Phage-encoded colanic acid-degrading enzyme permits lytic phage infection of a capsule-forming resistant mutant Escherichia coli strain.
In this study, we isolated a bacteriophage T7-resistant mutant strain of Escherichia coli (named S3) and then proceeded to characterize it. The mutant bacterial colonies appeared to be mucoid. Microarray analysis revealed that genes related to colanic acid production were upregulated in the mutant. Increases in colanic acid production by the mutant bacteria were observed when l-fucose was measured biochemically, and protective capsule formation was observed under an electron microscope. We found a point mutation in the lon gene promoter in S3, the mutant bacterium. Overproduction of colanic acid was observed in some phage-resistant mutant bacteria after infection with other bacteriophages, T4 and lambda. Colanic acid overproduction was also observed in clinical isolates of E. coli upon phage infection. The overproduction of colanic acid resulted in the inhibition of bacteriophage adsorption to the host. Biofilm formation initially decreased shortly after infection but eventually increased after 48 h of incubation due to the emergence of the mutant bacteria. Bacteriophage PBECO4 was shown to infect the colanic acid-overproducing mutant strains of E. coli. We confirmed that the gene product of open reading frame 547 (ORF547) of PBECO4 harbored colanic acid-degrading enzymatic (CAE) activity. Treatment of the T7-resistant bacteria with both T7 and PBECO4 or its purified enzyme (CAE) led to successful T7 infection. Biofilm formation decreased with the mixed infection, too. This procedure, using a phage cocktail different from those exploiting solely receptor differences, represents a novel strategy for overcoming phage resistance in mutant bacteria.


[Placebo effect in randomized clinical trials in neuropathic pain patients].
Metaanalysis of randomized, double-blind studies applying to neuropathic pain with placbo as a controlled group. The aim of the study was to analyze if placebo effect differs depending on the type of neuropathic pain syndrome. The obtained data shows the existing differences of placebo effect in different neuropathic pain syndromes. The decreased placebo effect is observed in patients with persistent neuropathic pain.


Ab initio study of hydrogen-bond formation between cyclic ethers and selected amino acid side chains.
Binding energies for hydrogen-bonded complexes of six cyclic ethers with five hydrogen-bond donor molecules that mimic selected amino acid side chains have been calculated at the MP2/6-31G*, MP2/6-31+G*, MP2/6-311++G**(single point), and MP2/aug-cc-pvtz levels, using geometries obtained with or without counterpoise corrections throughout the geometry optimization. The calculated basis set superposition error (BSSE) amounts to 10-20% and 5-10% of the uncorrected binding energies for the neutral and ionic species, respectively, at the MP2/aug-cc-pvtz level. The authors conclude that the O...H distances in the hydrogen bonds and binding energies for the studied systems may be determined with uncertainties of up to 0.08 A and 1-2 kcal/mol, respectively, in comparison with the MP2/aug-cc-pvtz values at a reasonable computational cost by performing standard geometry optimization at the MP2/6-31+G* level. Hydrogen-bond formation energies are more negative for cyclic ethers compared to their counterparts with a C=C double bond in the ring next to the oxygen atom. The less negative hydrogen-bonding energy and the increased O...H separation have been attributed to the reduced basicity of the ether oxygen when the lone pairs can enter conjugation with the pi-electrons of the Calpha=Cbeta double bond. The present study is the first step toward the development of an affordable computational level for estimating the binding energies of natural product, fused ring ether systems to the human estrogen receptor.


Cochlear Implantation in Postmeningitic Deafness.
The aim of this study is to evaluate long-term outcomes of cochlear implantation (CI) in patients with postmeningitic deafness. Twenty-seven patients with severe to profound hearing loss due to bacterial meningitis and received CI were the subjects of this study. Surgical findings and long-term audiological performances were evaluated. Speech perception and speech intelligibility of the implanted patients were evaluated with the categories of auditory performance-II (CAP-II) test and speech intelligibility rating (SIR) test, respectively. Eighteen of the 27 patients had received full electrode insertion through the patent cochlear lumen. Remaining 9 patients had varying degrees of ossification throughout the cochlea and needed to be drilled to achieve partial electrode insertion. None of the patients exhibited surgical complication. Scores in both test batteries (CAP-II and SIR) were comparable between patients who received full or partial electrode insertion (P > 0.05). Cochlear implantation after postmeningitic deafness has favorable outcomes especially in long term. Although this type of inner ear pathology may require special considerations during surgery, it is a relatively safe procedure.


Comparison of Helicobacter pylori colonization on the tonsillar surface versus tonsillar core tissue as determined by the CLO test.
We conducted a prospective study to determine the correlation between the presence or absence of Helicobacter pylori on the tonsillar surface and in the tonsillar core as determined by the Campylobacter-like organism (CLO) rapid urease enzyme test. Our study population was made up of 55 patients who underwent adenoidectomy, tonsillectomy, or both from December 2002 through April 2003 at Khalili Hospital in Shiraz, Iran. Of these 55 patients, 45 (82%) were positive and 10 (18%) were negative for H pylori colonization as determined by CLO testing. Analysis of samples obtained from individual patients revealed differences in H pylori colonization between tonsillar surface samples and the core tissue samples. Of 106 tonsils obtained from 53 patients who underwent adenotonsillectomy or tonsillectomy, H pylori was found on 56 tonsillar surface samples (53%) and 24 tonsillar core samples (23%); only 13 tonsils (12%) contained H pylori both on the surface and in the core. We conclude that a surface swab is neither specific nor sensitive as an indicator of the presence or absence of H. pylori colonization in tonsillar core tissue.


Identification, sequence analysis, and infectivity of H9N2 avian influenza viruses isolated from geese.
The subtype H9N2 avian influenza virus greatly threatens the Chinese poultry industry, even with annual vaccination. Waterfowl can be asymptomatically infected with the H9N2 virus. In this study, three H9N2 virus strains, designated A/Goose/Jiangsu/YZ527/2011 (H9N2, Gs/JS/YZ527/11), A/Goose/Jiangsu/SQ119/2012 (H9N2, Gs/JS/SQ119/12), and A/Goose/Jiangsu/JD564/2012 (H9N2, Gs/JS/JD564/12), were isolated from domestic geese. Molecular characterization of the three isolates showed that the Gs/JS/YZ527/11 virus is a double-reassortant virus, combining genes of A/Quail/Hong Kong/G1/97 (H9N2, G1/97)-like and A/Chicken/Shanghai/F/98 (H9N2, F/98)-like; the Gs/JS/SQ119/12 virus is a triple-reassortant virus combining genes of G1/97-like, F/98-like, and A/Duck/Shantou/163/2004 (H9N2, ST/163/04)-like. The sequences of Gs/JS/JD564/12 share high homology with those of the F/98 virus, except for the neuraminidase gene, whereas the internal genes of Gs/JS/YZ527/11 and Gs/JS/SQ119/12 are closely related to those of the H7N9 viruses. An infectivity analysis of the three isolates showed that Gs/JS/SQ119/12 and Gs/JS/YZ527/11 replicated well, with seroconversion, in geese and chickens, the Gs/JS/JD564/12 did not infect well in geese or chickens, and the F/98 virus only infected chickens, with seroconversion. Emergence of these new reassortant H9N2 avian influenza viruses indicates that these viruses can infect both chicken and goose and can produce different types of lesions in each species.


Regulation of calcium uptake/efflux from the islet-cell endoplasmic reticulum with regard to the secretion of insulin.
Figure 8 summarizes some of the processes that may impact on the secretion of insulin by regulating Ca2+ handling by the beta-cell endoplasmic reticulum. A role for calmodulin in controlling the rate of Ca2+ efflux is indicated by both the ability of the calmodulin antagonist, W7 to stimulate Ca2+ efflux and by the ability of exogenous calmodulin to antagonize Ca2+ efflux in response to inositol trisphosphate (IP3). The impact of calmodulin on this system may be to serve as link in the feedback control of cellular Ca2+. In addition to IP3, a second messenger that may link signal transduction to the release of Ca2+ is the guanine nucleotide, GTP. GTP stimulates the efflux of Ca2+ from the endoplasmic reticulum through a mechanism distinct from IP3. It will be important to determine whether extracellular glucose concentration, or other modifiers of secretion, acutely regulate the GTP concentrations in the beta-cell and to assess if this function may be altered with a decrease in beta-cell function. A variety of evidence indicates that metabolism of glucose by the beta-cell somehow plays a major role in the cellular control of insulin secretion (Hedeskov, 1980). An important link in this process may be the direct effects of glucose 6-phosphate on the handling of Ca2+ by the endoplasmic reticulum. Glucose 6-phosphate is able to increase the active uptake of Ca2+ by these membranes and also to specifically inhibit Ca2+ efflux produced by the IP3. Concentrations of glucose 6-phosphate needed to achieve these effects are likely achieved under physiological conditions (Aschroft et al., 1970). It is also easy to imagine that in diabetes when the islets are chronically exposed to high glucose that, as a result of the content of the high Km glucokinase in the islet (Meglasson and Matschinsky, 1986), higher concentrations of glucose 6-phosphate may be achieved. Under these conditions glucose 6-phosphate may contribute to the islet-cell pathology by interfering with the acute control of Ca2+ handling by the endoplasmic reticulum.


Bax Activation Blocks Self-Renewal and Induces Apoptosis of Human Glioblastoma Stem Cells.
Glioblastoma (GBM) is characterized by a poor response to conventional chemotherapeutic agents, attributed to the insurgence of drug resistance mechanisms and to the presence of a subpopulation of glioma stem cells (GSCs). GBM cells and GSCs present, among others, an overexpression of antiapoptotic proteins and an inhibition of pro-apoptotic ones, which help to escape apoptosis. Among pro-apoptotic inducers, the Bcl-2 family protein Bax has recently emerged as a promising new target in cancer therapy along with first BAX activators (BAM7, Compound 106, and SMBA1). Herein, a derivative of BAM-7, named BTC-8, was employed to explore the effects of Bax activation in different human GBM cells and in their stem cell subpopulation. BTC-8 inhibited GBM cell proliferation, arrested the cell cycle, and induced apoptosis through the induction of mitochondrial membrane permeabilization. Most importantly, BTC-8 blocked proliferation and self-renewal of GSCs and induced their apoptosis. Notably, BTC-8 was demonstrated to sensitize both GBM cells and GSCs to the alkylating agent Temozolomide. Overall, our findings shed light on the effects and the relative molecular mechanisms related to Bax activation in GBM, and they suggest Bax-targeting compounds as promising therapeutic tools against the GSC reservoir.


Heat shock protein 47 as indispensible participant in liver fibrosis: Possible protective effect of lactoferrin.
Lactoferrin (LF) was previously suggested to have a protective effect against liver fibrosis by preventing hepatic stellate cells (HSCs) activation. The effect of LF on heat shock protein 47 (HSP47) has not yet been studied so this study was designed to investigate LF effect on HSP47 as a potential target for management of liver fibrosis and comparing it with silymarin (SM) in a thioacetamide (TAA)-induced liver fibrosis model. Rats were divided into four groups; normal control, TAA (TAA-treated), LF (LF + TAA-treated), and SM (SM + TAA-treated). After 6 weeks, both LF and SM improved the grade of cirrhosis, reduced collagen fibers deposition, inactivated HSCs, significantly decreased elevated liver enzymes, HSP47, hydroxyproline content, transforming growth factor-beta 1, matrix metalloproteinase-2, 8-hydroxydeoxyguanosine, malondialdehyde, nitric oxide levels and the percentage of alpha smooth muscle actin positive HSCs compared with TAA group. Moreover, LF significantly increased the total antioxidant capacity compared with TAA group. It could be concluded that LF is a promising antifibrotic drug and could be considered as one of the HSP47 inhibitors but SM is still more potent. © 2018 IUBMB Life, 70(8):795-805, 2018.


Adenomyosis: A Clinical Review of a Challenging Gynecologic Condition.
Adenomyosis is a heterogenous gynecologic condition. Patients with adenomyosis can have a range of clinical presentations. The most common presentation of adenomyosis is heavy menstrual bleeding and dysmenorrhea; however, patients can also be asymptomatic. Currently, there are no standard diagnostic imaging criteria, and choosing the optimal treatment for patients is challenging. Women with adenomyosis often have other associated gynecologic conditions such as endometriosis or leiomyomas, therefore making the diagnosis and evaluating response to treatment challenging. The objective of this review was to highlight current clinical information regarding the epidemiology, risk factors, pathogenesis, clinical manifestations, diagnosis, imaging findings, and treatment of adenomyosis. Several studies support the theory that adenomyosis results from invasion of the endometrium into the myometrium, causing alterations in the junctional zone. These changes are commonly seen on imaging studies such as transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI). The second most common theory is that adenomyosis results from embryologic-misplaced pluripotent mullerian remnants. Traditionally, adenomyosis was only diagnosed after hysterectomy; however, studies have shown that a diagnosis can be made with biopsies at hysteroscopy and laparoscopy. Noninvasive imaging can be used to help guide the differential diagnosis. The most common findings on 2-dimensional/3-dimensional TVUS and MRI are reviewed. Two-dimensional TVUS and MRI have a respectable sensitivity and specificity; however, recent studies indicate that 3-dimensional TVUS is superior to 2-dimensional TVUS for the diagnosis of adenomyosis and may allow for the diagnosis of early-stage disease. Management options for adenomyosis, both medical and surgical, are reviewed. Currently, the only definitive management option for patients is hysterectomy.


B cell compartments in multiple myeloma: flow cytometric analysis of their labelling indices and Bcl-2 protein expression.
Because recent reports have suggested that non plasmacytic tumor B cells are very rare in Multiple Myeloma (MM), we tried to characterize the B lineage in this disease by comparing by flow cytometry in the PB and BM of MM patients and of controls the proliferative activity (BrdU incorporation) and the Bcl-2 expression of different B cell subsets defined by cytoplasmic light chain, CD19 or CD10 antigen expression. The labelling indices (LI) of CD19+ and CD10+ BM cells in treated patients were higher than in controls and untreated patients. Plasma cell LI (PCLI) were close to previously published values of PCLI flow assays and did not correlate with the LI of BM B cells. Bcl-2 expression by BM CD19+ and CD10+ cells in patients was inferior to controls. These results agree with previously published data about the likely polyclonal nature of most pre PC B cells in MM.


Studies on the helminth parasites of sheep in Southern Greenland.
The nematode population of sheep on Greenland is dominated by Ostertagia circumcincta and three Nematodirus species: N. spathiger, N. helvetianus and N. abnormalis. These results are compared with those for other Nordic countries. Great similarities exist with subarctic Norway but there is a lesser degree of correlation with Iceland and lowland Norway which tend to have a richer spectrum of species. N. helvetianus and N. abnormalis, however, have not been reported from sheep in these countries. The abomasal worm population was remarkable in that it contained specimens with an abomally large body size. The epidemiology of infection followed the pattern recognized throughout Europe with an early-season periparturient rise in the faecal egg-count of the ewe being followed by increasing levels of infection in lambs in late summer. The epidemiology of Nematodirus infections was quite distinct from that seen in most of Europe. Species differences and the cool summer climate were thought to account for this disparity and a hypothesis was advanced to explain the observed pattern of events. Levels of infection were apparently similar in undergrazed and fully-utilized grazing areas. Dosing ewes during the winter (between November to March) eliminated the periparturient egg rise. Lambs could be kept almost worm free by keeping them on clean rangeland and dosing at 3-5 week intervals. A clear weight-gain advantage over conventionally reared lambs was only recorded in one year of the study.


Suicide among adolescents. A psychological autopsy study of psychiatric, psychosocial and personality-related risk factors.
The suicide rate among young males in Belgium has doubled over the last decade. As more knowledge about risk factors is required to develop national prevention strategies, we investigated adolescent suicides using the psychological autopsy method. A total of 32 informants were interviewed regarding 19 suicide cases (aged 15-19). A semi-structured interview schedule, constructed by Houston et al. (J Affect Disord 63:159-170, 2001), was used. All adolescents were suffering from one or more mental disorder(s) at the time of their death, and almost half of them were diagnosed with personality disorders. Adjustment disorders were diagnosed in one fifth of the sample, which appears to be relevant in view of the multiple life events and other psychosocial problems which adolescents were facing shortly before death. This suggests that difficulties in coping with stressful psychosocial problems are important in the course of the suicidal process. Only a small minority was receiving treatment for their disorders. Mental disorders, commonly untreated and combined with personality disorders and psychosocial problems, are frequently found in young suicide victims. This study suggests that education in the diagnosis and treatment of depression, adjustment disorders and suicide is important in the prevention of suicide.


The Effect of Comorbidity on Glycemic Control and Systolic Blood Pressure in Type 2 Diabetes: A Cohort Study with 5 Year Follow-Up in Primary Care.
To explore the longitudinal effect of chronic comorbid diseases on glycemic control (HbA1C) and systolic blood pressure (SBP) in type 2 diabetes patients. In a representative primary care cohort of patients with newly diagnosed type 2 diabetes in The Netherlands (n = 610), we tested differences in the five year trend of HbA1C and SBP according to comorbidity profiles. In a mixed model analysis technique we corrected for relevant covariates. Influence of comorbidity (a chronic disease already present when diabetes was diagnosed) was tested as total number of comorbid diseases, and as presence of specific disease groups, i.e. cardiovascular, mental, and musculoskeletal disease, malignancies, and COPD. In subgroup effect analyses we tested if potential differences were modified by age, sex, socioeconomic status, and BMI. The number of comorbid diseases significantly influenced the SBP trend, with highest values after five years for diabetes patients without comorbidity (p = 0.005). The number of diseases did not influence the HbA1C trend (p = 0.075). Comorbid musculoskeletal disease resulted in lower HbA1C at the time of diabetes diagnosis, but in higher values after five years (p = 0.044). Patients with cardiovascular diseases had sustained elevated levels of SBP (p = 0.014). Effect modification by socioeconomic status was observed in some comorbidity subgroups. Presence of comorbidity in type 2 diabetes patients affected the long-term course of HbA1C and SBP in this primary care cohort. Numbers and types of comorbidity showed differential effects: not the simple sum of diseases, but specific types of comorbid disease had a negative influence on long-term diabetes control parameters. The complex interactions between comorbidity, diabetes control and effect modifiers require further investigation and may help to personalize treatment goals.


Exploring the Experiences of DNP-Prepared Nurses Enrolled in a DNP-to-PhD Pathway Program.
The advancement of the doctor of nursing practice (DNP) degree and the need for nurse researchers with a doctor of philosophy (PhD) has led to significant growth in doctoral nursing education. Some DNP graduates have chosen to pursue a second terminal degree. This descriptive study explored the experiences of students completing a DNP-to-PhD pathway program. Data analysis revealed that DNP-to-PhD students desired acceptance in academia. Implications suggest the need for additional pathway programs, clear communication about program outcomes for both degrees, formal teaching preparation for all nurse educators, and collaborative opportunities for DNP- and PhD-prepared faculty.


Patterns of protein carbonylation during Medicago truncatula seed maturation.
Seeds mainly acquire their physiological quality during maturation, whereas oxidative conditions reign within cells triggering protein carbonylation. To better understand the role of this protein modification in legume seeds, we compared by proteomics patterns of carbonylated proteins in maturing seeds of Medicago truncatula naturally desiccated or prematurely dried, a treatment known to impair seed quality acquisition. In both cases, protein carbonylation increased in these seeds, accompanying water removal. We identified several proteins whose extent of carbonylation varied when comparing natural desiccation and premature drying and that could therefore be responsible for the impairment of seed quality acquisition or expression. In particular, we focused on PM34, a protein specific to seeds exhibiting a high sensitivity to carbonylation and of which function in dicotyledons was not known before. PM34 proved to have a cellulase activity presumably associated with cell elongation, a process required for germination and subsequent seedling growth. We discuss the possibility that PM34 (abundance or redox state) could be used to assess crop seed quality.


An inquiry into the fate of the transference in psychoanalysis.
Despite universal agreement about the importance of transference, there is no single, comprehensive, generally accepted explanation for the place transference occupies in clinical psychoanalytic theory. In this presentation, I trace the origins of some major trends prominent in theoretical controversy to their antecedents. Some seminal contributions which introduced important issues into the evolving theory of transference are highlighted; this is followed by a brief outline of the ideas of a representative sample of current theorists. This comparison of the appearance of fundamental evolutionary modifications of transference theory with present-day differences in theoretical emphasis leads to the identification of four persistent themes: (1) the nature of the influence of the patient's relationship with the analyst in the analytic experience, (2) how to account for the analyst's subjectivity and its role in the analytic process, (3) what weight to assign to the interpersonal dimension of the transference, and (4) differences among theoretical perspectives as reflected in the precise content of transference interpretations. Difficulties in the path of comparative evaluation of differences in theoretical accounts of the transference and its handling are noted. A few reasons for my adherence to the theory I prefer are mentioned solely for the purpose of underlining areas of controversy that require serious attention and further clarification.


Insight into the structural determinants of imidazole scaffold-based derivatives as p38 MAP kinase inhibitors by computational explorations.
P38 kinase plays a vital role in the inflammation mediated by tumor necrosis factor-α and interleukin-1β pathways, and thus the inhibitors of p38 kinase provide effective approach for the treatment of inflammatory diseases. Presently, a combined study of three-dimensional quantitative structure-activity relationship, molecular docking and molecular dynamics (MD) was undertaken to explore the structural insights of 174 2-thioimidazole compounds influencing the p38α inhibitory activities. Both the ligand-based resultant comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models exhibited satisfactory predictability (with Q(2)=0.475, R(2)(ncv)=0.774, R(2)(pre)=0.668 and Q(2)=0.504, R(2)(ncv)=0.745, R(2)(pre)=0.709, respectively). Furthermore, good consistency was observed between the 3D-QSAR models, docking and MD results. Our findings are: i) hydrogen bonding and steric size of the molecules play crucial roles in the mechanisms of action that a medium-sized bulky substituent on the 2-position, an electropositive H-bond donor substituent on the 6-position of the pyridine ring are favorable for increasing the inhibition activity; ii) 2- Thioimidazole derivatives may bind to the p38α kinase with a "lobster" active conformation, which is fixed by four hydrogen bonds they formed with the adjacent residues (Lys53, Gly110, Met109 and Ala157) and two hydrophobic interactions (in hydrophobic pockets I and II respectively) in p38α binding site. These models and the derived information may afford valuable clues for design of new potent p38α inhibitors.


Preparing feminist facilitators. Assisting abused women in transitional or support-group settings.
This article has reviewed one approach to the preparation of support group facilitators to enable them to better meet the needs of abused women. Those women may still be in abusive relationships or they may have left one; they may be unsure whether they are abused; or they may be seeking practical suggestions about ways to tackle a particular problem. Whatever their specific situations, they can benefit from a supportive, accepting, and safe environment in which to explore their options.


Colon Conundrum: A Fascinating Case Report Unraveling the Enigmatic Tactoid Bodies.
Tactile corpuscle-like bodies (TCLBs) are specialized mechanoreceptors found in the dermal papilla of glabrous skin. They are normally not found in the gastrointestinal (GI) mucosa. There has been an increase in incidental detection in the GI mucosa due to the widespread use of colonoscopy procedures. However, TCLB's clinical implications in the GI tract remain unknown. We present a case of a 74-year-old man who was noted to have TCLBs in the rectosigmoid mucosa following resection for iatrogenic perforation. The TCLBs were spindle-shaped, positive for S-100, and negative for CD68. We review the literature on TCLBs in the GI tract and discuss their potential function in the GI mucosa.


Ultrasonic-assisted extrusion of ZK60Mg alloy micropins at room temperature.
A new model of ZK60 magnesium micropins formed through ultrasonic-assisted extrusion at room temperature was developed. The billet was transmitted by the ultrasonic wave during the micropin-forming process. A self-designed apparatus was applied for the ultrasonic-assisted extrusion experiments. The effects of amplitude on the load-displacement curve, load reduction, temperature, microstructure, diameter after extrusion, microhardness, and compressibility of micropins were investigated. The results showed that the punch was always in contact with the billet when the displacement of the punch was larger than the amplitude. The maximum reduction of load was approximately 80% because of the dynamic recrystallization and ultrasonic softening. In addition, load reduction was almost similar under different amplitudes when the diameters of micropins after extrusion were 0.3 and 0.5mm as a result of the size effect. The microhardness of the micropins increased at the amplitude of 39 and 42μm as compared with the traditional extrusion. This finding was inconsistent with the results for copper and aluminum. The compression ratio of micropins prepared through ultrasonic-assisted extrusion improved by 14-20% on average at room temperature.


Is this STS work-related? ISO 1999 predictions as an adjunct to clinical judgment.
Physicians and audiologists are often asked to decide whether standard threshold shifts (STSs) are work-related; epidemiological data can inform these decisions. Predictions of ISO (2013) for both age-related and noise-induced threshold shifts, for the 2, 3, and 4 kHz average used in calculating OSHA STSs, are presented, in tables, graphs, and an Excel spreadsheet calculator. Specifically, the ISO 1999 model estimates age-related thresholds based on age and sex; it estimates noise-induced threshold shifts based on noise level and duration. It specifies that to estimate the final hearing thresholds for a person of given percentile, age, sex, and noise exposure, the expected age-related threshold is to be added to the expected noise-induced threshold shift. Examples show how these data can predict the relative contributions of aging and occupational noise to an STS. Early-career STSs, especially with high levels of noise exposure, are more likely to be primarily noise-induced. After the first decade of exposure, most STSs will be primarily age-related. Given a worker's age, sex, and occupational noise exposure history, ISO 1999 estimates of the expected contributions of aging and noise can supplement clinical judgment.


Development of a computer-based quantification method for immunohistochemically-stained tissues and its application to study mast cells in equine wound healing (proof of concept).
There is a growing interest in the scientific community to use computer-based software programs for the quantification of cells during physiological and pathophysiological processes. Drawbacks of computer-based methods currently used to quantify immunohistochemical staining are the complexity of use, expense of software and overly-simplified descriptions of protocol thereby limiting reproducibility. The precise role of mast cells in equine cutaneous wound healing is unknown. Given the contribution of mast cells to the chronic inflammation observed in human keloid, a pathology similar to exuberant granulation tissue (EGT) in horses, mast cells might be present in high numbers in equine limb wounds predisposed to EGT. The main goal of this study was to develop a reliable and reproducible quantification method for immunostained tissues using a computer software that is widely available, at no cost, to the scientific community. A secondary goal was to conduct a proof of concept using the newly-established method to quantify mast cells during wound healing at different anatomical sites (body and limb) in horses to see if a different pattern is observed in limb wounds, which are predisposed to EGT. A good intraclass correlation coefficient (ICC, 0.67 p < 0.05) was found between the computer-based ImageJ method and manual counting. An excellent intra-operator ICC of 0.90 (p < 0.01) was found for the ImageJ quantification method while a good interoperator ICC of 0.69 (p < 0.01) was measured. No significant difference was observed between the variation of the ImageJ and that of the manual counting method. Mast cells were localized below the epidermis, around cutaneous appendages and blood vessels. Mast cell numbers did not differ significantly in relation to anatomical location or time of healing. The computer-based quantification method developed is reliable, reproducible, available, cost-free and could be used to study different physiological and pathological processes using immunohistochemistry.


Interleukin-6 inhibition attenuates hypertension and associated renal damage in Dahl salt-sensitive rats.
Immune cells in the kidney are implicated in the development of hypertension and renal damage in the Dahl salt-sensitive (SS) rat. Interestingly, interleukin 6 (IL-6) mRNA is 54-fold higher in T-lymphocytes isolated from the kidney compared with circulating T-lymphocytes. The present experiments assessed the role of IL-6 in the development of SS hypertension by treating rats (n = 13-14/group) with an IL-6 neutralizing antibody or normal IgG during an 11-day period of high-salt (4.0% NaCl chow) intake. The mean arterial pressure (MAP) and urine albumin excretion rates (Ualb) were not different between the groups fed low salt (0.4% NaCl). Following 11 days of drug treatment and high salt, however, the rats receiving anti-IL-6 demonstrated a 47% reduction of IL-6 in the renal medulla compared with control SS. Moreover, the increase in MAP following 11 days of high-NaCl intake was significantly attenuated in SS administered anti-IL-6 compared with the control group (138 ± 3 vs. 149 ± 3 mmHg) as was the salt-induced increase in Ualb and glomerular and tubular damage. To investigate potential mechanisms of action, a flow cytometric analysis of immune cells in the kidney (n = 8-9/group) demonstrated that the total number of monocytes and macrophages was significantly lower in the treatment vs. the control group. The total number of T- and B-lymphocytes in the kidneys was not different between groups. These studies indicate that IL-6 production may participate in the development of SS hypertension and end-organ damage by mediating increased infiltration or proliferation of macrophages into the kidney.


Use of an audience response system in an evidence-based mini-curriculum.
Since 2002, library faculty at the Indiana University School of Medicine have taught third-year medical students how to retrieve the best evidence from MEDLINE to address their clinical questions. In preparation for their Neurology, Medicine, and Psychiatry clerkships, students attended a review of evidence-based medicine principles and techniques for searching the literature. The session was team-taught by two faculty members, one from the Internal Medicine department and the other from the Library. The librarian reviewed important MEDLINE principles for constructing a good subject search and applying appropriate evidence-based filters. During the clerkships, students were asked to generate clinical questions arising from their patient encounters, searched MEDLINE for the best evidence, critiqued the results, and then applied them back to their patients' care. Library faculty provided individualized feedback on the student searches. A follow-up session two months later reinforced MEDLINE principles, used student searches as examples, and extended the discussion to other evidence-based, point-of-care resources. To add to the interactivity of the follow-up sessions, librarians used an audience response system to measure students' understanding of literature retrieval techniques and to gauge student preferences for information seeking on clinical topics. Overall, the sessions have been well-received by the students.


An indifference point for electrical impedance in humans.
Regional electrical impedance was used over eight sections of the human body (two thoracic; one abdominal; two thigh; two around the knee; and one lower leg) to determine the volume indifference point during passive head-up tilt in eight subjects. Head-up tilt was performed in 10 degrees increments from 0 degree to 60 degrees over 6 min. Electrical impedance increased over the thorax in proportion to the head-up tilt angle, while abdominal impedance did not change significantly, and over the thigh and the lower leg it decreased with increasing head-up tilt angle. No change in electrical impedance was noted just above the knee, and electrical impedance just below the knee decreased only marginally. Results demonstrate minimal fluid accumulation around the knee during head-up tilt. Furthermore, in humans the electrical impedance and therefore probably the volume indifference point is positioned between the umbilicus and crista iliaca.


Reuse of treated wastewater and non-potable groundwater in the manufacture of concrete: major challenge of environmental preservation.
This work concerns the reuse of treated wastewater from Er-Rachidia wastewater treatment plant (WWTP) in the mixing of ordinary C20/25 concrete, to reduce the overexploitation of non-potable groundwater, avoid its discharge into watercourses and reduce the risk of environmental pollution due to its mineral and organic matter load. In this respect, three types of mixing water were used in this study: drinking water (DW), non-potable groundwater (GW), and treated wastewater (TW). The results recorded for each type of mixing water, in the fresh and hardened state of concretes, were compared with the requirements of the standards. The obtained results show that the treated wastewater does not have any adverse effect upon the quality of the concrete; it has shown an improvement of the mechanical strength from the first stage, a similar density, setting time, and porosity and a slight decrease of the workability compared with the control concrete. A one-way analysis of variance (ANOVA) of the mechanical performance of concrete at different cure times (7, 14, 28, and 90 days) has shown that there is no significant decrease in the mechanical performance of concretes based on TW and GW compared with concretes formulated with DW. Through this study, the substitution of drinking water by treated TW and GW will help to minimize the footprint of construction materials on natural resources. From a point of view of the mechanical performance, TW and GW improve the mechanical performance of concrete. Additionally, it makes wastewater treatment plants more economically attractive and contributes to sustainable development.


MiR-377-3p inhibits atherosclerosis-associated vascular smooth muscle cell proliferation and migration via targeting neuropilin2.
Vascular smooth muscle cell (VSMC) proliferation and migration are vital to atherosclerosis (AS) development and plaque rupture. MicroRNA-377-3p (miR-377-3p) has been reported to inhibit AS in apolipoprotein E knockout (ApoE-/-) mice. Herein, the mechanism underlying the effect of miR-377-3p on alleviating AS is explored. In vivo experiments, ApoE-/- mice were fed with high-fat diet (HFD) to induce AS and treated with miR-377-3p agomir or negative control agomir (agomir-NC) on week 0, 2, 4, 6, 8, 10 after HFD feeding. MiR-377-3p was found to restore HFD-induced AS lesions and expressions of matrix metalloproteinase (MMP)-2, MMP-9, α-smooth muscle actin (α-actin) and calponin. In in vitro experiments, human VSMCs were tranfected with miR-377-3p agomir or agomir-NC, followed by treatment with oxidized low-density lipoprotein (ox-LDL). MiR-377-3p was observed to significantly inhibit ox-LDL-induced VSMC proliferation characterized by inhibited cell viability, expressions of proliferating cell nuclear antigen (PCNA), cyclin D1 and cyclin E and cell cycle transition from G1 to S phase accompanied with less 5-Ethynyl-2'-deoxyuridine (EdU)-positive cells. Furthermore, MiR-377-3p significantly inhibited ox-LDL-induced VSMC migration characterized by inhibited wound closure and decreased relative VSMC migration. Besides, neuropilin2 (NRP2) was verified as a target of miR-377-3p. MiR-377-3p was observed to inhibit NRP2 expressions in vivo and in vitro. Moreover, miR-377-3p significantly inhibited MMP-2 and MMP-9 expressions in human VSMCs. Additionally, miR-377-3p-induced inhibition of VSMC proliferation and migration could be attenuated by NRP2 overexpression. These results indicated that miR-377-3p inhibited VSMC proliferation and migration via targeting NRP2. The present study provides an underlying mechanism for miR-377-3p-based AS therapy.


Vemurafenib: a guide to its use in unresectable or metastatic melanoma.
Oral vemurafenib (Zelboraf(®)) is a first-in-class, small molecule BRAF(V600E) inhibitor indicated for the treatment of unresectable or metastatic melanoma in BRAF(V600) mutation-positive patients (EU) or BRAF(V600E) mutation-positive patients (USA). Compared with intravenous dacarbazine, vemurafenib significantly improved overall survival and progression-free survival in patients with unresectable, previously untreated, BRAF(V600E) mutation-positive, stage IIIC or IV melanoma. Oral vemurafenib was generally well tolerated, with cutaneous adverse events among the most commonly occurring adverse events.


Preconceptional use of folic acid and knowledge about folic acid among low-income pregnant women in Korea.
Folic acid supplementation before pregnancy is known to significantly reduce the risk of having a baby with neural tube defects (NTDs). Therefore, it is important for women to be aware of the effects of folic acid supplementation before pregnancy. The purpose of this study was to investigate the awareness and preconceptional use of folic acid and to assess the current knowledge about folic acid among low-income pregnant women in Korea. A questionnaire survey was conducted in 2012. Five hundred pregnant women were selected from the waiting list for the Nutriplus program implemented in public health centers using a multistage clustered probability sampling design. Data from 439 women were analyzed after excluding ones with incomplete answers. Among women who responded to the questionnaire, 65.6% had heard of folic acid before pregnancy, and 26.4% reported on the preconceptional use of folic acid. Women with a university degree or higher education were more likely to be aware of folic acid and to take folic acid in the preconception period. In a multivariate logistic regression, when age, education level, household income, employment status, gravidity, parity, and folic acid awareness were included in the model, folic acid awareness was a strong predictor of preconceptional folic acid use. As of interview, 85.4% and 77.7% of women were aware of the NTD-preventive role of folic acid and the appropriate time to take folic acid, respectively. The main sources of information on folic acid were healthcare professionals (41.2%), friends and family members (31.2%), and the media (26.5%). Our results suggest that public health strategies are needed to increase the preconceptional use of folic acid among Korean women.


Phase II study of recombinant alfa-2a interferon in patients with advanced bone sarcomas.
Twenty previously treated patients with advanced bone sarcomas received thrice weekly im 50 X 10(6) IU/m2 doses of human alfa-interferon (interferon alfa-2a, recombinant; Roche). Seventeen patients had metastatic osteosarcomas and one each had fibrosarcoma, mesenchymal chondrosarcoma, and malignant fibrous histiocytoma. Two patients with osteosarcoma and the one with malignant fibrous histiocytoma experienced objective partial tumor regression for 1, 3, and 2 months, respectively. Fever, anorexia, myalgia, fatigue, lethargy, and moderate myelosuppression were observed commonly, and some patients developed mild nausea, vomiting, and diarrhea. No patient withdrew because of toxicity and no dose reductions were necessary except adjustments for changes in body surface area secondary to weight loss.


[The composition and characteristics of the spread of the shot products from a gas-barrel weapon].
Chemical composition and diffusion of additional factors of a shot from barrel gun supplied with a standard chemical cartridge are studied. Experimental shots from gas pistols of three designs were made. During shots from gas barrel guns the victim is exposed to additional factors characteristic of both fire arms and gas barrel guns, namely, fragments of plastic cartridge container and pads, magnesium particles, and lacquer powder. The characteristics of the short range zone for gas barrel guns correspond to those of short barrel fire arms.


The Impact of an Institutional Grant Program on the Economic, Social, and Cultural Capital of Women Researchers.
Introduction: Early funding can have significant impact on a researcher's career. However, funding is not equal for men and women. Not only do female researchers apply for fewer grants than men, but they also experience a lower success rate when they do. The Zucker Grant Program (ZGP) was established in 2000 to promote the early success of women researchers. The purpose of this evaluation is to support other institutions hoping to grow the research careers of women scientists. Methods: This program evaluation reviewed the first 16 years of the program's history. Our mixed-methods, outcomes-based evaluation had four phases: (I) interviews with key stakeholders, (II) development and distribution of a survey to ZGP recipients, (III) focus groups and interviews with ZGP recipients, (IV) document analysis from the ZGP Center and the Tufts University School of Medicine (TUSM) Development Office. This article reports on the qualitative data collection and analysis. Results: Between 2000 and 2016, US$377,050 was awarded for 142 recipients. Qualitative data revealed how grant funding was critical to support pilot data in awardees' research to inform extramural grant applications. However, the program evaluation also identified effects on awardees' confidence as researchers and connection to a community. Conclusion: Outcomes are interpreted through the framework of Bourdieu's three forms of capital, including economic, social, and cultural capital. Viewed through this framework, they provide a critical infrastructure to the development and success of early career female investigators. This work offers other institutions a framework to consider when establishing intramural funding and support programs for their early career investigators.


The frequency, longitudinal course, clinical associations, and causes of emotional distress during primary treatment of cerebral glioma.
Relatively little is known about the frequency, longitudinal course, independent associations, and reported causes of emotional distress in adults with primary cerebral glioma. We aimed to describe these features in an observational study. This was a twin-center prospective cohort study. Eligible adults were those with a new histological diagnosis of glioma who were receiving active management. Distress was measured using the National Comprehensive Cancer Network Distress Thermometer and problem checklist. Subjects were sampled at 3 timepoints: T1 (shortly after starting chemo/radiotherapy), T2 (3 months later), and T3 (6 months later). T1 n = 154; T2 n = 103; T3 n = 83. Significant distress was present in 36.4 ± 7.6% at T1, 35.9 ± 9.3% at T2, and 33.7 ± 10.2% at T3. Longitudinally, subjects with high distress at T1 (median Distress Thermometer score = 8; interquartile range [IQR] 7-9) remained highly distressed on follow-up (T2 median = 8, IQR 6-8; T3 median = 7, IQR 5-8) (Friedman test P = .304). Younger age, functional impairment, and concurrent major depressive disorder were independently associated with high distress (logistic regression χ(2) for model = 39.882, P < .001, R(2) = 0.312). The most frequently reported causes of distress were worry, fatigue, sleep difficulties, and sadness. Emotional difficulties were among the most common causes of distress at all 3 timepoints. At each timepoint, one-third of patients reported significant emotional distress, which persisted during follow-up among those initially highly distressed. Young, functionally impaired, and depressed glioma patients may particularly benefit from increased support.


Complete mitochondrial genome of the acorn barnacle Striatobalanus amaryllis (Crustacea: Maxillopoda): the first representative from Archaeobalanidae.
The mitochondrial genome of the barnacle Striatobalanus amaryllis (Sessilia: family Archaeobalanidae) is 15,063 bp in length. All the 13 protein-coding genes (PCGs) initiate with ATD codon (ATG, ATA or ATT). Four PCGs (COX3, ND3, ND4 and ND4L) end with incomplete stop codon (T- -). Four PCGs (ND1, ND4, ND4L and ND5) are encoded on the light strand (underlined below). Refer to the pancrustacean ground pattern, there are not less than seven tRNAs rearranged in the S. amaryllis mitochondrial genome, including tRNA(Ala), tRNA(Glu)/tRNA(Ser)((AGY)), tRNA(Pro)/tRNA(Thr), tRNA(Pro)/tRNA(Thr), tRNA(Tyr), tRNA(Lys), tRNA(Gln) and tRNA(Cys). Three tRNAs (tRNA(Lys), tRNA(Gln) and tRNA(Cys)) are rearranged between S. amaryllis and Tetraclita japonica (Sessilia: Tetraclitidae), meanwhile one tRNA (tRNA(Cys)) inverted from one strand to another. Compared with Megabalanus volcano (Sessilia: Balanidae), an inversion of one large gene block is identified (including three PCGs and three tRNAs) in S. amaryllis mitochondrial genome: tRNA(Phe)-ND5-tRNA(His)-ND4-ND4L-tRNA(Pro).


[2018 scientific breakthroughs in ambulatory general internal medicine].
Mindfulness meditation and cognitive-behavioral therapy are more cost-effective than conventional management of chronic low back pain. Women with iron deficiency can be treated with oral iron substitution every other day to improve tolerance. Smokers who smoke four or less cigarettes per day have a disproportionately high risk of cardiovascular and cerebrovascular events. All antidepressants are effective in cases of severe depression. Cannabis derivatives have no analgesic effect and do not improve the quality of life of people with neuropathic pain. Cognitive training is effective in cases of mild cognitive impairment. Delegated medical protocols can aid with blood pressure control in hypertensive patients. Nitrofurantoin is the antibiotic of choice for uncomplicated cystitis.


Serological markers for hepatitis B and treponemal infection among HIV carriers from Ethiopia.
A group of 52 HIV carriers among immigrants who arrived in Israel from Ethiopia in Operation Solomon, 1991, is described. A control group was randomly chosen from the same population. HBV serology and treponemal antibodies were obtained from both groups. The frequency of HBV markers was similar in both groups (70% among the HIV carriers and 78.8% in the controls). HBsAg was more frequently found among HIV carriers (20%) than in the control group (8.6%). Treponemal antibodies were common among HIV carriers (31%), and infrequent in the controls (3%). These data indicate that HIV infection in this community is linked to treponemal infection and that these carriers handle HBV less efficiently then HIV-negative subjects.


Comparative Raman spectroscopy of magnetic topological material EuCd2X2(X=P, As).
EuCd2X2(X = P, As) is a new class of magnetic topological materials discovered recently. The electronic structure and the band topology are intimately coupled with its magnetism, giving rise to interesting properties such as spin fluctuation and colossal magnetoresistance. Phonon excitation can contribute to the quasi-particle response of the topological matters through spin-lattice and electron-phonon coupling. However, the phonon properties of this material family remain unexplored. Here we report a comparative study of Raman-active vibration modes in EuCd2X2(X = P, As) by means of angle-resolved, temperature-resolved, and magnetic-field-resolved Raman spectroscopy together with the first-principle calculations and Raman tensor analysis. The phonon properties can be tuned by chemical potential and temperature within the material family. All the phonon modes are softened with increased chemical pressure by replacing P with As. Angle-resolved polarized Raman spectroscopy reveals the configuration-sensitive Raman activity and the isotropic intensity response. In addition, the magneto-Raman spectrum indicates the stability of Raman-active vibration modes against the magnetic field at room temperature. Our work sheds light on the phonon dynamics of magnetic topological matters, which are potentially coupled with the topological charge and spin excitation.


Ploidy profile of morphologically normal squamous epithelium adjacent to high grade cervical intraepithelial neoplasia.
We have investigated the ploidy profile of morphologically normal mucosa adjacent to high grade CIN (n = 16) and also from normal cervix (n = 18). DNA ploidy was assessed using flow cytometry and image analysis. All cases were diploid by both modalities. Our results show that morphologically normal squamous mucosa has a stable ploidy profile even when it lies adjacent to high grade CIN. This finding supports the view that high grade CIN is a neoplastic expansion of transformed cells rather than the result of a field change effect.


Polarized growth in the absence of F-actin in Saccharomyces cerevisiae exiting quiescence.
Polarity establishment and maintenance are crucial for morphogenesis and development. In budding yeast, these two intricate processes involve the superposition of regulatory loops between polarity landmarks, RHO GTPases, actin-mediated vesicles transport and endocytosis. Deciphering the chronology and the significance of each molecular step of polarized growth is therefore very challenging. We have taken advantage of the fact that yeast quiescent cells display actin bodies, a non polarized actin structure, to evaluate the role of F-actin in bud emergence. Here we show that upon exit from quiescence, actin cables are not required for the first steps of polarized growth. We further show that polarized growth can occur in the absence of actin patch-mediated endocytosis. We finally establish, using latrunculin-A, that the first steps of polarized growth do not require any F-actin containing structures. Yet, these structures are required for the formation of a bona fide daughter cell and cell cycle completion. We propose that upon exit from quiescence in the absence of F-actin, secretory vesicles randomly reach the plasma membrane but preferentially dock and fuse where polarity cues are localized, this being sufficient to trigger polarized growth.


Prediction of disulfide dihedral angles using chemical shifts.
Cystine residues result from the formation of disulfide bonds between pairs of cysteine residues. This cross linking of the backbone is essential for the structure and activity of peptides and proteins. The conformation of a cystine side chain can be described using five dihedral angles, χ1, χ2, χ3, χ2', and χ1', with cystines favouring certain combinations of these angles. 2D NMR spectroscopy is ideally suited for structure determination of disulfide-rich peptides, because of their small size and constrained nature. However, only limited information of the cystine side chain conformation can be determined by NMR spectroscopy, leading to ambiguity in the deduced 3D structures. Resolving accurate structures is important as disulfide-rich peptides have proven to be promising drug candidates in a number of fields, either as bioactive leads or scaffolds. Using a database of NMR chemical shifts combined with crystallographic structures, we have developed a method called DISH that uses support vector machines to predict the dihedral angles of cysteine side chains. It is able to successfully predict χ2 angles with 91% accuracy, and has improved performance over existing prediction methods for χ1 angles, with 87% accuracy. For 81% of cysteine residues, DISH successfully predicted both the χ1 and χ2 angles. By revisiting published solution structures of peptides determined using NMR spectroscopy, we assessed the impact of additional cystine dihedral restraints on the quality of 3D models. DISH improved the resolution and accuracy, highlighting the potential for improving the understanding of structure-activity relationships and rational development of peptide drugs.


[Quantification of brain developmental trajectories based on histogram parameters at slice of the anterior and posterior horns of the lateral ventricles on routine brain MRI in normal children aged 0 to 5 years].
Objective: To investigate the value of histogram parameters in quantifying brain development trajectory at slice of anterior and posterior horns of lateral ventricles on conventional brain MRI in normal children aged 0-5 years. Methods: Routine brain MRI data [apparent diffusion coefficient (ADC) map, T1-weighted imaging (T1WI), and T2-weighted imaging (T2WI)] were retrospectively collected from 300 children aged 0-5 years who underwent MRI at Children 's Hospital of Nanjing Medical University from April 2014 to November 2021, 154 males and 146 females, aged [M (Q1, Q3) ] 35.57(17.98,50.66)months. According to the random sampling method, they were divided into training set (n=240) and validation set (n=60) in a ratio of 8∶2. The training set was divided into 6 groups according to age:≤0.5 years, 24 persons; >0.5-≤1 years,21 persons; >1-≤2 years,31 persons; >2-≤3 years,44 persons; >3-≤4 years,42 persons; >4-≤5 years,78 persons. MRIcron software was used to delineate the whole brain at the level of the anterior and posterior horns of the lateral ventricles of the three MRI data as the region of interest. Then gray histograms and their parameters [including mean, maximum, minimum, skewness, kurtosis, mode, variance, and percentiles at 5% intervals from 10% to 95%(10th-95th) ]were obtained. Intra-class correlation coefficients (ICC) were used to assess consistency of intra-observer and inter-observer measurement. Representative parameters were selected by Spearman correlation analysis and curve fitting. The linear regression coefficient β represented development rates at different ages. The selected curve regression models were applied to the validation set, and the reliability of the model was evaluated with accuracy. Results: Intra-observer and inter-observer histogram measurement parameters were generally in good consistency (ICC>0.800, all P<0.001). Histogram parameters ADC 10th-65th, T1WI 55th-80th and T2WI 10th-45th were highly correlated with age (∣r∣≥0.700, 0.600 and 0.600 respectively; all P<0.001). ADC 30th and T2WI 10th had the greatest goodness of fit (R²=0.871, 0.873; both P<0.001). Map of brain development trends showed that ADC 30th and T2WI 10th decreased with age. ADC 30th changed rapidly before the age of 2 years, most significantly within 6 months, and the rate of decrease slowed down after 2 years old. T2WI 10th decreased rapidly within 1 year, and moderately after 1 year old. The curve regression models of ADC 30th and T2WI 10th had higher accuracy in validation set [93% (56/60) and 95% (57/60), respectively]. Conclusion: Histogram parameters can quantify brain developmental trajectories at slice of anterior and posterior horns of lateral ventricles on conventional MRI in normal children aged 0-5 years, and obtain the brain development curves reflecting this slice of this age group.


Vulnerable atherosclerotic plaque features: findings from coronary imaging.
Pathological studies have suggested that features of vulnerable atherosclerotic plaques likely to progress and lead to acute cardiovascular events have specific characteristics. Given the progress of intravascular coronary imaging technology, some large prospective studies have detected features of vulnerable atherosclerotic plaques using these imaging modalities. However, the rate of cardiovascular events, such as acute coronary syndrome, has been found to be considerably reduced in the limited follow-up period available in the statin era. Additionally, not all disrupted plaques lead to thrombus formation with clinical presentation. If sub-occlusive or occlusive thrombus formation does not occur, a thrombus on a disrupted plaque will organize without any symptoms, forming a "healed plaque". Although vulnerable plaque detection using intracoronary imaging is focused on "thin-cap fibroatheroma" leading to plaque rupture, superficial plaque erosion is increasingly recognized; however, the underlying mechanism of thrombus formation on eroded plaques is not well understood. One of intravascular imaging, optical coherence tomography (OCT) has the highest image resolution and has enabled detailed characterization of the plaque in vivo. Here, we reviewed the status and limitations of intravascular imaging in terms of detecting vulnerable plaque through mainly OCT studies. We suggested that vulnerable plaque should be reconsidered in terms of eroded plaque and healed plaque and that both plaque and circulating blood should be assessed in greater detail accordingly.


Cloning and structure of the BepI modification methylase.
The gene coding for a CGCG specific DNA methylase has been cloned in E. coli from Brevibacterium epidermidis. The enzyme, named BepI methylase, is probably the cognate methylase of the FnuDII isoschizomer BepI endonuclease isolated from this strain. The expression of BepI methylase in E. coli is dependent on the orientation of the cloned fragment suggesting that the gene is transcribed from a promoter on the plasmid vector. No BepI endonuclease could be detected in the clones producing BepI methylase. The nucleotide sequence of the BepI methylase gene has been determined, it predicts a protein of 403 amino acids (MR: 45,447). Analysis of the amino acid sequence deduced from the nucleotide sequence revealed similarities between the BepI methylase and other cytosine methylases. M. BepI methylates the external cytosine in its recognition sequence.


[Retroperitoneal paraganglioma].
To report the radiological findings of retroperitoneal paragangliomas. A patient who presents with colic pain and undergoes intravenous urography and CT scan. KUB x-ray revealed an increase of radiodensity on the left flank. The urography showed a partially obstructive urinary lithiasis in the proximal third of the left ureter with a mass effect laterally displacing pelvis and ureter. The study was completed with an i.v. contrast abdominal CT scan which showed a left para-aortic solid mass under the kidney with heterogeneous contrast uptake. The correlation of symptoms and catecholamine levels is the best way to guide the etiological diagnosis after CT scan.


[Inflammatory bowel disease in children--an analysis of the clinical symptoms and selected biochemical parameters].
an analysis of clinical symptoms and laboratory tests in children with inflammatory bowel disease (IBD). eighty-nine children with IBD (58 with ulcerative colitis (UC) and 31 with Crohn's disease (CD) diagnosed on the basis of clinical symptoms, endoscopic and histopathological examination, were qualified into the studied group. Disease activity was evaluated by using Truelowe-Witts scale for UC and PCDA9 scale for CD cases. Forty-two children without acute or chronic inflammatory diseases constituted the control group. the frequency of such clinical symptoms as: diarrhea, fever, weight loss, abdominal pain, weakness, constipations, anemia, joints pain, vomits, and jaundice was comparable in children with UC and CD while intestinal bleeding was significantly more frequently observed in patients with UC than with CD (P<0.05). There was no statistically significant difference in BMI between patients with UC and CD. Cole's index was significantly higher in children with UC than with CD (P<0.05). Hemoglobin level and serum iron level were statistically significantly lower in patients with CD than in the control group (P<0.05). Mean leukocyte count in children with CD was significantly higher than in the control group (P<0.05). Neutrophils percentage in patients with UC and CD was significantly higher than in the control group (P<0.05). Platelet count was significantly higher in all children with IBD than in the control group (P<0.05). Mean serum CRP level was significantly higher only in children with CD while ESR was significantly higher in both groups of IBD patients. Mean serum gamma-globulin level was statistically significantly higher in children with UC and with CD but no significant differences were observed in serum IgA, IgG, and IgM levels among the analyzed groups. Serum GT level was higher in children with CD than in the control group while serum ALT and AST level did not differ significantly among the analyzed groups of patients. 1. Serum C-reactive protein level is one of the most valuable markers for monitoring the course of IBD, especially CD, in children. 2. In patients with IBD systematic monitoring of liver function parameters (especially parameters of cholestasis) is necessary as severe hepatic complications may occur. 3. Further search for new sensitive and specific markers monitoring the course of inflammatory bowel diseases is needed.


Intestinal endometriosis combined with colorectal cancer: a case series.
Intestinal endometriosis is a common benign disease among menstruating women that affects the intestinal tract. This case report presents seven Japanese cases of intestinal endometriosis with colorectal cancer treated by laparoscopic surgery. Five of the seven cases reported here are women presenting with bowel obstruction due to colorectal endometriosis with colorectal cancer. It can be confused with serious lesions such as advanced colorectal cancer with peritoneal involvement or invasion of adjacent organs (T4). Therefore, we should consider the probability that the cause of bowel obstruction is not T4 but intestinal endometriosis. For surgical treatment, we recommend laparoscopic surgery for colorectal resection because of its benefits of differential diagnosis of T4, preserving fertility, and preventing excessive surgical stress. We performed laparoscopic resection in seven patients with intestinal endometriosis and colorectal cancer. These cases demonstrate the difficulty of establishing a differential diagnosis of intestinal endometriosis with colorectal cancer from T4.


Minimally invasive abdominal cerclage compared to laparotomy: a comparison of surgical and obstetric outcomes.
The objective of this study is to report surgical and obstetric outcomes of patients following abdominal cerclage placement through either minimally invasive or open techniques. Subjects of this retrospective cohort study were patients at two referral centers specializing in high-risk pregnancy and minimally invasive gynecologic surgery. Electronic medical records of all patients who underwent abdominal cerclage placement between December 2011 and December 2015 at Yale New Haven Hospital and Bridgeport Hospital were reviewed. The patients included were women who underwent abdominal cerclage placement either during pregnancy or prior to conception. One cohort of women had their abdominal cerclage placed using traditional laparoscopy or robotic-assisted laparoscopy. The other cohort consisted of women whose abdominal cerclage was placed through laparotomy. Electronic medical charts were reviewed to collect baseline demographic and pre-procedure obstetric information, as well as surgical and subsequent obstetric outcomes. Eleven minimally invasive and nine open abdominal cerclages were performed during the study period. Seven of the minimally invasive and two open cerclages were done outside of pregnancy. Average operative time was longer in the minimally invasive cohort. Estimated blood loss was typically lower in the minimally invasive group. Length of hospital stay was shorter in the minimally invasive group. Obstetric outcomes were similar between the two cohorts, with a total of nine live births in the minimally invasive group and seven live births in the open group. Minimally invasive abdominal cerclage is a safe alternative when performed by a surgeon with appropriate training and technical skills, and obstetric outcomes are comparable to those after open abdominal cerclage.


Parental vocalizations and perceived immaturity in down syndrome.
Previous findings suggest that children with Down syndrome may be perceived as more youthful than other children with mental retardation. In this study whether perceptions of youthfulness can be linked to parenting behavior, in particular increased prosodic adjustments characteristic of infant-directed speech, is investigated. The prosodic characteristics of parental language targeted to children with Down syndrome and children with other etiologies of mental retardation were compared. Results show that parents of children with Down syndrome raised their voice pitch significantly more (i.e., spoke in a higher register) and spoke with a significantly wider mean pitch variance than parents of children in the comparison group. Implications are discussed for parent-child interactions in children with different genetic mental retardation syndromes.


HLA-F polymorphisms in a Euro-Brazilian population from Southern Brazil.
HLA-F is a non-classical major histocompatibility complex (MHC) gene. It codes class Ib MHC molecules with restricted distribution and less nucleotide variations than MHC class Ia genes. Of the 22 alleles registered on the IMGT database only four alleles encode for proteins that differ in their primary structure. To estimate genotype and allele frequencies, this study targeted on known protein coding regions of the HLA-F gene. Genotyping was performed by Sequence Base Typing (SBT). The sample was composed by 199-unrelated bone marrow donors from the Brazilian Bone Marrow Donor Registry (REDOME), Euro-Brazilians, from Southern Brazil. About 1673 bp were analyzed. The most frequent allele was HLA-F*01:01 (87.19%), followed by HLA-F*01:03 (12.31%), HLA-F*01:02 (0.25%) and HLA-F*01:04 (0.25%). Significant linkage disequilibrium (LD) was verified between HLA-F and HLA classes I and II alleles. This is the first study regarding HLA-F polymorphisms in a Euro-Brazilian population contributing to the Southern Brazilian genetic characterization.


Investigation of the prolonged hypoglycemic effect of human proinsulin in diabetes mellitus.
Human proinsulin possesses a clear hypoglycemic effect, the extent and kinetics of which were investigated in 8 insulin dependent diabetics. In addition, to adequate therapy with a controlled-release insulin, each patient received i.v. injections of insulin (e U) and proinsulin (9 U) on separate test days. After 9 U of proinsulin, the blood glucose decrease was delayed in comparison to 3 U of insulin. However, it reached identical maximum blood glucose decrease values. The elimination kinetics of proinsulin are delayed compared to insulin. There is a linear relation between the time and the reciprocal value of the measured insulin immuno-reactivity. The hypoglycemic effect of proinsulin which is protracted for hours corresponds to that of an extreme controlled-release insulin. Under certain conditions, proinsulin might therefore prove effective in the long-term treatment of the insulin-dependent diabetes mellitus.


Calcium-binding proteins in the retina of a calbindin-null mutant mouse.
Calcium-binding proteins are abundantly expressed in many neurons of mammalian retinae. Their physiological roles are, however, largely unknown. This is particularly true for calcium-modulating proteins ("calcium buffers") such as calbindin D28k. Here, we have studied retinae of wildtype (+/+) and calbindin-null mutant (-/-) mice by using immunocytochemical methods. Although calbindin immunoreactivity was completely absent in the calbindin (-/-) retinae, those cells that express the protein in wildtype retinae, such as horizontal cells, were still present and appeared normal. This was verified by immunostaining horizontal cells for various neurofilament proteins. In order to assess whether other calcium-binding proteins are upregulated in the mutant mouse and may thus compensate for the loss of calbindin, mouse retinae were also immunolabeled for parvalbumin, calretinin, and a calmodulin-like protein (CALP). In no instance could a change in the expression pattern of these proteins be detected by immunocytochemical methods. Thus, our results show that calbindin is not required for the maintenance of the light-microscopic structure of the differentiated retina and suggest roles for this protein in retinal function.


The effects of intraoperative mitomycin-C or 5-fluorouracil on glaucoma filtering surgery.
We compared the success rate of filtering surgery of a single 5-minute intraoperative application of mitomycin-C (MMC) or 5-fluorouracil (5-FU). Animal experiment and clinical study were done. In animal study, thirty pigmented rabbits (60 eyes) weighing 2.0 to 2.5 Kg were enrolled. We divided into 4 groups, such as BSS, 5-FU 50 mg/ml, MMC 0.2 mg/ml and MMC 0.4 mg/ml subconjunctival soaked group. Each group consisted of 15 eyes. In each group, 10 eyes was for examination of bleb survival and complications, 3 eyes for light microscopic examination and 2 eyes for electron microscopic examination. Bleb was survived 6.1 days (3 to 13 days) for BSS treated group, 16.3 days (9 to 23 days) for 5-FU 50mg/ml treated group, 32.7 days (17 to 55 days) in MMC 0.2 mg/ml treated group, and 64.4 days (49 to 84 days) in MMC 0.4 mg/ml treated group. Duration of bleb survival was significantly prolonged in 5-FU, MMC 0.2 mg/ml and MMC 0.4 mg/ml group respectively. In clinical study, fifty-five eyes of 40 patients were enrolled. 29 eyes of 21 patients were treated with MMC 0.2 mg/ml and 26 eyes of 19 patients were treated with 5-FU 50 mg/ml. The success rate was 89.7% in MMC 0.2 mg/ml treated group and 84.6% in 5-FU 50 mg/ml treated group at postoperative 3 months, and postoperative 6 months 89.7% in MMC 0.2 mg/ml treated group and 76.9% in 5-FU 50 mg/ml treated group. There was no statistical significance at postoperative 3 months (P > 0.05), but statistical significance at postoperative 6 months (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Chicken fetal antigen: association with lymphoid development and differentiation.
Rabbit antisera capable of detecting chicken fetal antigen (CFA) was prepared against 1-day chick red blood cells (RBCs) and made specific by exhaustive adsorption with adult chicken peripheral RBCs (PRBCs) from the same strain. Microcytotoxicity was used to study the incidence of CFA on lymphocytes obtained from several organs at different developmental stages in the chicken. Lymphocyte-associated CFA (LA-CFA) determinants and erythrocyte-specific CFA (ES-CFA) determinants were distinguished through the use of adsorption analysis. The high incidence of CFA-positive lymphocytes found in the fetal bursa and thymus was not equaled in the peripheral organs of the spleen, cecal tonsils, and gland of Harder. CFA expression on adult lymphocytes was restricted to the thymus and peripheral blood. It is suggested that these cells may represent a subpopulation of T lymphocytes. Adult spleen, cecal tonsils, and gland of Harder were virtually devoid of CFA-bearing lymphocytes. At fetal developmental stages when greater than 94% of the bursal B cells were CFA-positive, few, if any, of the highly differentiated Harderian B cells possessed CFA. It is suggested that LA-CFA expression is dependent upon B cell differentiation and/or the bursa (central) vs gland of Harder (peripheral) microenvironment. The pattern of CFA expression on bursacytes is discussed in light of the properties of age resistance and bursal-dependent target cells associated with virally induced lymphoid leukosis.


Real-time, in-situ, extinction spectroscopy studies on silver-nanoseed formation.
In this paper, real-time extinction spectroscopy was employed to analyze in situ the fast formation process of silver seeds. The influencing factors for silver-seed formation, including the concentration of the reducer (NaBH(4)), the amount of stabilizer (citrate), and the addition procedure of NaBH(4), were evaluated. The configuration of the surface plasmon resonance (SPR) spectra of silver nanoparticles, which reflected the morphology of the produced silver seeds, was found to be distinctly affected by the NaBH(4) concentration. Homogeneous silver nanoparticles were obtained when the added NaBH(4) was lower in concentration than 2.00 mM. In contrast, higher concentrations of reducing agent (≥3.00 mM NaBH(4)) resulted in uneven silver nanoparticles. Mie theory was applied to clarify the correlation of the SPR and the size of the silver seeds. Repeated additions of a small amount of the reducing agent could increase the monodispersity and isotropy of silver seeds. Real-time extinction spectroscopy is a convenient technique that achieves the in-situ and nondestructive measurement of intermediates in the formation process of silver nanoseeds.


Evaluation of an orthogonal pooling strategy for rapid high-throughput screening of proteases.
Orthogonal pooling was evaluated as a strategy for the rapid screening of multiple cysteine and serine proteases against large compound libraries. To validate the method the human cysteine protease cathepsin B was screened against a library of 64,000 individual compounds and also against the same library mixed 10 compounds per well. The orthogonal pooling method used resulted in each compound being present in two wells, mixed with a different set of nine other compounds in each location. Thus hits were identified based on activity in both locations, avoiding the need for retesting of each component of active mixtures. Hits were tested in dose-response both in the dithiothreitol (DTT)-containing buffer used in the primary HTS and in buffer containing cysteine in place of DTT to rule out artifacts due to oxidative inactivation of the enzyme. Comparison of the confirmed actives from single-compound and mixture screening showed that mixture screening identified all of the actives from single-compound HTS. Based on these results the orthogonal pooling strategy has been used successfully to rapidly screen several cysteine and serine proteases.


Isolated small bowel perforation following intrauterine treatment with indomethacin.
Indomethacin, a prostaglandin synthetase inhibitor, is an effective tocolytic agent that may have adverse fetal side effects such as constriction of the ductus arteriosus, pulmonary hypertension, and reduced urine production. We describe an unusual neonatal complication following 6 days of tocolysis with indomethacin. A 22-year-old gravida 5, para 3104 was admitted at 25 weeks of gestation in labor. Attempts to stop labor using magnesium sulfate and terbutaline failed. The contractions stopped following the administration of indomethacin, which was continued for 6 days. On day 7, due to contractions and vaginal bleeding, she underwent a classic cesarean section. The female newborn, weighting 1044 g, did well for 2 days, when she developed pneumoperitoneum. On laparotomy, an isolated midileal perforation was found, with otherwise normal-appearing bowel. Isolated intestinal perforation has been described in premature neonates who were treated with indomethacin for patent ductus arteriosus. This complication is caused by splanchnic ischemia secondary to the loss of the vasodilatory effect of prostaglandins. This case indicates that this rare but serious complication may also follow intrauterine exposure to indomethacin.


Single anastomosis sleeve ileal (SASI) bypass as a primary and revisional procedure: a single-centre experience.
To achieve effective weight loss and remission of comorbidities, various surgical methods are used in the treatment of obesity. The most common procedures performed worldwide are followed by the newest ones. To present the results of the first group of patients from a high-volume bariatric centre in central Europe and to compare single anastomosis sleeve ileal (SASI) as a primary and revisional procedure. We retrospectively analysed patients who underwent SASI for obesity from December 2018 to June 2022 by the same team of surgeons. There were 2 groups of patients. The first group consisted of patients who underwent SASI as their first bariatric procedure (primary group - PG). The second group consisted of patients who underwent SASI after previous SG procedure due to weight regain and/or symptoms of gastroesophageal reflux disease (GERD) (revisional group - RG). There were 15 patients (80% female) in the PG, and 14 patients (88% female) in the RG. In the PG, %TWL 12 and 36 months after surgery was 37.8% and 43.9% respectively. In the RG, %TWL 12 and 24 months after surgery was 13.8% and 20.9%, respectively. Most patients had complete remission of T2D and HT after surgery. In the RG, 9 (81.8%) patients had remission of GERD. The worsening of GERD was reported in 4 (40%) patients in the PG. SASI may be an effective and safe method of treatment of obesity. SASI may be an effective method of revisional bariatric surgery performed for GERD, but not for weight regain.


Mother-to-Children Plasmodium falciparum Asymptomatic Malaria Transmission at Saint Camille Medical Centre in Ouagadougou, Burkina Faso.
Background. Malaria's prevalence during pregnancy varies widely in parts of sub-Saharan Africa, including Burkina Faso. The objective of this study was to evaluate the incidence of mother-to-child malaria transmission during childbirth at St. Camille Medical Centre in the city of Ouagadougou. Methods. Two hundred and thirty-eight (238) women and their newborns were included in the study. Women consenting to participate in this study responded to a questionnaire that identified their demographic characteristics. Asymptomatic malaria infection was assessed by rapid detection test Acon (Acon Malaria Pf, San Diego, USA) and by microscopic examination of Giemsa-stained thick and thin smears from peripheral, placental, and umbilical cord blood. Birth weights were recorded and the biological analyses of mothers and newborns' blood were also performed. Results. The utilization of long-lasting insecticidal nets (LLINs) and intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) were 86.6% and 84.4%, respectively. The parasitic infection rates of 9.5%, 8.9%, and 2.8% were recorded, respectively, for the peripheral, placental, and umbilical cord blood. Placental infection was strongly associated with the presence of parasites in the maternal peripheral blood and a parasite density of >1000 parasites/µL. Conclusion. The prevalence of congenital malaria was reduced but was associated with a high rate of mother-to-child malaria transmission.


Polar residues and their positional context dictate the transmembrane domain interactions of influenza A neuraminidases.
Interactions that facilitate transmembrane domain (TMD) dimerization have been identified mainly using synthetic TMDs. Here, we investigated how inherent properties within natural TMDs modulate their interaction strength by exploiting the sequence variation in the nine neuraminidase subtypes (N1-N9) and the prior knowledge that a N1 TMD oligomerizes. Initially, consensus TMDs were created from the influenza A virus database, and their interaction strengths were measured in a biological membrane system. The TMD interactions increased with respect to decreasing hydrophobicity across the subtypes (N1-N9) and within the human N1 subtype where the N1 TMDs from the pandemic H1N1 strain of swine origin were found to be significantly less hydrophobic. The hydrophobicity correlation was attributed to the conserved amphipathicity within the TMDs as the interactions were abolished by mutating residues on the polar faces that are unfavorably positioned in the membrane. Similarly, local changes enhanced the interactions only when a larger polar residue existed on the appropriate face in an unfavorable membrane position. Together, the analysis of this unique natural TMD data set demonstrates how polar-mediated TMD interactions from bitopic proteins depend on which polar residues are involved and their positioning with respect to the helix and the membrane bilayer.


Functional development of prefrontal cortex in rats continues into adolescence.
Bilateral removal of the sulcal prefrontal cortex in rats at 60 days of age and older results in aphagia and adipsia, but removal of this area before 60 days of age does not affect food or water regulation. Apparently the development of the role of this neocortical region in feeding and drinking continues well beyond the time of weaning in the rat.


Mild Versus Conventional Ovarian Stimulation for Poor Responders Undergoing IVF/ICSI.
Mild stimulation protocols have been implemented to be offered to subfertile patients who respond poorly to ovarian stimulation. We aimed to compare the efficacy of mild versus conventional gonadotropin-releasing hormone (GnRH)-agonist and antagonist protocols in poor responders undergoing in vitro fertilization/intra-cytoplasmic sperm injection (IVF/ICSI) cycles. A total of 58 poorly-responding patients were divided into two groups: mild group (n=33), receiving clomiphene citrate 100 mg and 0.25 mg of cetrorelix with 150 IU of gonadotrophins daily; conventional group (n=25), undergoing the long GnRH-agonist or -antagonist protocols. The primary outcome was the number of cumulus oocyte complexes (COCs) retrieved. A lower number of COCs [median (range)=1 (0-4) vs. 3 (0-8.4), p<0.001] was retrieved in the mild stimulation compared to the conventional group. Secondary outcomes favored the conventional group, whereas live birth (9.1% vs. 12%), clinical pregnancy (12.1% vs. 20%) and miscarriage rate (40% vs. 40%) were similar in the two groups. Mild ovarian stimulation is inferior to conventional regimes when applied to poor responders undergoing IVF/ICSI, in terms of the numbers of retrieved COCs.


Adiponectin and its receptors in rodent models of fatty liver disease and liver cirrhosis.
To determine circulating and hepatic adiponectin in rodents with fatty liver disease or liver cirrhosis and investigate expression of the adiponectin receptors AdipoR1 on the mRNA and protein level and AdipoR2 on the mRNA level. Fat fed rats were used as a model for fatty liver disease and bile duct ligation in mice to investigate cirrhotic liver. Expression of AdipoR1 and AdipoR2 mRNA was determined by real time RT-PCR. AdipoR1 protein was analysed by immunoblot. Adiponectin was measured by ELISA. Systemic adiponectin is reduced in fat-fed rats but is elevated in mice after bile duct ligation (BDL). Hepatic adiponectin protein is lower in steatotic liver but not in the liver of BDL-mice when compared to controls. Adiponectin mRNA was not detected in human liver samples or primary human hepatocytes nor in rat liver but recombinant adiponectin is taken up by isolated hepatocytes in-vitro. AdipoR1 mRNA and AdipoR1 protein levels are similar in the liver tissue of control and fat fed animals whereas AdipoR2 mRNA is induced. AdipoR2 mRNA and AdipoR1 mRNA and protein is suppressed in the liver of BDL-mice. Our studies show reduced circulating adiponectin in a rat model of fatty liver disease whereas circulating adiponectin is elevated in a mouse model of cirrhosis and similar findings have been described in humans. Diminished hepatic expression of adiponectin receptors was only found in liver cirrhosis.


[Revision of JSH Guideline for Tumors of Hematopoietic and Lymphoid Tissues 2018: lymphoma].
The Japanese Society of Hematology has revised its clinical practice guidelines for Tumors of Hematopoietic and Lymphoid Tissues, and this version will be published in 2018. In the lymphoma section, the revised 4th edition (2017) of the WHO classification was adopted and reflected in all issues. The descriptions of all clinical questions (CQs) were thoroughly updated according to the latest published studies. The CQs were modified to reflect recent progress in the treatment of follicular, diffuse large B-cell, and Hodgkin lymphomas. Some of the treatment algorithms were amended aiming to become more useful tools in clinical practices. Because of rapid advances in lymphoma treatment, continuous revision of these clinical practice guidelines is critical.


A survey of career assistance programs at U.S. dental schools.
1. There is a perceived need among the leaders of our dental schools for career assistance programs for dental students. 2. Current programs and services for transmitting career assistance at a majority of dental educational institutions are either nonexistent or sporadic, and handled informally without carefully coordinated activities. 3. The most frequently used career assistance services, where programs do exist, are a library of career informational materials, formalized arrangements with outside professionals in the community, and placement services. 4. Among the variety of individuals coordinating current programs in career assistance in dental schools, the most common is a member of the administration (primarily the director of student affairs).


[Practice guideline for the treatment of mood disorders].
The fundamental treatment plan of major depression is described in this chapter. The successful treatment is promoted by an initial assessment of the patient. Treatment consists of an acute phase (6-8 weeks), continuation phase (16-20 weeks) and maintenance phase treatment. In psychiatric management, it is important to evaluate the following components; (1) indication of hospitalization, (2) the safety and functional impairment of patient, (3) establishment of the good relationship between the patient and the doctor, (4) education to patients. The treatment algorithms of the mild and moderate depression and the severe depression have been shown in the tables.


Comparison of Posterior and Antero-Lateral Renal Tumors in Retroperitoneal Laparoscopic Partial Nephrectomy: A Propensity Score Matching Analysis.
This study aimed to compare the antero-lateral and posterior localized renal masses in laparoscopic partial nephrectomy with the retroperitoneal approach in terms of operative, functional, and oncological outcomes. Patients who underwent retroperitoneal laparoscopic partial nephrectomy by a single surgeon between January 2013 and January 2021 were included in the study. A one-to-one propensity score matching (PSM) analysis was conducted to obtain two balanced groups. The patients were divided into two groups as posterior and antero-lateral according to the localization of the mass. A total of 239 patients were included in the PSM analysis, with 65 patients allocated to each group. The mean operative time was 79.2 ± 11.2 min in the posterior group, while it was 90.0 ± 11.6 min in the antero-lateral group (P < 0.001). Warm ischemia time was 15.9 ± 2.4 min in the posterior group and 18.6 ± 2.7 min in the antero-lateral group (P < 0.001). The median decrease in eGFR at 1 year was 4.8 (IQR, 2.9-6.9) mL/min in the posterior group and 5.0 (IQR, 2.8-11) mL/min in the antero-lateral group (P = 0.219). The warm ischemia time and clamping technique were found to be significant factors for predicting eGFR change after surgery (β:0.693, 95% CI: 0.39-0.99, P < 0.001; β:6.43, 95% CI: 1.1-11.7, P = 0.017, respectively). We report that retroperitoneal laparoscopic partial nephrectomy provided longer warm -ischemia and operative time for antero-lateral renal masses than posterior masses. However, long-term oncological and functional results were similar for both localizations.


Properties of the electron beam in a room-temperature electron beam ion source investigated by position sensitive x-ray detection.
The evolution of the charge state distribution inside an electron beam ion source or trap (EBIS/T) is determined by interactions of the electron beam with the ions in the trap region. Hence, detailed information about the electron beam is required for evaluations of spectroscopic and ion extraction measurements performed at EBIS/T facilities. This article presents the results of investigations on the electron beam properties of an ion source of the Dresden EBIS type. For the first time theoretical predictions of the shape of the beam were tested for a noncryogenic EBIS working with low magnetic flux densities provided by permanent magnets. Position and width of the electron beam were measured at different electron energies showing an oscillation in the beam structure. At an energy of E(e)=16 keV and an emission current of I(e)=30 mA the beam is compressed to a radius of r(e)=57 mum (80% current). This refers to an average current density of j(e)=232 A/cm(2).


Successful Pregnancies and Deliveries in a Patient With Evolving Hypopituitarism due to Pituitary Stalk Transection Syndrome: Role of Growth Hormone Replacement.
We herein report a 31-year-old Japanese woman with evolving hypopituitarism due to pituitary stalk transection syndrome. She had a history of short stature treated with growth hormone (GH) in childhood and had hypothyroidism and primary amenorrhea at 20 years old. Levothyroxine replacement and recombinant follicle stimulating hormone-human chorionic gonadotropin (FSH-hCG) therapy for ovulation induction were started. GH replacement therapy (GHRT) was resumed when she was 26 years old. She developed mild adrenocortical insufficiency at 31 years old. She succeeded in becoming pregnant and delivered twice. GHRT was partially continued during pregnancy and stopped at the end of the second trimester without any complications.


CD2 antigen mediated activation of the guanine nucleotide binding proteins p21ras in human T lymphocytes.
T cell stimulation via the TCR complex (TCR/CD3 complex) results in activation of the guanine nucleotide binding proteins encoded by the ras protooncogenes (p21ras). In the present study we show that the activation state of p21ras in T lymphocytes can also be controlled by triggering of the CD2 Ag. The activation state of p21ras is controlled by GTP levels on p21ras. In T cells stimulation of protein kinase C is able to induce an accumulation of "active" p21ras-GTP complexes due to an inhibitory effect of protein kinase C stimulation on the intrinsic GTPase activity of p21ras. The regulatory effect of protein kinase C on p21ras GTPase activity appears to be mediated via regulation of GAP, the GTPase activating protein of p21ras. In the present report, we demonstrate that the TCR/CD3 complex and the CD2 Ag control the accumulation of p21ras-GTP complexes via a regulatory effect on p21ras GTPase activity. The TCR/CD3 complex and CD2 Ag are also able to control the cellular activity of GAP. These data demonstrate that p21ras is part of the signal transduction responses controlled by the CD2 Ag, and reveal that the TCR/CD3 complex and CD2 Ag control the activation state of p21ras via a similar mechanism.


[Changes in gastric mucosa and Helicobacter pylori infection in young health volunteers].
They examined 114 young health volunteers to establish a frequency of inflammation of gastric mucous membrane and(or) duodenal bulbous, a frequency of Helicobacter pylori infection and interdependence between infection and inflammation, smoking and nourishment. They evaluated a frequency and intensity of inflammation in antrum, fundus and duodenal bulbus and present of Helicobacter pylori using an urease test and microscopic examination. They noted in young inhabitants of Warsaw, appearance of asymptomatic gastritis in more than 53% cases, an inflammation of duodenal bulbus in 34% and H.pylori infection in 50% cases.


Effect of lipopolysaccharide on P-glycoprotein-mediated intestinal and biliary excretion of rhodamine123 in rats.
The effects of lipopolysaccharide (LPS) on the ileal and biliary excretion of rhodamine123 were investigated in rats at different times after intraperitoneal (i.p.) injection (1 mg/kg and 5 mg/kg of body weight). P-gp protein decreased 8h after injection of LPS and returned to the control level 24h after i.p. injection of LPS in the ileum. There was a marked decrease in the expression level of mdr1a mRNA in the ileum and liver 8h after i.p. injection of LPS when compared with the control condition. Also, the ileal and biliary clearance of rhodamine123 significantly decreased 8h after i.p. injection of LPS, but returned to the control levels 24h after i.p. injection of LPS. These results suggest that LPS-induced decreases in P-gp-mediated ileal and biliary excretion of rhodamine123 were probably due to impaired P-gp-mediated transport ability. The levels of iNOS and IL-1beta mRNA in the ileum and liver increased 2 and 8h after i.p. injection of LPS, respectively, and returned to the control levels 24h after injection of LPS. These findings suggest that LPS markedly decreases P-gp-mediated ileal and biliary excretion of rhodamine123, probably by partly decreasing the expression of P-gp protein levels, likely due to increased lipid peroxidation levels through iNOS mRNA and inflammatory mediators such as IL-1beta.


Ischemic cerebral pathologies and K opioid receptors in rabbits.
Recently it has been suggested that endogenous k-opioid receptors may have a physiopathological role in ischemia induced neurodegeneration. The aim of this research is to show that in experimental thromboembolic (obtained mechanically using microspheres injected in the carotid) and atherosclerotic pathologies (obtained through a special diet) there is a common mechanism which involves mediation by dynorphine and the receptor compartment considered. The results, obtained using receptor binding techniques, showed a statistically significant increase in the number of k-opioid receptors (Bmax) without variations in the affinity (Kd) for the 3H dynorphine. We can therefore support the hypothesis that these changes in the modulation of the dynorphinergenic system may be part of a mechanism causing early cerebrovascular damage which results from embolic insults and is a consequence of such metabolic risk factors as are activated by atherogenesis.