A systematic review of the safety of kava extract in the treatment of anxiety.
This paper systematically reviews the clinical evidence relating to the safety of extracts of the herbal anxiolytic kava (Piper methysticum). Literature searches were conducted in four electronic databases and the reference lists of all papers located were checked for further relevant publications. Information was also sought from the spontaneous reporting schemes of the WHO and national drug safety bodies and ten manufacturers of kava preparations were contacted. Data from short-term post-marketing surveillance studies and clinical trials suggest that adverse events are, in general, rare, mild and reversible. However, published case reports indicate that serious adverse events are possible including dermatological reactions, neurological complications and, of greatest concern, liver damage. Spontaneous reporting schemes also suggest that the most common adverse events are mild, but that serious ones occur. Controlled trials suggest that kava extracts do not impair cognitive performance and vigilance or potentiate the effects of central nervous system depressants. However, a possible interaction with benzodiazepines has been reported. It is concluded that when taken as a short-term monotherapy at recommended doses, kava extracts appear to be well tolerated by most users. Serious adverse events have been reported and further research is required to determine the nature and frequency of such events.


Management of people with early- or very early-stage hepatocellular carcinoma: an attempted network meta-analysis.
Hepatocellular carcinoma (primary liver cancer) is classified in many ways. The Barcelona Clinic Liver Cancer (BCLC) group staging classifies the cancer based on patient's life expectancy. People with very early- or early-stage hepatocellular carcinoma have single tumour or three tumours of maximum diameter of 3 cm or less, Child-Pugh status A to B, and performance status 0 (fully functional). Management of hepatocellular carcinoma is uncertain. To assess the comparative benefits and harms of different interventions used in the treatment of early or very early hepatocellular carcinoma through a network meta-analysis and to generate rankings of the available interventions according to their safety and efficacy. However, it was not possible to assess whether the potential effect modifiers were similar across different comparisons. Therefore, we did not perform the network meta-analysis and instead assessed the benefits and harms of different interventions versus each other or versus sham or no intervention using standard Cochrane methodology. We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, and trials registers to September 2016 to identify randomised clinical trials (RCTs) on hepatocellular carcinoma. We included only RCTs, irrespective of language, blinding, or publication status, in participants with very early- or early-stage hepatocellular carcinoma, irrespective of the presence of cirrhosis, portal hypertension, aetiology of hepatocellular carcinoma, size and number of the tumours, and future remnant liver volume. We excluded trials including participants who were previously liver transplanted. We considered interventions compared with each other, sham, or no intervention. We calculated the odds ratio, mean difference, rate ratio, or hazard ratio with 95% confidence intervals using both fixed-effect and random-effects models based on available-participant analysis with Review Manager 5. We assessed the risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis using Stata, and the quality of the evidence using GRADE. Eighteen trials met the inclusion criteria for this review. Four trials (593 participants; 574 participants included for one or more analyses) compared surgery versus radiofrequency ablation in people with early hepatocellular carcinoma, eligible to undergo surgery. Fourteen trials (2533 participants; 2494 participants included for various analyses) compared different non-surgical interventions in people with early hepatocellular carcinoma, not eligible to undergo surgery. Overall, the quality of evidence was low or very low for all outcomes for both comparisons. Surgery versus radiofrequency ablationThe majority of participants had cirrhotic livers, and the hepatocellular carcinoma was of viral aetiology. The trials did not report the participants' portal hypertension status or whether they received adjuvant antiviral treatment or adjuvant immunotherapy. The average follow-up ranged from 29 months to 42 months (3 trials).There was no evidence of a difference in all-cause mortality at maximal follow-up for surgery versus radiofrequency ablation (hazard ratio 0.80, 95% confidence interval (CI) 0.60 to 1.08; 574 participants; 4 trials; I2 = 68). Cancer-related mortality was lower in the surgery group (20/115 (17.4%)) than in the radiofrequency ablation group (43/115 (37.4%)) (odds ratio 0.35, 95% CI 0.19 to 0.65; 230 participants; 1 trial). Serious adverse events (number of participants) was higher in the surgery group (14/60 (23.3%)) than in the radiofrequency ablation group (1/60 (1.7%)) (odds ratio 17.96, 95% CI 2.28 to 141.60; 120 participants; 1 trial). The number of serious adverse events was higher in the surgery group (adjusted rate 11.3 events per 100 participants) than in the radiofrequency ablation group (3/186 (1.6 events per 100 participants)) (rate ratio 7.02, 95% CI 2.29 to 21.46; 391 participants; 2 trials; I2 = 0%). None of the trials reported health-related quality of life. One trial was funded by a party with vested interests; three trials were funded by parties without any vested. Non-surgical interventionsThe majority of participants had cirrhotic livers, and the hepatocellular carcinoma was of viral aetiology. Most trials did not report the portal hypertension status of the participants, and none of the trials reported whether the participants received adjuvant antiviral treatment or adjuvant immunotherapy. The average follow-up ranged from 6 months to 37 months (11 trials). Trial participants, who were not eligible for surgery, were treated with radiofrequency ablation, laser ablation, microwave ablation, percutaneous acetic acid injection, percutaneous alcohol injection, a combination of radiofrequency ablation with systemic chemotherapy, a combination of radiofrequency ablation with percutaneous alcohol injection, a combination of transarterial chemoembolisation with percutaneous alcohol injection, or a combination of transarterial chemoembolisation with radiofrequency ablation.The mortality at maximal follow-up was higher in the percutaneous acetic acid injection (hazard ratio 1.77, 95% CI 1.12 to 2.79; 125 participants; 1 trial) and percutaneous alcohol injection (hazard ratio 1.49, 95% CI 1.18 to 1.88; 882 participants; 5 trials; I2 = 57%) groups compared with the radiofrequency ablation group. There was no evidence of a difference in all-cause mortality at maximal follow-up for any of the other comparisons. The proportion of people with cancer-related mortality at maximal follow-up was higher in the percutaneous alcohol injection group (adjusted proportion 16.8%) compared with the radiofrequency ablation group (20/232 (8.6%)) (odds ratio 2.18, 95% CI 1.22 to 3.89; 458 participants; 3 trials; I2 = 0%). There was no evidence of a difference in any of the comparisons that reported serious adverse events (number of participants or number of events). None of the trials reported health-related quality of life. Five trials were funded by parties without any vested interest; the source of funding was not available in the remaining trials. The evidence was of low or very low quality. There was no evidence of a difference in all-cause mortality at maximal follow-up between surgery and radiofrequency ablation in people eligible for surgery. All-cause mortality at maximal follow-up was higher with percutaneous acetic acid injection and percutaneous alcohol injection than with radiofrequency ablation in people not eligible for surgery. There was no evidence of a difference in all-cause mortality at maximal follow-up for the other comparisons. High-quality RCTs designed to assess clinically important differences in all-cause mortality and health-related quality of life, and having an adequate follow-up period (approximately five years) are needed.


Optical characterization of inhomogeneous thin films with randomly rough boundaries exhibiting wide intervals of spatial frequencies.
Results concerning the optical characterization of two inhomogeneous polymer-like thin films deposited by the plasma enhanced chemical vapor deposition onto silicon single crystal substrates are presented. One of these films is deposited onto a smooth silicon surface while the latter film is deposited on a randomly rough silicon surface with a wide interval of spatial frequencies. A combination of variable-angle spectroscopic ellipsometry and spectroscopic reflectometry applied at near-normal incidence are utilized for characterizing both the films. An inhomogeneity of the films is described by the method based on multiple-beam interference of light and method replacing inhomogeneous thin films by multilayer systems. Homogeneous transition layers between the films and substrates are considered. The Campi-Coriasso dispersion model is used to express spectral dependencies of the optical constants of the polymer-like films and transition layers. A combination of the scalar diffraction theory and Rayleigh-Rice theory is used to include boundary roughness into formulae for the optical quantities of the rough polymer-like film. Within the optical characterization, the spectral dependencies of the optical constants at the upper and lower boundaries of both the polymer-like films are determined together with their thickness values and profiles of the optical constants. Roughness parameters are determined for the rough film. The values of the roughness parameters are confirmed by atomic force microscopy. Moreover, the optical constants and thicknesses of both the transition layers are determined. A discussion of the achieved results for both the polymer-like films and transition layers is performed.


Long-lasting reductions of ethanol drinking, enhanced ethanol-induced sedation, and decreased c-fos expression in the Edinger-Westphal nucleus in Wistar rats exposed to the organophosphate chlorpyrifos.
Intermittent or continuous exposure to a wide variety of chemically unrelated environmental pollutants might result in the development of multiple chemical intolerance and increased sensitivity to drugs of abuse. Interestingly, clinical evidence suggests that exposure to organophosphates might be linked to increased ethanol sensitivity and reduced voluntary consumption of ethanol-containing beverages in humans. The growing body of clinical and experimental evidence emerging in this new scientific field that bridges environmental health sciences, toxicology, and drug research calls for well-controlled studies aimed to analyze the nature of the neurobiological interactions of drugs and pollutants. Present study specifically evaluated neurobiological and behavioral responses to ethanol in Wistar rats that were previously exposed to the pesticide organophosphate chlorpyrifos (CPF). In agreement with clinical data, animals pretreated with a single injection of CPF showed long-lasting ethanol avoidance that was not secondary to altered gustatory processing or enhancement of the aversive properties of ethanol. Furthermore, CPF pretreatment increased ethanol-induced sedation without altering blood ethanol levels. An immunocytochemical assay revealed reduced c-fos expression in the Edinger-Westphal nucleus following CPF treatment, a critical brain area that has been implicated in ethanol intake and sedation. We hypothesize that CPF might modulate cellular mechanisms (decreased intracellular cAMP signaling, alpha-7-nicotinic receptors, and/or cerebral acetylcholinesterase inhibition) in neuronal pathways critically involved in neurobiological responses to ethanol.


Evidence for plasmid contribution to the virulence of fish pathogen Vibrio anguillarum.
Analysis of the plasmid deoxyribonucleic acid complement of high- and low- virulent strains of the fish pathogen Vibrio anguillarum showed a correlation between enhanced virulence and the presence of a 50-megadalton plasmid class. All 50-megadalton plasmids isolated from different high-virulent V. anguillarum strains were homologous as judged by the analysis of plasmid deoxyribonucleic acid-deoxyribonucleic acid hybridization. The 50-megadalton plasmid class did not have polynucleotide sequences in common with plasmids of different incompatibility groups.


Catalytic importance of a protonated adenosine in the hairpin ribozyme active site.
The hairpin ribozyme accelerates the rate of phosphodiester transfer reactions by at least 5 orders of magnitude. To achieve this rate enhancement, the active site forms via a substrate helix docking event that constrains the scissile phosphate linkage and positions G8 and A38 for catalysis, both of which have been implicated as sites of proton transfer in general acid-base catalysis. To investigate the functional groups required for hairpin activity, we previously reported a series of nucleotide analogue interference mapping experiments [Ryder, S. P., et al. (2001) RNA 7, 1454-1463]. The critical functional groups implicated in those studies were largely consistent with subsequent X-ray crystal structures, but the lack of A38 interference with 8-azaadenosine (n(8)A), a pK(a) perturbed nucleotide analogue, argued against functional base ionization at this site. This is inconsistent with a transition state crystal structure and other biochemical studies. To address this discrepancy, we investigated the hairpin ribozyme with an expanded set of pK(a) perturbed adenosine analogues containing fluorine. A38 was the only site that showed persistent and strong interference with low pK(a) analogues across a variety of construct/substrate pairs. This interference pattern suggests that A38 base ionization is required for catalytic activity. The lack of n(8)A interference at A38, in spite of its reduced pK(a), likely results from n(8)A stabilization of the docked state, which requires an unusual syn glycosidic base conformation at A38 for active site assembly. The fluorinated adenosine analogues are better suited to identify sites of functional ionization in systems where structural rearrangements are closely coupled to catalytic steps. All pK(a) reduced analogues, including those of the previous study, produce selective interference at A38 when substrates are stably bound and docked, consistent with the importance of base ionization at this site.


Height and body composition determine arm propulsive force in youth swimmers independent of a maturation stage.
The aim of this study was to examine the relationship between anthropometric variables, body composition and propulsive force in swimmers aged 9-17 years. Anthropometric characteristics (body height and mass, sitting height, arm span, arm muscle area and body composition) and the propulsive force of the arm (tethered swimming test) were evaluated in 56 competitive male swimmers. Tanner's stages of genital maturation (P1-5) were used. The data analysis included correlations and multiple linear regression. The propulsive force of the arm was correlated with body height (r = 0.34; p =0.013), arm span (r = 0.29; p =0.042), sitting height (r = 0.36; p =0.009), % body fat (r = 0.33; p =0.016), lean body mass (r = 0.34; p =0.015) and arm muscle area (r = 0.31; p =0.026). Using multiple linear regression models, the percent body fat and height were identified as significant predictors of the propulsive force of the arm after controlling for the maturation stage. This model explained 22% (R2 = 0.22) of associations. In conclusion, the propulsive force of swimmers was related to body height and percent body fat.


Use of 2-octyl-cyanoacrylate skin adhesive (Dermabond) for wound closure following reduction mammaplasty: a prospective, randomized intervention study.
2-Octyl-cyanoacrylate skin adhesive may be used for surgical wound closure. However, its use in plastic surgery has not been properly assessed. The authors conducted a prospective, randomized, controlled clinical intervention study in which the scar characteristics after use of skin adhesive were compared with those after suture closure. Bilateral reduction mammaplasty was performed in 50 patients. The method of closure (sutures versus skin adhesive) applied to each breast was determined randomly, using each patient as her own control. Scars were assessed by the patient and by a blinded panel, at 1 week, 6 weeks, and 6 months after surgery, using a visual analogue scale, the modified Hollander Wound Evaluation Scale, and the Patient and Observer Scar Assessment Scale. Both patients and panelists expressed an overall preference for the adhesive side as of 1 week after surgery. Patients' visual analogue scale scores for scar comfort and scar appearance and panelists' visual analogue scale scores for aesthetic outcome were significantly better for the adhesive side after 6 weeks and 6 months (p < 0.05), as was the total Hollander Wound Evaluation Scale score of the panelists after 6 weeks (p < 0.02). The total Patient and Observer Scar Assessment Scale score after 6 months was significantly better for the adhesive side according to the patients (p < 0.01), but not according to the panelists (p = 0.11). The authors conclude that 2-octyl-cyanoacrylate is a sound alternative for wound closure.


Personalized Treatment Through Detection and Monitoring of Genetic Aberrations in Single Circulating Tumor Cells.
Circulating tumor cells (CTCs) present a viable alternative to access tumor materials other than primary biopsies in cancer. This disease is among the most widespread in the world and is difficult to target because of its complex nature, challenges in getting quality samples and dynamic temporal changes in response to treatment. Conventional methods of detection and monitoring the disease profile do not suffice to be able to target the heterogeneity that exists at the cellular level. CTCs have been identified as a possible substitute for tumor tissue samples, and can be used to complement current disease management. Challenges in CTCs molecular analysis lie in the purity of the sample, which is masked by the presence of large quantities of white blood cells (WBCs) . In this chapter, we present a microfluidic biochip platform that performs secondary purification to isolate single CTCs efficiently. Studying single CTCs will allow for sensitive detection of critical mutations and addressing intercellular variances that will be otherwise missed easily due to low mutation frequencies when evaluating bulk cell retrieval. Using the biochip, we isolated single CTCs, and conducted personalized integrated EGFR mutational analysis using conventional polymerase chain reaction (PCR) and Sanger sequencing. We also demonstrated that high quality next generation sequencing (NGS) libraries can be readily generated from these samples. In our initial study, we revealed that the dominant EGFR mutations such as L858R and T790M could be detected in Non Small Cell Lung Cancer (NSCLC) patients with low CTC counts. We envision the biochip will enable efficient isolation of rare single cells from samples. This technology coupled with downstream molecular characterization of CTCs will aid in realizing the personalized medicine for cancer patients.


Sequence of the Saccharomyces cerevisiae CTA1 gene and amino acid sequence of catalase A derived from it.
The nucleotide sequence of a 2785-base-pair stretch of DNA containing the Saccharomyces cerevisiae catalase A (CTA1) gene has been determined. This gene contains an uninterrupted open reading frame encoding a protein of 515 amino acids (relative molecular mass 58,490). Catalase A, the peroxisomal catalase of S. cerevisiae was compared to the peroxisomal catalases from bovine liver and from Candida tropicalis and to the non-peroxisomal, presumably cytoplasmic, catalase T of S. cerevisiae. Whereas the peroxisomal catalases are almost colinear, three major insertions have to be introduced in the catalase T sequence to obtain an optimal fit with the other proteins. Catalase A is most closely related to the C. tropicalis enzyme. It is also more similar to the bovine liver catalase than to the second S. cerevisiae catalase. The differences between the two S. cerevisiae enzymes are most striking within four blocks of amino acids consisting of a total of 37 residues with high homology between the three peroxisomal, but low conservation between the S. cerevisiae catalases. The results obtained indicate that the peroxisomal catalases compared have very similar three-dimensional structures and might have similar targeting signals.


Criteria for standard versus experimental therapy.
This paper demarcates the boundaries between experimental and standard therapy and the influence of this division on policy, payment, and practice. It proposes a new category, crossover therapy, to deal with the many therapies that fall in between. It establishes four criteria to separate these categories: (1) the populations and conditions for which use is helpful; (2) the expected outcomes of care; (3) the skill, personnel, and site requirements and the economic, ethical, and legal understandings essential for use; and (4) the level of knowledge needed to certify that prospective users can apply it well. The paper then explores the use of experimental therapy in desperate situations and of standard therapies in new areas and gives policy recommendations to facilitate these actions.


(18)F-FDG PET/CT predicts survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy.
The objective of this study was to evaluate the role of (18)F-FDG PET/CT in predicting overall survival in inflammatory breast cancer patients undergoing neoadjuvant chemotherapy. Included in this retrospective study were 53 patients with inflammatory breast cancer who had at least two PET/CT studies including a baseline study before the start of neoadjuvant chemotherapy. Univariate and multivariate analyses were performed to assess the effects on survival of the following factors: tumor maximum standardized uptake value (SUVmax) at baseline, preoperatively and at follow-up, decrease in tumor SUVmax, histological tumor type, grade, estrogen, progesterone, HER2/neu receptor status, and extent of disease at presentation including axillary nodal and distant metastases. By univariate analysis, survival was significantly associated with decrease in tumor SUVmax and tumor receptor status. Patients with decrease in tumor SUVmax had better survival (P = 0.02). Patients with a triple-negative tumor (P = 0.0006), a Her2/neu-negative tumor (P = 0.038) or an ER-negative tumor (P = 0.039) had worse survival. Multivariate analysis confirmed decrease in tumor SUVmax and triple-negative receptor status as significant predictors of survival. Every 10% decrease in tumor SUVmax from baseline translated to a 15% lower probability of death, and complete resolution of tumor FDG uptake translated to 80% lower probability of death (P = 0.014). Patients with a triple-negative tumor had 4.11 times higher probability of death (P = 0.004). Decrease in tumor SUVmax is an independent predictor of survival in patients with inflammatory breast cancer undergoing neoadjuvant chemotherapy. Further investigation with prospective studies is warranted to clarify its role in assessing response and altering therapy.


Facile synthesis of pyrazole- and benzotriazole-containing selenoethers.
Azole-containing selenoethers, 1,5-bis(3,5-dimethylpyrazol-1-yl)-3-selena pentane and 1,3-bis(1,2,3-benzotriazol-1-yl)-2-selena propane were prepared by the reaction of corresponding tosylate or chloride with sodium selenide generated in situ from elemental selenium and sodium formaldehydesulfoxylate (rongalite).


Impact of educational group strategy to improve clinical and glycemic parameters in individuals with diabetes and hypertension.
To evaluate the impact of an educational group strategy to improve clinical and glycemic parameters in individuals with diabetes and hypertension. This descriptive prospective study included 172 individuals living in São José do Rio Preto-SP, Brazil, who were enrolled in a well-integrated educational group called HIPERDIA (Record System for Follow-up of Hypertensive and Diabetic Individuals) coordinated by a qualified multidisciplinary team. We analyzed sociodemographic, anthropometric, clinical, and laboratory data. Data were collected in the first, fifth, and eighth meeting of the educational group. A total of 68.6% of patients were women, 85.4% were white, 64.0% had an incomplete basic education, 47.7% were retired, 79.7% had been diagnosed with diabetes for 6 or more years, 9.9% were smokers, and 9.9% used alcohol. Individuals' diastolic blood pressure decreased between the fifth and eighth meeting (p<0.05). Between the first and fifth meeting, both fasting glucose levels (p<0.05) and glycated hemoglobin decreased; the latter continue to drop at the fifth and eighth meetings (p<0.001). Anthropometric parameters remained unchanged. The results suggest that an educational group strategy is favorable for controlling diabetes mellitus and hypertension.


Autophagy-lysosome pathway alterations and alpha-synuclein up-regulation in the subtype of neuronal ceroid lipofuscinosis, CLN5 disease.
Neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative lysosomal storage disorders. CLN5 deficiency causes a subtype of NCL, referred to as CLN5 disease. CLN5 is a soluble lysosomal protein with an unclear function in the cell. Increased levels of the autophagy marker protein LC3-II have been reported in several subtypes of NCLs. In this report, we examine whether autophagy is altered in CLN5 disease. We found that the basal level of LC3-II was elevated in both CLN5 disease patient fibroblasts and CLN5-deficient HeLa cells. Further analysis using tandem fluorescent mRFP-GFP-LC3 showed the autophagy flux was increased. We found the alpha-synuclein (α-syn) gene SNCA was highly up-regulated in CLN5 disease patient fibroblasts. The aggregated form of α-syn is well known for its role in the pathogenicity of Parkinson's disease. Higher α-syn protein levels confirmed the SNCA up-regulation in both patient cells and CLN5 knockdown HeLa cells. Furthermore, α-syn was localized to the vicinity of lysosomes in CLN5 deficient cells, indicating it may have a lysosome-related function. Intriguingly, knocking down SNCA reversed lysosomal perinuclear clustering caused by CLN5 deficiency. These results suggest α-syn may affect lysosomal clustering in non-neuronal cells, similar to its role in presynaptic vesicles in neurons.


Lipid metabolism in malignant tumor brain metastasis: reprogramming and therapeutic potential.
Brain metastasis is a highly traumatic event in the progression of malignant tumors, often symbolizing higher mortality. Metabolic alterations are hallmarks of cancer, and the mask of lipid metabolic program rearrangement in cancer progression is gradually being unraveled. In this work, we reviewed clinical and fundamental studies related to lipid expression and activity changes in brain metastases originating from lung, breast, and cutaneous melanomas, respectively. Novel roles of lipid metabolic reprogramming in the development of brain metastasis from malignant tumors were identified and its potential as a therapeutic target was evaluated. Published literature and clinical studies in databases consisting of PubMed, Embase, Scopus and www.ClinicalTrials.gov from 1990 to 2022 were searched. Lipid metabolic reprogramming in brain metastasis is involved in de novo lipid synthesis within low lipid availability environments, regulation of lipid uptake and storage, metabolic interactions between brain tumors and the brain microenvironment, and membrane lipid remodeling, in addition to being a second messenger for signal transduction. Although some lipid metabolism modulators work efficiently in preclinical models, there is still a long way to go from laboratory to clinic. This area of research holds assurance for the organ-targeted treatment of brain metastases through drug-regulated metabolic targets and dietary interventions.


Prevalence and treatment of hepatitis C virus genotypes 4, 5, and 6.
Infection with hepatitis C virus (HCV) genotypes 4-6 (with the previously named genotypes 7-9 included as subtypes of genotype 6) is distributed and studied less widely than genotypes 1-3. However, genotypes 4-6 are very common in geographic areas where chronic hepatitis C is highly prevalent. In fact, the majority (87%) of the 169.7 million HCV-infected individuals worldwide are from western Pacific countries (62.2 million), southeast Asia (32.3 million), Africa (31.9 million), and eastern Mediterranean countries (21.3 million). It is among this large population outside of the Americas and Europe that these less well known genotypes are found: genotype 4 in Egypt and Africa, genotype 5 in South Africa, and genotype 6 in southeast Asia. The existing literature, although limited, suggests that patients with chronic hepatitis C genotypes 4-6 may exhibit different clinical courses and treatment outcomes. Ethnicity-related factors may contribute to the presence of more advanced disease in patients with genotype 4, who also tend to have a poor response to interferon-based therapy. HCV genotype 5 appears to be an easy-to-treat virus with response rates similar to those of genotypes 2 and 3 after a 48-week course of therapy. Response to treatment in patients with HCV genotype 6 may be at an intermediate level between that seen with genotype 1 and genotype 2 or 3. The optimal duration of treatment (24 vs 48 wk) for HCV genotype 6 is unclear and currently is under investigation.


[Adverse drug reactions in neonates hospitalized in neonatal intensive care units in Barranquilla, Colombia].
The appearance of adverse drug reactions in neonates is an important issue due to the lack of drug safety data. To identify the behavior of adverse drug reactions (ADR) in hospitalized neonates at two intensive care units in Barranquilla, Colombia. We conducted a cross-sectional prospective descriptive study based on patientcentered intensive pharmacosurveillance. We followed up and monitored the appearance of ADRs for six months. We used Naranjo's algorithm to assess causality, modified Hartwig and Siegel assessment scale to establish severity and Schumock and Thornton criteria to determine ADR preventability. We detected 123 adverse drug reactions in 78 neonates of the 284 monitored. The cumulative incidence of ADRs was 27.4% (78/284); incidence density was 30.60 ADRs per 1,000 patients/day (78/2,549). The most affected organ system was the digestive (33.6%). Systemic anti-infective drugs were the most involved pharmacological group. Most of the ADRs were mild (58.5%), 83% were classified as probable, 16.2% as possible and 0.8% as definite. ADR incidence was high in newborns, and it increased in preterm infants (less than 38 weeks of age).


Staged reconstruction brachytherapy has lower overall cost in recurrent soft-tissue sarcoma.
Adjuvant brachytherapy (AB) with immediate (IR) and staged reconstruction (SR) are distinct treatment modalities available for patients with recurrent soft tissue sarcoma (STS). Although SR may offer local control and toxicity benefit, it requires additional upfront procedures, and there is no evidence that it improves overall survival. With the importance of value-based care, our goal is to identify which technique is more cost effective. A retrospective review of 22 patients with recurrent extremity STS treated with resection followed by AB alone. Hospital charges were used to compare the cost between SR and IR at the time of initial treatment, at 6-month intervals following surgery, and cumulative cost comparisons at 18 months. Median follow-up was 31 months. Staged reconstruction (n = 12) was associated with an 18-month local control benefit (85% vs. 42%, p = 0.034), compared to IR (n = 10). Staged reconstruction had a longer hospital stay during initial treatment (10 vs. 3 days, p = 0.002), but at 18 months, the total hospital stay was no longer different (11 vs. 11 days). Initially, there was no difference in the cost of SR and IR. With longer follow-up, cost eventually favored SR, which was attributed primarily to the costs associated with local failure (LF). On multivariate analysis, cost of initial treatment was associated with length of hospital stay (~$4.5K per hospital day, p < 0.001), and at 18 months, the cumulative cost was ~175K lower with SR (p = 0.005) and $58K higher with LF (p = 0.02). In recurrent STS, SR has a longer initial hospital stay when compared to IR. At 18 months, SR had lower rates of LF, translating to lower total costs for the patient. SR is the more cost-effective brachytherapy approach in the treatment of STS, and should be considered as healthcare transitions into value-based medicine.


Conventional versus frozen elephant trunk surgery for extensive disease of the thoracic aorta.
To compare early and mid-term outcomes after repair of extensive aneurysm of the thoracic aorta using the conventional elephant trunk or frozen elephant trunk (FET) procedures. Fifty-seven patients with extensive thoracic aneurysmal disease were treated using elephant trunk (n = 36) or FET (n = 21) procedures. Patients with aortic dissection, descending thoracic aorta (DTA) diameter less than 40 mm, and thoracoabdominal aneurysms were excluded from the analysis, as were those who did not undergo antegrade selective cerebral perfusion during circulatory arrest. Short-term and mid-term outcomes were compared according to elephant trunk/FET surgical management. Preoperative and intraoperative variables were similar in the two groups, except for a higher incidence of female sex, coronary artery disease and associated procedures in elephant trunk patients. Hospital mortality (elephant trunk: 13.9% versus FET: 4.8%; P = 0.2), permanent neurologic dysfunction (elephant trunk: 5.7% versus FET: 9.5%; P = 0.4) and paraplegia (elephant trunk: 2.9% versus FET: 4.8%; P = 0.6) rates were similar in the two groups. Follow-up was 100% complete. In the elephant trunk group, 68.4% of patients did not undergo a second-stage procedure during follow-up for a variety of reasons. Of these patients, the DTA diameter was greater than 51 mm in 72.2% and two (6.7%) died due to aortic rupture while awaiting stage-two intervention. Endovascular second-stage procedures were successfully performed in all FET patients with residual DTA aneurysmal disease (n = 3), whereas nine of 11 elephant trunk patients who returned for second-stage procedures required conventional surgical replacement through a lateral thoracotomy. Kaplan-Meier estimate of 4-year survival was 75.8 ± 7.6 and 72.8 ± 10.6 in elephant trunk and FET patients, respectively (log-rank P = 0.8). In patients with extensive aneurysmal disease of thoracic aorta, elephant trunk and FET procedures seem to be associated with similar satisfactory early and mid-term outcomes. The FET approach leads to single-stage treatment of all aortic disease in most patients, and facilitates endovascular second-stage treatment in patients with residual DTA disease. The elephant trunk staged-approach appears to leave a considerable percentage of patients at risk for adverse aortic events.


Legal issues in clinical nursing education.
Nurse educators are concerned about legal implications of teaching students in clinical settings. Although literature is available about legal issues in working with students in the classroom, there is little recent information on clinical nursing faculty's legal liability when working with students and ways to reduce the risk of becoming involved in a lawsuit. This article discusses the major issues in clinical settings that contribute to lawsuits against faculty and offers suggestions to reduce legal liability with students in clinical settings.


Structure of ADP x AIF4(-)-stabilized nitrogenase complex and its implications for signal transduction.
The coupling of ATP hydrolysis to electron transfer by the enzyme nitrogenase during biological nitrogen fixation is an important example of a nucleotide-dependent transduction mechanism. The crystal structure has been determined for the complex between the Fe-protein and MoFe-protein components of nitrogenase stabilized by ADP x AIF4-, previously used as a nucleoside triphosphate analogue in nucleotide-switch proteins. The structure reveals that the dimeric Fe-protein has undergone substantial conformational changes. The beta-phosphate and AIF4- groups are stabilized through intersubunit contacts that are critical for catalysis and the redox centre is repositioned to facilitate electron transfer. Interactions in the nitrogenase complex have broad implications for signal and energy transduction mechanisms in multiprotein complexes.


Diagnostic Accuracy of Frailty Screening Instruments Validated for Use among Older Adults Attending Emergency Departments: A Systematic Review and Meta-Analysis.
Early identification of frailty can prevent functional decline. Although multiple frailty screens exist for use in Emergency Departments (EDs), few are validated against diagnostic standards such as comprehensive geriatric assessment. To examine the diagnostic accuracy of ED screens for frailty, scientific databases were searched for prospective diagnostic accuracy test studies from January 2000 to September 2022. Studies were assessed for risk of bias using QUADAS-C. Psychometric properties were extracted and analysed using R. Six studies involving 1,663 participants describing seven frailty screening instruments (PRISMA-7, CFS, VIP, FRESH, BPQ, TRST, and ISAR), representing 13 unique data points, were included. The mean age of participants ranged from 76 to 86 years. The proportion that was female ranged from 45 to 60%. The pooled prevalence rate of frailty was high at 59%. The pooled estimate for sensitivity was 0.85 (95% CI: 0.76-0.91) versus 0.77 (95% CI: 0.62-0.88) for specificity. Pooled accuracy based on area under the ROC curve was 0.89 (95% CI: 0.86-0.90). Although few studies were found, limiting the ability to conduct a meta-analysis of individual instruments, available frailty screens can accurately diagnose frailty in older adults attending the ED. As specificity was comparatively low, additional assessment may be required to identify those requiring inpatient management or onward community referral. Further study is therefore required.


Polymorphisms A387P in thrombospondin-4 and N700S in thrombospondin-1 perturb calcium binding sites.
Recent genetic studies have associated members of the thrombospondin (TSP) gene family with premature cardiovascular disease. The disease-associated polymorphisms lead to single amino acid changes in TSP-4 (A387P) and TSP-1 (N700S). These substitutions reside in adjacent domains of these highly homologous proteins. Secondary structural predictive programs and the homology of the domains harboring these amino acid substitutions to those in other proteins pointed to potential alterations of putative Ca2+ binding sites that reside in close proximity to the polymorphic amino acids. Since Ca2+ binding is critical for the structure and function of TSP family members, direct evidence for differences in Ca2+ binding by the polymorphic forms was sought. Using synthetic peptides and purified recombinant variant fragments bearing the amino acid substitutions, we measured differences in Tb3+ luminescence as an index of Ca2+ binding. The Tb3+ binding constants placed the TSP-1 region affected by N700S polymorphism among other high-affinity Ca2+ binding sites. The affinity of Ca2+ binding was lower for peptides (3.5-fold) and recombinant fragments (10-fold) containing the S700 vs. the N700 form. In TSP-4, the P387 form acquired an additional Ca2+ binding site absent in the A387 form. The results of our study suggest that both substitutions (A387P in TSP-4 and N700S in TSP-1) alter Ca2+ binding properties. Since these substitutions exert the opposite effects on Ca2+ binding, a decrease in TSP-1 and an increase in TSP-4, the two TSP variants are likely to influence cardiovascular functions in distinct but yet pathogenic ways.


Inhibitory effect of Angelica gigas on cold‑induced RhoA activation in vascular cells.
The herbal extract Angelica gigas (AG) has been applied as a vasodilating agent for patients suffering from vascular diseases for many years; however, the underlying mechanism has not been fully elucidated. The present study hypothesized that the anti‑vasoconstrictive effect of AG may be effective in the treatment of abnormal cold‑mediated vasospasms that occur in Raynaud's phenomenon (RP). The effect of AG on the activity of ras homolog gene family member A (RhoA) was investigated in cold‑exposed vascular cells. Vascular cells were pretreated to AG, followed by a warm (37˚C) or cold (25˚C) incubation for 30 min and investigated with western blotting, ELISA and confocal microscopy. Cold treatment induced the activation of RhoA in pericytes and vascular endothelial cells, however this was reduced by treatment with AG. Furthermore, AG treatment reduced the endothelin‑1 (ET‑1)‑mediated RhoA activation in pericytes; however, cold‑induced ET‑1 production by vascular endothelial cells was not affected by treatment with AG. In addition, AG treatment suppressed the formation of stress fibers and focal adhesion complexes, and the cold‑induced phosphorylation of focal adhesion kinase, proto‑oncogene tyrosine‑protein kinase Src and extracellular signal‑related kinase. Therefore, AG treatment demonstrated an ability to reduce cold‑induced RhoA activation in pericytes and vascular endothelial cells, and attenuated ET‑1‑mediated RhoA activation in pericytes. In conclusion, the present study indicated that AG may be useful for the treatment of RP.


The genetic structure of the Turkish population reveals high levels of variation and admixture.
The construction of population-based variomes has contributed substantially to our understanding of the genetic basis of human inherited disease. Here, we investigated the genetic structure of Turkey from 3,362 unrelated subjects whose whole exomes (n = 2,589) or whole genomes (n = 773) were sequenced to generate a Turkish (TR) Variome that should serve to facilitate disease gene discovery in Turkey. Consistent with the history of present-day Turkey as a crossroads between Europe and Asia, we found extensive admixture between Balkan, Caucasus, Middle Eastern, and European populations with a closer genetic relationship of the TR population to Europeans than hitherto appreciated. We determined that 50% of TR individuals had high inbreeding coefficients (≥0.0156) with runs of homozygosity longer than 4 Mb being found exclusively in the TR population when compared to 1000 Genomes Project populations. We also found that 28% of exome and 49% of genome variants in the very rare range (allele frequency < 0.005) are unique to the modern TR population. We annotated these variants based on their functional consequences to establish a TR Variome containing alleles of potential medical relevance, a repository of homozygous loss-of-function variants and a TR reference panel for genotype imputation using high-quality haplotypes, to facilitate genome-wide association studies. In addition to providing information on the genetic structure of the modern TR population, these data provide an invaluable resource for future studies to identify variants that are associated with specific phenotypes as well as establishing the phenotypic consequences of mutations in specific genes.


Metastasizing eccrine sweat gland carcinoma. Report of a case.
We report a case of eccrine sweat gland carcinoma arising from the occipital region, which later metastasized to the regional lymph nodes and spread widely to the viscera. After wide local excision of the primary tumor, it recurred locally, and then metastasized presumably via regional lymph nodes. Widespread metastasis to visceral organs occurred after a ten-year latent period from the appearance of the original tumor. Histochemical and enzymatic histochemical examinations of the specimens from the original tumor and metastasized lesions obtained at autopsy disclosed the characteristics of eccrine sweat gland tumor.


Human alpha fetoprotein enhances epidermal growth factor proliferative activity upon porcine granulosa cells in monolayer culture.
Alpha fetoprotein (AFP) is present at high concentrations in fetal fluids, certain neoplasias, and regenerating liver. Its physiological function remains largely unknown. Using a primary monolayer culture system, we investigated the proliferative activity of human (h) cord blood (CB) and highly purified AFP. hAFP, purified from hCB by Cibacron blue and immunoaffinity chromatography was homogeneous on SDS-PAGE and silver stain. Porcine granulosa cells from ovarian small follicles were cultured (25,000/cm2) for 2 days in medium (Ham's F-12:DMEM, 1:1) + 5% fetal calf serum (FCS) to facilitate attachment, followed by 6 days in medium containing: FCS, hCB or h amniotic fluid (1-20%)+/- EGF (10 ng/ml); or 0.25% plasma-derived serum (PDS) containing human low density lipoprotein (LDL, 25 ug/ml), +/- AFP (0.05-5 ug), and +/- EGF and IGF-I (10 ng/ml). In this system, single growth factors do not stimulate proliferation, a characteristic also exhibited by AFP. When combined with EGF, however, AFP dose-dependently increased proliferation to levels equal to that obtained with 10% FCS (2.3-fold increase vs PDS/LDL controls). When combined with EGF+IGF-I, AFP again dose-dependently increased proliferation to levels equal to that obtained with 10% FCS+EGF (6.7-fold increase vs controls). Purified human albumin used in place of AFP was not effective. TGF-a but not PDGF could replace the proliferative activity of EGF. These results suggest that AFP at physiological levels, although not itself mitogenic, can enhance the mitogenic activity of EGF and TGF-a and may function to modulate growth factor-mediated proliferation during development and neoplasia.


The HIV/AIDS/STI situation in Lao People's Democratic Republic.
Lao People's Democratic Republic (Lao PDR) is a landlocked country with a population of 5.5 million and a total land area of 236,800 square kilometers. It has a population density of 23.3. It borders Thailand, Myanmar, China, Vietnam, and Cambodia. Its population distribution is 54.9% below the age of 20 years, and 27.8% aged between 20 and 39 years (NSC, 2002). Women comprise 49.5% of the overall population. 1 National Statistics Center, Basic Statics, 2002; National Statics Center, Population Census.


Socio-demographic profile and clinical co-morbidities of cannabis users attending a tertiary care hospital in India: A retrospective case record study.
Cannabis use has been the most commonly used illicit psychoactive substance in India. Increasing use of cannabis has been associated with an increased risk of co-morbid psychotic spectrum disorders with worse outcomes. This risk increases with increased use in a dose-dependent manner. A very complex association exists between cannabis use and mental illness hence it is essential to understand the relationship between the two to facilitate better care and management. The present study was conducted to assess the socio-demographic profile and psychiatric co-morbidities of cannabis users attending a tertiary mental health establishment in Goa. A retrospective case record study was carried out among self-reported cannabis users attending services at a tertiary mental health establishment from June 2021 to June 2022. Data regarding cannabis use, clinical profile, and socio-demographic profile of the individuals was obtained and analyzed using appropriate statistical tests. One hundred and sixty-four cannabis users were evaluated which consisted of 140 males and 24 females, the mean age being 28 years with a standard deviation of 7.68. Ganja was the most commonly used form smoked as joints. The median age of initiation was 18 with females starting at a later age than males. Later initiation was associated with using lower quantities. Concurrent alcohol and nicotine use was present in 90% of the cases. The most commonly associated diagnosis was substance-induced psychosis. Cannabis use in individuals with mental illness is more common in males and an early age of initiation was linked to earlier age of onset of psychiatric illness.


Subjective symptoms in epileptic patients on anticonvulsant drugs. A controlled therapeutic trial on the effect of vitamin d.
The possibility (based on the recognised existence of anticonvulsant osteomalacia), of an osteomalacic origin of a number of subjective symptoms in epileptics (back pain, tiredness, sleepiness, irritability, and giddiness) was tested during a controlled therapeutic trial in 226 outpatients. There was no correlation between subjective symptoms and objective pathological indices of osteomalacia, and group treated with vitamin D (2000 international units daily for 3 months) showed no amelioration of subjective symptoms above that seen in the placebo group. The findings do not support the view that all epileptic patients on anticonvulsant therapy should be treated prophylactically with vitamin D.


Twelve tips for effective short course design.
Short courses are commonly used by physicians to stay up-to-date and acquire new skills for practice. Unfortunately, many short courses are not designed to maximize their impact on practice as they fail to acknowledge how people learn and change. Designers of effective short course planning should pay attention to writing outcomes based objectives; conducting needs assessments; determining the optimal content, resources, speakers and format; preparing ancillary materials (handouts and pre- and post-course assessments); and preparing speakers and evaluation. This paper discusses how each of the components of the curriculum design can be used to enhance the learning experience and obtain the desired course outcomes.


Quantitative investigation of the photodegradation of polyethylene terephthalate film by friction force microscopy, contact-angle goniometry, and X-ray photoelectron spectroscopy.
Studies of the UV-induced photodegradation of poly(ethylene terephthalate) (PET) have been carried out using contact-angle goniometry, X-ray photoelectron spectroscopy (XPS), and friction force microscopy (FFM). The advancing contact angle of water, theta, decreased following exposure of free-standing PET films to UV light. Measurements of surface friction by FFM showed that the coefficient of friction mu increased as the degradation proceeded, reaching a limiting value after ca 200 min, in agreement with the contact angle data. Using a modified form of the Cassie equation, a quantitative analysis of the extent of modification could be carried out. There was a very close correlation between the coefficient of friction determined by FFM and the value of cos theta. XPS provided more detailed information on surface bonding that also correlated closely with the FFM data. Although FFM provides quantitative data on surface modification with nanometer-scale spatial resolution, it does not provide detailed structural information such as is provided by XPS. The oxygen content at the surface was found to increase as photo-generated radicals within the PET reacted with atmospheric oxygen. Increases in both ester and carbonyl contributions within XPS data accompanied this increase. It was concluded that the photodegradation process follows mainly Norrish type I reaction pathways, following previous work by Fechine et al and Grosstete et al.


Taurine modulates kallikrein activity and glucose metabolism in insulin resistant rats.
Taurine, a potent antioxidant has been reported to show an anti-diabetic effect in streptozotocin-induced diabetes mellitus in which the development of hyperglycemia results from the damage to beta cells of pancreas by reactive oxygen species. In addition, taurine also increases the excretion of nitrite and enhances the formation of kinins and would be expected to improve insulin resistance. The effect of taurine on insulin sensitivity was examined in the high fructose-fed rats, an animal model of insulin resistance. Male Wistar rats of body weight 170-190g were divided into 4 groups: a control group and taurine-supplemented control group, taurine supplemented and unsupplemented fructose-fed group. An intravenous glucose tolerance test (IVGTT) and a steady state plasma glucose level (SSPG) were performed before the sacrifice. The fructose-fed rats displayed hyperglycemia and insulin resistance and they had a greater accumulation of glycogen than did control rats. Hyperglycemia and insulin resistance were significantly lower in the taurine supplemented fructose-fed group than in the unsupplemented fructose-fed group. Urinary kallikrein activity was higher in taurine-treated animals than in the rats fed only fructose. The activity of membrane bound ATPases were significantly lower in fructose-fed rats than in the control rats and were significantly higher in the taurine supplemented group than in the fructose-fed group. Taurine effectively improves glucose metabolism in fructose-fed rats presumably via improved insulin action and glucose tolerance.


Hand grip strength and dexterity function in children aged 6-12 years: A cross-sectional study.
Cross-sectional and clinical measurement. Assessment of hand function considers an essential part in clinical practice. To develop normative values of hand grip strength and dexterity function for 6-12-year-old children in Saudi Arabia. Grip strength and dexterity function was measured in 525 children using Grip Track hand dynamometer (JTECH Medical, Midvale, UT, USA) and 9-hole pegboard test respectively. The grip strength and dexterity function was improved as age progressed regardless of gender. Across all age groups, the hand grip strength of boys was significantly higher than girls for dominant hand (31.75 ± 10.33 vs 28.24 ± 9.35; P < .001) and nondominant hand (31.01 ± 10.27 vs 27.27 ± 9.30; P < .001). The girls performed slightly faster than boys for dominant hand (19.70 vs 20.68; P < .05) and nondominant hand (21.79 vs 23.46; P < .05). In general, girls completed a 9-HPT faster than boys in the 2 of 7 age groups: 11 years (9-HPT scores = 2.10 seconds; P < .01) and 12 years (9-HPT scores = 1.93 seconds; P < .01). The overall patterns of hand grip strength and dexterity function observed in the present study are similar to the previous studies that established acceleration of grip strength with advanced age, and faster performance scores in older children than younger children in both genders. Norms of hand grip strength and dexterity enable therapists to identify some developmental characteristics of hand function among Saudi children, determine the presence of impairment, and compare scores from children in different clinical settings. Not applicable.


Immunophenotypic profile of nucleated erythroid progenitors during maturation in regenerating bone marrow.
This study introduces an in-depth flow cytometric method for the analysis of nucleated erythroid progenitors during bone marrow regeneration. Initial immunophenotypic analysis with the conventional erythroid-associated markers CD36, CD71 and CD235a was supplemented with the analysis of additional markers, including CD105, CD117, CD45, CD38 and cell-scattered light characteristics. Our data show that the expression of CD105 and CD117 is critical for the distinction between four phenotypically different developmental stages of nucleated erythroid progenitors: pro-erythroblasts, basophilic erythroblasts, polychromatophilic erythroblasts and orthochromatophilic erythroblasts. CD105 antigen expression was specifically associated with pro-erythroblasts and basophilic erythroblasts, whereas CD117 was expressed at the earliest pro-erythroblast stage. Both antigens were progressively lost throughout the course of differentiation. These data allow for the identification of aberrant erythroid development in acute erythroid leukemia or myelodysplastic syndrome.


Metastatic Renal Cell Carcinoma Presenting as Gastric Ulcer: Case Report and Literature Review.
Renal cell carcinoma (RCC) accounts for approximately 3% of all adult malignancies. True gastrointestinal metastases, specifically to gastric wall, have been rarely observed. Herein we describe a case of delayed metastasis to gastric wall occurring more than a decade after previously curative nephrectomy for RCC. A 67-year-old male with history of right radical nephrectomy in 2001 for RCC was found to have an asymptomatic right lower lobe solitary lung mass upon routine follow-up in 2011, with final biopsy results showing metastatic RCC for which he was treated accordingly. In 2014, patient was evaluated for dyspepsia with microcytic anemia and underwent an esophagogastroduodenoscopy and colonoscopy. EGD revealed a solitary one-centimeter atypical ulcer in the posterior mid gastric body with biopsy results being consistent with metastatic RCC. Our literature review has yielded thirty-six reported cases of RCC in association with gastric wall metastases.


The analgesic efficacy of valdecoxib vs. oxycodone/acetaminophen after oral surgery.
The authors conducted two studies to compare the analgesic efficacy and safety of the cyclooxygenase, or COX, -2-specific inhibitor, valdecoxib, with oxycodone/ acetaminophen in patients who have undergone oral surgery. In total, 205 eligible subjects in Study A and 201 in Study B were randomized to receive a single oral dose of valdecoxib (20 or 40 milligrams), a combination of oxycodone 10 mg/acetaminophen 1,000 mg or placebo. Eligible subjects experienced moderate-to-severe pain within six hours of surgery during which two or more impacted third molars were extracted. Analgesic efficacy was assessed over 24 hours or until the patient required rescue analgesia. In both studies, subjects receiving either dose of valdecoxib experienced a rapid onset of analgesia and (among those who received valdecoxib 40 mg) a level of pain relief comparable with that of those who received oxycodone/ acetaminophen. Both valdecoxib doses had a significantly longer duration of analgesic effect than did oxycodone/acetaminophen. Pooled safety data demonstrated that each valdecoxib dose had a tolerability profile superior to that of oxycodone/ acetaminophen and similar to that of placebo. Orally administered valdecoxib is as rapidly acting and effective as oxycodone/acetaminophen, and it has a superior duration of analgesic effect in patients after oral surgery. Valdecoxib has a tolerability profile superior to that of oxycodone/acetaminophen. The current standard of care for alleviating acute pain after oral surgery has rested largely on conventional nonsteroidal anti-inflammatory drugs or opioid/analgesic combination products. The studies reported here suggest that the COX-2-specific inhibitor valdecoxib offers an efficacious and safe alternative to other analgesics used to treat pain after oral surgery.


The GRF10 homeobox gene regulates filamentous growth in the human fungal pathogen Candida albicans.
Candida albicans is the most common human fungal pathogen and can cause life-threatening infections. Filamentous growth is critical in the pathogenicity of C. albicans, as the transition from yeast to hyphal forms is linked to virulence and is also a pivotal process in fungal biofilm development. Homeodomain-containing transcription factors have been linked to developmental processes in fungi and other eukaryotes. We report here on GRF10, a homeobox transcription factor-encoding gene that plays a role in C. albicans filamentation. Deletion of the GRF10 gene, in both C. albicans SN152 and BWP17 strain backgrounds, results in mutants with strongly decreased hyphal growth. The mutants are defective in chlamydospore and biofilm formation, as well as showing dramatically attenuated virulence in a mouse infection model. Expression of the GRF10 gene is highly induced during stationary phase and filamentation. In summary, our study emphasizes a new role for the homeodomain-containing transcription factor in morphogenesis and pathogenicity of C. albicans.


[What Can Health Journalism Achieve? A Criterion-Based Evaluation of Print Media Coverage of the HPV Vaccine in Germany, 2006 to 2009].
In 2006, the first human papillomavirus (HPV) vaccine was licensed in Europe and in 2007 it was included in the service catalogue of the statutory health insurance. The HPV vaccine led to a controversy in public and print media even before it was licensed. We evaluated the quality of the newspaper coverage of the HPV vaccine during the controversy in Germany. The LexisNexis print media database was scanned for health journalism articles on HPV in 4 high-circulation national newspapers and 4 magazines using pre-defined search terms for the period 2006-2009. Articles were evaluated using established indicators and were graded using a decimal grading scale. 58 articles were identified and evaluated by 2 persons independently. The indicators reflecting health journalism quality received on average a grade of 4.6 out of 6. The major quality categories which give a comprehensive overview of the HPV vaccine scored low in the majority of the articles. Only categories like simplicity of language and structure/order scored high in most of them. Compliance with established quality standards is an important basis of health journalism but seems difficult to achieve in the news coverage on the HPV vaccine. When applying the indicators to the HPV coverage, some avoidable deficiencies was identified from a public health perspective, relating in particular to the evidence base of the vaccination. Monitoring public health media can help to systematically identify information shortfalls or errors and respond with appropriate educational campaigns.


A mixed arsenic-phosphorus centered biradicaloid.
Main-group singlet biradicaloids have been thoroughly investigated in the past two decades, especially derivatives of cyclobutane-1,3-diyl. However, in each of the known examples, the radical centers are identical. Therefore, we sought to prepare a mixed dipnictadiazanediyls with P and As bearing the radical character. To achieve this goal, the unprecedented cyclodichloro arsaphosphadiazane [ClP(μ-NTer)2AsCl] had to be prepared first. Treatment of [ClP(μ-NTer)2AsCl] with a halide-abstracting agent led to the novel cyclic cation [P(μ-NTer)2AsCl](+), while reduction with magnesium afforded the first arsaphosphadiazanediyl [P(μ-NTer)2As].


Integrated fiber-mirror ion trap for strong ion-cavity coupling.
We present and characterize fiber mirrors and a miniaturized ion-trap design developed to integrate a fiber-based Fabry-Perot cavity (FFPC) with a linear Paul trap for use in cavity-QED experiments with trapped ions. Our fiber-mirror fabrication process not only enables the construction of FFPCs with small mode volumes, but also allows us to minimize the influence of the dielectric fiber mirrors on the trapped-ion pseudopotential. We discuss the effect of clipping losses for long FFPCs and the effect of angular and lateral displacements on the coupling efficiencies between cavity and fiber. Optical profilometry allows us to determine the radii of curvature and ellipticities of the fiber mirrors. From finesse measurements, we infer a single-atom cooperativity of up to 12 for FFPCs longer than 200 μm in length; comparison to cavities constructed with reference substrate mirrors produced in the same coating run indicates that our FFPCs have similar scattering losses. We characterize the birefringence of our fiber mirrors, finding that careful fiber-mirror selection enables us to construct FFPCs with degenerate polarization modes. As FFPCs are novel devices, we describe procedures developed for handling, aligning, and cleaning them. We discuss experiments to anneal fiber mirrors and explore the influence of the atmosphere under which annealing occurs on coating losses, finding that annealing under vacuum increases the losses for our reference substrate mirrors. X-ray photoelectron spectroscopy measurements indicate that these losses may be attributable to oxygen depletion in the mirror coating. Special design considerations enable us to introduce a FFPC into a trapped ion setup. Our unique linear Paul trap design provides clearance for such a cavity and is miniaturized to shield trapped ions from the dielectric fiber mirrors. We numerically calculate the trap potential in the absence of fibers. In the experiment additional electrodes can be used to compensate distortions of the potential due to the fibers. Home-built fiber feedthroughs connect the FFPC to external optics, and an integrated nanopositioning system affords the possibility of retracting or realigning the cavity without breaking vacuum.


The enhancement of stress-related memory by glucocorticoids depends on synapsin-Ia/Ib.
The activation of glucocorticoid receptors (GR) by glucocorticoids increases stress-related memory through the activation of the MAPK signaling pathway and the downstream transcription factor Egr-1. Here, using converging in vitro and in vivo approaches, respectively, GR-expressing cell lines, culture of hippocampal neurons, and GR genetically modified mice (GR(NesCre)), we identified synapsin-Ia/Ib as one of the effectors of the glucocorticoid signaling cascade. Stress and glucocorticoid-induced activation of the GR modulate synapsin-Ia/Ib through two complementary mechanisms. First, glucocorticoids driving Egr-1 expression increase the expression of synapsin-Ia/Ib, and second, glucocorticoids driving MAPK activation increase its phosphorylation. Finally, we showed that blocking fucosylation of synapsin-Ia/Ib in the hippocampus inhibits its expression and prevents the glucocorticoid-mediated increase in stress-related memory. In conclusion, our data provide a complete molecular pathway (GR/Egr-1/MAPK/Syn-Ia/Ib) through which stress and glucocorticoids enhance the memory of stress-related events and highlight the function of synapsin-Ia/Ib as molecular effector of the behavioral effects of stress.


Morphological and anatomical evidence support a new wild cassava: Manihot fallax (Crotonoideae, Euphorbiaceae), from Mato Grosso, Brazil.
During the preparation of the taxonomic treatment of Manihot in the Midwest Region of Brazil, a new species was found. Manihot fallax M.J. Silva & L.S. Inocencio is described, illustrated and morphologically compared with similar simple-leaved species. The conservation status, geographic distribution (including map), ecology, phenology and notes about leaf anatomy of the new species are given. The synonymisation of M. robusta M. Mend. & T. B. Cavalc. under M. attenuata Müll. Arg. and lectotypes for M. attenuata and M. brachystachys Pax & K. Hoffm are also proposed. An emended description of M. attenuata is proposed as the original description is incomplete as it lacks information on the pistillate flowers, fruits and seeds.


Treatment of Orofacial Granulomatosis-9-Month Follow-up: A Case Report.
Orofacial granulomatosis is a condition that manifests clinically as painless labial enlargement, perioral and mucosal edema, oral ulcers, and gingivitis. It is characterized by non-necrotizing granulomatous inflammation of the oral and maxillofacial region. When the swelling only affects the lips, the pathology is called Miescher's granulomatous cheilitis; however, when it also causes facial paresis and lingua plicata, it is known as Melkersson-Rosenthal syndrome. We report a case that was successfully treated with a combination of a local (intralesional) steroid, a systemic antibiotic, and a systemic steroid. After 6 months of therapy, we observed improvement in gingival hyperplasia and buccal mucosa and lip edema.


A local platform for user-friendly FAIR data management and reproducible analytics.
Collaborative research is common practice in modern life sciences. For most projects several researchers from multiple universities collaborate on a specific topic. Frequently, these research projects produce a wealth of data that requires central and secure storage, which should also allow for easy sharing among project participants. Only under best circumstances, this comes with minimal technical overhead for the researchers. Moreover, the need for data to be analyzed in a reproducible way often poses a challenge for researchers without a data science background and thus represents an overly time-consuming process. Here, we report on the integration of CyVerse Austria (CAT), a new cyberinfrastructure for a local community of life science researchers, and provide two examples how it can be used to facilitate FAIR data management and reproducible analytics for teaching and research. In particular, we describe in detail how CAT can be used (i) as a teaching platform with a defined software environment and data management/sharing possibilities, and (ii) to build a data analysis pipeline using the Docker technology tailored to the needs and interests of the researcher.


Distilling Big Data: Refining Quality Information in the Era of Yottabytes.
Big Data is the buzzword of the modern century. With the invasion of pervasive computing, we live in a data centric environment, where we always leave a track of data related to our day to day activities. Be it a visit to a shopping mall or hospital or surfing Internet, we create voluminous data related to credit card transactions, user details, location information, and so on. These trails of data simply define an individual and form the backbone for user-profiling. With the mobile phones and their easy access to online social networks on the go, sensor data such as geo-taggings and events and sentiments around them contribute to the already overwhelming data containers. With reductions in the cost of storage and computational devices and with increasing proliferation of Cloud, we never felt any constraints in storing or processing such data. Eventually we end up having several exabytes of data and analysing them for their usefulness has introduced new frontiers of research. Effective distillation of these data is the need of the hour to improve the veracity of the Big Data. This research targets the utilization of the Fuzzy Bayesian process model to improve the quality of information in Big Data.


A host-plant-derived volatile blend to attract the apple blossom weevil Anthonomus pomorum - the essential volatiles include a repellent constituent.
Plant volatiles are promising cues for trapping pest insects. This study started with a recently identified complex blend released by prebloom apple trees and aimed to reduce the number of compounds in the blend while maintaining the attraction of the target pest, the apple blossom weevil Anthonomus pomorum. An evaluation was made to determine whether attraction to plant volatiles is a general feature in this species. Laboratory-based bioassays with field-collected weevils demonstrated repellency by volatiles from the non-host walnut, indicating that preference for plant odours is not a general feature in this species. By a subtractive bioassay approach, the original number of compounds in the apple-plant-released blend was stepwise reduced from 12 to 6 while maintaining weevil attraction. This resulting blend was as attractive as the full blend and as a blossom-bud-carrying apple twig. It was found to be composed of two synergistically interacting constituents, of which the first containing benzenoids was behaviourally inactive, and the second comprising the remaining compounds was even repellent. This study enhances knowledge of the interaction of behaviourally effective constituents in complex odour blends and contributes to the development of an efficient monitoring system involving plant volatiles for the apple blossom weevil.


Asymptotic dynamic scaling behavior of the (1+1)-dimensional Wolf-Villain model.
Extensive kinetic Monte Carlo simulations are presented for the Wolf-Villain model in (1+1) dimensions. Asymptotic dynamic scaling is found for lattice sizes L≥2048. The exponents obtained from our simulations, α=0.50±0.02 and β=0.25±0.02, are in excellent agreement with the exact values α=1/2 and β=1/4 for the one-dimensional Edwards-Wilkinson equation. Our findings explain the widespread discrepancies of previous reports for exponents of the Wolf-Villain model in (1+1) dimensions, and the results are also consistent with the theoretical predictions of López et al. [J. M. López, M. Castro, and R. Gallego, Phys. Rev. Lett. 94, 166103 (2005)].


SAGE: SLAM with Appearance and Geometry Prior for Endoscopy.
In endoscopy, many applications (e.g., surgical navigation) would benefit from a real-time method that can simultaneously track the endoscope and reconstruct the dense 3D geometry of the observed anatomy from a monocular endoscopic video. To this end, we develop a Simultaneous Localization and Mapping system by combining the learning-based appearance and optimizable geometry priors and factor graph optimization. The appearance and geometry priors are explicitly learned in an end-to-end differentiable training pipeline to master the task of pair-wise image alignment, one of the core components of the SLAM system. In our experiments, the proposed SLAM system is shown to robustly handle the challenges of texture scarceness and illumination variation that are commonly seen in endoscopy. The system generalizes well to unseen endoscopes and subjects and performs favorably compared with a state-of-the-art feature-based SLAM system. The code repository is available at https://github.com/lppllppl920/SAGE-SLAM.git.


[Thyroid gland hypofunction during separate and combined radiation-thermal injury].
A study was made of the dynamics of structural, morphological and histological changes in the thyroid gland of Wistar rats subjected to gamma-irradiation (7.5 Gy) and thermal burn (15% of a body surface) and a combined effect of these two factors. Concurrently, an estimation was made of the iodine content of the gland, using the roentgen-fluorescent method, and of the thyroxin concentration in blood. The results obtained were considered in relation to the clinical course and the outcome of the affection caused by the combined and individual effects of radiation and heat. It is conluded that the cell-tissue substrate providing the thyroid hormones synthesis does not undergo substantial variations from normal values which could be considered as a cause of the decrease in the hormone content of blood after burn, irradiation and the combined radiation and thermal injury. Other possible causes of hyperthyroxynemia are discussed.


The spectrum of expert reports on clinical biochemical toxicology and medicine from an Irish practice.
The compounds which generated an expert opinion report in the area of medical toxicology in the period 1999 to 2015 are presented from the toxicological case files of a specialist in chemical pathology and general internal medicine. There were 132 different compounds from 86 cases. Alcohol was involved in 43%, drugs of abuse in 18.6%, volatile carbon compounds in 17.4%, metals in 9.3%, and carbon monoxide in 4.6%. Many compounds appeared once. The duty of the medical expert witness to provide an objective report for the court irrespective of the payer is stated. The addition of references from peer reviewed literature to substantiate the pros and cons of each case is recommended as a standard operating procedure in completing each report.


Effect of benzimidazole configuration in polybenzimidazole chain on interaction with phosphoric acid: a DFT study.
Polybenzimidazole doped with phosphoric acid (PA) is a candidate for polymer electrolyte membranes in fuel cells. Understanding the interaction of benzimidazole in polybenzimidazole with PA is important for fuel-cell applications. Herein, the interaction of a PA-benzimidazole complex was investigated using density functional theory, with calculations performed at the ωB97X-D/6-311G(d,p) level of theory, with an aim to investigate the effects of bibenzimidazole configuration on the interaction energy. Benzimidazole and three different bibenzimidazole configurations (2,2'-bibenzo[d]imidazole (1), 2,5'-bibenzo[d]imidazole (2), and 5,5'-bibenzo[d]imidazole (3)) were used as models for bulk polybenzimidazole. Calculation of various types of hydrogen bond interaction showed that the interaction between the imino moiety of the monomer and the hydroxyl group of PA is the strongest, which agrees with previous studies. Our calculations indicated that π-H interactions between the hydrogen atoms of the PA molecule and the benzene rings should be considered, and these contribute to the interaction energy for some interaction complexes. The interaction energy between the monomer and PA is smaller than that of the PA dimer. However, the interaction energy between bibenzimidazole and PA is comparable to that of the PA dimer for bibenzimidazole configurations 1 and 2, highlighting the importance of considering the adjacent monomer unit.


Surgeon volumes and selected patient outcomes in cataract surgery: a population-based analysis.
To study the association of annual surgeon volume of cataract procedures with the risk of postoperative adverse events. We used population-based administrative health records to conduct a retrospective cohort study from 2001 through 2003. The number of surgeons who performed more than 50 cataract surgeries annually ranged from 231 to 243 over the 3 years. There were 284 797 cataract surgeries in patients older than 20 years performed at 70 hospitals or eye surgery centers in the province of Ontario, Canada. We calculated cataract surgery volume for each surgeon and tested for the presence of a volume-outcome association. We used generalized estimating equations to account for the effect of clustering of patients according to individual surgeons and to adjust estimates for the potential confounding effects of patient age and gender. We used a composite outcome of postoperative adverse events from cataract surgery that included billing claims for vitrectomy, vitreous aspiration or injection of medication, vitreous air or fluid exchange, and dislocated lens extraction performed by any ophthalmologist between 1 and 14 days after cataract surgery. These procedures are surrogate markers for the outcomes of retinal detachment, lost lens or lens fragment, and suspected endophthalmitis. In each year, fewer than 1 in 200 patients experienced an adverse event (range, 0.33%-0.41%). Surgeons performing 50 to 250 cataract surgeries per year had an adverse event rate of 0.8%. Surgeons performing 251 to 500 cataract surgeries per year had an adverse event rate of 0.4% and an adjusted odds ratio of postoperative adverse events of 0.52 (95% confidence interval [CI], 0.39-0.69) compared with surgeons performing 50 to 250 procedures per year. Surgeons performing 501 to 1000 cataract surgeries per year had an adverse event rate of 0.2% and an adjusted odds ratio of 0.31 (95% CI, 0.22-0.43), and surgeons performing more than 1000 cataract surgeries per year had an adverse event rate of 0.1% and an adjusted odds ratio of 0.14 (95% CI, 0.09-0.23). Selected adverse event rates for surgeons performing more than 50 cataract surgeries per year are low. There is a volume-outcomes relationship for cataract surgery, and this relationship persists even for very high-volume surgeons.


[Identification of the isoadenylate synthetase in the messenger RNA translation products of antiviral proteins].
A further study of conditions for induction, determinations of activity and products of mRNAs translation of AVP having nonspecific antiviral activity from L-929 cells treated with poly(I) . poly(C) was carried out. Under conditions of superinduction of interferon the yield of AVP mRNA is reduced unlike that of interferon mRNA. Manifestations of the antiviral effect of AVP mRNA translation products do not seem to require the stages of transcription as dihydrorifampicin exerts no influence on this process. The inhibiting effect of actinomycin D is more likely to be associated with its effect on the energy of cells and synthesis of macroergic compounds of ATP type. Active AVP mRNAs from L-929 cells like interferon mRNA consist mainly of poly-A-deficient mRNAs. The sedimentation rate of AVP mRNAs differs from that of interferon mRNA and is about 10S. AVP mRNA translation products in ovocytes of Xenopus laevis, in contrast to control mRNAs, contain isoadenylate synthetase responsible for synthesis of 2'5'-oligoisoadenylate, a nonspecific translation inhibitor the mechanism of action of which consists in activation of cellular endogenous nuclease. The results suggest that the mode of development of the antiviral condition by activation of isoadenylate synthetase is similar in the cells treated with interferon and poly(I) . poly(C).


Effects of inorganic mercury exposure in the alveolar bone of rats: an approach of qualitative and morphological aspects.
In comparison to organic mercury (MeHg), the environmental inorganic mercury (IHg) can be found in some skin-lightening cosmestics were considered "harmless" for a long time. However, recent studies have shown that long-term exposure to low doses of IHg may affect biological systems. Therefore, this study investigated the effects of IHg long-term exposure to the alveolar bone of adult rats. Adult Wistar rats were distributed in control and HgCl2 exposed (0.375 mg/kg/day). After 45 days, the rats were euthanized and both blood and hemimandibles were collected. Total blood Hg levels were measured and both inorganic and organic components of the alveolar bone were determined through XRD and ATR-FTIR. The microstructure of the alveolar bone was assessed by using micro-CT and the morphometric analysis was performed by using stereomicroscopy. Alterations in the physicochemical components of the alveolar bone of exposed animals were observed. The bone changes represented a tissue reaction at the microstructural level, such as bone volume increase. However, no significant dimensional changes (bone height) were observed. Exposure to IHg at this dose can promote microstructural changes and alteration in the organic and inorganic components in the alveolar bone.


10-Hydroxyaloin B 6'-O-Acetate, an Oxanthrone from Aloe claviflora
Analysis of the leaf exudate of Aloe claviflora resulted in the isolation of a new oxanthrone, 10-hydroxyaloin B 6'-O-acetate (1), whose structure was determined on the basis of spectral evidence as well as by conversion to the known compound 10-hydroxyaloin B (2).


Renal prostaglandins.
The renal prostaglandins PGS2 and PGE2 possess potent antihypertensive and vasodepressor activity. The mechanism of blood pressure lowering effect is through peripheral arteriolar dilation with a fall in total peripheral resistance. PGA unlike PGE escape degradation by the lung and thus could circulate as antihypertensive hormones. Since plasma PGA levels rise in humans on a low sodium intake, it has been postulated that the beneficial effects of a low sodium diet in some hypertensives may be the result of an increase in peripheral vasodilating PGA. Support that plasma PGA may be a regulator of systemic blood pressure is also derived from the fact a PGA-secreting renal tumor was associated with a fall in blood pressure and a rise in plasma PGA in a previously hypertensive woman. The removal of the tumor resulted in a return of blood pressure to elevated levels and a concomitant fall in PGA. Recently, a number of human patients with essential hypertension have been infused with PGA1 and PGA2. It was observed that there was an initial increase in renal blood flow, sodium and water excretion which was associated with no change in the elevated blood pressure. When blood pressure ultimately fell, there was a return of renal blood flow, sodium and water excretion to preinfusion levels. It would appear that PGA compounds act as 'ideal' antihypertensive agents since they favorably effect renal resistance, sodium and water homeostasis, plasma volume, total peripheral resistance, blood pressure and indirectly cardiac output through baroreceptor stimulation, all factors known to be important in etiology in human hypertension.


Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway.
Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O2(-)), nitric oxide (NO) and peroxynitrite (ONOO(-)) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O2(-), NO and ONOO(-), inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O2(-) and ONOO(-) and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of M. charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury.


High-Content Imaging Reveals Expansion of the Endosomal Compartment during Coxiella burnetii Parasitophorous Vacuole Maturation.
Coxiella burnetii is an obligate intracellular pathogen and the causative agent of human Q fever. Replication of the bacterium within a large parasitophorous vacuole (PV) resembling a host phagolysosome is required for pathogenesis. PV biogenesis is a pathogen driven process that requires engagement of several host cell vesicular trafficking pathways to acquire vacuole components. The goal of this study was to determine if infection by C. burnetii modulates endolysosomal flux to potentially benefit PV formation. HeLa cells, infected with C. burnetii or left uninfected, were incubated with fluorescent transferrin (Tf) for 0-30 min, and the amount of Tf internalized by cells quantitated by high-content imaging. At 3 and 5 days, but not 1 day post-infection, the maximal amounts of fluorescent Tf internalized by infected cells were significantly greater than uninfected cells. The rates of Tf uptake and recycling were the same for infected and uninfected cells; however, residual Tf persisted in EEA.1 positive compartments adjacent to large PV after 30 min of recycling in the absence of labeled Tf. On average, C. burnetii-infected cells contained significantly more CD63-positive endosomes than uninfected cells. In contrast, cells containing large vacuoles generated by Chlamydia trachomatis exhibited increased rates of Tf internalization without increased CD63 expression. Our results suggest that C. burnetii infection expands the endosomal system to increase capacity for endocytic material. Furthermore, this study demonstrates the power of high-content imaging for measurement of cellular responses to infection by intracellular pathogens.


Scaling of lifting forces in relation to object size in whole body lifting.
Subjects prepare for a whole body lifting movement by adjusting their posture and scaling their lifting forces to the expected object weight. The expectancy is based on visual and haptic size cues. This study aimed to find out whether lifting force overshoots related to object size cues disappear or persist over a number of repeated lifts. In addition, the influence of the degree of alternation between load sizes, and the influence of knowledge of actual object weights prior to the lifts, were investigated with regard to their effect on force overshoots. Four experiments were performed using a large and a small box, each of 8.4 kg weight, and varying degrees of alternation between boxes. In two of the experiments, subjects were informed about the weight of the objects, while in the other two experiments they were not informed about the weight of the objects. When boxes were lifted 15 times before switching to the other box, rapid diminishing of force scaling errors was observed. However, when boxes were alternated each lift or after three lifts, persisting force scaling overshoots were found in lifting the large box compared to the small one. When participants were given information regarding the actual object weight, force overshoots in the first pair of large and small box lifts were not different from overshoots in experiments where subjects were not informed about the weight of the objects. This shows that, for occupational lifting, risks related to force overshoots in lifting large objects can persist despite experience in lifting the objects and despite the use of labels indicating the weight of the objects.


[The role of the pineal gland and melatonin in the regulation of adenohypophysial hormone synthesis and secretion].
This paper reviews findings accumulated on the role of the pineal gland and its hormone,melatonin, in the regulation of hypothalamo-adenohypophysial system activity. The effect of melatonin on somatotrophin (GH), thyreotrophin (TSH), and adrenocorticotrophin (ACTH) synthesis and secretion is considered. Results of in vivo and in vitro experiments show that the influence of melatonin on adenohypophysial activity depends on the animal species, age, sex, the concentration of the hormone, and the experimental conditions. Melatonin modifies adenohypophysial hormone synthesis and secretion either directly by influencing the secretory activity of the cells in the anterior pituitary or indirectly by influencing the hypothalamic neurons producing the respective neurohormones which stimulate or inhibit the release of adequate adenohypophysial hormones. Melatonin acts via specific membrane receptors which have been demonstrated in several brain areas, with high concentrations in the hypothalamic suprachiasmatic nucleus and the pars tuberalis of the pituitary. It may also act directly on a genome. Moreover, the response of the hypothalamo-adenohypophysial system to melatonin may depend on this hormone's influence on the metabolism of some neuromediators and/or neuromodulators in the central nervous system.


The prospect of selective recognition of nerve agents with modular basket-like hosts. A structure-activity study of the entrapment of a series of organophosphonates in aqueous media.
We designed, prepared, and characterized three cup-shaped cavitands 1-3 for trapping organophosphonates (O═PR(OR')2, 118-197 Å(3)) whose shape and size correspond to G-type chemical warfare agents (132-186 Å(3)). With the assistance of computational (molecular dynamics) and experimental ((1)H NMR spectroscopy) methods, we found that host [1-H3](3+) orients its protonated histamine residues at the rim outside the cavity, in bulk water. In this unfolded form, the cavitand traps a series of organophosphonates 5-13 (K(app) = 87 ± 1 to 321 ± 6 M(-1) at 298.0 K), thereby placing the P-CH3 functional group in the inner space of the host. A comparison of experimental and computed (1)H NMR chemical shifts of both hosts and guests allowed us to derive structure-activity relationships and deduce that, upon the complexation, the more sizable P-OR functional groups in guests drive organophosphonates to the northern portion of the basket [1-H3](3+). This, in turn, causes a displacement of the guest's P-CH3 group and a contraction of the cup-shaped scaffold. The proposed induced-fit model of the recognition is important for turning these modular hosts into useful receptors capable of a selective detection/degradation of organophosphorus nerve agents.


Research and development of bronchodilators for asthma and COPD with a focus on G protein/KCa channel linkage and β2-adrenergic intrinsic efficacy.
Bronchodilators are used to improve symptoms and lung function in asthma and COPD. Airway smooth muscle tone is regulated by both muscarinic and β2-adrenergic receptor activity. Large-conductance Ca(2+)-activated K(+) (KCa) channels are activated by β2-adrenergic receptor agonists, via Gs, and suppressed by muscarinic receptor antagonists via Gi. This functional antagonism converges on the G protein/KCa channel linkages. Membrane potential regulated by KCa channels contributes to airway smooth muscle tension via Ca(2+) influx passing through voltage-dependent Ca(2+) (VDC) channels. The Gs/KCa/VDC channel linkage is a key process in not only physiological effects, but also in dysfunction of β2-adrenergic receptors and airway remodeling. Moreover, this pathway is involved in the synergistic effects between β2-adrenergic receptor agonists and muscarinic receptor antagonists. Intrinsic efficacy is also an important characteristic for both maintenance and loss of β2-adrenergic action. Allosteric modulators of G protein-coupled receptors contribute not only to this synergistic effect between β2-adrenergic and muscarinic M2 receptors, but also to intrinsic efficacy. The effects of weak partial agonists are suppressed by lowering receptor number, disordering receptor function, and enhancing functional antagonism; in contrast, those of full or strong partial agonists are not suppressed. Excessive exposure to full agonists causes β2-adrenergic desensitization; in contrast, exposure to partial agonists does not cause desensitization. Intrinsic efficacy may provide the rationale for the clinical use of β2-adrenergic receptor agonists in asthma and COPD. In conclusion, the G protein/KCa linkage and intrinsic efficacy (allosteric effects) may be therapeutic targets for research and development of novel agents against both airway obstruction and airway remodeling.


[Value of magnetic resonance imaging in the follow-up of children operated for portal hypertension].
The authors report their experience concerning nuclear magnetic resonance imaging (NMR) in 7 children. They emphasize its importance in the post-operative study of portal hypertension. All those children got surgically created porto-systemic shunts. NMR imaging is easy, safe and trustable. It is able to visualise the shunt itself and to demonstrate the patency of this shunt. So, it is interesting when the usual controls have failed, particularly abdominal ultrasonography.


Efficacy evaluation of bio trombina ® 400 in mini mall y invasive treatment of complications (pseudoaneurysms), after venipuncture for diagnostic purposes. Authors' own experience - case study of 38 patients.
Common use of venipuncture on upper and lower limbs for diagnostic purposes (such as coronarography or arteriography), and also during the course of treatment (angioplasty), very often bares a complication in the form of pseudoaneurysms. According to various reports, the incidence of pseudoaneurysms ranges from 0.005% to 0.5% of all vascular procedures requiring arterial cannulation (Common Femoral Artery, Brachial Artery, Radial Artery). The use of Bio Trombina® 400 in the embolization of pseudoaneurysms allows minimally invasive and effective treatment. The aim of the study was to evaluate the efficacy of pseudoaneurysm embolization with the use of Trombina 400, authors' own experience. In the years 2011 - 2013, the authors of this study performed 38 vascular interventional procedures involving pseudoaneurysms as complications of venipuncture in upper and lower limbs for diagnostic and treatment purposes. All procedures involved the direct injection of thrombin into the chamber of the pseudoaneurysm under the guidance of USG Doppler (6.2 MHz linear head). 34 cases presented single chamber pseudoaneurysms while 4 cases involved multi- chamber pseudoaneurysms, which required several thrombin reinjections (Bio Trombina® 400) into each of the chambers. Pseudoaneurysm maximum size of 4 cm was set as an inclusion criterion for the embolization procedure. Furthermore, all pseudoaneurysms with a significantly wide tract in transverse dimensions were treated as an exclusion criterion because of high risk of the peripheral arteries embolization. Initial success was observed in 36 patients (94.73%) in the first day after the procedure, 1 patient (2.63%) underwent thrombin reinjection procedure in the second day after the first embolization. Another patient (2.63%) underwent an open procedure in which the Common Femoral Artery was accessed, the clot evacuated, and CFA was sutured with continuous suture Prolene 6-0. 1. Embolization of pseudoaneurysms with USG Doppler-guided thrombin injection is an effective course of treatment for complications of cannulation. 2. The safety of pseudoaneurysm embolization depends on a surgeon's experience. It is also crucial to keep in mind the inclusion and exclusion criteria for this type of procedure (the size of a pseudoaneurysm, the width of its base). 3. Furthermore, its cost effectiveness and short hospitalization period make pseudoaneurysm embolization an effective and valuable alternative to the classic approach.