Fungal translocation measured by serum 1,3-ß-D-glucan correlates with severity and outcome of liver cirrhosis-A pilot study.
On a global scale, liver cirrhosis is attributable to ~1 million deaths per year. This systemic disease comes along with diverse sequelae, including microbiota alterations, increased gut permeability and translocation of microbial components into the systemic circulation. Alongside the extensively studied influence of bacterial translocation and its host-pathogen interactions, far less is known about the role and impact of fungal components once having crossed the intestinal barrier. Including 70 patients with different aetiologies of liver cirrhosis, we investigated the relationship between fungal translocation, measured by 1,3-β-D-glucan (BDG), and biomarkers of gut integrity, inflammation and severity/outcome of liver disease. Patients with cirrhosis Child-Pugh class (CPC)-B were more likely to have positive serum BDG (aOR 5.4, 95% CI 1.2-25.2) compared to patients with cirrhosis CPC-A. BDG showed a moderate positive correlation with several markers of inflammation (sCD206, sCD163, Interleukin 8, interferon-gamma-induced protein). Mortality differed significantly between patients with positive versus negative BDG (log-rank test, p = 0.015). The multivariable Cox regression model yielded an aHR of 6.8 (95% CI 1.8-26.3). We observed trends for increased fungal translocation depending on the severity of liver cirrhosis, an association of BDG with an inflammatory environment and the adverse effects of BDG on disease outcome. In order to gain more in-depth knowledge about (fungal-)dysbiosis and its detrimental consequences in the setting of liver cirrhosis, these trends need to be studied in more detail including prospective sequential testing in larger cohorts together with mycobiome analyses. This will further elucidate complex host-pathogen interactions and potentially introduce points of application for therapeutic interventions.


Verapamil, a Ca2+ channel inhibitor acts as a local anesthetic and induces the sigma E dependent extra-cytoplasmic stress response in E. coli.
Verapamil is used clinically as a Ca(2+) channel inhibitor for the treatment of various disorders such as angina, hypertension and cardiac arrhythmia. Here we study the effect of verapamil on the bacterium Escherichia coli. The drug was shown to inhibit cell division at growth sub inhibitory concentrations, independently of the SOS response. We show verapamil is a membrane active drug, with similar effects to dibucaine, a local anesthetic. Thus, both verapamil and dibucaine abolish the proton motive force and decrease the intracellular ATP concentration. This is accompanied by induction of degP expression, as a result of the activation of the RpoE (SigmaE) extra-cytoplasmic stress response, and activation of the psp operon. Such effects of verapamil, as a membrane active compound, could explain its general toxicity in eukaryotic cells.


Interaction between the hepatic growth hormone receptor and concanavalin A.
The interaction between the plant lectin concanavalin A (Con A) and hepatic receptors for human growth hormone (GH) has been studied in particulate and soluble microsomal membrane preparations from rabbit and rat liver. Con A shows a dose-dependent, partial (30%) inhibition of 125I-human GH binding which is reversed by the Con A competitor, alpha-methyl mannoside. The Con A effect is dependent on the receptor concentration. The inhibition by Con A in rabbit liver is a reflection of a decreased number of available binding sites--there is no effect on binding affinity. It would appear that Con A binds directly to the GH-binding protein and not to an adjacent membrane glycoprotein. The GH receptor may consist of more than one molecular species, differing only in the carbohydrate type or content.


Complete proximal hamstring avulsions: a series of 41 patients with operative treatment.
Complete proximal hamstring avulsions can cause considerable morbidity and are often associated with significant functional loss. Early surgical treatment leads to better results than does surgery in the chronic phase. Case series; Level of evidence, 4. Forty-one patients (21 men and 20 women) with a complete proximal hamstring avulsion were included. The cases were retrospectively analyzed, and a 4-category rating system was used to evaluate the overall result of the surgical treatment. The mean follow-up was 37 months (range, 12-72 months). Nineteen patients were rated as having an excellent result and 10 patients a good result. In 5 patients, the result was classified as moderate and in 7 patients poor. In the patients with an excellent or good result, the delay from the injury to surgery averaged 2.4 months, whereas in patients with a moderate or poor result, the delay averaged 11.7 months. The difference was statistically significant (P < .001). Excellent or good results can often be expected with surgery, and considerable improvement of symptoms may be achieved even in chronic cases. According to the results, early operative treatment in complete proximal avulsions of the hamstring muscles gives better results than does late surgery and is therefore recommended.


Urinary NGF, TGF-β1, TIMP-2 and bladder wall thickness predict neurourological findings in children with myelodysplasia.
Dimercapto-succinic acid scintigraphy and urodynamic studies are gold standards to evaluate renal scarring and neurogenic bladder dysfunction, respectively. We sought to establish the value of bladder wall thickness together with urine NGF, TGF-β1 and TIMP-2 to predict the urodynamic profile and upper urinary tract damage in children with myelodysplasia. A total of 80 children with myelodysplasia underwent urodynamic investigation, bladder wall thickness measurement and dimercapto-succinic acid scintigraphy with basic neurourological evaluation. Two study and 2 control groups were created according to presence or absence of renal scarring on dimercapto-succinic acid scan (study and control groups 1) and according to detrusor leak point pressure greater or less than 40 cm H2O (study and control groups 2). Urine samples were analyzed with ELISA. The study population consisted of 44 girls and 36 boys with a median ± SD age of 7.2 ± 3.6 years (range 2 to 17). Study and control groups 1 consisted of 35 and 45 children with abnormal and normal dimercapto-succinic acid scan findings, respectively. Study and control groups 2 included 30 and 50 children with detrusor leak point pressure greater and less than 40 cm H2O, respectively. Bladder wall thickness and urinary levels of TGF-β1, NGF and TIMP-2 were significantly increased in both study groups compared to controls. Urine markers and bladder wall thickness measurement may predict urinary tract impairment in children with myelodysplasia. Such markers may differentiate at risk patients with either renal scarring or high detrusor leak point pressure, and decrease the need for urodynamics and renal scintigraphy.


Presentations, Signs of Activity, and Differential Diagnosis of Vitiligo.
Vitiligo has a variety of presentations, including focal, acrofacial, segmental, and generalized forms. Thorough knowledge of these presentations is important to make the correct diagnosis. Signs of activity are important to recognize so that treatment is optimized. Clinical findings of confettilike depigmentation, trichrome and inflammatory vitiligo, and the Koebner phenomenon should alert the clinician that a patient's disease is likely to worsen. These patients may require systemic treatment to stabilize their disease. Many other skin disorders present with hypopigmentation or depigmentation and must be distinguished to determine the right diagnosis, advise the patient on prognosis, and prescribe the correct treatment.


Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin.
Ghrelin, released from the stomach, stimulates food intake through activation of the ghrelin receptor (GHS-R) located on neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons in the hypothalamus. A role for the energy sensor AMP-activated protein kinase (AMPK) and its downstream effector uncoupling protein 2 (UCP2) in the stimulatory effect of exogenous ghrelin on NPY/AgRP expression and food intake has been suggested. This study aimed to investigate whether a rise in endogenous ghrelin levels is able to influence hypothalamic AMPK activity, pACC, UCP2 and NPY/AgRP expression through activation of GHS-R. An increase in endogenous ghrelin levels was established by fasting (24h) or by induction of streptozotocin(STZ)-diabetes (15 days) in GHS-R(+/+) and GHS-R(-/-) mice. GHS-R(+/+) mice showed a significant increase in AgRP and NPY mRNA expression after fasting, which was not observed in GHS-R(-/-) mice. Fasting did not affect AMPK activity nor ACC phosphorylation in both genotypes and increased UCP2 mRNA expression. The hyperghrelinemia associated with STZ-induced diabetes was accompanied by an increased NPY and AgRP expression in GHS-R(+/+) but not in GHS-R(-/-) mice. AMPK activity and UCP2 expression in GHS-R(+/+) mice after induction of diabetes were decreased to a similar extent in both genotypes. Exogenous ghrelin administration tended to decrease hypothalamic AMPK activity. In conclusion, an increase in endogenous ghrelin levels triggered by fasting or STZ-induced diabetes stimulates the expression of AgRP and NPY via interaction with the GHS-R. The changes in AMPK activity, pACC and UCP2 occur independently from GHS-R suggesting that they do not play a major role in the orexigenic effect of endogenous ghrelin.


Comparative acute toxicity of twenty-four insecticides to earthworm, Eisenia fetida.
In this study, we used two different types of bioassay, a contact filter paper toxicity bioassay and a soil toxicity bioassay, to compare the acute toxicity of twenty-four insecticides belonging to six chemical categories on earthworm species, Eisenia fetida. Results of the contact filter paper toxicity bioassay indicated that neonicotinoids were super toxic to E. fetida (48 h-LC(50) value ranged from 0.0088 to 0.45 μg cm(-2)), pyrethroids were very toxic (48 h-LC(50) values ranged from 10.55 to 25.7 μg cm(-2)) and insect growth regulators (IGRs) were moderately toxic (48 h-LC(50) values ranged from 117.6 to 564.6 μg cm(-2)) to the worms. However, antibiotics, carbamates and organophosphates induced variable toxicity responses in E. fetida, and were very to extremely toxic (48 h-LC(50) values ranged from 3.64 to 75.75 μg cm(-2)). Results of the soil toxicity bioassays showed a different pattern of toxicity except that neonicotinoids were the most toxic even under the soil toxicity bioassay system. The acute toxicity of neonicotinoids was higher than those of antibiotics, carbamates, IGRs and organophosphates. In contrast, pyrethroids were the least toxic to the worms under the soil toxicity bioassay system. It was concluded that irrespective of bioassay systems, earthworms were more susceptible to neonicotinoids than other modern synthetic insecticides.


A severe case of cutaneous myiasis in São Gonçalo, Brazil, and a simple technique to extract New World screw-worm Cochliomyia hominivorax (Coquerel) (Diptera: Calliphoridae).
This work describes a severe case of myiasis by Cochliomyia hominivorax (Coquerel) in a 59-year-old patient living in an urban area of São Gonçalo, Rio de Janeiro. The patient had an open wound on the right shoulder parasitized by 287 larvae. In order to remove the larvae, the wound was washed with NaCl and solid vaseline was applied onto the wound and covered with gauze and adhesive tape. After 90 min, the larvae were killed by asphyxiation and were removed using sterile forceps and NaCl. This procedure left the wound completely clean.


Myelokathexis associated with multiple congenital malformations: immunological study on phagocytic cells and lymphocytes.
A 5-year-old boy was first seen at the age of 11 months when he presented with growth retardation, skeletal dysmorphisms and neutropenia. Since then he has remained leukopenic except when he has pulmonary infections with a marked leukocytosis. Despite his neutropenia, marked myeloid hyperplasia was evident on marrow smear examination; many cells showed abnormally hypersegmented nuclei, with unusual shape or pyknotic nuclei. Phagocytic cells showed impaired phagocytosis, candidacidal activity, metabolic burst and chemotaxis. Moreover, the patient's serum generated less chemotactic activity than normal serum. These data indicate a selectively complex defect of the neutrophil during differentiation associated with the presence of an inhibitor of chemotactic factors in the patient's serum.


Infection trials in pigs with a human isolate of Brucella ( isolate 02/611 'marine mammal type' ).
To determine if pigs could support infection of a human Brucella isolate (Brucella 02/611) from New Zealand, and to study seroconversion to this isolate using a competitive ELISA. Ten weaner piglets were challenged with 4.8 x 10(8) cfu of organisms by the oral and ocular routes. Culture was attempted on blood samples taken prior to challenge, and 4, 7, 9, 11, 14, 21 and 28 days post-challenge, and on tissue samples taken at the termination of the trial, 1 month after challenge. Sera were analysed for antibody using an ELISA. For reference comparison, similar trials were conducted in two pigs using an isolate of Brucella suis biovar 1, and two pigs using an isolate of B. suis biovar 3. Brucella 02/611 organisms were re-isolated from one lymph node each from three pigs; all other samples were negative. Low and transient antibody titres were detected using a competitive ELISA in three pigs, two of which were culture negative. Organisms of B. suis reference strains were re-isolated from multiple samples from each of the four animals. Brucella 02/611 does not seem to replicate readily in pigs. It is unlikely that pigs were the original maintenance hosts for Brucella 02/611.


Reporting child abuse cases by dentists working in the United Arab Emirates (UAE).
Reporting of suspicious cases of child abuse is a sensitive issue that is often hindered by uncertainty of diagnosis. This cross sectional study aimed to assess the UAE dentists' experiences in child abuse recognition, the factors that prevent them from reporting suspicious cases to authorities and their perceived training needs. A closed-ended, self-administered questionnaire was distributed to 350 dentists working in the UAE. Chi Square test was used to determine association between training needs on child abuse and its reporting rate. Logistic regression was used to determine the association between perceived training needs and other covariates. One hundred and ninety three respondents satisfied the inclusion criteria. Forty seven (25%) dentists reported encountering a suspicious child abuse case at least once in their career, but only 15 (32%) of those reported their suspicion. Fear of making the wrong diagnosis was the most frequent challenge hindering reporting and dentists who demonstrated a need for specialized training were more likely to express this fear (OR = 5.88, 95% CI: 0.07, 0.45; P = 0.00). The majority of UAE dentists do not report their suspicion to authorities and specialized training should be offered to build dentists' capacity in diagnosing and appropriately reporting suspicious child abuse cases.


Development and performance evaluation of tube-type direct solar oven for baking bread.
Solar ovens are not widely used for baking bread. There are some attempts to bake bread using solar energy and obtained a promising result. The aim of this research was to develop and test a tube type direct solar oven that a potential to be easily fabricated and largely produced at a low cost locally in the developing world. The developed solar oven has an overall dimension of (diameter and length) 0.1 m × 1 m and the height of the parabola is 0.35 m. Simulation of the design to obtain the focal point and bread baking process was done using SOLTRACE and COMSOL soft wares, respectively. Both simulation and experiments revealed that almost all the rays fall over the trough. Similarly, COMSOL software showed the baking process which was verified through experimental work. The prototype took 67 min s to reach its stagnation temperature of 127 °C, with an F1 of 0.32. Three WBT tests were taken at different days and the result showed that the direct tube solar oven overall thermal efficiency of 43.9%, 42.1% and 38.3% at an average solar isolation of 305 W/m2, 259 W/m2 and 232 W/m2, respectively. The tube type direct solar oven has better efficiency compared to most of the direct type solar cookers. This is due to the air tight cover around the oven which reduces the thermal loss of the oven to ambient air, which is also a cause for the oven's good performance under low solar isolation. Further bread baking test showed that the solar oven has an overall utilization efficiency of 35.0% at an average solar isolation of 396 W/m2. The time taken for baking is 16 min longer than its COMSOL analysis. This is due to the difference in design and prototype, especially while producing an air tight cover locally. Addressing this and other performance improvement issues, the solar oven could be disseminated to the wider community especially for people living in the rural parts of the developing world.


Identification of cultured Brachionus rotifers based on RFLP and SSCP screening.
The marine finfish industry worldwide depends greatly on the mass culture of Brachionus rotifers. Recently, molecular data have revealed a more complicated view about the species status of Brachionus rotifers than previous mainly morphological assessments. Under this view, Brachionus rotifers are comprised of many morphologically similar, albeit genetically differentiated, cryptic members of larger groups. A redefinition of the cultured rotifer species/biotypes is therefore needed if aquaculture is to reach higher levels of standardization and predictability. In this work, restriction fragment length polymorphism (RFLP) and single-strand conformational polymorphism (SSCP) methods are applied to the COI and 16S rRNA mitochondrial genes. A detailed COI restriction map was constructed, using sequence data from all known representatives of Brachionus phylogroups. Therefore, it is the first time that such an extended restriction database has been produced. Several restriction endonucleases are proposed for the discrimination of the different Brachionus species/biotypes. Furthermore, eight different SSCP gel alleles are described for the 16S region. Using these data, five Brachionus species/biotypes were identified in 78 samples collected from laboratories and hatcheries around the world.


Neurotransmission: emerging roles of endocannabinoids.
Postsynaptic release of endocannabinoids can inhibit presynaptic neurotransmitter release on short and long timescales. This retrograde inhibition occurs at both excitatory and inhibitory synapses and may provide a mechanism for synaptic gain control, short-term associative plasticity, reduction of synaptic crosstalk, and metaplasticity.


Perceived Social Support and Mental Health Problems Among Pakistani University Students.
Despite the growing number of cross-cultural studies focusing on psychological problems, little is known about social support outside of western civilization, particularly among people in South Asian cultures. This study examined the cultural orientation regarding perceived social support and psychological problems among 912 undergraduate students (age 19-26) studying at COMSATS Institute of Information Technology, Lahore, Pakistan. The present study supported variance in cultural values regarding the relative prominence of sources of support in collectivist culture indicating that low levels of family support were related to various psychological problems. Further, low levels of peer support were related to depression, anxiety, and interpersonal sensitivity. While familial support played a bigger role than peer support in affecting psychological problems, peer support also had a role to play. The results may help counsellors and researchers to identify more effectively the population of students at high risk for mental illness and develop culturally effective interventions to address this significant and growing public health issue.


Transmucosal pterygomaxillary disjunction using a piezoelectric device, in the context of the minimally invasive Le Fort I osteotomy protocol.
The aim of this study was to assess the accuracy and clinical implications of pterygomaxillary junction (PMJ) disjunction with a transmucosal PMJ osteotomy using a piezoelectric hand-piece device, in the context of Le Fort I osteotomy, by evaluating the level of PMJ disarticulation and the need for bone trimming around the pedicle. An ambidirectional 1-month follow-up cohort study was designed involving consecutive patients undergoing minimally invasive maxillary Le Fort I osteotomy through the twist technique. Two cohorts were defined according to whether or not the transmucosal PMJ osteotomy was performed. The site of PMJ disjunction was analysed radiographically. A total of 114 patients were included in the study, 57 in each group. The overall accuracy of the PMJ disjunction path was higher in the test group (43.9%) than in the control group (15.8%). Multiple logistic regression analysis identified the need for bone trimming (odds ratio 0.02; P < 0.001) and removal of the upper third molar (odds ratio 0.17; P < 0.001) as relevant factors. In conclusion, compared with the originally described twist technique, combination of the latter with the PMJ osteotomy increased its accuracy at the level of the PMJ. As a result, there is a decrease in resistance during down-fracture and decrease in the need for bone trimming around the pedicle, with preservation of the minimally invasive concept.


Prospective associations between total, animal, and vegetable calcium intake and metabolic syndrome in adults aged 40 years and older.
Calcium (Ca) consumption may contribute to a decreased risk of developing metabolic syndrome (MetS). However, epidemiologic evidence on the association between Ca intake and MetS is limited. This study aimed to evaluate the association between dietary Ca intake (animal-based Ca and vegetable-based Ca separately, as well as total Ca intake) and the incidence risk of MetS and its components in the Korean Multi-Rural Communities Cohort (MRCohort). A total of 5509 participants who did not have MetS were enrolled. Dietary Ca intake was calculated using a food frequency questionnaire composed of 106 items. After 18,880 person-years of follow-up, 876 participants had developed de novo MetS. A significant inverse association between dietary total Ca intake and MetS were observed (incidence rate ratio (IRR) = 0.62, 95% confidence interval (CI) = 0.48-0.81, P for trend = 0.002 for the highest quartile of total Ca intake compared with the lowest quartile). Trends for animal Ca (IRR = 0.77, 95% CI = 0.62-0.97, P for trend = 0.039) and vegetable Ca (IRR = 0.54, 95% CI = 0.40-0.73, P for trend <0.001) were similar. The individual components of overall MetS were also inversely related to total, animal, and vegetable Ca. The tendency for an inverse association was more evident in the group with two of any of the metabolic abnormalities of MetS at baseline than in the group with no more than one MetS component. Our findings indicate that a relatively high dietary intake of Ca is associated with lower risk of MetS.


Dilation of porcine retinal arterioles to nobiletin, a polymethoxyflavonoid: Roles of nitric oxide and voltage-dependent potassium channel.
We examined the effects of nobiletin, a polymethoxyflavonoid, on the retinal microvascular diameter to determine if they depend on the endothelium and/or smooth muscle to reveal the signaling mechanisms involved in this vasomotor activity. Porcine retinal arterioles were isolated, cannulated, and pressurized without flow in vitro. Video microscopic techniques recorded diametric responses to nobiletin. The retinal arterioles dilated in a nobiletin concentration-dependent (100 pM-10 μM) manner and decreased by 50% after endothelial removal. The nitric oxide (NO) synthase inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME), reduced nobiletin-induced vasodilation comparable to denudation. Blockade of soluble guanylyl cyclase by 1H-[1,2,4] oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ) produced a similar inhibitory effect as that by L-NAME. Nobiletin-induced vasodilation was also inhibited by the nonselective potassium channel inhibitor, tetraethylammonium (TEA), and the voltage-gated K (Kv) inhibitor, 4-aminopyridine. Co-administration of L-NAME and TEA almost eliminated nobiletin-induced vasodilation. Nobiletin elicits both endothelium-dependent and -independent dilation of retinal arterioles mediated by NO release and Kv channel activation, respectively.


Impact of Intramural Scar on Mapping and Ablation of Premature Ventricular Complexes.
This study sought to determine intramural scar characteristics associated with successful premature ventricular complex (PVC) ablations. Ablating ventricular arrhythmias (VAs) originating from intramural scarring can be challenging. Imaging of intramural scar location may help to determine whether the scar is within reach of the ablation catheter. Mapping and ablation of premature ventricular complexes (PVCs) was performed in a consecutive series of patients with intramural scarring and frequent PVCs. Data from delayed enhanced cardiac magnetic resonance were assessed and the proximity of the endocardium containing the breakout site to the intramural scar was correlated with outcomes. Fifty-six patients were included, and intramural VAs were successfully targeted in 42 patients (75%) and ablation failed in 14 patients (25%). Scarring was more superficial to the endocardium in patients with successful ablations compared with patients with failed procedures (0.35 mm [interquartile range (IQR): 0.22 to 1.20 mm] vs. 2.45 mm [IQR: 1.60 to 3.13 mm]; p < 0.001). In 18 (32%) patients, ablation at the breakout site resulted in a significant change of the PVC-QRS morphology that could successfully be ablated in 9 of 12 patients from another anatomical aspect of the wall harboring the intramural scar. The scar was larger in size (1.79 cm3 [IQR: 1.25 to 2.85 cm3] vs. 1.00 cm3 [IQR: 0.59 to 1.68 cm3]; p < 0.005) compared with patients who did not have a change in the PVC-QRS morphology with ablation. VAs in patients with intramural scaring can be successfully ablated especially if the intramural scar is within close proximity to the anatomic area containing the breakout site. Changes in the QRS-PVC morphology often precede successful ablation at another breakout site and indicate larger intramural scars.


Imaging in CNS lupus.
The diagnosis of neuropsychiatric systemic lupus erythematosus (NPSLE) is complex not only on account of the heterogeneous nature of neurological presentation but also because of the difficulty of differentiating lupus-related pathology from other neuropsychiatric diseases. Magnetic resonance imaging (MRI) remains the gold standard for the non-invasive assessment of NPSLE but there are problems, both with sensitivity and specificity. Both T(2) quantitation and the use of gadolinium have shown promise in differentiating acute from chronic lesions. Nonetheless, the lack of sensitivity of conventional MRI has led to the exploration of other MR-based techniques. Magnetic resonance spectroscopy (MRS) allows the measurement of brain metabolites, whereas diffusion weighted imaging and diffusion tensor imaging allow assessment of white matter structure and integrity. MRS studies in NPSLE have consistently shown a reduction in N-acetyl aspartate (a neuronal marker). Diffusion weighted imaging has had only limited application in lupus and the results to date have shown abnormal diffusivity in lupus patients consistent with inflammation and loss of white matter structure. These techniques remain research tools at this early stage. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) have also been explored as functional imaging tools in lupus and both appear to be more sensitive in detecting subtle brain changes in NPSLE but there are issues with specificity which deter their use in the clinical setting.


Clinical models for testing chemopreventative agents in prostate cancer and overview of SELECT: the Selenium and Vitamin E Cancer Prevention Trial.
Target populations for chemoprevention trials should include those at higher than average risk for the development of prostate cancer as defined by explicit epidemiologic and genetic criteria. Such populations include a "primary prevention" group without histologic or clinical evidence of cancer, and several clinical models of "secondary prevention," including those with clinically evident disease prior to definitive therapy and those at high risk of recurrence after therapy based on histology and/or biochemical status. Each risk group and clinical model has potential advantages and disadvantages, and the mechanisms which underlie disease development and progression in each group may be unique. These observations give rise to many potential clinical trials of specific agents. These trials should also include collection of data on potentially confounding influences on disease development and progression. Preclinical, epidemiologic, and Phase II data suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. The experience of the Prostate Cancer Prevention Trial (PCPT) demonstrates the interest and dedication of healthy men to long-term studies of cancer prevention. SELECT, the Selenium and Vitamin E Cancer Prevention Trial, is an intergroup phase III, randomized, double-blind, placebo-controlled, population-based clinical trial designed to test the efficacy of selenium and vitamin E alone and in combination in the prevention of prostate cancer which builds on secondary analyses of large-scale chemoprevention trials for other cancers and the lessons of PCPT.


[Preventive measures in the management of the environment].
The natural and the man made environment influence the wellbeing and the health of the population. The management of the environments aims at the improvement of health and the disposal of health risks. The physical and psycho-social environment has to be taken into consideration, especially in connection with work, housing, energy consumption and spare time activities. Laws concerning environmental protection and energy supply could contribute to improvement of the environment.


Biomarkers of Alzheimer's disease in Black and/or African American Alzheimer's Disease Neuroimaging Initiative (ADNI) participants.
Majority of dementia research is conducted in non-Hispanic White participants despite a greater prevalence of dementia in other racial groups. To obtain a better understanding of biomarker presentation of Alzheimer's disease (AD) in the non-Hispanic White population, this study exclusively examined AD biomarker abnormalities in 85 Black and/or African American participants within the Alzheimer's Disease Neuroimaging Initiative (ADNI). Participants were classified by the ADNI into 3 clinical groups: cognitively normal, mild cognitive impairment, or dementia. Data examined included demographics, apolipoprotein E (APOE) ε4, cerebrospinal fluid (CSF) Aβ1-42, CSF total tau (t-tau), CSF phosphorylated tau (p-tau), 3T magnetic resonance imaging (MRI), and measures of cognition and function. Analyses of variance and covariance showed lower cortical thickness in 5 of 7 selected MRI regions, lower hippocampal volume, greater volume of white matter hyperintensities, lower measures of cognition and function, lower measures of CSF Aβ1-42, and greater measures of CSF t-tau and p-tau between clinical groups. Our findings confirmed greater AD biomarker abnormalities between clinical groups in this sample.


Association of Combined Complement Factor H Y402H and ARMS/LOC387715 A69S Polymorphisms with Age-related Macular Degeneration: A Meta-analysis.
Complement factor H (CFH) Y402H (rs1061170) and age-related maculopathy susceptibility2 (ARMS2)/LOC387715 A69S (rs10490924) polymorphisms shown to have significant association with age-related macular degeneration (AMD). In this meta-analysis, we pooled the results of the available association studies between combined ARMS2/LOC387715A69S-CFHY402H genotypes and AMD to estimate the possible synergistic or multiplicative effects. Heterogeneity of studies was evaluated using the Cochran Q-test and the I-square index. To modify the heterogeneity in the variables, we used random effects model. Meta-analysis was performed using STATA. To estimate the additive or supra-additive effects, we calculated relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), synergy index (S), and multiplicative index (V). We included eight studies with 2915 AMD patients and 3505 control subjects. Considering the GGTT genotypes as reference lines, the pooled AMD Odds Ratios for stratified combined genotypes were 2.32 (95% CI 1.64-3.28) for GGnon-TT, 2.49 (95% CI 1.72-3.60) for non-GGTT, and 7.82 (95% CI 5.09-12.00) for non-GGnon-TT. Pooled synergy analysis revealed RERI = 4.08 (95% CI 3.15-5.27), AP = 0.50 (95% CI 0.42-0.57), S = 2.31 (95% CI 1.9-2.82), and V = 1.21 (95% CI 0.93-1.49). This analysis revealed the synergistic and positive multiplicative effect of these two genes indicating that there is a common pathway of ARMS2/LOC387715 and CFH in AMD pathogenesis which may be the complement system pathway.


Ammonia and methane emissions during drying of dewatered biogas digestate in a two-belt conveyor dryer.
Aim of the present study was to identify type and amount of emissions during the drying of biogas digestate in a two-belt conveyor dryer at different temperature settings and to investigate the effect on its nutrient content. Furthermore, the possibility of recovering nitrogen from the exhaust air was investigated. Emissions of CH4, CO2 and NH3 were measured by Fourier transform infrared spectroscopy. Biogas is mainly composed of CH4 and CO2, hence gas release from the digestate during drying was expected to increase the concentration of these components. Although CO2 concentration was elevated above the background concentration, CH4 did not exceed the background concentration. Maximum NH3 concentration of 183.3mg·m-3 was detected during drying. A NH3 concentration of 10.8mg·m-3 was measured in the exhaust air of the ammonia scrubber, which is equal to a NH3 reduction rate of 94%.


Pigmentary complications after non-medical male circumcision.
A wide spectrum of complications are reported after male circumcision (MC), the non-aesthetic complications are well known, but the pigmentary complications scale are not reported precisely. This is a prospective cohort study of 550 circumcised boys; aged from 6 months to 14 years (62% aged 5 years) who were examined and appropriately investigated for the incidence of pigmentary complications after circumcision. Most diagnoses were clinically, but dermoscopy was done for 17 case and a skin biopsy for 14 cases. Patients with personal or family history of vitiligo, or congenital nevi were excluded. Available hospital records details and parents' statements were revised. The main outcome measures are the incidence of different pigmentary complications and circumcision details; data were analyzed by a non-parametric tests including the Mann-Whitney U test. 69 cases had 72 confirmed pigmentary complications discovered at 2-36 months after commencement of circumcision (mean 18). 48 cases had pigmentary complications directly related to MC, 11 cases were probably related and 10 unrelated to MC. The most common lesion is the circular hyperpigmented scar (29 cases); liner hyperpigmented scar in 13, spotted exogenous melanosis in 18 cases, melanocytic nevi (7), hypopigmentation diagnosed in 3 cases, but kissing nevus is the rarest finding (2). Topical corticosteroid was tried in 15 cases, surgical excision of pigmented scar were done for 19 cases, local laser used for 4 resistant cases and reassurance with follow up for the rest. Pigmentary complications after male circumcision are not rare and its management is challenging.


NMDA receptor permeation: a light in the tunnel.
A single amino acid residue determines single-channel conductance, ion permeation and channel block in the NMDA receptor, three of the key features of this ligand-gated ion channel.


Phase 2 trial of pemetrexed disodium and gemcitabine in advanced urothelial cancer (E4802): a trial of the Eastern Cooperative Oncology Group.
There is a need to identify active new regimens in patients with advanced urothelial cancer. Pemetrexed and gemcitabine are active agents in advanced urothelial cancer. A phase 2 trial of the combination of these 2 agents was performed in patients with advanced urothelial cancer who were previously untreated for metastatic disease. Forty-six patients with advanced urothelial carcinoma received pemetrexed disodium 500 mg/m2 and gemcitabine 1000 mg/m2 intravenously on Day 1, with gemcitabine repeated on Day 8. Cycles were repeated every 3 weeks for a maximum of 6 cycles. Two patients attained a complete response, and 12 patients attained a partial response for an overall response rate of 31.8% (90% confidence interval, 20.4%-45.2%). The median time to disease progression was 5.8 months, and the median overall survival was 13.4 months. Thirty-three patients (75%) experienced grade>or=3 neutropenia, and 5 patients (11%) had febrile neutropenia. There were 2 therapy-related deaths. The combination of pemetrexed and gemcitabine had moderate antitumor activity in previously untreated patients with advanced urothelial cancer at the expense of significant myelosuppression.


Analysis of the hypoplastic right ventricle utilizing electrocardiographic body surface potential mapping (BSPM).
The authors present electrocardiographic body surface potential maps (BSPMs) of 11 patients with hypoplastic right ventricle (HRV) of three types: type I, HRV with pulmonary atresia; type II, HRV with tricuspid atresia; and type III, HRV with tricuspid artesia and transposition of the great arteries. The BSPMs of all 11 patients demonstrated evidence for epicardial right ventricular breakthrough, indicating conduction through an intact right bundle branch and Purkinje system. Nonetheless, the BSPMs strongly suggested profound morphological, probably embryological, differences among the right ventricles of the three groups. The four patients with type I HRV had no evidence for conduction abnormality. The five patients with type II, HRV however, had very marked conduction abnormality. In four of these five, the standard ECG and VCG had initial forces suggesting left lateral wall myocardial infarction. The BSPMs showed no evidence for infarction but demonstrated very complicated slow initial activation, explaining why the initial QRS vector was to the right and posterior before extending leftward. In addition, in all five the initial positive potentials were unusually inferior and the initial negative potentials unusually superior. After the evidence for epicardial right ventricular breakthrough, the positive and negative potentials rapidly changed positions so that the positive potentials were unusually superior and the negative potentials unusually inferior, consistent with the BSPM of endocardial cushion defects. In four of these five there was marked delay of total ventricular activation time. Of the two patients with type III HRV, one had an initial QRS similar to that of type II. Neither had rapid change of inferior and superior positive and negative potentials after right ventricular breakthrough, and both had intraventricular slowing, one with partial left bundle branch block.


The genetics of euthyroid familial goiter.
In endemic goiters, thyroidal enlargement reflects an increase in cell proliferation triggered by low dietary iodine. However, not all individuals in the same iodine-deficient regions develop a goiter, and iodine supplementation does not prevent goiter development in all treated subjects. Familial clustering of goiters, usually with an autosomal-dominant pattern of inheritance, has repeatedly been reported. Moreover, other environmental and etiological factors are likely to be involved in the development of euthyroid goiter. Therefore, a multifactorial etiology based on complex interactions of an individual's genetic makeup and environment is likely. Family and twin studies suggest a considerable influence by a strong genetic component in euthyroid familial goiter.


Exercise testing as a rehabilitative/training tool.
Exercise testing is an exceedingly useful noninvasive method for assessing cardiovascular function not only at rest but also during programmed, supervised physical exercise. Exercise testing has been intensively studied to delineate the cardiovascular response in various disorders [3-5, 15, 19, 22, 23, 26, 32]. Exercise testing as a tool for rehabilitation and for training to perform physical activity is discussed here.


Effects of testosterone on cancellous bone, marrow adipocytes, and ovarian phenotype in a young female rat model of polycystic ovary syndrome.
To investigate the effects of testosterone on cancellous bone and marrow adipocytes in a young female rat model of polycystic ovary syndrome (PCOS). Comparative and controlled study. University animal research laboratory. Fifty-one Sprague-Dawley rats. The rats were divided into four groups based on the day of testosterone propionate (0.1 mg/weight (g)) injection: no testosterone treatment (control group, C); injected on the ninth day after birth (9D); injected 4 weeks after birth (4W); and injected 8 weeks after birth (8W). About 16 weeks after birth, all animals were killed. Bone mineral density (BMD) and bone and fat histomorphometry for the proximal tibia and serum hormonal parameters were measured. The ovaries of group 9D showed many cystic follicles without corpora lutea. The BMD of group 9D (0.309 +/- 0.023 g/cm2) was significantly higher than the other groups groups (CONT, 0.262 +/- 0.017; 4W, 0.256 +/- 0.017; 8W, 0.256 +/- 0.022 g/cm2; P < .0001). Based on bone histomorphometry, group 9D had a higher bone volume (BV/TV), lower bone formation (OV/BV, OS/BS, sLS/BS, MAR, BFR/BS), lower bone resorption (ES/BS, Oc.S/BS), and lower rate of longitudinal growth compared to the other groups. Based on fat histomorphometry, group 9D had a lower bone fat volume and number of fat cells in the bone marrow compared to the other groups. On the other hand, groups 4W and 8W showed similar values of bone and fat histomorphometric parameters to group C. Female rats receiving testosterone within nine days of birth develop polycystic ovaries, high bone volume, low bone turnover, and lower fat content in the bone marrow.


Melatonin treatment improves the antioxidant status and decreases lipid content in brain and liver of rats.
This study examines the effect of a daily administration of melatonin for 45 days at two doses (0.5 and 1.0 mg/kg body wt.) on antioxidant status, lipid peroxidation and lipid profile in the brain and liver in rats. Both doses of melatonin caused a significant decrease in lipid peroxidation and the levels of cholesterol, phospholipids, triglycerides and free fatty acids in the examined tissues. Concomitantly, the treatment with melatonin augmented the activity of the brain and liver antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase as well as increased glutathione levels. These results offer a support to the hypothesis that melatonin in pharmacological amounts effectively reduces oxidative stress and acts as an antihyperlipidemic agent.


Treatment of porphyria cutanea tarda with chloroquine and phlebotomy.
Treatment of porphyria cutanea tarda (PCT) with chloroquine risks serious side-effects so we have combined it with phlebotomy. One to four venesections were performed before the administration of chloroquine in 10 PCT patients. Equally high excretion of urinary porphyrins was achieved but the side-effects were reduced. Chloroquine may be used as a provocative diagnostic test for patients with a questionably latent PCT but this is safe if phlebotomy is performed beforehand.


Vaccinia virus early gene transcription termination factors VTF and Rap94 interact with the U9 termination motif in the nascent RNA in a transcription ternary complex.
The vaccinia virus core contains a 195 kb double stranded DNA genome, a multi-subunit RNA polymerase, transcription initiation and termination factors and mRNA processing enzymes. Upon infection, vaccinia virus early gene transcription takes place in the virus core. Transcription initiates at early promoters and terminates in response to a termination motif, UUUUUNU, in the nascent mRNA. Early gene transcription termination requires the vaccinia virus termination factor, VTF, a single stranded DNA-dependent ATPase, and NPH I, the Rap94 subunit of the virion RNA polymerase, as well as the presence of the UUUUUNU motif in the nascent RNA. The position of UUUUUNU in the ternary complex suggests that it serves as a site of interaction with one or more components of the transcription termination complex. In order to identify the factor(s) that interact with UUUUUNU a series of direct UV photo crosslinking and ribonuclease A protection studies were undertaken. Through these analyses both VTF and Rap94 were shown to interact with UUUUUNU in the isolated ternary complex. Evidence indicates that the interaction is not mutually exclusive. VTF was shown to bind to UUUUUNU through the N-terminal domain of the large D1 subunit. Furthermore, VTF protects from RNAse A digestion both the 5' region of the nascent transcript as well as a large central component containing UUUUUNU. The addition of an oligonucleotide containing the (5Br)U9 sequence both directly inhibits transcription termination, in vitro and inhibits UV photo crosslinking of VTF to the nascent RNA in the ternary complex. These results support a model in which the availability of the UUUUUNU motif outside of the transcribing RNA polymerase permits binding of both transcription termination factors, VTF and Rap94, to UUUUUNU. The assembly of this termination complex initiates the transcription termination sequence.


Glycaemic control for people with type 2 diabetes in Saudi Arabia - an urgent need for a review of management plan.
The aim of this study was to assess inadequate glycaemic control and its associated factors among people with type 2 diabetes in Saudi Arabia. A cross-sectional study design was used. Adults with type 2 diabetes attending diabetes centres in Riyadh, Hofuf and Jeddah cities were interviewed and their anthropometrics were measured. Their medical records were also reviewed to collect information related to recent lab tests, medications, and documented comorbidities. Multivariable logistic regression were used for data analysis. A total of 1111 participants were recruited in the study. Mean age was 57.6 (±11.1) years, 65.2% of the participants were females, and mean HbA1c was 8.5 ± 1.9%. About three-fourths of participants had inadequate glycaemic control (≥ 7%). Multivariable analysis showed that age ≤ 60 years, longer duration of diabetes, living in a remote location, low household income, low intake of fruits and vegetable, low level of physical activity, lack of knowledge about haemoglobin A1c, high waist-hip ratio, low adherence to medication, and using injectable medications were independent risk factors for inadequate glycaemic control. Inadequate glycaemic control is prevalent among people with type 2 diabetes in Saudi Arabia. In order to improve glycaemic control diabetes management plan should aim at controlling the modifiable risk factors which include low intake of fruits and vegetable, low level of physical activity, lack of knowledge about haemoglobin A1c, high waist-hip ratio, and low adherence to medications.


Diagnostic yield of preoperative computed tomography imaging and the importance of a clinical decision for lung cancer surgery.
This study aimed to evaluate the diagnostic yield of preoperative computed tomography (CT) imaging and the validity of surgical intervention based on the clinical decision to perform surgery for lung cancer or suspected lung cancer. We retrospectively evaluated 1755 patients who had undergone pulmonary resection for lung cancer or suspected lung cancer. CT scans were performed on all patients. Surgical intervention to diagnose and treat was based on a medical staff conference evaluation for the suspected lung cancer patients who were pathologically undiagnosed. We evaluated the relation between resected specimens and preoperative CT imaging in detail. A total of 1289 patients were diagnosed with lung cancer by preoperative pathology examination; another 466 were not pathologically diagnosed preoperatively. Among the 1289 patients preoperatively diagnosed with lung cancer, the diagnoses were confirmed postoperatively in 1282. Among the 466 patients preoperatively undiagnosed, 435 were definitively diagnosed with lung cancer, and there were 383 p-stage I disease patients. There were 38 noncancerous patients who underwent surgery with a diagnosis of confirmed or suspected lung cancer. Among the 1755 patients who underwent surgery, 1717 were pathologically confirmed with lung cancer, and the diagnostic yield of preoperative CT imaging was 97.8%. Among the 466 patients who were preoperatively undiagnosed, 435 were compatible with the predicted findings of lung cancer. Diagnostic yields of preoperative CT imaging based on clinical evaluation are sufficiently reliable. Diagnostic surgical intervention was acceptable when the clinical probability of malignancy was high and the malignancy was pathologically undiagnosed.


Uvular Necrosis Following Esophagogastroduodenoscopy: A Case Report.
BACKGROUND Uvular necrosis is an uncommon complication of esophagogastroduodenoscopy. It usually presents with sore throat, fever, foreign-body sensation, and odynophagia following esophagogastroduodenoscopy. It occurs due to impairment of local circulation, which is caused by impingement of the uvula between the endoscope and the hard palate. It may also arise from excessive suctioning of the area surrounding the uvula. We present a case of uvular necrosis following esophagogastroduodenoscopy and describe current strategies to prevent this rare complication. CASE REPORT A 19-year-old man presented with a 4-day history of odynophagia, severe sore throat, and foreign-body sensation that started within 24 h after esophagogastroduodenoscopy. Uvular necrosis was observed on physical examination. The patient was treated conservatively with nonsteroidal anti-inflammatory drugs and antibiotics, and his symptoms resolved completely. CONCLUSIONS We believe that this is the sixth reported case of uvular necrosis following an uncomplicated diagnostic esophagogastroduodenoscopy in a young patient. Esophagogastroduodenoscopy is a routine procedure performed by gastroenterologists. Uvular necrosis can occur as a rare complication of esophagogastroduodenoscopy; therefore, it is important to monitor patients for odynophagia and abnormal foreign-body sensation following the procedure for at least 72 h. Uvular necrosis should be suspected if odynophagia persists after this period despite adequate treatment with conventional analgesics. Prompt diagnosis and management can relieve the patient's symptoms, given that uvular necrosis is a self-limiting complication with a good prognosis.


[Lithium salts in child and adolescent psychiatry].
Lithium is--besides neuroleptics--the drug of choice for the treatment of manic episodes. If the use of antidepressive drugs, during unipolar depressive illness, does not lead to a positive response, the additional administration of lithium is appropriate, even during a depressive episode. Lithium is also considered as the drug of choice for prophylactic treatment of bipolar affective disorders. This holds true also for adolescents. In contrast to the indications in adults, in adolescents an early administration is desirable to reduce risk factors of psychosocial development. Additional indications may be the presence of severe aggressivity in conduct disordered children. In these cases, a treatment with lithium salts can result in a behavioral improvement. This may be also the case in impulsive self-injurious behavior. The dosage and serum levels of lithium, as well as its adverse effects are comparable with those known from adults. At present, lithium treatment cannot be recommended for children under 12 years of age--except under in-patient conditions.


Nutrient limitation regulates the properties of extracellular electron transfer and hydraulic shear resistance of electroactive biofilm.
Understanding the roles of nutrient restriction in extracellular electron transfer (EET) and stability of mixed electroactive biofilm is essential in pollutant degradation and bioenergy production. However, the relevant studies are still limited so far. Herein, the effect of nutrient restriction on the EET pathways and stability of mixed electroactive biofilm was explored. It was found that the electroactive Pseudomonas and Geobacter genera were selectively enriched in the biofilms cultured under total nutrient and P-constrained conditions, and two EET pathways including direct and indirect were found, while Rhodopseudomonas genus was enriched in the N-constrained biofilm, which only had the direct EET pathway. Moreover, multiple analyses including 2D confocal Raman spectra revealed that P-constrained biofilm was rich in extracellular polymeric substances (EPS) especially for polysaccharide, presented a dense and uniform layered distribution, and had better stability than N-constrained biofilm with lower EPS and biofilm with heterostructures cultured under total nutrient conditions.


Label-free quantification using MALDI mass spectrometry: considerations and perspectives.
Profound knowledge of protein abundances in healthy tissues and their changes in disease is crucial for understanding biological processes in basic science and for the development of novel diagnostics and therapeutics. Mass spectrometrybased label-free protein quantification is used increasingly often to gain insights into physiological changes observed in perturbed systems. Although the soft ionization techniques electrospray ionization and matrix-assisted laser desorption/ionization have both been used for protein quantification, this article focuses on instrumental setups with a MALDI ion source. Beside reviewing current bioinformatic data-processing tools for label-free quantification and elaborating on the technical benefits of combining UHPLC and MALDI-MS, we outline the potential of state-of-the-art instruments by reporting unpublished results obtained from twenty-four complex biological samples. This review points out that the capabilities of LC-MALDI MS systems have not yet been fully utilized because of a lack of suitable software tools.


The Prognostic Value of Human Papilloma Virus Infection in Oral Cavity Squamous Cell Carcinoma: A Meta-Analysis.
Human papilloma virus (HPV) infection has been confirmed as a favorable prognostic factor in oropharyngeal cancer. However, the prognostic value of HPV in oral squamous cell carcinoma (OSCC) is still unclear. Therefore, a systematic review and meta-analysis was performed to evaluate the prognostic value of HPV infection in OSCC patients. Systematic literature review with meta-analysis. A systematic literature review was conducted in accordance with PRISMA guidelines in PubMed, EMBASE, and MEDLINE databases. The primary outcomes were overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), and secondary outcomes were local control (LC), regional control (RC), and distant control (DC). A total of 22 articles with 3065 OSCC patients were included in this study. Meta-analysis demonstrated that compared to HPV-negative OSCC patients, HPV-positive OSCC patients had a significantly shorter OS (hazard ratio [HR] = 1.45, 95% confidence intervals [CI], 1.10-1.93) and lower DC (HR = 2.16, 95% CI, 1.54-3.04). There was no significant difference in DFS (HR = 1.20, 95% CI, 0.63-2.26), DSS (HR = 1.20, 95% CI, 0.63-2.26), LC (HR = 1.44, 95% CI, 0.97-2.14), and RC (HR = 1.50, 95% CI, 0.98-2.30) between HPV-positive and negative OSCC patients. Sensitivity analysis confirmed the above results. Our systematic review and meta-analysis reveal that HPV-positive is associated with significantly decreased OS and DC, suggesting HPV infection is an adverse prognostic factor in OSCC. Laryngoscope, 132:1760-1770, 2022.


Achromobacter xylosoxidans (Alcaligenes xylosoxidans subsp. xylosoxidans) bacteremia associated with a well-water source: case report and review of the literature.
A case of community-acquired Achromobacter xylosoxidans bacteremia in a patient with metastatic breast carcinoma is described. The patient's home drinking water was identified as the source of her bacteremia. The case represents the first in which a community-acquired infection due to this organism has been attributed to a documented water source.


Sentinel node biopsy prior to neoadjuvant chemotherapy.
Several studies have explored sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy, but false negative rates and the loss of pretreatment nodal staging are limitations. Sentinel lymph node biopsy prior to induction chemotherapy may address both. Sentinel lymph node biopsy was performed in clinically node negative patients prior to initiating chemotherapy. Standard level I/II axillary lymph node dissection (ALND) was performed at the time of surgery in those patients who had metastases in the sentinel lymph node (SLN). Twenty-five patients had 26 SLNB prior to the initiation of chemotherapy. The SLN was identified in all cases (100%). Twelve patients (48%) were found to be node negative and did not require axillary node dissection after chemotherapy. Of the patients who were SLN positive and underwent completion ALND, residual nodal disease was identified in 60%. There were no surgical complications or delay of chemotherapy. Sentinel lymph node biopsy prior to neoadjuvant chemotherapy can avoid the morbidity of ALND without compromising the accuracy of axillary staging. It allows for identification of node positive patients subsequently rendered disease free in the regional nodes, which can assist in planning additional chemotherapy or radiation.


Life satisfaction, self-esteem, and body image: a psychosocial evaluation of aesthetic and reconstructive surgery candidates.
Psychology should be an important part of a plastic surgery procedure in order to buoy up the patient so that he gains a consequent relief of psychiatric and social problems. It is a fact that reconstructive surgery patients also seek psychological stability and a better appearance that is acceptable to society. While the life satisfaction, self-esteem, and body image of the individual who seeks aesthetic plastic surgery has been a special concern in the plastic surgery literature, data about reconstructive surgery patients are usually lacking. To understand the factors influencing the aim of an individual seeking plastic surgery, this prospective controlled clinical study was designed. We hypothesized that they should have lower life satisfaction and self-esteem and more distorted body images than the "normal" population. Three hundred individuals were included in the study. Both the aesthetic surgery group (AG) and the reconstructive surgery group (RG) consist of 100 (n = 100) subjects. Individuals chosen randomly from the total population seen in the 12-month period were included regardless of the type of procedure, body region, or type of trauma as well as whether or not their wish for surgery was justified by the staff. The third group, the control group (CG), also consists of 100 (n = 100) subjects and was chosen from the "normal" population. All 300 subjects were asked to complete four scales: the Socio-Demographic Questionnaire, Life-Satisfaction Index (LSI), Self-Esteem Inventory (SEI), and Body-Image Inventory (BII). Results were collected and compared. The LSI results for the two surgical groups were found to be similar to those for the CG, with the RG demonstrating the lowest level. For the SEI there was a significant difference between the two surgical groups, being in favor of the AG, and a greater difference was noted between the CG and the RG. BII results showed no significant difference among the three groups. As a result, although there may be some, a regular person who seeks an aesthetic procedure should not be considered a psychologically disturbed individual at face value and each case should be evaluated individually in the preoperative consultation. Similarly, individuals who present for reconstructive procedures and wish further aesthetic refinements should be evaluated and treated exactly as pure aesthetic candidates.


Uridine uptake inhibition assay: an automated micromethod for the screening of cytotoxicity.
The uridine uptake inhibition assay is a sensitive microassay for measuring cytotoxicity. This assay is normally performed with Hela S3 cells, which lack metabolic activity. In an earlier study, we adapted the test to HepG2 cells, a human hepatoma cell line that retains many hepatocyte characteristics, such as functional metabolic enzymes. This study describes a new automated protocol for the assay that makes it much more rapid. In the previous protocol, after the cells were treated with the test compounds and allowed to take up uridine for 30 min, samples were taken manually one by one and spotted onto 3MM Whatman paper. After drying, the paper sheet was then chromatographed in 5% (P/V) TCA for 2 h in order to precipitate and measure the total amount of RNA. In the new method, instead of paper chromatography, samples are transferred onto a 96-well microplate equipped with GF/C glass filters. Then, RNA precipitation by TCA is carried out with a manifold system, and the amount of radiolabeled uridine taken up by the cells is counted directly with a radioactivity microplate reader. This method makes it possible to screen many compounds simultaneously for cytotoxicity. To evaluate its sensitivity, we compared the IC(50) values obtained with new and original protocol for each eight toxic compounds. We found an excellent correlation between the two methods (r(2)=0.99). With the automated protocol, the uridine uptake inhibition assay is both sensitive and rapid enough for high-throughput daily screening.


A comparative categorization of gene flux in diverse microbial species.
Microbial genomes harbor genomic islands (GIs), genes presumably acquired via horizontal gene transfer (HGT). We compared GIs of hyperthermophilic, thermophilic, mesophilic, and pathogenic/nonpathogenic species and of small and large genomes. The COG database was used to characterize gene-encoded functions. Putative donors were determined to quantify gene flux between superkingdoms. In hyperthermophiles, more than 10% of the genes were on average acquired across the superkingdom border. For thermophiles and particularly mesophiles, we identified a nearly unidirectional export from bacteria to archaea. Additionally, we analyzed GI composition for Escherichia, and pairs of Listeria, Rhizobiales, Methanosarcinaceae, and Thermus thermophilus/Deinococcus radiodurans. For Escherichia and Listeria, the composition of GIs in pathogenic and nonpathogenic species did not differ significantly with respect to encoded COG classes. The analysis of related genomes showed that the composition of GIs cannot be explained with trends of gene content known to depend on genome size.


Percutaneous transhepatic cholecystoscopic gallstone fragmentation: a novel approach for the medically unfit patient?
Management of the surgically unfit patient with symptomatic cholelithiasis can be fraught with difficulty. We describe the case of on such gentleman in whom percutaneous transhepatic cholecystoscopy was used to completely fragment a large gallbladder calculus through the use of a nephroscope and Swiss lithoclast Master.


Posterior inferior cerebellar artery aneurysm in the fourth ventricle.
We report a patient with a ruptured aneurysm of the choroidal branch of the right posterior inferior cerebellar artery (PICA), lying in and causing an isolated haemorrhage in the fourth ventricle. MRI on the first day after bleeding revealed an abnormal vessel in the fourth ventricle, which was surrounded by a mass of intermediate signal on T1- and T2-weighted images. The aneurysm was clipped via partial splitting of the lower vermis and opening the inferior medullary velum. A postoperative angiogram confirmed complete obliteration of the aneurysm. With PICA aneurysms the rate of intraventricular haemorrhage is high and in most cases due to reflux of blood. If there is an isolated intraventricular haemorrhage, a peripheral PICA aneurysm, lying in or near the fourth ventricle, may be suspected.


Identification of a Novel Mycoplasma Species in a Patient With Septic Arthritis of the Hip and Seal Finger.
An Alaska Native hunter developed fever, swollen finger, and septic hips after harvesting seals. Evaluation of hip tissue by 16S rRNA gene polymerase chain reaction and sequencing revealed a putative novel mycoplasma species. We report the identification of this organism and describe the first known case of disseminated seal finger mycoplasmosis.


Modulation of pulmonary desmosomes by inhaler therapy in preterm-born children with bronchopulmonary dysplasia.
Despite evidence demonstrating persistent lung function deficits in preterm-born children, especially in those who had bronchopulmonary dysplasia (BPD) in infancy, the underlying biological mechanisms explaining these lung function deficits remain poorly understood. We characterised the exhaled breath condensate (EBC) proteome in preterm-born children, with and without BPD; and before and after inhaler treatment. EBC from children aged 7-12 years, from the Respiratory Health Outcomes in Neonates (RHiNO) study, were analysed by Nano-LC Mass Spectrometry with Tandem Mass Tag labelling. Children with percent predicted forced expiratory volume in 1 second ≤ 85% were enrolled to a 12-week blinded randomised trial of inhaled corticosteroids alone (ICS) or with long-acting β2-agonist (ICS/LABA) or placebo. EBC was analysed from 218 children at baseline, and 46 children received randomised inhaled therapy. 210 proteins were detected in total. For the 19 proteins present in every sample, the desmosome proteins: desmoglein-1, desmocollin-1 and plakoglobin were significantly decreased, and cytokeratin-6A was increased in preterm-born children with BPD when compared to preterm- and term-born controls. ICS/LABA treatment significantly increased abundance of desmoglein-1, desmocollin-1 and plakoglobin in the BPD group with low lung function, and significantly increased plakoglobin in those without BPD. No differences were noted after ICS treatment. Exploratory analyses of proteins not detected in all samples suggested decreased abundance of several antiproteases. This study provides proteomic evidence of ongoing pulmonary structural changes with decreased desmosomes in school-aged preterm-born children with BPD and low lung function, which was reversed with combined inhaled corticosteroids and long-acting β2-agonists therapy.


The Smc complexes in DNA damage response.
The structural maintenance of chromosomes (Smc) proteins regulate nearly all aspects of chromosome biology and are critical for genomic stability. In eukaryotes, six Smc proteins form three heterodimers--Smc1/3, Smc2/4, and Smc5/6--which together with non-Smc proteins form cohesin, condensin, and the Smc5/6 complex, respectively. Cohesin is required for proper chromosome segregation. It establishes and maintains sister-chromatid cohesion until all sister chromatids achieve bipolar attachment to the mitotic spindle. Condensin mediates chromosome condensation during mitosis. The Smc5/6 complex has multiple roles in DNA repair. In addition to their major functions in chromosome cohesion and condensation, cohesin and condensin also participate in the cellular DNA damage response. Here we review recent progress on the functions of all three Smc complexes in DNA repair and their cell cycle regulation by posttranslational modifications, such as acetylation, phosphorylation, and sumoylation. An in-depth understanding of the mechanisms by which these complexes promote DNA repair and genomic stability may help us to uncover the molecular basis of genomic instability in human cancers and devise ways that exploit this instability to treat cancers.


Guanosine Dianions Hydrated by One to Four Water Molecules.
Intermolecular interactions such as those present in molecule···water complexes may profoundly influence the physicochemical properties of molecules. Here, we carried out an experimental-computational study on doubly deprotonated guanosine monophosphate···water clusters, [dGMP - 2H]2-·nH2O (n = 1-4), using a combination of negative anion photoelectron spectroscopy (NIPES) with molecular dynamics (MD) and quantum chemical (QM) calculations. Successive addition of water molecules to [dGMP - 2H]2- increases the experimental adiabatic detachment (ADE) and vertical detachment energy (VDE) by 0.5-0.1 eV, depending on the cluster size. In order to choose the representative conformations, we combined MD simulations with a clustering procedure to identify low energy geometries for which ADEs and VDEs were computed at the CAM-B3LYP/6-31++G(d,p) level. Our results demonstrate that the assumed approach leads to sound geometries and energetics of the studied microsolvates since the calculated ADEs and VDEs are in pretty good agreement with the experimental characteristics. The evolution of hydrogen bonding with cluster size indicates the possibility of the occurrence of proton transfer for clusters comprising a larger number of water molecules.


Determination of fluoride content in teas and herbal products popular in Poland.
Fluoride level, due to its narrow therapeutical range, must be constantly monitored in beverages, especially in daily-consumed plant infusions. Fluoride is important for prevention of tooth decay and osteoporosis, but its excess leads to fluorosis. Since tea can selectively absorb fluorides from soils, the question arises if a long-term consumption can pose an adverse effect on human health. Infusions of 33 popular teas (black, green, white, earl grey, pu-erh), tea-like products (rooibos, yerba mate) and herbs (chamomile, mint, nettle, purges, yarrow) available in the Polish market were analyzed with respect to a fluoride level by means of a validated ion-selective electrode method, which is proven to be fast and reliable. Significantly different fluoride concentrations in infusions were observed, with black tea on top, where extraction of fluoride is the highest (average 2.65 mg F-/L, range 0.718-6.029 mg/L). Two-fold higher fluoride contents were measured in infusions made from black tea bags than from leaves (average 3.398 mg/L and 1.529 mg/L, respectively). Green teas released comparable amounts of fluoride as black teas, while in herbal extracts the fluoride content was negligible. The rank with respect to the fluoride concentration in an infusion is as follows: black tea > green tea > earl grey > pu-erh > white tea>>>rooibos, yerba mate, herbal products. Increasing of brewing time results in an increased fluoride content, but the overall content of fluoride in the analyzed infusions of teas and herbs was not high enough to cause a risk of fluorosis, even if left to brew up to 15 min.


Individual differences in delay discounting are associated with dorsal prefrontal cortex connectivity in children, adolescents, and adults.
Delay discounting is a measure of impulsive choice relevant in adolescence as it predicts many real-life outcomes, including obesity and academic achievement. However, resting-state functional networks underlying individual differences in delay discounting during youth remain incompletely described. Here we investigate the association between multivariate patterns of functional connectivity and individual differences in impulsive choice in a large sample of children, adolescents, and adults. A total of 293 participants (9-23 years) completed a delay discounting task and underwent 3T resting-state fMRI. A connectome-wide analysis using multivariate distance-based matrix regression was used to examine whole-brain relationships between delay discounting and functional connectivity. These analyses revealed that individual differences in delay discounting were associated with patterns of connectivity emanating from the left dorsal prefrontal cortex, a default mode network hub. Greater delay discounting was associated with greater functional connectivity between the dorsal prefrontal cortex and other default mode network regions, but reduced connectivity with regions in the dorsal and ventral attention networks. These results suggest delay discounting in children, adolescents, and adults is associated with individual differences in relationships both within the default mode network and between the default mode and networks involved in attentional and cognitive control.


Structural insights into initial and intermediate steps of the ribosome-recycling process.
The ribosome-recycling factor (RRF) and elongation factor-G (EF-G) disassemble the 70S post-termination complex (PoTC) into mRNA, tRNA, and two ribosomal subunits. We have determined cryo-electron microscopic structures of the PoTC·RRF complex, with and without EF-G. We find that domain II of RRF initially interacts with universally conserved residues of the 23S rRNA helices 43 and 95, and protein L11 within the 50S ribosomal subunit. Upon EF-G binding, both RRF and tRNA are driven towards the tRNA-exit (E) site, with a large rotational movement of domain II of RRF towards the 30S ribosomal subunit. During this intermediate step of the recycling process, domain II of RRF and domain IV of EF-G adopt hitherto unknown conformations. Furthermore, binding of EF-G to the PoTC·RRF complex reverts the ribosome from ratcheted to unratcheted state. These results suggest that (i) the ribosomal intersubunit reorganizations upon RRF binding and subsequent EF-G binding could be instrumental in destabilizing the PoTC and (ii) the modes of action of EF-G during tRNA translocation and ribosome-recycling steps are markedly different.


Treatment of retinal detachment with congenital optic pit by krypton laser photocoagulation.
Five patients with a congenital pit of the optic nerve and serous detachment of the macular retina were treated with krypton laser photocoagulation to the juxtapapillary region in an attempt to induce resolution of the retinal detachment. The subretinal fluid resolved after laser therapy in four of the patients. In the fifth, the retinal detachment was successfully treated with pars plana vitrectomy. One patient developed a macular hole and decreased visual acuity, despite resolution of the subretinal fluid.


Primary fusion versus open reduction internal fixation for purely ligamentous lisfranc injuries: A Prospective comparative study and analysis of factors affecting the outcomes.
The studies evaluating the outcomes of treatment of purely ligamentous unstable Lisfranc injuries are scarce. This study aimed at comparing outcomes of primary tarso-metatarsal joints fusion versus open reduction and internal fixation in treatment of such condition and determining the possible factors that may alter the outcomes. This study comprised 30 patients; 16 in fusion group and 14 in ORIF group. One column was operated on in 2 patients, two columns in 21, and three columns in 7. The mean follow-up period was 36 months. There was no statistically significant difference between both groups regarding patients or injury characteristics. The mean AOFAS and FFI-Rs scores were 88.9 and 22.7 in the fusion group, compared to 61.7 and 34.5 in the ORIF group (P = .03,.04 respectively). At final follow-up all patients in the primary arthrodesis group were maintaining an anatomical reduction versus 71.5% in the ORIF group. Sixteen patients (53%) reported prominent hardware troubles that required removal. Five patients in ORIF group developed osteoarthritis, and four of them underwent secondary fusion. There was significantly higher incidence of posttraumatic osteoarthritis in patients with non-anatomical reduction and complete injuries. Better mean AOFAS and FFI-Rs scores occurred with non-smokers and with anatomical reduction. Based on this limited case series, purely ligamentous Lisfranc injuries were found to have better outcomes when managed with a primary fusion as compared to ORIF. Achieving and maintaining anatomical reduction was the most important factor that is significantly attributed to improved outcomes. Possible arthritic changes and additional surgeries apart from implant removal could be avoided by primary fusion. level I- prospective comparative case study.


Coexistence of two main folded G-quadruplexes within a single G-rich domain in the EGFR promoter.
EGFR is an oncogene which codifies for a tyrosine kinase receptor that represents an important target for anticancer therapy. Indeed, several human cancers showed an upregulation of the activity of this protein. The promoter of this gene contains some G-rich domains, thus representing a yet unexplored point of intervention to potentially silence this gene. Here, we explore the conformational equilibria of a 30-nt long sequence located at position -272 (EGFR-272). By merging spectroscopic and electrophoretic analysis performed on the wild-type sequence as well as on a wide panel of related mutants, we were able to prove that in potassium ion containing solution this sequence folds into two main G-quadruplex structures, one parallel and one hybrid. They show comparable thermal stabilities and affinities for the metal ion and, indeed, they are always co-present in solution. The folding process is driven by a hairpin occurring in the domain corresponding to the terminal loop which works as an important stabilizing element for both the identified G-quadruplex arrangements.


Computational modeling of an ion-driven nanomotor.
The dynamics of an ion-driven rotary nanomotor, mimicking the F(0) part of the ATPase biomolecular motor, in the presence, and absence, of an external electric field have been simulated via the application of the stochastic molecular dynamics (MD) method. The rotary motion of the proposed motor arises as a result of an ion gradient established between the outer and inner parts of the environment within which the motor is embedded. We show that the operation of this motor can be controlled by such parameters as the amount of the positive ions placed in the stator part of the motor, the density of the positive ions, and the strength and frequency of the applied electric field.


Survival of corneal endothelium following exposure to a vitrification solution.
Corneal endothelium, a monolayer of cells lining the inner surface of the cornea, is particularly susceptible to freezing injury. Ice formation damages the structural and functional integrity of the endothelium, and this results in a loss of corneal transparency. Instead of freezing, an alternative method of cryopreservation is vitrification, which avoids damage associated with ice formation. Vitrification at practicable cooling rates, however, requires exposure of tissues to very high concentrations of cryoprotectants, and this can cause damage through chemical toxicity and osmotic stress. The effects of a vitrification solution (VS1) containing 2.62 mol/liter (20.5%, w/v) dimethyl sulfoxide, 2.62 mol/liter (15.5%, w/v) acetamide, 1.32 mol/liter (10%, w/v) propane-1,2-diol, and 6% (w/v) polyethylene glycol were studied on corneal endothelium. Endothelial function was assessed by monitoring corneal thickness during 6 hr of perfusion at 35 degrees C with a Ringer solution supplemented with glutathione and adenosine. Various dilutions of the vitrification solution were introduced and removed in a stepwise manner to mitigate osmotic stress. Survival of endothelium after exposure to VS1 or a solution containing 90% of the cryoprotectant concentrations in VS1 (90% VS1) was dependent on the duration of exposure, the temperature of exposure, and the dilution protocol. The basic dilution protocol was performed at 25 degrees C: corneas were transferred from 90% VS1 or VS1 into 50% VS1 for 15 min, followed by 25% VS1 for 15 min and finally into isosmotic Ringer solution. Using this protocol, corneal endothelium survived exposure to 90% VS1 for 15 min at -5 degrees C, but 5 min in VS1 at -5 degrees C was harmful and resulted in some very large and misshapen endothelial cells. This damage was not ameliorated by using a sucrose dilution technique; but endothelial function was improved when the temperature of exposure to VS1 was reduced from -5 to -10 degrees C. Exposure to VS1 for 5 min at -5 degrees C was well tolerated, however, when the temperature of the first dilution step into 50% VS1 was reduced from 25 to 0 degree C. The large, misshapen cells were not observed under these conditions nor after exposure to VS1 at -10 degrees C. These results suggested that damage was the result of cryoprotectant toxicity rather than osmotic stress. Thus, corneal endothelium survived exposure to two solutions of cryoprotectants, namely, 90% VS1 and VS1, that were sufficiently concentrated to vitrify. Whether corneas can be cooled fast enough in these solutions to achieve vitrification and warmed fast enough to avoid devitrification remains to be determined.


Long-Term Treatment with the Combination of Rivaroxaban and Aspirin in Patients with Chronic Coronary or Peripheral Artery Disease: Outcomes During the Open Label Extension of the COMPASS trial.
To describe outcomes of patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial who were treated with the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily during long-term open-label extension (LTOLE). Of the 27 395 patients enrolled in COMPASS, 12 964 (mean age at baseline 67.2 years) from 455 sites in 32 countries were enrolled in LTOLE and treated with the combination of rivaroxaban and aspirin for a median of 374 additional days (range 1-1191 days). During LTOLE, the incident events per 100 patient years were as follows: for the primary outcome [cardiovascular death, stroke, or myocardial infarction (MI)] 2.35 [95% confidence interval (CI) 2.11-2.61], mortality 1.87 (1.65-2.10), stroke 0.62 (0.50-0.76), and MI 1.02 (0.86-1.19), with CIs that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major and minor bleeding were 1.01 (0.86-1.19) and 2.49 (2.24-2.75), compared with 1.67 (1.48-1.87) and 5.11 (95% CI 4.77-5.47), respectively, during the randomized treatment phase with the combination. In patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to or lower than those seen during the randomized treatment phase, without any new safety signals.


Treatment and survival in children with pulmonary arterial hypertension: the UK Pulmonary Hypertension Service for Children 2001-2006.
A retrospective study of the UK Pulmonary Hypertension Service for Children for the first 5-year period of its existence. Records of 216 children with idiopathic pulmonary arterial hypertension (IPAH) and associated pulmonary arterial hypertension (APAH) were reviewed. Kaplan-Meier survival curves were constructed for different diagnostic groups and for different therapies. At cardiac catheterisation only 7.4% of those with IPAH and 6% of those with APAH responded positively to vasodilator testing and so were treated with nifedipine. Others needing treatment were given continuous intravenous epoprostenol, bosentan or sildenafil singly or in combination. For IPAH survival rates were 85.6%, 79.9% and 71.9% at 1, 3 and 5 years, respectively, compared with a survival time of less than a year in historical untreated controls. A combination of intravenous epoprostenol with either bosentan or sildenafil, or both, appeared to achieve the best outcome. Six children underwent lung transplantation. In APAH survival rates were 92.3%, 83.8% and 56.9% at 1, 3 and 5 years, respectively, postoperative congenital heart disease with severe pulmonary hypertension having the worst outcome. New pulmonary hypertension-specific medicines have improved survival in children as in adults. Outcome in this series compares favourably with international outcome data.


Use of final irrigant potassium titanyl phosphate laser; Sapindus Mukorossi and Fotoenticine on the bond values of zirconia post-to-canal dentin.
Assessment of the efficacy of final root canal irrigants Sapindus mukorossi (SM), Potassium titanyl phosphate laser (KTPL), and Fotoenticine (FTC) on the push-out bond strength (PBS) of zirconia post. The root canal procedure was initiated using the 10 K file and the working length was determined on single-rooted human premolar teeth after decoration. The canals were then enlarged using ProTaper universal system and filled using single cone gutta-percha (GP) and AH Plus resin sealer. Post space was prepared by removing 10 mm of GP from the canal. All the teeth were then allocated into four groups based on the final irrigating regime used (n = 10) Group 1: 5.25% NaOCl+17% EDTA, Group 2: 5.25% NaOCl + KTPL, Group 3: 5.25% NaOCl + FTC and Group 4: 5.25% NaOCl+ SM. Zirconia posts were cemented in the canal space. The specimens were sectioned and implanted in auto-polymerizing acrylic resin. A universal testing machine and stereomicroscope at 40x magnification were used for PBS and failure mode analysis. ANOVA and Tukey post hoc test were used to make group comparisons(p = 0.05). Group 4 (5.25% NaOCl+ SM) coronal section displayed the highest PBS (9.29±0.24 MPa). However, group 3 (5.25% NaOCl+ FTC) apical third (4.08±0.14 MPa) showed the lowest bond values. Group 2 (5.25% NaOCl+ KTP laser) and Group 3 at all three-thirds unveiled no significant difference in PBS(p>0.05). However, Group 1 (5.25% NaOCl+17%EDTA) and Group 4 displayed comparable outcomes of bond strength(p>0.05) CONCLUSION: Sapindus mukorossi has the ability to be used as a final root canal irrigant alternative to EDTA. However, future studies are still required to conclude the outcomes of existing research.


Catalyst recognition of cis-1,2-diols enables site-selective functionalization of complex molecules.
Carbohydrates and natural products serve essential roles in nature, and also provide core scaffolds for pharmaceutical agents and vaccines. However, the inherent complexity of these molecules imposes significant synthetic hurdles for their selective functionalization and derivatization. Nature has, in part, addressed these issues by employing enzymes that are able to orient and activate substrates within a chiral pocket, which increases dramatically both the rate and selectivity of organic transformations. In this article we show that similar proximity effects can be utilized in the context of synthetic catalysts to achieve general and predictable site-selective functionalization of complex molecules. Unlike enzymes, our catalysts apply a single reversible covalent bond to recognize and bind to specific functional group displays within substrates. By combining this unique binding selectivity and asymmetric catalysis, we are able to modify the less reactive axial positions within monosaccharides and natural products.


A comparison of machine learning methods for survival analysis of high-dimensional clinical data for dementia prediction.
Data collected from clinical trials and cohort studies, such as dementia studies, are often high-dimensional, censored, heterogeneous and contain missing information, presenting challenges to traditional statistical analysis. There is an urgent need for methods that can overcome these challenges to model this complex data. At present there is no cure for dementia and no treatment that can successfully change the course of the disease. Machine learning models that can predict the time until a patient develops dementia are important tools in helping understand dementia risks and can give more accurate results than traditional statistical methods when modelling high-dimensional, heterogeneous, clinical data. This work compares the performance and stability of ten machine learning algorithms, combined with eight feature selection methods, capable of performing survival analysis of high-dimensional, heterogeneous, clinical data. We developed models that predict survival to dementia using baseline data from two different studies. The Sydney Memory and Ageing Study (MAS) is a longitudinal cohort study of 1037 participants, aged 70-90 years, that aims to determine the effects of ageing on cognition. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a longitudinal study aimed at identifying biomarkers for the early detection and tracking of Alzheimer's disease. Using the concordance index as a measure of performance, our models achieve maximum performance values of 0.82 for MAS and 0.93 For ADNI.


Effect of methotrexate on the deoxyuridine suppression test: results with different cell preparations.
Recently, the deoxyuridine suppression test was used to detect folate deficiency. Several cell preparations were used in this test, and the sensitivity of the test seems to vary with them. We used whole blood (micro-dU test) and bone marrow cells for the deoxyuridine suppression test, and the effects of methotrexate were compared. [3H]Thymidine incorporation into DNA was highest when the concentration of methotrexate was 1 microM in the whole blood culture and bone marrow culture. Methotrexate concentrations from 100 nM to 1 mM did not affect the results of the micro-dU test. However, the bone marrow deoxyuridine test became abnormal with methotrexate, and the abnormality in test values was corrected by the addition of N5-formyltetrahydrofolate. Differences in the results between the micro-dU test and the bone marrow deoxyuridine suppression test seem to represent specificity of each dU test.


The non-specific esterases of mouse lung.
The non-specific esterases of the lung of the house mouse, M. musculus, were examined by polyacrylamide electrophoresis and by isoelectric focusing. At least 13 different esterases were distinguished and identified, mainly by their catalytic properties, susceptibility to inhibition, developmental patterns and phenotypic variation amongst different strains. A list of diagnostic features of the 13 esterases was presented. None of the esterases was lung-specific. However, the pattern of esterases found in the adult lung was characteristic of that organ. It was pointed out that this pattern is associated with the high degree of tissue differentiation in the adult lung. At least 8 esterases were found which belong to the isozyme system of carboxylesterase EC 126.96.36.199, under the control of genes located on chromosome 8. These esterases accounted for about 90% of the esterase activity in the lung.


A new species of Neuraphes Thomson, 1859 (Coleoptera: Staphylinidae: Scydmaeninae) from Kazakhstan.
Neuraphes (s. str.) kazakhstanicus, new species of the tribe Cyrtoscydmini, is described from Kazakhstan. The genus is for the first time recorded from Central Asia. A detailed morphological study is presented.


Formation and optical properties of silver perfluorodecanethiolate nanoparticles.
This article reports a new catalytic method for preparing nanoparticles of silver thiolate from silver nanoparticles scattered on a ZrO2-coated substrate. Such nanoparticles transform into silver (perfluoro) decanethiolate after immersion in a solution of (perfluoro) decanethiol in heptane. These transformations occur at room temperature and are catalysed by ZrO2. The silver decanethiolate is obtained as lamellar crystals while the silver perfluorodecanethiolate is obtained in amorphous state. The modifications of the sample optical properties due to this latter compound are studied in correlation with its surface morphology, according to different preparation conditions. It is shown that an antireflective effect in addition to the damping of the plasmon band of the silver nanoparticles can be responsible for a large transmittance enhancement in the near-UV and visible ranges. These effects are modulated by the possible oxidation of the silver nanoparticle surface. In the absence of silver oxidation, the silver perfluorodecanethiolate is obtained as contiguous spheroidal nanoparticles, while, in the presence of silver oxidation, this compound is mainly obtained as entangled nanowires.


Transcriptional activation of adrenocortical steroidogenic genes by high potassium or low sodium intake.
We have previously shown that the long-term alterations in the intake of sodium and potassium which stimulated aldosterone production in the rat adrenal significantly increased cytochrome P450scc (P450scc) and P45011 beta (P45011 beta) mRNA's and also the mRNA of their electron donor adrenodoxin. In the present study run-on analyses showed an accumulation of nascent RNA in isolated nuclei of zona glomerulosa cells in K(+)-supplemented and Na(+)-depleted rats for P450scc (5- and 6-fold), 3 beta-HSD (3.6- and 2.0-fold) and P45011 beta (6.0- and 6.1-fold), but not for P450c21 (1.4- and 1.1-fold). In contrast, that of adrenodoxin decrease (0.6-fold) in high K+ and remained near control (1.3-fold) in low Na+ intake. Moderate variations in the rate of transcription of P450scc, P450c21, P45011 beta and adrenodoxin genes were observed in the zona fasciculata-reticularis cells of the treated rats. Our results thus demonstrated that positive modulators of aldosterone such as long-term K+ supplementation and Na+ restriction provoked an increase in transcription of the genes encoding key regulatory steroidogenic enzymes of aldosterone biosynthesis in the zona glomerulosa. The rates of transcription of the genes encoding 3 beta-HSD and P450c21, two enzymes catalyzing intermediate steps in the aldosterone pathway, were moderately affected by such treatments. However, according to the known stimulation of adrenodoxin mRNA levels following these treatments, a decreased turnover of the adrenodoxin mRNA rather than initiation of transcription of its gene might be involved in the response to K+ ions, and partially so in the response to Na+ restriction. Finally, the effects of salt-modified intake were mainly restricted to the zona glomerulosa cells, which are solely responsible for aldosterone production.


Signalling molecules, growth regulators and cell cycle control in Drosophila.
During the development of a given organ or tissue within a multicellular organism, growth and patterning are controlled in a coordinated manner by the activity of a discrete number of signalling molecules and their corresponding pathways to give rise to a well-formed structure with a particular size, shape and pattern. Understanding how cells of different tissues or organs translate the activity of these pathways into an activation or repression of the cell cycle machinery in a context-dependent manner is at present one of the most intriguing questions in developmental and cancer biology. In this article we review the different roles of the Notch and Wingless signalling molecules in the regulation of cell cycle progression in the developing eye and wing imaginal discs of Drosophila and propose that, depending on how growth regulators are controlled in a context-dependent manner by the activity of these pathways, signalling molecules might have tumour suppressor or oncogene activity.


Laparoscopic adrenalectomy for benign adrenal neoplasms.
Since first reported in 1992, laparoscopic adrenalectomy has been used to remove a wide variety of adrenal neoplasms. Indications for use of this technique have not been clearly defined, nor has it been demonstrated to be more cost effective than open adrenalectomy. A retrospective comparison was made of 19 consecutive laparoscopic and open adrenalectomies performed in patients with benign adrenal neoplasms in a tertiary-care university teaching hospital over a 3-year period. The two groups were well matched for side of tumor and age. Laparoscopic adrenalectomy was completed in 11 of 12 patients in whom it was attempted. The laparoscopic group had significantly smaller tumor size; shorter operative time, postoperative ileus, and postoperative stay; and decreased operative blood loss and postoperative narcotic requirement. There were no significant differences between groups for operating room or hospital charges. Laparoscopic adrenalectomy is cost effective and should be the preferred treatment for patients with small benign adrenal neoplasms.


Demonstration of amyloid with Mesitol WLS-Congo Red: application of a textile auxiliary to histochemistry.
Previous histochemical investigations demonstrated similarities in the binding of Congo Red and other direct cotton dyes by amyloid and cellulose. It seemed therefore of interest to determine whether or not the cellulose-like reactivity of amyloid extends also to dye solutions containing an anionic reserving agent. These reagents are used in the dyeing of wool-cellulose (Halbwolle) fabrics to prevent binding of direct cotton dyes by proteins. Mesitol WLS-Congo Red solutions stained amyloid selectively; other tissue structures, except some hyaline deposits in arterioles, remained unstained. The cause of this non-specific reaction could not be determined with certainty. Therefore, the alkaline Congo Red method is recommended for histochemical identification of amyloid. However, the Mesitol WLS-Congo Red technic was very useful for demonstration of amyloid after prolonged storage of tissues in formalin; amyloid in such material showed little or no reactivity with the alkaline Congo Red or the Sirius dye methods. This pilot study indicates that anionic reserving agents can be effectively employed under conditions of histochemical technics.