Sonographic evaluation of knee cartilage defects implanted with preconditioned scaffolds.
The purpose of this study was to develop a novel method for creating an acellular bioactive scaffold, to prove its efficacy in vivo and in vitro for the augmentation of biological repair, and to confirm that sonographic microscopy is a viable modality for monitoring the healing process of osteochondral defects implanted with preconditioned bioactive scaffolds. Rabbit marrow stromal cells were retrovirally transduced with either bone morphogenetic protein 7 (BMP-7) or insulinlike growth factor 1 (IGF-1) genes, cultured for 9 weeks in nonwoven poly-L-lactic acid scaffolds, and then frozen and lyophilized. The knees were evaluated at 3, 6, and 12 weeks after surgery using 20-MHz ultrasound and then prepared for routine histologic analysis. B-scans of the extracellular matrix defects were compared to histologic results. Control defects showed a void or a mixture of fibrocartilage tissue. Both types of scaffolds resulted in a higher percentage (both P< .001) of primarily hyaline cartilage tissue with intact articular surfaces. The osteochondral defects were clearly observed in each sonographic signature. There were no differences between images of scaffolds treated with IGF-1 or BMP-7. Extracellular matrix regrowth was found to closely parallel (R(2) = 0.968; P < .003) the histologic images. A 3-mm defect depth and a 2.5-mm scaffold thickness were measured on the sonograms, comparing well to actual dimensions. There was a gradual increase in healing bordering the defects for the 3-, 6-, and 12-week samples. Also, we have shown that sonography can aid in monitoring implantation of preconditioned scaffolds in osteochondral defects and thus assessing the healing process and cartilage/bone quality.


Purification and kinetic study of glyoxalase-I from rat liver, erythrocytes, brain and kidney.
Glyoxalase-I (S-lactoyl-glutathione methylglyoxal-lyase (isomerizing), EC 126.96.36.199) was purified from rat liver, erythrocytes, brain and kidney using two different purification procedures. The similarities of the purification profiles, electrophoretic mobilities and kinetics suggest that a single major form of the enzyme exists in these tissues. The highest purification (9300-fold) of the erythrocyte enzyme gave nearly homogeneous protein, molecular weight 50 000, specific activity 2410 mumol/min per mg. Kinetic studies of the rat glyoxalase-I-catalyzed disproportionation of the hemimercaptals of GSH and aromatic or aliphatic alpha-ketoaldehydes revealed broad substrate specificity with V and Km values quite insensitive to the nature of the alpha-ketoaldehydes. Use of deuterated analogs of the alpha-ketoaldhydes methylglyoxal and phenylglyoxal showed that the intramolecular hydride migration is the rate-determining step.


Attention Bias Modification training in individuals with depressive symptoms: A randomized controlled trial.
Negative attentional biases are often considered to have a causal role in the onset and maintenance of depressive symptoms. This suggests that reduction of such biases may be a plausible strategy in the treatment of depressive symptoms. The present clinical randomized controlled trial examined long-term effects of a computerized attention bias modification (ABM) procedure on individuals with elevated depressive symptoms. In a double-blind study design, 77 individuals with ongoing mild to severe symptoms of depression were randomly assigned to one of three conditions: 1) ABM training (n = 27); 2) placebo (n = 27); 3) assessment-only (n = 23). In both the ABM and placebo conditions, participants completed 8 sessions of 216-trials (1728 in total) during a 2-week period. Assessments were conducted at pre-training and post-training (0, 2, 4, 8-week, 3, 7-month follow-ups). Change in depressive symptoms and restoration of asymptomatic level were the primary outcome measures. In the ABM, but not the other two conditions, significant reductions in depressive symptoms were found at post-training and maintained during the 3-month follow-up. Importantly, more participants remained asymptomatic in the ABM condition, as compared to the other two conditions, from post-training to 7-month follow-up. ABM also significantly reduced secondary outcome measures including rumination and trait anxiety, and notably, the ABM effect on reducing depressive symptoms was mediated by rumination. Generalization of the findings may be limited because the present sample included only college students. The ABM effect on reducing depressive symptoms was maintained for at least 3-month duration in individuals with elevated depressive symptoms, and these results suggest that ABM may be a useful tool for the prevention of depressive symptoms. CLINICALTRIALS.GOV: NCT01628016.


Outcome of components separation for contaminated complex abdominal wall defects.
Contaminated large abdominal wall defects can pose a formidable challenge to the surgeon. This study compared the outcome of components separation (CS) for complex ventral defects with or without contamination. A retrospective review was conducted of all patients who underwent CS over an 8-year period. Pre-operative factors such as the presence/absence of contamination were analyzed for their effect on length of hospitalization, readmission rate, post-operative complications, re-intervention rate, and long-term recurrence. A total of 34 patients was analyzed. There were 18 males (53%) with a mean age of 57 years. Mean body mass index was 31 kg/m(2). Seventeen patients (50%) had prior repair (mean 2.1 repairs per patient, median 2). Mean size of abdominal defect was 255 cm(2). Out of the 34 patients, 13 had infected or contaminated defects, including 5 patients with infected mesh. Length of stay was longer in the contaminated group (11.1 vs 3.1 days, P < 0.01). A higher complication rate was noted in the setting of contamination (77 vs 38%, P = 0.03). During a mean follow-up of 47 months, no difference was noted in the re-intervention rate (38 vs 29%, P = 0.70) or long-term recurrence rate of the defect (8 vs 5%, P = 1.0) (contaminated vs non-contaminated group, respectively). CS is a good option for closure of large contaminated complex abdominal wall defects. Despite an increased risk of postoperative complications and longer hospitalization length, long-term outcomes are favorable.


Toxicity and metabolism of p-chlorophenol in the marine microalga Tetraselmis marina.
Toxicity and metabolism of para-chlorophenol (p-CP) in the marine microalga Tetraselmis marina have been studied. The inhibition constant EC(50) for p-CP was 272+/-17 microM (34.8+/-2.2 mg L(-1)) under the experimental conditions. Two metabolites were detected in the growth medium in the presence of p-CP by reverse phase HPLC and their concentrations increased at the expense of p-CP. The two metabolites, which were found to be more polar than p-CP, were isolated by a C18 column. They were identified as p-chlorophenyl-beta-D-glucopyranoside (p-CPG) and p-chlorophenyl-beta-D-(6-O-malonyl)-glucopyranoside (p-CPGM) by electrospray ionization-mass spectrometric analysis in a negative ion mode. The molecular structures of p-CPG and p-CPGM were further confirmed by enzymatic and alkaline hydrolyses. Treatment with beta-glucosidase released free p-CP and glucose from p-CPG, whereas p-CPGM was completely resistant. Alkaline hydrolysis completely cleaved the esteric bond of the malonylated glucoconjugate and yielded p-CPG and malonic acid. It was concluded that the pathway of p-CP metabolism in T. marina involves an initial conjugation of p-CP to glucose to form p-chlorophenyl-beta-d-glucopyranoside, followed by acylation of the glucoconjugate to form p-chlorophenyl-beta-D-(6-O-malonyl)-glucopyranoside. The metabolism of p-CP in T. marina was mainly driven by photosynthesis, and to a lesser extent by anabolic metabolism in the dark. Accordingly, the detoxification rate under light was about seven times higher than in the darkness. This work provides the first evidence that microalgae can adopt a combined glucosyl transfer and malonyl transfer process as a survival strategy for detoxification of such xenobiotics as p-CP.


[Systematic screening tests for Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum in urogenital specimens of infertile couples].
We conducted a prospective study on 100 couples consulting for infertility at the teaching Hospital of Tours, with the scope to determine if there is a benefit for systematic screening of Chlamydia trachomatis, Mycoplasma hominis and Ureaplasma urealyticum among genito-urinary specimen when exploring couples infertility. C. trachomatis was detected by PCR on sperm, endocervix and urine specimen. M. hominis and U. urealyticum were detected by culture on A7 agar medium and with minigaleries on sperm and endocervix specimen. Standard cultures were also performed on sperm, endocervix, vaginal and urine specimen. Only one specimen (sperm) was positive for C. trachomatis. Three percent of the specimen were positive for U. urealyticum (from which 2,5% of the sperm specimen). No specimen was positive for M. hominis. Our results show that screening of C. trachomatis, M. hominis and U. urealyticum is not systematically required for among check up of infertile couples, given the prevalence of chlamydiosis among the population studied. However, it would be interesting to perform it on a targeted population, according to anamnestic or clinical criteria. In addition, an important modification of vaginal flora was observed in 12% of cases, and 2 vaginosis were diagnosed; the putative consequences of this disequilibrium has to be further investigated.


Comparison of molecular and serological assays on cerebrospinal fluid for the diagnosis of neurosyphilis.
Many assays are available on cerebrospinal fluid (CSF) for the diagnosis of neurosyphilis (NS) but there is no 'gold standard'. The aim of this study was to evaluate different molecular and serological assays used in NS. We evaluated two PCR assays and three serological techniques in parallel on CSF samples collected between 2019 and 2020 from patients suspected of NS. The study included 143 patients comprising 30 early NS, 7 late NS and 106 patients without a diagnosis of NS. All patients with NS were symptomatic and had either neurological (67.6%) or ophthalmological signs (54.1%). The qPCR and nPCR assays had overall sensitivities (Se) of 41% and 27%, respectively; with each an overall specificity (Sp) of 100%. VDRL had a Se of 51% and a Sp of 92%. Immunoblot had a Se of 62% and a Sp of 85%. Finally, treponemal tests (TT) had a Se of 96% and a Sp of 69%. Our study confirms the excellent specificity of molecular techniques allowing to avoid overdiagnosis of NS, and thus, unjustified intensive antibiotic therapy protocols. CSF TT, although not very specific, has an excellent Se confirming that there is almost never NS with negative CSF TT. VDRL and immunoblot tests have better overall diagnostic performance. However, none of these techniques has sufficient diagnostic performance to represent a 'gold standard'. Thus, the diagnosis of NS relies on a combination of clinical and biological parameters with the association of PCR with serology, associating VDRL and immunoblot, in CSF.


Unusual electrocardiographic changes in spontaneous pneumothorax.
A young woman with spontaneous left pneumothorax had a phasic voltage alternation of her electrocardiogram that resolved with expansion of the lung. Likely explanations for this phenomenon are a respiratory dependent change in cardiac anatomy and a change in the volume conductor with respiration.


A polymer containing a repeating peptide sequence can stimulate T-cell-independent IgG antibody production in vivo.
The immunogenicity of a CD4 peptide sequence 303-315 (V4 domain) was determined for three forms of the peptide: (a) a polymer consisting of repeating peptide units, (b) a peptide linked to a large protein carrier, chicken serum albumin, and (c) unmodified free peptide. Two in vivo systems were used: a T-cell-competent BALB/c mouse and a T-cell-deficient nude mouse. In BALB/c mice the IgG antibody responses to the peptide-CSA conjugate were at least 100-fold greater than the response to the polymer, and the free peptide gave no response. However, in contrast to the normal BALB/c mice, in the nude mice the polymer produced the only significant response. Nude mice immunized with the polymer produced a predominantly IgG response with almost equal amounts of IgG1 and IgG 2a + 2b. This IgG subclass distribution was very similar to that obtained in the BALB/c for the peptide-CSA conjugate. Positive sera from both groups were able to react with immobilized CD4 molecule on Western blots, confirming the specificity of both the T-cell-independent as well as T-cell-dependent response. These results suggest that repeating epitopes on the same peptide polymer molecule may cause cross-linking of antigen-specific immunoglobin receptors on B-cells, and thus behave as a relatively T-cell-independent immunogen which can induce isotype switching.


Acquired resistance for immune checkpoint inhibitors in cancer immunotherapy: challenges and prospects.
Drug resistance has become an obstacle to the further development of immunotherapy in clinical applications and experimental studies. In the current review, the acquired resistance to immunotherapy was examined. The mechanisms of acquired resistance were based on three aspects as follows: The change of the tumor functions, the upregulated expression of inhibitory immune checkpoint proteins, and the effects of the tumor microenvironment. The combined use of immunotherapy and other therapies is performed to delay acquired resistance. A comprehensive understanding of acquired drug resistance may provide ideas for solving this dilemma.


Anemia prevalence at the time of pregnancy detection.
Anemia in the first trimester of pregnancy is the situation as described by the World Health Organization when the level of hemoglobin (Hb) is less than 11 g in 100 cc of blood. The prevalence of this problem is 18% in developed countries, whereas it is between 35-75% in developing countries. In this study, we aimed to determine the prevalence of anemia at the time of pregnancy detection. A retrospective cross-sectional study was designed to determine the prevalence of anemia. A total of 5228 first trimester pregnant women were admitted to the study between 2012 and 2014. Hb levels of 11 to 9.5 g/dL, 9.5 to 8 g/dL, and less than 8 g/dL were considered as mild, moderate, and severe anemia, respectively. We detected mild, modarate, and severe anemia at rates of 16.64%, 3.07%, and 0.28%, respectively, in our population. The overall prevalence of anemia at the time of detection of pregnancy was 20.0%. Anemia is a significant risk factor for maternal mortality in developing countries. The prevalence of anemia at the time of pregnancy detection was 20% and this rate is close to those indicated in developed countries.


Acute deterioration of a Chiari I malformation: an uncommon neurosurgical emergency.
Report and discuss acute neurological deterioration of Chiari I malformation (CMI), surgical treatment and timing, clinical outcome and literature review. We report a recent case of a 15-year-old girl admitted for an acute neurological deterioration caused by an undiagnosed hindbrain herniation that required an urgent foramen magnum decompression and external ventricular drainage insertion. Moreover, we report and discuss the literature. To the authors' knowledge, this is only the third paediatric patient identified in this setting to be treated for an acute neurological deterioration due to a previous asymptomatic hindbrain herniation. The patient made an uncomplicated recovery and was discharged home on the seventh postoperative day and has remained well at review. Acute deterioration of CMI in completely asymptomatic patients in absence of concomitant pathological findings is rarely reported in the literature, and exceptional in children. CMI is typically treated electively, but as this case illustrates, it can present with rapidly deteriorating neurological signs. Symptoms usually respond well to surgical intervention with rapid improvement.


The synthetic opioid fentanyl increases HIV replication and chemokine co-receptor expression in vitro.
The US is experiencing a major public health crisis that is fueled by the illicit use of synthetic opioids including fentanyl. While several drugs of abuse can enhance viral replication and/or antagonize immune responses, the impact of specific synthetic opioids on HIV pathogenesis is poorly understood. Thus, we evaluated the effects of fentanyl on HIV replication in vitro. HIV-susceptible or HIV-expressing cell lines were incubated with fentanyl. HIV p24 synthesis and chemokine receptor levels were quantified by ELISA in culture supernatants and cell lysates, respectively. Addition of fentanyl resulted in a dose-dependent increase in HIV replication. Fentanyl enhanced expression of the HIV chemokine co-receptors CXCR4 and CCR5 and caused a dose-dependent decrease in cell viability. The opioid antagonist naltrexone blocked the effect of fentanyl on HIV replication and CCR5 receptor levels but not CXCR4 receptor levels. TLR9 expression was induced by HIV; however, fentanyl inhibited TLR9 expression in a dose-dependent manner. These data demonstrate that the synthetic opioid fentanyl can promote HIV replication in vitro. As increased HIV levels are associated with accelerated disease progression and higher likelihood of transmission, additional research is required to enhance the understanding of opioid-virus interactions and to develop new and/or optimized treatment strategies for persons with HIV and opioid use disorder.


Molecular ecological perspective of methanogenic archaeal community in rice agroecosystem.
Methane leads to global warming owing to its warming potential higher than carbon dioxide (CO2). Rice fields represent the major source of methane (CH4) emission as the recent estimates range from 34 to 112 Tg CH4 per year. Biogenic methane is produced by anaerobic methanogenic archaea. Advances in high-throughput sequencing technologies and isolation methodologies enabled investigators to decipher methanogens to be unexpectedly diverse in phylogeny and ecology. Exploring the link between biogeochemical methane cycling and methanogen community dynamics can, therefore, provide a more effective mechanistic understanding of CH4 emission from rice fields. In this review, we summarize the current knowledge on the diversity and activity of methanogens, factors controlling their ecology, possible interactions between rice plants and methanogens, and their potential involvement in the source relationship of greenhouse gas emissions from rice fields.


Leucocyte ascorbate levels and postoperative deep venous thrombosis.
Forty-four general surgical patients were included in a prospective, randomized double-blind controlled trial of ascorbic acid (500 mg b.d.) or placebo for 7 days before operation. This was to test the hypothesis that vitamin C may reduce the instance of deep venous thrombosis postoperatively. Venous blood samples were taken before entering the trial, just immediately before surgery, on the day of operation and on three further occasions at 3-day intervals postoperatively for leucocyte ascorbic acid concentration (LAC). Venous thrombosis was diagnosed using the 125I-fibrinogen test and the leg scans interpreted by Roberts' criteria. There was no significant difference in the incidence of DVT between the treatment and placebo groups. In those with DVT (n = 23) the mean LAC on the day of operation was not significantly different from that in those without DVT. However, on the sixth and ninth postoperative days LAC levels were significantly lower in the DVT group. These results suggest that the administration of ascorbic acid preoperatively does not reduce the incidence of DVT, but a striking decrease in the LAC levels in the DVT patients is in keeping with the hypothesis that the initial event in the pathogenesis of DVT is adherence of leucocytes to the venous endothelium.


Malrotation and intestinal atresias.
This review encompasses four congenital conditions which present with symptoms of bowel obstruction in the neonatal period. The antenatal and postnatal features of malrotation, jejuno-ileal atresia, duodenal atresia and colonic atresia are discussed. Each condition is outlined including the classification, epidemiology, aetiology and presentation, and a summary of the surgical management is described.


The Unmet Rehabilitation Needs in an Inclusion Health Integrated Care Programme for Homeless Adults in Dublin, Ireland.
People who become homeless have higher morbidity and mortality, use a disproportionate amount of healthcare resources, and generate a large volume of potentially preventable healthcare and other costs compared to more privileged individuals. Although access to rehabilitation is a human right under article 26 of the United Nations Convention on the Rights of Persons with Disabilities, the rehabilitation needs of individuals with homelessness have not been explored, and this project's purpose was to establish a baseline of need for this cohort. A prospective audit of case discussions at an inclusion health service over a 2-month period in 2018. Four multidisciplinary inclusion health clinics were observed with over 20 cases discussed in each and data were extracted using a bespoke audit data extraction tool. The inclusion health needs were diverse and complex with many unmet rehabilitation needs. Physical and cognitive rehabilitation needs were identified in over 50% of cases discussed. Musculoskeletal problems and acquired brain injuries were the most common cause of activity limitation. Most had concurrent medical conditions and addiction and/or mental health needs. None had access to rehabilitation services. The results of this study show that the rehabilitative needs of this cohort are significant and are not being met through traditional models of care. We are currently exploring innovative ways to provide appropriate services to these individuals.


Mercury removal, methylmercury formation, and sulfate-reducing bacteria profiles in wetland mesocosms.
A pilot-scale model was constructed to determine if a wetland treatment system (WTS) could effectively remove low-level mercury from an outfall located at the Department of Energy's Savannah River Site. Site-specific hydrosoil was planted with giant bulrush, Scirpus californicus, and surface amended with gypsum (CaSO4) prior to investigating the biogeochemical dynamics of sediment-based sulfur and mercury speciation. On average, the pilot WTS decreased total mercury concentrations in the outfall stream by 50%. Transformation of mercury to a more "bioavailable" species, methylmercury, was also observed in the wetland treatment system. Methylmercury formation in the wetland was ascertained with respect to sediment biogeochemistry and S. californicus influences. Differences in sulfate-reduction rates (SRRs) were observed between mesocosms that received additional decomposing Scirpus matter and mesocosms that were permitted growth of the submerged macrophyte, Potamogeton pusillus. Relative abundance measurements of sulfate-reducing bacteria (SRB) as characterized using oligonucleotide probes were also noticeably different between the two mesocosms. A positive correlation between increased sulfide, dissolved total mercury, and dissolved methylmercury concentrations was also observed in porewater. The data suggest that soluble mercury-sulfide complexes were formed and contributed, in part, to a slight increase in mercury solubility. Observed increases in methylmercury concentration also suggest that soluble mercury-sulfide complexes represent a significant source of mercury that is "available" for methylation. Finally, a volunteer macrophyte, Potamogeton pusillus, is implicated as having contributed additional suspended particulate matter in surface water that subsequently reduced the pool of dissolved mercury while also providing an environment suitable for demethylation.


Strain-dependent modulation of phosphate transients in rabbit skeletal muscle fibers.
When inorganic phosphate (Pi) is photogenerated from caged Pi during isometric contractions of glycerinated rabbit psoas muscle fibers, the released Pi binds to cross-bridges and reverses the working stroke of cross-bridges. The consequent force decline, the Pi-transient, is exponential and probes the kinetics of the power-stroke and Pi release. During muscle shortening, the fraction of attached cross-bridges and the average strain on them decreases (Ford, L. E., A.F. Huxley, and R.M. Simmons, 1977. Tension responses to sudden length change in stimulated frog muscle fibers near slack length. J. Physiol. (Lond.). 269:441-515; Ford, L. E., A. F. Huxley, and R.M. Simmons, 1985. Tension transients during steady state shortening of frog muscle fibers. J. Physiol. (Lond.). 361:131-150. To learn to what extent the Pi transient is strain dependent, muscle fibers were activated and shortened or lengthened at a fixed velocity during the photogeneration of Pi. The Pi transients observed during changes in muscle length showed three primary characteristics: 1) during shortening the Pi transient rate, Kpi, increased and its amplitude decreased with shortening velocity; Kpi increased linearly with velocity to > 110 s-1 at 0.3 muscle lengths per second (ML/s). 2) At a specific shortening velocity, increases in [Pi] produce increases in Kpi that are nonlinear with [Pi] and approach an asymptote. 3) During forced lengthening Kpi and the amplitude of the Pi transient are little different from the isometric contractions. These data can be approximated by a strain-dependent three-state cross-bridge model. The results show that the power stroke's rate is strain-dependent, and are consistent with biochemical studies indicating that the rate-limiting step at low strains is a transition from a weakly to a strongly bound cross-bridge state.


Micafungin pharmacodynamics predict clinical outcomes in hospitalized patients with candidemia caused by certain Candida species.
Echinocandins are guideline-preferred therapies for invasive candidiasis (IC). Fixed dosing of echinocandins is commonly used despite variations in body mass index and echinocandin susceptibility. The purpose of this study was to evaluate clinical outcomes of micafungin based on population-predicted pharmacokinetic/pharmacodynamic (PK/PD) factors and susceptibility. Candida isolate results were screened from bloodstream or intraabdominal cultures of hospitalized patients admitted to a quaternary-care teaching hospital. Patients with a first episode of IC who received micafungin for at least 48 h were included. Patients with mixed cultures or Candida species with no minimum inhibitory concentration (MIC) differences were excluded. Breakpoints for micafungin MIC and area under the curve (AUC)/MIC ratio were calculated using classification and regression tree (CART) analysis and related to clinical outcomes. Primary efficacy outcome was candida-contributable mortality, defined as mortality within 28 days of positive culture with concomitant micafungin treatment failure; secondary outcome was micafungin treatment failure within 28 days, MAIN RESULTS: Seventy-two patients were included of whom 15 (21%) had Candida-contributable mortality and 34 (47%) experienced micafungin treatment failure. C. albicans and C. tropicalis did not have differing MICs and these patients were excluded from the study. Mortality using a CART-derived MIC breakpoint of ≥1.0 mg/L was 38% compared to 9% in patients infected with lower MIC strains (p = 0.003). Patients with a CART-derived AUC/MIC value >138.5 had a mortality rate of 9% compared to 41% for patients with AUC/MIC values below the breakpoint (p = 0.0013). Results were similar for treatment failure rates, and both were confirmed using multivariable models. CART-derived micafungin MIC and AUC/MIC breakpoints predicted patient mortality and treatment failure for certain Candida species. These results support the need for further PK/PD studies to optimize echinocandin dosing and improve patient outcomes.


Management of Ear Trauma.
Facial trauma remains a common reason for visits to the emergency department or urgent care facility. The ear remains susceptible to trauma given its delicate anatomy and position in the maxillofacial region. Understanding the anatomy and recognizing the circumstances regarding the mechanism of injury help dictate treatment. The goals of treatment should remain to restore the physiologic form and function of the ear. Middle ear injuries should also be addressed during the process. Although primary repair remains feasible in most cases, there are instances when delayed and staged reconstruction is necessary to achieve successful results.


Pedometer steps-per-minute, moderate intensity, and individual differences in 12- to 14-year-old youth.
Researchers have noted both the utility and limitations of using pedometers to measure physical activity (PA). While these unobtrusive devices are widely accepted for their ability to measure accumulated PA, they have been criticized for their inability to measure exercise intensity. However, recent steps-per-minute (SPM) research provides reasonably accurate measures of intensity allowing users to assess time spent at recommended PA levels. Therefore, the purpose of this study was to determine the SPM taken that are associated with moderate physical activity in 12- to 14-year-old youth. Ninety-three participants (49 boys and 44 girls; ages 12 to 14) walked on a treadmill for 3 minutes at each of 4 different speeds while wearing a pedometer and a heart rate monitor. On average boys and girls reached their moderate activity intensity threshold at 122 SPM and 102 SPM, respectively. However, individual differences must be taken into account when determining appropriate SPM intensities for youth. The impact of individual differences underscores the need to address SPM for moderate intensity individually rather than with a single guideline for everyone at this age.


Medial sided articular impaction in tibial plateau fractures.
Tibial plateau fractures are a heterogenous group of injuries with a variable amount of articular injury and are commonly associated with lateral sided articular impaction. Previous work has focused on describing the morphology of tibial plateau fractures, but has neglected description of medial sided articular impaction. The aim of this investigation was to assess the morphology of medial sided articular impaction in tibial plateau fractures, with specific attention directed toward the frequency, location, size, and associated fracture patterns. Skeletally mature patients presenting to a Level I trauma center from 2008-2018 with a tibial plateau fracture (AO/OTA 41B-C) were identified retrospectively. Fractures were classified by AO/OTA and Schatzker type. Radiographs and computed tomography (CT) scans were reviewed to identify and localize medial sided articular impaction. The location and surface area of impaction was characterized by creating frequency diagram heat maps from axial CT scans. Descriptive statistics were performed using standard measures. Of the 1032 tibial plateau fractures included, 82 (7.9%) were noted to have medial sided articular impaction. Rate of impaction varied by fracture type (p = 0.03): Schatzker II, 2% (7 of 381); Schatzker IV, 21% (19 of 96); and Schatzker VI, 11% (56 of 524). Average total surface area of impaction was 9% of the total and 19% of the medial plateau area. Area of impaction varied by fracture type (p = 0.004): Schatzker II, 6% (95% confidence interval [CI], 4%-7%); Schatzker IV, 11% (95% CI, 9%-13%), and Schatzker VI, 9% (95% CI, 7%-11%). The area of impaction occurred primarily along the lateral aspect of the medial plateau in Schatzker II fractures, in the anteromedial quadrant of Schatzker IV fractures, and was evenly distributed across the medial plateau in Schatzker VI fractures. Surgeons should be aware that medial articular impaction is present in approximately 8% of tibial plateau fractures. Schatzker IV fractures are most likely to have medial impaction and a larger proportion of the joint surface involved in these injuries.


Local muscle cooling does not impact expression of mitochondrial-related genes.
Recovery that takes place in a cold environment after endurance exercise elevates PGC-1α mRNA whereas ERRα and NRF2 mRNA expression are inhibited. However, the effect of local skeletal muscle cooling on mitochondrial-related gene expression is unknown. To determine the impact of local skeletal muscle cooling during recovery from an acute bout of exercise on mitochondrial-related gene expression. Recreationally-trained male cyclists (n=8, age 25±3 y, height 181±6cm, weight 79±8kg, 12.8±3.6% body fat, VO2peak 4.52±0.88L·min-1 protocol) completed a 90-min variable intensity cycling protocol followed by 4h of recovery. During recovery, ice was applied intermittently to one leg (ICE) while the other leg served as a control (CON). Intramuscular temperature was recorded continuously. Muscle biopsies were taken from each vastus lateralis at 4h post-exercise for the analysis of mitochondrial-related gene expression. Intramuscular temperature was colder in ICE (26.7±1.1°C) than CON (35.5±0.1°C) throughout the 4h recovery period (p<0.001). There were no differences in expression of PGC-1α, TFAM, NRF1, NRF2, or ERRα mRNA between ICE and CON after the 4h recovery period. Local muscle cooling after exercise does not impact the expression of mitochondrial biogenesis-related genes compared to recovery from exercise in control conditions. When these data are considered with previous research, the stimuli for cold-induced gene expression alterations may be related to factors other than local muscle temperature. Additionally, different intramuscular temperatures should be examined to determine dose-response of mitochondrial-related gene expression.


Vigor and aspiration levels in neuroeconomics.
In this contribution, we criticize the demanding assumption of vigor that economic agents are maximizers. We discuss the link between vigor and subjective value through the alternative notion of aspiration levels, arguing that vigor can help articulate the ecological balance - central in bounded and ecological rationality - between minimum expected reward (aspiration level) and the efforts made for its attainment.


Serotonin-induced vasoconstriction is mediated by thromboxane release and action in the human fetal-placental circulation.
The possibility that prostanoids mediate the contractile response of serotonin on placental vessels was investigated. Rings of chorionic plate arteries and veins with and without endothelium were suspended in an organ bath for recording isometric mechanically activity. Serotonin caused dose-dependent contractions that were significantly attenuated by indomethacin (cyclo-oxygenase inhibitor, 10 microM) and SQ29,548 (thromboxane receptor antagonist, 1 microM). Pretreatment of placental venous and arterial rings with indomethacin decreased sensitivity (EC50) to serotonin of 2.3- and 1.9-fold, respectively. Pretreatment with SQ29,548 decreased sensitivity to serotonin of twofold in veins and 2.1-fold in arteries. In the endothelium-denuded placental arteries and veins, pretreatment with indomethacin and SQ29,548 reduced the serotonin-induced contraction in a similar way to that obtained in the endothelium-intact vessels. In isolated perfused cotyledon through the fetal circulation, serotonin caused a significant increase in perfusion pressure and stimulated thromboxane release 1.9-fold compared with basal values. Therefore, serotonin-induced vasoconstriction in the human fetoplacental circulation appears to be mediated in part by thromboxane release or action. This effect is not dependent on mediators released from the endothelium. The present study provides evidence for the participation of thromboxane A2 in the contractile response to serotonin in the human placental circulation. The ability of serotonin to release thromboxane A2 which is also a potent vasoconstrictor agent, may be important in increase fetoplacental resistance, one of the features of pre-eclampsia.


Patterns and Outcomes of Recurrent Esophageal Cancer After Curative Esophagectomy.
The recurrence patterns and therapeutic outcomes of patients with recurrent esophageal cancer after curative esophagectomy are not fully understood. Data on recurrence patterns and sites of recurrence in patients with recurrent esophageal cancer after curative esophagectomy from 2005 to 2015 were retrospectively analyzed. Time to recurrence after curative esophagectomy and survival after recurrence were compared among groups stratified by recurrence pattern and site. Multivariate analysis was performed to identify clinicopathological parameters influencing survival after recurrence. Of the 290 patients identified, a single pattern of recurrence occurred in 224 patients (77.2%) and a multiple pattern of recurrence occurred in 66 patients (22.8%). The most frequent recurrence pattern was lymph node in 173 patients (59.7%), followed by distant organ in 133 patients (45.9%). Median time to recurrence and median survival after recurrence of all patients were 228 and 327 days, respectively. Among patients with lymph node or lung recurrence, there were 5-year survivors after recurrence who underwent multimodal therapy. Multivariate analysis revealed that longer disease-free interval [hazard ratio (HR) 0.70, 95% confidence interval (95% CI) 0.52-0.93], single pattern of recurrence (HR 0.54, 95% CI 0.39-0.74), and curative treatment for recurrence (HR 0.17, 95% CI 0.10-0.28) were significantly associated with favorable prognosis. Although the prognosis of recurrent esophageal cancer remains unfavorable, if multimodal treatment that includes local therapy was curative, prognosis could improve, especially in patients with lymph node or lung recurrence.


[Ischemic heart failure making the diagnosis of a Vaquez disease: a rare event].
We present the case of a 46-year-old patient without any past medical history, admitted to our ICU for cardiogenic shock complicating acute coronary syndrome. The blood tests found polycethemia, a polycethemia vera was suspected and confirmed by genetic analysis. Ischemic heart failure as an initial symptom of polycethemia vera and its treatment by arterial bleeding is a rare event that we describe in this article.


Calcium-dependent stimulation of 3-O-methylglucose uptake in rat thymocytes by the divalent cation ionophore A23187.
A23187 (0.2 TO 1.0 Nmol/mg of cell protein) stimulates the transport of 3-O-methylglucose by rat thymocytes more than 2-fold within 10 min in the presence of 1.9 mM Ca2+. Under these conditions, Ca2+ uptake by the cells increases 3- to 10-fold. The ionophore is less effective at lower Ca2+ concentrations and it has no effect on 3-O-methylglucose uptake when ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetate (EGTA) is present in excess over Ca2+. Excess EGTA does not reduce the elevated rates of 3-O-methylglucose transport in cells already stimulated with A23187 on 3-O-methylglucose transport is completely blocked by inhibitors of oxidative phosphorylation. The results suggest that elevated cytoplasmic Ca2+ concentrations activate some ATP-dependent mechanism that modifies the glucose transport system in a manner that is not readily reversible.


[An evaluation method for analysis of correlation between traditional Chinese medicine syndrome and seasonal changes of weather based on information entropy].
A method based on dubious condition of information entropy was introduced and applied to discuss a complexity problem in the analysis of correlation between traditional Chinese medicine (TCM) syndrome and season. Eight hundred and seventy one cases of chronic virus hepatitis B (hepatitis B) with TCM clinical data were analyzed by information entropy method. It was found that hepatitis B with Yin deficiency of liver and kidney happened more often in summer than in other seasons. It is inferred that the difference of seasons may influence the variation of TCM syndromes.


Salivary gland neoplasia: an outcome of modified morphogenesis and cytodifferentiation.
Regeneration and replenishment of salivary tissues proceed in a manner analogous to stages in the embryonic development of salivary glands. The regenerative potential of the salivary unit resides in the reserve or stem cells of the intercalated and excretory ducts. Neoplastic development in salivary glands may be regarded as an epigenetic event, imposed by an ocogenic stimulus onto morphogenesis and cell differentiation. Depending on the level of differentiation of the reserve cell's progeny at the time of oncogenesis, the corresponding neoplasm can be poorly differentiated or anaplastic or as well differentiated as a histologically low-grade acinous cell carcinoma.


In vitro analyses of the anti-fibrotic effect of SPARC silencing in human Tenon's fibroblasts: comparisons with mitomycin C.
Failure of glaucoma filtration surgery (GFS) is commonly attributed to scarring at the surgical site. The human Tenon's fibroblasts (HTFs) are considered the major cell type contributing to the fibrotic response. We previously showed that SPARC (secreted protein, acidic, rich in cysteine) knockout mice had improved surgical success in a murine model of GFS. To understand the mechanisms of SPARC deficiency in delaying subconjunctival fibrosis, we used the gene silencing approach to reduce SPARC expression in HTFs and examined parameters important for wound repair and fibrosis. Mitomycin C-treated HTFs were used for comparison. We demonstrate that SPARC-silenced HTFs showed normal proliferation and negligible cellular necrosis but were impaired in motility and collagen gel contraction. The expression of pro-fibrotic genes including collagen I, MMP-2, MMP-9, MMP-14, IL-8, MCP-1 and TGF-β(2) were also reduced. Importantly, TGF-β(2) failed to induce significant collagen I and fibronectin expressions in the SPARC-silenced HTFs. Together, these data demonstrate that SPARC knockdown in HTFs modulates fibroblast functions important for wound fibrosis and is therefore a promising strategy in the development of anti-scarring therapeutics.


MEMS fabricated chip for an implantable drug delivery device.
We present a silicon-based implantable drug delivery system (IDDS) for the administration of compounds in vivo. The implanted device contains the drug-filled silicon microchip, control circuitry, telemetry capability, and a battery. At the heart of the IDDS is the drug-containing microchip, a MEMS (MicroElectroMechanical Systems)-based device. A process was developed for the fabrication of the silicon chip. MicroCHIPS' drug release technology has been successfully demonstrated in vitro and in vivo using the therapeutic peptide leuprolide as a model compound.


[The estimation of serum concentration of vascular endothelial growth factor in patients with non-small cell lung cancer].
Vascular endothelial growth factor (VEGF) is main angiogenic factor, which stimulates endothelial cells migration and proliferation. The extensive angiogenesis plays important role in tumor growth and metastasis. Analysis of serum concentrations of vascular endothelial growth factor in patients with non-small cell lung cancer depending on clinicopathologic findings. The study group consisted of 50 patients with non-small cell lung cancer (16 females and 34 males) ranging in age from 47 - 80 years (mean age 63 +/- 8.2). Serum VEGF concentration was evaluated by ELISA. VEGF concentrations in serum did not differ significantly between groups of patients with different T-, N- and M-factor. Patients with inoperable tumor (IIIB and IV) had significantly higher serum VEGF concentrations compared with resected tumor (I-IlIA) and locally advanced cancer (IIIA). Serum VEGF may be a marker of tumor progression in non-small cell lung cancer.


An unusual case of malignant pilocytic astrocytoma occurring in the eye.
Pilocytic astrocytoma is a central nervous system neoplasia that arises during pediatric age. Only few cases have been documented in patients older than 50 years old. It is a low-grade lesion that can rarely undergo malignant changes presenting the histologic features of a high-grade glioma. We report a case of a pilocytic astrocytoma arising in the eyeball of a 53-year-old man affected by glaucoma that underwent malignant evolution.


Internal audit of a comprehensive IMRT program for prostate cancer: a model for centers in developing countries?
With improving regional prosperity, significant capital investments have been made to rapidly expand radiotherapy capacity across Southeast Asia. Yet little has been reported on the implementation of adequate quality assurance (QA) in patient management. The objective of this study is to perform an in-depth QA assessment of our definitive intensity-modulated radiotherapy (IMRT) program for prostate cancer since its inception. The department's prostate IMRT program was modeled after that of the University of California San Francisco. A departmental protocol consisting of radiotherapy volume/dose and hormone sequencing/duration and a set of 18 dose objectives to the target and critical organs were developed, and all plans were presented at the weekly departmental QA rounds. All patients treated with definitive IMRT for nonmetastatic prostate cancer were retrospectively reviewed. Protocol adherence, dosimetry data, toxicities, and outcomes were evaluated. Since 2005, 76 patients received IMRT: 54 with whole-pelvis and 22 with prostate-only treatment. Of the 1,140 recorded dosimetric end points, 39 (3.3%) did not meet the protocol criteria. At QA rounds, no plans required a revision. Only one major protocol violation was observed. Two and two cases of Grade 3-4 acute and late toxicities, respectively, were observed. Five (8.8%) patients developed proctitis, but only one required argon laser therapy. Our comprehensive, practice-adapted QA measures appeared to ensure that we were able to consistently generate conforming IMRT plans with acceptable toxicities. These measures can be easily integrated into other clinics contemplating on developing such a program.


Adjunctive use of delayed and adjustable low-dose 5-fluorouracil in refractory glaucoma.
We used delayed 5-mg subconjunctival injections of 5-fluorouracil as an adjunct to filtering surgery in ten eyes with refractory glaucoma. The first 5-fluorouracil injection was made three to 15 days postoperatively and was used only when clinical signs suggested an impending bleb failure. These signs included flattening and localization of bleb, increased vascularity, early subconjunctival scarring, loss of microcystic conjunctival changes, and increased intraocular pressure. After a follow-up of ten to 17 months (mean, 13.7 months), an intraocular pressure of less than 21 mm Hg was attained in five eyes without medication and in four eyes with medication. The treatment failed in one eye. The average dose of 5-fluorouracil was 28 +/- 12 mg per eye. There were no conjunctival wound leaks. Six eyes developed transient corneal epithelial defects. The modified administration of 5-fluorouracil can result in fewer conjunctival wound leaks. Its use can be limited to those patients who show evidence of impending bleb failure.


A Tcf/Lef element within the enhancer region of the human NANOG gene plays a role in promoter activation.
NANOG is a homeodomain-containing transcription factor that is essential for the maintenance of pluripotency and self-renewal in embryonic stem cells. However, the molecular mechanisms underlying the regulation of NANOG expression in human cells remain largely unknown. Here, we investigated the role of Tcf/Lef response elements located in the enhancer of the human NANOG gene. We found that forced expression of Lef1 or β-catenin stimulated human NANOG promoter activity, while shRNA-mediated knockdown of β-catenin reduced Lef1-induced NANOG promoter activation. Deletion or mutation of the Tcf/Lef element within the enhancer region of the human NANOG gene completely abrogated Lef1-induced NANOG promoter activity. The results of a chromatin immunoprecipitation assay demonstrated that Lef1 and β-catenin bind to the Tcf/Lef element in the enhancer region of the NANOG gene. Forced expression of GSK-3β inhibited basal, Lef1-induced, and β-catenin-induced NANOG promoter activity, while treatment with the GSK-3β inhibitor SB216763 resulted in the accumulation of β-catenin and NANOG protein. Furthermore, Dvl-1-induced NANOG promoter activity was abrogated by the expression of β-catenin shRNA. Stable overexpression of Dvl-1 caused β-catenin and NANOG to accumulate. These results indicate that the Tcf/Lef response element in the enhancer region of the human NANOG gene is able to stimulate NANOG gene transcription.


Clinicopathologic features, tumor immune microenvironment and genomic landscape of EBV-related and EBV-unrelated poorly differentiated nonkeratinizing squamous cell carcinoma of the thymus.
Knowledge regarding thymic EBV-related poorly differentiated nonkeratinizing squamous cell carcinoma (PDNKSCC), also known as lymphoepithelial carcinoma (LEC), is extremely limited due to its rarity. This multi-institutional study enrolled 85 patients with thymic PDNKSCC. DNA in situ hybridization was performed to evaluate the EBV status of all 85 cases. Immunohistochemistry and next generation sequencing were performed to compare the differences in the clinicopathological and molecular features between EBV-related and EBV-unrelated PDNKSCC. Tumor-infiltrating lymphocytes (TILs) were also analyzed by these methods. The 85 cases were classified into 27 EBV-related PDNKSCCs (31.8 %) and 58 EBV-unrelated PDNKSCCs (68.2 %) according to the EBV status, and 35 Lymphoepithelioma pattern (LP) (41.2 %) and 50 desmoplastic pattern (DP) (58.8 %) according to the histological characteristics. Compared to the EBV-unrelated PDNKSCC, EBV-related PDNKSCC showed a younger patient predominance and more commonly displayed a LP subtype. Additionally, LP-type cases were divided into two groups: Group 1 (EBV-related, 20/85) and Group 2 (EBV-unrelated, 15/85); the DP-type cases were divided into Group 3 (EBV-unrelated, 43/85) and Group 4 (EBV-related, 7/85). The four Groups showed a significant association with patients' OS and PFS. EBV-related PDNKSCC had significantly higher PD-L1 + tumor cells (TCs) and PD-L1 + and CD8 + immune cells (ICs) than EBV-unrelated PDNKSCC. The tumor microenvironment immune type (TMIT) I (PDL1-Tumor+/CD8-High) was more common in EBV-related PDNKSCC, especially in Group 1(LP and EBV related) with more than 90 % cases belonged to TMIT I. Molecular analysis demonstrated that EBV-related PDNKSCC had a significantly higher tumour mutational burden and frequency of somatic mutations than EBV-unrelated cases. EBV-related PDNKSCC, especially the Group 1, could be a candidate for immunotherapy and EBV positivity may provide an indication for the selection of targeted therapy due to their high tumour mutational burden.


Independent Influence of Skin Temperature on Whole-Body Sweat Rate.
It is often assumed that a person with a higher mean skin temperature (Tsk) will sweat more during exercise. However, it has not yet been demonstrated whether Tsk describes any individual variability in whole-body sweat rate (WBSR) independently of the evaporative requirement for heat balance (Ereq). One hundred forty bouts of 2-h treadmill walking completed by a pool of 21 participants (23 ± 4 yr, 174 ± 8 cm, 76 ± 11 kg, 1.9 ± 0.2 m) under up to nine conditions were analyzed. Trials employed varying rates of metabolic heat production (Hprod; 197-813 W), and environmental conditions (15°C, 20°C, 25°C, 30°C; all 50% relative humidity), yielding a wide range of Ereq (86-684 W) and Tsk values (26.9°C-34.4°C). The individual variation observed in WBSR was best described using Ereq (in watts; R = 0.784) as a sole descriptor, relative to Ereq (in watts per meter squared; R = 0.735), Hprod (in watts; R = 0.639), Hprod (in watts per meter squared; R = 0.584), ambient air temperature (Ta) (R = 0.263), and Tsk (R = 0.077; all, P < 0.001). A multiple stepwise linear regression included only Ereq (in watts; adjusted R = 0.784), with Tsk not significantly correlating with the residual variance (P = 0.285), independently of Ereq (in watts). Hprod (in watts) had similar predictive strength to Ereq (in watts) at a fixed air temperature, explaining only 5.2% at 30°C, 4.9% at 25°C, 2.7% at 20°C, and 0.5% at 15°C (all, P < 0.001) less variance in WBSR compared with Ereq. However, when data from all ambient temperatures were pooled, Hprod alone was a markedly worse predictor of WBSR than Ereq (R = 0.639 vs 0.784; P < 0.001). Ereq (in watts) explained approximately four-fifths of the individual variation in WBSR over a range of ambient temperatures and exercise intensities, whereas Tsk did not explain any residual variance independently of Ereq.


13 C NMR spectra of some halocarbons. Shift predictions in polychloro-quinolines and -isoquinolines.
Three methods, two empirical and one semi-empirical, for predicting 13 C chemical shifts in six poly-chloroheterocyclics are considered. It was found that the semi-empirical correlations with CNDO/2 calculated charges, although useful, could not be used in isolation from the other two methods. Of these, the MSCS (multiple substituent chemical shifts) method could be used to predict all eighteen carbon shifts in perchloroquinoline and perchloroisoquinoline, whilst the NIMS method (hypothetical nitrogen insertion method) was limited to the carbons in the heterocyclic ring. In brief, it was found that the MSCS method was the most accurate (less than ± 1 ppm) for predicting chemical shifts, intrinsically compensating for some of the errors arising from mutual atom-atom interactions. New 13 C data are reported for heptachloroquinoline, a mixture of two polychloroquinolines, hepta-chloroisoquinoline and two, separable, new polychloroisoquinolines.


Effect of ethanol on neuromuscular function in rats. Its interaction with alcuronium.
The effect of chronic ethanol intake on neuromuscular function has been analyzed by using a rat tibial muscle preparation. The time-course of single twitches, trains-of-four, tetanus and post-tetanic facilitation with and without blockade with alcuronium was evaluated. A decrease in these parameters was observed, being more pronounced in ethanol fed rats during 10 than 30 days. The twitch was the most affected parameter. After recovery of alcuronium blockade, the depressant effects of ethanol were completely reversed. These data suggest that low but sustained ethanol blood levels causes evident alterations of neuromuscular function due, probably, to a postjunctional action.


Simultaneous electrophysiological and morphological assessment of functional damage to neural networks in vitro after 30-300 g impacts.
An enigma of mild traumatic brain injury are observations of substantial behavior and performance deficits in the absence of bleeding or other observable structural damage. Altered behavior and performance reflect changes in action potential (AP) patterns within neuronal networks, which could result from subtle subcellular responses that affect synaptic efficacy and AP production. The aim of this study was to investigate and quantify network activity changes after simulated concussions in vitro and therewith develop a platform for simultaneous and direct observations of morphological and electrophysiological changes in neural networks. We used spontaneously active networks grown on microelectrode arrays (MEAs) to allow long-term multisite monitoring with simultaneous optical observations before and after impacts delivered by a ballistic pendulum (30 to 300 g accelerations). The monitoring of AP waveshape templates for long periods before and after impact provided an internal control for cell death or loss of cell-electrode coupling in the observed set of neurons. Network activity patterns were linked in real-time to high power phase contrast microscopy. There was no overt loss of glial or neuronal adhesion, even at high-g impacts. All recording experiments showed repeatable spike production responses: a loss of activity with recovery to near reference in 1 hr, followed by a slow activity decay to a stable, level plateau approximately 30-40% below reference. The initial recovery occurred in two steps: a rapid return of activity to an average 24% below reference, forming a level plateau lasting from 5 to 20 min, followed by a climb to within 10% of reference where a second plateau was established for 1 to 2 hrs. Cross correlation profiles revealed changes in firing hierarchy as well as in Phase 1 in spontaneous network oscillations that were reduced by as much as 20% 6-8 min post impact with only a partial recovery at 30 min. We also observed that normally stable nuclei developed irregular rotational motion after impact in 27 out of 30 networks. The evolution of network activity deficits and recovery can be linked with microscopically observable changes in the very cells that are generating the activity. The repeatable electrophysiological impact response profiles and oscillation changes can provide a quantitative basis for systematic evaluations of pharmacological intervention strategies. Future expansion to include fluorescent microscopy should allow detailed investigations of damage mechanisms on the subcellular level.


Biomechanical considerations for strategies to improve outcomes following volar plating of distal radius fractures.
This article is a systematic review of the recent published literature on the biomechanics of volar locking plate fixation of distal radius fractures. PUBMED/MEDLINE and EMBASE databases were searched on 13th Sep 2018. Biomechanical papers on volar locking plate fixation of distal radius fractures since 2010 were included. Papers were analysed and included studies were appraised by the author using the validated quality assessment GRADE tool. The search revealed 456 papers between January 2010 and the present day whose abstracts were reviewed for relevance and 21 papers were included for full paper review. The aim of this systematic review was to evaluate the evidence to determine the surgical techniques and strategies that are associated with the best biomechanical outcomes of volar plating for distal radius fractures. Review of the literature revealed that it was not necessary to fill all available distal locking screws, there was little evidence to support the use of 2 rows of screws distally over 1 row. Screws of 75% length of the distal cortex are sufficient to withstand standard postoperative regimes in extrarticular fractures. The was a paucity of evidence to conclude multidirectional locking plates were superior to fixed angle plates or that one brand of plate was superior to another.


Synthesis and optimization of novel 4,4-disubstituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors.
The synthesis and SAR of a series of 4,4-disubstituted cyclohexylbenzamide inhibitors of 11β-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models.


Adherence to Biopsy and Follow-Up Guidelines in a Population-Based Cohort of Children With Eosinophilic Esophagitis.
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated condition that is becoming more widely recognized in children. Recent EoE practice guidelines provide clear recommendations on adequate biopsy sampling at diagnostic endoscopy and necessity of close follow-up endoscopy with biopsy to ensure mucosal healing with therapy.1 Despite these recommendations, adherence to biopsy guidelines, time to first follow-up endoscopy, and overall surveillance endoscopy rates have not been robustly studied. Using a population-based cohort of children diagnosed with EoE in Utah, we assessed adherence to guidelines across multiple provider types, including academic pediatric gastroenterologists (PGIs), private practice PGIs, and adult-trained providers performing endoscopy in children.


Prodromal symptoms in panic disorder with agoraphobia: a replication study.
The majority of 20 patients suffering from panic disorder with agoraphobia reported experiencing agoraphobic avoidance, generalized anxiety, and/or hypochondriacal fears and beliefs before the first panic attack. The results replicated those of a previous investigation and are in accordance with an increasing number of studies concerned with prodromal symptoms, epidemiologic surveys, and analysis of mechanisms of change upon treatment.


Characterization of the metabolites of GW1929 in rat by liquid chromatography coupled with electrospray ionization tandem mass spectrometry.
GW1929 is a potent PPAR-γ activator. To fully understand its mechanism of action, it is necessary to study the in vitro and in vivo metabolism. For in vitro metabolism, GW1929 was incubated with rat hepatocytes at 37°C for 2 h. For in vivo metabolism, rats were orally administered with GW1929 at a single dose of 10 mg/kg and plasma, urinary and fecal samples were collected at defined time points. All the samples were analyzed by the developed ultra-high-performance liquid chromatography combined with tandem mass spectrometry. The structures of metabolites were proposed according to their accurate masses and product ions. A total of 17 metabolites, including seven glucuronide conjugates, were detected and structurally identified. M4 (hydroxylation), M13 (demethylation) and M14 (hydroxylation) were the most abundant metabolites. The metabolic pathways of GW1929 referred to hydroxylation, demethylation, deamination and glucuronidation. The present study provided new information on the in vitro and in vivo metabolic profiles of GW1929 which will be helpful for a better understanding of the mechanism of the elimination of GW1929.


Inhibitors of histone deacetylases induce tumor-selective cytotoxicity through modulating Aurora-A kinase.
The molecular basis of the antitumor selectivity of histone deacetylase inhibitors (HDIs) remains unclear. Centrosomal Aurora-A kinase regulates chromosomal segregation during mitosis. The overexpression or amplification of Aurora-A leads to genetic instability, and its inhibition has shown significant antitumor effects. In this paper, we report that structurally related hydroxamate LAQ824 and SK-7068 induce tumor-selective mitotic defects by depleting Aurora-A. We found that HDI-treated cancer cells, unlike nontransformed cells, exhibit defective mitotic spindles. After HDI, Aurora-A was selectively downregulated in cancer cells, whereas Aurora-B remained unchanged in both cancer and nontransformed cells. LAQ824 or SK-7068 treatment inhibited histone deacetylase (HDAC) 6 present in Aurora-A/heat shock protein (Hsp) 90 complex. Inhibition of HDAC6 acetylated Hsp90 and resulted in dissociation of acetylated Hsp90 from Aurora-A. As a result, Hsp70 binding to Aurora-A was enhanced in cancer cells, leading to proteasomal degradation of Aurora-A. Overall, these provide a novel molecular basis of tumor selectivity of HDI. LAQ824 and SK-7068 might be more effective HDIs in cancer cells with Aurora-A overexpression.


Proteins of the camel erythrocyte membrane.
Electrophoresis on polyacrylamide gels containing dodecyl sulphate has revealed that the major proteins of the camel erythrocyte membrane are similar to those of the human and bovine species in both electrophoretic mobility and relative abundance. The major difference lies in the major intrinsic membrane protein of molecular weight approx. 100 000. In the camel, this protein has a higher apparent molecular weight than in the human and bovine species. The very high molecular weight water-soluble protein "spectrin" appears to be very tightly bound to the camel erythrocyte membrane, and is only partially extracted after prolonged low ionic strength dialysis. Total release of spectrin is only achieved by means of more drastic treatment such as incubation with urea, guanidine hydrochloride, sodium hydroxide of p-chloromercuribenzoate. Concurrent with the total release of spectrin, the camel cells undergo a shape change from flat ellipsoids to spheres, suggesting an important shape-maintaining role for spectrin in the erythrocytes of this species.


Eye development: random precision in color vision.
In insect and vertebrate eyes, different types of color-detecting photoreceptors are randomly distributed throughout the retina. A recent study has provided important new insights into the developmental mechanisms that generate the retinal mosaic required for color vision.


Assessing cytochrome P450 function using genetically engineered mouse models.
The ability to knock out and/or humanize different genes in experimental animals, globally or in cell- and tissue-specific patterns, has revolutionized scientific research in many areas. Genetically engineered mouse models, including knockout models, transgenic models, and humanized models, have played important roles in revealing the in vivo functions of various cytochrome P450 (CYP) enzymes. These functions are very diverse, ranging from the biotransformation of drugs and other xenobiotics, events that often dictate their pharmacokinetic or toxicokinetic properties and the associated therapeutic or adverse actions, to the metabolism of endogenous compounds, such as steroid hormones and other bioactive substances, that may determine susceptibility to many diseases, such as cancer and metabolic diseases. In this review, we provide a comprehensive list of Cyp-knockout, human CYP-transgenic, and CYP-humanized mouse models that target genes in the CYP1-4 gene families, and highlight their utility in assessing the in vivo metabolism, bioactivation, and toxicity of various xenobiotic compounds, including therapeutic agents and chemical carcinogens. We aim to showcase the advantages of utilizing these mouse models for in vivo drug metabolism and toxicology studies, and to encourage and facilitate greater utility of engineered mouse models to further improve our knowledge of the in vivo functions of various P450 enzymes, which is integral to our ability to develop safer and more effective therapeutics and to identify individuals predisposed to adverse drug reactions or environmental diseases.


Visual Outcomes and Patient Satisfaction After Bilateral Refractive Lens Exchange with a Trifocal Intraocular Lens in Patients with Presbyopia.
Refractive lens exchange (RLE) patients represent a unique population with a different baseline and set of expectations compared to their cataract counterparts. Visual outcomes and patient satisfaction following RLE with bilateral implantation of a trifocal intraocular lens (IOL) were assessed in a cohort of patients with presbyopia and without cataract. Charts of patients with presbyopia who underwent femtosecond laser-assisted RLE with bilateral implantation of the PanOptix trifocal IOL (toric and non-toric) at a single-surgeon, private practice center from September 2019 to August 2020 were retrospectively reviewed. Eyes with prior keratorefractive surgery, amblyopia, or underlying pathology were excluded. Primary endpoints included corrected and uncorrected visual acuity at distance (CDVA and UDVA), intermediate (DCIVA and UIVA), and near (DCNVA and UNVA) at 6 months. Secondary endpoints included residual refractive error, patient-reported satisfaction, spectacle independence, and visual disturbance profile as assessed by a validated questionnaire at 6 months. Seventy-eight eyes of 39 patients (mean age 56 ± 6 years; 79% female) were included. Most eyes were hyperopic (mean SE 2.35 ± 1.81). Postoperatively, 100% and 92% of eyes were within ± 1.00 D and ± 0.50 D of emmetropia, respectively. One hundred percent, 97%, and 97% of patients achieved UDVA, UNVA, and UIVA of logMAR 0.1 or better. Starbursts were the most frequent (67%) and bothersome (41%) visual disturbance cited, but nearly half (41%) of patients rated them as absent or "not bothersome at all." Overall, 77% of patients reported achieving complete spectacle independence with 87% and 90% of patients stating they were satisfied with their vision and would recommend the same procedure to others, respectively. RLE with bilateral implantation of the PanOptix IOL is a safe and effective procedure with good patient satisfaction. Because of their relatively clear native lenses and visually demanding needs compared to their cataract counterparts, surgeons should take extra precautions to counsel RLE patients on the limitations of trifocal technology.


Clinical efficacy and safety of first-line treatments in patients with mantle cell lymphoma: A systematic literature review.
Mantle cell lymphoma (MCL) is a rare form of non-Hodgkin's lymphoma (NHL) with a median overall survival (OS) of approximately 3-5 years. Systematic literature reviews (SLRs) identified efficacy and safety data for first-line therapies, reported in randomised controlled trials (RCTs) and non-randomised interventional studies (NRISs). Nine and 20 independent studies were included in the RCT and NRISs SLRs, respectively. Differences in the regimens and patient outcomes varied according to patient age and suitability for autologous stem cell transplantation (ASCT). In elderly patients ineligible for transplant, OS ranged from 40 months to 69.6 months. In young transplant-eligible patients, OS ranged from 53 months to 152.4 months. Despite the paucity of directly comparable evidence on the efficacy and safety of MCL therapies, these SLRs highlight that MCL remains a difficult NHL subtype to treat, with short survival highlighting the unmet need for newer treatments that improve patient outcomes.


Comparison of simultaneous 99mTc-HMPAO and 111In oxine labelled white cell scans in the assessment of inflammatory bowel disease.
Forty-seven patients, 29 with chronic inflammatory bowel disease (IBD) and 18 with presumed irritable bowel syndrome, including one with uncomplicated diverticular disease, were studied with simultaneous technetium-99m hexamethylpropylene amine oxime and indium-111 oxine labelled leucocyte scans performed at 1, 3 and 24 h. Twenty-seven patients with IBD had active disease as judged by clinical and laboratory criteria and all of these had positive scans with both agents. No false positive studies were obtained. The 1-h 99mTc-HMPAO WBC scans showed the same distribution to disease as the 3-h 111-In WBC scans, with no difference in intensity (P < 0.92); they showed more extensive disease (P < 0.02) and more intense uptake (P < 0.001) than did the 1-h 111-In scans. The 3-h 99mTc-HMPAO WBC scans showed more extensive disease (P < 0.002), with greater intensity (P < 0.0005), than did the 3-h 111In WBC scans. Physiological bowel activity on 3-h 99mTc-HMPAO WBC scans was present in 12 patients but was faint and did not interfere with assessment of disease extent and activity. It is concluded that in terms of isotope availability, radiation dosimetry and image quality, 99mTc-HMPAO is the agent of choice in detecting active IBD, with localization of disease possible at 1-h after re-injection and optimal resolution and definition of disease extent at 3 h. A negative scan reliably excludes active disease.


Compensatory mutations suggest that base-pairing with a small nuclear RNA is required to form the 3' end of H3 messenger RNA.
Processing of the 3' end of sea urchin H3 histone pre-mRNA requires conserved sequence elements and the presence of U7 snRNA. A mutation in the conserved CAAGAAGA sequence of the H3 pre-mRNA that renders 3' processing of this precursor defective is shown to be suppressed by a compensatory change in the U7 snRNA, restoring the base-pairing potential of the two RNAs. RNA-RNA contacts between these two molecules appear to be an essential feature of the 3' processing reaction.


General kinetic and dynamic principles and their application to continuous infusion anaesthesia.
The use of intravenous anaesthetic agents by continuous infusion requires knowledge of their pharmacokinetic properties. In this article, the general pharmacokinetic principles behind the use of infusions of intravenous agents are presented and the literature with regard to the individual drugs used in this way is reviewed.


Sexual Morbidity Assessment in Gyne-Oncology Follow-Up: Development of the Sexual Well-Being After Cervical or Endometrial Cancer (SWELL-CE) Patient-Reported Outcome Measure.
Clinical assessment and management of sexual difficulties after gynecological cancer remain a neglected aspect of women's rehabilitation. To develop and validate a patient-reported outcome measure of sexual well-being for women experiencing sexual consequences of cervical and endometrial cancer treatment for use in routine follow-up. This is a sequential mixed method study comprising (i) in-depth qualitative interviews (n=21 of 118) to generate items regarding sexual consequences of cervical or endometrial cancer and treatment; (ii) questionnaire construction with 51 core items (all respondents) and 4 subsections (18-58 items), depending on the relationship status and whether or not participants were sexually active (SA/NSA); (iii) item refinement following cognitive debriefing (n=13 of 21); (iv) validation of resultant items via postal survey (n=788 women) and Rasch analysis; and (v) creation of brief (14-item) clinical screener. Women attending routine follow-up (3 months to 5 years) at 6 English cancer centers and members of 3 UK cancer patient websites, who met the study inclusion criteria, were invited to participate. The primary outcome of this study was the construction and initial psychometric testing of SWELL-CE short and long form versions. 21 women participated in interviews and 250 of 788 (32%) returned the postal survey (T1). 110 draft items were evaluated using cognitive testing (n=13) to refine instrument design and test face validity, comprehension, and acceptability. Exploratory factor analysis of survey data (n=250) produced an initial 6 domain structure as a guidance for the Rasch analysis. Subsequent Rasch analysis yielded a 3 domain structure: physical sexual function, sexual and relationship concerns, and sexual desire and sexual self-esteem, each satisfying Rasch model requirements within their respective SA (item pool =59) and NSA (item pool =53) categories, including the absence of local response dependency and all showing strict unidimensionality. The 3 subscales demonstrated good psychometric properties, external validity, and test-retest reliability. A valid Rasch short form of 14 items was created from the larger item pool. This PROM may assist clinicians to improve identification, discussion, and management of women who could benefit from sexual rehabilitation. Initial evaluation supports psychometric validity and reliability in the assessment of physical sexual function, sexual interest and sexual self-esteem, and sexual and relationship concerns in this study sample. However, given this study's modest response rate (32%, n=250), findings should be interpreted with caution. This PROM identifies sexual concerns in women who are sexually active or sexually non-active due to illness or treatment-associated sexual difficulties. Sexual Well-being after Cervical or Endometrial Cancer is a novel and psychometrically valid sexual well-being measure for clinical assessment of female sexual difficulties after cervical or endometrial cancer treatment. White ID, Tennant A, Taylor C, Sexual Morbidity Assessment in Gyne-Oncology Follow-Up: Development of the Sexual Well-Being After Cervical or Endometrial Cancer (SWELL-CE) Patient-Reported Outcome Measure. J Sex Med 2020;17:2005-2015.


Effectiveness of a warm-up programme to reduce injuries in youth volleyball players: a quasi-experiment.
To establish the effectiveness of the 'VolleyVeilig' programme on reducing injury rate, injury burden and injury severity in youth volleyball players. We conducted a quasi-experimental prospective study over one season of youth volleyball. After randomisation by competition region, we instructed 31 control teams (236 children, average age 12.58±1.66) to use their usual warm-up routine. The 'VolleyVeilig' programme was provided to 35 intervention teams (282 children, average age 12.90±1.59). This programme had to be used during each warm-up before training sessions and matches. We sent a weekly survey to all coaches, collecting data on each player's volleyball exposure and injuries sustained. Multilevel analyses estimated differences in injury rates and burden between both groups, and we used non-parametric bootstrapping to compare the differences in injury numbers and injury severity. We found an overall reduction in injury rates of 30% for intervention teams (HR 0.72; 95% CI 0.39 to 1.33). Detailed analyses revealed differences for acute (HR 0.58; 95% CI 0.34 to 0.97) and upper extremity injuries (HR 0.41; 95% CI 0.20 to 0.83). Compared with control teams, the intervention teams had a relative injury burden of 0.39 (95% CI 0.30 to 0.52) and a relative injury severity of 0.49 (95% CI 0.03 to 0.95). Only 44% of teams fully adhered to the intervention. We established that the 'VolleyVeilig' programme was associated with reduced acute and upper extremity injury rates and lower injury burden and severity in youth volleyball players. While we advise implementation of the programme, programme updates to improve adherence are needed.


RCT Testing Bystander Effectiveness to Reduce Violence.
Bystander-based programs have shown promise to reduce interpersonal violence at colleges, yet limited rigorous evaluations have addressed bystander intervention effectiveness in high schools. This study evaluated the Green Dot bystander intervention to reduce sexual violence and related forms of interpersonal violence in 26 high schools over 5 years. A cluster RCT was conducted. Kentucky high schools were randomized to intervention or control (wait list) conditions. Green Dot-trained educators conducted schoolwide presentations and recruited student popular opinion leaders to receive bystander training in intervention schools beginning in Year 1. The primary outcome was sexual violence perpetration, and related forms of interpersonal violence victimization and perpetration were also measured using anonymous student surveys collected at baseline and annually from 2010 to 2014. Because the school was the unit of analysis, violence measures were aggregated by school and year and school-level counts were provided. A total of 89,707 students completed surveys. The primary, as randomized, analyses conducted in 2014-2016 included linear mixed models and generalized estimating equations to examine the condition-time interaction on violence outcomes. Slopes of school-level totals of sexual violence perpetration (condition-time, p<0.001) and victimization (condition-time, p<0.001) were different over time. During Years 3-4, when Green Dot was fully implemented, the mean number of sexual violent events prevented by the intervention was 120 in Intervention Year 3 and 88 in Year 4. For Year 3, prevalence rate ratios for sexual violence perpetration in the intervention relative to control schools were 0.83 (95% CI=0.70, 0.99) in Year 3 and 0.79 (95% CI=0.67, 0.94) in Year 4. Similar patterns were observed for sexual violence victimization, sexual harassment, stalking, and dating violence perpetration and victimization. Implementation of Green Dot in Kentucky high schools significantly decreased not only sexual violence perpetration but also other forms of interpersonal violence perpetration and victimization.


Study of optical properties of electropolymerized melanin films by photopyroelectric spectroscopy.
Photopyroelectric (PPE) spectroscopy, in the 350-1,075 nm wavelength range, was used to study the optical properties of electropolymerized melanin films on indium tin oxide (ITO) coated glass. The PPE intensity signal as a function of the wavelength lambda, V (n)(lambda) and its phase F (n)(lambda) were independently measured. Using the PPE signal intensity and the thermal and optical properties of the pyroelectric detector, we were able to calculate the optical absorption coefficient beta of melanin in the solid-state. We believe this to be the first such measurement of its kind on this material. Additionally, we found an optical gap in these melanin films at 1.70 eV.


Facilitating Transitions to Adulthood in Pediatric Brain Tumor Patients: the Role of Neuropsychology.
Transition-age patients with history of a pediatric brain tumor are at significant risk for difficulties transitioning to adulthood. We review current transition models and the potential role of neuropsychology in the transition process for adolescent and young adult brain tumor survivors. Several recently developed healthcare transition models include consideration of patients' cognitive and functional capacities, yet currently available transition readiness tools are limited in scope and do not possess adequate normative data across pediatric medical populations. We explore the potential utility and added benefit of systematically incorporating neuropsychology in the transition process for pediatric brain tumor survivors. The literature supports increased evaluation and intervention targeted at psychosocial barriers to transition. Based on these findings, we propose a family-centered and multidisciplinary care model that promotes both medical and broader psychosocial transition processes. Neuropsychology is ideally suited to assess the wide-ranging areas encompassed in transition readiness and to facilitate the transition process.


Therapy of primary headaches: the role of antidepressants.
Antidepressants are included in evidence-based guidelines for the prophylactic therapy of migraine. Although they can cause several side effects depending on the neurochemical activity, and are to be used with caution in older patients, some of them have a well-documented efficacy. Amitriptyline is classified as a Group 1 drug, whereas Fluoxetine is included in Group 2. There is fair support for the effectiveness of other serotonine reuptake inhibitors in migraine prevention. Amitriptyline has demonstrated a consistent efficacy in Chronic Tension Type Headache, and Mirtazapine has a promising profile for the treatment of the same disease.


Niche diversity can explain cross-cultural differences in personality structure.
The covariance structure of personality traits derived from statistical models (for example, Big Five) is often assumed to be a human universal. Cross-cultural studies have challenged this view, finding that less-complex societies exhibit stronger covariation among behavioural characteristics, resulting in fewer derived personality factors. To explain these results, we propose the niche diversity hypothesis, in which a greater diversity of social and ecological niches elicits a broader range of multivariate behavioural profiles and, hence, lower trait covariance in a population. We formalize this as a computational model, which reproduces empirical results from recent cross-cultural studies and also yields an additional prediction for which we find empirical support. This work provides a general explanation for population differences in personality structure in both humans and other animals and suggests a substantial reimagining of personality research: instead of reifying statistical descriptions of manifest personality structures, research should focus more on modelling their underlying causes.


Sequence and phylogenetic analyses of the twin-arginine targeting (Tat) protein export system.
Twin-arginine targeting (Tat) protein secretion systems consist of two protein types, members of the TatA and TatC families. Homologues of these proteins are found in many archaea, bacteria, chloroplasts and mitochondria. Every prokaryotic organism with a fully sequenced genome exhibits either neither family member, or between one and three paralogues of these two family members. The Arabidopsis thaliana genome encodes three of each. Although many mitochondrially encoded TatC homologues have been identified, corresponding TatA homologues have not been found in this organelle. Phylogenetic analyses reveal that most prokaryotic Tat systems consist of one TatC homologue and two sequence-divergent TatA homologues (TatA and TatB). When only one TatA homologue is present, TatB is missing, and when three TatA homologues are present, the third one arose by duplication of TatA, not TatB. Further, homologues most resembling TatB are more sequence-divergent than those more closely resembling TatA. In contrast to the TatA family, the TatC family shows phylogenetic clustering in strict accordance with organismal type. These results are discussed in terms of their probable structural, functional and evolutionary significance.


Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease.
To determine whether pre-hospitalization use of aspirin is associated with all-cause mortality in coronavirus disease 2019 (COVID-19) patients with coronary artery disease (CAD). We recruited 183 adult patients with CAD diagnosed with COVID-19, including 52 taking low-dose aspirin (mean [SD] age, 69.7 [1.1] years; 59.6% men) and 131 without using aspirin (mean [SD] age, 71.8 [0.9] years; 51.9% men), who were admitted in the Tongji hospital in Wuhan, China from January 10, 2020 to March 30, 2020. There was no difference on in-hospital mortality between aspirin group and non-aspirin group (21.2% vs. 22.1%, P = .885). Similarly, for critically severe COVID-19 patients, the mortality in aspirin group was close to that in non-aspirin group (44% vs. 45.9%, P = .872). Moreover, the percentage of patients with CAD taking low-dose aspirin did not differ between those survivors and non-survivors (28.7% vs. 27.5%, P = .885). Meanwhile, the usage of aspirin was not correlated with all-cause mortality in multivariate analysis (OR = 0.944, 95% CI: 0.411-2.172, P = .893). Collectively, our study suggested that the pre-hospitalization use of low-dose aspirin was not associated with the clinical outcome of patients with CAD hospitalized with COVID-19 infections.


The impact of simulation-based mastery learning, booster session timing and clinical exposure on confidence in intercostal drain insertion: a survey of internal medicine trainees in Scotland.
Intercostal chest drain (ICD) insertion is a skill that medical trainees lack confidence in performing. This study explores the impact of a national programme of Simulation-Based Mastery Learning (SBML) on procedural confidence, including the impact of time intervals between booster sessions and interim clinical experience. Internal Medicine Trainees in Scotland were surveyed about confidence and clinical experience with ICD insertion before and immediately after SBML and booster session. Data were matched and analysed using paired sample t-tests. Short interval and long interval groups were compared using Student's unpaired t-test. The impact of interim clinical experience was assessed using Analysis of Variance. Mean confidence in ICD insertion rose following SBML, fell between initial and booster session, and increased again following booster session (P = < 0.001). 33 of 74 trainees had successfully inserted an ICD between sessions. Fall in confidence was unaffected by the time interval between training sessions, but was mitigated by interim clinical experience. SBML boosts trainee confidence in ICD insertion. However, there is evidence of confidence decay, possibly due to a lack of clinical experience between sessions. More research is needed to explore barriers to transfer of skills from simulated to real-world environments.


An unusual cause of complete distal ureteral obstruction: giant fibroepithelial polyp.
Fibroepithelial polyp of the ureter is a rare benign neoplasm of mesodermal origin. It is an extremely rare cause of hydronephrosis in children. It usually causes partial ureteral obstruction without loss of renal function. The preferred treatment is endoscopic or surgical resection of the polyp with preservation of the renal unit. The authors present an adolescent patient with a nonfunctioning left hydronephrotic kidney caused by complete ureteral obstruction caused by a giant fibroepithelial polyp of the distal ureter. This is an extremely rare presentation and outcome of this benign ureteral neoplasm with resultant loss of renal unit.


Revisiting Trypanosome Mitochondrial Genome Mysteries: Broader and Deeper.
What do the products of a genome do, and when and why are they needed? For the protein products of the trypanosomatid parasites' mitochondrial genomes, the total expressed protein repertoire and the identities of the more difficult-to-characterize products have been challenging to acquire. Comparative genomics and new technologies may resolve that.


Ledebouria socialis As a Key to Understanding the Evolution of Gynoecium in Asparagales.
For Ledebouria socialis, a superior ovary with interlocular septal nectaries that are confined to both ascidiate and plicate zones of the carpel is typical. It is impossible to describe the gynoecium zonation consistently, since the existing terminology does not allow us to display all its peculiarities. A part of the nectaries located in the gynophore and ascidiate zone is internalized from the very beginning of development and postgenital fusion is not required for their formation. For the formation of the distal part of the nectary confined to the plicate zone of the carpel, postgenital fusion is required to isolate nectar cavities from the center of the gynoecium. The nectary is internalized along the gynoecium periphery through the outgrowth of receptacle tissues. The structure of nectaries, as in Ledebouria, can be found in many Asparagales with a superior ovary.


Current practice for the treatment of benign intrauterine polyps: a national questionnaire survey of consultant gynaecologists in UK.
To determine current practice regarding removal of endometrial polyps. A self-administered questionnaire to all 1509 UK consultant gynaecologists to enquire about their current practice and potential willingness to participate in a randomised trial. Treatment methods varied considerably. Inpatient polypectomy was used by 91% and the favoured method was blind removal of polyp following hysteroscopic localisation (53%). Direct hysteroscopic polypectomy was more commonly performed by 46% members of endoscopic societies compared to 33% of non-members. Outpatient polypectomy was performed by 19% of users of outpatient diagnostic hysteroscopy compared to 2.5% of non-users. One-third of respondents were willing to enter patients into a randomised controlled trial to determine the optimal intrauterine polyp removal technique. Opinion regarding the relative roles of inpatient or outpatient, and blind or hysteroscopic methods, is divided and a randomised trial comparing the efficacy and safety of these methods is practicable.


Comparison of membrane phospholipids of the rabbit and pig crystalline lens.
Crystalline lenses excised from 5-7-month-old rabbits and pigs were extracted for lipids with chloroform/methanol, 2/1 using the Folch method. The extracted crude lipids were analyzed at 202 MHz by 31P-NMR spectroscopy. Twelve membrane phospholipids were detected. Both rabbit and pig phospholipid profiles contained phosphatidylcholine (PC), lysophosphatidylcholine, phosphatidylcholine plasmalogen, phosphatidylethanolamine (PE), phosphatidylethanolamine plasmalogen (PE plas), phosphatidylserine, sphingomyelin (SPH), and an uncharacterized phospholipid. In addition, pig lens profiles contained lysophosphatidylethanolamine, phosphatidylinositol, cardiolipin and phosphatidylglycerol. The data indicate that these two animal models have significant differences in membrane phospholipid profiles. In each species, however, the bulk phospholipid component resides in the neutral phospholipids PC, PE, PE plas, and SPH.


Docosahexaenoic acid selectively augments muscarinic stimulation of epithelial Cl- secretion.
We investigated the effect of various fatty acids on electrogenic chloride secretion in T84 cells, a model for intestinal epithelium. T84 intestinal epithelial cells grown on permeable supports were studied by conventional current-voltage clamping. Membrane lipids from T84 cells were extracted, transmethylated, and analyzed by gas chromatography. Lipid extracts were fractionated into nonpolar, free fatty acids, and phospholipids by amynopropil column chromatography. Docosahexaenoic acid (DHA) but not eicosapentanoic acid or other fatty acids selectively enhanced the secretory response to the muscarinic agonist carbachol but not the response to other Ca2+ agonists (histamine, thapsigargin, or ionomycin) or the response to the cAMP agonist forskolin. The ability of DHA to augment Cl- secretion appeared to correlate closer with free DHA levels than with membrane-bound DHA. Other effects of DHA on T84 cells included a reduction in transepithelial resistance (a measure of barrier function), actions that were dissociated from the effect on Cl- secretion. The results suggest that DHA, which has been shown to reverse organ pathology in experimental cystic fibrosis, may selectively affect agonist-regulated transport events and other fundamental properties of epithelial cells.


[Relationship between premature labor and maternal age, as well as between premature labor and parity].
Various publications of the last years and own studies, too demonstrate that birth rank and maternal age, as well, in each case independently influence the risk of prematurity. The rate of prematurity for primiparous and multiparous women is above the average; it is just the same for very young and comparatively old women. Basing on a review of literature eventual causes are briefly discussed.


Some lessons learned from using participatory methods in asbestos worker training.
A nonprofit worker training center changed its teaching methods in response to teacher feelings of burnout, student expressions of boredom, and the requests of new staff members. The paper presents one problem-solving case study that was developed. The author discusses some obstacles to using the case study, and her experiences in overcoming those obstacles.


Mitochondrial pharmacology.
Mitochondria are being recognized as key factors in many unexpected areas of biomedical science. In addition to their well-known roles in oxidative phosphorylation and metabolism, it is now clear that mitochondria are also central to cell death, neoplasia, cell differentiation, the innate immune system, oxygen and hypoxia sensing, and calcium metabolism. Disruption to these processes contributes to a range of human pathologies, making mitochondria a potentially important, but currently seemingly neglected, therapeutic target. Mitochondrial dysfunction is often associated with oxidative damage, calcium dyshomeostasis, defective ATP synthesis, or induction of the permeability transition pore. Consequently, therapies designed to prevent these types of damage are beneficial and can be used to treat many diverse and apparently unrelated indications. Here we outline the biological properties that make mitochondria important determinants of health and disease, and describe the pharmacological strategies being developed to address mitochondrial dysfunction.


Erratum: 20(S)-Ginsenoside Rg3 Promotes Senescence And Apoptosis In Gallbladder Cancer Cells Via The P53 Pathway [Corrigendum].
[This corrects the article DOI: 10.2147/DDDT.S84527.].


Mental rehearsal of a task before or after ethanol: tolerance facilitating effects.
Two groups of six male social drinkers learned a psychomotor skill task and then drank the same dose of ethanol (0.62 g/kg) on each of five sessions. Sessions 1 and 5 provided pre-treatment and post-treatment measures of task performance under ethanol. During treatment sessions 2, 3 and 4, one group (MRBD) mentally rehearsed the task before drinking and the other group (MRAD) mentally rehearsed the task after drinking. On the post-treatment session, the MRAD group was significantly less impaired (i.e. more tolerant) than the MRBD group. Thus, mental rehearsal of a task under ethanol facilitates the development of tolerance to the behavioral effects of the drug.


The effects of rotational setup errors in total body irradiation using helical tomotherapy.
Helical tomotherapy (HT) is a form of intensity-modulated radiation therapy that is employed in total body irradiation (TBI). Because TBI targets the whole body, accurate setup positioning at the edge of the treatment volume is made difficult by the whole-body rotational posture. The purpose of this study is to clarify the tolerance for rotational setup error (SE) in the vertical direction. In addition, we perform a retrospective analysis of actually irradiated dose distributions using previous patients' irradiation data. To clarify the effects of rotational SE on the dose distribution, the planned CT images of 10 patients were rotated by 1-5° in the vertical (pitch) direction to create a pseudo-rotational SE image. Then, the effect of the magnitude of the rotational SE on the dose distribution was simulated. In addition, the irradiated dose to the patients was analyzed by obtaining recalculated dose distributions using megavoltage CT images acquired before treatment. The simulation results showed that the average value of the lung volume receiving at least 10 Gy did not exceed the allowable value when the SE value was ≤2°. When the rotational SE was ≤3°, it was possible to maintain the clinical target volume dose heterogeneity within ±10% of the prescribed dose, which is acceptable according to the guidelines. A retrospective analysis of previous patients' irradiation data showed their daily irradiation dose distribution. The dose to the clinical target volume was reduced by up to 3.4% as a result of the residual rotational SE. Although whole-course retrospective analyses showed a statistically significant increase in high-dose areas, the increase was only approximately 1.0%. Dose errors induced by rotational SEs of ≤2° were acceptable in this study.