The relationship between lower-extremity stress fractures and the ground reaction force: a systematic review.
lower-limb stress fracture is one of the most common types of running injuries. There have been several studies focusing on the association between stress fractures and biomechanical factors. In the current study, the ground reaction force and loading rate are examined. There is disagreement in the literature about whether the history of stress fractures is associated with ground reaction forces (either higher or lower than control), or with loading rates. a systematic review of the literature was conducted on the relationship between the history of tibial and/or metatarsal stress fracture and the magnitude of the ground reaction force and loading rate. Fixed-effect meta-analysis techniques were applied to determine whether or not the ground reaction force and/or loading rate are different between the stress fracture and control groups. thirteen articles were identified through a systematic search of the literature. About 54% of these articles reported significantly different vertical ground reaction force and/or loading rate between the stress fracture and control groups. Other studies (~46%) did not observe any significant difference between the two groups. Meta-analysis results showed no significant differences between the ground reaction force of the lower-limb stress fracture and control groups (P>0.05). However, significant differences were observed for the average and instantaneous vertical loading rates (P<0.05). the currently available data does not support the hypothesis that there is a significant difference between the ground reaction force of subjects experiencing lower-limb stress fracture and control groups. Instead, the vertical loading rate was found to be significantly different between the two groups.


Causal evidence of the roles of the prefrontal and occipital cortices in modulating the impact of color on moral judgement.
Moral judgment is known to be affected by factors such as color. Previous research has shown that the colors black and white are particularly important, however, the neural mechanisms underlying this effect remain unclear. This study aimed to investigate the causal relationship between specific brain regions (left dorsolateral prefrontal cortex, left DLPFC and occipital cortex, OC) and their impact of black and white moral judgement by using transcranial direct current stimulation (tDCS). The results of Experiment 1 (N = 54) and Experiment 2 (N = 66) showed that anodal tDCS over the left DLPFC inhibited the impact of black and white on moral judgment while cathodal tDCS over the left DLPFC enhanced the effect. Conversely, anodal tDCS over the OC enhanced the impact of white on moral judgment, while cathodal tDCS over the OC inhibited it. Together these results suggest that moral judgment relies not only on the cognitive control network, but also brain regions important for sensory perception. The current findings provide enhanced insight into how colors can impact moral judgments.


Racial Difference in Response to Vitamin D Supplementation.
This manuscript is the result of work supported by the use of resources and facilities at the Louis Stokes Cleveland Department of Veterans Affairs Medical Center, specifically, the Geriatric Research Education and Clinical Center (GRECC). Deficiency in 25-hydroxyvitamin D (25[OH]D) is common, especially in the elderly and African Americans (AA). While 25(OH) D deficiency is associated with multiple negative health outcomes, current recommendations for supplementation of this deficiency may be insufficient. To determine the prevalence of 25(OH)D deficiency, the extent of vitamin D supplementation, and the effect of supplementation on 25(OH) D levels in an elderly Veteran population. The study also focused specifically on the role of race in the risk for 25(OH)D deficiency and in the response to vitamin D supplementation. A retrospective chart review was conducted of information including 25(OH)D serum levels pre and post-supplementation, race, and vitamin D supplementation. Subjects were community-dwelling Veterans (≥60years) followed by a VA geriatric clinic. A total of 234 charts were reviewed (124 Caucasian, 78 AA, 32 other/unknown race). Information collected through the chart review was analyzed by comparing the means of 25(OH)D levels pre and post-supplementation across races and across times. At Baseline 206 subjects (88%) were 25(OH)D deficient (<32ng/ml). While 80.6% of them were supplemented, only 10.24% (17 of 166) achieved normal 25(OH)D serum levels. AAs (n=78) had significantly lower Baseline levels compared to Caucasians (n=124) and differences were consistent across time. Fewer AAs than Caucasians increased to normal (AA:6.3%; Caucasian:12.8%). Conservative oral vitamin D supplementation is largely ineffective at achieving therapeutic serum levels, especially for AAs. Future research is needed to focus on individualized supplementation strategies and targeted risk factors such as race.


[Clinical application and animal experiment of thoracic tracheal reconstruction by using pulmonary tissue flap].
To study the usability of pulmonary tissue flap in the reconstruction of the thoracic trachea. Over half perimeter anterior and posterior wall and 6 to 8 tracheal cartilagious rings of dog trachea were resected. The nickel-titanium alloy mesh stent was placed inside the lumen for repair of the defect of the tracheal wall by nearby pulmonary tissue flap with the vascularized segment. The dogs were killed from 2 months to 12 months after operation. Specimens were taken and observed under light and electron microscope. Clinically, 4 patients were treated by this way operation [right common tracheal scarred stenosis and atresia (1), mixed cancerization in the lower part of the common trachea (1) and left common tracheal carcinoid (2)]. No stenosis and granulation tissue were observed in the prosthetic lumen, in which there was comparative continuous stratified ciliated columnar epithelium. All patients recovered respiratory function. Pulmonary tissue flap is a promising prosthesis of thoracic tracheal reconstruction.


Effect of gravity on the spreading of a droplet deposited by liquid needle deposition technique.
This study represents an experimental investigation, complemented with a mathematical model, to decipher the effect of gravity on the spreading dynamics of a water droplet. For the theoretical discussion, an overall energy balance approach is adopted to explain the droplet spreading under both microgravity (μg) and terrestrial gravity condition. Besides explaining the mechanism of the droplet spreading under microgravity condition achieved during the parabolic flight, a technique with a detailed experimental set-up has also been developed for the successful deposition of droplet. A rational understanding is formulated through experimental investigation and theoretical analysis, which allows us to distinguish the transient variation of the spreading of a droplet, between microgravity and terrestrial gravity condition. The spreading of the droplet is predicted by the non-linear overall energy balance equation, which accounts for the operating parameters in the form of non-dimensional groups like Reynolds number ([Formula: see text]), Weber number (We) and Bond number (Bo). To distinctly identify the difference in the drop spreading at terrestrial and microgravity conditions, the Bo with transient gravitational field obtained through the on-board accelerometer is considered. The obtained theoretical results are further corroborated by experimental results which are obtained from the parabolic flight.


The issue of aging faculty in higher education.
The aging of faculty in higher education is upon us. Certain features of the trend could become problematic over the next 20 years. This issue holds particular relevance for nurse educators as they strive to establish and maintain a foothold in the collegiate milieu, simultaneously facing the impact of the aging trend and associated events. In addition to consideration of the ramifications of the aging faculty and with particular regard for nursing faculty in higher education, certain strategies may be available to allay the detrimental outcomes often associated with the issue of aging faculty in higher education.


Prise en charge chirurgicale du cancer épithélial de l'ovaire - première ligne et première rechute: Surgical management of epithelial ovarian cancer - first line and first relapse.
Based on recently published data, these recommendations present some evolutions in the surgical management of high grade epithelial ovarian cancers. In apparently early stages (FIGO I and II), surgical staging must be undertaken to confirm the absence of both peritoneal lesions and lymph node involvement (that might change stage and management). Neoadjuvant chemotherapy is not indicated, surgical exploration should be performed upfront, by laparotomy, to reduce the risk of rupture of the primary tumor. In advanced stages, the first step is to evaluate the feasibility of primary surgery with complete tumor cytoreduction. If it appears unfeasible, 3 or 4 cycles of neoadjuvant chemotherapy are administered before interval surgey. Whether it is implemented in the primary or interval setting, surgery must be performed by experimented teams, in an approved facility, having developed a rehabilitation program. Lymph node dissection is not mandatory if no adenopathies have been identified by imaging and by peroperative palpation. At first relapse, the surgical decision must be made by a multidisciplinary team, using scores predictive of complete cytoreduction (AGO or iMODEL criteria). Similarly as in first line, the objective is to achieve resection without any residual disease. Surveillance after first-line treatment must be adapted, according to the probability of another complete cytoreduction in case of late relapse, especially in patients who benefited from primary complete surgery and maintained good performance status.


Cytokines are increased in the rat hippocampus after serotonergic neuron degeneration and upregulate the expression of GDH, an enzyme involved in glutamate detoxification.
The degeneration of serotonergic neurons increases the expression of glutamate dehydrogenase (GDH) in hippocampal astrocytes. This process was demonstrated to be independent of the serotonin level. At the same time, upregulation of tumor necrosis factor (TNF) alpha and interleukin (IL)-1 alpha mRNA were observed, whereas levels of transforming growth factor (TGF) beta 1 mRNA remained unchanged. The level of GDH mRNA was increased in primary cultures of hippocampal astrocytes treated with TNF alpha and IL-1 alpha suggesting that these cytokines act on the GDH metabolism. TNF alpha and IL-1 alpha induced an increase in GDH promoter activity in C8S (an astrocytic cell line) transfected with constructs containing 5' flanking genomic sequences of GDH driving the expression of a reporter gene. These observations suggest that cytokines may be signals that upregulate the astrocytic GDH expression in response to the degeneration of serotonergic terminals in the hippocampus.


Proteasome inhibitor does not enhance MPTP neurotoxicity in mice.
Dysfunction of the proteasome function is known to be a potential mechanism for dopaminergic neuron degeneration. Here, we investigated to determine whether systematic administration of proteasome inhibitor, carbobenzoxy-L-gamma-t-butyl-L-glutamyl-L-alanyl-L-leucinal (PSI), causes the increased susceptibility in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. PSI was injected into MPTP-treated mice over a period of 2 weeks. Thereafter, we evaluated the effect of PSI 2, 4, and 8 weeks after the cessation of treatment with PSI. In the present study with HPLC analysis, PSI did not enhance MPTP-induced dopaminergic neurotoxicity in mice. Our present study with Western blot analysis also demonstrated that the reduction of tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP) protein levels in MPTP-treated mice was more pronounced than that in MPTP + PSI-treated animals. These results suggest that proteasome inhibitor did not enhance MPTP neurotoxicity in mice. Our findings suggest that proteasome inhibition is not a reliable model for PD. Thus, our findings provide further valuable information for the pathogenesis of Parkinson's disease.


English language proficiency, prior knowledge, and student success in an international Chinese accounting program.
International student exchange programs have gained popularity as a means to increase enrollments, support international academic partnerships, and improve student preparedness for globalized work environments. However, the relationships between English language proficiency, cultural intelligence, teamwork, self-efficacy, academic success, and other factors within these programs are not clear. This study investigates the correlations among international accounting students' English language proficiency, accounting knowledge, and academic performance in a transnational education program in mainland China. Data were obtained from academic records of 104 accounting students enrolled in the program. A quantitative measuring of the Pearson correlation statistical tests were employed to measure the relationships between English language proficiency and academic performance, as well as between previous accounting knowledge and academic success. The results indicate a statistically significant relationship between English language proficiency and academic performance, and between previous accounting knowledge and academic success. This study has significant implications for transnational education programs, academic institutions, and policymakers and provides insights into effective strategies for enhancing the quality of transnational education programs and promoting the internationalization of higher education.


Trajectories of Infant Weight Gain from Birth to 12 Months and Adult-Onset Coronary Heart Disease.
To investigate associations between infant weight gain trajectories and coronary heart disease (CHD). We followed 3645 Danish individuals born between 1959 and 1961 with information on weight at birth and at age 2 weeks and 1, 2, 3, 4, 6, or 12 months. Sex-specific weight trajectories were generated using latent class modeling. Cases of CHD (n = 279) were identified from national health registers. Hazard ratios (HRs) were estimated by Cox regression with sequential adjustment for sex, socioeconomic status, prepregnancy body mass index, maternal smoking, preterm birth, parity, and birth weight. We identified 5 trajectories of weight development in infancy in our cohort: very low-moderate increase (11.5% of the population), low-marked increase (13.9%), low-stable increase (32.4%), average-stable increase (29.8%), and high-moderate increase (12.4%). Compared with the average-stable increasing trajectory, having a very low-moderately increasing weight trajectory in infancy was associated with a higher frequency of adult CHD (HR, 1.56; 95% CI, 1.04-2.33). The higher frequency remained after adjustment for maternal factors but was slightly attenuated after additional adjustment for preterm birth and parity (HR, 1.41; 95% CI, 0.91-2.23) and disappeared after adjustment for birth weight (HR, 0.78; 95% CI, 0.44-1.37). The associations with CHD did not differ between the other trajectories and the average-stable increasing trajectory. Although a pattern of very low-moderate increasing weight during infancy was associated with a higher frequency of adult CHD, the association did not persist after adjustment for birth weight, highlighting the importance of prenatal exposures.


Transformation of chenodeoxycholic acid and ursodeoxycholic acid by human intestinal bacteria.
Feces from normal subjects and patients with cerebrotendinous xanthomatosis were incubated anaerobically with labeled chenodeoxycholic acid and ursodeoxycholine acid for known periods, and the bile acids formed were analyzed by TLC and scintillation counting. In the normal subjects, 80% of the chenodeoxycholic acid and 41% of the ursodeoxycholic acid were 7-dehydroxylated to lithocholic acid during 2 hr of incubation. In contrast, the fecal flora of the CTX patients transformed only 5% of chenodeoxycholic acid and less than 1% of ursodeoxycholic acid to lithocholic acid during the same time period. In several subjects (normals and CTX), the intestinal flora converted chenodeoxycholic acid to ursodeoxycholic acid without the accumulation of the hypothetical intermediate 7-ketolithocholic acid (3 alpha-hydroxy-7-keto-5 beta-cholanoic acid). These results indicate that the fecal bacterial flora is capable of 7-dehydroxylating chenodeoxycholic acid and ursodeoxycholic acid to yield lithocholic acid. Apparently the enzymes involved are relatively stereospecific since the 7 beta-hydroxy group of ursodeoxycholic acid was removed more slowly than the 7 alpha-hydroxy group of chenodeoxycholic acid.


Site-specific characterization of the Asp- and Glu-ADP-ribosylated proteome.
Poly(ADP-ribosyl)ation is catalyzed by a family of enzymes known as PARPs. We describe a method to characterize the human aspartic acid- and glutamic acid-ADP-ribosylated proteome. We identified 1,048 ADP-ribosylation sites on 340 proteins involved in a wide array of nuclear functions; among these were many previously unknown PARP downstream targets whose ADP-ribosylation was sensitive to PARP inhibitor treatment. We also confirmed that iniparib had a negligible effect on PARP activity in intact cells.


Reduction of FeII(EDTA)-NO by Mn powder in wet flue gas denitrification technology: stoichiometry, kinetics, and thermodynamics.
Conversion of FeII(EDTA)-NO or FeIII(EDTA) into FeII(EDTA) is a key process in a wet flue gas denitrification technology with FeII(EDTA) solution. In this work, the stoichiometry, kinetics, and thermodynamics of FeII(EDTA)-NO reduction by Mn powder were investigated. We first studied the FeII(EDTA)-NO reduction and product distribution to speculate a possible stoichiometry of FeII(EDTA)-NO reduction by Mn powder. Then, the effects of major influencing factors, such as pH value, temperature, and Mn concentration, were studied. The pseudo-second-order model was established to describe the FeII(EDTA)-NO reduction. Simultaneously, according to Arrhenius and Eyring-Polanyi equations, the reaction activation energy (Ea), enthalpy of activation (∆H‡), and entropy of activation (∆S‡) were calculated as 23.68 kJ/mol, 21.148 kJ/mol, and - 149.728 J/(k mol), respectively. Additionally, simultaneous reduction of FeIII(EDTA) and FeII(EDTA)-NO was investigated to better study the mechanism of FeII(EDTA) regeneration, suggesting that there was a competition between the two reduction processes. Finally, a simple schematic mechanism of NO absorption by FeII(EDTA) combined with regeneration of manganese ion and ammonium was proposed. These fundamental researches could offer a valuable guidance for wet flue gas denitrification technology with FeII(EDTA) solution.


Increased cholesterylester transfer activity in complicated type 1 (insulin-dependent) diabetes mellitus--its relationship with serum lipids.
In Type 1 (insulin-dependent) diabetes mellitus, macrovascular complications and the increased risk for cardiovascular disease in patients with microvascular complications may be related to alterations in plasma cholesterylester transfer. The activity of cholesterylester transfer protein, which mediates cholesterylester transfer between lipoproteins and lipoprotein lipid levels, was assessed in 7 normolipidaemic control subjects, 7 Type 1 diabetic control subjects without complications, 11 Type 1 diabetic patients with microvascular complications (retinopathy, incipient nephropathy) and in 7 Type 1 diabetic patients with macrovascular atherosclerotic lesions. The cholesterylester transfer activity was 30% higher in the diabetic groups with macrovascular and microvascular lesions than in the 2 control groups. Very low + low density lipoprotein cholesterol was higher in the 3 diabetic groups than in the non-diabetic control group. High density lipoprotein cholesterol was not different. The cholesterylester transfer activity was correlated positively with HbA1, urinary albumin excretion rate, serum cholesterol, very low + low density lipoprotein cholesterol and apolipoprotein B. The high density lipoprotein over very low + low density lipoprotein cholesterylester molar ratio was lower in the diabetic groups with micro- and macrovascular complications. A role for cholesterylester transfer activity in the lipoprotein abnormalities found in complicated Type 1 diabetes is suggested. A high cholesterylester transfer activity might be indicative of mechanisms which promote atherogenesis.


IgE-mediated anaphylaxis and allergic reactions to idursulfase in patients with Hunter syndrome.
Enzyme replacement therapy (ERT) with recombinant human idursulfase is effective for the treatment of Hunter syndrome, mucopolysaccharidosis (MPS) type II. However, various adverse events can occur by the infusion of idursulfase. The purpose was to evaluate the occurrence of infusion-related allergic reactions, including anaphylaxis, to idursulfase in patients with MPS II receiving ERT and to elucidate its possible mechanism. A total of 34 patients with MPS II were enrolled to receive ERT with Elaprase(®) at a dose of 0.5 mg/kg intravenously once a week. Information regarding the symptoms, frequency, and timing of anaphylaxis during treatment was analyzed. Presence of anti-idursulfase IgE antibody was assessed by skin prick test (SPT) and enzyme-linked immunosorbent assay (ELISA). Western blotting was performed to confirm the reaction between idursulfase and specific IgE. Three patients (8.8%) showed anaphylaxis by infusion of idursulfase. No deaths occurred during the study. Anti-idursulfase IgE antibody was detected by SPT and ELISA. Immunoblotting with patients' sera and Elaprase(®) showed a single band of specific IgE binding to the protein around 70 kD, and idursulfase did not display amino acid sequence homology to known allergens. SPT with idursulfase demonstrated positive results in all patients with anaphylaxis. However, we failed to reveal any risk factors for the development of infusion-related immediate-type allergic reactions. Anaphylaxis related to infusion of idursulfase is mediated by anti-idursulfase IgE antibody, which might be produced by de novo synthesis. SPT is useful in predicting the occurrence of anti-idursulfase IgE-mediated anaphylaxis during infusion.


Associations between pigment epithelium-derived factor, insulin resistance and high density lipoprotein.
To measure serum pigment epithelium-derived factor in control subjects with normal fasting glucose, and in subjects with impaired fasting glucose and those with newly diagnosed Type 2 diabetes, before treatment initiation, and to measure pigment epithelium-derived factor prospectively in patients being treated with HDL-raising therapy, niacin. We enrolled 89 individuals attending an institutional health screen. Biochemical indices including lipids, homeostasis model assessment-insulin resistance, high-sensitivity C-reactive protein and pigment epithelium-derived factor were analysed in fasting blood. To validate the association between HDL and pigment epithelium-derived factor, we analysed samples from a separate study cohort with low HDL, followed up for 12-weeks while on niacin treatment. Secreted pigment epithelium-derived factor from 3T3-L1 adipocytes, after HDL treatment (24-h), was measured using Western blot analysis. Mean (± sd) serum pigment epithelium-derived factor was significantly higher in subjects with impaired fasting glucose [13.99 (± 3.06) μg/ml] and Type 2 diabetes [12.94 (± 2.61)] μg/ml, compared with control subjects [11.83 (± 2.85) μg/ml (P = 0.014)]. In multivariate analyses, serum pigment epithelium-derived factor concentration was associated with BMI (β = 0.32, 0.007), homeostasis model assessment-insulin resistance (β = 0.33, P = 0.01) and HDL (β = -0.24, P = 0.05), after adjustment for age, gender and high-sensitivity C-reactive protein. In the niacin study, on-treatment HDL was an independent determinant of pigment epithelium-derived factor (β = -0.439, P = 0.033), after adjusting for age, homeostasis model assessment-insulin resistance and treatment. Adipocytes treated with HDL were found to have reduced pigment epithelium-derived factor secretion [24.8% (50 μg/ml), 28.4% (100 μg/ml) HDL; P < 0.05)], compared with the control samples. Serum pigment epithelium-derived factor is positively associated with homeostasis model assessment-insulin resistance and negatively associated with HDL. Further studies are needed to understand the mechanism of low HDL and raised pigment epithelium-derived factor and to determine if they are causally related to the pathobiology of insulin resistance.


[Application of vacuum-assisted venous drainage technology in minimally invasive cardiac surgery].
To summarize the method and experience of cardiopulmonary bypass (CPB) with vacuum-assisted venous drainage technology (VAVD) in the minimally invasive cardiac surgery (MICS). 35 cases of patients undergoing MICS were achieved femoral arterial cannula and femoral venous cannula. During the course of the CPB, we used the VAVD technology. At the same time, we selected 35 cases as control group.The time of the CPB, mechanical ventilation and ICU, and the amount of the urine, blood products, and chest drainage were recorded. The time of mechanical ventilation and ICU staying, the volume of the blood products and the volume drainage within 48 h postoperatively in the MICS group were significantly shorter and less than that in control group (P < 0.05). The use of VAVD in the MICS can increase the vena cava drainage effectively, and ensure the surgery safe and successful.


Purification, kinetic studies, and homology model of Escherichia coli fructose-1,6-bisphosphatase.
Previous kinetic characterization of Escherichia coli fructose 1,6-bisphosphatase (FBPase) was performed on enzyme with an estimated purity of only 50%. Contradictory kinetic properties of the partially purified E. coli FBPase have been reported in regard to AMP cooperativity and inactivation by fructose-2,6-bisphosphate. In this investigation, a new purification for E. coli FBPase has been devised yielding enzyme with purity levels as high as 98%. This highly purified E. coli FBPase was characterized and the data compared to that for the pig kidney enzyme. Also, a homology model was created based upon the known three-dimensional structure of the pig kidney enzyme. The kcat of the E. coli FBPase was 14.6 s(-1) as compared to 21 s(-1) for the pig kidney enzyme, while the K(m) of the E. coli enzyme was approximately 10-fold higher than that of the pig kidney enzyme. The concentration of Mg2+ required to bring E. coli FBPase to half maximal activity was estimated to be 0.62 mM Mg2+, which is twice that required for the pig kidney enzyme. Unlike the pig kidney enzyme, the Mg2+ activation of the E. coli FBPase is not cooperative. AMP inhibition of mammalian FBPases is cooperative with a Hill coefficient of 2; however, the E. coli FBPase displays no cooperativity. Although cooperativity is not observed, the E. coli and pig kidney enzymes show similar AMP affinity. The quaternary structure of the E. coli enzyme is tetrameric, although higher molecular mass aggregates were also observed. The homology model of the E. coli enzyme indicated slight variations in the ligand-binding pockets compared to the pig kidney enzyme. The homology model of the E. coli enzyme also identified significant changes in the interfaces between the subunits, indicating possible changes in the path of communication of the allosteric signal.


Synthetic plant promoters containing defined regulatory elements provide novel insights into pathogen- and wound-induced signaling.
Pathogen-inducible plant promoters contain multiple cis-acting elements, only some of which may contribute to pathogen inducibility. Therefore, we made defined synthetic promoters containing tetramers of only a single type of element and present evidence that a range of cis-acting elements (boxes W1, W2, GCC, JERE, S, Gst1, and D) can mediate local gene expression in planta after pathogen attack. The expression patterns of the promoters were monitored during interactions with a number of pathogens, including compatible, incompatible, and nonhost interactions. Interestingly, there were major differences in the inducibilities of the various promoters with the pathogens tested as well as differences in the speed of induction and in the basal expression levels. We also show that defense signaling is largely conserved across species boundaries at the cis-acting element level. Many of these promoters also direct local wound-induced expression, and this provides evidence for the convergence of resistance gene, nonhost, and wound responses at the level of the promoter elements. We have used these cis-acting elements to construct improved synthetic promoters and show the effects of varying the number, order, and spacing of such elements. These promoters are valuable additions to the study of signaling and transcriptional activation during plant-pathogen interactions.


An efficient and economic enhancer mix for PCR.
Polymerase chain reaction (PCR) has become a fundamental technique in molecular biology. Nonetheless, further improvements of the existing protocols are required to broaden the applicability of PCR for routine diagnostic purposes, to enhance the specificity and the yield of PCRs as well as to reduce the costs for high-throughput applications. One known problem typically reported in PCR experiments is the poor amplification of GC-rich DNA sequences. Here we designed and tested a novel effective and low-cost PCR enhancer, a concentration-dependent combination of betaine, dithiothreitol, and dimethyl sulfoxide that broadly enhanced the quantitative and/or qualitative output of PCRs. Additionally, we showed that the performances of this enhancer mix are comparable to those of commercially available PCR additives and highly effective with different DNA polymerases. Thus, we propose the routine application of this PCR enhancer mix for low- and high-throughput experiments.


The relationship between vitamin D levels in seasonal variations and Chinese patients with first-episode drug-naive depression.
Vitamin D deficiency is highly prevalent worldwide and is associated with various diseases, including depression. Previous studies on vitamin D and depression have different conclusions. Our study aimed to examine the association between vitamin D levels in seasonal variation and depression. A total of 324 patients with first-episode depression aged 18-50 years were recruited for our study. Vitamin D levels were recorded, and PHQ-9 scale evaluation was performed in different seasons. Seasonal variations in vitamin D levels and depressive symptoms were examined. The cohort comprised 77 males and 247 females. 98.1% of patients had insufficient or deficient vitamin D levels. The median vitamin D level was 12 ng/mL; 14.5 ng/mL in summer and 13 ng/mL in autumn, which was significantly higher than 9 ng/mL in spring, and the correlation between vitamin D level and PHQ-9 score was more significant in spring but not in summer and autumn. Our study used cross-sectional data and could not examine the causal relationship of the vitamin D level and depressive symptoms. There are also some possible influencing factors, such as the dietary habits, outdoor sports, and the use of sunscreen were not investigated. Observational data showed that the vitamin D level of depression is lower than the normal (30 ng/mL), and it is closely related to depressive symptoms in spring. The seasonal variations in vitamin D levels might play a critical role in Chinese patients with first-episode depression.


Effects of differences in media and methods on MIC values for anaerobes.
In vitro susceptibility of Bacteroides fragilis isolates to cefoxitin at the breakpoint of 32 micrograms/ml varied little when tested by eight different methods. We found that broth disk elution results were difficult to read and interpret and did not correlate with other methods.


Emergency Cricothyrotomy in a Harsh Environment: A Case Report of Complete Airway Obstruction Following a Lightning Strike.
A lightning strike is an extreme event with the highest mortality rate among electrical injuries. Death from a lightning strike is caused by either cardiac arrest or respiratory arrest. It is rare for upper airway damage to occur, but in these cases, airway control is recommended. If transoral intubation is unsuccessful, an emergency cricothyrotomy should be considered. Our case report describes an emergency cricothyroidotomy performed in a harsh environment on a mountain 2300 m above sea level on a patient with extensive burns of his supraglottic structures, after being directly hit by a lightning strike.


Seasonal variations in acidogenic fermentation of filter primary sludge.
Primary treatment of municipal wastewater by rotating belt filtration followed by hydrolysis and acidogenic fermentation of the filter primary sludge (FPS) at ambient temperature was studied at pilot-scale during one year. The seasonal variations of volatile fatty acids (VFAs), nutrient release and soluble COD production as well as microbial community assembly were assessed, leading to novel findings for fermentation at ambient temperature. The reproducibility of VFA production performance was first established by operating the two fermentation reactors under the same conditions, showing similar results regarding VFA production and microbial community structure. One year of operation at 5 d retention time (RT) and 16-29 °C resulted in an average VFA yield of 180±35 mg COD/g VSin and soluble COD yield of 242±40 mg COD/g VSin. The VFA formation was temperature-dependent, with ϴ=1.033±0.005 ( [Formula: see text] . The seasonal variations of the acetic and propionic acid productions were pronounced, whereas the productions of VFAs with longer chains were more stable regardless of temperature. The community structure of the reactor microbiomes was also clearly affected by season and temperature and linked with the production spectrum of VFAs. The ammonium and phosphate releases were stable during the year, leading to a decrease in ratios of soluble COD to NH4+-N and PO43--P during winter. The soluble COD yield was 11% and 27% higher at 5 d RT compared to 3 and 2 d RT respectively, but the corresponding volumetric productivities were lower. The dissimilarities between microbiomes in influent FPS and fermenters were significant even at a short RT of 2 d, and increased with longer RT of 3 and 5 d, primarily caused by selection of bacteria within Bacteroidota in the fermentation reactors.


Lactoferrin-Decorated Cerium Oxide Nanoparticles Prevent Renal Injury and Fibrosis.
Renal fibrosis is a hallmark feature of chronic kidney diseases (CKDs). However, despite the increased prevalence of renal fibrosis, there is no approved antifibrotic drug for the management of renal fibrosis. Cerium oxide nanoparticles (CONPs) have been demonstrated to possess a number of properties including antioxidant, anti-inflammatory and nephroprotective activity. As the kidneys are rich in lactoferrin (Lf) receptors, we synthesised the lactoferrin-CONP (Lf-CONP) system to be used for active targeting of the kidneys and provide antifibrotic effects of CONPs to the kidneys. We used the unilateral ureteral obstruction (UUO)-induced renal fibrosis model and treated the animals with Lf-CONP to observe the antifibrotic effects of Lf-CONP. Lf-CONP was found to inhibit the progression of renal fibrosis in a superior manner when compared to CONPs alone.


Residues in the longitudinal, hydrophobic strip-of-helix relate to terminations and crossings of alpha-helices.
An alpha-helix terminates when the virtual extension of its most hydrophobic, longitudinal strip containing Leu, Ile, Val, Phe, and Met lacks those residues. In each of 247 helices a template was fitted to maximize the mean hydrophobicity of positions forming a longitudinal strip-of-helix. The template was then extended into sequences beyond the ends of the helices. Leu, Ile, Val, Phe, and Met occurred in positions in the longitudinal strip-of-helix at an increased frequency (p less than 0.001), but in the first and second positions beyond either end of each true helix, they occurred at the same frequency as for their empirical distribution over all the proteins. Excesses of Asp and Glu were found in the N-terminal loop, and of Arg, His, and Lys in specific positions about the C terminus of helices. The longitudinal hydrophobic strip, the smallest amino acid in that strip, and charged amino acids in that strip, related to rotational and longitudinal orientation of alpha-helices in 15 proteins. Adjacent helices generally crossed through their longitudinal hydrophobic strips. They usually crossed through the smallest residue in the strip. Charged residues, when they occurred in the strips, were excluded from the crossing regions.


Drug related hospital admissions. Results from an intervention program.
As part of a high-intensity monitoring study of drug events as the cause of admission to departments of internal medicine, the effect of an educational intervention programme was studied. Two departments were included, one specialising in geriatrics and one that received patients by non-selected referral. The series consisted of 607 consecutive admissions studied before and 703 after the intervention. The drug events considered were adverse drug reactions and dose-related therapeutic failures, mainly due to non-compliance. A modest, statistically non-significant decrease in drug related hospital admissions (DRH) was seen, from 14% before to 13% after the intervention period. However, DRHs classified as definitely avoidable showed the significant decrease of 83%. There was no apparent relationship between the topics selected for the intervention programme and changes in the pattern of DRHs. No relationship between alterations in sales data and hospital admissions caused by a given drug could be demonstrated. A blinded external evaluation of case abstracts did not disclose any significant shift in the investigators' assessments. The intervention may have had an non-specific effect on avoidable DRHs.


Hemodynamic advantage of left atrial epinephrine administration after cardiac operations.
Cardiac surgical patients frequently require catecholamines, typically administered via the central venous circulation. Potential disadvantages of this route of administration include catecholamine metabolism by the pulmonary vascular bed before gaining access to the heart and pulmonary vasoconstriction producing increased pulmonary vascular resistance. We therefore prospectively compared administration of epinephrine via the left atrium versus central venous administration of epinephrine with particular interest in cardiac output, mean pulmonary artery pressure, and pulmonary vascular resistance. Fifteen consecutive aortocoronary bypass patients were studied after cardiopulmonary bypass. Epinephrine (mean dose, 0.07 +/- 0.02 micrograms.kg-1.min-1) was administered via the central venous route, then via the left atrium, then via the central venous route again. Hemodynamic data were collected 10 minutes after changing the route of administration. Left atrial administration of epinephrine produced a 35% greater cardiac output, 25% lower pulmonary artery pressure, and 32% lower pulmonary vascular resistance when compared with central venous administration (all significant; p < 0.05). Left atrial epinephrine administration may offer hemodynamic advantage in cardiac surgical patients in whom central venous administration does not produce an adequate cardiac output or in patients with pulmonary hypertension to avoid any further increase in pulmonary vascular resistance.


Chloroquine protects mice from challenge with CpG ODN and LPS by decreasing proinflammatory cytokine release.
Bacterial DNA (bDNA) and lipopolysaccharide (LPS) are potent activators of immune cells such as monocytes and macrophages, which contribute to systemic inflammatory response syndrome (SIRS) and sepsis. To date, no effective anti-sepsis drugs have been developed for clinical use. Chloroquine (CQ), a diprotic weak base traditionally used for treating malaria, was recently shown to decrease cytokine release from macrophages induced by LPS and CpG oligonucleotide (CpG ODN). In the present study, Escherichia coli DNA (EC DNA), CpG ODN and LPS were used to induce SIRS/sepsis in animal models. We found that 30 mg/kg of CQ could protect mice from lethal challenge by CpG ODN and LPS, and 25 mg/kg of CQ could decrease serum TNF-alpha and IL-6 in rats injected with sublethal doses of CpG ODN and LPS. In addition, treatment of murine macrophage ANA-1 cells with 2 mM CQ potently inhibited the release of TNF-alpha, IL-6 and IL-12 induced by CpG ODN and LPS. In human peripheral blood mononuclear cells (hPBMC), 100-200 microM CQ almost completely abrogated release of both TNF-alpha and IL-6 induced by CpG ODN and LPS, whereas IL-6 release induced by EC DNA was not significantly affected by 50 microM CQ. Furthermore, CQ reduced the expression of TLR9 and TLR4 mRNA and the activation of NFkappaB and AP-1 stimulated by CpG ODN and LPS in ANA-1 cells. Flow cytometry and confocal microscopy revealed that CQ increased the accumulation of CpG ODN within ANA-1 cells without influence on its uptake, suggesting that the delayed degradation of CpG ODN was associated with the reduction of proinflammatory cytokine release from the cells. Our results demonstrated that CQ-mediated protection of lethal challenge by CpG ODN and LPS was associated with the reduction of proinflammatory cytokine release.


A closer look into close packing: pentacoordinated silicon in a high-pressure polymorph of danburite.
Due to their high technological and geological relevance, silicates are one of the most studied classes of inorganic compounds. Under ambient conditions, the silicon in silicates is almost exclusively coordinated by four oxygen atoms, while high-pressure treatment normally results in an increase in the coordination from four- to sixfold. Reported here is a high-pressure single-crystal X-ray diffraction study of danburite, CaB2Si2O8, the first compound showing a step-wise transition of Si coordination from tetrahedral to octahedral through a trigonal bipyramid. Along the compression, the Si2O7 groups of danburite first transform into chains of vertice-sharing SiO5 trigonal bipyramids (danburite-II) and later into chains of edge-sharing SiO6 octahedra (danburite-III). It is suggested that the unusual formation of an SiO5 configuration is a consequence of filling up the pentacoordinated voids in the distorted hexagonal close packing of danburite-II.


Retracted: Effect of Stereotactic Body Radiation Therapy Combined with Thermoplastic Fixation on Set-Up Errors in Breast Cancer Patients Undergoing Radiotherapy.
[This retracts the article DOI: 10.1155/2022/8370842.].


Dynamics of Akt activation during mouse embryo development: distinct subcellular patterns distinguish proliferating versus differentiating cells.
Akt is a highly conserved serine-threonine protein kinase which has been implicated in a wide variety of cellular functions, from the regulation of growth and metabolism, to activation of pro-survival pathways and cell proliferation, and promotion of differentiation in specific cell types. However, very little is known about the spatial and temporal pattern of Akt activity within cells and whether this pattern changes as cells enter and proceed in their differentiation programs. To address this issue we profiled Akt activation in E8.5-E13.5 mouse embryos and in C2C12 cells. We used a commercial antibody against Akt, phosphorylated on one of its activating residues, Thr-308, and performed high resolution confocal imaging of the immunofluorescence in labeled embryos. We observe strong Akt activity during mitosis in the dermomyotome, the neuroepithelium and some mesenchymal cells. This burst of activity fills the whole cell except for heterochromatin-positive areas in the nucleus. A surge in activity during mitosis is also observed in subconfluent C2C12 cells. Later on in the differentiation programs of skeletal muscle and neural cells, derivatives of the dermomyotome and neuroepithelium, respectively, we find robust, sustained Akt activity in the cytoplasm, but not in the nucleus. Concomitantly with skeletal muscle differentiation, Akt activity becomes concentrated in the sarcomeric Z-disks whereas developing neurons maintain a uniform cytoplasmic pattern of activated Akt. Our findings reveal unprecedented cellular and subcellular details of Akt activity during mouse embryo development, which is spatially and temporally consistent with proposed functions for Akt in mitosis and myogenic and neural differentiation and/or survival. Our results thus demonstrate a subcellular change in the pattern of Akt activation when skeletal muscle and neural progenitor cells cease dividing and progress in their differentiation programs.


Trypan blue staining of epiretinal membranes in proliferative vitreoretinopathy.
To determine whether trypan blue staining facilitates epiretinal membrane (ERM) removal in proliferative vitreoretinopathy. In 10 patients undergoing vitrectomy for proliferative vitreoretinopathy, ERM peeling was performed without staining the tissue, until no additional ERMs were clearly visible. Then, after a fluid-air exchange, 0.06% trypan blue solution was applied onto the retinal surface. After 1 minute, all excess dye was removed and, after an air-fluid exchange, ERM peeling was completed. Excised ERM specimens were analyzed by transmission electron microscopy. For each patient, the efficacy of trypan blue staining of ERMs during surgery was scored. In all patients, intraoperative staining of ERMs with trypan blue was found to be a useful adjunct, since the dye consistently improved direct visualization and delineation of ERMs and facilitated ERM removal. A clear contrast was created between the stained ERMs and the nonstaining, underlying retina. Electron microscopy showed that only ERM tissue was removed. No adverse reactions related to the use of the dye were observed up to 3 months after surgery. Trypan blue may be an important new tool in the surgical management of proliferative vitreoretinopathy, since it may allow a more complete and safer ERM removal.


Broader utilization of origins of DNA replication in cancer cell lines along a 78 kb region of human chromosome 2q34.
Human DNA replication depends on the activation of thousands of origins distributed within the genome. The actual distribution of origins is not known, nor whether this distribution is unique to a cell type, or if it changes with the proliferative state of the cell. In this study, we have employed a real-time PCR-based nascent strand DNA abundance assay, to determine the location of origins along a 78 kb region on Chr2q34. Preliminary studies using nascent DNA strands isolated from either HeLa and normal skin fibroblast cells showed that in both cell lines peaks of high origin activity mapped in similar locations. However, the overall origin profile in HeLa cells corresponded to broad origin activation zones, whereas in fibroblasts a more punctuated profile of origin activation was observed. To investigate the relevance of this differential origin profile, we compared the origin distribution profiles in breast cancer cell lines MDA-MB-231, BT-474, and MCF-7, to their normal counterpart MCF-10A. In addition, the CRL7250 cell line was also used as a normal control. Our results validated our earlier observation and showed that the origin profile in normal cell lines exhibited a punctuated pattern, in contrast to broader zone profiles observed in the cancer cell lines. A quantitative analysis of origin peaks revealed that the number of activated origins in cancer cells is statistically larger than that obtained in normal cells, suggesting that the flexibility of origin usage is significantly increased in cancer cells compared to their normal counterparts.


What Are the Key Diagnostic Cognitive Impairment and Dementia Subtypes and How to Integrate all of the Diagnostic Data to Establish a Diagnosis?
Diagnosis of dementia requires a detailed history, physical examination, imaging, and sometimes neuropsychological testing or ancillary tests. Mild cognitive impairment is defined as an objective impairment in cognitive performance but preserved ability to do activities of daily living. Dementia is diagnosed once impairment in activities of daily living develops. Common types of dementia covered here include mild cognitive impairment, Alzheimer's disease, Lewy body dementia, frontotemporal dementia, the primary progressive aphasias, and vascular dementia.


Limit cycle dynamics can guide the evolution of gene regulatory networks towards point attractors.
Developmental dynamics in Boolean models of gene networks self-organize, either into point attractors (stable repeating patterns of gene expression) or limit cycles (stable repeating sequences of patterns), depending on the network interactions specified by a genome of evolvable bits. Genome specifications for dynamics that can map specific gene expression patterns in early development onto specific point attractor patterns in later development are essentially impossible to discover by chance mutation alone, even for small networks. We show that selection for approximate mappings, dynamically maintained in the states comprising limit cycles, can accelerate evolution by at least an order of magnitude. These results suggest that self-organizing dynamics that occur within lifetimes can, in principle, guide natural selection across lifetimes.


Exercise-induced expression of angiogenic growth factors in skeletal muscle and in capillaries of healthy and diabetic mice.
Diabetes has negative, and exercise training positive, effects on the skeletal muscle vasculature, but the mechanisms are not yet fully understood. In the present experiment the effects of running exercise on the mRNA expression of pro- and antiangiogenic factors were studied in healthy and diabetic skeletal muscle. The responses in capillaries and muscle fibers, collected from the muscle with laser capture microdissection, were also studied separately. Healthy and streptozotocin-induced diabetic mice were divided into sedentary and exercise groups. Exercise was a single bout of 1 h running on a treadmill. Gastrocnemius muscles were harvested 3 h and 6 h post exercise, and angiogenesis-related gene expressions were analyzed with real-time PCR. In addition to muscle homogenates, capillaries and muscle fibers were collected from the muscle with laser capture microdissection method and analyzed for vascular endothelial growth factor-A (VEGF-A) and thrombospondin-1 (TSP-1) mRNA expression. Of the proangiogenic factors, VEGF-A and VEGF receptor-2 (VEGFR-2) mRNA expression increased significantly (P < 0.05) in healthy skeletal muscle 6 h post exercise. VEGF-B also showed a similar trend (P = 0.08). No significant change was observed post exercise in diabetic muscles in the expression of VEGF-A, VEGFR-2 or VEGF-B. The expression of angiogenesis inhibitor TSP-1 and angiogenic extracellular matrix protein Cyr61 were significantly increased in diabetic muscles (P < 0.05-0.01). Capillary mRNA expression resembled that in the muscle homogenates, however, the responses were greater in capillaries compared to muscle homogenates and pure muscle fibers. The present study is the first to report the effects of a single bout of exercise on the expression of pro- and antiangiogenic factors in diabetic skeletal muscle, and it provides novel data about the separate responses in capillaries and muscle fibers to exercise and diabetes. Diabetic mice seem to have lower angiogenic responses to exercise compared to healthy mice, and they show markedly increased expression of angiogenesis inhibitor TSP-1. Furthermore, exercise-induced VEGF-A expression was shown to be greater in capillaries than in muscle fibers.


Impact of prohepcidin levels and iron parameters on early post-transplantation toxicities.
Recent reports show the adverse impact of pre-transplantation iron overload on the outcome of haematopoietic stem cell transplantation (HSCT). We studied the pre-transplantation serum iron (SI) parameters including prohepcidin levels - a regulatory peptide of systemic iron homeostasis - and their role in early post-transplantation toxicities in allogeneic HSCT recipients. One hundred consecutive patients [36 women and 64 men; median age 27·5 years (range 16-63 years)] who underwent allogeneic HSCT between September 2003 and October 2007 at Gazi University were included in the study. Pre-transplantation serum prohepcidin levels did not show correlation with SI parameters and interleukin-6 levels (P>0·05). Prohepcidin levels were inversely correlated with the National Cancer Institute grade of mucositis (P=0·060), neutropenic fever (P<0·001), and the number of days with febrile neutropenia (P=0·003). SI levels were correlated with the severity of hepatotoxicity (P=0·015) while pre-transplantation transferrin saturation levels were positively correlated with the severity of hepatotoxicity (P=0·055), pulmonary toxicity (P=0·032), and sinusoidal obstruction syndrome (P=0·049). Pre-transplantation serum ferritin levels were positively correlated with the development of sinusoidal obstruction syndrome (P=0·010) and inversely correlated with the day of neutrophil engraftment (P=0·012). Overall survival was 41·26% with a median follow-up time of 13 months (range 0·0-60 months). Pre-transplantation serum prohepcidin levels and iron overload were not associated with survival in Cox regression analysis. Our results suggest that pre-transplantation iron parameters and prohepcidin levels might predict some of the early post-transplantation toxicities, however, without an impact on overall survival.


Modified Buie amputation for extensive hemorrhoidal disease.
Radical anal surgery of the type described for complicated hemorrhoidal and mucosal prolapse has good to excellent anatomic and functional results in 90 per cent of patients. This has been demonstrated in a group of 100 consecutive patients followed for an average of more than two years.


Peripheral venous nutrition: the equal relevance of volume load and osmolarity in relation to phlebitis.
This study aimed to investigate the peripheral vein tolerance for total parenteral nutrition (TPN) and to point out the factors which induce phlebitis. TPN was administered from 'all-in-one' bags. Five different types of TPN were investigated, wherein the amounts of amino-acids, dextrose, lipids, osmolarity and volume were varied. Type I (829 mOsm/l) was a low energy (1570 NPE kcal) nutritive mixture of 2425 ml with 9.5 g N. Type II (842 mOsm/l) was an intermediate energy (1800 NPE kcal) mixture of 2525 ml with 9.5 g N. Type III (860 mOsm/l) contained 1800 NPE kcal and 13.5 g N in 2775 ml. Type IV (790 mOsm/l) was only a dilution of Type III with 250 ml water. Type V (1044 mOsm/l) covered normal energy needs (2000 NPE kcal) and 13.5 g N in 2580 ml. All bags contained standard amounts of electrolytes, vitamines, trace elements and heparin (1.000 IE/l). The infusion site was not changed until phlebitis developed or oral feeding could be started. Type I, II, III and IV were given to at least 30 patients, and Type V to only 11 patients because of an unacceptable high phlebitis rate (91% after 2.8 days). The phlebitis rate for Type I, II, III and IV was 4%, 12%, 24% and 27% respectively after 48h increasing to 14%, 37%, 55% and 73% respectively after 14 days. The mean infusion time and phlebitis rate were related to each component of the nutritive mixture. A poor relation was found between the phlebitis rate and the amount of amino-acids, dextrose or lipid respectively. Both osmolarity (with variabl volume) and volume (with variable osmolarity) correlated poorly with the phlebitis rate (r = 0.37 and 0.29 respectively). However, the osmolarity rate, defined as the number of milliOsmols infused per hour, correlated well with the phlebitis rate (r = 0.95). Our results demonstrate that the peripheral route can be used as a practical alternative for central venous administration, if the osmolarity rate is limited.


Structure of the products of condensation of hydroxylamine with trifluoromethyl-beta-diketones: assignments of the diastereotopic protons of the 4-methylene group in 5-hydroxy-5-trifluoromethyl-delta2-isoxazolines.
The combined use of 1H NMR spectroscopy with theoretical calculations of chemical shifts (GIAO) and coupling constants (B3LYP/6-311 ++G**) of a 5-hydroxy-5-trifluoromethyl-Delta2-isoxazoline has enabled solving the problem of the assignments of the diastereotopic protons in this compound. This result has been extended to 5-hydroxy-5-trifluoromethyl-Delta2-pyrazolines and the corresponding 5-trichloromethyl derivatives.


Effect of delayed supine positioning after induction of spinal anaesthesia for caesarean section.
The study tested the hypothesis that the incidence of hypotension during spinal anaesthesia for caesarean section is less in parturients who remain in the sitting position for 3 min compared with parturients who are placed in the modified supine position immediately after induction of spinal anesthesia. Spinal anaesthesia was induced with the woman in the sitting position using 2.8 ml hyperbaric bupivacaine 0.5% at the L(3-4) or L(2-3) interspace. Ninety-eight patients scheduled for elective caesarean section under spinal anaesthesia were randomised to assume the supine position on an operating table tilted 10 degrees to the left (modified supine position) immediately after spinal injection (group 0, n=52) or to remain in the sitting position for 3 min before they also assumed the modified supine position (group 3, n=46). Isotonic saline 2-300 ml was given intravenously over 15 min before spinal injection followed by 15 ml/kg over 15-20 min after induction of spinal anaesthesia. If the systolic blood pressure decreased to less than 70% of baseline or to less than 100 mmHg or if there was any complaint of nausea, ephedrine was given in 5 mg boluses intravenously every 2 min. The blood pressure decreased significantly in both groups following spinal injection (P<0.001). Blood pressure variations over time differed significantly between the two groups (P<0.05). However, the incidence of maternal hypotension before delivery was similar in the two groups. The difference was caused by the time to the blood pressure nadir being significantly shorter in group 0 compared with group 3 (9.1+/-4.5 min vs. 11.7+/-3.7 min, P<0.01). Similar numbers of patients received rescue with ephedrine before delivery: 35 (67%) in group 0 vs. 26 (57%) in group 3 (NS). The mean total dose of ephedrine before delivery was 10.9 mg in group 0 vs. 9.2 mg in group 3 (NS). There were no differences in neonatal outcome between the two groups. At elective caesarean section, a 3-min delay before supine positioning does not influence the incidence of maternal hypotension after induction of spinal anaesthesia in the sitting position with 2.8 ml of bupivacaine 0.5% with 8% dextrose.


Dermatofibrosarcoma Protuberans of the Neck: A Brief Review of the Literature.
Dermatofibrosarcome protuberance (DFSP) is a rare, slow growing soft tissue sarcoma with fibroblastic origin, which has a great, potential of local invasion and recurrence. Because of its unspecific appearance and slow growth features it is commonly misdiagnosed as other benign lesions that leads to a late accurate diagnosis or an inadequate initial treatment. A young female patient with DFSP on the neck who was initially misdiagnosed as lipoma and then underwent inadequate initial resection is presented in this case.


Intracellular Detection of Viral Transcription and Replication Using RNA FISH.
Many hemorrhagic fever viruses require BSL-3 or BSL-4 laboratory containment for study. The necessary safety precautions associated with this work often contribute to longer assay times and lengthy decontamination procedures. Here we will discuss recent advances in RNA fluorescence in situ hybridization (FISH) that not only allow entirely new investigations into the replication of these viruses but also demonstrate how this method can be applied to any virus with a known sequence and how it can be rapidly performed to minimize time spent in high containment. We have adapted existing protocols for mRNA detection with appropriate changes for examining viruses in a variety of containment laboratories (Shaffer et al., PLoS One 8:e75120, 2013; Raj et al., Nat Methods 5:877-879, 2008).


Pelvic floor dysfunction and its influencing factors during radiotherapy in cervical cancer survivors: A cross-sectional study.
Radiotherapy can negatively affect the pelvic floor function of patients with cervical cancer; however, the impact of different radiotherapy times and other related factors on pelvic floor function in cervical cancer survivors during radiotherapy remains unclear. We aimed to investigate the status of pelvic floor dysfunction (PFD) in cervical cancer survivors during radiotherapy and to analyze the factors influencing PFD. In this cross-sectional study, a convenience sampling method was used to recruit cervical cancer survivors undergoing radiotherapy from January 2022 to July 2022 at a tertiary first-class hospital located in northeastern China. The Pelvic Floor Distress Inventory-Short Form 20 was used for participants' self-report of their PFD during radiotherapy. Data from 120 cervical cancer survivors were included in this study. The results showed that the mean PFDI-20 total score was 32.69 ± 7.76. Multiple stepwise linear regression analysis showed that 56.9% of the variance in PFD was explained by age (β = 0.25, p < 0.001), body mass index (β = 0.32, p < 0.001), recurrence (β = 0.29, p < 0.001), number of radiotherapy sessions (β = 0.39, p < 0.001), and number of deliveries (β = 0.35, p < 0.001). It is important to pay more attention to the PFD status of cervical cancer survivors receiving radiotherapy. Future therapeutic approaches should involve early identification of relevant risk factors early to provide patients with personalized care at different stages of radiotherapy for reducing their discomfort and improving their health-related quality of life.


Preparation of magnesium ferrite nanoparticles by ultrasonic wave-assisted aqueous solution ball milling.
Magnesium ferrite, MgFe2O4 nanoparticles with high saturation magnetization were successfully synthesized using ultrasonic wave-assisted ball milling. In this study, the raw materials were 4MgCO3·Mg(OH)2·5H2O and Fe2O3 powders and the grinding media was stainless steel ball. The average particle diameter of the product MgFe2O4 powders was 20 nm and the saturation magnetization of them reached 54.8 emu/g. The different results of aqueous solution ball milling with and without ultrasonic wave revealed that it was the coupling effect of ultrasonic wave and mechanical force that played an important role during the synthesis of MgFe2O4. In addition, the effect of the frequency of the ultrasonic wave on the ball milling process was investigated.


A novel weight-bearing strengthening program during rehabilitation of older people is feasible and improves standing up more than a non-weight-bearing strengthening program: a randomised trial.
What is the feasibility and effectiveness of a novel weight-bearing strengthening program compared with that of a traditional non-weight-bearing strengthening program for older inpatients undergoing rehabilitation? Randomised, controlled trial with concealed allocation, assessor blinding, and intention-to-treat analysis. Eighty-eight inpatients (11% loss to follow-up) aged on average 82 years old from three rehabilitation units with no contraindications to exercise. Both the weight-bearing and non-weight-bearing strengthening programs were supervised by physiotherapists and were of similar intensities (10 to 15 RM) for two weeks. The primary outcomes were standing up performance measured as minimum chair height, and strength measured as maximum isometric knee extensor force of both legs. The secondary outcomes were other mobility measures such as standing-up rate, walking, standing and overall mobility, and other strength measures such as maximum isometric hip extensor, hip abductor, and knee flexor force of both legs. After the two-week intervention, the weight-bearing strengthening group had decreased their minimum chair height by 5.3 cm (95% CI 0.7 to 9.8) and increased their hip extensor strength on the weaker leg by 9 N (95% CI 1 to 17) more than the non-weight-bearing strengthening group. There were no clinically-worthwhile or statistically-significant differences between the groups for any other measures. This novel weight-bearing strengthening program was feasible and safe in an inpatient rehabilitation setting and had some additional benefits over a traditional non-weight-bearing strengthening program.


Preoperative Neutrophil-to-Lymphocyte Ratio Level is a Predictor of Postoperative Fertility in Infertile Patients with Ovarian Endometrioma.
To investigate the predictive efficacy of the preoperative neutrophil-lymphocyte ratio (NLR) for natural pregnancy outcome after laparoscopic cystectomy in infertile patients with ovarian endometrioma (OMA). Current evidence suggests that endometriosis likely induces local and systemic inflammatory processes. The NLR has been demonstrated to be of great utility in the diagnosis of endometriosis. However, the association between NLR and natural pregnancy outcome after laparoscopic surgery for endometriosis remains unknown. Data on infertile OMA patients undergoing laparoscopic surgery from January 2014 to October 2019 were retrospectively analyzed. Cox regression analysis was used to identify predictors of natural pregnancy outcome. A predictive model was then established using the nomogram. Among 217 patients, 115 patients (53.0%) experienced natural pregnancy after surgery. Compared with patients with pregnancy failure, those with pregnancy success had a significantly higher NLR (P < 0.05). Multivariate analysis revealed that age, least function (LF) score, and NLR were independent predictors of postoperative pregnancy (all P < 0.05). The NLA (NLR, LF score and age) scoring was then established and had a high predictive ability (AUC = 0.725). Patients were divided into three groups (low-, intermediate- and high-risk) based on the scoring, and the 1-year pregnancy rates were 43.5%, 34.4%, and 21.0%, respectively (P < 0.05). The preoperative NLR level was significantly associated with natural pregnancy outcome in infertile OMA patients after surgery. A predictive model combining NLR, LF score, and age could assist in the clinical decision-making process.


Feasibility, Utility, and Safety of Midodrine During Recovery Phase From Septic Shock.
We describe the feasibility, utility, and safety of oral midodrine to replace IV vasopressors during recovery from septic shock. This was a retrospective study performed in a medical ICU. All study subjects had a diagnosis of septic shock requiring at least 24 hours of IV vasopressors and demonstrated clinical stability with stable or decreasing doses of IV vasopressors. The two groups compared were those who received IV vasopressors only and those who received IV vasopressors with adjunctive midodrine. Of the 275 study patients, 140 received an IV vasopressor only and 135 received midodrine in addition to an IV vasopressor. There was no difference between the groups' demographics (age, sex, Acute Physiology and Chronic Health Evaluation 4 score). Mean IV vasopressor duration was 3.8 days in the IV vasopressor only group and 2.9 days in the IV vasopressor with midodrine group (P < .001). An IV vasopressor was reinstituted after discontinuation in 21 of 140 (15%) patients in the IV vasopressor only group and in 7 of 135 (5.2%) patients in the IV vasopressor with midodrine group (P = .007). ICU length of stay was 9.4 days in the IV vasopressor only group and 7.5 days in the IV vasopressor with midodrine group (P = .017). There were no complications associated with midodrine use except transient bradycardia in one patient, which resolved upon discontinuation of midodrine. Midodrine may reduce the duration of IV vasopressors during recovery phase from septic shock and may be associated with a reduction in length of stay in the ICU.


Hepatic portal venous gas due to endoscopic sphincterotomy.
This report describes a patient with sickle cell disease and cholelithiasis with choledocholithiasis who developed benign hepatic portal venous gas following endoscopic sphincterotomy. The portal venous gas was rapidly absorbed without untoward sequelae.


A simple self-assembly nanomicelle based on brain tumor-targeting peptide-mediated siRNA delivery for glioma immunotherapy via intranasal administration.
The blood-brain barrier (BBB) has a key role in preventing drugs from entering the brain. Non-invasive intranasal drug delivery routes that bypass the BBB are increasing in popularity because of their ability to shorten the journey and reduce the loss of genetic drugs such as siRNA in transit. However, the complex synthesis and quality control process of most nose-to-brain delivery carriers and the limited mass production are the main obstacles to their clinical application. Here, we constructed a siRNA delivery system with simple synthesis and quality control methods using cholesterol-modified T7 (T7-C), in which T7 can bind to the transferrin receptor (TfR) expressed on glioma cells to target gliomas. In our results, T7-C had dual functions as a glioma-targeting carrier and immune adjuvant. As a targeted delivery carrier, T7-C intranasally delivered siRNA into the mouse brain through the olfactory bulb pathway and was taken up by glioma cells by the caveolin- and transferrin-dependent pathway. As an immune adjuvant, T7-C could promote DC maturation and combined with slit2 siRNA could promote polarization of M2 subtype macrophages to M1 subtype macrophages and then increase the proportion of effector T cells to remodel the tumor environment. In conclusion, T7-C with glioma targeting as a delivery system of slit2 siRNA showed a good therapeutic effect in the treatment of glioma after intranasal administration and had potential application prospects. STATEMENT OF SIGNIFICANCE: In contrast to the existing literature that uses complex materials to deliver drugs across the blood-brain barrier (BBB) in an invasive manner for glioma treatment, we developed a simple, self-assembling siRNA delivery system (T7-C) based on brain tumor-targeted T7 peptide to treat glioma by intranasal administration. T7-C/siRNA could reach the tumor site through the olfactory bulb route and adjust the "cold" tumor microenvironment to the "hot" tumor microenvironment and non-invasive intranasal delivery route could shorten the journey and reduce the loss of genetic drugs. Therefore, our design has good application prospects and is expected to serve as a general strategy for intranasal drug delivery in the treatment of brain tumors.


An r-strategist in Antarctic pack ice.
The Antarctic copepod Drescheriella glacialis, an inhabitant of sea ice, is the first polar invertebrate metazoan to have been cultured throughout its life cycle. We describe its demographic characteristics on the basis of a laboratory cohort study and correlative field data. When compared to its closest temperate-zone relatives, D. glacialis shows temperature compensation of developmental and reproductive rates. A genuine r-strategist in every respect, it does not fit established trends for Antarctic invertebrates but appears well adapted to the peculiar spatio-temporal variability of the sea ice habitat.


Long-term effects of restriction of intravenous fluid in adult ICU patients with septic shock.
To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC) trial. We conducted the pre-planned analyses of mortality, health-related quality of life (HRQoL) using EuroQol (EQ)-5D-5L index values and EQ visual analogue scale (VAS), and cognitive function using Mini Montreal Cognitive Assessment (Mini MoCA) test at 1 year. Deceased patients were assigned numerical zero for HRQoL as a state equal to death and zero for cognitive function outcomes as worst possible score, and we used multiple imputation for missing data on HRQoL and cognitive function. Among 1554 randomized patients, we obtained 1-year data on mortality in 97.9% of patients, HRQoL in 91.3%, and cognitive function in 86.3%. One-year mortality was 385/746 (51.3%) in the restrictive-fluid group versus 383/767 (49.9%) in the standard-fluid group, absolute risk difference 1.5%-points [99% confidence interval (CI) - 4.8 to 7.8]. Mean differences were 0.00 (99% CI - 0.06 to 0.05) for EQ-5D-5L index values, - 0.65 for EQ VAS (- 5.40 to 4.08), and - 0.14 for Mini MoCA (- 1.59 to 1.14) for the restrictive-fluid group versus the standard-fluid group. The results for survivors only were similar in both groups. Among adult ICU patients with septic shock, restrictive versus standard IV fluid therapy resulted in similar survival, HRQoL, and cognitive function at 1 year, but clinically important differences could not be ruled out.


Efficient coupling of a quantum cascade laser to a few-mode chalcogenide fiber: erratum.
The authors wish to acknowledge an additional funding source which was absent from our manuscript.


Agents used in the prevention and treatment of nonsteroidal anti-inflammatory drug-associated symptoms and ulcers.
Coprescription of gastroprotective agents is a common practice for patients requiring nonsteroidal anti-inflammatory drug (NSAID) therapy, although there is limited evidence that some of these agents are effective. The prostaglandin analog misoprostol and the proton pump inhibitor omeprazole appear to be efficacious in decreasing NSAID-associated ulcers. Misoprostol has also been shown to decrease NSAID-associated gastrointestinal (GI) complications by 40% compared with placebo. Despite the efficacy of these drugs, their effectiveness in the general population has not yet been adequately determined with respect to reduction of symptoms and improvement in patient quality of life. Sucralfate and bismuth appear to be largely ineffective, and histamine receptor antagonists, when given at traditional ulcer-healing doses, decrease symptoms and duodenal ulcers only. The issue of outcomes research, therefore, needs to be more fully incorporated into any analysis of the effectiveness or cost-effectiveness of the widespread clinical use of such gastroprotective drugs.


Weight gain prevention interventions in the Study of Novel Approaches to Weight Gain Prevention (SNAP) trial promote ideal cardiovascular health in young adults.
Cardiovascular health (CVH) declines in young adulthood. This study assessed whether weight gain prevention interventions promoted ideal CVH. Young adults (n = 599; age 18-35 years; BMI: 21.0-30.9 kg/m2 ) from a randomized controlled trial comparing two weight gain prevention interventions (self-regulation with large or small changes) and a self-guided control group completed anthropometric and clinical assessments at baseline and 2 years. CVH was quantified via the American Heart Association's Life's Simple 7 (LS7) number of ideal components met. Both interventions showed significant improvements in the average number of ideal LS7 components met at 2 years compared with control (pre- to post-treatment means; large change: 0.24, small change: 0.34, control: -0.2, p < 0.05). Moreover, a greater percentage of participants in both interventions improved by ≥1 ideal component (large change: 35%, small change: 37%, control: 29%) and a smaller percentage declined by ≥1 ideal component (large change: 16%, small change: 20%, control: 30%) compared with control. For individual LS7 components, the odds of having an ideal BMI and glucose varied by treatment condition at 2 years. Two weight gain prevention interventions led to improvements in ideal CVH at 2 years. Interventions explicitly focused on a broader constellation of LS7 domains might lead to even greater changes in CVH.


Characteristics of Carpal Tunnel Syndrome in Wild-Type Transthyretin Amyloidosis.
Carpal tunnel syndrome (CTS) is one of the most common extra-cardiac manifestations of wild-type transthyretin amyloidosis (wtATTR); however, the characteristics of CTS in this population remain poorly understood. This retrospective cohort study reports findings from a single-centre experience of comprehensive neurological screening at the time of wtATTR diagnosis by nerve conduction studies (NCS) and neurologist assessment. Seventy-nine patients underwent neurological screening, 73 (92%) males, mean age 79.2 ± 7.5 years. Seventy-four (94%) had electrodiagnostic findings of median neuropathy at the wrist (MNW), 37 (50%) of which had a prior diagnosis of CTS and 37 (50%) had a new diagnosis of MNW. Over half of wtATTR patients (42, 53%) had bilateral MNW on screening. Most with pre-existing CTS had bilateral disease (28, 76%) and underwent bilateral carpal tunnel release (CTR) (23, 62%) prior to screening. Twenty-one (19%) wrists had mild MNW, 43 (38%) moderate and 49 (43%) severe. Twenty-one (28%) wtATTR patients with MNW were asymptomatic, 10 of which (48%) had moderate disease. Nineteen (36%) wtATTR patients with symptomatic MNW had recurrent disease despite previous CTR. As a result of screening, 36 (68%) patients with symptomatic MNW were referred for CTR. MNW is exceptionally common at the time of wtATTR diagnosis, affecting 94% of our patients. Most had severe, bilateral MNW on NCS. Some were asymptomatic, despite having moderate disease. The rate of recurrence following CTR was observed to be higher in wtATTR patients than the general population.


Effect of noradrenaline on retinal blood flow in healthy subjects.
To gain insight into the role of circulating catecholamines on retinal blood flow in vivo. Nonrandomized, open, crossover design. In 10 healthy male subjects, tyramine and noradrenaline were administered in stepwise increasing doses. These doses were selected to induce comparable changes in systemic blood pressure. During each infusion step, retinal vessel diameter and retinal venous blood speed were measured with the Zeiss retinal vessel analyzer (Zeiss, Jena, Germany) and laser Doppler velocimetry, respectively. Retinal blood flow through a major temporal vein was calculated. As expected, tyramine and noradrenaline induced a systemic hypertensive response. Tyramine caused a moderate increase in noradrenaline plasma levels, whereas exogenous noradrenaline increased noradrenaline plasma levels more than 10-fold. Nevertheless, neither tyramine nor noradrenaline induced any effect on retinal hemodynamic parameters. These data indicate that even high levels of circulating noradrenaline have little impact on retinal vascular tone and retinal blood flow. Hence, the adrenergic system appears not to play a major role in retinal blood flow regulation.


NOXA, a sensor of proteasome integrity, is degraded by 26S proteasomes by an ubiquitin-independent pathway that is blocked by MCL-1.
Ubiquitin (Ub)-mediated proteasome-dependent proteolysis is critical in regulating multiple biological processes including apoptosis. We show that the unstructured BH3-only protein, NOXA, is degraded by an Ub-independent mechanism requiring 19S regulatory particle (RP) subunits of the 26S proteasome, highlighting the possibility that other unstructured proteins reported to be degraded by 20S proteasomes in vitro may be bona fide 26S proteasome substrates in vivo. A lysine-less NOXA (NOXA-LL) mutant, which is not ubiquitinated, is degraded at a similar rate to wild-type NOXA. Myeloid cell leukemia 1, but not other anti-apoptotic BCL-2 family proteins, stabilizes NOXA by interaction with the NOXA BH3 domain. Depletion of 19S RP subunits, but not alternate proteasome activator REG subunits, increases NOXA half-life in vivo. A NOXA-LL mutant, which is not ubiquitinated, also requires an intact 26S proteasome for degradation. Depletion of the 19S non-ATPase subunit, PSMD1 induces NOXA-dependent apoptosis. Thus, disruption of 26S proteasome function by various mechanisms triggers the rapid accumulation of NOXA and subsequent cell death strongly implicating NOXA as a sensor of 26S proteasome integrity.


Limitations of Resting-State Functional MR Imaging in the Setting of Focal Brain Lesions.
Methods of image acquisition and analysis for resting-state functional MR imaging (rsfMR imaging) are still evolving. Neurovascular uncoupling and susceptibility artifact are important confounds of rsfMR imaging in the setting of focal brain lesions such as brain tumors. This article reviews the detection of these confounds using rsfMR imaging metrics in the setting of focal brain lesions. In the near future, with the wide range of ongoing research in rsfMR imaging, these issues likely will be overcome and will open new windows into brain function and connectivity.


Meyer's surgical procedure for the treatment of lip carcinoma.
Lip carcinomas are generally treated by surgery. A reconstruction is often required if the resected segment exceeds one-third of the lip. Meyer's plasty is an alternate way of reconstructing the lower or upper lip. The aim of this study is to describe the technique, its indications and results. A retrospective review of all patients who underwent a Meyer's plasty in our institution is presented. Twenty-four consecutive patients were treated in Lausanne for T1 and T2 lip carcinomas between 1983 and 2001. Primary surgery associated with Meyer's plasty was performed in all cases. Data were collected from the medical records, and eight patients were recalled for clinical evaluation. The oncological, functional and aesthetic results were analyzed. The 5-year local control was 100%. Three patients developed metachronous lymph node metastasis. No patient died from the disease. A hindering microstomy was found in three cases, and two patients suffered from temporary oral leakage. No speech difficulty was encountered. The aesthetics was described as satisfying or good in 87% of the patients. Meyer's plasty following lip surgery of the upper or lower lip allows an aesthetic and functional one-stage reconstruction without compromising the oncological outcome.


A replica technique for the evaluation of human skin by scanning electron microscopy.
A detailed reproducible procedure has been developed for the replication of human skin for scanning electron-microscopic evaluation. Utilizing a test surface, a number of negative and positive materials were evaluated for consistence and clarity of replication. Optimal replication parameters were determined and the method was successfully applied to the evaluation of human skin in vivo. Furthermore, a method was established which permitted repetitive examination of selected skin sites. Experimental results suggest that this replicating procedure can be used to monitor changes in the stratum corneum over time, and extend the range of stratum corneum magnifications.


Laser scanning as a tool for assessment of HIV-related facial lipoatrophy: evaluation of accuracy and reproducibility.
Facial lipoatrophy (LA) is a common complication of highly active antiretroviral therapy (HAART). Research into causes and treatment of facial LA is hindered by the lack of an objective measurement tool. To evaluate the accuracy and reproducibility of three-dimensional laser scanning (LS) for estimating cheek volume changes. Paired laser scans were performed and the images superimposed using commercial software. The volume difference between images was computed within a circle of radius 25 mm placed in a standardized position over the cheek area. Accuracy was tested by scanning before and after known volumes of plasticine (0.5--5 mL) were applied to the cheek area of a mannequin to simulate volume change. Reproducibility was tested by repeated scanning of the mannequin with and without 2 mL of plasticine, and repeated scanning of 10 healthy subjects over the course of 1 week. The mean difference between actual and estimated volume change was small across the range of volumes tested [mean difference 0.08 mL; 95% confidence interval (CI)-0.36 to 0.20 mL). The coefficient of variation for repeated measurements of 2-mL volume change was 5.8%. The intraclass correlation coefficient for scan-to-scan variability was 0.812 (95% CI 0.515--0.947) and for day-to-day variability it was 0.764 (95% CI 0.332--0.935). Conclusions LS is an accurate and reproducible method for estimating cheek volume changes. It may be useful as an objective tool for assessment of facial LA in clinical research studies.


Food-triad: An index for sustainable consumption.
This study proposes an index for food labeling in order to promote sustainable consumption. The index is calculated by ranking multiple features from the environmental, health and nutritional dimensions of the target product in relation to a pre-set reference value; the obtained scores from each dimension are plotted in a radar chart resulting in a triangular area. An increase in area represents a greater impact. As examples, tuna and the potato-based foods at three different processing levels (in natura or minimally processed, processed and ultra-processed) were analyzed. For both cases, the index increases according to the processing grades and has proved to be capable of expressing in numbers and graphically a wide range of environmental, nutritional and health issues.


Detection of murine intestinal adenomas using targeted molecular autofluorescence.
There is a significant need for noninvasive methods of evaluating dysplastic and neoplastic lesions in the luminal gastrointestinal tract. We have optimized an approach based on autofluorescence to study dysplastic adenomatous polyps in Apc(min/+) mice. We made recordings from both normal intestinal mucosa and from polyps using a xenon lamp-based fiberoptic device. Seventy-eight polyps in 11 mice revealed an increase in mean autofluorescence intensity ratios of 1.29 +/- 0.04 (72 small intestinal polyps; P < 0.0001) and 1.28 +/- 0.05 (6 colon polyps; P = 0.0016). Serial measurements of autofluorescence discriminated polyps from normal mucosa with a sensitivity, verified histologically, of 95%. To understand the chemical basis for increased autofluorescence, we examined the tryptophan content of intestinal polyps and the adjacent normal mucosa in a small subset of animals. The findings revealed an increased concentration of tryptophan in polyps (990 +/- 240 ng/mg) compared to normal mucosa (720 +/- 150 ng/mg; P = 0.03). In conclusion, these findings suggest that autofluorescence intensity increases in the setting of intestinal neoplasia and can be used to detect adenomas in the mouse intestine in real time.


Expression of the transcription factor 7-like 2 gene (TCF7L2) in human adipocytes is down regulated by insulin.
Variants in the TCF7L2 gene (transcription factor 7-like 2) have shown strong association with type 2 diabetes with two defined risk haplotypes, HapA and HapB(T2D). TCF7L2 may play a role in both glucose homeostasis and adipogenesis. Our aim was to characterize the TCF7L2 mRNA expression and regulation in human adipose tissue. We quantified TCF7L2 mRNA levels in cultured human adipocytes and in biopsies from visceral (VAT) and subcutaneous (SAT) adipose tissue from 38 obese non-diabetic subjects, using real-time PCR. The influence of haplotype and clinical traits on TCF7L2 mRNA levels were investigated. In vitro, insulin decreased TCF7L2 mRNA expression. This effect was attenuated in cells incubated with the free fatty acids palmitate or oleate. In vivo, we found significantly higher expression in SAT from more insulin resistant subjects. No correlations between TCF7L2 mRNA expression and obesity measures were observed. TCF7L2 expression was higher in VAT than in SAT and when stratifying for haplotype, this difference was seen in HapA carriers but not in non-HapA carriers. In conclusion, TCF7L2 mRNA levels in adipocytes are decreased by insulin and seem to increase in insulin resistant subjects and in HapA carriers.


Prospective randomized trial comparing efficacy and safety of intravenous and intra-articular tranexamic acid in total knee arthroplasty.
Total knee arthroplasty (TKA) is associated with significant perioperative blood loss and postoperative allogenic blood transfusion. Tranexamic acid (TXA) reversibly blocks lysine binding sites on plasminogen molecules and inhibits plasmin formation. Comparisons of the efficacy and safety of intra-articular and intravenous TXA in primary TKA have not previously been reported. A prospective randomized trial was conducted in 150 patients who underwent TKA, and these patients were randomized into three groups. Patients in Group A were injected by intra-articular TXA according to body weight (20 mg/kg). Patients in Group B received a standard dose of intra-articular TXA (2000 mg), and those in Group C were infused with TXA according to body weight (20 mg/kg) before tourniquet deflation and again 3 h later. Baseline characteristics and data collected at blood transfusion were compared. Differences among four time points (baseline, day 0, day 2, and day 5) were carried out using ANOVA. The hemoglobin levels at postoperative day 5 were 10.6 g/dL for Group A, 10.6 g/dL for Group B, and 10.7 g/dL for Group C. The drain output was 399 ml for Group A, 314 ml for Group B, and 305 ml for Group C (p = 0.03). Group C had significantly less drain output than Group A after post hoc comparisons (p = 0.05), whereas no significant difference was observed between Group A and B (p = 0.09) or between Group B and C. The weight-adjusted dose of TXA administered intravenously significantly reduced the drain output but not the total blood loss when compared with the weight-adjusted dose of TXA administered intra-articularly. No significant difference was observed in the other parameters among the three groups. The Joint CUHK-NTEC CREC, CRE-2013.644-T . Registered 1 March 2014.


Acquisition of Basic Microsurgical Skills Using Low-Cost, Readily Available Models: The Orange Model.
Attainment of basic microsurgical skills in neurosurgery presents a departmental challenge worldwide. Models for teaching are either not readily available or expensive and are incompatible with a resident's busy schedule, requiring lengthy and proper setup. We present a model and a set of measurable tasks, based on a fruit (orange) that is cheap, easy to set up instantly when desired, and useful for training of basic microsurgical skills. Basic microsurgical skills were identified, necessitating hand-eye coordination working with the microscope. The goal was to dissect an orange segment while preserving adjacent segments. Assessment was based on the number of side tears and task completion duration. The task was repeated in a sequential manner (n = 10), for validation purposes, for 3 operators at different seniority levels. An improvement in the number of side tears (mean of 12.66 ± 9.01 in the first trial vs. 4 ± 4.35 in the 10th trial, P < 0.01), as well as duration of time required for task completion (mean initial duration of 28:16 ± 19:00 minutes to a duration of 16:33 ± 10:50 minutes in the last attempt, P < 0.01), was observed. Daily practice scores and time gradually improved, and the seniority level of operators was correlated with scoring between individuals. The orange model is an easily accessible, cheap model that enables the acquisition of basic microneurosurgical skills. In this work, we validated and defined reproducible tasks that can be scored and tracked, correlated with operator's proficiency and experience. This model can be incorporated into a resident's workflow environment and provides a platform for attainment of elementary microsurgical skills for neurosurgical residents.


Effectiveness of Rituximab for the Treatment of Rheumatoid Arthritis in Patients with Prior Exposure to Anti-TNF: Results from the CORRONA Registry.
To characterize the real-world effectiveness of rituximab (RTX) in patients with rheumatoid arthritis. Clinical effectiveness at 12 months was assessed in patients who were prescribed RTX based on the Clinical Disease Activity Index (CDAI). Change in CDAI was calculated (CDAI at 12 mos minus at initiation). Achievement of remission or low disease activity (LDA; CDAI ≤ 10) among those with moderate/high disease activity at the time of RTX initiation was compared based on prior anti-tumor necrosis factor agent (anti-TNF) use (1 vs ≥ 2) using logistic regression models. Patients (n = 265) were followed for 12 months with a mean change in CDAI of -8.1 (95% CI -9.8 - -6.4). Of the 218 patients with moderate/high disease activity at baseline, patients with 1 prior anti-TNF (baseline CDAI 25.0) demonstrated a mean change in CDAI of -10.1 (95% CI -13.2 - -7.0); patients with ≥ 2 prior anti-TNF (baseline CDAI 30.0) demonstrated a mean change of -10.5 (95% CI -12.9 - -8.0). The unadjusted OR for achieving LDA/remission in patients with moderate/high disease activity at baseline exposed to ≥ 2 versus 1 prior anti-TNF was 0.40 (95% CI 0.22-0.73), which was robust to 4 different adjusted models (OR range 0.38-0.44). A good clinical response was observed in all patients; however, patients previously treated with 1 anti-TNF, who had lower baseline CDAI and a greater opportunity for clinical improvement compared with patients previously treated with ≥ 2 anti-TNF, were more likely to achieve LDA/remission.


Planar and tomographic imaging with technetium 99m-labeled tetrofosmin: correlation with thallium 201 and coronary angiography.
This study compared the results of planar and single-photon emission computed tomographic (SPECT) imaging with tetrofosmin with those of 201Tl and coronary angiography. In three normal volunteers the images were normal by both 201Tl and tetrofosmin (planar and SPECT). In 23 patients with coronary artery disease, the images were abnormal in 20 patients by SPECT tetrofosmin, in 19 by planar tetrofosmin, in 20 by SPECT thallium, and in 18 by planar thallium (difference not significant). Both planar and SPECT images were divided into five segments per patient. There were 58 perfusion defects by SPECT tetrofosmin, 50 by planar tetrofosmin (difference not significant), 47 by SPECT thallium, and 42 by planar thallium (difference not significant). Perfusion defects were reversible in 47 segments (36%) by SPECT tetrofosmin, 35 (27%) by planar tetrofosmin, 31 (24%) by SPECT thallium (p < 0.05 vs SPECT tetrofosmin), and 31 (24%) by planar thallium (difference not significant). Among the 23 patients with coronary artery disease, 19 underwent coronary angiography. In these patients there were 32 diseased coronary arteries. Perfusion defects were present in 21 territories (66%) by SPECT tetrofosmin, 19 (59%) by planar tetrofosmin, 20 (63%) by SPECT thallium, and 18 (56%) by planar thallium. There was agreement between thallium and tetrofosmin in 108 of 130 segments (kappa statistics = 0.69 +/- 0.06). The images, especially with SPECT, are better with tetrofosmin than with 201Tl. Thus myocardial imaging with tetrofosmin provides results that are at least as good as those of 201Tl. Slightly more abnormal segments and more reversible defects are detected by tetrofosmin than by thallium imaging, especially with SPECT imaging.


Size, scatter and coverage of ganglion cell receptive field centres in the cat retina.
1. Receptive field centre sizes of brisk-sustained (X) and brisk-transient (Y) ganglion cells of the cat retina were assessed by three different methods: small spot mapping, area threshold method and spatial resolution. 2. Centre sizes of brisk-sustained (X) cells increased from 20' in the central area to about 70' at an eccentricity of 4.5 mm, centre sizes of brisk-transient (Y) cells from 50' in the central area to about 140' at 5 mm eccentricity. 3. The scatter of centre sizes at one retinal location was measured by recording as many ganglion cells as possible in one cat in a small field of retina. The centre sizes of the individual classes were homogeneous and exhibited only a small amount of scatter. 4. The coverage of the retina by the different ganglion cell classes was assessed from their density and their receptive field centre area. At every retinal location the receptive field centres of seven to twenty brisk-sustained (X) cells and of three to six brisk-transient (Y) cells were found to overlap. Sluggish concentric and non-concentric cells taken together have a coverage factor of about 60.


Recognizing comorbid personality disorder can help manage and treat the "untreatable".
Personality disorder is surprisingly prevalent. Clinical syndromes accompanied by personality disorder tend to be more severe, more treatment resistant, and more likely to recur than their counterparts. Learning to recognize personality disorder can enhance the efficacy of the clinician's management style and his or her ability to make appropriate plans for long-term psychotherapy. To assist diagnosis of personality disorder according to the DSM-IV, the authors present interpersonal descriptions and necessary and exclusionary conditions.