long and is identical to a part of the MTA16 cDNA in its 5' region, but it is completely divergent in the 3' region. Characterization of the MTA13 mRNA as well as its genomic organization are presented. The results herein reported support the hypothesis that MTA13 and MTA16 mRNAs are encoded by the same gene.


Variation and genetic control of surface antigen expression in mycoplasmas: the Vlp system of Mycoplasma hyorhinis.
Surface antigenic diversity in the swine pathogen Mycoplasma hyorhinis is generated by random combinatorial expression and high-frequency phase variation of multiple, size-variant membrane surface lipoproteins (Vlps) which represent the major coat proteins of this wall-less procaryote. The distinctive structural basis for Vlp variation was revealed in a family of several related but divergent vlp genes. These occur in one cluster as single chromosomal copies, each encoding a conserved domain for membrane insertion and lipoprotein processing, and a divergent external domain that changes size by deletion or insertion of repetitive intragenic coding sequences while retaining a distinctive charge motif. Lack of detectable changes in restriction fragment patterns or DNA sequence of vlp structural genes during phase transitions between ON and OFF expression states ruled out long range genomic rearrangements and frameshift mutations as a means of controlling Vlp phase variation. However, highly homologous vlp promoter regions contain a homopolymeric tract of contiguous adenine residues [poly(A)] upstream of the transcriptional start site which is subject to frequent mutations altering its length. These mutations are the only sequence changes detected during phase transitions, and are highly correlated with the expression state of each vlp gene. This suggests a mechanism of transcriptional control regulating Vlp phase variation by critical changes within the poly(A) region affecting the spacing between the -10 and -35 hexamers or a putative regulator binding site. The multiple levels of structural and antigenic diversity embodied in the vlp gene family may provide essential adaptive capabilities for this wall-less microbial pathogen.


Escherichia coli as a cause of diarrhea.
Escherichia coli is the best-known member of the normal microbiota of the human intestine and a versatile gastrointestinal pathogen. The varieties of E. coli that cause diarrhea are classified into named pathotypes, including enterotoxigenic, enteroinvasive, enteropathogenic and enterohemorrhagic E. coli. Individual strains of each pathotype possess a distinct set of virulence-associated characteristics that determine the clinical, pathological and epidemiological features of the diseases they cause. In the present brief review, we summarize the key distinguishing features of the major pathotypes of diarrheagenic E. coli. Knowledge of the pathogenic mechanisms of these bacteria has led to the development of rational interventions for the treatment and prevention of E. coli-induced diarrhea. In addition, investigations into E. coli virulence are providing useful insights into the origins and evolution of bacterial pathogens more generally.


Strategic development of the conserved region of the M protein and other candidates as vaccines to prevent infection with group A streptococci.
Group A streptococcal (Streptococcus pyogenes) diseases remain a major public health problem in developing countries as well as in the indigenous populations of developed countries. In view of the large number of Group A streptococcal infections and the potential for sequelae such as rheumatic heart disease, control strategies including the development of an anti-streptococcal vaccine that is able to prevent infection and colonization is important. In this article, we discuss the epidemiology and strain variability of Group A streptococcus and how this is rendering vaccine development more challenging. We discuss vaccine strategies with a focus on the conserved region of the M protein and present a viewpoint for the impediments and the way forward.


Patient-reported lung symptoms as an early signal of impending radiation pneumonitis in patients with non-small cell lung cancer treated with chemoradiation: an observational study.
Clinician ratings of concurrent chemoradiation (CRT)-induced radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) are based on both imaging and patient-reported lung symptoms. We compared the value of patient-reported outcomes versus normal-lung uptake of 18F-fluoro-2-deoxyglucose in positron emission computed tomography (FDG PET/CT) during the last week of treatment, for indicating the development of grade ≥ 2 RP within 4 months of CRT completion. 132 patients with NSCLC-reported RP-related symptoms (coughing, shortness of breath) repeatedly using the validated MD Anderson Symptom Inventory lung cancer module. Of these patients, 68 had FDG PET/CT scans that were analyzed for normal-lung mean standardized FDG uptake values (SUVmean) before, during, and up to 4 months after CRT. Clinicians rated RP using CTCAE version 3. Logistic regression models examined potential predictors for developing CTCAE RP ≥ 2. For the entire sample, patient-rated RP-related symptoms during the last week of CRT correlated with clinically meaningful CTCAE RP ≥ 2 post-CRT (OR 2.74, 95% CI 1.25-5.99, P = 0.012), controlled for sex, age, mean lung radiation dose, comorbidity, and baseline symptoms. Moderate/severe patient-rated RP-related symptom score (≥ 4 on a 0-10 scale, P = 0.001) and normal-lung FDG uptake (SUVmean > 0.78, P = 0.002) in last week of CRT were equally strong predictors of post-CRT CTCAE RP ≥ 2 (C-index = 0.78, 0.77). During the last week of CRT, routine assessment of moderate-to-severe RP-related symptoms provides a simple way to identify patients with NSCLC who may be at risk for developing significant post-CRT RP, especially when PET/CT images of normal-lung FDG uptake are not available.


Chemical moieties and interactions involved in the binding of zearalenone to the surface of Lactobacillus rhamnosus strains GG.
Viable, heat-and acid-killed Lactobacillus rhamnosus strain GG (LGG) has shown high binding properties with zearalenone (ZEN). To identify the type of chemical moieties and interactions involved in binding with the ZEN, LGG was subjected to different chemical and enzymatical treatments, prior to the binding experiments. Pretreating the viable, heat- and acid-killed bacteria with m-periodate significantly decreased ZEN binding, suggesting that ZEN binds predominantly to carbohydrate components. Pretreatment with Pronase E had no effect on the ability of viable cells to bind ZEN, however, a reduction in the binding of ZEN by heat- and acid-killed cells, suggesting that the new binding sites exposed by heat or acid are proteins in nature. Pretreatment with urea also decreased binding, suggesting that hydrophobic interactions play a role in ZEN binding. The binding of ZEN in concentrations ranging from 0.79 to 62.82 microM and its subsequent dissociation by repetitive aqueous washes was also studied. The binding sites of the bacteria were not saturated by the maximum ZEN concentration studied.


Cholinesterase reactivators and bioscavengers for pre- and post-exposure treatments of organophosphorus poisoning.
Organophosphorus agents (OPs) irreversibly inhibit acetylcholinesterase (AChE) causing a major cholinergic syndrome. The medical counter-measures of OP poisoning have not evolved for the last 30 years with carbamates for pretreatment, pyridinium oximes-based AChE reactivators, antimuscarinic drugs and neuroprotective benzodiazepines for post-exposure treatment. These drugs ensure protection of peripheral nervous system and mitigate acute effects of OP lethal doses. However, they have significant limitations. Pyridostigmine and oximes do not protect/reactivate central AChE. Oximes poorly reactivate AChE inhibited by phosphoramidates. In addition, current neuroprotectants do not protect the central nervous system shortly after the onset of seizures when brain damage becomes irreversible. New therapeutic approaches for pre- and post-exposure treatments involve detoxification of OP molecules before they reach their molecular targets by administrating catalytic bioscavengers, among them phosphotriesterases are the most promising. Novel generation of broad spectrum reactivators are designed for crossing the blood-brain barrier and reactivate central AChE. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.


Percutaneous dilational tracheostomy: an initial experience in community based teaching hospital.
Percutaneous dilational tracheostomy (PDT) is frequently performed in the intensive care unit to prevent the long term complications associated with prolonged endotracheal intubation. To report the analysis of our experience with percutaneous dilation tracheostomy. A prospective documentation of 40 patients who received percutaneous dilational tracheostomy in a multidisciplinary intensive care unit during a 12-month period. The patients demographic, indications of intubation and PDT, time required to perform the procedure, complications and the outcome of these patients in the intensive care unit were noted. Among 425 patients, 40 underwent percutaneous dilational tracheostomy that included 22 females and 18 males with the median age of 35 years. Prolonged ventilatory support was the most common indication for tracheostomy. The average duration of intubation before PDT was 5 days. Median procedure time was 20 minutes. Complications included minor bleeding in two (5%), subcutaneous emphysema with pneumothorax in two patients (5%), tracheal stenosis in three (7.5%), tracheo-esophageal fistula and glottic granuloma in one patient each (2.5%). Among forty patients, 28 (70%) were discharged to the ward, 8 died in intensive care unit and 4 left hospital against medical advice. Percutaneous dilational tracheostomy is a safe, quick and effective way for long term airway management in critically ill patients.


Lymphotoxin-LIGHT pathway regulates the interferon signature in rheumatoid arthritis.
A subset of patients with autoimmune diseases including rheumatoid arthritis (RA) and lupus appear to be exposed continually to interferon (IFN) as evidenced by elevated expression of IFN induced genes in blood cells. In lupus, detection of endogenous chromatin complexes by the innate sensing machinery is the suspected driver for the IFN, but the actual mechanisms remain unknown in all of these diseases. We investigated in two randomized clinical trials the effects on RA patients of baminercept, a lymphotoxin-beta receptor-immunoglobulin fusion protein that blocks the lymphotoxin-αβ/LIGHT axis. Administration of baminercept led to a reduced RNA IFN signature in the blood of patients with elevated baseline signatures. Both RA and SLE patients with a high IFN signature were lymphopenic and lymphocyte counts increased following baminercept treatment of RA patients. These data demonstrate a coupling between the lymphotoxin-LIGHT system and IFN production in rheumatoid arthritis. IFN induced retention of lymphocytes within lymphoid tissues is a likely component of the lymphopenia observed in many autoimmune diseases. ClinicalTrials.gov NCT00664716.


Cutaneous infection due to acremonium.
We report an immunocompromised patient who developed a cutaneous infection caused by acremonium which is a rare opportunistic fungi. With the increasing number of immunocompromised patients opportunistic fungal infection can cause serious diseases and early recognition is mandatory.


Contribution to the study of the development and ossification of human sternum.
We have studied the development of sternum in man. Complete microscopic series of sections through thorax of human embryos and fetuses from the second and third months of gestation served as the research material. Preparations were stained by Alcian blue and Mayer's haematoxyline, counterstained by eosine. We also had a set of macroscopic preparations of sterna and adjacent parts of ribs from fetuses of the fifth and sixth months of gestation. These specimens were stained by Alcian blue and by Alizarine and subsequently cleared by glycerine method. We have found that sternum develops by a fusion of sternal bars. Sternal bars develop from anterior bent parts of ribs, lying one over another like tiles. The newly formed sternum has different proportions in comparison to its definitive state. In all the cases its manubrium is wider and bigger, its xiphoid process is longer, in almost all the cases doubled or at least bifurcated. The sternocostal junctions are provided with interzones with the exception of the first rib. Its primordium continues into sternum without any border. Clavicle is connected with sternal anlage without any visible border and this interzone quickly develops as the primordia of the sternoclavicular articulation and the disc. In the medial part, there is a cartilaginous model which ossifies very early--as the first bone of the body. In young embryos from the end of the second month of gestation the clavicle and sternum show very different structures. Ossification of the sternum begins in the fifth month by developing a large number of very small centers of ossification which are not yet detectable by X-ray or CT.(ABSTRACT TRUNCATED AT 250 WORDS)


Nucleophilic substitution of phosphorothionate ester pesticides with bisulfide (HS-) and polysulfides (S(n)2-).
The reactions of five organophosphorus insecticides (OPs) (chlorpyrifos-methyl, parathion-methyl, fenchlorphos, chlorpyrifos, and parathion) with hydrogensulfide/ bisulfide (H2S/HS-) and polysulfides (S(n)2-) were examined in well-defined aqueous solutions over a pH range from 5 to 9. The rates are first-order in the concentration of the different reduced sulfur species. Experiments at 25 degrees C demonstrated that the reaction of the five OPs with the reduced sulfur species follows a SN2 mechanism. The activation parameters of the reaction of OPs with bisulfide were determined from the measured second-order rate constants over a temperature range of 5-60 degrees C. The determined second-order rate constants show that the reaction of an OP with polysulfides is from 15 to 50 times faster than the reaction of the same OP with bisulfide. The dominant transformation products are desalkyl OPs, which indicate that the nucleophilic substitution of reduced sulfur species occurs at the carbon atom of the alkoxy groups. And also the results show that these reduced sulfur species are much better nucleophiles, and thus degrade these pesticides faster than the well-studied base hydrolysis by OH-. When the determined second-order rate constants are multiplied with the concentration of HS- and S(n)2- reported in salt marshes and porewater of sediments, predicted half-lives show that abiotic degradation by sulfide species may be of comparable importance to microbially mediated degradation in anoxic environments.


[Evolution of non-coding nucleotide sequences in Newcastle disease virus genomes ].
[OBJECTIVE] Although much is done in the coding genes of Newcastle disease virus (NDV) , limited papers can be found with non-coding sequences. In this paper, the evolution tendency of non-coding sequences was studied. [METHODS] NDV strain LC12 isolated from duck with egg drop syndrome in 2012, and others 35 strains genome cDNA of different NDV genotype were sought and obtained from GenBank. Analytical approaches including nucleotide homology, nucleotide alignment and phylogenetic tree were associated with the leading sequences, trailer sequences, intergenic sequences (IGS), and coding gene between 5 'and 3' UTR nucleotide, respectively. [RESULTS] The location and the length of the non-coding sequences highly conserve, and the variation trend of non-coding sequences is synchronous with the entire genomes and coding genes. [ CONCLUSION] The molecular variation of the coding gene was indistinguishable with the non-coding gene in view of the NDV genome.


Need and responsiveness in the treatment of a severely traumatized patient: a relational perspective.
Severely traumatized patients may exhibit poor functioning and a great deal of dependence upon the therapist. The question is raised as to what such patients truly need from a therapist, and the concept of optimal responsiveness is described. These patients may display complex blends of deficits, resulting from inadequate structuralization, together with pathological internal representations. Their expressed needs in therapy may be true requirements and/or expressions of wishes to be compensated for past suffering and refusal to assume adult functioning. Discerning what might constitute optimal responsiveness to true needs may be further complicated by the propensity some of these patients have for dysfunctional and impulsive behavior. A case is presented that illustrates some of the difficulties in determining how to respond to intense expressions of need, including needs for constant availability of the therapist and for physical contact. It is concluded that although this patient did not need everything from the therapist that she initially thought that she did, her needs were so great that an outpatient treatment situation often seemed insufficient. Despite an overall positive outcome for the patient, the treatment experience was very difficult for the therapist.


Synchronous primary diffuse large B-cell lymphoma and papillary thyroid carcinoma: A case report highlighting "Lymphoma first approach".
Papillary thyroid carcinoma (PTC) is the most common type of all thyroid carcinomas and accounts for up to 90% of all thyroid malignancies. It is the most indolent form of the disease and has an excellent prognosis. On the other hand, Primary thyroid lymphoma (PTL) is a rare entity accounting for only about 1% to 5% of all thyroid malignancies and only 2% of extranodal lymphomas. Synchronous PTC and PTL is a very rare condition and only a few cases have been reported in the literature up till now. We report one such case in a 52-year-old lady who was referred to us with goiter and progressively increasing difficulty in breathing.


Characterization of baboon testicular antigens using monoclonal anti-sperm antibodies.
Sperm antigens that appear during spermatogenesis in the baboon were identified by using three monoclonal antibodies generated in culture from mice immunized with baboon caudal epididymal spermatozoa. Antibodies BSA1 and BSA2 recognize trypsin-sensitive 84,000 and 45,000 dalton determinants that are restricted to the tail and anterior acrosomal regions of the sperm, respectively, as determined by Western blot and immunofluorescence techniques. The tail antigen absent in 2- and 3-yr-old baboon testes first appears in spermatid cells at about 4 yr of age. In contrast, the acrosomal antigen recognized by BSA2 is present in 3-yr-old primitive testicular germ cells. In the mature testis, the 45,000 molecular weight determinant is predominantly localized in the nucleus of late pachytene spermatocytes and round spermatid cells as observed via the avidinbiotin immunoperoxidase method. Antibody BSA3 reacted only with sailidase-treated sections of adult testis. This trypsin-resistant determinant, not expressed on testicular sperm, is recognized by antibody BSA3 only on epididymal sperm, thus indicating a post-testicular sperm modification.


National Infectious Diseases Surveillance data of South Korea.
The Korea Centers for Disease Control and Prevention (KCDC) operate infectious disease surveillance systems to monitor national disease incidence. Since 1954, Korea has collected data on various infectious diseases in accordance with the Infectious Disease Control and Prevention Act. All physicians (including those working in Oriental medicine) who diagnose a patient with an infectious disease or conduct a postmortem examination of an infectious disease case are obliged to report the disease to the system. These reported data are incorporated into the database of the National Infectious Disease Surveillance System, which has been providing web-based real-time surveillance data on infectious diseases since 2001. In addition, the KCDC analyzes reported data and publishes the Infectious Disease Surveillance Yearbook annually.


Electric Field-Responsive Mesoporous Suspensions: A Review.
This paper briefly reviews the fabrication and electrorheological (ER) characteristics of mesoporous materials and their nanocomposites with conducting polymers under an applied electric field when dispersed in an insulating liquid. Smart fluids of electrically-polarizable particles exhibit a reversible and tunable phase transition from a liquid-like to solid-like state in response to an external electric field of various strengths, and have potential applications in a variety of active control systems. The ER properties of these mesoporous suspensions are explained further according to their dielectric spectra in terms of the flow curve, dynamic moduli, and yield stress.


A bioavailability model predicting the toxicity of nickel to rainbow trout (Oncorhynchus mykiss) and fathead minnow (Pimephales promelas) in synthetic and natural waters.
The effects of Ca, Mg and pH on the toxicity of Ni to juvenile rainbow trout (Oncorhynchus mykiss) were examined during 17-26-day exposures to Ni in 15 synthetic test solutions. Higher chemical activities of Ca2+, Mg2+ and H+ reduced Ni toxicity, as demonstrated by increased 17-day median lethal concentrations expressed as Ni2+ activity (17-d LC50(Ni2+)). A non-linear increase of the 17-d LC50(Ni2+) with increasing H+ suggested that the effect of pH could not be appropriately described by single-site competition between Ni(2+) and H+ for sensitive sites on the fish gill. Instead, a linear increase of pNi2+ (=-log 17-d LC50(Ni2+)) with increasing pH was observed with a slope of 0.32. This slope was used as the basis for modelling the effect of pH. The effects of Ca and Mg were modelled according to single-site competition with logK(CaBL)=logK(MgBL)=3.6, both assumed to be independent of pH. The effect of pH was superimposed on this competition effect and was also assumed to be independent of Ca and Mg concentrations. The model was able to predict 17-d LC50s (expressed as dissolved Ni) in most synthetic test waters within a factor 2 deviation from observed toxicity. The model's predictive capacity was also evaluated using results of similar laboratory toxicity tests with juvenile rainbow trout in Ni-spiked European natural surface waters. For most of these waters, predicted 17-d LC50s did not deviate more than a factor 2 from observed toxicity. The same model, calibrated to account for sensitivity differences between species, life stages and/or exposure durations, was able to accurately predict 96-h LC50s for larval and juvenile fathead minnow (Pimephales promelas) and juvenile rainbow trout, based on data taken from literature. Although the developed model seems very promising, the uncertainty around the role of alkalinity and the exact mechanisms by which Ca, Mg and pH modify Ni toxicity need to be further explored.


Urinary tract involvement in peritoneal metastatic disease: Is this a contraindication to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy?
Urinary tract involvement in resectable peritoneal malignancies might require extensive resections and reconstructions in the genitourinary tract during the performance of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), a fact which could impair the postoperative course and survival of these patients. We performed a review of the literature to assess whether urinary tract involvement in patients with peritoneal metastases undergoing CRS and HIPEC could affect the postoperative outcomes with respect to morbidity, mortality and survival rates, identifying a total of 6 retrospective studies addressing these clinical questions. Despite their heterogeneity, the existing studies demonstrate that despite a possible increase in postoperative complications when urological procedures are required as part of cytoreduction, survival outcomes do not seem to be affected. This review therefore concludes that urinary tract 6 in peritoneal metastatic disease is not a contraindication to CRS and HIPEC.


Kinetics in surface reconstructions on GaAs(001).
We have successfully controlled the surface structures of GaAs(001) by changing incident As-molecular species. Under As4 fluxes, the c(4 x 4) reconstruction with Ga-As dimers [c(4 x 4)alpha structure] is obtained, but the formation of three As-As dimer structures [c(4 x 4)beta structure] is kinetically limited. On the other hand, the structure change from the (2 x 4), through c(4 x 4)alpha, to c(4 x 4)beta phases is observed under As2 fluxes. We found that the c(4 x 4)alpha structure is energetically metastable and provides a kinetic pathway for the structure change between the (2 x 4) and c(4 x 4)beta phases under As2 fluxes.


Depression and alcoholism: clinical considerations in management.
When alcohol abuse occurs with depression, both the substance abuse and the mood disorder necessitate treatment. These conditions may have some similar manifestations, making differential diagnosis difficult. Depressed alcoholics report more previous treatment for substance abuse, withdrawal symptoms, and marital problems than those without depression. They also incur greater loneliness, unemployment, and social ineptness. Depressive symptoms found commonly in this group include work inhibition, guilt, self-disgust, dissatisfaction, and social disinterest. A history of depression among relatives favors a dual diagnosis of alcoholism and depression. Distinguishing those alcoholics with specific depressive illness enhances the therapeutic efficacy. Alcohol abusers need treatment, but those with concomitant depression persisting well beyond detoxification often require antidepressant medications. In long-term care, lithium may reduce alcohol-related rehospitalizations. A strong doctor-patient relationship with or without pharmacotherapy promotes continuation in a therapeutic regimen. Involvement in Alcoholics Anonymous and disulfiram maintenance therapy are other deterrents to drinking relapse.


Internalizing and externalizing psychopathology in middle age: genetic and environmental architecture and stability of symptoms over 15 to 20 years.
Internalizing and externalizing psychopathology factors explain much of the covariance among psychiatric conditions, especially at the level of genetic risk. However, few studies have examined internalizing and externalizing factors in middle-aged samples, especially their ability to predict later symptoms across midlife. The goals of the current study were (i) to quantify the genetic and environmental influences on internalizing and externalizing psychopathology in individuals in their early 40s, and (ii) examine the extent to which these genetic and environmental influences predict self-reported measures of internalizing and externalizing symptoms 15-20 years later. 1484 male twins completed diagnostic interviews of psychopathology at mean age 41 and self-reported measures of anxiety, depression, substance use, and related variables at up to two time-points in late middle age (mean ages 56 and 62). Structural equation modeling of the diagnostic interviews confirmed that internalizing and externalizing factors accounted for most of the genetic variance in individual disorders, with substantial genetic (ra = 0.70) and environmental (re = 0.77) correlations between the factors. Internalizing psychopathology at age 41 was correlated with latent factors capturing anxiety, depression, and/or post-traumatic stress symptoms at ages 56 (r = 0.51) and 62 (r = 0.43). Externalizing psychopathology at age 41 was correlated r = 0.67 with a latent factor capturing aggression, tobacco use, and alcohol use at age 56. Stability of both factors was driven by genetic influences. These findings demonstrate the considerable stability of internalizing and externalizing psychopathology symptoms across middle age, especially their genetic influences. Diagnostic interviews effectively predict self-reported symptoms and behaviors 15-20 years later.


Soft x-ray Ar + 8 laser excited by low-voltage capillary discharge.
We demonstrated the operation of a 46.9-nm capillary discharge Ar + 8-laser excited by electrical pulses at a very low voltage (35 - 45 kV), which is approximately two times lower than previously reported. The decrease in pulse voltage not only allows for further reduction in the size of the laser's excitation part, but also a principal shift to the experimental methods, techniques, and technologies used in ordinary pulsed gas lasers operating in the ultraviolet, visible, and infrared regions of the spectra. In an argon-filled alumina capillary with an inner diameter of 3.1 mm and a length of 22 cm, laser pulses with an energy of 4 µJ and a duration of 1.6 ns were generated. The laser produces a beam with a Gaussian intensity distribution and an FWHM divergence of 1.9 mrad. The results could be particularly useful in the development of compact, practical soft x-ray capillary lasers for use in small laboratories at educational and research institutions.


Normal esophageal high-resolution manometry and impedance values in the supine and sitting positions in the population of Northern China.
The aim of this study was to investigate the normal high-resolution manometry and impedance (HRiM) values in the supine and sitting positions in the population of Northern China, and to investigate the influence of different body positions and bolus consistency on esophageal HRiM findings. In this study, healthy volunteers in the supine position underwent esophageal HRiM examination of 10 swallows of 5 mL normal saline solution and 10 swallows of 5 mL synthetic gel of known viscosity, and in the sitting position of an additional five swallows of a synthetic gel of known viscosity. Total bolus transit time (TBTT), complete bolus transit rate (CBTR), distal contractile integral (DCI), distal esophageal amplitude (DEA), and integrated relaxation pressure (IRP) were measured. Sixty-two healthy volunteers were examined in the supine position and 45 of these performed additional swallows of the viscous gel in the sitting position. In the supine position, normal values for swallowing the liquid and viscous boli were as follows: TBTT 6.9 ± 0.9 and 8.0 ± 1.2 s (P < 0.001), CBTR 90.3 ± 14.0 and 77.9 ± 20.3% (P < 0.001), DCI 1891.5 ± 1131.9 and 1967.8 ± 1140.1 mmHg.s.cm (P = 0.227), DEA 95.3 ± 35.4 and 98.7 ± 37.5 mmHg (P = 0.148), and IRP 10.4 ± 4.9 and 9.0 ± 4.2 mmHg (P < 0.001), respectively. For swallows of the viscous boli in the sitting position, TBTT, DCI, DEA, and IRP were significantly decreased, while CBTR was unchanged (P = 0.075). Normal HRiM values of the population of Northern China were established. Esophageal transit times of viscous boli were significantly slower, more often incomplete and produced less normal peristalsis in the supine position than swallows of liquid boli. Independent reference values for different manometric systems, body positions, and population need to be established before clinical application.


Potential Pathways From Peer Victimization to Alcohol Use Among Biracial Adolescents: The Intervening Role of Parental Support.
This study examined pathways from peer victimization to alcohol use and the role of parental support in mediating potential peer effects among biracial youth. Given a significant dearth of research on biracial youth, this study addresses this significant gap in the extant literature. Secondary data analyses were conducted using the Health Behavior in School-Aged Children (HBSC) study in the United States. This study enrolled 492 self-identified biracial school-aged youth using a nationally representative sampling of public and private schools. Structural equation modeling was computed to test the mediational effects of low number of close friends, affiliation with delinquent friends, and parental support on alcohol use. Major findings indicated that affiliation with delinquent friends was correlated with higher alcohol use, higher levels of parental support were correlated with lower peer victimization, and higher levels of parental support were negatively correlated with affiliation with delinquent peers and alcohol use. Parental and peer effects remain salient for biracial youth who are navigating adolescence and experiencing peer victimization. School-based interventions that include parents and friends of biracial youth are likely to be effective in reducing peer victimization and its negative sequelae.


Polyethylenimine-mediated synthetic insertion of gold nanoparticles into mesoporous silica nanoparticles for drug loading and biocatalysis.
Mesoporous silica nanoparticles (MSNPs) have been used as an efficient and safe carrier for drug delivery and biocatalysis. The surface modification of MSNPs using suitable reagents may provide a robust framework in which two or more components can be incorporated to give multifunctional capabilities (e.g., synthesis of noble metal nanoparticles within mesoporous architecture along with loading of a bioactive molecule). In this study, the authors reported on a new synthetic route for the synthesis of gold nanoparticles (AuNPs) within (1) unmodified MSNPs and (2) 3-trihydroxysilylpropyl methylphosphonate-modified MSNPs. A cationic polymer, polyethylenimine (PEI), and formaldehyde were used to mediate synthetic incorporation of AuNPs within MSNPs. The AuNPs incorporated within the mesoporous matrix were characterized by transmission electron microscopy, energy dispersive x-ray analysis, and high-resolution scanning electron microscopy. PEI in the presence of formaldehyde enabled synthetic incorporation of AuNPs in both unmodified and modified MSNPs. The use of unmodified MSNPs was associated with an increase in the polycrystalline structure of the AuNPs within the MSNPs. The AuNPs within modified MSNPs showed better catalytic activity than those within unmodified MSNPs. MSNPs with an average size of 200 nm and with a pore size of 4-6 nm were used for synthetic insertion of AuNPs. It was found that the PEI coating enabled AuNPs synthesis within the mesopores in the presence of formaldehyde or tetrahydrofuran hydroperoxide at a temperature between 10 and 25 °C or at 60 °C in the absence of organic reducing agents. The as-made AuNP-inserted MSNPs exhibited enhanced catalytic activity. For example, these materials enabled rapid catalytic oxidation of the o-dianisidine substrate to produce a colored solution in proportion to the amount of H2O2 generated as a function of glucose oxidase-catalyzed oxidation of glucose; a linear concentration range from 80 to 800 μM and a detection limit as low as 80 μM were observed. The mesoscale pores of the as developed AuNP-inserted MSNPs were also used to entrap the hydrophobic drug paclitaxel. The results of this study indicate the potential use of the AuNP-inserted MSNPs in biocatalysis and drug delivery.


[Struma ovarii: a rare case of giant ovarian cyst].
Struma ovarii is a rare tumor, which accounts for 2.7% of ovarian teratomas and 0.01% of ovarian tumors. It usually affects women in the fifth decades of life and is most often detected incidentally during ultrasound and then confirmed histologically. The gold standard treatment is surgery and prognosis is excellent. We here report the particular case of a young female patient with giant struma ovarii whose radiological features were classified as unusual presentation. We match patient's data with those from the literature.


Fabrication of Ag-decorated BiOBr-mBiVO4 dual heterojunction composite with enhanced visible light photocatalytic performance for degradation of malachite green.
A visible light active Ag-decorated BiVO4-BiOBr dual heterojunction photocatalyst was prepared using a facile hydrothermal method, followed by the photodeposition of Ag. The photocatalytic activity of the synthesized samples was investigated by monitoring the change in malachite green (MG) concentration upon visible light irradiation. The synthesized sample was highly effective for the degradation of non-biodegradable MG. The enhanced activity observed was ascribed to the efficient separation and transfer of charge carriers across the dual heterojunction structure as verified by photoluminescence measurements. The removal of MG was primarily initiated by hydroxyl radicals and holes based on scavenger's effect. To gain insight into the degradation mechanism, both high performance liquid chromatography and high resolution-quantitative time of flight, electrospray ionization mass spectrometry measurements during the degradation process were carried out. The degradation primarily followed the hydroxylation and N-demethylation process. A possible reaction pathway is proposed on the basis of all the information obtained under various experimental conditions.


A phase 1b, open-label study of trebananib plus bevacizumab or motesanib in patients with solid tumours.
To examine the angiopoietin pathway inhibitor trebananib IV plus the anti-VEGF agents bevacizumab or motesanib in advanced solid tumours. In this open-label phase 1b study, patients received IV trebananib 3 mg kg-1 QW plus bevacizumab 15 mg kg-1 Q3W (cohort 1) or motesanib orally 75 mg (cohort 2); or trebananib 10 mg kg-1 plus bevacizumab 15 mg kg-1 (cohort 3) or motesanib 125 mg (cohort 4). If <33% of patients had dose-limiting toxicities (DLTs), dose escalation occurred. Endpoints were treatment-related adverse events (AEs) incidence and pharmacokinetics (primary); anti-trebananib antibodies, biomarkers, and tumour response (secondary). Thirty-six patients received ≥ 1 dose of trebananib (cohorts 1, 2, 3, 4; n = 6, 8, 19, 3). DLT of G3 intestinal perforation and G3 tumor haemorrhage occurred in cohorts 2 and 3, respectively (both n = 1). Across both trebananib plus bevacizumab cohorts, the most common AEs included fatigue (n = 8), diarrhoea (n =4), constipation (n = 3), nausea (n = 3), and epistaxis (n = 3). Three patients across those cohorts had grade ≥ 3 AEs. Across the trebananib plus motesanib cohorts, the most common AEs included hypertension (n = 4), diarrhoea (n = 4), nausea (n = 3), fatigue (n = 3), vomiting (n = 2), and decreased appetite (n = 2). Two patients had grade ≥ 3 AEs. Trebananib did not markedly affect motesanib pharmacokinetics. Across the trebananib plus bevacizumab cohorts, two patients had a partial response; 11 patients had stable disease lasting >6 months. Across the trebananib plus motesanib cohorts, one patient had a partial response; five patients had stable disease lasting >6 months. Trebananib IV 3 mg kg-1 or 10 mg kg-1 plus bevacizumab or motesanib in advanced solid tumours may be associated with less severe toxicities relative to those emerging when combining two anti-VEGF agents.


Cardiac considerations in the operative management of the patient with Duchenne or Becker muscular dystrophy.
Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) is a progressive multisystem neuromuscular disorder. In addition to the skeletal muscle, the myocardium in the DMD/BMD patient is dystrophin deficient which results in a progressive cardiomyopathy. The myopathic myocardium poses significant risk of increased morbidity and mortality at the time of major surgical procedures. Careful attention must be given to the DMD/BMD patient during the intraoperative and postoperative period. Anesthesia selection is critical and anesthetics should be avoided which have been shown to be harmful in this patient population. Preanesthesia assessment should include cardiac consultation and detailed preoperative evaluation. Intraoperative management needs to insure that the weakened myocardium is not compromised by physiologic changes such as hypotension or major fluid shifts. Finally, attention to the cardiac status of the patient must continue into the postoperative period. The surgical care of the DMD/BMD patient requires a multispecialty approach to insure operative success.


Optimization, purification, and characterization of xylanase production by a newly isolated Trichoderma harzianum strain by a two-step statistical experimental design strategy.
Xylanases are hydrolytic enzymes with a wide range of applications in several industries such as biofuels, paper and pulp, food, and feed. The objective of this study was to optimize the culture conditions and medium components for maximal xylanase production from a newly isolated Trichoderma harzianum strain using the Plackett-Burman Design (PBD) and Box Behnken Design (BBD) experimental strategies. Xylanase production was enhanced 4.16-fold to 153.80 U/ml by BBD compared to a preliminary one-factor-at-a-time (OFAT) activity of 37.01 U/ml and 2.24-fold compared to the PBD (68.70 U/ml). The optimal conditions for xylanase production were: 6 days of fermentation, incubation temperature of 70 °C, pH 5.0, agitation of 160 rpm, and 1.2% wheat bran and ammonium sulphate. The experimental design effectively provided conditions for the production of an acidic-thermostable enzyme with exciting potential for application in animal feed improvement. The acidic-thermostable xylanase was purified from the submerged culture and SDS-PAGE analysis revealed a molecular weight of 72 kDa. This protein had maximum xylanolytic activity at pH 6.0 and 65 °C and was stable for 4 h retaining > 70% activity and exhibited substrate specificity for beechwood xylan with a Km of 5.56 mg/ml and Vmax of 1052.63 µmol/min/mg. Enzyme activity was enhanced by Fe2+, Mg2+, and Zn2+. There was an absence of strong inhibitors of xylanase activity. Overall, these characteristics indicate the potential for at least two industrial applications.


Representing Global Reactive Potential Energy Surfaces Using Gaussian Processes.
Representation of multidimensional global potential energy surfaces suitable for spectral and dynamical calculations from high-level ab initio calculations remains a challenge. Here, we present a detailed study on constructing potential energy surfaces using a machine learning method, namely, Gaussian process regression. Tests for the 3A″ state of SH2, which facilitates the SH + H ↔ S(3P) + H2 abstraction reaction and the SH + H' ↔ SH' + H exchange reaction, suggest that the Gaussian process is capable of providing a reasonable potential energy surface with a small number (∼1 × 102) of ab initio points, but it needs substantially more points (∼1 × 103) to converge reaction probabilities. The implications of these observations for construction of potential energy surfaces are discussed.


Identification of Differential Roles of MicroRNA-33a and -33b During Atherosclerosis Progression With Genetically Modified Mice.
Background Micro RNA (miR)-33 targets cholesterol transporter ATP -binding cassette protein A1 and other antiatherogenic targets and contributes to atherogenic progression. Its inhibition or deletion is known to result in the amelioration of atherosclerosis in mice. However, mice lack the other member of the miR-33 family, miR-33b, which exists in humans and other large mammals. Thus, precise evaluation and comparison of the responsibilities of these 2 miRs during the progression of atherosclerosis has not been reported, although they are essential. Methods and Results In this study, we performed a comprehensive analysis of the difference between the function of miR-33a and miR-33b using genetically modified mice. We generated 4 strains with or without miR-33a and miR-33b. Comparison between mice with only miR-33a (wild-type mice) and mice with only miR-33b (miR-33a-/-/miR-33b+/+) revealed the dominant expression of miR-33b in the liver. To evaluate the whole body atherogenic potency of miR-33a and miR-33b, we developed apolipoprotein E-deficient/miR-33a+/+/miR-33b-/- mice and apolipoprotein E-deficient/miR-33a-/-/miR-33b+/+ mice. With a high-fat and high-cholesterol diet, the apolipoprotein E-deficient/miR-33a-/-/miR-33b+/+ mice developed increased atherosclerotic plaque versus apolipoprotein E-deficient/miR-33a+/+/miR-33b-/- mice, in line with the predominant expression of miR-33b in the liver and worsened serum cholesterol profile. By contrast, a bone marrow transplantation study showed no significant difference, which was consistent with the relevant expression levels of miR-33a and miR-33b in bone marrow cells. Conclusions The miR-33 family exhibits differences in distribution and regulation and particularly in the progression of atherosclerosis; miR-33b would be more potent than miR-33a.


Fluoro-deoxi-glucose uptake and angiogenesis are independent biological features in lung metastases.
Neoangiogenesis and enhanced glucose metabolism in neoplasms are likely to be activated by the same biochemical stimulus; hypoxia. A correlation between these two parameters has been postulated. The objective of this study was to evaluate the relationship between Fluoro-desoxi-glucose uptake at positron emission tomography scan and angiogenesis in lung metastasis. Fluoro-desoxi-glucose activity, expressed as a standard uptake value, and microvessel intratumoural density, were retrospectively calculated in a series of 43 lung metastasis resected in 19 patients. Primary sites were colorectal cancer in 16 metastases, sarcoma in eight, gynaecological in four and other sites in 15. The correlation between the two parameters was tested by logistic regression and multivariate analysis. Positron emission tomography scan was positive in 17 patients (sensitivity 89%). No correlation was observed between standard uptake value and microvessel intratumoural density in this series of lung metastasis. Positron emission tomography negative and positive nodules presented comparable value of microvessel intratumoural density (12.9 vs 11.3). Standard uptake value was significantly correlated with nodules size and was higher in colon cancer metastasis than in sarcoma ones. Microvessel intratumoural density was independent from nodule size but significantly higher in sarcoma than in colon cancer metastasis. The lack of correlation was confirmed by multivariate analysis after adjustment for tumour type and nodules size. The present study demonstrated that positron emission tomography scan is positive in a high proportion of patients regardless of microvessel density. Glucose uptake and angiogenesis appear to be independent biological features in lung metastasis. This observation may have implications for future antiangiogenic therapies.


Ethnobotanical study on medicinal plants used by Mulam people in Guangxi, China.
The Mulam are an ethnic group native to Guangxi, and nearly 80% of the Mulam population lives in Luocheng Mulam Autonomous County, northern Guangxi, southern China. They have accumulated rich medicinal folk knowledge through practice and experience in their long-term struggles with disease and the harsh natural environment. However, their traditional medicinal knowledge is threatened due to a lack of written records, conservative inheritance patterns, and rapid economic development. Therefore, the investigation and documentation of medicinal plants and their associated indigenous wisdom are necessary. Ethnobotanical data were collected from 12 villages and five communities in Luocheng County from January 2013 to April 2017. A total of 128 informants were interviewed through semistructured interviews, field observations, group discussions, and guided field walks. Quantitative indices such as use categories, preference ranking exercises, the informant consensus factor (ICF), and the fidelity level (FL) were used to evaluate the importance of medicinal plant species. Additionally, group discussions were conducted about the conservation of and threats to medicinal plants and traditional knowledge. A total of 456 medicinal plant species from 350 genera and 132 families were recorded and documented in our ethnobotanical investigation. Most of them (335 species, 73.47%) were obtained from wild habitats. Most of the documented species (246) were herbaceous (54%), followed by shrubs, with 76 species (17%), lianas, with 75 species (16%), and trees, with 59 species (13%). The most common method of administration was oral administration, which was used for 390 species (62.70%). The most common method of preparation was decoction (316 species, 54.11%). The plants were used to treat 312 human diseases in 12 disease categories, and most of the categories had a high ICF value. The highest ICF value was recorded for gynecological ailments (0.92), followed by nervous and psychosomatic problems (0.90) and digestive system diseases (0.89). Traditional medicinal knowledge and medicinal plants are under threat due to conservative inheritance processes and anthropogenic pressures for various reasons. A rich diversity of medicinal plants is distributed in the Mulam area, and these plants play an important role in healthcare among the Mulam people. Mulam people are skilled in using the plants in their surroundings to treat diseases in their daily lives. However, their traditional medicinal knowledge and medicinal plants are greatly threatened by rapid economic development for various reasons. Thus, policies and practices for the conservation of medicinal plants and the associated traditional knowledge are necessary.


Graphite-mediated reduction of 2,4-dinitrotoluene with elemental iron.
The mechanism and pathway through which 2,4-dinitrotoluene (DNT) is reduced with elemental iron were investigated through batch experiments performed utilizing the same iron surface area, with high-purity iron powder and Master Builders scrap iron. In addition to different kinetics and adsorption patterns, the distribution of two intermediates, 4-amino-2-nitrotoluene (4A2NT) and 2-amino-4-nitrotoluene (2A4NT), contrasted sharply. This suggests that different mechanisms are involved in DNT reduction with pure iron and scrap iron. We hypothesized that exposed graphite in scrap iron transferred reductants from iron to adsorbed nitroaromatic molecules. This hypothesis was supported by an experiment conducted using two-compartment dialysis cells in which ONT and pure iron powder were separated by a graphite sheet. Results indicate that graphite-mediated, indirect reduction of DNT occurred primarily through reduction of the ortho nitro group to form 2A4NT, whereas DNT reduction at the iron (hydr/oxide) surface occurred via para nitro reduction to give 4A2NT. Based on pH and product analysis, atomic hydrogen probably accounted for most of the reducing equivalents that passed through the graphite, reacting with adsorbed DNT mainly through ortho nitro reduction. In contrast, electron was a minor fraction of the reducing equivalents, reducing DNT mainly through para nitro reduction. The implications of graphite as a reaction site and conductor of electron and atomic hydrogen are discussed with respect to treatment processes involving iron.


[Biliary sludge: pathogenesis, etiology and drug therapy].
To evaluate the effectiveness of the use of ursodeoxycholic acid (UDCA) for the treatment of biliary sludge (BS) and to compare the therapeutic effectiveness of the German substance UDCA and generic drugs from other manufacturers. The study involved 65 patients diagnosed with BS (K80.8). To assess the severity of BS, ultrasound of the gallbladder was performed before treatment, after 1, 3, 6 months during therapy, as well as an assessment of its contractility. All patients were randomized into 2 groups. Patients of the main group received UDCA Ursofalk (Germany) at a dose of 10 mg/kg for at least 6 months. Patients in the comparison group received UDCA (another manufacturer) at a dose of 10 mg/kg for at least 6 months. After 3 months of follow-up, the number of patients with dissolved sludge in the main group was 87.1%, while in the comparison group 50%. In 71% of patients, the normalization of the lean volume of the gallbladder was noted, and in the comparison group only in 47.1%. After 6 months of follow-up, complete resolution of BS in the main group was observed in 93.5% of cases, and in the comparison group in 73.6% of cases. As a result of the study, the high effectiveness of Ursofalk during oral litolysis in patients with stage I GI (BS) in the first 3 months of therapy, as well as the normalization of the contractile function of the gallbladder, were noted.


Comparison of melatonin with growth factors in promoting precursor cells proliferation in adult mouse subventricular zone.
Melatonin, secreted mainly by the pineal gland, plays roles in various physiological functions including protecting cell death. We showed in previous study that the proliferation and differentiation of precursor cells from the adult mouse subventricular zone (SVZ) can be modulated by melatonin via the MT1 melatonin receptor. Since melatonin and epidermal growth factor receptor (EGFR) share some signaling pathway components, we investigated whether melatonin can promote the proliferation of precursor cells from the adult mouse SVZ via the extracellular signal-regulated protein kinase /mitogen-activated protein kinase (ERK/MAPK) pathways in comparison with epidermal growth factor (EGF). Melatonin-induced ERK/MAPK pathways compared with EGF were measured by using in vitro and vivo models. We used neurosphere proliferation assay, immunocytochemistry, and immuno-blotting to analyze significant differences between melatonin and growth factor treatment. We also used specific antagonist and inhibitors to confirm the exactly signaling pathway including luzindole and U0126. We found that significant increase in proliferation was observed when two growth factors (EGF+bFGF) and melatonin were used simultaneously compared with EGF + bFGF or compared with melatonin alone. In addition, the present result suggested the synergistic effect occurred of melatonin and growth factors on the activating the ERK/MAPK pathway. This study exhibited that melatonin could act as a trophic factor, increasing proliferation in precursor cells mediated through the melatonin receptor coupled to ERK/MAPK signaling pathways. Understanding the mechanism by which melatonin regulates precursor cells may conduct to the development of novel strategies for neurodegenerative disease therapy.


Should I Ask Doctor Google? Reliability of Israeli Web-based Information Regarding General Orthopedic Injuries and Symptoms.
Websites serve as a source of medical information for a large part of the public, some claim to be a substitute for a physician's consultation. Many patients meet a physician after conducting internet research. Medical staff are concerned that internet sources of information are unreliable and may lead to erroneous decisions by patients. To examine the reliability of web-based sources of information (through the Google™ search engine) regarding five common orthopedic complaints and injuries. We performed a search of five common orthopedic complaints and injuries using the Google search engine. The reliability of web-based information was measured by the DISCERN tool, which is a valid and verified tool for examining the reliability of medical information sources to the public. The reliability of 47 websites was examined by two orthopedic surgeons and two senior residents. The overall average score given to the sites was 2.8, on a scale of 1 to 5. We found that the higher the site appeared in the search results, the higher the quality of its information. Commercial sites scored higher than general internet information sources. The internet network is a very broad source of information. For those who lack scientific education and training it is not easy to distinguish between reliable and unreliable or biased sources. The trend of searching for medical information and self-healing is increasing. We must strengthen the network with reliable sources by creating official scientific position papers by medical teams and promoting them online.


Comparison of Glaucoma Progression Between Unilateral and Bilateral Disc Hemorrhage Eyes and Associated Risk Factors for Progression.
To compare glaucoma progression between unilateral and bilateral disc hemorrhage (DH) eyes and to determine the associated risk factors. A total of 78 bilateral primary open-angle glaucoma (POAG) patients who had shown one or more occurrences of DH (48 eyes of 38 unilateral DH patients and 30 eyes of 30 bilateral DH patients) were included. Glaucoma progression was defined by visual field (VF) deterioration. The mean VF global indices progression rates in the pre-DH, post-DH and total follow-up periods were compared between the unilateral and bilateral DH groups. The cumulative probability of glaucoma progression between the 2 groups was compared by the Kaplan-Meier survival analysis. Univariate and multivariate Cox proportional hazard models were used to identify the risk factors for glaucoma progression. Among the mean VF global indices progression rates, only the mean pattern standard deviation progression rate showed a statistically significant difference between the groups (unilateral DH group: 0.30±0.38 dB/y; bilateral DH group: 0.13±0.27 dB/y) (P=0.042). The Kaplan-Meier analysis revealed a greater cumulative probability of progression in the unilateral than in the bilateral DH group (P=0.008). The multivariate Cox's proportional hazard model indicated unilaterality of DH to be a factor associated with glaucoma progression (hazard ratio, 2.587; P=0.030). In bilateral POAG patients with DH, unilaterality of DH is associated with glaucoma progression. Therefore, clinicians need to perform careful and frequent follow-up on bilateral POAG patients showing DH in only 1 eye during the follow-up period.


Persistent pulmonary hypertension of the newborn. Trends in incidence, diagnosis, and management.
Persistent pulmonary hypertension of the newborn ( PPHN ) has become a more commonly recognized problem in neonatal intensive care nurseries. In 62 neonates, 27 from 1980 and 35 from 1981, we compared classification, methods of diagnosis, modes of therapy, and survival. Thirty neonates (48%) had primary and 32 (52%) had secondary PPHN . Overall survival was 71% with significant differences in primary v secondary PPHN . Survival was also higher in 1981 than 1980 and was related to earlier diagnosis and to the more rapid initiation of therapy.


Which Anti-Incontinence Surgery Option is Better in Patients Undergoing Total Laparoscopic Hysterectomy? Burch Colposuspension or Transobturator Tape Procedure.
Stress urinary incontinence (SUI) surgery and hysterectomy are often performed in the same session. The aim of this study was to determine which urinary incontinence surgery would be a better option for patients who would undergo a hysterectomy for various indications. This retrospective study included 65 patients who had undergone total laparoscopic hysterectomy and anti-incontinence surgery (TOT or Burch).A retrospective chart review was performed to record the patient data including demographic features, duration of operations, postoperative complete blood count values and post-void residual urine volumes. ICIQ-UI and UDI-6 interrogations related to urinary incontinence were compared pre- and postoperatively between two groups. There was no difference in demographic characteristics and menopausal status between groups. No significant difference was found between two groups in postoperative period for urinary incontinence scores (p>0,05). When the duration of operation was compared, the duration was significantly higher in the TOT group. And the hematocrit drop in the group with TOT was significantly higher (p<0.05). Because the success rates of Burch colposuspension and transobturator procedures are similar, either of these two methods can be selected according to patient characteristics and surgeon experience. But Burch colposuspension seems to be more preferable in terms of blood loss and operation time than TOT.


Measurements of the critical power for self-injection of electrons in a laser wakefield accelerator.
A laser wakefield acceleration study has been performed in the matched, self-guided, blowout regime producing 720 +/- 50 MeV quasimonoenergetic electrons with a divergence Deltatheta_{FWHM} of 2.85 +/- 0.15 mrad using a 10 J, 60 fs 0.8 microm laser. While maintaining a nearly constant plasma density (3 x 10{18} cm{-3}), the energy gain increased from 75 to 720 MeV when the plasma length was increased from 3 to 8 mm. Absolute charge measurements indicate that self-injection of electrons occurs when the laser power P exceeds 3 times the critical power P{cr} for relativistic self-focusing and saturates around 100 pC for P/P{cr} > 5. The results are compared with both analytical scalings and full 3D particle-in-cell simulations.


Phase diagram and aqueous solubility of the lidocaine-prilocaine binary system.
The phase behavior of the lidocaine-prilocaine binary system has been studied by X-ray diffraction, differential thermal analysis, hot-stage microscopy, and IR spectrometry. No intermediate compounds or solid solubilities have been detected. The eutectic composition is close to 1:1, and the eutectic temperature is 18 +/- 1 degrees C. Aqueous solubility studies show that the lidocaine heat of solubility from the eutectic mixture is different from that of the pure drug, whereas it is the same for prilocaine. Investigations of various lidocaine-prilocaine ratios indicate that the two local anesthetics decrease the solubility of each other. The total solubility, however, is affected only to a minor extent.


Anti-selective direct catalytic asymmetric aldol reaction of thiolactams.
An anti-selective direct catalytic asymmetric aldol reaction of thiolactam is described. A soft Lewis acid/hard Brønsted base cooperative catalyst comprised of mesitylcopper/(R,R)-Ph-BPE exhibited high catalytic performance to produce an anti-aldol product with high stereoselectivity. The highly chemoselective nature of the present catalysis allows for the use of enolizable aldehydes as aldol acceptors. The diverse transformations of the thiolactam moiety highlight the synthetic utility of the present anti-aldol protocol.


Spatiotemporal brain dynamics in response to muscle stimulation.
The objective of the present study was to assess the spatiotemporal scenario of brain activity associated with sensory stimulation of the abductor pollicis brevis muscle. Spatiotemporal dipole models, using realistic individual boundary element head models, were built from somatosensory evoked potentials (SEPs; 64 Ch. EEG) to nonpainful and painful intramuscular electrostimulation (IMES) as well as to cutaneous electrostimulation delivered to the distal phalanx of the thumb. Nonpainful and painful muscle stimuli resulted in activation of the same brain regions. In temporal order, these were: the contralateral primary sensorimotor cortex, contralateral dorso-lateral premotor area (PM), bilateral operculo-insular cortices, caudal cingulate motor area (CMA), and posterior cingulate cortex/precuneus. Brain processing induced by muscle sensory input showed a characteristic pattern in contrast to cutaneous sensory input, namely: (1) no early SEP components to IMES; (2) an initial IMES component likely generated by proprioceptive input is not present for digit stimulation; (3) one source was located in the PM only for IMES. This source was unmasked by the lower stimulus intensity; (4) a source for IMES was located in the contralateral caudal CMA rather than being located in the cingulate gyrus. Cerebral sensory processing of input from the muscle involved several sensory and motor areas and likely occurs in two parallel streams subserving higher order somatosensory processing as well as sensory-motor integration. The two streams might on one hand involve sensory discrimination via SI and SII and on the other hand integration of sensory feedback for further motor processing via MI, lateral PM area, and caudal CMA.


[Analysis of clinical manifestations and surgical treatment of Crohn disease: a report of 82 cases].
To elucidate the clinical types of Crohn disease and evaluate its surgical treatment. Clinical data of 82 cases with Crohn disease were retrospectively analyzed from June 1972 to June 2003. Among 82 cases with Crohn disease,38 cases were diagnosed before operation,and 44 cases(53.7% ) were misdiagnosed. Main clinical manifestations included abdominal pain(96.3% ),diarrhea(89.0% ) and abdominal mass(28.0% ),other clinical manifestations included fistulation,intestinal hemorrhage and extra- intestinal manifestations such as ulcerative stomatitis,mycotic stomatitis. Patients received different surgical procedures as following: partial enterectomy in 57 cases,hemicolectomy and colostomy in 4 patients,partial ileectomy and ileostomy in 2,ileocolic bypass procedure in 3 patients,partial enterectomy and colectomy and anastomosis in 3 patients because of internal fistula,repair of ileal perforation in 2,lysis of adhesion in 6,drainage of intraperitoneal abscess and ostomy in 3,radical operation in 2 due to colon cancerization. Seventy- three cases(89.0% ) were cured by operation,postoperative complications occurred in 9 patients and 2 cases died. It is the key point to achieve successful operation that the corresponding operative modes respectively for varied types of Crohn disease should be adopted.


Quantitation of silica-induced type II cell hyperplasia by using alkaline phosphatase histochemistry in glycol methacrylate embedded lung.
A light microscopic technique based on alkaline phosphatase histochemistry was developed to specifically quantitate Type II cells in the intact rat lung. Lungs were fixed in 4% neutral-buffered formalin containing 0.25 M sucrose and embedded in glycol methacrylate. Two micron thick sections were mounted on glass microscope slides. Alkaline phosphatase activity was localized by using naphthol AS-BI phosphate as substrate in 0.125 M 2-amino-2-methyl-1-propanol buffer containing 0.625 mM MgCl2 (pH 8.9). Sections were counterstained with Harris hematoxylin. Type II cells were the only cell type in the alveolar region containing alkaline phosphatase activity, an observation that was confirmed by using electron microscopic histochemistry. By combining the alkaline phosphatase staining technique with standard morphometric procedures, the proliferative response to a single intratracheal dose of 10 mg silica was followed as a function of time. Type II cells were significantly increased at all time points examined. Twenty eight days following silica, Type II cells had increased to (252 +/- 16) X 10(6) cells per set of lungs compared to a control value of (141 +/- 32) X 16(6) cells. The method presented is a simple and rapid technique for examining Type II cell population kinetics.


PanWeb: A web interface for pan-genomic analysis.
With increased production of genomic data since the advent of next-generation sequencing (NGS), there has been a need to develop new bioinformatics tools and areas, such as comparative genomics. In comparative genomics, the genetic material of an organism is directly compared to that of another organism to better understand biological species. Moreover, the exponentially growing number of deposited prokaryote genomes has enabled the investigation of several genomic characteristics that are intrinsic to certain species. Thus, a new approach to comparative genomics, termed pan-genomics, was developed. In pan-genomics, various organisms of the same species or genus are compared. Currently, there are many tools that can perform pan-genomic analyses, such as PGAP (Pan-Genome Analysis Pipeline), Panseq (Pan-Genome Sequence Analysis Program) and PGAT (Prokaryotic Genome Analysis Tool). Among these software tools, PGAP was developed in the Perl scripting language and its reliance on UNIX platform terminals and its requirement for an extensive parameterized command line can become a problem for users without previous computational knowledge. Thus, the aim of this study was to develop a web application, known as PanWeb, that serves as a graphical interface for PGAP. In addition, using the output files of the PGAP pipeline, the application generates graphics using custom-developed scripts in the R programming language. PanWeb is freely available at http://www.computationalbiology.ufpa.br/panweb.


Causes and consequences of pathogenic processes in evolution: implications from experimental epilepsy in animals.
Examples from experimental epilepsy in animals are used to illustrate the view that a crucial role of the transfer of mechanisms from compensatory into pathogenic (e.g. lethal ones in the course of a disease), is played by the power of pathologic stimuli. In the genesis of epilepsy it is suggested that a critical increase of endogenous factors may underlie the conversion of the absence form of epilepsy into a generalized self-supporting form. The ability to precipitate endogenous self-augmenting mechanisms of diseases may have increased in the course of evolution. The lethal result of a serious pathogenic process leads to the suggestion that organisms cope with the disease by dying. This prevents spreading of the putative infectious disease within the population. This mechanism of disease aggravation could play a role in the survival of the species and in further evolutionary progress. This may explain why certain species may have survived in evolution and supports the theory of synthetic evolution.


Insulator to metal transition in fluid deuterium.
We have investigated the insulator to metal transition in fluid deuterium using first principles simulations. Both density functional and quantum Monte Carlo calculations indicate that the electronic energy gap of the liquid vanishes at about ninefold compression and 3000 K. At these conditions the computed conductivity values are characteristic of a poor metal. These findings are consistent with those of recent shock wave experiments but the computed conductivity is larger than the measured value. From our ab initio results we conclude that the transition is driven by molecular dissociation rather than disorder and that both temperature and pressure play a key role in determining structural changes in the fluid.


Freeze-thaw cycles enhance decellularization of large tendons.
The use of decellularized tendon tissue as a scaffold for tendon tissue engineering provides great opportunities for future clinical and current research applications. The aim of this study was to assess the effect of repetitive freeze-thaw cycles and two different detergents, t-octyl-phenoxypolyethoxyethanol (Triton X-100) and sodium dodecyl sulfate (SDS), on decellularization effectiveness and cytocompatibility in large tendons. Freshly collected equine superficial and deep digital flexor tendons were subjected to decellularization according to four different protocols (1 and 2: freeze-thaw cycles combined with either Triton X-100 or SDS; 3 and 4: Triton X-100 or SDS). Decellularization effectiveness was assessed based on the reduction of vital cell counts, histologically visible nuclei, and DNA content. Transmission electron microscopy was performed to evaluate cellular and extracellular matrix integrity. Further, cytocompatibility of scaffolds that had been decellularized according to the protocols including freeze-thaw cycles (protocols 1 and 2) was assessed by seeding the scaffolds with superparamagnetic iron oxide labeled mesenchymal stromal cells and monitoring the cells histologically and by magnetic resonance imaging for two weeks. Decellularization was significantly more effective when using the protocols including freeze-thaw cycles, leaving only roughly 1% residual nuclei and 20% residual DNA, whereas samples that had not undergone additional freeze-thaw cycles contained roughly 20% residual nuclei and 40% residual DNA. No morphological extracellular matrix alterations due to decellularization could be observed. Scaffolds prepared by both protocols including freeze-thaw cycles were cytocompatible, but the cell distribution into the scaffold tended to be better in scaffolds that had been decellularized using freeze-thaw cycles combined with Triton X-100 instead of SDS.


Regulation of differentiation potential of human mesenchymal stem cells by intracytoplasmic delivery of coactivator-associated arginine methyltransferase 1 protein using cell-penetrating peptide.
Recent studies suggest that epigenetic modifications, such as DNA methylation and histone modification, can alter the differentiation potential of stem cells or progenitor cells. Specifically, coactivator-associated arginine methyltransferase 1 (CARM1) is known to act as a coactivator for various transcription factors and to regulate gene expression by chromatin remodeling through histone methylation. Here, for the first time, we have used direct protein delivery of CARM1 using cell-penetrating peptide (CPP) to regulate the differentiation potential of human mesenchymal stem cells (hMSCs). Immunofluorescence showed that the CPP-CARM1 protein is successfully delivered into the nuclei of hMSCs. Further experiments using immunofluorescence and Western blotting showed that the delivered CARM1 protein can effectively methylate the arginine 17 residue of histone H3 in both bone marrow (BM)- and adipose-derived (AD)-hMSCs, thus suggesting that the CARM1 protein delivered by the CPP system is biologically active in hMSCs. Chromatin immunoprecipitation (ChIP) assay and genome-wide gene expression profiling supported the result that delivered CARM1 protein can cause chromatin remodeling through histone methylation. Finally, the CPP-CARM1 protein efficiently elevated the differentiation efficiency of BM-hMSCs and AD-hMSCs into adipogenic, osteogenic, and myogenic cell lineages in vitro. Altered expression of critical genes after hMSC differentiation was reconfirmed by real-time reverse transcription polymerase chain reaction (qRT-PCR). Collectively, our results suggest that CPP-CARM1 can elevate the differentiation potential of hMSCs into various cell types, and that this system using CPP is a useful tool for exogenous protein delivery in clinical applications of cell-based therapy.


Unilateral, 3D Arm Movement Kinematics Are Encoded in Ipsilateral Human Cortex.
There is increasing evidence that the hemisphere ipsilateral to a moving limb plays a role in planning and executing movements. However, the exact relationship between cortical activity and ipsilateral limb movements is uncertain. We sought to determine whether 3D arm movement kinematics (speed, velocity, and position) could be decoded from cortical signals recorded from the hemisphere ipsilateral to the moving limb. By having invasively monitored patients perform unilateral reaches with each arm, we also compared the encoding of contralateral and ipsilateral limb kinematics from a single cortical hemisphere. In four motor-intact human patients (three male, one female) implanted with electrocorticography electrodes for localization of their epileptic foci, we decoded 3D movement kinematics of both arms with accuracies above chance. Surprisingly, the spatial and spectral encoding of contralateral and ipsilateral limb kinematics was similar, enabling cross-prediction of kinematics between arms. These results clarify our understanding that the ipsilateral hemisphere robustly contributes to motor execution and supports that the information of complex movements is more bihemispherically represented in humans than has been previously understood.SIGNIFICANCE STATEMENT Although limb movements are traditionally understood to be driven by the cortical hemisphere contralateral to a moving limb, movement-related neural activity has also been found in the ipsilateral hemisphere. This study provides the first demonstration that 3D arm movement kinematics can be decoded from human electrocorticographic signals ipsilateral to the moving limb. Surprisingly, the spatial and spectral encoding of contralateral and ipsilateral limb kinematics was similar. The finding that specific kinematics are encoded in the ipsilateral hemisphere demonstrates that the ipsilateral hemisphere contributes to the execution of unilateral limb movements, improving our understanding of motor control. Additionally, the bihemisheric representation of voluntary movements has implications for the development of neuroprosthetic systems for reaching and for neurorehabilitation strategies following cortical injuries.


Irinotecan-based regimens for recurrent glioblastoma multiforme: [corrected] a systematic review.
This systematic review aims to assess irinotecan-based salvage regimens for patients with recurrent glioblastoma multiforme (GBM) beyond first line treatment. Eligible trials were identified using databases search and 25 studies were included in the final analysis. Among the 25 studies, PFS-6 rate was reported in 15 studies and it ranged from 16% to 63%. Median PFS was reported in 18 studies and it ranged from 1 to 7.6 months. While for median OS, it was reported in 17 studies and it ranged from 5.8 months to 17.9 months. The available data suggests that routine use of irinotecan-based salvage regimens cannot be recommended outside the setting of well-controlled prospective randomized studies investigating novel combinations of irinotecan.


[Immunology in medical practice. II. Antiphospholipid antibodies in pregnancy].
Antibodies against phospholipids are a risk factor for thrombotic disorders, but also for foetal death, pre-eclampsia, foetal distress and dysmaturity. This group of antibodies (aPLab) includes lupus anticoagulant (LAC) and anticardiolipin antibodies (aCL). These antibodies are encountered in patients with systemic lupus erythematosus (SLE), but also in patients with lupus-like disease and in women with (a history of) symptoms compatible with the antiphospholipid syndrome. Screening for a aPLab is advisable in these patients when they want to conceive and in women with recurrent foetal death after the 12th week of pregnancy. It is not clear if the antibodies exert a direct noxious action or are an accompanying phenomenon. Secondary prevention is possible with acetylsalicylic acid (80 mg/day), if desired in combination with subcutaneous heparin (5000-12,000 units twice daily). The thrombosis prophylaxis should be continued for 6 weeks after delivery.


Gene expression profiling by cDNA array in human hepatoma cell line in response to cisplatin treatment.
Gene expression profiling with cDNA array allows simultaneous analysis of the gene expression pattern of a large number of genes and may enhance the investigation of the molecular mechanisms involved in the treatment of hepatocellular carcinoma with cisplatin. We used cDNA array technology to assess the gene expression profiles related to cell cycle regulation and apoptosis in human hepatoma Hep3B cells in response to cisplatin treatment. In Hep3B cells, apoptosis induced by cisplatin was p53-independent, and was associated with up-regulation of cell cycle regulators, pro-apoptotic genes, growth receptors, and genes involved in signal transduction. These included p33ING1, c-Abl, Bax, insulin-like growth factor binding protein 3, Siva, cyclin D1, RhoA, and Raf-1. Down-regulation of cell cycle regulator CDC2 was observed. Semi-quantitative reverse transcription-polymerase chain reaction and/or Western blot analysis performed on seven of these genes confirmed their upregulation of gene expression. Such global analysis of the cytotoxic response to chemotherapeutic drugs may yield insight into the mechanisms of drug action and allow rational design of more effective treatment strategies.


Interrogation of EGFR Targeted Uptake of TiO2 Nanoconjugates by X-ray Fluorescence Microscopy.
We are developing TiO2 nanoconjugates that can be used as therapeutic and diagnostic agents. Nanoscale TiO2 can be surface conjugated with various molecules and has the unique ability to induce the production of reactive oxygen species after radiation activation. One way to improve the potential clinical usefulness of TiO2 nanoparticles is to control their delivery to malignant cells by targeting them to cancer cell specific antigens. Epidermal Growth Factor Receptor is one potential target that is enriched in epithelial cancers and is rapidly internalized after ligand binding. Hence, we have synthesized TiO2 nanoparticles and functionalized them with a short EGFR binding peptide to create EGFR-targeted NCs. X-ray Fluorescence Microscopy was used to image nanoconjugates within EGFR positive HeLa cells. Further labeling of fixed cells with antibodies against EGFR and Protein A nanogold showed that TiO2 nanoconjugates can colocalize with receptors at the cell's plasma membrane. Interestingly, with increased incubation times, EGFR targeted nanoconjugates could also be found colocalized with EGFR within the cell nucleus. This suggests that EGFR-targeted nanoconjugates can bind the receptor at the cell membrane, which leads to the internalization of NC-receptor complexes and the subsequent transport of nanoconjugates into the nucleus.


Temperature effects in first-principles solid state calculations of the chemical shielding tensor made simple.
We study the effects of atomic vibrations on the solid-state chemical shielding tensor using first principles density functional theory calculations. At the harmonic level, we use a Monte Carlo method and a perturbative expansion. The Monte Carlo method is accurate but computationally expensive, while the perturbative method is computationally more efficient, but approximate. We find excellent agreement between the two methods for both the isotropic shift and the shielding anisotropy. The effects of zero-point quantum mechanical nuclear motion are important up to relatively high temperatures: at 500 K they still represent about half of the overall vibrational contribution. We also investigate the effects of anharmonic vibrations, finding that their contribution to the zero-point correction to the chemical shielding tensor is small. We exemplify these ideas using magnesium oxide and the molecular crystals L-alanine and β-aspartyl-L-alanine. We therefore propose as the method of choice to incorporate the effects of temperature in solid state chemical shielding tensor calculations using the perturbative expansion within the harmonic approximation. This approach is accurate and requires a computational effort that is about an order of magnitude smaller than that of dynamical or Monte Carlo approaches, so these effects might be routinely accounted for.


The effect of four-phonon interaction on phonon thermal conductivity of hexagonal VTe2 and puckered pentagonal VTe2.
The traditional view is that complex structures have lower lattice thermal conductivity. However, it is observed that complex structures have higher lattice thermal conductivity than simple atomic structures in VTe2 systems after considering the four-phonon scattering effect. In this work, we calculate the lattice thermal conductivity of an H-VTe2 monolayer with a simple atomic structure and that of a PP-VTe2 monolayer with a complex atomic arrangement using first-principles calculations combined with the Boltzmann transport theory under the conditions of with and without the four-phonon scattering process. Our findings reveal that the lattice thermal conductivity of the PP-VTe2 monolayer along the x or y direction is 3-4 times lower than that of the H-VTe2 monolayer when only considering the three-phonon scattering process. After taking into account the four-phonon scattering process, the lattice thermal conductivity of both monolayers decreases. For the H-VTe2 monolayer, the lattice thermal conductivity decreases by 88.7% (from 1.33 to 0.15 W m-1 K-1) compared to only considering the three-phonon scattering process, mainly due to strong four-phonon scattering. In addition, the PP-VTe2 monolayer experiences a lower decrease in lattice thermal conductivity, with reductions of 12.5% (from 0.4 to 0.35 W m-1 K-1) and 11.7% (from 0.34 to 0.3 W m-1 K-1) in the x and y directions, respectively, because of the weak four-phonon scattering. Notably, the lattice thermal conductivity with the four-phonon scattering process of the H-VTe2 monolayer is twice as low as that of the PP-VTe2 monolayer. Hence, our findings suggest that even simple atomic structures can exhibit lower lattice thermal conductivity than complex structures when considering four-phonon interaction.


Gamma-vinyl-GABA (vigabatrin) in the therapy of Lennox-Gastaut syndrome: an open study.
The antiepileptic effect of vigabatrin (gamma-vinyl GABA, VGB) in children has been demonstrated in controlled and open studies. According to the literature, results were good to excellent in partial seizures (with and without becoming secondarily generalized) and promising in infantile spasms (IS). In patients with myoclonic epilepsies of early childhood and especially those with Lennox-Gastaut syndrome (LGS), the effect of VGB has been investigated only to a limited extent and the pattern of response was variable. The present open, add-on, dose-ranging study was initiated to assess the long-term effect and safety of VGB in a cohort of 20 children with LGS who were not responding sufficiently to first-line drug monotherapy with valproate (VPA) instead of adding classical second-line antiepileptic drugs [AEDs: benzodiazepines (BZD), phenobarbital (PB), primidone (PRM)], which usually are associated with rapid diminution of their antiepileptic properties and a high frequency of side effects. Eighty-five percent of children experienced a 50-100% reduction in seizure frequency, even after dose reduction of VPA. No serious side effects occurred except in 1 patient who experienced dyskinesia. Mood changes, sedation, ataxia, and hypersalivation, well-known complications of other AEDs, were not observed.


Functional characterization of the extranasal OR2A4/7 expressed in human melanocytes.
Olfactory receptors (ORs) were first described as specialized chemoreceptors in the nasal epithelium. In the last two decades, ORs have also been detected to be functionally expressed and active in different nonolfactory tissues of the human body, because they used to react to specific odour stimuli. In this study, we conducted a characterization of the extranasal OR2A4/7 expressed in primary human melanocytes and sections of the human skin. OR2A4/7 expression could be demonstrated at the transcript and protein level. We uncovered elevated intracellular cAMP and Ca2+ levels accompanied by elevated p38 and reduced p42/44 MAPK phosphorylation following odourant (cyclohexyl salicylate; CHS) stimulation of melanocytes. These results were associated with enhanced melanin biosynthesis in conjunction with the growth inhibition and differentiation of melanocytes. Our findings highlight the participation of OR2A4/7 in human primary melanocyte physiology and suggest an alternate mechanism that regulates melanogenesis.


Morphological and functional changes in the gut after massive small bowel resection and colon interposition in rhesus monkeys.
An experimental model of massive small bowel resection and colonic autograft in an antiperistaltic fashion in between the remnants of jejunum and ileum was developed in Rhesus monkeys. The gross morphological changes showed significant (p less than 0.001) lengthening and dilatation of the remnant jejunum, ileum and the colonic graft. Hypertrophy and hyperplasia of the mucosal and muscular layers of all the 3 segments was revealed by morphometric studies and the estimation of the nucleic acid content of the mucosa. All the 3 segments of the bowel showed a significant increase (p less than 0.001) in the uptake of D-glucose, L-alanine and L-phenylalanine when compared to the control animals. These changes were more pronounced in the animals kept for longer duration. Phlorizin was found to be inhibitory for the uptake of D-glucose in the grafted colon, suggesting the induction of an active nonelectrolyte transport process in the autografted colon. The present study suggests that the colonic loop adapts itself to the functions of the small bowel along with the compensatory adaptation of the remnant jejunum and the ileum for the loss of absorptive surface secondary to massive small bowel resection .


Versatile polarization interferometer.
A new form of polarizing interferometer has been assembled from six calcite-glass prisms and two halfwave plates. The interferometer has the large shear and long beam path capabilities needed for the examination of large objects and is capable of providing a stable interference pattern even when the two ends of the interferometer are supported independently. Lenses can be conveniently added to the system either to facilitate alignment or to extend its useful length.


The effect of spironolactone (Aldactone) and methyldopa in low and normal renin hypertension.
The effect on BP of 100 and 200 mg spironolactone/day has been compared with that of methyl-dopa, 750 mg/day, and with combined treatment with both drugs in 32 patients with essential hypertension. The 28 patients who completed the entire investigation were treated for 30 weeks, divided into 4 treatment periods and 4 placebo periods of equal duration. BP did not fall significantly during the initial placebo period, and at the end of each of the intervening placebo periods it rose to pretreatment levels. A signifcant decrease in mean BP was found during the 4 treatment periods. A fall exceeding 14% was registered in 32% of the patients after methyldopa, 750 mg/day, in 50% of the patients after spironolactone, 200 mg/day, in 89% after combined treatment with both drugs, and in 29% after spironolactone, 100 mg/day. Low renin hypertension was found in 9 of the 28 patients. The average decrease in mean BP after sironolactone, 200 mg/day, methyldopa, 750 mg/day, and after combined treatment did not differ significantly between the low and the normal renin group. The rationale for using diuretics such as spironolactone or thiazide as the basic therapy in essential hypertension is discussed. It is concluded that both are useful in the treatment of essential hypertension and might be used alone or in combination.


Age-related changes in the visual organ of WBN/Kob rats--an ophthalmoscopical study.
Changes in the visual organ with aging were investigated non-surgically in male WBN/Kob rats, in which spontaneous diabetic mellitus commonly occurs. Male Wistar/ST rats at the ages of 5, 9, 13, 17, 23, 27, 36, 45, 54, 67 and 80 weeks were examined for changes in the peri-orbital region, eyelid, lens, corpus vitreum and ocular fundus by macroscopic inspection and fundoscopy. The area around the eyelid was stained with reddish-brown excretions from the Harderian gland. This stain was frequently observed in rats of both strains aged 54 weeks or over, showing no difference in frequency between WBN/Kob rats and Wistar/ST rats. Lens opacity was observed in male WBN/Kob rats aged 67 weeks or over, and narrowing of the retinal artery and vein in those aged 36 weeks or over. The occurrence of lens opacity was consistent with that of visual dysfunction as determined by a test of the ability to differentiate light from dark using a Y-shaped apparatus (Kiyosawa et al., 1993).


Mesophotic coral bleaching associated with changes in thermocline depth.
As global temperatures continue to rise, shallow coral reef bleaching has become more intense and widespread. Mesophotic coral ecosystems reside in deeper (30-150 m), cooler water and were thought to offer a refuge to shallow-water reefs. Studies now show that mesophotic coral ecosystems instead have limited connectivity with shallow corals but host diverse endemic communities. Given their extensive distribution and high biodiversity, understanding their susceptibility to warming oceans is imperative. In this multidisciplinary study of an atoll in the Chagos Archipelago in the central Indian Ocean, we show evidence of coral bleaching at 90 m, despite the absence of shallow-water bleaching. We also show that the bleaching was associated with sustained thermocline deepening driven by the Indian Ocean Dipole, which might be further enhanced by internal waves whose influence varied at a sub-atoll scale. Our results demonstrate the potential vulnerability of mesophotic coral ecosystems to thermal stress and highlight the need for oceanographic knowledge to predict bleaching susceptibility and heterogeneity.


Gold-catalyzed cycloisomerization of 1,7-enyne esters to structurally diverse cis-1,2,3,6-tetrahydropyridin-4-yl ketones.
A synthetic method that relies on gold(I)-catalyzed cycloisomerization of 1,7-enyne esters to prepare highly functionalized cis-1,2,3,6-tetrahydropyridin-4-yl ketone derivatives in good to excellent yields and as a single regio-, diastereo-, and enantiomer is described. By taking advantage of the distinctive differences in the electronic and steric properties between an NHC (NHC = N-heterocyclic carbene) and phosphine ligand in the respective gold(I) complexes, a divergence in product selectivity was observed. In the presence of [PhCNAuIPr](+)SbF6(-) (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidine) as the catalyst, tandem 1,3-acyloxy migration/6-exo-trig cyclization/1,5-acyl migration of the substrate was found to selectively occur to give the δ-diketone-substituted 1,2,3,6-tetrahydropyridine adduct. In contrast, reactions with the gold(I) phosphine complex [MeCNAu(JohnPhos)](+)SbF6(-) (JohnPhos = (1,1'-biphenyl-2-yl)-di-tert-butylphosphine) as the catalyst was discovered to result in preferential 1,3-acyloxy migration/6-exo-trig cyclization/hydrolysis of the 1,7-enyne ester and formation of the cis-1,2,3,6-tetrahydropyridin-4-yl ketone derivative. The utility of this piperidine forming strategy as a synthetic tool that makes use of 1,7-enyne esters was exemplified by its application to the synthesis of an enantiopure analogue of the bioactive 2,3,4,4a,5,9b-hexahydroindeno[1,2-c]pyridine family of compounds.


Perspectives on zebrafish models of hallucinogenic drugs and related psychotropic compounds.
Among different classes of psychotropic drugs, hallucinogenic agents exert one of the most prominent effects on human and animal behaviors, markedly altering sensory, motor, affective, and cognitive responses. The growing clinical and preclinical interest in psychedelic, dissociative, and deliriant hallucinogens necessitates novel translational, sensitive, and high-throughput in vivo models and screens. Primate and rodent models have been traditionally used to study cellular mechanisms and neural circuits of hallucinogenic drugs' action. The utility of zebrafish ( Danio rerio ) in neuroscience research is rapidly growing due to their high physiological and genetic homology to humans, ease of genetic manipulation, robust behaviors, and cost effectiveness. Possessing a fully characterized genome, both adult and larval zebrafish are currently widely used for in vivo screening of various psychotropic compounds, including hallucinogens and related drugs. Recognizing the growing importance of hallucinogens in biological psychiatry, here we discuss hallucinogenic-induced phenotypes in zebrafish and evaluate their potential as efficient preclinical models of drug-induced states in humans.


Measurement of the viscosity of irreversible hydrocolloids.
Three techniques have been used to assess the shear rate dependence of the viscosity of mixed alginate impression materials prior to setting. Two methods used a cone-plate viscometer, and one method was a capillary extrusion technique. Data from the three sets of experiments have been critically compared. It has been shown that an unset alginate material exhibits Bingham behaviour.


[Toxicity of cationic liposome Lipofectamine 2000 in human pancreatic cancer Capan-2 cells].
To investigate the toxicity of cationic liposome Lipofectamine 2000 (Lipo) in human pancreatic cancer Capan-2 cells. Capan-2 cells were cultured in the presence of Lipo at toxic concentrations, and the cell growth, apoptosis and cell cycle changes were evaluated by cell counting and flow cytometry. The concentrations of both Lipo and siRNA affected the transfection efficiency. In a transfection volume of 2 ml, the presence of 5 microl Lipo resulted in slowed growth of Capan-2 cells, which was especially obvious after 3 days (P<0.001). Prolonged culture of the transfected cells caused significant increases in early apoptotic cells (P<0.05) and in the damaged or necrotic cells (P<0.001), and resulted in reduced viable cells (P<0.01); these changes became obvious after a 48-hour culture, which also increased the ratio of G(0)/G(1) phase cells (P<0.05) and decreased those of G(2)/M phase cells (P<0.01), S phase cells (P<0.01), and the late apoptotic cells (P<0.05). Toxic concentrations of Lipo can affect the growth, apoptosis and cell cycles of Capan-2 cells in vitro, and this urges careful concentration selection when using Lipo for gene transfer into different cells.