Cyclic-di-GMP-mediated signalling within the sigma network of Escherichia coli.
Bis-(3'-5')-cyclic-di-guanosine monophosphate (c-di-GMP) is a bacterial signalling molecule produced by diguanylate cyclases (DGC, carrying GGDEF domains) and degraded by specific phosphodiesterases (PDE, carrying EAL domains). Neither its full physiological impact nor its effector mechanisms are currently understood. Also, the existence of multiple GGDEF/EAL genes in the genomes of most species raises questions about output specificity and robustness of c-di-GMP signalling. Using microarray and gene fusion analyses, we demonstrate that at least five of the 29 GGDEF/EAL genes in Escherichia coli are not only stationary phase-induced under the control of the general stress response master regulator sigma(S) (RpoS), but also exhibit differential control by additional environmental and temporal signals. Two of the corresponding proteins, YdaM (GGDEF only) and YciR (GGDEF + EAL), which in vitro show DGC and PDE activity, respectively, play an antagonistic role in the expression of the biofilm-associated curli fimbriae. This control occurs at the level of transcription of the curli and cellulose regulator CsgD. Moreover, we show that H-NS positively affects curli expression by inversely controlling the expression of ydaM and yciR. Furthermore, we demonstrate a temporally fine-tuned GGDEF cascade in which YdaM controls the expression of another GGDEF protein, YaiC. By genome-wide microarray analysis, evidence is provided that YdaM and YciR strongly and nearly exclusively control CsgD-regulated genes. We conclude that specific GGDEF/EAL proteins have very distinct expression patterns, and when present in physiological amounts, can act in a highly precise, non-global and perhaps microcompartmented manner on a few or even a single specific target(s).


Ferric citrate decreases ruminal hydrogen sulphide concentrations in feedlot cattle fed diets high in sulphate.
Dissimilatory reduction of sulphate by sulphate-reducing bacteria in the rumen produces sulphide, which can lead to a build-up of the toxic gas hydrogen sulphide (H2S) in the rumen when increased concentrations of sulphate are consumed by ruminants. We hypothesised that adding ferric Fe would competitively inhibit ruminal sulphate reduction. The effects of five concentrations and two sources (ferric citrate or ferric ammonium citrate) of ferric Fe were examined in vitro (n 6 per treatment). Rumen fluid was collected from a steer that was adapted to a high-concentrate, high-sulphate diet (0·51 % S). The addition of either source of ferric Fe decreased (P< 0·01) H2S concentrations without affecting gas production (P= 0·38), fluid pH (P= 0·80) or in vitro DM digestibility (P= 0·38) after a 24 h incubation. An in vivo experiment was conducted using eight ruminally fistulated steers (543 (sem 12) kg) in a replicated Latin square with four periods and four treatments. The treatments included a high-concentrate, high-sulphate control diet (0·46 % S) or the control diet plus ferric ammonium citrate at concentrations of 200, 300 or 400 mg Fe/kg diet DM. The inclusion of ferric Fe did not affect DM intake (P= 0·21). There was a linear (P< 0·01) decrease in the concentration of ruminal H2S as the addition of ferric Fe concentrations increased. Ferric citrate appears to be an effective way to decrease ruminal H2S concentrations, which could allow producers to safely increase the inclusion of ethanol co-products.


Teaching preschool children to avoid poison hazards.
We evaluated the effectiveness of group safety training and in situ feedback and response interruption to teach preschool children to avoid consuming potentially hazardous substances. Three children ingested ambiguous substances during a baited baseline assessment condition and continued to ingest these substances following group safety training. In situ feedback and response interruption resulted in a decrease in opening ambiguous containers; this decrease was maintained when ambiguous novel containers were presented and when assessments occurred in a novel setting and with a novel experimenter. For 2 children, these gains were also maintained during a brief follow-up period. Twelve children did not ingest ambiguous substances prior to training, and group safety training did not evoke inappropriate ingestion.


Olfactory dysfunction in dementia.
The natural aging process brings about some inevitable consequences, such as olfactory dysfunction, which is also frequently linked to numerous neurodegenerative disorders. Many age-related dementia, such as Alzheimer's disease, Vascular dementia, Parkinson's disease, and Frontotemporal Dementia often display olfactory dysfunction. Despite the overwhelming evidence of above mentioned facts, the symptomatic relevance and potential clinical and pre-clinical value of olfactory dysfunction remains overlooked by many clinicians and public alike. Olfactory dysfunction has strong practical implications on daily activities and, although not as prominent as in other mammals, olfaction is still an evolutionarily relevant sense involved in human survival (e.g., smelling gas; bad food). In this work, we provide a brief review of current research related to the olfactory dysfunction profiles in different types of dementia. Additionally, we present a compilation of accessible, easy to use olfaction assessment tools; and highlight future directions in terms of improving clinical diagnosis in patient care and research.


Did the APA misrepresent the scientific literature to courts in support of homosexual custody?
In 1994, American Psychological Association amicus briefs informed two state Supreme Courts that (a) homosexual parents are not more apt to have homosexual children; (b) lesbians "score significantly higher than heterosexual parents" on a measure of parental effectiveness; and (c) no differences between the children raised by homosexuals and nonhomosexuals had been found "regardless of the geographic region within the United States where the children were raised." In fact, the evidence from these briefs shows to the contrary that (a) homosexual parents are more apt to have homosexual children; (b) the findings on parental effectiveness consisted of 15 fathers being less verbal than 45 mothers; and (c) the finding of no differences between homosexually and heterosexually raised children consisted of investigators visiting 11 states to test 89 offspring of 83 lesbian vs. 81 children of 69 nonlesbian volunteers. The APA's support for gay rights in these briefs may have violated its own ethical principles that "psychologists base their statements on scientifically acceptable psychological findings and techniques with full recognition of the limits and uncertainties of such evidence" and that psychologists must "provide thorough discussion of the limitations of their data, especially where their work touches on social policy" (APA, 1981).


Perceptions and work-readiness of Australian physiotherapists in cancer care: a national evaluation.
Physiotherapy interventions can improve health outcomes for people across the cancer continuum yet little is known of the work-readiness and perceptions of physiotherapists working in cancer care. This study described perceptions of Australian physiotherapists. Electronic, national cross-sectional survey. One hundred nineteen Australian hospitals and 35 rehabilitation programmes in July 2019 were invited. Clinical physiotherapists responsible for the provision of cancer care. Custom-designed survey targeted clinical knowledge, physiotherapy management, physical activity/exercise, and learning/preparedness. Relationships between domains and demographic characteristics eg: clinical experience and work setting, were analysed. One hundred twenty eight surveys were completed. Median [IQR] experience was 8 [4 to 19] years (2 [0.5 to 5] years specifically in oncology). Most participants (99/128, 77%) felt poorly prepared to commence work in oncology. Confidence was consistently lower among physiotherapists in their first year compared to others. Confidence and knowledge was rated high for people with early stage cancers (median 4 [3 to 5]) and lower for prescribing exercise for patients with cardiotoxicity and knowledge of precautions/contraindications regarding hormone and targeted therapies (median 2 [1 to 3]). High importance ratings (Likert scores 4 or 5) were reported for exercise (115/127, 91%) and physical activity (120/126, 95%). Learning needs were identified for medical management, treatment side-effects/precautions and management of cancer-related pain and fatigue. Australian physiotherapists feel underprepared to work in cancer care, but report good confidence and knowledge. Professional development opportunities appear indicated.


Clinical Study on the Treatment of Benign Prostatic Hyperplasia by Embolization of Prostate Artery Based on Embosphere Microspheres and Gelatin Sponge Granules.
Prostatic hyperplasia can cause dysuria, such as frequent urination, urgency of urination, increased nocturia, poor urination, and other symptoms, which seriously affect the quality of life of old men. We aim to compare and analyze the safety and clinical effect of embolization of the target blood vessels of ruptured prostatic hyperplasia with gelatin sponge particles and embosphere microspheres. Methods. The transcatheter MRI was performed in 422 patients. Among them, 198 patients were treated with gelfoam particles and 224 patients were treated with embosphere microspheres. The clinical effect and adverse reactions were observed and analyzed by biochemical and imaging examination. Four hundred and twenty two cases were hemostasis. In the gelatin sponge group, 34 patients had recurrent bleeding 24-36 hours after embolization, 122 patients had different degrees of elevation of prostatic hyperplasia transaminase (31 cases increased to more than 1000 U/L), 198 patients had different degrees of elevation of bilirubin; in the microsphere group, there was no significant difference in prostatic hyperplasia function indexes between the two groups. Conclusion. Compared with the gelfoam embolic agent, the embosphere embolic microsphere has a good efficacy and safety in the treatment of prostatic hyperplasia rupture and hemorrhage, with a light adverse reaction, a low probability of recanalization, and little damage to the postoperative prostatic hyperplasia function, which is conducive to the benign recovery of perioperative patients and is worthy of clinical application.


In-role perceptions buffer the negative impact of low LMX on helping and enhance the positive impact of high LMX on voice.
In 2 field studies, we demonstrated that the relationship between leader-member exchange (LMX) and organizational citizenship behavior (OCB) is moderated by employee role perceptions--the extent to which employees view specific types of OCB as in-role behavior (IRB) versus extra-role behavior (ERB). In addition, we predicted and demonstrated that the form of these interactions differs on the basis of the type of OCB. For helping (aimed at the supervisor or the organization), results show a substitute effect in which viewing helping as IRB buffers the negative effect of low-quality LMX on helping. In contrast, for voice (aimed at the supervisor or the organization), results demonstrate an enhancer effect in which viewing voice as IRB amplifies the positive effect of high-quality LMX on voice. We discuss theoretical and practical implications with an emphasis on how conceptual differences in types of OCB influence the interactive effects of role perceptions on LMX-OCB relationships.


A rigid and bioabsorbable material for anterior chest wall reconstruction in a canine model.
The optimal material for anterior chest wall reconstruction following chest wall resection remains controversial. The aim of this experimental study was to evaluate short-term, morphological and histological outcomes of anterior chest wall reconstruction with a rigid and bioabsorbable material in a canine model. Twenty adult beagle dogs underwent anterior chest wall resection. In the experimental group (n = 10), the anterior chest wall was reconstructed with a rigid and bioabsorbable material composed of poly-L-lactide acid matrix (60 wt%) and uncalcined and unsintered hydroxyapatite particles (40 wt%), whereas in the control group it was (n = 10) reconstructed with dual polypropylene mesh sheets. Short-term complication rates were compared with a χ(2) test. Postoperative sternal deviations were evaluated with sternal alignment angles using computed tomography and multiplanar reconstruction and were compared with Mann-Whitney U-test immediately after reconstruction, and at 1, 3, 6, 9 and 12 months postoperatively. Histological findings of the regenerated chest wall tissue were obtained after staining with haematoxylin and eosin and Elastica van Gieson (EVG) and compared at 3, 6, 9 and 12 months. There was not a significant difference in the short-term postoperative complication rate (P = 0.53) and the complication rate was 20% (wound infection, n = 1 and lethal mediastinitis, n = 1) in the control group and 10% (wound infection, n = 1) in the experimental group. The postoperative sternal deviation was significantly less remarkable at 1 month (123.3 ± 32.2° vs 159.4 ± 19.7°, P = 0.027), 3 months (109.8 ± 34.7° vs 150.9 ± 34.2°, P = 0.039) and 12 months (61 ± 15.6° vs 170.3 ± 6.6°, P = 0.046) in the experimental group than in the control group, whereas no significant difference was noted immediately after reconstruction (165.7 ± 6.4° vs 168.4 ± 9.1°, P = 0.50). Histological findings showed dense connective tissue in the regenerated chest wall in both groups and showed chondroblasts in the regenerated chest wall tissue at 3 and 6 months only in the experimental group. Our results suggest that anterior chest wall reconstruction with a rigid and bioabsorbable material is feasible and may be a valuable alternative to reconstruction with a non-rigid and non-absorbable material.


Effects of nicotine self-administration on incentive salience in male Sprague Dawley rats.
Prolonged use of nicotine appears to enhance incentive salience, a motivational-cognitive process that transforms an otherwise neutral stimulus into a "wanted" stimulus. It has been suggested that nicotinic enhancement of incentive salience contributes to the potential of relapse in individuals with tobacco addiction. However, there are two main limitations of prior research that caution this claim: (a) the use of passive experimentally delivered nicotine and (b) the use of sign-tracking as an index of incentive salience, without acknowledging the competing nature of goal- and sign-tracking responses. To determine whether nicotinic enhancement of incentive salience attributed to non-nicotinic stimuli occurs when rats self-administer nicotine, and whether it is facilitated by a prior history of nicotine self-administration. Twenty-three male rats were trained daily, for 24 days, on a nicotine self-administration (SA) paradigm in the morning, and on a four-conditioned-stimuli Pavlovian conditioned approach (4-CS PCA) task in the afternoon. Self-administration was followed by extinction and cue reinstatement. A subcutaneous nicotine challenge was performed during the last 7 days of the study. Nicotine self-administration selectively enhanced sign-tracking in the 4-CS PCA. Upon extinction, sign-tracking quickly declined to control levels. Experimenter-administered nicotine enhanced sign-tracking similarly regardless of nicotine history. The results suggest that nicotinic enhancement of incentive salience is transient, and a previous history of nicotine use does not cause further sensitization. Taken together, these results suggest that nicotine enhances incentive salience, particularly-and perhaps exclusively-while onboard.


Comparison of three different HbA1c measurement methods - the Atellica®CH930, Capillary 3 Tera, and BioRad Variant Turbo II.
HbA1c measurement is very useful for the follow-up and detection of glycemic disorder, since it is easier and faster test and is independent of the patient's fasting status. In this study, we aimed to perform the comparative evaluation of 3 different methods for HbA1c measurement including capillary electrophoresis, immunoturbidimetric assay and high-performance liquid chromatography-HPLC. This study comprised 134 leftover whole blood samples obtained from the subjects submitted for routine HbA1c testing. All blood samples were collected in EDTA-containing vacutainer tubes. The HbA1c levels were measured simultaneously using three different methods. Bias estimation, method agreement and concordance between the pairwise methods comparisons were evaluated by Bland-Altman plot and Passing-Bablok regression test. HbA1c levels ranged from 3.8% to 13.4% and measured by three different methods to make the comparison. The median values of samples based on immunoturbidimetric method (6.05%, IQR = 1.80) were higher than capillary electrophoresis method (5.90%, IQR = 1.80) and HPLC (5.85%, IQR = 1.80) method. The study group was classified into three subgroups based on the HbA1c levels measured with the HPLC method: Group 1 (n = 57) was composed of subjects with HbA1c levels less than 5.7%, Group 2 (n = 35) had HbA1c levels between 5.7% and 6.4%, Group 3 (n = 42) had HbA1c levels equal and more than 6.5%. To our knowledge, there is no study evaluating the HbA1c measurement on the Atellica® CH 930 Analyzer. We compared the Atellica®CH930 Analyzer with both HPLC and capillary electrophoresis. The Atellica®CH930 Analyzer showed acceptable performance and a strong correlation with both mentioned methods.


[Modern esophageal surgery and late functional results as equations with several unknowns--Hungarian Academy of Sciences Doctoral Thesis].
Using the same surgical method and anatomically ideal primary healing, the functional results could even be different later. Trying to identify various factors being responsible for the above differences, 637 patient's data, who underwent previous oesophago-gastric surgery between 1985-2005, were analyzed. Biochemical, histological and electrophysiological examinations had been evaluated. Developing hypertrophy-like metabolic changes and enteric ganglionitis as morphological alternations of LES muscles induced by GERD may be reasons for complaints after antireflux surgery. The marking of Z-line with endoscopic clips followed by an immediately upright contrast study and substractional evaluation is appropriate for detecting true short esophagus. Open surgical procedures are justified even in the new millennium in cases when the patient already underwent previous upper abdominal operations - due to an increased risk of injury because of adhesions - in cases of primarily recurrent paraesophageal hernias after an unsuccessful open and/or laparoscopic reconstruction, as well as in cases of reflux with complications. When adenocarcinomas of the gastro-oesophageal junction are examined preoperatively, the ratio of the performed catabolic - AMAN, CB, and DPP I - enzymatic activity of the tissue sample from the tumour and adjacent intact mucosa within 2 cm of the tumour may have a prognostic value even in the preoperative examination period, and neo-adjuvant treatment should be considered in these group of patients. The patients' post-operative complaints and symptoms change during the post-operative period and correlate with the parameters of the myoelectric and contractile activities of the "Akiyama stomach". Tachygastria seems to be the major pathogenetic factor involved in the contractile dysfunction. Gastro-jejuno-duodenal interposition represents an adequate 'second-best' method of choice if technical difficulties emerge with jejunal or colon interposition following limited resection of the oesophagus performed due to early Barrett's carcinoma or non-dilatable peptic stricture.


Does maltreatment beget maltreatment? A systematic review of the intergenerational literature.
In this article, the authors critically review the literature testing the cycle of maltreatment hypothesis which posits continuity in maltreatment across adjacent generations. That is, the authors examine whether a history of maltreatment victimization is a significant risk factor for the later perpetration of maltreatment. The authors begin by establishing 11 methodological criteria that studies testing this hypothesis should meet. They include such basic standards as using representative samples, valid and reliable measures, prospective designs, and different reporters for each generation. The authors identify 47 studies that investigated this issue and then evaluate them with regard to the 11 methodological criteria. Overall, most of these studies report findings consistent with the cycle of maltreatment hypothesis. Unfortunately, at the same time, few of them satisfy the basic methodological criteria that the authors established; indeed, even the stronger studies in this area only meet about half of them. Moreover, the methodologically stronger studies present mixed support for the hypothesis. As a result, the positive association often reported in the literature appears to be based largely on the methodologically weaker designs. Based on this systematic methodological review, the authors conclude that this small and methodologically weak body of literature does not provide a definitive test of the cycle of maltreatment hypothesis. The authors conclude that it is imperative to develop more robust and methodologically adequate assessments of this hypothesis to more accurately inform the development of prevention and treatment programs.


Malyngamide 2, an oxidized lipopeptide with nitric oxide inhibiting activity from a Papua New Guinea marine cyanobacterium.
A Papua New Guinea collection of the marine cyanobacterium cf. Lyngbya sordida yielded three known compounds as well as a new PKS-NRPS-derived malyngamide with anti-inflammatory and cytotoxic activity. Malyngamide 2 features an extensively oxidized cyclohexanone ring. Resolution of the ring core as a 6,8,9-triol rather then a 7,8,9-triol and relative configuration was based on chemical shift and bond geometry modeling in conjunction with homonuclear and heteronuclear coupling constants, NOE and ROE correlations, and other structural information. Malyngamide 2 exhibited anti-inflammatory activity in LPS-induced RAW macrophage cells (IC(50) = 8.0 μM) with only modest cytotoxicity to the mammalian cell line.


[Thrombocyte function and problems of blood coagulation and fibrinolysis in head and neck cancer].
Platelet aggregation induced by ADP and collagen and five parameters of blood coagulation and fibrinolysis, (levels of fibrinogen, fibrinolytic activity of euglobulin, fibrinogen and/or fibrin degradation products, antiplasmin activity and antithrombin activity) were measured in patients with cancer of the head and neck. The results were compared with those from healthy controls. Enhancement of platelet aggregation, hyperfibrinolysis and hypercoagulable state were found in the circulatory blood of patients with cancer of the head and neck.


Pharmacology of vitamin C.
A better understanding of the functions of ascorbic acid would help clarify the magnitude of the influence of this vitamin on health-related conditions. Many of the purported benefits require confirmation as well as a knowledge of the mechanism of action. The majority of investigations of the association of vitamin C with various types of cancer, with cardiovascular risk, and with cataract formation were epidemiologic studies. Often it was not possible to discern whether the apparent protective effect was due to vitamin C, vitamin E, or carotene, or to a combined effect of these nutrients or of additional factors. Human intervention trials may provide definitive and quantitative assessments of the role of vitamin C in health maintenance. We need to gain a more thorough understanding of the interactions of vitamin C with other nutrients, such as vitamin E and carotenoids, in order to appreciate the role of vitamin C in disease prevention. Investigators are increasingly recognizing the diverse functions of vitamin C in the body in addition to its role in collagen synthesis. However, the functional consequences of these many important roles of vitamin C remain essentially unknown. Excluding scurvy, the health consequences of inadequate vitamin C status are not well characterized. Nonetheless, epidemiologic evidence suggests a role for vitamin C in cancer and heart disease as well as in a number of other diseases.


Suicidal Ideation, Planning, and Attempts Among Synthetic Cannabinoid Users Across Different Demographic Subgroups.
Background: Case studies have linked synthetic cannabinoid (SC) use to suicide risk both during and following acute psychoactive effects. No study has explored whether a meaningful relationship exists between SC use and suicidal ideation, planning, and attempts within a generalizable sample. Aims: This work attempted to determine whether SC use is significantly associated with suicidal thoughts, planning, or attempts and whether the association between SC use and suicide may be stronger in certain demographic groups. Method: Cross-sectional self-report data from the Youth Risk Behavior Surveillance System were utilized. Logistic regression models were explored within a sample of 29,384 adolescents. Results: A clear connection emerged between SC use and suicidal thoughts and attempts. SC use and suicide risk were strongly related within the lesbian, gay, and bisexual and African Americans populations, even after controlling for depressive symptoms. Limitations: The study was cross-sectional and respondents may have underreported substance use or suicidal thoughts. Conclusion: Whether SC use has an impact on suicidal ideation directly, indirectly, or if it is simply a co-occurring phenomenon, it may serve as a flag of enhanced risk. Physicians must remain cognizant of the SC-suicide risk connection, particularly among African American and/or lesbian, gay, or bisexual patients.


[Detection of DNA specific for Mycobacterium tuberculosis in archeological material using the polymerase chain reaction].
The paleopathological diagnosis of bone tuberculosis in archeological findings may be confirmed by the polymerase chain reaction (PCR). If the M. tuberculosis-specific DNA fragment is amplified, then the presence of this microorganism in the sample is demonstrated. The pilot study presented investigated whether our molecular biology laboratory can collaborate with anthropologists in paleopathological analyses and to verify the use of the commercial diagnostic kit Cleanmix (Talent, Italy), for DNA isolation from archeological samples. The results were compared with the conclusions of anthropologists. Successful amplification of specific DNA fragments was achieved in a specimen from the period of the 13th to 15th century. The specimen consists of four thoracic vertebrae modified by osseous tuberculosis (gibbus). The PCR result was also positive in a five-year-old femur sample of a patient with chronic pulmonary tuberculosis. All other specimens of various ages but without macroscopic symptoms of osseous tuberculosis, were PCR negative. These results suggest that it is possible to detect former infections with pathogenic microorganisms in archeological bones find.


A novel model of demyelination and remyelination in a GFP-transgenic zebrafish.
Demyelinating diseases consist of a variety of autoimmune conditions in which the myelin sheath is damaged due to genetic and/or environmental factors. During clinical treatment, some patients undergo partial remyelination, especially during the early disease stages. However, the mechanisms that regulate demyelination remain unclear. The myelin structure, myelin formation and myelin-related gene expression are highly conserved between mammals and zebrafish. Therefore, the zebrafish is an ideal model organism to study myelination. In this study, we generated a transgenic zebrafish Tg(mbp:nfsB-egfp) expressing a fusion protein composed of enhanced green fluorescent protein (EGFP) and NTR from the myelin basic protein (mbp) promoter. Tg(mbp:nfsB-egfp) expressed NTR-EGFP reproducibly and hereditarily in oligodendrocytes along the spinal cord. Treatment of zebrafish larvae Tg(mbp:nfsB-egfp) with metronidazole (Mtz) resulted in the selective ablation of oligodendrocytes and led to demyelination, accompanied by behavioral changes, including decreased total movement distance, velocity, total movement time and fast movement time. After withdrawal of Mtz for a seven day recovery period, the expression of EGFP and MBP protein was observed again which indicates remyelination. Additionally, locomotor capacity was restored. Collectively, Tg(mbp:nfsB-egfp), a heritable and stable transgenic line, provides a novel, powerful tool to study the mechanisms of demyelination and remyelination.


Theory of spin hall conductivity in n-doped GaAs.
We develop a theory of extrinsic spin currents in semiconductors, resulting from spin-orbit coupling at charged scatterers, which leads to skew-scattering and side-jump contributions to the spin-Hall conductivity. Applying the theory to bulk n-GaAs, without any free parameters, we find spin currents that are in reasonable agreement with experiments by Kato et al. [Science 306, 1910 (2004)].


Lipid screening in children and adolescents.
Despite enormous advances in research supporting lipid screening among adults, there are critical research gaps in our understanding of the potential benefit and harm of routine screening of young children and adults. Although clear clinical opportunities exist to test and treat individual children from high risk backgrounds, building the case for systematically screening all children as part of a comprehensive cardiovascular disease prevention program requires more convincing evidence that this type of screening will yield true net positive clinical and public health outcomes. This should not prevent the pediatric community from aggressive promotion of healthy lifestyles, both in the office and through effective public policy.


Dose-dependent suppression of norepinephrine appearance rate in plasma by clonidine in man.
Clonidine is an alpha 2-receptor agonist which lowers both blood pressure and plasma norepinephrine (NE) levels in man. To determine whether the clonidine-induced fall in plasma NE is due to decreased NE appearance into plasma or increased NE clearance from plasma, NE infusions [( 3H]NE; 15 microCi/m2 bolus and 0.35 microCi/m2 X min infusion) were performed in 10 normal subjects, aged 25-56 yr. Arterialized plasma samples were obtained for measurements of steady state [3H]NE specific activity and plasma NE to allow calculation of plasma NE appearance rate and NE clearance before and 120-140 min after 1.5 and 5.0 micrograms/kg oral clonidine. Using an identical protocol, responses were compared in 4 subjects after placebo administration. Clonidine produced a dose-related reduction in mean arterial blood pressure, but no significant change in heart rate. The basal supine plasma NE concentration of 204 +/- 21 pg/ml (mean +/- SEM) fell by 27% (P less than 0.02) after low dose clonidine and by 51% (P less than 0.001) after high dose clonidine. There was no change in plasma epinephrine levels. The basal plasma NE appearance rate of 0.25 +/- 0.03 microgram/m2 X min was reduced by 32% (P less than 0.01) after low dose clonidine and by 52% (P less than 0.001) after high dose clonidine. The basal plasma NE clearance of 1.2 +/- 0.08 liters/m2 X min was unchanged after clonidine treatment. There was no change in mean plasma NE levels, plasma NE appearance rate, or mean arterial pressure after placebo administration. These findings demonstrate that the clonidine-induced fall in plasma NE levels is due to a dose-dependent suppression of plasma NE appearance rate and provide evidence for alpha 2-adrenergic inhibition of sympathetic nervous system activity in normotensive subjects.


Impairment of renal vasodilation with l-arginine is related to more severe disease in untreated hypertensive patients.
Data remain insufficient to place the decreased response to L-arginine in hypertensive patients within a consistent pathophysiological sequence. The aim of the present study in patients with essential hypertension was to assess the relationships between the response to L-arginine and a set of relevant clinical and laboratory parameters. In this prospective, interventional study, we administered L-arginine to untreated hypertensive individuals and healthy control subjects and measured the clearance of inulin and of para-aminohippurate and a set of biochemical and clinical variables. L-Arginine infusion revealed major differences between control subjects and 1 subgroup (group B) of hypertensive individuals. Group B hypertensives (n=18) had no increase in inulin clearance and no decrease in renal vascular resistance with L-arginine; however, in another subset of hypertensive patients (group A, n=27), the insulin clearance increased and renal vascular resistance decreased similar to the control group (group C, n=11). The ambulatory blood pressure monitoring in group B showed both an increased mean diastolic pressure and a "nondipper" pattern in the nocturnal regulation of arterial pressure. These findings in group B were accompanied by significant alterations in optic fundus and left ventricle hypertrophy and increased microalbuminuria (all, P<0.05). Furthermore, group B individuals had significantly lower values of HDL cholesterol and a higher baseline atherogenic index, plasma insulin level, and glucose/insulin index. We disclose a previously undescribed relationship between end organ repercussion and decreased renal hemodynamic response to L-arginine. Our results may help to understand the mechanisms that lead to target organ damage in hypertension.


Comparative study of mutagenesis by O6-methylguanine in the human Ha-ras oncogene in E. coli and in vitro.
Single residues of O6-methylguanine (O6-meG) were introduced into the first or second position of codon 12 (GGC; positions 12G1 or 12G2, respectively) or the first position of codon 13 (GGT; position 13G1) of the human Ha-ras oncogene in phage M13-based vectors. After transformation of E.coli, higher mutant plaque frequencies (MPF) were observed at 12G1 and 13G1 than at 12G2 if O6-alkylguanine-DNA alkyltransferase (AGT) had been depleted, while similar MPF were observed at all three positions in the presence of active AGT. Taken together, these observations suggest reduced AGT repair at 12G2. Kinetic analysis of in vitro DNA replication in the same sequences using E. coli DNA polymerase I (Klenow fragment) indicated that variation in polymerase fidelity may contribute to the overall sequence specificity of mutagenesis. By constructing vectors which direct methyl-directed mismatch repair to the (+) or the (-) strand and comparing the MPF values in bacteria proficient or deficient in mismatch repair and/or AGT, it was concluded that, while mutS-mediated mismatch repair did not remove O6-meG from O6-meG:C pairs, this repair mechanism can affect O6-meG mutagenesis by repairing G:T pairs generated through AGT-induced demethylation of O6-meG:T replication intermediates.


Concise total synthesis of (+/-)-cis-trikentrin A and (+/-)-herbindole A via intermolecular indole aryne cycloaddition.
An efficient nine-step total synthesis of the annulated indole natural products (+/-)-cis-trikentrin A and (+/-)-herbindole A was accomplished via an intermolecular Diels-Alder cycloaddition using our recently developed indole aryne (indolyne) methodology as the key step. This strategy provides rapid access into the trikentrins and the related herbindoles and represents the first application of this methodology to natural products total synthesis. The required 6,7-indolyne precursor was readily constructed by means of the Bartoli indole synthesis with substituted nitrobenzenes and vinyl magnesium bromide.


Are Blacks at Higher Risk for Vancomycin-Related Acute Kidney Injury?
Black individuals have a higher lifetime risk of acute kidney injury (AKI) and chronic kidney disease than whites. Vancomycin has a potential for nephrotoxicity. The objective of this study was to determine whether the incidence of AKI among patients being treated with vancomycin differs by race. Retrospective study of adult (3 ≥18 years) inpatients who were on vancomycin for 348 hours between January 2012 and December 2014. Data on demographics, comorbid conditions, clinical characteristics, vancomycin dose, duration, and nephrotoxic drugs were collected. Patients with a creatinine clearance <30 mL/min or undergoing dialysis were excluded. We identified 1130 patients during the study period; 48.1% (544) were black. The overall incidence of AKI was 8.2% (10.1% blacks, 6.5% whites; P = .03). Independent predictors of AKI included black race (P = .011); higher Charlson score (P = .006); higher body mass index (BMI; P = .002); higher vancomycin trough level (P < .0001); and sepsis/systemic inflammatory response syndrome (<.0001), pneumonia (P = .001) or gastrointestinal/genitourinary (P = .025) as the source of infection. The incidence of vancomycin-related AKI was higher in blacks, independent of other risk factors. Based on our study, vancomycin trough levels and renal function need to be closely monitored in blacks.


Modulation of anabolic and catabolic responses via a porous polymer scaffold manufactured using thermally induced phase separation.
We describe two studies encompassing the iterative refinement of a polymer-based rhBMP-2 delivery system for bone tissue engineering. Firstly, we compared the bone-forming capacity of porous poly(D,L-lactic-co-glycolic acid) (PLGA) scaffolds produced by thermally induced phase separation (TIPS) with non-porous solvent cast poly(D,L-lactic acid) (PDLLA) used previously. Secondly, we examined the potential synergy between rhBMP-2 and local bisphosphonate in the PLGA scaffold system. In vivo ectopic bone formation studies were performed in C57BL6/J mice. Polymer scaffolds containing 0, 5, 10 or 20 µg rhBMP-2 were inserted into the dorsal musculature. At all rhBMP-2 doses, porous PLGA produced significantly higher bone volume (BV, mm3) than the solid PDLLA scaffolds. Next, porous PLGA scaffolds containing 10 µg rhBMP-2 ± 0.2, or 2 µg zoledronic acid (ZA) were inserted into the hind-limb musculature. Co-delivery of local 10 µg rhBMP-2/2 µg ZA significantly augmented bone formation compared with rhBMP-2 alone (400 % BV increase, p < 0.01). Hydroxyapatite microparticle (HAp) addition (2 % w/w) to the 10 µg rhBMP-2/0.2 µg ZA group increased BV (200 %, p < 0.01). We propose that this was due to controlled ZA release of HAp-bound ZA. Consistent with this, elution analyses showed that HAp addition did not alter the rhBMP-2 elution, but delayed ZA release. Moreover, 2 % w/w HAp addition reduced the scaffold's compressive properties, but did not alter ease of surgical handling. In summary, our data show that refinement of the polymer selection and scaffold fabrication can enhance rhBMP-2 induced bone formation in our bone tissue engineering implant, and this can be further optimised by the local co-delivery of ZA/HAp.


Moderation and mediation of the relationships between masculinity ideology and health status.
The purpose of this study was to assess the direct and indirect relationships between the endorsement of traditional masculinity ideology (TMI) and self-reported health status through potential mediating variables of expectations of benefits from health risk behaviors and actual health risk behaviors. In addition, the objective was to test the moderating effect of gender identity, broadly defined (including cisgender and transgender men and women and nonbinary persons). Participants (N = 1233; 34.3% transgender) participated in an online survey, responding to measures of TMI, expectations of benefits, health behaviors, health status, and demographics. Data were analyzed using conditional process modeling. TMI was positively and directly associated with general health status for self-identified men (regardless of their sex assigned at birth), and with mental health for both men and women, but was not associated with physical health for persons of any gender identity. TMI was positively and directly associated with expectations of benefits for both men and women. Expectations of benefits from engaging in health risk behaviors was positively associated with health risk behaviors, and health risk behaviors had a large negative association with health status, for people of all gender identities. TMI may be a general and mental health protective factor for self-identified men, and a mental health protective factor for women, regardless of assigned sex at birth. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Long-term outcomes of dose-escalated intensity modulated radiation therapy alone without androgen deprivation therapy for patients with intermediate and high-risk prostate cancer.
The addition of androgen deprivation therapy (ADT) to conventional radiation therapy improves overall survival (OS) in intermediate- and high-risk prostate cancer. The benefit of ADT to added to dose-escalated radiotherapy is less clear. The aim of this study was to report disease control outcomes and to identify prognostic variables associated with favorable outcomes in patients with intermediate- and high-risk prostate cancer treated with dose-escalated radiation therapy without ADT. From September 2001 to March 2010, 127 patients with intermediate- or high-risk prostate cancer were treated with dose-escalated radiation otherapy without ADT. Biochemical recurrence-free survival (bRFS), distant metastases-free survival (DMFS), prostate cancer-specific mortality, and OS were assessed. Univariate and multivariate analyses using Cox regression modeling were performed. The median follow-up was 6.5 years, and the 5-year estimated bRFS, DMFS, prostate cancer-specific mortality, and OS for all patients was 89%, 96.1%, 98.4%, and 96.9% respectively. On multivariate analysis, factors that predict bRFS include risk group and PSA nadir, and factors that predict DMFS include perineural invasion, risk group, and PSA nadir. Patients with favorable intermediate-risk cancer could likely be treated with dose-escalated radiation therapy without ADT. Patients with high-risk and unfavorable intermediate-risk cancer, perineural invasion, and PSA nadir ≥1ng/dL had worse outcomes and likely need distinct therapeutic approaches.


Blistering on a squamous cell carcinoma graft site in a patient with bullous pemphigoid.
Bullous pemphigoid is a blistering disorder with blisters arising from normal, otherwise uninvolved tissue or from urticarial or erythematous plaques localized mainly on the trunk or upper extremities. Neoplasms, such as squamous cell carcinomas, have also been reported in patients with bullous pemphigoid. Large squamous cell carcinomas (greater than 8 cm in diameter) are best treated by surgical excision. We report a patient with bullous pemphigoid and squamous cell carcinoma who showed blisters on his graft site.


A Computer-Based Farnsworth-Munsell 100-Hue (CFM-100) Test in Pilots' Medical Assessments.
OBJECTIVES: This study investigated the effectiveness and identified the cutoff values of the computer-based Farnsworth-Munsell 100-Hue (CFM-100) test for screening color vision deficiencies in the pre-employment examination of civil aviators in China.METHODS: Firstly, subjects were stratified into normal, color weakness, and color blindness with the Ishihara pseudoisochromatic plate test (IPPT) by two ophthalmologists. Then they randomly completed CFM-100 and Farnsworth-Munsell 100-Hue (FM-100) tests. Total error scores (TES) and the time taken for the CFM-100 and FM-100 were analyzed and the cutoff values for the CFM-100 were determined.RESULTS: Of 218 subjects, 159 were normal while 59 were diagnosed with dyschromatopsia. The TES of the CFM-100 were congruent with those of the FM-100 (20.0 ± 18.8 vs. 20.6 ± 17.7, 160.9 ± 66.0 vs. 151.1 ± 66.4). The testing time for the CFM-100, however, was less than the FM-100 (10.3 ± 2.8 min vs. 12.9 ± 2.9 min, 7.8 ± 2.5 min vs. 12.6 ± 3.3 min). The correlation coefficient R was 0.93 and Cohen's kappa was 0.89 for the two methods. Further analyses defined 34 as the cutoff value to differentiate excellent from fair color discrimination (sensitivity 58.0%, specificity 94.7%) and 101 as the cutoff value to judge fair vs. poor (sensitivity and specificity both 98.8%) for the CFM-100. The cut-off value was 72 for distinguishing normal from defective color vision (sensitivity 96.6%, specificity 98.7%) and 110 was for distinguishing color weakness from color blindness (sensitivity 97.6%, specificity 97.7%) for the CFM-100.CONCLUSIONS: The CFM-100 is an effective method for the diagnosis of dyschromatopsia with high sensitivity in screening airline pilots.Zhang Y, Ma J, Cheng S, Hu W. A computer-based Farnsworth-Munsell 100-Hue (CFM-100) test in pilots' medical assessments. Aerosp Med Hum Perform. 2022; 93(4):362-367.


Insulin restores metabolic function in cultured cortical neurons subjected to oxidative stress.
We previously demonstrated that insulin has a neuroprotective role against oxidative stress, a deleterious condition associated with diabetes, ischemia, and age-related neurodegenerative diseases. In this study, we investigated the effect of insulin on neuronal glucose uptake and metabolism after oxidative stress in rat primary cortical neurons. On oxidative stress, insulin stimulates neuronal glucose uptake and subsequent metabolism into pyruvate, restoring intracellular ATP and phosphocreatine. Insulin also increases intracellular and decreases extracellular adenosine, counteracting the effect of oxidative stress. Insulin effects are apparently mediated by phosphatidylinositol 3-K and extracellular signal-regulated kinase signaling pathways. Extracellular adenosine under oxidative stress is largely inhibited after blockade of ecto-5'-nucleotidase, suggesting that extracellular adenosine results preferentially from ATP release and catabolism. Moreover, insulin appears to interfere with the ATP release induced by oxidative stress, regulating extracellular adenosine levels. In conclusion, insulin neuroprotection against oxidative stress-mediated damage involves 1) stimulation of glucose uptake and metabolism, increasing energy levels and intracellular adenosine and, ultimately, uric acid formation and 2) a decrease in extracellular adenosine, which may reduce the facilitatory activity of adenosine receptors.


Dynamical relations for left ventricular ejection: flow rate, momentum, force and impulse.
An investigation was carried out to quantitatively evaluate left ventricular volume flow rate, momentum, force and impulse derived from application of conservation principles for mass and momentum of blood within the ventricle during the ejection phase. An automated digital image processing system was developed and applied to left ventricular angiograms which are computer processed and analyzed frame by frame to determine the dynamical relations by numerical methods. Our initial experience with force and impulse has indicated that neither quantity seemed to be a sensitive indicator of coronary artery disease as evaluated by qualitative angiography for the particular patient group studied. Utilization of the dynamical relations in evaluating human left ventricular performance requires improved means of measurement and interpretation of clinical studies.


Molecular Modeling Analysis of CO2 Absorption by Glymes.
The properties of diglyme + CO2 systems were analyzed through density functional theory and molecular dynamics methods with the objective of inferring the microscopic properties of CO2 capture by glyme-based solvents and the effect of ether group regarding solvents affinity toward CO2. Calculations of diglyme + CO2 molecular clusters using density functional theory allowed accurate quantification and characterization of short-range intermolecular forces between these molecules, whereas the molecular dynamics simulation of diglyme + CO2 liquid mixtures, for different CO2 contents, were the means to infer the properties and dynamics of bulk liquid phases upon CO2 absorption. Likewise, liquid diglyme + CO2 gas interfaces were also studied using molecular dynamics methods to examine the kinetics of CO2 capture, adsorption at the gas-liquid interface, and the mechanism of interface crossing, which is of pivotal importance for the design of CO2 capturing units.


Conditions associated with Clostridium sporogenes growth as a surrogate for Clostridium botulinum in nonthermally processed canned butter.
The objective of this study was to better understand the effect of butter composition and emulsion structure on growth and survival of Clostridium sporogenes, used as a surrogate for C. botulinum in canned butter. The lack of a thermal process step in commercially available canned butter raises questions of potential safety, because it is hermetically sealed and generally exhibits anaerobic growth conditions, which are optimal for Clostridium botulinum growth. Without thermal processing, low-acid canned foods must have inhibitory factors present to prevent C. botulinum growth. Some potential intrinsic inhibitory factors, or hurdles, within butter include: reduced water activity, acidity in cultured products, elevated salt content, and the micro-droplet nature of the aqueous phase in the butter emulsion. It was hypothesized that a normal, intact butter emulsion would have sufficient hurdles to prevent C. botulinum growth, whereas a broken butter emulsion would result in a coalesced aqueous phase that would allow for C. botulinum growth. Batch-churned butter was inoculated with C. sporogenes; butter samples with varying salt contents (0, 0.8, 1.6, and 2.4% wt/wt NaCl) were prepared and stored in coated steel cans for varying times (1 or 2 wk) and temperatures (22 or 41°C) to determine temperature and emulsion structure effects on C. sporogenes growth. Samples stored at 41°C showed a significant increase in C. sporogenes growth compared with those stored at 22°C. Furthermore, NaCl addition was found to have a significant effect on C. sporogenes growth, with 0.8% NaCl promoting more growth than 0%, but with decreases in growth observed at 1.6 and 2.4%. Uninoculated control plates were also found to have bacterial growth; this growth was attributed to other anaerobic bacteria present within the cream. It was concluded that removal of the hurdle created by the micro-droplet size of the emulsion aqueous phase could result in C. botulinum growth even at elevated salt levels and, therefore, home preparation of canned butter is not advisable. It is also possible that commercially canned butter, if heat abused, could potentially allow for C. botulinum growth and, therefore, consumption is not recommended.


[Specific immunotherapy of respiratory allergies].
Specific immunotherapy has been in routine use since 1911 for the treatment of respiratory allergic diseases. There is however a certain amount of controversies regarding its overall indications. Its efficacy has been demonstrated in double-blind placebo controlled studies in both allergic rhinoconjunctivitis and allergic asthma. The improvement of allergenic extracts (in particular by standardization), the better understanding of the mechanisms of action of immunotherapy, the recently proposed use of other administration routes and the publication of guidelines have legitimated its definite role to play in the therapeutic management of allergic respiratory diseases.


Metastases of renal cell carcinoma to the thyroid gland with synchronous benign and malignant follicular cell-derived neoplasms.
Clear cell renal cell carcinoma (CCRCC) is the most common origin for metastasis in the thyroid. A 51-year-old woman was referred to our hospital for a subcarinal lesion. Ten years before, the patient had undergone a nephrectomy for CCRCC. Whole-body fluorodeoxyglucose positron emission tomography revealed elevated values in the thyroid gland, while the mediastinum was normal. An endoscopic ultrasonography-guided fine-needle aspiration biopsy of the mediastinal mass was consistent with CCRCC, and this was confirmed after resection. The thyroidectomy specimen also revealed lymphocytic thyroiditis, nodular hyperplasia, one follicular adenoma, two papillary microcarcinomas, and six foci of metastatic CCRCC involving both thyroid lobes. Curiously two of the six metastatic foci were located inside two adenomatoid nodules (tumor-in-tumor). The metastatic cells were positive for cytokeratins, CD10, epidermal growth factor receptor, and vascular endothelial growth factor receptor 2. No BRAF gene mutations were found in any of the primary and metastatic lesions. The patient was treated with sunitinib and finally died due to CCRCC distant metastases 6 years after the thyroidectomy. In CCRCC patients, a particularly prolonged survival rate may be achieved with the appropriate therapy, in contrast to the ominous prognosis typically found in patients with thyroid metastases from other origins.


Analysis of orbital malignancies presenting in a tertiary care hospital in Pakistan.
To determine the frequencies of various orbital malignancies amongst orbital lesions in patients presenting in a tertiary care hospital in Pakistan. A retrospective analysis of 666 orbital cases with an established histopathological diagnosis of malignant tumors treated in Mayo Hospital Lahore from 1996 to 2015 (20 years). About 66% of the malignant tumors were primary, 25% secondary, 8% haematopoietic and 1% metastatic. Almost 50% of the cases were children. Retinoblastoma is the commonest tumor (43% overall and 87% among children). Squamous cell carcinoma is the second commonest (15.6% overall and 31% among adults). These are then followed by Adenoid cystic carcinoma of Lacrimal Gland (9%), Lymphoma/Leukaemia (8%) and Rhabdomyosarcoma (6.3%). Frequencies of various orbital malignancies show geographical variation in both paediatric and adult population.


Are Expectations Too High for Transitioning Adolescents With Inflammatory Bowel Disease? Examining Adult Medication Knowledge and Self-Management Skills.
Transition readiness assessment has focused attention on adolescent knowledge and skills, but data-driven benchmarks have not been established. Patients with inflammatory bowel disease (IBD), ages 25 to 50 years, attending an outpatient gastroenterology clinic, were recruited to complete a voluntary, confidential survey asking patients to recall medications and potential side effects, and to rate their degree of independence performing health maintenance tasks. The 141 respondents (48% response rate) had mean age of 36 years with median disease duration of 11 years. They were 60% female, 54% had Crohn disease, and 23% were diagnosed before age 18. Nearly all patients were fully independent answering doctor's questions during the visit (93%) and scheduling office visits (92%). Excluding pharmacy pick up, full independence seen in only 57%, whereas 16% significantly delegated tasks. No differences by sex, disease type, medication class, age at disease onset, or disease duration were found across levels of self-management. Almost all (97%) respondents could recall medication name, whereas fewer were able to recall dose (63%) or frequency (65%). Side effect knowledge was poor; among 81 patients on a biologic or immunomodulator, only 17 (21%) cited cancer and 22 (27%) cited infection. Adolescent IBD transition programs now have empirical data from the present study about adult benchmarks for independence in self-management skills. Further research can establish which skills correlate with medication adherence and active collaboration with the medical team. The present study also exposes important gaps in medication risk knowledge and may allow improved patient education for subgroups of adult patients with IBD.


Novel mechanism of action on Hedgehog signaling by a suppressor of fused carboxy terminal variant.
The Suppressor of Fused (SUFU) protein plays an essential role in the Hedgehog (HH) signaling pathway, by regulation of the GLI transcription factors. Two major isoforms of human SUFU are known, a full-length (SUFU-FL) and a carboxy-terminal truncated (SUFU- ΔC) variant. Even though SUFU- ΔC is expressed at an equivalent level as SUFU-FL in certain tissues, the function of SUFU-ΔC and its impact on HH signal transduction is still unclear. In two cell lines from rhabdomyosarcoma, a tumor type associated with deregulated HH signaling, SUFU-ΔC mRNA was expressed at comparable levels as SUFU-FL mRNA, but at the protein level only low amounts of SUFU-ΔC were detectable. Heterologous expression provided support to the notion that the SUFU-ΔC protein is less stable compared to SUFU-FL. Despite this, biochemical analysis revealed that SUFU-ΔC could repress GLI2 and GLI1ΔN, but not GLI1FL, transcriptional activity to the same extent as SUFU-FL. Moreover, under conditions of activated HH signaling SUFU-ΔC was more effective than SUFU-FL in inhibiting GLI1ΔN. Importantly, co-expression with GLI1FL indicated that SUFU-ΔC but not SUFU-FL reduced the protein levels of GLI1FL. Additionally, confocal microscopy revealed a co-localization of GLI1FL with SUFU-ΔC but not SUFU-FL in aggregate structures. Moreover, specific siRNA mediated knock-down of SUFU-ΔC resulted in up-regulation of the protein levels of GLI1FL and the HH signaling target genes PTCH1 and HHIP. Our results are therefore suggesting the presence of novel regulatory controls in the HH signaling pathway, which are elicited by the distinct mechanism of action of the two alternative spliced SUFU proteins.


BF3 ⋅Et2 O-Catalyzed Selective C-4 Alkylation of Isoquinolin-1(2H)-ones Employing p-Quinone Methides.
The direct C-4 alkylation of isoquinolin-1(2H)-one moiety is a challenging transformation in organic synthesis. Here we present a practical and efficient synthesis of C-4 alkylated isoquinolin-1(2H)-ones through conjugate addition of isoquinolin-1(2H)-ones to p-quinone methides for the first time. The process is facilitated by Lewis acid catalysis and this operationally straightforward, mild, metal-free and one-pot transformation provides a wide range of C-4 alkylated isoquinolin-1(2H)-ones at ambient temperature in good to excellent yields.


Interferon responses of leukocytes in multiple sclerosis.
In vitro interferon (IFN) responses of peripheral blood leukocytes to measles virus and to other IFN inducers were determined for multiple sclerosis patients and normal donors. The group mean IFN response to measles virus was significantly lower in patients (15 units) than in normal donors (100 units), and a greater proportion of the patients failed to exhibit a significant IFN response. This defect was not specific for measles virus and was also observed consistently in response to Newcastle disease virus, Poly(I).Poly(C), and concanavalin A. The level of IFN response was not related to the clinical stage of disease.


[An evocation of Pasteur].
This work is a very summarized Louis Pasteur's biography. As a scientist he discovered the dimorphism of the tartric acid crystals, the fermentation of several compounds (beer, wine, vinegar, butter) and how to avoid them thru the pasteurization, he also discovered the bacterial cause of many diseases of man and animals, changing the ways of human life. Thru sterilization, since him, the fatal outcome of many patients is avoided and surgery was made safe. He established bacteriology and immunology as branches of medicine and biology.


Discovery of the Cyclic Lipopeptide Gacamide A by Genome Mining and Repair of the Defective GacA Regulator in Pseudomonas fluorescens Pf0-1.
Genome mining of the Gram-negative bacterium Pseudomonas fluorescens Pf0-1 showed that the strain possesses a silent NRPS-based biosynthetic gene cluster encoding a new lipopeptide; its activation required the repair of the global regulator system. In this paper, we describe the genomics-driven discovery and characterization of the associated secondary metabolite gacamide A, a lipodepsipeptide that forms a new family of Pseudomonas lipopeptides. The compound has a moderate, narrow-spectrum antibiotic activity and facilitates bacterial surface motility.


Time management in the operating room: an analysis of the dedicated minimally invasive surgery suite.
Dedicated minimally invasive surgery suites are available that contain specialized equipment to facilitate endoscopic surgery. Laparoscopy performed in a general operating room is hampered by the multitude of additional equipment that must be transported into the room. The objective of this study was to compare the preparation times between procedures performed in traditional operating rooms versus dedicated minimally invasive surgery suites to see whether operating room efficiency is improved in the specialized room. The records of 50 patients who underwent laparoscopic procedures between September 2000 and April 2002 were retrospectively reviewed. Twenty-three patients underwent surgery in a general operating room and 18 patients in an minimally invasive surgery suite. Nine patients were excluded because of cystoscopic procedures undergone prior to laparoscopy. Various time points were recorded from which various time intervals were derived, such as preanesthesia time, anesthesia induction time, and total preparation time. A 2-tailed, unpaired Student t test was used for statistical analysis. The mean preanesthesia time was significantly faster in the minimally invasive surgery suite (12.2 minutes) compared with that in the traditional operating room (17.8 minutes) (P=0.013). Mean anesthesia induction time in the minimally invasive surgery suite (47.5 minutes) was similar to time in the traditional operating room (45.7 minutes) (P=0.734). The average total preparation time for the minimally invasive surgery suite (59.6 minutes) was not significantly faster than that in the general operating room (63.5 minutes) (P=0.481). The amount of time that elapses between the patient entering the room and anesthesia induction is statically shorter in a dedicated minimally invasive surgery suite. Laparoscopic surgery is performed more efficiently in a dedicated minimally invasive surgery suite versus a traditional operating room.


Refinements in mathematical models to predict aneurysm growth and rupture.
The growth of aneurysms and eventually their likelihood of rupture depend on the determination of the stress and strain within the aneurysm wall and the exact reproduction of its geometry. A numerical model is developed to analyze pulsatile flow in abdominal aortic aneurysm (AAA) models using real physiological resting and exercise waveforms. Both laminar and turbulent flows are considered. Interesting features of the flow field resulting from using realistic physiological waveforms are obtained for various parameters using finite element methods. Such parameters include Reynolds number, size of the aneurysm (D/d), and flexibility of the aneurysm wall. The effect of non-Newtonian behavior of blood on hemodynamic stresses is compared with Newtonian behavior, and the non-Newtonian effects are demonstrated to be significant in realistic flow situations. Our results show that maximum turbulent fluid shear stress occurs at the distal end of the AAA model. Furthermore, turbulence is found to have a significant effect on the pressure distribution along AAA wall for both physiological waveforms. Related experimental work in which a bench top aneurysm model is developed is also discussed. The experimental model provides a platform to validate the numerical model. This work is part of our ongoing development of a patient-specific tool to guide clinician decision making and to elucidate the contribution of blood flow-induced stresses to aneurysm growth and eventual rupture. These studies indicate that accurately modeling the physiologic features of real aneurysms and blood is paramount to achieving our goal.


Reclassification of Marinococcus albus Hao et al. 1985 as Salimicrobium album gen. nov., comb. nov. and Bacillus halophilus Ventosa et al. 1990 as Salimicrobium halophilum comb. nov., and description of Salimicrobium luteum sp. nov.
A Gram-positive, non-motile, coccoid-shaped, non-spore-forming halophilic bacterial strain, BY-5(T), was isolated from a marine solar saltern in Korea and its taxonomic position was investigated by using a polyphasic approach. The novel strain grew optimally at 37 degrees C and in the presence of 10 % (w/v) NaCl. Strain BY-5(T) had meso-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan, MK-7 as the predominant menaquinone and anteiso-C(15 : 0), iso-C(15 : 0), anteiso-C(17 : 0) and iso-C(17 : 0) as the major fatty acids. The DNA G+C content was 47.9 mol%. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain BY-5(T) formed a coherent cluster with Bacillus halophilus and Marinococcus albus. Strain BY-5(T) exhibited 16S rRNA gene sequence similarity values of 98.7 and 97.4 % to the type strains of B. halophilus and M. albus, respectively. Strain BY-5(T) was distinguished from B. halophilus and M. albus by several phenotypic properties and DNA-DNA relatedness data. On the basis of the combined chemotaxonomic and phylogenetic data, it is proposed that M. albus, B. halophilus and strain BY-5(T) should be placed in a new genus as three separate species. Marinococcus albus and Bacillus halophilus are reclassified in a new genus, Salimicrobium gen. nov., as Salimicrobium album comb. nov. and Salimicrobium halophilum comb. nov., respectively. The type species of the new genus is Salimicrobium album. Strain BY-5(T) (=KCTC 3989(T)=CIP 108918(T)) is placed in the genus Salimicrobium as a novel species Salimicrobium luteum sp. nov.


Prevention of autoimmune disease due to lymphocyte modulation by the B-subunit of Escherichia coli heat-labile enterotoxin.
We demonstrate that the receptor binding moiety of Escherichia coli heat-labile enterotoxin (EtxB) can completely prevent autoimmune disease in a murine model of arthritis. Injection of male DBA/1 mice at the base of the tail with type II collagen in the presence of complete Freund's adjuvant normally leads to arthritis, as evidenced by inflammatory infiltration and swelling of the joints. A separate injection of EtxB at the same time as collagen challenge prevented leukocyte infiltration, synovial hyperplasia, and degeneration of the articular cartilage and reduced clinical symptoms of disease by 82%. The principle biological property of EtxB is its ability to bind to the ubiquitous cell surface receptor GM1 ganglioside, and to other galactose-containing glycolipids and galactoproteins. The importance of receptor interaction in mediating protection from arthritis was demonstrated by the failure of a non-receptor-binding mutant of EtxB to elicit any protective effect. Analysis of T cell responses to collagen, in cultures of draining lymph node cells, revealed that protection was associated with a marked increase in interleukin 4 production concomitant with a reduction in interferon gamma levels. Furthermore, in protected mice there was a significant reduction in anti-collagen antibody levels as well as an increase in the IgG1/IgG2a ratio. These observations show that protection is associated with a shift in the Th1/Th2 balance as well as a general reduction in the extent of the anti-type II collagen immune response. This suggests that EtxB-receptor-mediated modulation of lymphocyte responses provides a means of preventing autoimmune disease.


Optimization of the Retinal Vein Occlusion Mouse Model to Limit Variability.
Mouse models of retinal vein occlusion (RVO) are often used in ophthalmology to study hypoxic-ischemic injury in the neural retina. In this report, a detailed method pointing out critical steps is provided with recommendations for optimization to achieve consistently successful occlusion rates across different genetically modified mouse strains. The RVO mouse model consists primarily of the intravenous administration of a photosensitizer dye followed by laser photocoagulation using a retinal imaging microscope attached to an ophthalmic guided laser. Three variables were identified as determinants of occlusion consistency. By adjusting the wait time after rose bengal administration and balancing the baseline and experimental laser output, the variability across experiments can be limited and a higher success rate of occlusions achieved. This method can be used to study retinal diseases that are characterized by retinal edema and hypoxic-ischemic injury. Additionally, as this model induces vascular injury, it can also be applied to study the neurovasculature, neuronal death, and inflammation.


Presence of a distinct extracellular matrix-degrading metalloproteinase activity in renal tubules.
Renal tubular homogenates incubated with [3H]laminin (2 micrograms, 10(5) cpm) at 37 degrees C resulted in time- and protein-dependent laminin degradation (e.g., at 24 h, control = 6,533 +/- 771; experimental = 27,610 +/- 1,023 cpm +/- SE; N = 20). Gel chromatography confirmed that laminin (800 to 900 kd) was degraded to 20- to 50-kd fragments. Laminin degradation was not significantly decreased by serine or cysteine protease inhibitors. In contrast, metal chelators produced marked inhibition (EDTA, 93 +/- 3%; 1,10-phenanthroline, 99 +/- 1%) indicating that, at neutral pH, metalloproteinases were responsible for the laminin degradation. Laminin-degrading activity in renal tubules was not inhibited by the tissue inhibitor of metalloproteinase and was present in an active form. This activity was also present in high concentrations in the renal cortex and medulla but was only minimal in the liver. Further studies of the renal cortex revealed a similar metalloproteinase activity against type IV collagen (11,075 +/- 305; N = 6) and gelatin (41,026 +/- 1,373; N = 6), and this activity was membrane associated (97 +/- 1%; N = 4). Taken together, the characteristics of this renal metalloproteinase indicate that it is distinct from classic matrix-degrading metalloproteinases. The release of this distinct metalloproteinase from damaged renal tubular epithelial cells during injury may result in the production of fragments of laminin or other extracellular matrix components with biologic effects relevant to renal regeneration.


Is moving from targeted culling to BCG-vaccination of badgers (Meles meles) associated with an unacceptable increased incidence of cattle herd tuberculosis in the Republic of Ireland? A practical non-inferiority wildlife intervention study in the Republic of Ireland (2011-2017).
Bovine tuberculosis (BTB) remains as a costly disease of cattle-herds in the Republic of Ireland (ROI). This persistence is partially attributable to the presence of M. bovis infection in a wildlife reservoir, the European badger (Meles meles). Thus, both area-wide and limited-area targeted-badger-culling have been part of the ROI-BTB control/eradication program to help reduce the future incidence of a cattle-herd BTB breakdown (i.e. a "new herd-level occurrence of BTB"). However, neither badger-culling practice can be sustained as a major component in the ongoing BTB eradication program in the ROI. Vaccination of badgers with Bacille Calmette-Guérin (BCG) has been proposed as an alternative to badger culling. Thus, in 2011, a five-year non-inferiority study was implemented in seven counties in the ROI. This study was designed to compare and contrast the cattle-herd-BTB-incidence in areas where intramuscular badger vaccination would be implemented versus the cattle-herd-BTB-incidence in the remaining area of the same county where targeted-badger-culling was maintained as the standard treatment response to probable badger-sourced BTB breakdowns. Our outcome of interest was a new cattle-herd-BTB-episode (breakdown) with a total of >2 standard skin-test (SICTT) reactors detected during the episode. Treatments (badger vaccination or targeted badger culling) were cluster allocated based on where the majority of the herd owner's land was located. To assess the impact of the two treatments, we compared the incidence-risk, of our defined outcome, for cattle herds in the area under vaccination to the outcome incidence-risk for cattle herds in the remainder of the same county after 4 and 5 years of having implemented badger vaccination. A random-effects logit model with adjustment for clustering by treatment, and statistical control of herd-type, herd-size and five-year prior-BTB-episode history was used for our analyses. Although not included in the logistic model, a relative badger density metric based on the annual number of badgers captured-per-sett-night of capturing effort was developed for each treatment area; this metric indicated that relative badger density was approximately 40 % higher in vaccination areas than in the targeted badger-culling areas during our study. Overall, our study results indicated that vaccination was not inferior to targeted badger-culling in four counties and badger vaccination was deemed to produce ambivalent results in one (County Cork North) of the seven study sites in the ROI. A post-study investigation, in County Galway, where vaccination was deemed inferior to target culling, revealed that widespread purchases of cattle from a nearby cattle mart, by herd owners in the vaccination-area, was associated with the increased herd and vaccination-area risk of BTB. No single "biasing hypothesis" was evident for the apparent vaccine inferiority in the second study site (County Monaghan) where vaccination was deemed inferior to targeted culling; hence no further investigations were conducted.


Palmoplantar eccrine hidradenitis: three new cases and review.
Palmoplantar eccrine hidradenitis (PEH) is characterized by painful erythematous papules and nodules of abrupt onset on the soles of young individuals. The histologic hallmark is a predominant neutrophilic infiltrate surrounding the eccrine gland apparatus. A total of 28 cases have been published since 1988, with a broad variation in the age of patients, symptomatology, associated diseases, clinical course, and histologic features. These different histologic pictures have resulted in several names for this entity, including idiopathic plantar hidradenitis, neutrophilic eccrine hidradenitis, recurrent palmoplantar hidradenitis in children, and idiopathic palmoplantar hidradenitis. We present three cases of this disorder and review the literature on the varying symptomatology, clinical course, and histology that have led to the myriad of names for this disease.


Feeding responses to free-flow formula in term and preterm infants.
Although introducing freely flowing formula into the infant's mouth is a common feeding practice, its effect on feeding behavior is largely unknown. We evaluated the effects of free flow of formula from the nipple on infant feeding activity (sucking, swallowing, ingestion rate) and documented potential adverse behaviors such as cough, restless behavior, drooling, apnea, and bradycardia. We studied 13 preterm and 7 term infants. During a feeding, bottle pressure was adjusted every 2 to 3 minutes to increase or decrease free flow from the nipple. Increase in free flow of formula from the nipple caused rapid increases in suck and swallow frequency in term and preterm infants and increased ingestion rate. The response was reversed by decreasing flow and was repeatable throughout the feeding. Peak suck and swallow rates were highest in term infants. Although drooling increased with increased milk flow, no effect of flow on coughing, restless behavior, or apnea was observed. Free-flow formula is a potent stimulus for feeding activity in both preterm and term infants and is not associated with increased apnea or other adverse behaviors. The ability of the infant to divert excess formula flow by drooling is an efficient airway protective behavior. Reduced maximum suck and swallow frequency may be a primary basis for slow feeding in preterm infants.


Rapid determination of estrogens in milk samples based on magnetite nanoparticles/polypyrrole magnetic solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry.
In this study, a nanocomposite of polypyrrole-coated magnetite nanoparticles (denoted as MNPs/PPy) was prepared and employed as magnetic solid-phase extraction (MSPE) sorbent for extraction of estrogens from milk samples. Because the polypyrrole coating possessed a highly π-conjugated structure and hydrophobicity, MNPs/PPy showed excellent performance for the estrogen extraction. Estrogens could be captured directly by MNPs/PPy from milk samples without protein precipitation. Moreover, the extraction could be carried out within 3 min. Thus, a rapid, simple, and effective method for the analysis of estrogens in milk samples was established by coupling MNPs/PPy-based MSPE with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The limits of detections for estrogens investigated were in the range of 5.1-66.7 ng/L. The recoveries of estrogens (concentration range of 0.5-20 ng/mL) from milk samples were in the range of 83.4-108.5%, with relative standard deviations ranging between 4.2 and 15.4%.


Substituent effect on color tuning of red light emission in photoluminescence and electroluminescence of red fluorophore.
Typical small red light-emitting molecules for organic light emitting diodes (OLEDs) were highly susceptible to fluorescence concentration quenching in solid state. Red fluorophores, (2Z, 2'Z)-3, 3'-[4,4"-bis(dimethylamino)-1,1':4',1"-terphenyl-29',5'-diyl]bis(2-phenylacrylonitrile) (ABCV-P), (2E, 2'E)-3,3'-[4,4"-bis(dimethylamino)-1,1':4',1"-terphenyl-2',5'-diyl]bis[2-(2-thienyl)acrylonitrile] (ABCV-Th) and (2Z, 2'Z)-3,3'-[4,4"-bis(dimethylamino)-1,1':4',1"-terphenyl-2',5'-diyl]bis[2-(2-naphthyl)acrylonitrile] (ABCV-Np), capable of preventing fluorescence concentration quenching were designed and synthesized. These compounds have intramolecular charge transfer (ICT) properties which were estimated by measurement of UV-Visible absorption and photoluminescence (PL) emission spectra with variation of solvent polarity (n-Hexane/Chloroform = 99/1, 1/1; Chloroform; Methylene chloride). The magnitude of ICT for ABCV-Th was measured to be the largest and that for ABCV-Np was slightly larger compared to that for ABCV-P. The magnitude of ICT resulted in a shift of peak wavelength of PL emission. Therefore, this result well supported substituent effect on the color change of PL emission. The peak wavelengths of photoluminescence for ABCV-P, ABCV-Np and ABCV-Th were observed to be 607.5, 611.5 and 617.5 nm, respectively, and those of EL spectra were measured to be 612.5, 619.5, 621.0 nm, respectively. The emission maxima of PL and EL spectra for these red fluorescent compounds were well correlated with substituent effect on ICT for them.


Diagnostic accuracy of Xpert MTB/RIF for tuberculosis detection in different regions with different endemic burden: A systematic review and meta-analysis.
To estimate the diagnostic accuracy of Xpert MTB/RIF, a systematic review and meta-analysis were carried out. Up to June 20, 2015, multiple databases were screened for relevant studies. Accordingly, 106 studies included 52,410 samples were selected. Diagnostic accuracy of Xpert MTB/RIF for TB detection was validated against either culture or a composite reference standard (CRS). Additionally, selected studies were further subgrouped in four groups based on sample's type, subject's age, status of HIV co-infection and smear-positivity. The overall pooled sensitivity and specificity of Xpert MTB/RIF was 0.85 (95% confidence interval [CI] 0.82-0.88) and 0.98 (95% CI 0.96-0.98), respectively, compared to culture; while it was 0.59 (95% CI 0.44-0.72) and 0.99 (95% CI 0.97-1.00) compared to CRS. The overall sensitivity was lower in countries with high TB prevalence than countries with middle/low prevalence (0.84, 95% CI: 0.80-0.88 versus 0.89, 95% CI: 0.84-0.93). Furthermore, Xpert MTB/RIF has higher sensitivity in patients with positive smears (0.99, 95% CI 0.97-0.99), in patients with pulmonary TB samples (0.87, 95% CI 0.83-0.90), in adults (0.82, 95% CI 0.76-0.86) and in HIV-positive patients (0.81, 95% CI 0.73-0.87). Taken together, Xpert MTB/RIF is a quick and accurate diagnostic assay for TB which will significantly help the physicians to make their clinical decisions.


A novel monoclonal antibody recognizing a unique antigen of rat osteoclasts induced by the calcified matrices.
The morphology of osteoclasts, primary cells that resorb bone, is well documented; however, the precise details of their terminal differentiation remains obscure. To date, the only morphological criterion for identifying activated functional osteoclasts has been the presence of ruffled borders. We have developed a rat bone marrow culture system in which osteoclast-like cells formed. These cells fulfilled most of the criteria of osteoclasts, and when they were reseeded on calcified tissue, formed numerous resorption lacunae in vitro. To find an immunological marker for functional osteoclasts, we have used these cells in a functional state as antigens for the preparation of monoclonal antibodies (mAb) that reacted with rat osteoclasts; we obtained mAb Ch1 and Ch2. Interestingly, these mAbs reacted with the marginal portion of authentic osteoclasts, where they attached to the bone surface on frozen sections. The reactivity of Ch1 to rat osteoclasts was more restricted than that of Ch2: Ch1 reacted with few tartrate-resistant acid phosphatase (TRAP)-positive cells on a culture plate. These TRAP-positive cells (including mono- and multinucleated cells) were, however, converted to Ch1-positive cells when they were reseeded on calcified tissues. These findings suggested that the antigen recognized by the Ch1 antibody was induced by some factors of matrix proteins released from calcified tissues.


Saturated adsorption of CO and coadsorption of CO and O2 on AuN- (N=2-7) clusters.
A first-principles quantum chemistry method, based on the Kohn-Sham density-functional theory, is used to investigate the adsorption of CO and O2 on small gas-phase gold cluster anions. The saturated adsorption of carbon monoxide on gold cluster anions AuN- (N=2-7) is discussed. The adsorption ability of CO reduces with the increase of the number of CO molecules bound to gold cluster anions, resulting in saturated adsorption at a certain amount of absorbed CO molecules, which is determined by geometric and electronic properties of gold clusters cooperatively. The effect of CO preadsorption on the electronic properties of gold cluster anions depends on the cluster size and the number of adsorbed CO, and the vertical detachment energies of CO-adsorbed gold cluster anions show a few changes with respect to corresponding pure gold cluster anions. The results indicate that the impinging adsorption of CO molecules may lead to geometry structure transformation on Au3- cluster. For the coadsorption of CO and O2 on Au2-, Au3- isomers, Au4-, and Au6-, we describe the cooperative adsorption between CO and O2, and find that the O2 dissociation is difficult on gas-phase gold cluster anions even with the preadsorption of CO.


Characteristics of risk-taking behaviors, HIV and AIDS knowledge, and risk perception among young males in southwest China.
A cross-sectional survey was undertaken to describe risk-taking behaviors and to assess the knowledge and risk perception of HIV and AIDS among young males aged 18 to 29 years in 82 villages in Longchuan, Yunnan, China, in 1994. Information on demographic, behavioral, and drug-using factors, and knowledge of HIV transmission and prevention, and risk perception was collected using an interviewer-administered anonymous questionnaire. A total of 1,548 individuals were interviewed and 433 drug users, including 52 nonsharing injectors and 140 sharing injectors, were identified. Over half the individuals scored 0 on HIV knowledge, but knowledge was greater among nonsharing drug injectors. Most drug injectors had initiated drug injection after 1990. The reported incidence continues to increase in all three major ethnic groups. Sharing of equipment was common (73%) among injectors. Drug users were four times more likely to have had premarital or extramarital sex, but condoms were used by only 2.5%. Thus, factors promoting spreading of HIV are common in this area. We recommend that a community-based intervention program, targeting both young men and women, be implemented and evaluated in Longchuan as soon as possible.


Monoclonal immunoglobulin G1-kappa fibrillary glomerulonephritis.
We report here a case of fibrillary glomerulonephritis arising in a 43-year-old man with a polyclonal gammopathy, who presented with progressive renal insufficiency, microscopic hematuria, and mild proteinuria (0.7 g/d). Ultrastructural studies showed deposits of randomly oriented fibrils in the glomerular mesangium and adjacent portions of some glomerular basement membranes, with a mean fibril thickness of 14.3 nm, highly consistent with fibrillary glomerulonephritis. The Congo red stain was negative on histologic sections. Immunofluorescence studies revealed strong mesangial and focal glomerular capillary staining for immunoglobulin (Ig) G, complement (C) 3, and kappa light chains, with minimal staining for IgA, IgM, C1q, or lambda light chains. The IgG present was entirely of the IgG1 subclass. This case is quite unusual for fibrillary glomerulonephritis, which typically presents with polyclonal IgG deposits and IgG4 as the dominant IgG subclass present. Monoclonal deposits are more frequently associated with immunotactoid glomerulopathy, characterized ultrastructurally by microtubule-like structures 30 to 50 nmn thick, often in parallel arrays. The present case illustrates that although fibrillary glomerulonephritis and immunotactoid glomerulopathy might be distinguishable on ultrastructural grounds, there is overlap between these two entities with respect to the potential composition of the glomerular deposits present.


Study of the Etiological Causes of Toe Web Space Lesions in Cairo, Egypt.
Background. The etiology of foot intertrigo is varied. Several pathogens and skin conditions might play a role in toe web space lesions. Objective. To identify the possible etiological causes of toe web space lesions. Methods. 100 Egyptian patients were enrolled in this study (72 females and 28 males). Their ages ranged from 18 to 79 years. For every patient, detailed history taking, general and skin examinations, and investigations including Wood's light examination, skin scraping for potassium hydroxide test, skin swabs for bacterial isolation, and skin biopsy all were done. Results. Among the 100 patients, positive Wood's light fluorescence was observed in 24 and positive bacterial growth was observed in 85. With skin biopsy, 52 patients showed features characteristic for eczema, 25 showed features characteristic for fungus, 19 showed features characteristic for callosity, and 3 showed features characteristic for wart while in only 1 patient the features were characteristic for lichen planus. Conclusion. Toe web space lesions are caused by different etiological factors. The most common was interdigital eczema (52%) followed by fungal infection (25%). We suggest that patients who do not respond to antifungals should be reexamined for another primary or secondary dermatologic condition that may resemble interdigital fungal infection.


Oscillatory activity in the cortico-basal ganglia-thalamic neural circuits in Parkinson's disease.
Dopamine is an important neurotransmitter that maintains the balance within the basal ganglia between the direct pathway, which promotes movement, and the indirect pathway, which inhibits movement. Degeneration of dopaminergic neurons in the substantia nigra increases the influence of the indirect pathway, resulting in motor dysfunction in Parkinson's disease (PD). The direct and indirect pathways are composed of basal ganglia and thalamic nuclei, which are interconnected via independent parallel loop circuits with cortical areas and often referred to as cortico-basal ganglia-thalamic (CBT) neural circuits. CBT circuits have been useful in generating hypotheses to describe slowness in PD. Recent work has focused on aberrant neural oscillations within CBT circuits. Although beta (13-30 Hz) oscillations are a common feature of the CBT network, there is growing evidence that abnormally exaggerated beta oscillations, observed after dopamine loss in the CBT circuits, may contribute to motor symptoms of PD. Disruption of abnormal beta oscillations has been associated with the improvement of motor functions during pharmacological treatments, surgical lesions, and electrical stimulation. However, it is not clear how abnormal oscillations originate in the CBT motor network and resonate specifically in the beta band after the loss of dopamine. Most studies have addressed these questions by simultaneous recordings of oscillations in the motor cortex, basal ganglia nuclei, and motor regions of the thalamus in animal models of parkinsonism as well as in PD patients. This review further discusses previous and current studies of the changes in oscillatory activity at the level of CBT neural network in PD.


Endovascular papillary angioendothelioma in an elderly female.
Endovascular papillary angioendothelioma (EPA) is a rare vascular tumor of low grade malignancy, encountered primarily in children. However some cases have also been reported in adults. A sixty year old female with EPA is described here. She presented with a swelling in the neck. Total surgical excision was performed. Histomorphology revealed anastomosing lymphatic channels showing intraluminal papillary fronds with hyaline vascular cores and hobnailing of endothelial cells. A diagnosis of EPA was made based on this picture. This tumor is recurrent and nodal metastasis has been reported in some cases.


Condyloma-like penis carcinoma.
A squamous cell carcinoma is described which showed clinical and histological features of condyloma acuminatum on the glans penis of a 43-year-old man.


Balance control in sitting and standing in children and young adults with benign cerebellar tumors.
Children and young adolescents with chronic surgical cerebellar lesions show persistent balance control problems during standing when lesions affect the deep cerebellar fastigial and adjacent interposed nuclei. The purpose of this study is to confirm that the same lesion sites are also associated with permanent signs of trunkal ataxia during sitting. A second aim is to demonstrate that examining the postural control of patients while sitting or standing on a foam cushion may constitute a simple clinical exam yielding results commensurate to a more involved dynamic posturography exam. Balance control was assessed in 16 patients after surgery of a benign cerebellar tumor in chronic state and healthy age- and gender-matched control subjects. Using an ultrasound-based kinematic recording system, trunkal and shoulder sway was measured during sitting and standing in different conditions. High-resolution MRI scans were acquired in the cerebellar patients. Voxel-wise statistical lesion symptom mapping was performed to compare lesioned areas between affected and unaffected patients in a given condition using χ² tests. During sitting, 56% of cerebellar patients exhibited trunkal sway outside the range of healthy controls, and 87.5% of cerebellar patients revealed abnormal sway patterns during standing. Abnormalities were most pronounced when visual information was absent, and somatosensory information became unreliable and/or when the base of support along the medio-lateral axis was minimized during tandem stance. Lesion symptom mapping revealed that pathological values in the behavior data were more likely in patients with surgical lesions involving the fastigial nuclei (NF) and adjacent interposed nuclei (NI). In patients with surgery <1-year lesions of the inferior cerebellar vermis also had an impact on balance function. Our results corroborate previous evidence that the extent of permanent damage to the deep cerebellar nuclei greatly impacts on the recovery on balance function.


The role of cell hydration in realization of biological effects of non-ionizing radiation (NIR).
The weak knowledge on the nature of cellular and molecular mechanisms of biological effects of NIR such as static magnetic field, infrasound frequency of mechanical vibration, extremely low frequency of electromagnetic fields and microwave serves as a main barrier for adequate dosimetry from the point of Public Health. The difficulty lies in the fact that the biological effects of NIR depend not only on their thermodynamic characteristics but also on their frequency and intensity "windows", chemical and physical composition of the surrounding medium, as well as on the initial metabolic state of the organism. Therefore, only biomarker can be used for adequate estimation of biological effect of NIR on organisms. Because of the absence of such biomarker(s), organizations having the mission to monitor hazardous effects of NIR traditionally base their instruction on thermodynamic characteristics of NIR. Based on the high sensitivity to NIR of both aqua medium structure and cell hydration, it is suggested that cell bathing medium is one of the primary targets and cell hydration is a biomarker for NIR effects on cells and organisms. The purpose of this article is to present a short review of literature and our own experimental data on the effects of NIR on plants' seeds germination, microbe growth and development, snail neurons and heart muscle, rat's brain and heart tissues.


Comparing the Fracture Resistance of Alternatively Engineered Zirconia Abutments with Original Equipment Manufactured Abutments with Different Implant Connection Designs.
Aftermarket computer-aided design/computer-assisted manufacture (CAD/CAM) milled zirconia (Zr) abutments were recently introduced with minimal independent research regarding their fracture resistance. Third-party manufacturers often alter the original equipment manufacturers' (OEM) design with unknown effects on fracture resistance. These alterations include elimination of the titanium insert with subsequent introduction of Zr into the implant, changes to connection designs and shapes, and/or alterations to prosthetic screw design. This in vitro study compares the static load fracture resistance and mode of failure of alternatively engineered Zr abutments with those of prefabricated (OEM) Zr abutments with internal, external, and conical connections. Twenty Zr stock abutments (five per group) from OEMs were selected to demonstrate fracture resistance of external hex, internal connection, and conical connection implant designs (control groups). Atlantis abutments (Dentsply) (test group) were manufactured by means of CAD/CAM to match the OEM abutments (control groups). All samples had full-coverage all-ceramic crowns luted to the abutments. Static load fracture resistance was evaluated with an Instron test device. Modes of abutment failure were evaluated using both light and scanning electron microscopy. A Welch two-sample t test evaluated the OEM control groups vs the Atlantis test groups. Static load to failure (N) for each representative control group vs test group revealed (1) conical design OEM (387 N) vs Atlantis (211 N) (P < .011), (2) external-hex OEM (408 N) vs Atlantis (218 N) (P < .035), (3) trilobe internal connection OEM (430 N) vs Atlantis (260 N) (P < .014), and (4) internal connection OEM (448 N) vs Atlantis (244 N) (P < .02). Atlantis CAD/CAM Zr abutments demonstrated static fracture loads lower than those of their OEM counterparts. Failure modes were Zr fractures in the conical and external hex groups. The internal connection groups demonstrated a mixed mode of failure, with screw head fracture 100% of the failures in the internal Zr connection group. The trilobe internal connection group exhibited screw-head fracture in two of five samples and Zr fracture in the remaining three samples. Clinicians should consider avoiding the alternatively engineered Atlantis Zr abutment for restoration of posterior single teeth in cases in which occlusal forces may exceed 350 to 400 N.


Structure of the GDP-bound G domain of the RGK protein Rem2.
RGK proteins are atypical small GTP-binding proteins that are involved in the regulation of voltage-dependent calcium channels and actin cytoskeleton remodelling. The structure of the Rem2 G domain bound to GDP is reported here in a monoclinic crystal form at 2.66 Å resolution. It is very similar to the structure determined previously from an orthorhombic crystal form. However, differences in the crystal-packing environment revealed that the switch I and switch II regions are flexible and not ordered as previously reported. Comparison of the available RGK protein structures along with those of other small GTP-binding proteins highlights two structural features characteristic of this atypical family and suggests that the conserved tryptophan residue in the DXWEX motif may be a structural determinant of the nucleotide-binding affinity.


[Plasmapheresis in the complex treatment of psoriatic arthritis].
Thirty-five psoriatic arthritis patients underwent combined treatment including plasmapheresis given in 3 sessions with a 7-day interval. Plasma elimination reached 500-600 ml per session. Additional polyglucin and saline administration was introduced to correct circulating plasma. Chemotherapy involved nonsteroid antiinflammatory drugs, cytostatics, corticosteroids. It is believed++ that plasmapheresis is a beneficial adjuvant to chemotherapy in psoriatic arthritis potentiating the drugs action and correcting immunity.