Using a two site-reactive model for simulating one century changes of Zn and Pb concentration profiles in soils affected by metallurgical fallout.
Predicting the transfer of contaminants in soils is often hampered by lacking validation of mathematical models. Here, we applied Hydrus-2D software to three agricultural soils for simulating the 1900-2005 changes of zinc and lead concentration profiles derived from industrial atmospheric deposition, to validate the tested models with plausible assumptions on past metal inputs to reach the 2005 situation. The models were set with data from previous studies on the geochemical background, estimated temporal metal deposition, and the 2005 metal distributions. Different hypotheses of chemical reactions of metals with the soil solution were examined: 100% equilibrium or partial equilibrium, parameterized following kinetic chemical extractions. Finally, a two-site model with kinetic constant values adjusted at 1% of EDTA extraction parameters satisfactory predicted changes in metal concentration profiles for two arable soils. For a grassland soil however, this model showed limited applicability by ignoring the role of earthworm activity in metal incorporation.


Architecture of human translation initiation factor 3.
Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans.


Preeclampsia and depression: a case-control study in Tehran.
This study was conducted to determine the correlation between preeclampsia and depression. Participants in this study included 156 cases with preeclampsia and 156 controls without any history of preeclampsia who were all newly admitted to antepartum wards, emergency room wards, and labor and delivery wards of the study hospitals (Valieasr, Shariatti, Mirza Koochak Khan, Shahid Akbar Abadi, Baharloo and Arash). They consented and completed a questionnaire on demographic characteristics, obstetric, delivery and infant information and Patient Health Questionnaire (PHQ-9) to assess their depression status. Data were analyzed through independent t test, Mann-Whitney U test, Chi-squared test, Fisher's exact test and multiple regression by SPSS and STATA. Moderate to severe depression was found in 31.2% of the cases and 24.8% of the controls. Women with no depression in comparison with women with mild depression had a 1.81-fold (95% CI 1.05-3.14; P = 0.03) increased risk of preeclampsia, while moderate to severe depression correlated with a 2.52-fold increase (95% CI 1.05-6.02; P = 0.03) after adjustment of the probable confounding variables. With regard to the high prevalence of moderate to severe depression and its association with preeclampsia, our findings support and suggest efforts for screening depression among pregnant women and appropriate educational studies for mental and psychological problems during pregnancy.


Decoding syntax during reading in aphasia.
Aphasic subjects' syntactic-based comprehension strategies during reading were investigated. Syntactic distinctions involving tense, word order, and relativization were tested. The results were compared to those previously obtained in the auditory modality (Pierce, 1981; in press). The results indicate that aphasics apply a strategy based on a subject-verb object present tense construction during both reading and listening. Their comprehension improves when additional surface-structure markers are available to indicate the exceptions to this strategy. This is evident for tense judgments during reading and listening but only during listening for word-order judgments.


Effects of Pregnancy and Breastfeeding on Clinical Outcomes and MRI Measurements of Women with Multiple Sclerosis: An Exploratory Real-World Cohort Study.
Pregnancy represents an important event for women with multiple sclerosis (MS) and is often accompanied by post-partum disease reactivation. To date, the influence of this reproductive phase on long-term MS outcomes is still largely unexplored. The objective of the study was characterise a large real-world cohort of women with MS to evaluate the effects of pregnancy and breastfeeding on short- and long-term clinical and magnetic resonance imaging (MRI) outcomes while exploring the relationships with MRI measurements of brain atrophy. MS patients with and without pregnancy were recruited. Clinical relapses and MRI activity of the year before conception versus the year after delivery were evaluated. Regression models were performed to investigate the relationships between long-term MS outcomes (EDSS score and MRI brain measurements obtained by SIENAX software) and pregnancy and breastfeeding duration. Two hundred ten women with MS were enrolled; of them, 129 (61.4%) had at least one pregnancy. Of all pregnancies (n = 212), those that occurred after MS onset (90 [42.4%]) were examined to evaluate the short-term outcomes. A higher annualised relapse rate in the post-partum year versus the pre-conception year (0.54 ± 0.84 vs. 0.45 ± 0.71; p = 0.04) was observed. A regression analysis showed that clinical activity after delivery was associated with clinical activity of the year before conception (p = 0.001) as well as duration of breastfeeding (p = 0.022). Similarly, post-partum MRI activity was associated with pre-conception MRI activity (p = 0.026) and shorter breastfeeding duration (p = 0.013). Regarding long-term outcomes, having had at least one pregnancy during MS was associated with a lower EDSS score (p = 0.021), while no relationships were reported with MRI measurements. Conversely, a breastfeeding duration > 6 months was associated with lower white matter volume (p = 0.008). Our study underlines the importance of considering the effects of pregnancy and breastfeeding on short- and long-term MS outcomes. In the current therapeutic landscape, pregnancy planning and treatment optimisation in the post-partum period, in particular for women who choose to breastfeed, are fundamental for the management of these biological phases so central in a woman's life.


Synthesis and enzymic activity of 8-acyl and 8-alkyl derivatives of guanosine 3, 5-cyclic phosphate.
Several new 8-alkyl and 8-acyl derivatives of quanosie 3',5'-cyclic phosphate (cGMP) and inosine 3',5'-cyclic phosphate (cGMP) were prepared by direct alkylation or acylation of the parent cyclic nucleotide via free radicals generated in situ. These compounds have been examined for their ability to stimulate a cGMP-dependent protein kinase, and several of the cGMP derivatives were as active in this regard as cGMP. These compounds proved to be quite ineffective when tested for their ability to activate an adenosine 3',5'-cyclic phosphate (cAMP) dependent protein kinase. In addition, these 8-substituted cGMP derivatives are not substrates for a phosphodiesterase preparation from rabbit kidney, but do show inhibition of the hydrolysis of cAMP by crude phosphodiesterase preparations from rabbit lung and beef heart.


Residual apical space following surgery for pneumothorax increases the risk of recurrence.
Residual air spaces on chest radiographs after pneumothorax surgery are not uncommon. We aimed to study their incidence and impact on surgical outcomes. Four hundred and twenty-seven patients [283 men and 144 women with a median age of 31 (14-96) years] underwent surgery for pneumothorax from 1995 to 2005 in a single unit. Video-assisted thoracoscopy was used in 225 cases (53%). Outcomes were: duration of intercostal drainage and hospital stay, recurrence, re-operation and referral to chronic pain clinic. Median duration of intercostal drainage and hospital stay were 5 and 6 days, respectively. We found a recurrence rate of 6.6% (n=28), re-operation rate of 2.8% (n=12) and need for referral to pain clinic of 7% (n=30). In 129 patients (30%) a small residual apical space (RAS) was reported on chest radiograph prior to discharge. Hospital stay and duration of drainage were longer in these cases (p=0.002 and 0.02, respectively). On multivariate analysis RAS on chest radiograph was associated with increased risk of recurrence [hazard ratio 3.1 (1.4-6.8 95% CI)] (p=0.005); but no need for re-operation or referral to pain clinic. Re-operation was associated with VATS surgery (p=0.001) and when no abnormalities were identified at operation (p=0.04). Referral to pain clinic was more common after open surgery (p=0.01). The risk of recurrence after pneumothorax surgery is low. But the presence of a residual apical space on chest radiography after surgery increases it significantly. Recurrence may be due to the failure to achieve early pleural symphysis.


Inhibition of 11β-hydroxysteroid dehydrogenase type 1 ameliorates obesity-related insulin resistance.
Excess 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) may be implicated in the development of obesity related metabolic disorders. The present study measured the expression level of 11β-HSD1 in visceral adipose tissues from 23 patients undergoing abdominal operation. Correlation of 11β-HSD1 expression with BMI, waist-to-hip ratio (WHR), HOMA-IR, and serum lipids was evaluated by spearman correlation analysis. High-fat diet-induced obese (DIO) rats were orally dosed with BVT.2733 for 4 weeks. Weight, plasma insulin, and lipids were detected at the end of the treatment. The effects of 11β-HSD1 inhibition on the key insulin-signaling cascade and adipocytokines were measured by western blot and ELISA respectively. 11β-HSD1 was increased in patients with central obesity, the expression level of which was closely related with WHR (r = 0.5851), BMI (r = 0.4952), and HOMA-IR (r = 0.4637). Obesity related insulin resistance in high-fat DIO rats, as reflected by a marked decrease in IRS-1, IRS-2, GLUT4, and PI3K, could be attenuated by 11β-HSD1 inhibition. Furthermore, the down-regulation of 11β-HSD1 could correct the disordered profiles of adipocytokines including adiponectin, IL-6, and TNF-α. These findings indicated that 11β-HSD1 inhibition can give a potential benefit in reducing obesity and lowering insulin resistance by modulating the insulin-signaling pathway and adipocytokine production.


Piebaldism, Waardenburg's syndrome, and related disorders. "Neural crest depigmentation syndromes"?
The striking parallel between the melanin pigmentary abnormalities of the hair and skin in piebaldism, Waardenburg's syndrome, piebaldism with deafness, and piebaldism or Waardenburg's syndrome with aganglionosis of the gut suggests that all these disorders belong to the same category. At present, the most logical way to link these syndromes is to consider them the results of defective development of the neural crest. The reason that in certain circumstances only melanoblasts are affected whereas in other situations other neural crest derivatives also are involved is not yet clear. In addition, some features, such as the upper limb abnormalities observed in Klein's syndrome, are not explained by a neural crest defect. Our knowledge of the interaction between the neural crest and neighboring structures closely related to it during embryonic life is limited. Some clues allowing us to better understand these complex syndromes combining depigmentation of hair and skin will come from future research in this field.


Highly sensitive detection of molecular interactions with plasmonic optical fiber grating sensors.
Surface Plasmon resonance (SPR) optical fiber biosensors constitute a miniaturized counterpart to the bulky prism configuration and offer remote operation in very small volumes of analyte. They are a cost-effective and relatively straightforward technique to yield in situ (or even possibly in vivo) molecular detection. The biosensor configuration reported in this work uses nanometric-scale gold-coated tilted fiber Bragg gratings (TFBGs) interrogated by light polarized radially to the optical fiber outer surface, so as to maximize the optical coupling with the SPR. These gratings were recently associated to aptamers to assess their label-free biorecognition capability in buffer and serum solutions. In this work, using the well-acknowledged biotin-streptavidin pair as a benchmark, we go forward in the demonstration of their unique sensitivity. In addition to the monitoring of the self-assembled monolayer (SAM) in real time, we report an unprecedented limit of detection (LOD) as low as 2 pM. Finally, an immunosensing experiment is realized with human transferrin (dissociation constant Kd~10(-8) M(-1)). It allows to assess both the reversibility and the robustness of the SPR-TFBG biosensors and to confirm their high sensitivity.


Acid phosphatase elevation with symptoms following transurethral prostatic resection.
Symptoms following transurethral prostatic resection for benign prostatic hypertrophy were evaluated in 100 patients. The occurrence of post-transurethral resection symptoms was monitored postoperatively and was found to be associated with an increase in serum acid phosphatase. The transient elevation of serum acid phosphatase after transurethral prostatic resection indicates that intraoperative absorption of prostatic tissue substances occurs. The intraoperative absorption of prostatic tissue substances may have a significant role in producing symptoms of post-transurethral resection syndromes.


Use of recommended ambulatory care services: is the Veterans Affairs quality gap narrowing?
Veterans Affairs medical centers (VAMCs) provide better preventive and chronic disease care when compared with other health care organizations, although recent health care quality improvement initiatives outside the VAMC sector may have narrowed quality differences. Using the nationally representative 2000 and 2004 surveys of the Behavior Risk Factor Surveillance System, which included 152,310 community-dwelling insured adults in 2000 and 251,570 in 2004, we compared self-reported use of 17 recommended ambulatory care services for cancer prevention, cardiovascular risk reduction, diabetes mellitus management, and infectious disease prevention among insured adults receiving and not receiving care at VAMCs. A total of 2852 insured adults (1.9%) received care at VAMCs in 2000 and 7155 (2.4%) received care at VAMCs in 2004. Use of 9 of the 17 services was greater in 2004 when compared with 2000 (P < or = .05). In 2000, receiving VAMC care was associated with greater use of 6 of the 17 services; in 2004, receiving VAMC care was associated with greater use of 12 of the 17 services (P < or = .05). In 2004, greater use among these 12 services ranged from 10% greater use of cholesterol screening to 40% greater use of colorectal cancer screening. For 13 of the 17 services, the likelihood of service use among adults receiving VAMC care when compared with adults not receiving VAMC care was not significantly different in 2004 than in 2000. However, this likelihood was significantly greater (for VAMC vs non-VAMC use) in 2004 than in 2000 for breast cancer screening (relative risk [RR], 1.21 [95% confidence interval {CI}, 1.15-1.25] vs 0.80 [95% CI, 0.58-0.98]; P < .001), dilated eye examination among adults with diabetes (RR, 1.12 [95% CI, 1.07-1.15] vs 1.01 [95% CI, 0.88-1.09]; P = .04), and influenza (RR, 1.30 [95% CI, 1.24-1.36] vs 1.06 [95% CI, 0.89-1.21]; P = .006) and pneumococcal (RR, 1.27 [95% CI, 1.23-1.31] vs 1.04 [95% CI, 0.86-1.21]; P = .005) vaccinations. Despite increasing emphasis on quality of care and improved performance throughout the US health care system, adults receiving VAMC care remain more likely to receive recommended ambulatory care.


The mTORC1 component RPTOR is required for maintenance of the foundational spermatogonial stem cell pool in mice†.
The self-renewal, proliferation, and differentiation of the spermatogonial populations must be finely coordinated in the mammalian testis, as dysregulation of these processes can lead to subfertility, infertility, or the formation of tumors. There are wide gaps in our understanding of how these spermatogonial populations are formed and maintained, and our laboratory has focused on identifying the molecular and cellular pathways that direct their development. Others and we have shown, using a combination of pharmacologic inhibitors and genetic models, that activation of mTOR complex 1 (mTORC1) is important for spermatogonial differentiation in vivo. Here, we extend those studies to directly test the germ cell-autonomous requirement for mTORC1 in spermatogonial differentiation. We created germ cell conditional knockout mice for "regulatory associated protein of MTOR, complex 1" (Rptor), which encodes an essential component of mTORC1. While germ cell KO mice were viable and healthy, they had smaller testes than littermate controls, and no sperm were present in their cauda epididymides. We found that an initial cohort of Rptor KO spermatogonia proliferated, differentiated, and entered meiosis (which they were unable to complete). However, no self-renewing spermatogonia were formed, and thus the entire germline was lost by adulthood, resulting in Sertoli cell-only testes. These results reveal the cell autonomous requirement for RPTOR in the formation or maintenance of the foundational self-renewing spermatogonial stem cell pool in the mouse testis and underscore complex roles for mTORC1 and its constituent proteins in male germ cell development.


The influence of dynamic visual cues for postural control in children aged 7-12 years.
Young children rely heavily on vision for postural control during the transition to walking. Although by 10 years of age, children have automatic postural responses similar to adults, it is not clear when the integration of sensory inputs becomes fully developed. The purpose of this study was to examine this transition in the sensory integration process in children aged 7-12 years. Healthy children and adults stood on a fixed or sway-referenced support surface while viewing full-field optic flow scenes that moved sinusoidally (0.1 and 0.25 Hz) in an anterior-posterior direction. Center of pressure was recorded, and measures of sway amplitude and phase were calculated at each stimulus frequency. Children and adults had significant postural responses during approximately two-thirds of the trials. In adults, there was a 90% decrease in sway on the fixed surface compared with the sway-referenced surface, but only a 50% decrease in children. The phase between the optic flow stimulus and postural response in children led that of adults by 52 degrees at 0.1 Hz and by 15 degrees at 0.25 Hz. Adults and children aged 7-12 years have similar ability to use dynamic visual cues for postural control. However, 7-12-year-old children do not utilize somatosensory cues to stabilize posture to the same extent as adults when visual and somatosensory cues are conflicting.


Effect of thyroid status on lipid composition and peroxidation in the mouse liver.
In order to analyze the possible relationship between metabolic rate and oxidative stress, OF1 female mice were rendered hyper- or hypothyroid for 4-5 weeks by administration of 0.0012% L-thyroxine (T4) or 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water. Treatment with T4 resulted in increased basal metabolic rate measured by oxygen consumption and liver cytochrome oxidase activity without altering the glutathione redox system. Endogenous lipid peroxidation, sensitivity to lipid peroxidation and fatty acid unsaturation were decreased in the hyperthyroid group. Hypothyroidism also decreased phosphatidylcholine and cardiolipin fatty acid unsaturation but not in total lipids, and thus lipid peroxidation was not altered. Cardiolipin, a mainly mitochondrial lipid, was the most profoundly altered fraction by both hyper- and hypothyroidism. It is suggested that the lipid changes observed in hyperthyroid animals can protect them against an increased oxidative attack to tissue lipids due to their increased mitochondrial activities.


[Coma in France today].
Comas result from acute life-threatening neurological failure. To understand coma, it is firstly necessary to define it, to cite the aetiologies and their epidemiology and to describe the chronic disorders of consciousness. It is also important to address the challenges and principles of treatment during the acute phase.


Long-term effects of transdermal and oral estrogens on serum lipids and lipoproteins in postmenopausal women.
The transdermal and oral administration of estrogens for one year were compared with respect to the effects on lipid metabolism. Eighty-one postmenopausal women (1.5-3 years after menopause) were randomly divided into three groups. The first two groups received sequential estrogen treatment with either transdermal estradiol (Estraderm TTS, Ciba Geigy; 50 micrograms/day; 24 women) or 0.625 mg/day conjugated estrogens (Premarin, Wyeth; 20 subjects), respectively. In both groups medroxyprogesterone (10 mg/day per os) was added for 12 days of each cycle. Thirty-five subjects served as control group without therapy. No significant changes in the lipid profile was observed in control subjects after 1 year of follow-up. Serum triglycerides decreased significantly (-10.9 +/- 26% S.D.; P < 0.05) in transdermal treated women, whereas it slightly rose in oral estrogen group. Comparable significant decreases in total and low density lipoprotein (LDL) cholesterol (mean range -6.5/-18.0%) were observed in women on estrogen replacement therapy. High density lipoprotein (HDL) cholesterol significantly diminished in transdermal estradiol group, but it rose slightly in the oral estrogen group. Thus the fraction of HDL cholesterol over LDL cholesterol did not change in the transdermal group whereas it significantly rose in subjects treated with oral estrogens. It remains to be established to what extent these differences on lipid metabolism are relevant for the prevention of cardiovascular diseases.


Biochemical and structural analysis of substrate promiscuity in plant Mg2+-dependent O-methyltransferases.
Plant S-adenosyl-l-methionine-dependent class I natural product O-methyltransferases (OMTs), related to animal catechol OMTs, are dependent on bivalent cations and strictly specific for the meta position of aromatic vicinal dihydroxy groups. While the primary activity of these class I enzymes is methylation of caffeoyl coenzyme A OMTs, a distinct subset is able to methylate a wider range of substrates, characterized by the promiscuous phenylpropanoid and flavonoid OMT. The observed broad substrate specificity resides in two regions: the N-terminus and a variable insertion loop near the C-terminus, which displays the lowest degree of sequence conservation between the two subfamilies. Structural and biochemical data, based on site-directed mutagenesis and domain exchange between the two enzyme types, present evidence that only small topological changes among otherwise highly conserved 3-D structures are sufficient to differentiate between an enzymatic generalist and an enzymatic specialist in plant natural product methylation.


Application of green synthesized bimetallic nZVI-Cu nanoparticle as a sustainable alternative to chemical fertilizers to enhance growth and photosynthetic efficiency of rice seedlings.
Application of nanomaterials in agriculture has been extensively explored over the past decade leading to a wide ambit of nanoparticle-based agrochemicals. Metallic nanoparticles consisting of plant macro- and micro-nutrients have been used as nutritional supplements for plants through soil amendments, foliar sprays, or seed treatment. However, most of these studies emphasize monometallic nanoparticles which limit the range of usage and effectivity of such nanoparticles (NPs). Hence, we have employed a bimetallic nanoparticle (BNP) consisting of two different micro-nutrients (Cu & Fe) in rice plants to test its efficacy in terms of growth and photosynthesis. Several experiments were designed to assess growth (root-shoot length, relative water content) and photosynthetic parameters (pigment content, relative expression of rbcS, rbcL & ChlGetc.). To determine whether the treatment induced any oxidative stress or structural anomalies within the plant cells, histochemical staining, anti-oxidant enzyme activities, FTIR, and SEM micrographs were undertaken. Results indicated that foliar application of 5 mg L-1 BNP increased vigor and photosynthetic efficiency whereas 10 mg L-1 concentration induced oxidative stress to some extent. Furthermore, the BNP treatment did not perturb the structural integrity of the exposed plant parts and also did not induce any cytotoxicity. Application of BNPs in agriculture has not been explored extensively to date and this study is one of the first reports that not only documents the effectivity of Cu-Fe BNP but also critically explores the safety of its usage on rice plants making it a useful lead to design new BNPs and explore their efficacy.


Intracranial Dislocation of the Mandibular Condyle: A Case Report and Literature Review.
Intracranial dislocation of the mandibular condyle is an infrequent injury that can follow traumatic upward force at the chin. A limited number of cases have been reported, and an individualized approach for patients is often recommended. Nevertheless, several consistent strategies for reduction have emerged. We present the case of a 20-year-old pregnant woman with multiple facial and skeletal injuries who required open reduction after a motor vehicle accident. We also reviewed the English literature for all reported cases of traumatic mandibular dislocation into the middle cranial fossa. The demographics, presentation, surgical approach, and follow-up were examined. A total of 52 cases were identified, with most events occurring in the younger and female population, usually after motor vehicle (54%) or bicycle trauma (25%). At least one neurological finding was reported in 60% of initial presentations. Most reductions required an open procedure (73%), for which either a preauricular or temporal approach was used at comparatively similar rates. Additional condylotomy or condylectomy was sometimes incorporated, but most open reductions were achieved by traction (62%). At follow-up, half of reporting patients noted persistent mandibular deviation and mean maximal opening was 37.7 mm. Appropriate surgical and nonsurgical approaches for addressing mandibular dislocation have emerged during the past several decades. When deciding on an optimal strategy, variables including patient age, time-to-diagnosis, accompanying injuries, prior failed maneuvers, and risk of resubluxation should be considered. Coordinated care between neurosurgery and otolaryngology teams can minimize complications and achieve successful reductions.


Triggers of heavier and lighter cigarette smoking in college students.
This preliminary study examined the relationship between cigarette smoking and several environmental and psychological cues to smoke in college students who were lighter (2-8 cigarettes per day) and heavier (greater than 10 cigarettes per day) smokers. Nineteen lighter and 16 heavier smokers monitored their smoking behavior and certain smoking cues, and reported this information daily to an interactive voice response (IVR) system over a 13-day period. Results indicated the lighter smokers consumed a significantly greater proportion of cigarettes when drinking alcohol and during the evening hours compared to heavier smokers. No differences were found between groups on smoking in the presence of negative affect or coffee, although heavier smokers smoked a greater proportion of cigarettes when experiencing low energy positive affect (e.g., calm). If a replication of this study produces similar results, there could be implications for public policy, particularly the regulation of smoking in venues where alcohol is served.


Tracheocutaneous fistula closure in the pediatric population: should secondary closure be the standard of care?
Tracheocutaneous fistula (TCF) closure is achieved by excision followed either by primary closure or healing by secondary intention. Although primary closure provides immediate resolution of the fistula, it is associated with more severe potential complications. Healing by secondary intention minimizes these potential complications; however, it is inconvenient for the patient and may be more likely to require revision surgery. We have had 2 life-threatening complications after primary closure, and as a result, we largely changed our practice pattern. We compared complication and success rates of the 2 methods since this change to determine its ramifications. Historical cohort study. Academic tertiary care pediatric otolaryngology practice. Subjects and Methods Two hundred sixteen patients who underwent TCF closure between January 2004 and August 2012. Forty-six (21.3%) fistulae were addressed by primary closure, and 170 (78.7%) were addressed by secondary intention. The complication and revision rates were not significantly different between the 2 methods (8.7% vs 10% and 8.7% vs 14.7%, respectively). In our study, we did not see any statistical differences between the 2 methods studied but could not exclude clinically important differences that may have favored one method over the other. Although our comparative results were inconclusive, we have adopted secondary closure as standard practice for management of pediatric TCF. Individual surgeons and patients may use the data presented to help guide decisions concerning which procedure is most appropriate.


Stereotactic Body Radiation Therapy to the Prostate Bed: Results of a Phase 1 Dose-Escalation Trial.
The primary objectives of this study were to evaluate toxicity of escalating doses of prostate bed stereotactic body radiation therapy and to provide dose recommendations for a phase 2 study. Patients with organ-confined, node-negative prostate cancer who had biochemical failure (prostate-specific antigen [PSA] less than 2.0) after prostatectomy were eligible for this phase 1 dose-escalation trial. Doses delivered were 35 Gy, 40 Gy, and 45 Gy in 5 fractions, given every other day. Dose-limiting toxicity (DLT) was defined as Common Terminology Criteria for Adverse Events (version 4.0) grade 3 or higher gastrointestinal or genitourinary (GU) toxicity within 90 days of treatment. Maximum tolerated dose was the highest dose to be tested where fewer than 2 of the patients experienced DLT. Patients completed quality-of-life questionnaires at regular time intervals. Twenty-six patients completed treatment between October 2013 and December 2017. Three patients received 35 Gy, 8 patients received 40 Gy, and 15 patients received 45 Gy. The median follow-up was 60 months for 35 Gy, 48 months for 40 Gy, and 33 months for 45 Gy. No acute DLT events were observed. Late grade ≥2 and ≥3 gastrointestinal toxicity occurred in 11% and 0%, respectively, and late grade ≥2 and ≥3 GU toxicity occurred in 38% and 15%, respectively. No difference was observed in late GU toxicity between 40 Gy and 45 Gy. Sexual function scores were significantly lower in the patients receiving androgen deprivation therapy (P < .01). In all patients, the crude rate of PSA control (<0.2 ng/mL) was 11 out of 26 (42%). Dose escalation to 45 Gy did not result in acute DLT events, had similar rates of late grade 3 toxicity, and did not demonstrate higher rates of PSA control, compared with 40 Gy. While allowing for higher plan heterogeneity, the recommended dose for phase 2 study will be 40 Gy in 5 fractions.


Application of a new preclinical drug screening system for cancer of the large bowel.
We report a prospective evaluation of three human, continuous colorectal cancer cell lines and a new semiautomated radiometric technique (Bactec system) as a primary screening procedure for cytotoxic compounds with activity against cancer of the large bowel. COLO 320DM, Ht-29, and the metastatic OM-1 colon cancer cell line that have previously been shown to yield clinically relevant information in terms of drug sensitivity patterns in humans were all tested against 11 new compounds currently being investigated in phase I or early phase II clinical trials. Our results suggest that trimetrexate, DUP-785, didemnin B, and flavone-8-acetic acid may be clinically effective for the treatment of colorectal cancer.


Early hospital discharge of infants born to group B streptococci-positive mothers: a decision analysis.
To compare the cost-effectiveness of an additional 24-hour inpatient observation for asymptomatic term neonates born to group B streptococcus (GBS)-colonised mothers with adequate intrapartum antibiotic prophylaxis (IAP) after an initial 24-hour in-hospital observation. Cost-effectiveness analysis from a societal perspective. United States. Asymptomatic term neonates born to GBS-colonised mothers with IAP after an initial 24-hour in-hospital observation. Monte Carlo simulation for a decision tree model incorporating the following chance events: development of GBS sepsis during the second 24 hours of life, development of GBS sepsis between 48 hours and 7 days of life, prompt versus delayed treatment for sepsis, neonatal mortality and long-term health sequelae. Expected cost and quality-adjusted life years (QALYs), Incremental cost-effectiveness ratio (ICER). Delayed, versus early, hospital discharge results in similar mean expected QALYs, but substantially higher expected cost. The mean difference in QALY is 0.00016 (95% CI 0.00005-0.00040), whereas the mean difference in cost is $1170.96 (95% CI $750.13-1584.32). The ICER is estimated to be $9,771,520.87 per QALY (95% CI $2,573,139.89-24,407,017.82). The proportion of early-onset GBS that develops during the second 24 hours of life, the cost of 24 hours of inpatient observation, and the probability of long-term sequelae following prompt versus delayed treatment play important roles in determining the cost-effectiveness of delayed hospital discharge. Cost-effectiveness analysis suggests that with adequate IAP, discharging asymptomatic term neonates to home after 24 hours is the preferred approach compared with 48 hours inpatient observation.


Microbial ecology of Antarctic aquatic systems.
The Earth's biosphere is dominated by cold environments, and the cold biosphere is dominated by microorganisms. Microorganisms in cold Southern Ocean waters are recognized for having crucial roles in global biogeochemical cycles, including carbon sequestration, whereas microorganisms in other Antarctic aquatic biomes are not as well understood. In this Review, I consider what has been learned about Antarctic aquatic microbial ecology from 'omic' studies. I assess the factors that shape the biogeography of Antarctic microorganisms, reflect on some of the unusual biogeochemical cycles that they are associated with and discuss the important roles that viruses have in controlling ecosystem function.


The Phosphate Content of Prescription Medication: A New Consideration.
Phosphate restriction is needed in most dialysis patients. The package inserts from some medications indicate that phosphate may be part of the excipient fraction of drugs. It is unclear whether its amount may be clinically significant since the phosphate content is unquantified. We reviewed the package inserts for the branded formulations of the most widely used drugs at a dialysis chain. We measured the phosphate levels in a sample of the branded form of these drugs and some of their generic formulations. We also reviewed the available package inserts of 16 selected generic drug manufacturers for the presence of phosphate in drugs that were phosphate free in their branded formulation. We identified 12 prescription products that contained phosphate, 9 of which contained clinically significant quantities (>10 mg per daily dose) notably in both branded and generic forms of amlodipine, lisinopril, paroxetine and bisoprolol. Phosphate was rarely present in a generic drug when its corresponding branded formulation was phosphate free. Commonly prescribed drugs may contain clinically important levels of phosphate.


The acceleration in papillary thyroid cancer incidence rates is similar among racial and ethnic groups in the United States.
Reports of similar age-specific incidence rates and a female-to-male gender disparity by racial/ethnic groups suggests that further consideration of race-specific patterns may confer insight into the possible causes of thyroid cancer or explanations for the increase in incidence. We used the National Cancer Institute's (NCIs) surveillance, epidemiology, and end results (SEER) program and Joinpoint Regression for cases diagnosed during 1992-2009 to investigate trends and rates of acceleration for papillary thyroid cancer by gender and race/ethnicity. We determined the annual percent change (APC) and found a yearly increase of 7.0 % for papillary thyroid cancer for the most recent APC trend, with an APC of 6.3 and 7.1 % for white males and females, respectively; an APC of 4.3 and 8.4 % for black males and females, respectively; an APC of 4.2 and 6.7 % for Hispanic males and females, respectively; and an APC of 3.4 and 6.4 % in Asian/PI males and females, respectively. The APC projections show the rates of papillary thyroid cancer rising in males, but the patterns are more dramatic in females, with rates of papillary thyroid cancer in females surpassing rates of common cancers and becoming the third most common cancer in women of all ages by 2019. Although the lowest rates of thyroid cancer are observed in blacks, the greatest rate of acceleration is occurring in black females. Our data also show that the rate of papillary thyroid cancer will continue to surpass rates of ovarian cancer, and in white women: it is projected to be more incident than colorectal cancer as well; and in Hispanic and Asian/Pacific Islander women, rates of papillary thyroid cancer are projected to be higher than lung, colorectal, and ovarian cancers in the near future.


Vitamins and lung cancer.
Several factors are known to promote the development of a lung cancer. Smoking, occupation, environment, chronic bronchitis, and scars in the lung are all risk factors. Many studies have stressed the importance of nutrition, in particular vitamins. Vitamin A is necessary for cell differentiation. Retrospective and prospective studies have proven the inverse relation between provitamin A, beta-carotene, and lung cancer of the squamous and oat cell types. Studies in which beta-carotene or natural vitamin A are supplied to smokers, controls, and patients after resection for lung cancer are in progress. The study of other vitamins such as vitamin C and vitamin E has not led to definitive conclusions. The trace element selenium may also exert a beneficial effect.


Studies on platelet aggregation inhibitors in vivo. VIII. Effect of pentoxifylline on spontaneous tumor metastasis.
Pentoxifylline (Trental), a phosphodiesterase inhibitor with platelet aggregation inhibitory effect, was shown to decrease spontaneous metastases in a Wilms' tumor model in Furth-Wistar rats and in neuroblastoma C1300 in A/J mice. It was ineffective in the NIH renal adenocarcinoma in BALB/cCr mice.


Temperature tolerances of Southeast Australian reptiles examined in relation to reptile thermoregulatory behaviour and distribution.
The Critical temperatures (defined as the upper and lower limits at which the animal can still right itself) were determined for 29 lizard species (13 genera) and four snake species (four genera) of Southeast Australia. In addition to these Critical temperatures, acclimation of the Critical temperatures and also some lethal temperatures were recorded for several of these species. The mean summer Critical Minimum values ranged between 2.2 and 9.8°C. Thigmotherms (Gekkonidae, Lygosominae, Elapidae) and posturing heliotherms (Agamidae, Scincinae, Varanidae) generally had high Critical Minimum values and the shuttling heliotherms (Lygosominae, Elapidae) had the lowest values. The rate of acclimation of the Critical Minimum of ten lizard species was similar and complete acclimation took place within ten days. Following acclimation the final or ultimate Critical Minimum of some species fell below the body freezing point of-0.52°C and locomotion could occur while the lizard was supercooled. Mean summer Critical Maximum values ranged between 37.0 and 44.8°C. Determination of the Lethal Minimum temperatures by continuously cooling the specimens was complicated by the fact that supercooling occurred followed by nucleation or sudden freezing of the body tissues. The Lethal Minimum was best determined by holding specimens at different constant temperature levels then calculating the body temperature at which the species could survive for an indefinite time period. It is concluded, from the data presented in this paper, that if environmental temperatures were to limit the distribution of reptiles then the Critical Minimum level would have more ecological significance than the Critical Maximum.


Effect of CGS 9896 on stress-induced gastric ulcer in rat.
1. The effects of CGS 9896, a partial benzodiazepine agonist, and chlordiazepoxide, a full benzodiazepine agonist, on stress-induced gastric ulcers as well as blood glucose were compared. 2. Ulceration in the glandular stomach was induced by 2 h restraint at 4 degrees C. 3. CGS 9896 reduced significantly the ulcer parameters but did not affect blood glucose. The effect of CGS 9896 was dose-dependently blocked by the benzodiazepine antagonist flumazepil. 4. Chlordiazepoxide reduced the ulcer parameters but increased blood glucose. 5. Since CGS 9896 lacks sedative effects but reduced ulcer parameters, the anti-ulcer and sedative effects of drugs acting at benzodiazepine receptors are disassociated. 6. Benzodiazepine-induced hyperglycaemia does not play a major role in the anti-ulcer effects.


Mapping ion-induced mesophasic transformation in lyotropic in situ gelling system and its correlation with pharmaceutical performance.
To investigate influence of ion induced mesophasic transformation on pharmaceutical performance of in situ gelling system consisting of glyceryl monooleate. The prepared system showed mesophasic transformation during its conversion from sol to gel upon controlled hydration. The process of mesophasic transformation was studied by SAXS, DSC, rheology and plane polarized light microscopy. Further the influence of additives i.e. naproxen salts (sodium and potassium) and naproxen (base) on the process of mesophasic transformation was also elucidated. It was observed that addition of salt form of naproxen transformed W/O emulsions into cubic mesophase whereas addition of base form of naproxen formed reverse hexagonal (HII) phase upon controlled hydration. The cubic mesophase formed by naproxen salts retarded the drug release for initial 3 h whereas HII phase showed sustained drug release characteristics for naproxen base following Higuchi drug release kinetics. The current work suggests that formulations with tailor made pharmaceutical performance can be developed by selecting proper additives in the system so as to obtain the desired mesophase 'on demand' thereby controlling drug release characteristics.


Acute retention of urine due to isolated sacral myeloradiculitis.
Two cases of isolated sacral myeloradiculitis are described with retention of urine, sensory disorders in sacral segments and pleocytosis in the CSF. The patients were treated with steroids and recovered after 30 days of treatment. The differential diagnosis and literature are reviewed.


The influence of stimulants on truck driver crash responsibility in fatal crashes.
Given the monotony and extended driving periods inherent in transport truck driving, drivers might rely on stimulants to sustain attention and combat fatigue. Research indicates that stimulant use improves some cognitive functions but impairs driving ability and is linked to crashes. The research on crash responsibility among stimulant-positive truck drivers is inconclusive due to small sample sizes and a lack of control over confounding variables. The present study investigated the influence of stimulants on unsafe driving actions (UDAs) in fatal crashes contained in the Fatality Analysis Reporting System (FARS) database. Logistic regression was used to calculate the odds ratio of an UDA (cases committed an UDA; controls did not) by stimulant status (present; absent) while accounting for the influence of confounding variables (age, previous driving record, and other drug use). For all truck drivers, we found that 372 truck drivers tested stimulant-positive representing 0.57% of the entire truck driver sample and 3.7% of truck drivers who were actually tested for drug use. Stimulant-positive truck drivers had a greater proportion of driving record infractions and narcotic drug use compared to stimulant-negative truck drivers. The adjusted odds of committing an UDA were 78% greater for truck drivers who were stimulant-positive (OR: 1.78, 95% CI: 1.41-2.26) compared to truck drivers stimulant-negative. The results suggest stimulants are associated with crash responsibility and warrant further study into their impact on truck drivers.


PECSS: Pulmonary Embolism Comprehensive Screening Score to safely rule out pulmonary embolism among suspected patients presenting to emergency department.
Pulmonary embolism is a severe cardiovascular disease and can be life-threatening if left untreated. However, the detection rate of pulmonary embolism using existing pretest probability scores remained relatively low and clinical rule out often relied on excessive use of computed tomographic pulmonary angiography. We retrospectively collected data from pulmonary embolism suspected patients in Zhongshan Hospital from July 2018 to October 2022. Pulmonary embolism diagnosis and severity grades were confirmed by computed tomographic pulmonary angiography. Patients were randomly divided into derivation and validation set. To construct the Pulmonary Embolism Comprehensive Screening Score (PECSS), we first screened for candidate clinical predictors using univariate logistic regression models. These predictors were then included in a searching algorithm with indicators of Wells score, where a series of points were assigned to each predictor. Optimal D-Dimer cutoff values were investigated and incorporated with PECSS to rule out pulmonary embolism. In addition to Wells score, PECSS identified seven clinical predictors (anhelation, abnormal blood pressure, in critical condition when admitted, age > 65 years and high levels of pro-BNP, CRP and UA,) strongly associated with pulmonary embolism. Patients can be safely ruled out of pulmonary embolism if PECSS ≤ 4, or if 4 < PECSS ≤ 6 and D-Dimer ≤ 2.5 mg/L. Comparing with Wells approach, PECSS achieved lower failure rates across all pulmonary embolism severity grades. These findings were validated in the held-out validation set. Compared to Wells score, PECSS approaches achieved lower failure rates and better compromise between sensitivity and specificity. Calculation of PECSS is easy and all predictors are readily available upon emergency department admission, making it widely applicable in clinical settings. The study was retrospectively registered (No. CJ0647) and approved by Human Genetic Resources in China in April 2022. Ethical approval was received from the Medical Ethics Committee of Zhongshan Hospital (NO.B2021-839R).


Association of Both Scapular Upward Rotation and Scapulothoracic Muscle Lengths With Shoulder Pain, Function, and Range of Movement.
Our aim was to analyze whether shoulder pain is related to scapular upward rotation (SUR) or to the lengths of the pectoralis minor and levator scapulae muscles. This cross-sectional, observational study was carried out in 3 primary-care centers; 54 individuals with chronic shoulder pain participated. Scapular upward rotation and the lengths of the pectoralis minor and levator scapulae muscles were assessed. The level of association was small between shoulder pain and function and (1) the lengths of the pectoralis minor (r = 0.08, P = .93) and levator scapulae (r = -0.01, P = .57) muscles and (2) SUR at 45° (r = 0.17, P = .21), 90° (r = 0.08, P = .57), and 135° (r = 0.10, P = 0.45) of shoulder elevation. The relationship was small between shoulder pain and function and (1) SUR (45°, 90°, and 135° of shoulder elevation) and (2) the lengths of the pectoralis minor and levator scapulae muscles. Thus, the use of SUR and pectoralis minor and levator scapulae lengths in shoulder assessment should be undertaken with caution. Other factors such as psychological factors, central/peripheral sensitization, and intrinsic properties of the tissue have to be taken into account.


Bariatric Surgery and Cardiovascular Disease Risk in Patients with Pulmonary Hypertension: A Propensity Score Matched Analysis of US National Inpatient Sample.
Previous research has suggested the ameliorating effect of bariatric surgery (BaS) on patients with pulmonary hypertension (PH), but there is a lack of data on the effect of bariatric surgery on the odds of cardiovascular diseases in PH patients. The current study aims to evaluate the association of BaS and coronary artery diseases (CAD), heart failure with reduced ejection fraction (HFrEF), heart failure with preserved ejection fraction (HFpEF), cardiac valve diseases, cardiac rhythm disorders, acute pulmonary embolism, and in-hospital mortality in patients with PH. The national inpatient sample (NIS) data from 2016 to 2019 were analyzed by using ICD-10 codes. A propensity score matching in a 3:1 ratio was performed to match the BaS and non-BaS groups. A total of 3605 patients with a history of BaS and 501419 patients without a history of BaS were included. After propensity matching, BaS was independently associated with a lower CAD hospital admission and a lower rate of in-hospital mortality. On the contrary, BaS was associated with a higher prevalence of atrial fibrillation (AF) and acute pulmonary embolism in patients with PH. HFpEF, HFrEF, other cardiac rhythm disorders, complete heart block, cardiac valve diseases, and ischemic stroke were not significantly different between the two groups in patients with PH. BaS is independently associated with a reduced rate of in-hospital mortality and CAD hospital admission in patients with PH. However, the risk of atrial fibrillation and acute pulmonary embolism was higher in these patients.


A critical role of epigenetic inactivation of miR-9 in EVI1high pediatric AML.
Ectopic Viral Integration site 1 (EVI1) upregulation is implicated in 10-25% of pediatric acute myeloid leukemia (AML) and has an inferior outcome with current chemotherapy regimens. Here we report that EVI1 upregulation is associated with methylation of the miR-9 promoter and correlated with downregulation of miR-9 in human AML cell lines and bone marrow (BM) cells from pediatric patients. Reactivation of miR-9 by hypomethylating agents and forced expression of miR-9 in EVI1high leukemia cell lines and primary leukemia cells results in apoptosis and decreased proliferation of EVI1high leukemia cells. Furthermore, re-expression of miR-9 delays disease progression in EVI1high leukemia-xenograft mice. Our results suggest that EVI1-induced hypermethylation and downregulation of the miR-9 plays an important role in leukemogenesis in EVI-1high pediatric AML, indicating that hypomethylating agents may be a potential therapeutic strategy for EVI1high pediatric AML.


DNA Replication-A Matter of Fidelity.
The fidelity of DNA replication is determined by many factors, here simplified as the contribution of the DNA polymerase (nucleotide selectivity and proofreading), mismatch repair, a balanced supply of nucleotides, and the condition of the DNA template (both in terms of sequence context and the presence of DNA lesions). This review discusses the contribution and interplay between these factors to the overall fidelity of DNA replication.


Physical interaction between SLX4 (FANCP) and XPF (FANCQ) proteins and biological consequences of interaction-defective missense mutations.
SLX4 (FANCP) and XPF (FANCQ) proteins interact with each other and play a vital role in the Fanconi anemia (FA) DNA repair pathway. We have identified a SLX4 region and several amino acid residues that are responsible for this interaction. The study has revealed that the global minor allele, SLX4(Y546C), is defective in this interaction and cannot complement Fancp knockout mouse cells in mitomycin C-induced cytotoxicity or chromosomal aberrations. These results highly suggest this allele, as well as SLX4(L530Q), to be pathogenic. The interacting partner XPF is involved in various DNA repair pathways, and certain XPF mutations cause progeria, Cockayne syndrome (CS), and/or FA phenotypes. Because several atypical xeroderma pigmentosum (XP) phenotype-causing XPF missense mutations are located in the SLX4-interacting region, we suspected the disruption of the interaction with SLX4 in these XPF mutants, thereby causing severer phenotypes. The immunoprecipitation assay of cell extracts revealed that those XPF mutations, except XPF(C236R), located in the SLX4-interacting region cause instability of XPF protein, which could be the reason for the FA, progeria and/or CS phenotypes.


Exogenously applied zinc improves sugar-acid profile of loquat (Eriobotrya japonica Lindl.) by regulating enzymatic activities and expression of their metabolism-related genes.
Soluble sugars and organic acids are the most abundant components in ripe fruits, and they play critical roles in the development of fruit flavor and taste. In this study, loquat trees were sprayed with 0.1, 0.2 and 0.3% zinc sulphate. The contents of soluble sugars and organic acids were determined using HPLC-RID and UPLC-MS, respectively. The activities of key enzymes involved in sugar-acid metabolism were measured and expression profiling of related genes was done using RT-qPCR. The results revealed that 0.1% zinc sulphate was a promising treatment among other Zn applications with respect to the increased levels of soluble sugars and decreased acid contents in loquats. Correlation analysis showed that the enzymes i.e., SPS, SS, FK, and HK were may be involved in the regulation of fructose and glucose metabolism in the fruit pulp of loquat. While, the activity of NADP-ME showed negative and NAD-MDH showed a positive correlation with malic acid content. Meanwhile, EjSPS1-4, EjSS2-4, EjHK1-3, and EjFK1-6 may play an important role in soluble sugar metabolism in the pulp of loquat fruits. Similarly, EjPEPC2, EjPEPC3, EjNAD-MDH1, EjNAD-MDH3-5, EjNAD-MDH6 and EjNAD-MDH13 may have a vital contribution to malic acid biosynthesis in loquat fruits. This study provides new insights for future elucidation of key mechanisms regulating soluble sugars and malic acid biosynthesis in loquats.


Biocidal activity of some Mannich base cationic derivatives.
A novel series of cationic surfactants was prepared based on Mannich base (produced from the condensation of piperidine and/or morpholine as secondary amine and paraformaldehyde in the presence of 8-hydroxyquinoline). The chemical structures of the synthesized cationic surfactants were confirmed using elemental analyses, FTIR spectroscopy and 1H NMR. Surface activities of the prepared surfactants were measured including: surface tension (gamma), critical micelle concentration (CMC), effectiveness (pi(CMC)), efficiency (Pc20), maximum surface excess (Gamma(max)), minimum surface area (A(min)), interfacial tension (gamma(IT)), emulsification power and foaming power at 25 degrees C. The structural influences on their surface activities and adsorption free energy were discussed. The synthesized cationic surfactants were evaluated for their biocidal activity towards Gram +ve bacteria (Staph. Cocu., Bacillus), Gram -ve bacteria (Salmonella, E. coli), fungi (A. terrus., A. flav.) and yeast (Candida) at 1.0, 2.5 and 5.0mg/mL, respectively. The target compounds showed good inhibition towards Gram +ve bacteria, Gram -ve bacteria and yeast. Meanwhile, excellent fungicidal results were obtained against the various types of fungi under investigation.


A network-based approach to identify deregulated pathways and drug effects in metabolic syndrome.
Metabolic syndrome is a pathological condition characterized by obesity, hyperglycemia, hypertension, elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol that increase cardiovascular disease risk and type 2 diabetes. Although numerous predisposing genetic risk factors have been identified, the biological mechanisms underlying this complex phenotype are not fully elucidated. Here we introduce a systems biology approach based on network analysis to investigate deregulated biological processes and subsequently identify drug repurposing candidates. A proximity score describing the interaction between drugs and pathways is defined by combining topological and functional similarities. The results of this computational framework highlight a prominent role of the immune system in metabolic syndrome and suggest a potential use of the BTK inhibitor ibrutinib as a novel pharmacological treatment. An experimental validation using a high fat diet-induced obesity model in zebrafish larvae shows the effectiveness of ibrutinib in lowering the inflammatory load due to macrophage accumulation.


Authentication of Meat and Meat Products Using Triacylglycerols Profiling and by DNA Analysis.
Two alternative, complementary analytical strategies were successfully used to identify the most common meat species-beef, pork and chicken-in meat products. The first innovative high-throughput approach was based on triacylglycerols fingerprinting by direct analysis in real time coupled with high-resolution mass spectrometry (DART-HRMS). The second was the classic commonly used DNA analysis based on the use of nuclear or mitochondrial DNA in multiplex polymerase chain reaction (mPCR). The DART-HRMS method represents a rapid, high throughput screening method and was shown to have a good potential for the authentication of meat products. Nevertheless, it should be noted that due to a limited number of samples in this pilot study, we present here a proof of concept. More samples must be analyzed by DART-HRMS to build a robust classification model applicable for reliable authentication. To verify the DART-HRMS results, all samples were analyzed by PCRs. Good compliance in samples classification was documented. In routine practice under these conditions, screening based on DART-HRMS could be used for identification of suspect samples, which could be then examined and validated by accurate PCRs. In this way, saving of both labor and cost could be achieved. In the final phase, commercially available meat products from the Czech market were tested using this new strategy. Canned meats-typical Czech sausages and luncheon meats, all with declared content of beef, pork and chicken meat-were used. Compliance with the label declaration was confirmed and no adulteration was found.


Dynamic properties of eye movements in mitochondrial chronic progressive external ophthalmoplegia.
To relate dynamic properties of eye movements to visual disability in a patient with chronic progressive external ophthalmoplegia (CPEO) due to mitochondrial DNA deletion. Visual function was evaluated by neuro-ophthalmological examination and visual function index (VF-14). Eye movements were measured using the magnetic search coil technique. The patient denied diplopia or oscillopsia at rest or during locomotion. His range of eye movements was limited to <12 degrees horizontally, and <19 degrees vertically with smaller movements of the left eye. All classes of movements were impaired, but the eyes accelerated to over 1000 degrees /s/s at the onset of saccades and in response to brisk head rotations. Diplopia and oscillopsia were suppressed, probably due to visual system adaptation during the slow disease progression. We postulate that relative sparing of pale global extraocular fibres accounted for preserved acceleration of saccades and vestibular eye movements.


Modelling spatiotemporal properties of directionally sensitive multi-input single-output systems.
The dynamics of directionally tuned linear multi-input single-output systems varies generally as a function of the spatial orientation of the inputs. A linear system receiving directionally specific inputs is represented by a linear combination of the respective input transfer functions. The input-output behaviour of such systems can be described by a vector transfer function which specifies the polarization directions of the system in real space. These directions, which can be either one (undirectional vector transfer function) or two (bidirectional vector transfer function) but never three, are obtained by computing the eigenvectors and eigenvalues of the system matrix that is defined by the gain and phase values of the system's response to harmonic stimulation directed along three orthogonal directions in space. The spatial tuning behaviour is determined by the quadratic form associated with the system matrix. Neuronal systems with bidirectional vector transfer functions process input information in a plane-specific way and exhibit novel characteristics, very much different from those of systems with unidirectional vector transfer functions.


Molecular Basis of Laminin-Integrin Interactions.
Laminins are composed of three polypeptide chains, designated as α, β, and γ. The C-terminal region of laminin heterotrimers, containing coiled-coil regions, short tails, and laminin globular (LG) domains, is necessary and sufficient for binding to integrins, which are the major laminin receptor class. Laminin recognition by integrins critically requires the α chain LG domains and a glutamic acid residue of the γ chain at the third position from the C-terminus. Furthermore, the C-terminal region of the β chain contains a short amino acid sequence that modulates laminin affinity for integrins. Thus, all three of the laminin chains act cooperatively to facilitate integrin binding. Mammals possess 5 α (α1-5), 3 β (β1-3), and 3 γ (γ1-3) chains, combinations of which give rise to 16 distinct laminin isoforms. Each isoform is expressed in a tissue-specific and developmental stage-specific manner, exerting its functions through binding of integrins. In this review, we detail the current knowledge surrounding the molecular basis and physiological relevance of specific interactions between laminins and integrins, and describe the mechanisms underlying laminin action through integrins.


Dynamic monitoring of bacteriostatic process by SERS analysis based on a simple but effective detection strategy.
Investigating antibacterial process at a molecular level is helpful to fully understand the mechanism of bacteriostasis and develop new antimicrobial agents. Herein, a simple but effective sensor strategy of antibacterial nanocomposite combined with surface-enhanced Raman scattering (SERS) substrate was applied for the robust detection of bacteriostatic process. The synergistic SERS effect of nanocomposite and Ag nanoparticles (NPs) substrate was confirmed by finite difference time domain (FDTD) solutions. A curcumin liposome@Au NPs nanocomposite was designed and prepared as a kind of bacteriostatic agent and SERS material as well. By means of electrostatic attraction between the nanocomposite and bacteria (methicillin resistant staphylococcus aureus, MRSA), specific detection of MRSA and monitoring of the molecular structure changes after bacteriostaticeffect were realized by SERS. Important intermediates produced in the bacteriostatic process were also measured at the same time. The relationship between the relative peak intensities and the structure of MRSA were thus established. The results were verified by high performance liquid chromatography-mass spectrometry (HPLC-MS), reactive oxygen species (ROS) kit, and flow cytometry. The detection strategy we proposed could not only be used for real-time detection of bacteriostatic processes with a high efficiency, but also a powerful tool for analyzing the mechanism in biochemical processes.


Global shape discrimination at reduced contrast in enucleated observers.
Previous research has shown that observers with early unilateral enucleation have selectively better sensitivity to luminance contrast than monocular viewing controls [González et al., 2002; Vision Research 36 (1) (1996) 175; Vision Research 36 (1996) 3011; Vision Research 37 (17) (1997) 2465]. We asked whether unilateral enucleation specifically enhances all levels of luminance processing. Enucleated observers, as well as binocular and monocular viewing controls, detected global shape in radial frequency (RF) patterns [Vision Research 38 (1998) 2555] at low contrast. Control observers were tested in two monocular conditions in which the stimulus was presented to one eye, while the fellow eye: (1) viewed a luminance-matched grey field or (2) was covered by a dark eye patch. Sensitivity to low-contrast global shape was equivalent in enucleated observers and binocular controls. More importantly, enucleated observers showed superior performance to that of controls in either monocular condition. At low contrast, the dichoptic control group was more sensitive than controls wearing an eye patch, which suggests that dichoptic viewing is a superior method of testing when comparing monocular control performance to that of monocularly deprived populations. The previously reported enhanced sensitivity to luminance-defined form in early enucleated observers also occurs for low-contrast global shape discrimination.


Regulatory mechanisms in postsynaptic phosphorylation networks.
The modulation of the postsynaptic signaling machinery by protein phosphorylation has attracted much interest since it is key for the understanding of the regulation of a variety of synaptic functions. While advances in mass spectrometry have allowed us to begin performing large-scale analysis of protein phosphorylation in components of the PSD, the systematic collection of datasets and their functional significance within the context of regulatory signaling networks is in its infancy. Here, we will focus on the composition of the PSD phosphoproteome describing kinase, phosphatase, and protein domain modules involved in the regulation of phosphorylation signaling. We will discuss the impact of synaptic plasticity mechanisms such as long-term potentiation (LTP) in mammalian kinomes and describe the general rules of signaling organization in the PSD phosphoproteome.


Bioaccumulated provitamin A in black soldier fly larvae is bioavailable and capable of improving vitamin A status of gerbils.
The aim was to study whether provitamin A (proVA), which can bioaccumulate in black soldier fly larvae (BSFL), is bioavailable and can restore VA status in mammals. A model for studying the metabolism of this vitamin, the gerbil, was either fed a standard diet (C+ group), a diet without VA (C-), a diet in which VA was provided by β-carotene (β-C) from sweet potatoes (SP), or a diet in which VA was provided by β-C from BSFL that had been fed sweet potatoes (BSFL). The animals were killed at the end of the supplementation period and β-C, retinol and retinyl esters were measured in plasma and liver. As expected β-C was not detected in plasma and liver of the C+ and C- groups. β-C concentrations were lower (p < 0.05) in plasma and liver of the BSFL group as compared to the SP group. Liver retinol and retinyl ester concentrations were lower in the C- group than in all the other groups (p < 0.05). These concentrations were not significantly different in the C+ and SP groups while they were lower in the BSFL group (p < 0.05 for retinyl oleate and retinyl linoleate). In total, the liver stock of retinol equivalent was almost twice lower in the BSFL group than in the SP group. Thus, β-C present in the BSFL matrix is bioavailable and capable of improving VA status, but this matrix decreases its effectiveness by a factor of around two compared to the sweet potato matrix.


Provision of long-term mechanical ventilation.
When patients suffer prolonged mechanical ventilation, physicians are faced with a series of decisions beginning in the intensive care unit (ICU) and extending into a broadening spectrum of post-ICU levels of care. This article reviews current thinking and outcome data on when and how to perform the tracheostomy, as well as when and where the patient should be transferred from the ICU for continued weaning efforts or support. Decannulation after success in weaning and continuation of ventilation at home are also addressed.


Inhibition of methamphetamine sensitization by post-methamphetamine treatment with SCH 23390 or haloperidol.
Methamphetamine (2 mg/kg SC) increased ambulation in mice for about 3 h, with a peak effect at around 40 min after the administration, and its repeated administration induced sensitization. Both SCH 23390 (0.03 mg/kg SC) and haloperidol (0.4 mg/kg SC), dopamine D1 and D2 receptor antagonists, respectively, completely inhibited not only the acute stimulant effect of methamphetamine but also its sensitization when repeated methamphetamine was repeatedly combined with either of these drugs. Moreover, treatment with SCH 23390 2-5 h or haloperidol 1-5 h after each methamphetamine administration significantly antagonized methamphetamine sensitization. The maximal inhibitory effect was observed in the schedules of 3-h post-methamphetamine treatment for both drugs. However, treatments with SCH 23390 or haloperidol at 0.5 h, 6 h and 24 h after methamphetamine had no such inhibitory effect. The mice treated with SCH 23390 or haloperidol after each saline administration (the control administration for methamphetamine) did not show significant change in the sensitivity to methamphetamine. These results suggest that methamphetamine has an effect on both dopamine D1 and D2 receptors for several hours even after cessation of its acute stimulant effect, and that such an effect is involved in the induction of sensitization to the stimulant effect of methamphetamine on ambulation in mice.


Low serum zinc levels in patients undergoing coronary angiography correlate with immune activation and inflammation.
Low serum zinc concentrations are associated with adverse outcomes. To explain this phenomenon we aimed to investigate whether low zinc levels are related to immune activation, renal function and coronary artery disease (CAD). Serum concentrations of zinc and the immune activation markers neopterin and C-reactive protein (CRP) were measured in 2048 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography. Zinc concentrations did not differ between patients with CAD (mean±SD: 13.3±2.4 μmol/L) and controls (13.3±2.2 μmol/L; Welch's t test: p=n.s.) but CAD patients had higher neopterin (8.6±7.4 nmol/L) and CRP (9.7±19.6 mg/L) concentrations compared to controls (neopterin: 7.5±4.8 nmol/L, p=0.0005; CRP: 5.5±10.0 mg/L, p<0.0001). There was an inverse correlation between serum zinc concentrations and neopterin (Spearman's rank correlation: r(s)=-0.222) and CRP (r(s)=-0.166; both p<0.0001) concentrations. Our results indicate increased inflammatory processes in patients with low zinc levels. Further studies should clarify whether inflammation related processes such as renal wasting contribute to zinc deficiency and underlie the adverse health consequences of low serum zinc levels.


Absence of 18 F-fluorodeoxyglucose uptake using Positron Emission Tomography/Computed Tomography in Madelung's disease: A case report.
Madelung's disease is characterized by the manifestation of multiple ectopic lipomas, usually found in the cervical-thoracic region, however, clinical manifestation may vary among patients. It has been postulated that lipomas associated with Madelung's disease are linked to brown adipose tissue (BAT) due to the presence of uncoupling protein 1 (UCP1). Therefore, we here investigated whether BAT activity is present in a patient with Madelung's disease. 18 F-fluorodeoxyglucose (18 F-FDG) uptake using PET/CT after a cooling procedure was measured together with body temperature and energy expenditure. Finally, adipose tissue biopsies were taken from the lipomas for gene expression analysis and histology. 18 F-FDG uptake was not detected after the cooling procedure in the lipomas. Furthermore, adipose tissue biopsies derived from the lipomas did not express UCP1. We thus conclude that cold-stimulated BAT activity was not detected in lipomas associated with Madelung's disease. Additional research in other patients is needed to unravel the role of dysfunctional BAT in Madelung's disease.


Rice protein suppresses 4-hydroxy-2-nonenal-induced inflammation owing to methionine availability.
4-Hydroxy-2-nonenal (HNE) is one of the most important products of lipid peroxidation, which induces inflammation. To investigate the effects of rice protein (RP) on suppressing HNE-induced inflammation and the role of methionine in regulating the anti-inflammatory function of RP, Wistar rats (male, weighing 180-200 g) were either ad libitum fed a pellet diet with oral administration of methionine or ad libitum fed RP for 2 weeks. RP and methionine significantly reduced HNE levels and effectively suppressed the expressions of cyclooxygenase-2, tumor necrosis factor alpha, interleukin-1β (IL-1β) and IL-6, and inducible nitric oxide synthase. The anti-inflammatory action of RP was evident from the upregulation of IL-10 and glutathione S-transferase (GST), which played a role in the detoxification of HNE. The results show that the molecular mechanism responsible for the anti-inflammatory function of RP is the inhibition of nuclear factor kappa B (NF-κB) activation by the downregulation of protein kinase B/phosphoinositide 3 kinase. Further, this study demonstrates that Met availability contributes to the suppression of HNE-induced inflammation through upregulating IL-10 and GST in rats fed RP. Novelty: RP suppresses HNE-induced inflammation. Methionine plays a role in upregulating IL-10 and GST. Methionine availability regulates the inhibition of NF-κB by RP.


The relationship between excess body weight and the risk of death from unnatural causes.
The purpose is to exam whether excess body weight is associated with an increased risk of death from unnatural causes, particularly, injury. We analyzed nationally representative data of 14,453 adults (19 and older) who participated in the third National Health and Nutrition Examination Survey, 1988-1994, and were followed up with vital statuses through December 31, 2006. We used Cox proportional hazard regression to estimate the hazard ratio (HR) of death from all unnatural causes combined and specific ones. Gray's test was performed to assess the equality of cumulative incidence functions between body mass index (BMI) levels. A total of 128 unnatural deaths were recorded during an 18-year follow-up with 193,019 person-years accumulated. Compared with healthy weight participants, a person with excess body weight had a low hazard of death from unnatural causes [HR=1.00 (reference), 0.58 (0.39-0.87), and 0.50 (0.30-0.82) for healthy weight, overweight and obese participants, respectively]. Injuries, including motor vehicle accidents and falls, were the major types of unnatural deaths (n=91, 71% of all unnatural deaths), and the risk of death from injuries was linearly and reversely associated with BMI. The HRs of injury were 1.00 (reference), 0.57 (0.36-0.91), and 0.36 (0.19-0.69) for healthy weight, overweight and obese participants, respectively. All these estimates were obtained after adjustment of socio-demographic variables. Excess body weight appears to be associated with a low risk of death from unnatural causes, particularly, injuries. Additional investigations on the mechanism underlying the relationship between BMI and unnatural deaths are warranted.


Dynamic polarization of the microtubule cytoskeleton during CTL-mediated killing.
Efficient unidirectional killing by cytotoxic T lymphocytes (CTL) requires translocation of the microtubule organizing center (MTOC) to the target cell contact site. Here we utilize modulated polarization microscopy and computerized 3D reconstruction of tubulin and LFA-1 immunofluorescence images to investigate how this is accomplished. The results show that the MTOC is drawn vectorially to the contact site by a microtubule sliding mechanism. Once the MTOC arrives at the contact site, it oscillates laterally. Microtubules loop through and anchor to a ring-shaped zone (pSMAC) defined by the dense clustering of LFA-1 at the target contact site. Microtubules that run straight between the MTOC and pSMAC and then turn sharply may indicate the action of a microtubule motor such as dynein.


Dissipation and residues of the diamide insecticide chlorantraniliprole in ginseng ecosystems under different cultivation environments.
Ginseng is a valuable herb, the roots of which have been consumed for medicinal use since ancient times in Asian countries. Currently, its cultivation in China is conducted in either forests or non-forest areas. In this study, we investigated the dissipation and residues of the diamide insecticide chlorantraniliprole (CAP) in ginseng ecosystems in these two cultivation environments. The half-life of CAP in ginseng leaves was calculated to be 16.5 days in non-forest areas and 23.9 days in forests, while the half-life of CAP in the soil under non-forest and forest cultivation was 33.0 and 53.3 days, respectively. The relatively long persistence of CAP in ginseng leaves and soil could be attributed to the unique cultivation techniques of ginseng, which prevents exposure to direct sunlight irradiation and rainfall. The residual amounts of CAP in ginseng leaves, roots, and soil in non-forest areas were 0.168, 0.011, and 0.013 mg kg-1 21 days after CAP application at the maximum label-allowed dosage and frequency versus 0.564, 0.013, and < 0.005 mg kg-1 in forests. CAP application strategies for the control of Lepidoptera pests such as armyworms, and the safety of harvested ginseng roots are recommended for ginseng cultivated in forests and non-forest areas based on the results of the CAP residue experiments.


Effect of dl-sotalol on mortality and recurrence of ventricular tachyarrhythmias: ischemic compared to nonischemic cardiomyopathy.
We compared the effectiveness of sotalol on mortality and the recurrence of ventricular tachyarrhythmia (VTA) between idiopathic dilated cardiomyopathy (IDCM) and coronary artery disease (CAD). Forty patients with spontaneous VTA and induced VTA associated with CAD (n = 23) and IDCM (n = 17) were studied. In all patients, sotalol was prescribed and an electrophysiologic study (EPS) was performed to evaluate its effect on the induction of VTA. There were no significant differences in left ventricular ejection fraction (LVEF) between CAD and IDCM (35%+/- 10% vs. 35%+/- 12%). After sotalol, there were no significant differences in the QTc interval on electrocardiogram (ECG) or in the effective refractory period in the apex of the right ventricle between the two groups, but sotalol was more effective in preventing the induction of VTA in CAD than in IDCM (65% vs. 29%; P < 0.05). During a mean follow-up period of 47 +/- 27 months, the overall VTA recurrence rate was significantly lower in CAD than in IDCM (P < 0.01). The all-cause mortality rate tended to be lower in CAD than in IDCM, but the difference was not significant (P = 0.07). Electrical storm (ES) occurred more frequently in IDCM than in CAD, (41% vs. 13%; P < 0.05), and all patients with ES (n = 10) failed to respond to sotalol as assessed by EPS. Sotalol reduced the overall VTA recurrence rate and all-cause mortality more in CAD than in IDCM.


Structure elucidation of olasubscorpioside C, a new rotameric biflavonoid glycoside from the stem barks of Olax subscorpioidea (Oliv).
From the n-butanol soluble fraction of the ethanol extract of the medicinal plant Olax subscorpioidea, a previously unreported rotameric biflavonoid glycoside constituted of 4'-O-methylgallocatechin-(4α → 8)-4'-O-methylgallocatechin as aglycone named olasubscorpioside C (1) along with the known 4'-O-methylgallocatechin (2) were isolated. Their structures were determined on the basis of spectrometric and spectroscopic techniques including HRFABMS, 1 H and 13 C NMR, DEPT 135o , HSQC, HMBC, ROESY, and CD followed by comparison with the reported data.


The Effect of Staged Transverse Preputial Island Flap Urethroplasty for Proximal Hypospadias with Severe Chordee.
We compare the effects of staged tranverse preputial island flap urethroplasty and the Byars 2-stage procedure in patients with proximal hypospadias and severe chordee. We studied 87 consecutive children referred for proximal hypospadias with severe chordee between March 2011 and March 2014. Of the cases 42 were repaired with staged tranverse preputial island flap (group 1) and 45 were managed by 2-stage Byars urethroplasty (group 2). Mean ± SD age at first stage surgery was 26.6 ± 13.3 months in group 1 and 24.8 ± 14.7 months in group 2. Postoperative complications in both groups were assessed regarding fistulas, urethral strictures, diverticula, meatal stenosis and glanular dehiscence. After the second stage 2 patients (4.8%) in group 1 and 10 (23.2%) in group 2 had urethrocutaneous fistulas (p <0.05). One patient (2.4%) in group 1 and 2 patients (4.4%) in group 2 had urethral strictures (p >0.05). All patients with stricture were cured by repeated dilation and no patient required reoperation. One patient (2.4%) in group 1 and no patient in group 2 had diverticulum (p >0.05). No patient in either group had signs or symptoms of meatal stenosis or residual chordee. Three patients (7.1%) in group 1 and 12 (26.7%) in group 2 needed reoperation (p <0.05). Two-stage urethroplasty, particularly tranverse preputial island flap partial urethroplasty, is appropriate for treating patients with proximal hypospadias and severe chordee. Use of the tranverse preputial island flap can decrease complications associated with the second stage and significantly improve the success rate.


Random Forest Models for Accurate Identification of Coordination Environments from X-Ray Absorption Near-Edge Structure.
Analyzing coordination environments using X-ray absorption spectroscopy has broad applications in solid-state physics and material chemistry. Here, we show that random forest models trained on 190,000 K-edge X-ray absorption near-edge structure (XANES) spectra can identify the main atomic coordination environment with a high accuracy of 85.4% and all associated coordination environments with a high Jaccard score of 81.8% for 33 cation elements in oxides, significantly outperforming other machine-learning models. In a departure from prior works, the coordination environment is described as a distribution over 25 distinct coordination motifs with coordination numbers ranging from 1 to 12. More importantly, we show that the random forest models can be used to predict coordination environments from experimental K-edge XANES with minimal loss in accuracy. A drop-variable feature importance analysis highlights the key roles that the pre-edge and main-peak regions play in coordination environment identification.


[Network of surgical wound centers using a new electronic data processing documentation system].
Care of chronic wounds is of enormous medical, social and economic importance. Nevertheless there is a lack of epidemiological and economical data. A network of ten wound care centers was created and data were documented in a new computerized wound documentation system. Treatment was performed according to a comprehensive and standardized wound care protocol. The new documentation system is a network-capable solution. Digital images and planimetry as well as patient and wound related data are recorded. During the first year the ten centers treated and documented already 3281 wounds. There is a wide spectrum of different chronic wounds treated in the participating centers. Despite of long wound duration of several wounds with a median of 5 weeks (range 0-62 years), the healing rate was 80% within 455 days. Large amounts of data can be collected and scientifically evaluated in the wound net. This is realized by a new computerized documentation system, which was integrated into the clinical routine and enables clear and standardized documentation. Therefore even large multicenter therapy studies may be performed easily in the wound net and economical data could be collected.


Characterization of DNA damages by filtration through nitrocellulose filters: a simple probe for DNA-modifying agents.
A simple technique for the detection of DNA-modifying agents is described. The double-stranded covalently closed circular DNA of phage PM2 is exposed to the modifying agent and then analysed for DNA damages by assays involving only incubation steps and filtration through nitrocellulose filters. The technique described allows the measurement of DNA modifications which lead to local denaturation of the DNA double helix, interstrand cross-links, single- and double-strand breaks, damages which render the phosphodiester bonds of the DNA sensitive to hydrolysis and damages which labilise the glycosylic bond between base and sugar moiety.


Post-transcriptional dynamics and RNA homeostasis in autophagy and cancer.
Autophagy is an essential recycling and quality control pathway which preserves cellular and organismal homeostasis. As a catabolic process, autophagy degrades damaged and aged intracellular components in response to conditions of stress, including nutrient deprivation, oxidative and genotoxic stress. Autophagy is a highly adaptive and dynamic process which requires an intricately coordinated molecular control. Here we provide an overview of how autophagy is regulated post-transcriptionally, through RNA processing events, epitranscriptomic modifications and non-coding RNAs. We further discuss newly revealed RNA-binding properties of core autophagy machinery proteins and review recent indications of autophagy's ability to impact cellular RNA homeostasis. From a physiological perspective, we examine the biological implications of these emerging regulatory layers of autophagy, particularly in the context of nutrient deprivation and tumorigenesis.


Metastatic melanoma to the brain: prognostic factors after gamma knife radiosurgery.
To identify important prognostic factors predictive of survival and tumor control in patients with metastatic melanoma to the brain who underwent gamma knife radiosurgery. A total of 122 consecutive patients with 332 intracranial melanoma metastases underwent gamma knife radiosurgery over a 5-year period. Of these, 39 (32%) also received whole-brain irradiation (WBI). The median tumor volume was 0.8 cm(3) (range: 0.02-30.20 cm(3)), and the median prescribed dose was 20 Gy (range: 14-24 Gy). Median follow-up was 6.8 months. Univariate and multivariate analyses of survival and freedom from progression were performed using the following parameters: status of systemic disease, intracranial tumor volume, number of lesions, tumor location, Karnofsky performance status, gender, age, and WBI. Overall median survival was 7.0 months from time of radiosurgery and 9.1 months from the onset of brain metastasis. In multivariate analysis, improved survival was noted in patients with total intracranial tumor volume <3 cm(3) (p = 0.003) and inactive systemic disease (p = 0.0065), whereas other parameters studied were of lesser importance (tumor location, p = 0.056, and Karnofsky performance status, p = 0.086), or of no significance (number of lesions, WBI, age, and gender). Freedom from subsequent brain metastasis depended on intracranial tumor volume (p = 0.0018) and status of systemic disease (p = 0.034). Stereotactic radiosurgery is an effective treatment modality for patients with intracranial metastatic melanoma. Tumor volume and status of systemic disease are good independent predictors of survival and freedom from tumor progression.


Staircase but not posttetanic potentiation in rat muscle after spinal cord hemisection.
Spinal cord hemisection (SCH) results in atrophy of skeletal muscle and altered contractile properties. In this study our purpose was to assess staircase and posttetanic potentiation in the rat gastrocnemius muscle in situ, 1 week after SCH. Tetanic force was reduced by SCH, but twitch amplitude was not. The time course and magnitude of staircase during stimulation at 5 HZ (for 21 s) was similar in the control, sham-operated, and SCH groups. However, posttetanic potentiation observed after 100-, 500-, and 1000-ms tetanic (200 HZ) contractions was absent or drastically reduced after SCH. Twitch force increased 44+/-8.7%, 47+/-7.4%, and 15+/-2.8% for the control, sham, and SCH groups, respectively, after the 1000-ms tetanic contraction. After the 1000-ms tetanic contraction, twitch active force decreased in all groups and was significantly reduced at 5 min relative to pretetanic twitch. In the control and sham groups, but not SCH, the active force recovered to the pretetanic level by 15 min. Resting regulatory light chain (RLC) phosphorylation was 15.4+/-2.5% and 10.97+/-3.3% for the control and SCH groups, respectively. After the 1-s tetanic contraction, values were 41.6+/-2.8% and 9.3+/-2.9%, respectively. The potentiation observed in the SCH animals with 1000-ms contraction apparently occurred without increases in RLC phosphorylation. One week after SCH there were clear changes in the contractile properties typically associated with prior activation. It is concluded that activity-dependent potentiation can occur by a mechanism that is independent of RLC phosphorylation, and accelerated fatigue can mask the potentiating effects of prior activity.


Properties of nonfused liposomes immobilized on an L1 Biacore chip and their permeabilization by a eukaryotic pore-forming toxin.
The L1 chip is used intensively for protein-membrane interaction studies in Biacore surface plasmon resonance systems. The exact form of captured lipid membranes on the chip is, however, not precisely known. Evidence exists that the vesicles both remain intact after the binding to the chip and fuse to form a large single-bilayer membrane. In this study, we were able to bind up to approximately 11,500 resonance units of zwitterionic liposomes (100 nm in diameter) at a low flow rate. We show by fluorescence microscopy that the entire surface of the flow cell is covered homogeneously by liposomes. Negatively charged vesicles (i.e., those composed of phosphatidylcholine/phosphatidylglycerol [1:1]) always deposited less densely, but we were able to increase the density slightly with the use of calcium chloride that promotes fusion of the vesicles. Finally, we used zwitterionic liposomes loaded with fluorescent probe calcein to show that they remain intact after the capture on the L1 chip. The fluorescence was lost only after we used equinatoxin, a well-studied pore-forming toxin, to perform on-chip permeabilization of vesicles. The characteristics of permeabilization process for chip-immobilized liposomes are similar to those of liposomes free in solution. All results collectively suggest that liposomes do not fuse to form a single bilayer on the surface of the chip.


Irrational use of antibiotics among university students.
The aim of the presented study was to evaluate the knowledge, attitude and behaviour of antibiotic usage in the student groups of a University in a country where the antibiotics are taken without prescriptions. Out of 5345 students (excluding those from the Faculty of Medicine) of Ege University, 678 were chosen by systematic sampling methods. The sampling group was divided into two groups. Group A included students from the Faculties of Pharmacy and Dentistry and Group B was composed of students of all other faculties. A questionnaire was used. The mean age was 21.0+/-3.0 and 58% were females. The aim of antibiotic use for common cold was 83.1% (P>0.05) and, to decrease fever was 32.1% (P<0.05) in both Groups. In Group A 36.1% and in Group B 44.9% of the respondents started antibiotics by themselves when they were ill (P>0.05) although 89.1% of both groups agree that antibiotics should be started with doctors' prescription. During their last infection in Group A 11.7% and in Group B 27.3% of the respondents used the same antibiotic as previously prescribed by their doctors and the use of antibiotics as advised by the doctors during their last infection was 50.8% in Group A and 35.3% in Group B. The use of antibiotics are found to be irrational among university students. National education programmes about the dangers of irrational antibiotic use and restriction of antibiotics without prescriptions should be the priority. This study indicated that knowledge regarding antibiotics cannot be evaluated alone since it did not always correlate with behaviour.


Flavone inhibits Staphylococcus aureus virulence via inhibiting the sae two component system.
The rising prevalence of antibiotic resistance in Staphylococcus aureus calls for the development of innovative antimicrobial agents targeting novel pathways. S. aureus generates various virulence factors that compromise host defense mechanisms. Flavone, a core structure of flavonoids, has been shown to diminish the production of staphyloxanthin and alpha-hemolysin. Nonetheless, the influence of flavone on the majority of other virulence factors in S. aureus and its underlying molecular mechanism remain elusive. In this study, we examined the impact of flavone on the transcriptional profile of S. aureus using transcriptome sequencing. Our findings revealed that flavone substantially downregulated the expression of over 30 virulence factors implicated in immune evasion by the pathogen. Gene set enrichment analysis of the fold change-ranked gene list in relation to the Sae regulon indicated a robust association between flavone-induced downregulation and membership in the Sae regulon. Through the analysis of Sae target promoter-gfp fusion expression patterns, we observed a dose-dependent inhibition of Sae target promoter activity by flavone. Moreover, we discovered that flavone protected human neutrophils from S. aureus-mediated killing. Flavone also decreased the expression of alpha-hemolysin and other hemolytic toxins, resulting in a reduction in S. aureus' hemolytic capacity. Additionally, our data suggested that the inhibitory effect of flavone on the Sae system operates independently of its capacity to lower staphyloxanthin levels. In conclusion, our study proposes that flavone exhibits a broad inhibitory action on multiple virulence factors of S. aureus by targeting the Sae system, consequently diminishing the bacterium's pathogenicity.


Downregulation of METTL14 improves postmenopausal osteoporosis via IGF2BP1 dependent posttranscriptional silencing of SMAD1.
Osteoporosis (OP) tends to occur in postmenopausal women, making them prone to fractures. N6-methyladenosine (m6A) methylation plays a crucial role in OP. Herein, we aimed to explore the effects of METTL14 on osteogenesis and the underlying mechanism. Osteogenic differentiation was assessed through osteoblast markers expression, cell proliferation, ALP activity, and mineralization, which were detected by qRT-PCR, CCK-8, EdU assay, ALP staining assay, and ARS staining assay, respectively. Osteoporosis was evaluated in OVX mice using qRT-PCR, microcomputed tomography, and H&E staining assay. The levels of METTL14 and SMAD1 were measured using qRT-PCR and western blot, and their interaction was assessed using RIP and luciferase reporter assay. M6A methylation was analyzed using the Me-RIP assay. The results indicated that m6A, METTL14, and SMAD1 levels were downregulated in patients with OP and OVX mice, and upregulated in osteogenic BMSCs. Knockdown of METTL14 suppressed osteogenesis of BMSCs and reduced bone mass of OVX mice. Moreover, silencing of METTL14 positively related to SMAD1 and inhibited m6A modification of SMAD1 by suppressing its stability. IGF2BP1 was identified as the methylation reader, and which knockdown reversed the upregulation induced by SMAD1. Overexpression of SMAD1 reversed the suppression of osteogenic differentiation induced by METTL14 knockdown. In conclusion, interference with METTL14 inhibited osteogenic differentiation of BSMCs by m6A modification of SMAD1 in an IGFBP1 manner, suggesting that METTL14 might be a novel approach for improving osteoporosis.


Neuronal Correlation Parameter and the Idea of Thermodynamic Entropy of an N-Body Gravitationally Bounded System.
Understanding how the brain encodes information and performs computation requires statistical and functional analysis. Given the complexity of the human brain, simple methods that facilitate the interpretation of statistical correlations among different brain regions can be very useful. In this report we introduce a numerical correlation measure that may serve the interpretation of correlational neuronal data, and may assist in the evaluation of different brain states. The description of the dynamical brain system, through a global numerical measure may indicate the presence of an action principle which may facilitate a application of physics principles in the study of the human brain and cognition.


[Relationship of the expression of CD44v6 and paxillin to the prognosis of non-small cell lung carcinoma].
To investigate the expression and significance of CD44v6 and Paxillin in non-small cell lung carcinoma. Immunohistochemical staining was used to detect the expression of CD44v6 and Paxillin in 79 cases of non-small cell lung carcinoma, and the relationships of the expression with histological type, lymph node metastasis and prognosis were detected. The expression rates of CD44v6 and Paxillin were 60.8% and 34.1% respectively. The expression of CD44v6 was positively correlated with metastasis and negatively correlated with the 2-year survival rate (P < 0.05). The expression of Paxillin was positively correlated with metastasis (P < 0.05). The expression of CD44v6 and Paxillin is closely correlated with the lymph node metastasis and the prognosis of non-small cell lung carcinoma.