Path analysis modeling indicates free transport increases ambulance use for minor indications.
Clinically unnecessary ambulance transport is increasing, diverting limited resources from patients needing ambulance transport. It was anecdotally observed that inappropriate ambulance use increased after abolition of a direct patient cost for ambulance transport. In July 2003, direct patient fees were abolished in favor of a universally applied ambulance levy, potentially leading to increased ambulance use by patients with low illness acuity and admission rates. The influence of age, illness acuity, and need for admission on ambulance use was assessed for 55,397 emergency department attendances in 2002 and 2004. Ambulance users were compared with nonusers in both years and attendances for 2002 compared with 2004 using chi-square test for two groups. Logistic regression provided a multivariate model leading to ambulance use. Path analysis modeling to assess interrelationships between factors associated with ambulance use was developed. Ambulance users in both years were older, had more acute illness, and had greater need for admission compared with nonusers. The odds ratio (OR) of arrival by ambulance in 2004 compared with 2002 was 1.14 (95% confidence interval, [CI], 1.12 to 1.17). In 2002, ambulance users were older (OR, 1.42; 95% CI, 1.40 to 1.43), were more likely to need admission (OR, 2.28; 95% CI, 2.16 to 2.4) and had higher illness acuity (OR, 2.02; 95% CI, 1.94 to 2.09). There was a negative correlation between 2004 and illness acuity. Ambulance use increased in 2004 after patient transport fees were abolished. Increased use was associated with decreased age, clinical acuity, and admission need. Abolishing direct patient cost stimulates ambulance use, potentially including inappropriate transport. Path analysis to assess the effect of changed funding on ambulance use could be used to the influence of other locally relevant factors contributing to ambulance use.


Integrated Bioinformatics and Validation Reveal IL1B and Its Related Molecules as Potential Biomarkers in Chronic Spontaneous Urticaria.
The etiopathogenesis of chronic spontaneous urticaria (CSU) has not been fully understood, and there has been extensive interest in the interaction between inflammatory dermatosis and pyroptosis. This study intends to investigate the molecular mechanism of pyroptosis-related genes in CSU via bioinformatic ways, aiming at identifying the potential key biomarker. GSE72540, the RNA expression profile dataset of CSU, was utilized as the training set, and GSE57178 as the validation set. Differently expressed pyroptosis-related genes (DEPRGs), GO, KEGG, and DO analyses were performed. The hub genes were explored by the protein-protein interaction analysis. Moreover, CIBERSORT was employed for estimating immune cell types and proportions. Then, we constructed a DEmRNA-miRNA-DElncRNA ceRNA network and a drug-gene interaction network. Finally, ELISA was used for gene expression analysis. We recognized 17 DEPRGs, whose enrichment analyses showed that they were mostly enriched in inflammatory response and immunomodulation. Moreover, 5 hub genes (IL1B, TNF, and IRF1 are upregulated, HMGB1 and P2RX7 are downregulated) were identified via the PPI network and verified by a validation set. Then immune infiltration analysis displayed that compared with normal tissue, CSU owned a significantly higher proportion of mast cells activated, but a lower proportion of T cells CD4 naive and so on. Furthermore, IL1B was statistically and positively associated with mast cells activated in CSU, and SNHG3, the upstream factor of IL1B in the ceRNA we constructed, also related with mast cells in CSU. Further analysis exhibited that the protein subcellular localization of IL1B was extracellular, according with its intercellular regulation role; IL1B was significantly correlated with key immune checkpoints; and the NOD-like receptor signaling pathway was the mainly involved pathway of IL1B based on the couple databases. What is more, the result of ELISA of CSU patients was the same as the above analyses about IL1B. In addition, the drug-gene interaction network contained 15 potential therapeutic drugs targeting IL1B, and molecular docking might make this relationship viable. IL1B and its related molecules might play a key role in the development of CSU and could be potential biomarkers in CSU.


[Etiopathogenesis of endometriosis related infertility].
In the last years the entire scientific community has devoted remarkable resources to the understanding of endometriosis. In spite of this, endometriosis remains one of the most complex gynecological diseases, in nearly all of its physiopathological aspects and implications. In particular, the association between endometriosis and infertility has proven to be complex and it has been widely discussed. It is generally accepted that moderate/severe endometriosis related sterility is due to mechanical factors, namely to the distortion/subversion of the regular pelvic anatomy. On the contrary, the factors behind infertility/subfertility related to minimal/mild endometriosis are less clear. None of the hypothesized mechanisms exhaustively explained the infertility related to endometriosis, while it is possible that such disease is caused by multiple factors altogether. The aim of this thorough review of the international literature is to analyze the main etiological factors (i.e. alterations in oocyte maturation and/or growth, defects of fertilization, impairments of implantation or aberrant immunological mechanisms) that are potentially involved, as well as the role that each of the above mentioned factors has in determining the endometriosis related infertility/subinfertility.


Novel effect of berberine on thermoregulation in mice model induced by hot and cold environmental stimulation.
The purpose of this study was to assess the effects of berberine (BBR) on thermoregulation in mice exposed to hot (40°C) and cold (4°C) environmental conditions. Four groups of mice were assembled with three different dosages of BBR (0.2, 0.4, and 0.8 mg/kg) and normal saline (control). In room temperature, our largest dosage of BBR (0.8 mg/kg) can reduce rectal temperatures (Tc) of normal mice. In hot conditions, BBR can antagonize the increasing core body temperature and inhibit the expression of HSP70 and TNFα in mice; conversely, in cold conditions, BBR can antagonize the decreasing core body temperature and enhance the expression of TRPM8. This study demonstrates the dual ability of BBR in maintaining thermal balance, which is of great relevance to the regulation of HSP70, TNFα and TRPM8.


Immediate effect of subliminal priming with positive reward stimuli on standing balance in healthy individuals: A randomized controlled trial.
Information received subconsciously can influence exercise performance; however, it remains unclear whether subliminal or supraliminal reward is more effective in improving standing balance ability when priming stimuli are subconsciously delivered. The present study aimed to compare the effects of subliminal priming-plus-subliminal reward stimuli (experimental) with subliminal priming-plus-supraliminal reward stimuli (control) on standing balance ability. This was a single-blind (outcome assessor), parallel-group, randomized controlled trial involving healthy young adults recruited from a university in Japan. Assessments were conducted at baseline and immediately after intervention. The primary outcome was the functional reach test (FRT) measurement. The secondary outcome was one-leg standing time (OLST) with eyes closed. Of the 52 participants screened, 25 were randomly assigned to experimental and control groups each. Both interventions were effective for improving the FRT between the baseline and intervention; however, smaller improvements were observed in the experimental group. We found a large between-groups effect size immediately after the intervention for the FRT (d = -0.92). In contrast, there were no differences in improvements in OLST between the 2 groups (d = -0.06); furthermore, neither intervention was found to be effective for this parameter. We concluded that subliminal priming with conscious reward stimuli results in improvements in immediate-term forward reach ability, which is superior to that achieved by subliminal priming with subconscious reward stimuli.


Base-Free Aqueous-Phase Oxidation of 5-Hydroxymethylfurfural over Ruthenium Catalysts Supported on Covalent Triazine Frameworks.
The base-free aqueous-phase oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxilic acid (FDCA) was performed at 140 °C and 20 bar of synthetic air as the oxidant. Ru clusters supported on covalent triazine frameworks (CTFs) enabled superior conversion (99.9%) and FDCA yields in comparison to other support materials such as activated carbon and γ-Al2O3 after only 1 h. The properties of the CTFs such as pore volume, specific surface area, and polarity could be tuned by using different monomers. These material properties influence the catalytic activity of Ru/CTF significantly as mesoporous CTFs showed superior activity compared to microporous materials, whereas high polarities provide further beneficial effects. The recyclability of the prepared Ru/CTF catalysts was comparable to that of Ru/C at high conversions and product yields. Nevertheless, minor deactivation in five successive recycling experiments was observed.


[Rosuvastatin for the treatment of dyslipidemia in HIV-infected patients receiving highly active antiretroviral therapy. Preliminary experience].
Highly active antiviral therapy (HAART) results in a sharp decrease in HIV-related morbidity and mortality, but also induces adverse effects such as dyslipidemia, which is difficult treat because of drug interactions. Guidelines recommend lipid-lowering therapy with pravastatin or atorvastatin to reduce LDL cholesterol in these patients, and gemfibrozil or fenofibrate for treating hypertriglyceridemia. The use of statins in the management of dyslipidemia is complicated by drug interactions with some of the components of HAART. Rosuvastatin, a statin with minimal cytochrome P-450-mediated metabolism, could be an alternative option for this population. Retrospective study to evaluate the efficacy and safety of rosuvastatin (10 mg/day) for 16 weeks in HAART-treated HIV-infected patients with dyslipidemia, and moderate to high cardiovascular risk. Results were analyzed with the Shapiro-Wilks, K-S Lilliefors, and sign tests. Percentages were analyzed with the chi-square test. Seventy-eight patients were started on rosuvastatin for dyslipidemia, 60 as single therapy. After 16 weeks of treatment, a significant median decrease was seen in both LDL-cholesterol and non-HDL cholesterol (31.3% reduction in LDL and 29.9% in non-HDL). The therapeutic goal for non-HDL was achieved in 65.8% of patients. The decrease in triglyceride levels was also significant (34.1%); 35% of subjects achieved the therapeutic goal. The drug was withdrawn in 2 patients because of myositis, and in 1 because of gastrointestinal intolerance. There were no differences in efficacy or toxicity between patients receiving protease inhibitors, non-nucleoside reverse transcriptase inhibitors, or fibrates. Rosuvastatin was safe and effective for treating dyslipidemia in HAART-treated HIV-infected patients. Results were similar to those observed in the HIV-uninfected population.


ASSOCIATION OF FOXP3 GENE VARIANTS WITH RISK OF HASHIMOTO'S THYROIDITIS AND CORRELATION WITH ANTI-TPO ANTIBODY LEVELS.
Regulatory T cells (Tregs) have critical roles in preventing autoimmune diseases such as Hashimoto's thyroiditis (HT). Forkhead box P3 (Foxp3), the master transcription factor of Tregs, plays a pivotal role in Treg function. Herein, we investigated the association of two single nucleotide polymorphisms (SNPs) of the Foxp3 gene with HT development. A total of 129 HT patients and 127 healthy subjects were genotyped for rs3761548 (-3279 A/C) and rs3761549 (-2383 C/T) in the Foxp3 gene, using polymerase chain reaction-restriction fragment length polymorphism. Genotypic and allelic distribution of rs3761548 SNP showed a significant association with HT. The CC genotype was observed in 37.2% of patients versus 22.1% of the controls [P<0.008, odds ratio (OR): 2.1; 95% confidence interval (CI): 1.2-3.6] and the AC genotype in 41.1% of patients compared to 54.3% of the controls (P<0.025, OR: 2.1; CI: 1.2-3.6). In addition, higher frequency of C allele in patients compared to controls (P=0.05, OR: 1.4; 95% CI: 0.9-2) suggested that patients with the CC genotype and C allele had increased susceptibility to HT. There were significantly higher serum levels of anti-thyroid peroxidase (ATPO) antibody in patients with the rs3761548 CC genotype (1156±163 IU/mL) compared to the other genotypes (≈582-656 IU/mL; P<0.004). We observed a greater frequency of the AC genotype in patients who had decreased ATPO antibody levels (P=0.02). The association of the rs3761548 SNP with risk of HT and its influence on ATPO antibody levels suggested an important role for Foxp3 in the biology and pathogenesis of HT.


Glutathione and cysteines suppress cytotoxicity of gas phase of cigarette smoke by direct reacting with unsaturated carbonyl compounds in the gas phase.
Unsaturated carbonyl compounds, such as acrolein (ACR) and methyl vinyl ketone (MVK), are environmental pollutants, and are contained in smoke, automobile exhaust, and heated oil. We have previously reported that major cytotoxic factors in the gas phase of cigarette smoke are ACR and MVK. ACR and MVK induce cell damage by reactive oxygen species generation via protein kinase C and NADPH oxidases, and antioxidants, such as glutathione (GSH) and N-acetylcysteine (NAC), can effectively suppress their cytotoxic activities. In this study, we attempted to elucidate the molecular mechanism(s) for suppression of ACR- and MVK-induced cytotoxic activities by these antioxidants. GSH, NAC, L- and D-cysteines completely suppressed cell damage induced by gas phase extract of cigarette smoke. The results of HPLC and mass spectrometry showed that GSH and NAC directly reacted with ACR and MVK. Cysteines and cysteine derivatives suppressed ACR-induced GAPDH carbonylation, a representative protein for carbonylation. The current results suggest that GSH, NAC, and cysteines directly reacted with ACR and MVK, and suppressed these unsaturated carbonyl compounds-induced cell damage by inhibition of protein carbonylation.


Sterically hindered ortho-substituted phosphatriptycenes as configurationally stable P-chirogenic triarylphosphines.
ortho-Substituted and unsymmetrical 9-phospha-triptycenes were synthesized via two synthetic approaches involving densely functionalized ortho-halogenated triarylmethane or phosphine precursors. ortho-Substituents imposed a considerable steric shielding due to the tricyclic cage-shaped structure with the aryl rings p-systems orthogonal to the phosphorus electron pair. A series of Au(i) and Rh(i) complexes were analysed in the solid state to determine Tolman electronic parameters, cone angles and buried volumes of these unprecedented functionalized phosphines. Quantum chemical calculations of electronic and steric descriptors revealed that these cage-shaped phosphines are electron-poor and that single methyl substituent is enough to provide the largest effect on steric shielding reported so far in triarylphosphines. An unsymmetrically substituted 9-phosphatriptycene was resolved by chiral HPLC, opening the avenue towards stable P-chirogenic triarylphosphines with unlimited configurational stability for new catalyst development in asymmetric transition-metal catalysis.


Challenges and solutions to incorporation of nutraceuticals in foods.
Manufacturers often cannot simply add a nutraceutical to a food when formulating functional foods that have acceptable sensory appeal as well as the desired health benefits. The appropriate application of microencapsulation for stabilizing nutraceuticals enables their effective delivery through food. Careful design of the delivery system helps protect sensitive nutraceuticals from the environment and processing stresses encountered during food manufacture, and prevents undesirable interactions of the nutraceutical with components in the food matrix. Microencapsulation technologies overcome hurdles associated with the successful delivery of nutraceuticals in healthy foods if due consideration is given to challenges at all stages throughout the supply chain. This encompasses stabilizing and protecting nutraceuticals from degradation in ingredient formats, during processing, in the final food product, and during intestinal transit until they are released at the desired site in the gastrointestinal tract to impart their targeted health effects.


Low frequency of adverse sequelae of obesity in South African rural black women.
In a series of 210 black women aged 25-45 years in a village in Eastern Transvaal, South Africa, 40 (19.0%) were obese, having a Body Mass Index (kg/m2) of 30 or more. Mean triceps skinfold was 23.5 mm; in 10 (25%) it was 25 mm or more) Hypertension (greater than or equal to 160/95 mm Hg) was present in 3 women (7.5%), hyperglycaemia (greater than or equal to 7.8 mmol/l) in 1 (2.5%), hypercholesterolaemia (greater than or equal to 5.2 mmol/l) in 3 (7.5%), and hypertriglyceridaemia (greater than or equal to 1.8 mmol/l) in 3 (7.5%). Dietarily, mean intake of energy was 2260 kcals, protein 73 g (12.9% energy), fat 55 g (20.8% energy), and carbohydrate 369 g (65.3%). In this context, of low fat, low animal food intakes, together with high physical activity, one or more of the adverse sequelae enumerated were present in 5 women (12.5%). Accordingly, in 35 women (87.5%), their obesity could be regarded as "healthy" obesity.


Polymorphism in the promoter region of the gene for 5-HTT in individuals with aggressive periodontitis.
Susceptibility to and development of periodontal disease have been associated with psychological conditions. Previous studies have associated the presence of polymorphism in the promoter region of the serotonin transporter with several behavioral traits and psychological conditions such as depression, anxiety, and stress. The short allele S has a reduced transcriptional efficiency and is associated with lowered serotonin expression and uptake. The purpose of the present study was to investigate the association between 5-HTTLPR polymorphism and aggressive periodontitis in a sample of Brazilian individuals. This study involved 61 individuals affected by aggressive periodontitis and 71 without periodontitis. Genomic DNA was obtained from oral swabs, amplified by polymerase chain reaction (PCR), and genotyped at 5-HTTLPR. The Chi-square test and multivariate logistic regression were used for statistical analysis. The aggressive periodontitis group displayed a significantly higher occurrence of genotype SS (P < 0.01) and of allele S (P < 0.01). After adjustment for gender and age, it was observed that genotype SS occurred 8 times more frequently in this group. Our findings suggest that 5-HTTLPR polymorphism might be associated with aggressive periodontitis in the Brazilian population.


Initial observations concerning developmental characteristics of labio-mandibular kinematics.
Acoustic measurements have shown that children's segment durations are often longer than those of adults. It is unclear from previous research, however, why this occurs. One possibility is that children's less mature peripheral speech mechanisms limit the rate at which they can perform articulatory movements and that this results in longer acoustic segment durations. Another possible cause of children's longer segment durations is that "higher-order," organizational factors might affect their ability to plan and sequence phonetic strings. This too could limit the rate at which they produce speech gestures, thus resulting in longer segment durations. The present study attempted to clarify such issues by obtaining articulatory movement data from four children and three adults using strain gage instrumentation to monitor superior-inferior lip and jaw displacement and velocity. Results indicate that the children tended to move their articulators more slowly than the adults, despite the fact that both groups exhibited comparable articulatory displacements. Differences observed between the adults and children concerning vocal tract size and movement variability indicate that "lower-level," physical factors may be partially involved in children's slower articulatory movements. However, differences between the two groups regarding anticipation of certain articulatory sequences suggest that "higher-order," organizational effects may also be associated with children's slower movements and, therefore, their longer segment durations.


Duration of Heightened Risk of Acute Ischemic Stroke After Hospitalization for Acute Systolic Heart Failure.
Background The duration and magnitude of increased stroke risk after a hospitalization for acute systolic heart failure (HF) remains uncertain. Methods and Results The authors performed a retrospective cohort study using claims (2008-2018) from a nationally representative 5% sample of Medicare beneficiaries aged ≥66 years. Cox regression models were fitted separately for the groups with and without acute systolic HF to examine its association with the incidence of ischemic stroke after adjustment for demographics, stroke risk factors, and Charlson comorbidities. Corresponding survival probabilities were used to compute the hazard ratio (HR) in each 30-day interval after discharge. The authors stratified patients by the presence of atrial fibrillation (AF) before or during the hospitalization for acute systolic HF. Among 2 077 501 eligible beneficiaries, 94 641 were hospitalized with acute systolic HF. After adjusting for demographics, stroke risk factors, and Charlson comorbidities, the risk of ischemic stroke was highest in the first 30 days after discharge from an acute systolic HF hospitalization for patients with AF (HR, 2.4 [95% CI, 2.1-2.7]) and without AF (HR, 4.6 [95% CI, 4.0-5.3]). The risk of stroke remained elevated for 60 days in patients with AF (HR, 1.4 [95% CI, 1.2-1.6]) and was not significantly elevated afterward. The risk of stroke remained significantly elevated through 330 days in patients without AF (HR, 2.1 [95% CI, 1.7-2.7]) and was no longer significantly elevated afterward. Conclusions A hospitalization for acute systolic HF is associated with an increased risk of ischemic stroke up to 330 days in patients without concomitant AF.


LARVICIDAL ACTIVITY OF PERESKIA BLEO (KUNTH) DC. (CACTACEAE) FRUIT ENDOCARP CRUDE AND FRACTIONATED EXTRACTS AGAINST AEDES AEGYPTI (L.) (DIPTERA: CULICIDAE).
The use of insecticides can cause adverse effects in vector control, a plant bio-insecticide is an advantageous substitute. Currently, the promising mosquito larvicidal activity from plant extracts has been reported worldwide, including Thailand. In this study, the endocarp of Pereskia bleo (Kunth) DC. fruit was extracted with distilled water and ethanol. Crudes and fractionated groups of the extracts were evaluated for their larvicidal efficacy against the 3rd instar larvae of Aedes aegypti. At 48 hours of exposure, it was found that the activities of the extracts were higher than 24-hour's. The ethanolic extracts showed stronger activities than the aqueous ones, indicating the lower LC50 values of both crude and fractionated group extracts. The most toxic activity was found in a fractionated group of the ethanolic extract, E-Gr3, with significantly lowest LC50 values of 707.94 and 223.12 ppm for 24- and 48-hour detection times, respectively. The bioassay results indicated the larvicidal property against the Ae. aegypti mosquito of the P. bleo plant extracts. A safety for non-target organisms or an action on other mosquito vectors of this plant, should be further investigated.


Cancer patients admitted in the emergency department: A single-centre observational study.
This study aims to analyse patients' clinical profiles seen at an emergency unit of a public oncology reference hospital in Belo Horizonte, Brazil. This is a cross-sectional, observational, retrospective study, with data collection through patients' medical records seen between 2016 and 2018. The identification of patients was carried out through research on hospital admission authorization guides. A total of 2932 medical records were evaluated, of which only 21.5% were cancer patients. A cancer diagnosis was made for 21.5% of patients during hospitalisation. In this group, pain and weight loss are frequent symptoms, and haematological diseases (15.2%) were the most frequent tumour type. Patients with a previous cancer diagnosis presented the most prevalent tumour breast (18.3%) and altered consciousness level as a leading symptom. Analgesics were the most prescribed drugs in both groups. This study showed two distinct groups of cancer patients: with or without a previous cancer diagnosis. However, these two groups are comparable in almost all the variables analysed. Therefore, we believe that the factors that could guide the care in an emergency are related to education on cancer symptoms for the population to contribute to an early diagnosis and cancer training for emergency department (ED) professionals' to better monitor advanced-stage patients for symptom management.


[Salvage chemotherapy in resistant malignant lymphomas (author's transl)].
A salvage chemotherapy was used in advanced malignant lymphomas resistant to previous chemotherapy. The chemotherapy schedule consisted by the monthly administration of vindesine and continuous infusions of bleomycins, associated with cis-diammine-dichloro-platinum in Hodgkin's disease (patients resistant to MOPP and ABVD protocols) and with DTIC in non-Hodgkin lymphomas (patients resistant to CHOP or equivalent protocol). In 10 patients with advanced Hodgkin's disease (stages III and IV), one complete remission and four partial regressions were achieved. Five patients are still alive after 6 and 14 months. In 15 non-Hodgkin lymphoma patients, two complete remissions and seven partial regressions were achieved. Eight patients are still alive after 4 to 12 months. Severe toxicities related to the chemotherapy protocol have never been observed. These results demonstrate the efficiency of the described chemotherapy schedules in advanced malignant lymphomas resistant to visual therapy.


Cognitive functions of intracellular mechanisms for contextual amplification.
Evidence for the hypothesis that input to the apical tufts of neocortical pyramidal cells plays a central role in cognition by amplifying their responses to feedforward input is reviewed. Apical tufts are electrically remote from the soma, and their inputs come from diverse sources including direct feedback from higher cortical regions, indirect feedback via the thalamus, and long-range lateral connections both within and between cortical regions. This suggests that input to tuft dendrites may amplify the cell's response to basal inputs that they receive via layer 4 and which have synapses closer to the soma. ERP data supporting this inference is noted. Intracellular studies of apical amplification (AA) and of disamplification by inhibitory interneurons targeted only at tufts are reviewed. Cognitive processes that have been related to them by computational, electrophysiological, and psychopathological studies are then outlined. These processes include: figure-ground segregation and Gestalt grouping; contextual disambiguation in perception and sentence comprehension; priming; winner-take-all competition; attention and working memory; setting the level of consciousness; cognitive control; and learning. It is argued that theories in cognitive neuroscience should not assume that all neurons function as integrate-and-fire point processors, but should use the capabilities of cells with distinct sites of integration for driving and modulatory inputs. Potentially 'unifying' theories that depend upon these capabilities are reviewed. It is concluded that evolution of the primitives of AA and disamplification in neocortex may have extended cognitive capabilities beyond those built from the long-established primitives of excitation, inhibition, and disinhibition.


[Chromosomal localization of M/SAR from DNA of the clone lambda20p1.4 in Drosophila melanogaster salivary glands].
M/SAR of Drosophila melanogaster DNA clone gamma 20p 1.4 was localized on chromosomes by in situ hybridization of the gamma 20p 1.4 DNA fragment and its deletion mutants with salivary gland chromosomes of third instar larvae of the lines Canton S and Oregon R. The M/SAR sequence, capable of specifically binding to lamin in vitro, was detected in the pericentric regions 20CD, 40EF, 41AB, the proximal part of region 81 of chromosome 3, and region 101 of chromosome 4, which attach to the nuclear envelope in cells of D. melanogaster salivary glands, and in region 49D, which does not come into contact with the nuclear periphery. This is the first M/SAR localized in pericentric chromatin of D. melanogaster.


Efficiency of minimal oblique resection of the uncinate process during an anterior cervical discectomy and fusion.
Hypertrophy of the uncinate process (UP) can cause radiculopathy. Minimal UP resection is considered to remove the lesion while minimizing the risk of complications. This study aimed to elucidate the surgical results of minimal oblique resection of the UP. This study is a retrospective review of about sixty segments in 34 patients who underwent anterior cervical discectomy and fusion (ACDF) with minimal oblique uncinectomy between 2016 and 2018. The cross-sectional area of the UP was measured pre- and postoperatively. The interspinous distance, segmental Cobb angle, subsidence, fusion rate, surgical time, estimated blood loss, and postoperative complications were evaluated. The mean resected areas of the UP were 17.4 ± 8.7 mm2 (25.9%) on the right and 17.3 ± 11.2 mm2 (26.2%) on the left. The difference in interspinous distance in flexion-extension was 7.1 ± 3.2 and 1.6 ± 0.6 mm pre- and postoperatively, respectively (P = .000). The fusion rate after ACDF was 91.7% when measured according to segment (55/60) and 91.2% when measured according to patients (31/34). The difference in the segmental Cobb angle in flexion-extension was 8.3 ± 6.2° and 1.9 ± 0.3° pre and postoperatively, respectively (P = .000). Subsidence occurred in 4 (11.8%) patients and 5 (8.3%) segments. The average surgical time per segment was 68.8 ± 9.3 minute, and the estimated blood loss was 48.5 ± 25.0 mL. Postoperative complications comprised 1 case each of neck swelling, wound infection, pneumonia, and gastrointestinal bleeding. Our findings therefore revealed that minimal oblique uncinectomy during an ACDF can maintain the stability of the uncovertebral joint while sufficiently decompressing the neural foramen.


Drought-induced expression of aquaporin genes in leaves of two common bean cultivars differing in tolerance to drought stress.
Aquaporin proteins are part of the complex response of common bean (Phaseolus vulgaris L.) to drought which affects the quality and quantity of yield of this important crop. To better understand the role of aquaporins in common bean, drought-induced gene expression of several aquaporins was determined in two cultivars, the more drought tolerant Tiber and the less tolerant Starozagorski čern. The two bean cultivars were selected among 16 European genotypes based on the tolerance to drought determined by time needed for plants to wilt after withholding irrigation and yield at harvest. The expression patterns of two plasma membrane intrinsic proteins, PvPIP1;2 and PvPIP2;7, and two tonoplast intrinsic proteins, PvTIP1;1 and PvTIP4;1 in leaves of 21 day old plants were determined by RT-qPCR in both cultivars under three degrees of drought stress, and under rehydration and control conditions. Gene expression of all four examined aquaporins was down-regulated in drought stressed plants. After rehydration it returned to the level of control plants or was even higher. The responses of PvPIP2;7 and PvTIP1;1 during drought and rehydration were particularly pronounced. The gene expression of PvPIP2;7 and PvTIP4;1 during drought was cultivar specific, with greater down-regulation of these two aquaporins in drought tolerant Tiber. Under drought stress the relative water content and water potential of leaves were higher in Tiber than in Starozagorski plants. The differences in these physiological parameters indicate greater prevention of water loss in Tiber during drought, which may be associated with rapid and adequate down-regulation of aquaporins. These results suggest that the ability of plants to conserve water during drought stress involves timely and sufficient down-regulation of gene expression of specific aquaporins.


Non-β Lactam Inhibitors of the Serine β-Lactamase blaCTX-M15 in Drug-Resistant Salmonella typhi.
Antibiotic resistance by bacterial pathogens against widely used β-lactam drugs is a major concern to public health worldwide, resulting in high healthcare cost. The present study aimed to extend previous research by investigating the potential activity of reported compounds against the S. typhi β-lactamase protein. 74 compounds from computational screening reported in our previous study against β-lactamase CMY-10 were subjected to docking studies against blaCTX-M15. Site-Identification by Ligand Competitive Saturation (SILCS)-Monte Carlo (SILCS-MC) was applied to the top two ligands selected from molecular docking studies to predict and refine their conformations for binding conformations against blaCTX-M15. The SILCS-MC method predicted affinities of -8.6 and -10.7 kcal/mol for Top1 and Top2, respectively, indicating low micromolar binding to the blaCTX-M15 active site. MD simulations initiated from SILCS-MC docked orientations were carried out to better characterize the dynamics and stability of the complexes. Important interactions anchoring the ligand within the active site include pi-pi stacked, amide-pi, and pi-alkyl interactions. Simulations of the Top2-blaCTX-M15 complex exhibited stability associated with a wide range of hydrogen-bond and aromatic interactions between the protein and the ligand. Experimental β-lactamase (BL) activity assays showed that Top1 has 0.1 u/mg BL activity, and Top2 has a BL activity of 0.038 u/mg with a minimum inhibitory concentration of 1 mg/mL. The inhibitors proposed in this study are non-β-lactam-based β-lactamase inhibitors that exhibit the potential to be used in combination with β-lactam antibiotics against multidrug-resistant clinical isolates. Thus, Top1 and Top2 represent lead compounds that increase the efficacy of β-lactam antibiotics with a low dose concentration.


Using item response theory (IRT) to reduce patient burden when assessing desire for hastened death.
Desire for hastened death (DHD) represents a wish to die sooner than might occur by natural disease progression. Efficient and accurate assessment of DHD is vital for clinicians providing care to terminally ill patients. The Schedule of Attitudes Toward Hastened Death (SAHD) is a commonly used self-report measure of DHD. The goal of this study was to use methods grounded in item response theory (IRT) to analyze the psychometric properties of the SAHD and identify an abbreviated version of the scale. Data were drawn from 4 studies of psychological distress at the end of life. Participants were 1,076 patients diagnosed with either advanced cancer or AIDS. The sample was divided into 2 subsamples for scale analysis and development of the shortened form. IRT was used to estimate item parameters. A 6-item version of the SAHD (SAHD-A) was identified through examination of item parameter estimations. The SAHD-A demonstrated adequate convergent validity. Receiver operating characteristic analyses indicated comparable cut scores to identify patients with high levels of DHD. These analyses support the utility of the SAHD-A, which can be more easily integrated into research studies and clinical assessments of DHD. (PsycINFO Database Record


Alteration of podocytes in a murine model of crescentic glomerulonephritis.
Recent observations suggest a central role of podocytes in crescent formation. In experimental glomerulonephritis podocytes disrupt the parietal epithelial layer and attach on its basement membrane, thus forming bridges between the tuft and Bowman's capsule, and they are a major constituent of crescents. In order to explain these findings we hypothesize that inflammation triggers motility in podocytes. In the present study we asked whether podocytes display alterations which suggest a migratory behavior in glomerulonephritis. Glomerulonephritis was induced in mice by injection of a rabbit serum against the glomerular basement membrane. The kidneys were perfusion-fixed 6 days later and examined by light and electron microscopy as well as by immunohistochemistry. In glomerulonephritis the apical cytoplasm of podocytes displayed numerous actin-containing microprotrusions. Cortactin, a protein involved in the regulation of actin polymerization, was predominantly expressed in foot processes of podocytes in control mice. It was redistributed to the cell body in glomerulonephritis. In untreated mice betal-integrin was restricted to the foot processes. In glomerulonephritis it was additionally found in the cytoplasm and in the apical cell membrane. Recycling of integrins is a crucial event in initiation of cell migration. ICAM-1 and CD44, the ligation of which induces migratory behaviors, were absent from healthy podocytes but expressed by some podocytes in glomerulonephritis. Thus, in glomerulonephritis podocytes display some characteristic features of migrating cells. This might explain their ability to break through the parietal epithelium and to become a constituent of early crescents.


C-Plasma of Hierarchical Graphene Survives SnS Bundles for Ultrastable and High Volumetric Na-Ion Storage.
Tin and its derivatives have provoked tremendous progress of high-capacity sodium-ion anode materials. However, achieving high areal and volumetric capability with maintained long-term stability in a single electrode remains challenging. Here, an elegant and versatile strategy is developed to significantly extend the lifespan and rate capability of tin sulfide nanobelt electrodes while maintaining high areal and volumetric capacities. In this strategy, in situ bundles of robust hierarchical graphene (hG) are grown uniformly on tin sulfide nanobelt networks through a rapid (5 min) carbon-plasma method with sustainable oil as the carbon source and the partially reduced Sn as the catalyst. The nucleation of graphene, CN (with size N ranging from 1 to 24), on the Sn(111) surface is systematically explored using density functional theory calculations. It is demonstrated that this chemical-bonded hG strategy is powerful in enhancing overall electrochemical performance.


[Amisulpride in Huntington's disease].
Amisulpride is a substituted benzamide derivative with atypical antipsychotic properties and low side effects. We report four cases of patients with clinically and genetically established Huntington's disease and signs of psychosis who were treated with Amisulpride. Two patients developed extrapyramidal side effects due to the treatment. The antipsychotic therapy of all patients was effective. Due to degeneration of striatal neurons patients suffering from Huntington's disease react early with development of extrapyramidal side effects after therapy with amisulpride.


[Indomethacin induces apoptosis through inhibition of survivin regulated by beta-catenin/TCF4 in human colorectal cancer cells].
Although Wnt pathway plays important role in colorectal carcinogenesis, but the mechanism of this pathway in anti-apoptosis is not clear. This study is to investigate the molecular mechanism of Wnt pathway in anti-apoptosis. Survivin promoter region was constructed into luciferase reporter system (pGL3-sur1.8kb). The recombinants pGL3-sur1.8kb were cotransfected with pRL-SV40 into HCT116 cells and the activities were detected with Dual-luciferase reporter assay system. Cell apoptosis was analyzed by flow cytometry. Protein level of survivin and beta-catenin was detected by Western Blot. Survivin could be up-regulated by beta-catenin and down-regulated by TCF4DeltaN in transcriptional level. beta-catenin/TCF4 dependent apoptosis induced by indomethacin could suppress survivin transcription. Overexpression of survivin could partially recover the beta-catenin/TCF4 dependent apoptosis. Down-regulation of survivin affected by beta-catenin/TCF4 pathway plays an important role in apoptosis induced by NSAIDs indomethacin in HCT116 cells. The beta-catenin/TCF4-survivin pathway may be a potential target in treatment of colon cancer.


Quantitative estimation of 17alpha-hydroxypregn-4-ene-3,20-dione (17alphaOH-progesterone) in adrenal venous blood and adrenal glands.
1. A method is described for the accurate estimation of small quantities of 17alpha-hydroxypregn-4-ene-3,20-dione (17alphaOH-progesterone) in blood and adrenal glands.2. The dog adrenal was found to secrete 17alphaOH-progesterone under conditions of operative stress at a rate of 5-10 mug/g tissue/hr. This is similar to the secretion rate of aldosterone.3. The secretion of 17alphaOH-progesterone was decreased after hypophysectomy and increased in response to adrenocorticotrophic hormone (ACTH).4. The adrenal gland of the dog, the monkey and the guinea-pig was found to contain between 0.6 and 6 mug of 17alphaOH-progesterone/g tissue. The concentration was usually somewhat smaller than that of pregnenolone or progesterone and between 1 and 20% of the concentrations of the glucocorticoids.5. A comparison of adrenal steroid contents and secretion rates under conditions of stress indicates a rate of synthesis in the order of 30-40 n-moles of 17alphaOH-progesterone/g adrenal tissue/min.


The Improvement of Flaw Detection by the Configuration of Uniform Eddy Current Probes.
In this review, the principles to detect flaws with uniform eddy currents were presented based on the shape and orientation of the excitation coils and detection coils of the probe. Techniques are applied to detect flaws like cracks, especially on the weld zone surface, of test pieces of non-magnetic and ferromagnetic materials, and have unique features which are immune to the effects of lift-off. In the technique of interest, almost all the probe models developed are the type with tangential rectangular excitation coils. The induction condition and the flaw signal for each probe were discussed based on the shape and orientation of the excitation coils and detection coils of the probe. Finally, the challenge of increasing sensitivity to detect flaws with a uniform eddy current was also presented.


Recent advances in combinatorial cancer therapy via multifunctionalized gold nanoparticles.
The diverse behavior of nanogold in the therapeutic field is related to its unique size and shape. Nanogold offers improvements in modern diagnostic and therapeutic implications, increases disease specificity and targeted drug delivery, and is relatively economical compared with other chemotherapeutic protocols. The diagnosis of cancer and photothermal therapy improve drastically with the implementation of nanotechnology. Different types of nanoparticles, that is, gold silica nanoshells, nanorods and nanospheres of diverse shapes and geometries, are used widely in the photothermal therapy of cancerous cells and nodules. Numerous reviews have been published on the therapeutic applications of gold nanoparticles, but studies on combinatorial applications of nanogold in cancer therapy are limited. This review focuses on the combinatorial cancer therapy using optical properties of nanogold with different shapes and geometries, and their therapeutic applications in cancer diagnosis, photothermal therapy, cancer imaging and targeted drug delivery.


Mammographic density and breast cancer risk: the multiethnic cohort study.
In a nested case-control study (2001-2004), the authors investigated the association between mammographic density and breast cancer risk among women of Caucasian, Japanese, and Native Hawaiian ancestry in the Hawaii component of the Multiethnic Cohort Study. The authors retrieved several prediagnostic mammograms for breast cancer cases and for controls frequency-matched to cases by age and ethnicity. A reader who was blinded to case status and year of mammogram performed computer-assisted density assessment. Suitable mammographic readings were obtained for 607 cases and 667 controls. The authors used unconditional logistic regression to estimate odds ratios and 95% confidence intervals while adjusting for confounders. Mean percent density and mean dense area were significantly greater for cases than for controls: 39.6% vs. 29.7% and 37.3 cm2 vs. 28.4 cm2, respectively. For the earliest mammogram taken, the overall odds ratio for a 10% increase in breast density was 1.22 (95% confidence interval: 1.14, 1.30), and the overall odds ratio for a 10-cm2 increase in dense area was 1.17 (95% confidence interval: 1.11, 1.24). The similar sizes of the areas under the receiver operating characteristic curve (0.66) confirmed that percent density and dense area predicted breast cancer equally well. Because the risk estimates appeared higher for Caucasians and Native Hawaiians than for Japanese women, ethnicity-specific models may be necessary to predict risk from breast density in different ethnic groups.


Ginkgolide B functions as a determinant constituent of Ginkgolides in alleviating lipopolysaccharide-induced lung injury.
Ginkgolides are the major bioactive components of Ginkgo biloba extracts, however, the exact constituents of Ginkgolides contributing to their pharmacological effects remain unknown. Herein, we have determined the anti-inflammatory effects of Ginkgolide B (GB) and Ginkgolides mixture (GM) at equivalent dosages against lipopolysaccharide (LPS)-induced inflammation. RAW 264.7 cell culture model and mouse model of LPS-induced lung injury were used to evaluate in vitro and in vivo effects of GB and GM, respectively. In RAW 264.7 cells, GB and GM at equivalent dosages exhibit an identical capacity to attenuate LPS-induced inducible nitric oxide synthase mRNA and protein expression and subsequent NO production. Likewise, GB and GM possess almost the same potency in attenuating LPS-induced expression and activation of nuclear factor kappa B (p65) and subsequent increases in tumor necrosis factor-α mRNA levels. In LPS-induced pulmonary injury, GB and GM at the equivalent dosages have equal efficiency in attenuating the accumulation of inflammatory cells, including neutrophils, lymphocytes, and macrophages, and in improving the histological damage of lungs. Moreover, GB and GM at equivalent dosages decrease the exudation of plasma protein to the same degree, whereas GM is superior to GB in alleviating myeloperoxidase activities. Finally, though GB and GM at equivalent dosages appear to reduce LPS-induced IL-1β mRNA and protein levels and IL-10 protein levels to the same degree, GM is more potent than GB to attenuate the IL-10 mRNA levels. Taken together, this study demonstrates that GB functions as the determinant constituent of Ginkgolides in alleviating LPS-induced lung injury.


Key players in the immune response to biomaterial scaffolds for regenerative medicine.
The compatibility of biomaterials is critical to their structural and biological function in medical applications. The immune system is the first responder to tissue trauma and to a biomaterial implant. The innate immune effector cells, most notably macrophages, play a significant role in the defense against foreign bodies and the formation of a fibrous capsule around synthetic implants. Alternatively, macrophages participate in the pro-regenerative capacity of tissue-derived biological scaffolds. Research is now elucidating the role of the adaptive immune system, and T cells in particular, in directing macrophage response to synthetic and biological materials. Here, we review basic immune cell types and discuss recent research on the role of the immune system in tissue repair and its potential relevance to scaffold design. We will also discuss new emerging immune cell types relevant to biomaterial responses and tissue repair. Finally, prospects for specifically targeting and modulating the immune response to biomaterial scaffolds for enhancing tissue repair and regeneration will be presented.


A Case of Macrolide-Refractory Mycoplasma pneumoniae Pneumonia in Pregnancy Treated with Garenoxacin.
Pneumonia in pregnancy is associated with adverse maternal and foetal outcomes, and intensive treatment with appropriate antibiotics is essential. However, cases caused by pathogens that are resistant to antibiotics suitable for the developing foetus are challenging. We herein report a case of macrolide-refractory Mycoplasma pneumoniae pneumonia in pregnancy. A 40-year-old multigravida with twin pregnancy complained of cough and fever at 13 weeks of gestation and was diagnosed with pneumonia. Even though empiric treatment with ceftriaxone and oral azithromycin was started, her condition deteriorated rapidly. The findings of chest computed tomography suggested Mycoplasma pneumoniae pneumonia. Since azithromycin did not work, this strain was considered to be macrolide-refractory. Garenoxacin, an oral quinolone, was selected and was dramatically effective. The use of quinolone could be justified with the emergence of drug-resistant bacterial/atypical pneumonia and in the maternal life-threatening condition.


All-trans retinoic acid induces proliferation of an irradiated stem cell supporting stromal cell line AFT024.
We have previously shown that all-trans retinoic acid (ATRA) enhanced the maintenance of early human hematopoietic progenitor cells (HPCs) in the presence of an irradiated stromal cell line AFT024. In this study, we examined the effects of ATRA on the stromal cell component with particular reference to cellular proliferation and gene expression. Irradiated AFT024 cells were cultured in Dulbecco's Modified Eagle's Medium supplemented with fetal bovine serum and were incubated with ATRA at 1 mumol/L up to 21 days. The cells were examined in terms of immunostaining for proliferative cell nuclear antigen (PCNA) and BrdU incorporation, apoptosis assay, cell cycle analysis, and gene expression using semiquantitative reverse-transcriptase polymerase chain reaction. In the control experiments, AFT024 cells lost their confluence in culture after 15-Gy irradiation and were arrested in G2/M phase on days 7 and 21. ATRA restored the cellular confluence with an increase in proliferation on day 21 (BrdU incorporation: 20.6-fold; PCNA staining: 51.7-fold) with reversal of cell cycle arrest (S phase: 2.7-fold increase; G2/M phase: 2.0-fold decrease). There was no effect on apoptosis as shown by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. ATRA significantly upregulated the expression of cell cycle genes for checkpoint transition, including cyclin A2, B2, and aurora kinase B, as well as genes associated with a putative role in HPC maintenance, including osteopontin, HoxA5, enhancer of zeste homolog 2, and peroxisome proliferator-activated receptor gamma. We concluded that ATRA induced cellular proliferation of irradiated AFT024 cells and expression of a number of genes whose relevance to HPC homeostasis would have to be further examined.


Are we witnessing the start of a therapeutic revolution in acute myeloid leukemia?
The 5-year overall survival rate of AML patients remains 25-40%. The prognosis is even more dismal for older patients who are ineligible for intensive chemotherapy and patients with secondary or relapsed/refractory AML. In 2017, 4 new drugs were approved by the US Food and Drug Administration for AML treatment: The FLT3 inhibitor midostaurin, the isocitrate dehydrogenase (IDH)-2 inhibitor enasidenib, a liposomal formulation of cytarabine and daunorubicin (CPX-351), and the anti-CD33 antibody gemtuzumab ozogamicin. Additionally, the IDH1 inhibitor ivosidenib has received FDA approval in July 2018. However, all these drugs were approved in certain settings and/or for certain subsets of AML patients. Herein, we review the mechanisms of actions and preclinical data, highlight pivotal clinical trial data, and discuss future directions and challenges for further development of these 5 novel therapeutics. Finally, we briefly overview some of the highly promising agents that are currently in advanced stages of clinical development.


An algorithm for the prenatal detection of chromosome anomalies by QF-PCR and G-banded analysis.
The objective of this study was to examine in theory the clinical utility of a prenatal algorithm that uses rapid aneuploidy detection in all cases and G-banded analysis for selected cases (RAD/G algorithm). Over a 4-year period, amniotic fluid samples were prospectively assigned into RAD (limited analysis) or RAD/G (intensive analysis) categories based upon the likelihood of the fetus having a chromosome anomaly. The samples were cultured and analyzed by standard cytogenetic methods. The rates of clinically significant chromosomal anomalies potentially undetectable by the RAD/G algorithm were calculated. The karyotype was normal in 3861/4054 (95.24%) cases and abnormal in 193 (4.76%). From these data, the detection rate of the RAD/G algorithm was 87.6% if all abnormalities detected by G-banding were taken into consideration and 97.6% if abnormalities having reduced predictive value were excluded (balanced rearrangements and most mosaic cases). Compared to G-banding alone, the RAD/G algorithm has a reduction in sensitivity due to undetectable abnormalities and mosaicism in the RAD group. However, it provides a rapid and inexpensive alternative to traditional G-banded analysis, and might be more appropriate for patients with uncomplicated, low risk pregnancies.


Synthesis, biological activity of salidroside and its analogues.
Salidroside is a phenylpropanoid glycoside isolated from Rhodiola rosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this paper, about 18 novel salidroside analogues were prepared through Koenigs-Knorr method, the effects of these compounds over PC12 was assessed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The novel compounds differ in the substituents attached to the benzene ring or in the glycosyl donor. According to the data, compounds (3,5-dimethoxyphenyl)methyl β-D-glucopyranoside and (3,5-dimethoxyphenyl)methyl β-D-galactopyranoside with methoxy group at 3 and 5-positions of the benzene ring were the most viability at concentration of 300 µmol/l and 60 µmol/l, respectively.


Patients as Partners in Research: There Is Plenty of Help for Researchers.
If including patients as equal partners in health care research is increasingly regarded as "the right thing to do," then it is important that researchers and patients "do it right." The research community should be aware of, use, and share resources that support best practices in this domain. The first editorial in the series focused on why researchers should engage patient partners on research teams. In this, the second editorial in the series, we concentrate on how to engage patient partners and highlight a selection of resources to help researchers and to demystify patient partnerships in research. J Orthop Sports Phys Ther 2020;50(5):219-221. doi:10.2519/jospt.2020.0104.


TAKOTSUBO-LIKE CARDIOMYOPATHY IN A LARGE COHORT OF PATIENTS WITH PHEOCHROMOCYTOMA AND PARAGANGLIOMA.
Pheochromocytoma (PHEO) and paraganglioma (PGL) (PPGL) may cause acute Takotsubo-like catecholamine cardiomyopathy (TLC). The objective of this study was to determine the prevalence and clinical presentation of TLC in a large cohort of patients with PPGL. We reviewed retrospectively the records of consecutive patients with PPGL investigated in our center from 1995 to 2016. We collected clinical and paraclinical data of patients that had TLC in this cohort. We performed a literature review of cases of Takotsubo cardiomyopathy related to PPGL described between 1990 and 2015. Our cohort included 275 patients with PPGL. Acute TLC was found in 4 of 152 (2.6%) patients with secreting PPGL. There was no event recorded in 123 patients with unknown presurgical secretion (n = 51) or nonsecreting PPGL (n = 72). Four patients (44 to 79 years old) fulfilled the criteria for TLC, including 2 PHEO and 2 PGL patients. A precipitating stressor event was identified in 3 cases including surgery (n = 2) and upper respiratory tract infection. In all cases, the diagnosis of PPGL came after the cardiac event and following the investigation of a lesion incidentally found at imaging. Moreover, we identified in the literature 59 cases described in the last 25 years and analyzed this cohort together with our 4 new cases. Acute TLC may be found in up to 3% of patients with secreting PPGL. Considering that the diagnosis of PPGL was performed following incidental finding of radiologic mass, the real prevalence of PPGL in TTC remains to be determined. ECG = electrocardiogram; LVEF = left ventricular ejection fraction; MIBG = metaiodobenzylguanidine; PGL = paraganglioma; PHEO = pheochromocytoma; PPGL = pheochromocytoma and paraganglioma; TLC = Takotsubo-like cardiomyopathy; TTC = Takotsubo cardiomyopathy; ULN = upper limit of normal.


In vitro synergistic action of TAT-RasGAP317-326 peptide with antibiotics against Gram-negative pathogens.
Multidrug-resistant (MDR) bacteria are a continuously increasing threat for medicine, causing infections recalcitrant to antibiotics. Antimicrobial peptides (AMPs) were identified as alternatives to antibiotics, being naturally occurring short peptides and part of the innate immune system of a vast majority of organisms. However, the clinical application of AMPs is limited by suboptimal pharmacokinetic properties and relatively high toxicity. Combinatorial treatments using AMPs and classical antibiotics may decrease the concentrations of AMPs required for bacterial eradication, thus lowering the side effects of these peptides. Here, we investigate the in vitro efficiency of combinations of the recently described antimicrobial peptide TAT-RasGAP317-326 with a panel of commonly used antimicrobial agents against three Gram-negative bacteria, Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii, using checkerboard and time-kill assays. We identified synergistic combinations towards all three bacteria and demonstrated that these combinations had an increased bactericidal effect compared to individual drugs. Moreover, combinations were also effective against clinical isolates of A. baumannii. Finally, combination of TAT-RasGAP317-326 and meropenem had a promising antibiofilm effect towards A. baumannii. Taken together, our results indicate that combinations of TAT-RasGAP317-326 with commonly used antimicrobial agents may lead to the development of new treatment protocols against infections caused by MDR bacteria.


Optimization and Interpretation of Serial QuantiFERON Testing to Measure Acquisition of Mycobacterium tuberculosis Infection.
Conversion from a negative to positive QuantiFERON-TB test is indicative of Mycobacterium tuberculosis (Mtb) infection, which predisposes individuals to tuberculosis disease. Interpretation of serial tests is confounded by immunological and technical variability. To improve the consistency of serial QuantiFERON-TB testing algorithms and provide a data-driven definition of conversion. Sources of QuantiFERON-TB variability were assessed, and optimal procedures were identified. Distributions of IFN-γ response levels were analyzed in healthy adolescents, Mtb-unexposed control subjects, and patients with pulmonary tuberculosis. Individuals with no known Mtb exposure had IFN-γ values less than 0.2 IU/ml. Among individuals with IFN-γ values less than 0.2 IU/ml, 0.2-0.34 IU/ml, 0.35-0.7 IU/ml, and greater than 0.7 IU/ml, tuberculin skin test positivity results were 15%, 53%, 66%, and 91% (P < 0.005), respectively. Together, these findings suggest that values less than 0.2 IU/ml were true negatives. In short-term serial testing, "uncertain" conversions, with at least one value within the uncertainty zone (0.2-0.7 IU/ml), were partly explained by technical assay variability. Individuals who had a change in QuantiFERON-TB IFN-γ values from less than 0.2 to greater than 0.7 IU/ml had 10-fold higher tuberculosis incidence rates than those who maintained values less than 0.2 IU/ml over 2 years (P = 0.0003). By contrast, "uncertain" converters were not at higher risk than nonconverters (P = 0.229). Eighty-seven percent of patients with active tuberculosis had IFN-γ values greater than 0.7 IU/ml, suggesting that these values are consistent with established Mtb infection. Implementation of optimized procedures and a more rigorous QuantiFERON-TB conversion definition (an increase from IFN-γ <0.2 to >0.7 IU/ml) would allow more definitive detection of recent Mtb infection and potentially improve identification of those more likely to develop disease.


Conditions and pathological features of rapidly destructive, experimental periodontitis in dogs.
In order to analyze the conditions for rapidly destructive periodontitis and to describe the early histopathological changes and bone degradation, periodontitis lesions were produced in five male Beagle dogs, 8 to 12 months of age. Cotton floss ligatures were placed around the crowns of upper and lower third and fourth premolars for periods of 4, 7, 14, 21 days. The buccal gingival tissues, being slightly inflamed initially, were clinically scored for various symptoms of inflammation. Block biopsies of premorlars and the adjacent buccal periodontal tissues were taken and processed for light and electron microscopy. Depending on the ligature position in relation to the gingival margin (above, at, deep below) at the day of biopsy harvest, three groups of selected biopsies were formed, and randomly selected sections of these were used for various histometric measurements, for stereological estimation of the size and composition of the connective tissue infiltrate and the osteoclast density, and for general histopathological evaluation. The resulting data and observations implied that (1) onset and maintenance of this periodontitis lesion depend on subgingival ulceration, (2) rapid bone desstruction is the result of osteoclast activity stimulated by acute inflammation, and (3) bone degradation occurs independently of the loss of collagen fiber attachment and the apical migration of the junctional epithelium.


[Activity of propriospinal neurons in cats during the scratch reflex].
In the thalamic cats immobilized with flaxedil, the tactile stimulation of the pinna evoked fictitious scratching, i.e. rhythmical activity of the hindlimb motoneurons with a pattern of discharge typical of the actual scratching. Activity of propriospinal neurons from the segments C1--C2 and Th4--Th7 was recorded during such scratching. The neurons were identified by the antidromic response to L1 stimulation. Most neurons did not respond to the pinna stimulation, but some neurons did. They were tonically active during fictitious scratching. The neurons from cervical segments responded also to some other peripheral stimuli, but neurons from thoracic segments did not. Their activity could be inhibited by stimulation of the contralateral pinna. A role of propriospinal neurons in the activation of the spinal mechanisms of scratching is discussed.


Self-motivation moderates effect of exercise-induced feelings on adherence.
The effect of cardiovascular exercise-induced feeling state changes on exercise program attendance was assessed with mixed-sex, adult new exercisers (N = 72) using the Exercise-induced Feeling Inventory. Positive/Nonpositive patterns of after-exercise affective change were not significantly associated with attendance. When participants' scores on the Self-motivation Inventory of 1980 were analyzed, a significant portion of the variance in attendance (R2 = .10, F = 3.94, p<.03) was explained. A similar, but not significant R2 of .077 was noted when the single Exercise-induced Feeling Inventory subscale of Physical Exhaustion was assessed using the same multiple regression method. Implications for adherence of new exercisers and its dependence on self-motivation and exercise-induced changes in feeling states were discussed. The need to replicate findings across various types of participant, exercise, and setting was emphasized.


Skeletal Muscle Depletion Predicts the Prognosis of Patients with Advanced Pancreatic Cancer Undergoing Palliative Chemotherapy, Independent of Body Mass Index.
Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at diagnosis and loss of skeletal muscle during palliative chemotherapy were associated with survival in patients with pancreatic cancer. We retrospectively reviewed the clinical outcomes of pancreatic cancer patients receiving palliative chemotherapy between 2003 and 2010. The cross-sectional area of skeletal muscle at L3 by computed tomography was analyzed with Rapidia 3D software. We defined sarcopenia as a skeletal muscle index (SMI)< 42.2 cm2/m2 (male) and < 33.9 cm2/m2 (female) using ROC curve. Among 484 patients, 103 (21.3%) patients were sarcopenic at diagnosis. Decrease in SMI during chemotherapy was observed in 156 (60.9%) male and 65 (40.6%) female patients. Decrease in body mass index (BMI) was observed in 149 patients (37.3%), with no gender difference. By multivariate analysis, sarcopenia (P< 0.001), decreasedBMI and SMI during chemotherapy (P = 0.002, P = 0.004, respectively) were poor prognostic factors for overall survival (OS). While the OS of male patients was affected with sarcopenia (P< 0.001) and decreased SMI (P = 0.001), the OS of female patients was influenced with overweight at diagnosis (P = 0.006), decreased BMI (P = 0.032) and decreased SMI (P = 0.014). Particularly, while the change of BMI during chemotherapy did not have impact on OS within the patients with maintained SMI (P = 0.750), decrease in SMI was associated with poor OS within the patients with maintained BMI (HR 1.502; P = 0.002). Sarcopenia at diagnosis and depletion of skeletal muscle, independent of BMI change, during chemotherapy were poor prognostic factors in advanced pancreatic cancer.


Purification and characterization of single-chain urokinase-type plasminogen activator from human cell cultures.
A urokinase-type plasminogen activator was purified from conditioned media of several human cell cultures, but preferably from the human lung adenocarcinoma line CALU-3 (ATCC, HTB-55), using a combination of chromatography on zinc chelate-Sepharose, SP-Sephadex C-50, and Sephadex G-100. Final yields of 65-100 micrograms/liter of starting material were obtained with a 290-fold purification factor and a recovery of 30%. The purified plasminogen activator consists of a single polypeptide chain with Mr 54,000 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and is very similar or identical to single-chain urokinase-type plasminogen activator on the basis of immunodiffusion, amino acid composition, and the lack of specific binding to fibrin. It has very low amidolytic activity on Pyroglu-Gly-Arg-rho-nitroanilide and is converted to two-chain urokinase by limited exposure to plasmin. It has a specific activity of 60,000 IU/mg on fibrin plates and directly activates plasminogen following Michaelis-Menten kinetics with Km = 1.1 microM and kappa cat = 0.0026 S-1. It is concluded that the plasminogen activator purified from CALU-3-conditioned media is physically and kinetically identical to single-chain urokinase-type plasminogen activator. With the present straightforward purification method and a readily available source, sufficient amounts of single-chain urokinase-type plasminogen activator can be obtained for more detailed investigations of its biochemical, biological, and thrombolytic properties.


Beyond LDL-C--the importance of raising HDL-C.
Epidemiological studies have established that low levels of high-density lipoprotein cholesterol (HDL-C) are associated with an increased risk of coronary heart disease (CHD). Recent studies have demonstrated that low HDL-C levels, and high triglycerides and total cholesterol levels are independent predictors of CHD, and that the combination of these lipid abnormalities increases the risk of coronary events. In lipid-modifying intervention studies, agents that raise HDL-C levels have been shown to reduce the incidence of major coronary events. The VA-HIT study consisted of patients with low-density lipoprotein cholesterol (LDL-C) levels similar to those recommended by several guidelines but with low levels of HDL-C. This trial demonstrated that raising HDL-C levels with gemfibrozil reduced the risk of CHD-related events. While the mechanisms by which HDL-C exerts its anti-atherogenic effects have yet to be fully elucidated, its role in the reverse transport of cholesterol and the beneficial effects on endothelial function are plausible explanations for these actions. Although LDL-C reduction is the primary goal in the treatment of dyslipidaemia, current guidelines recognise low HDL-C levels as a major risk factor for CHD. Indeed, the NCEP ATP III guidelines suggest that the treatment of isolated low HDL-C levels in CHD patients or individuals with CHD risk equivalents should be considered. The differing abilities of statins to raise HDL-C levels may be an important factor when making treatment decisions. New lipid-modifying drugs with beneficial effects on both HDL-C and LDL-C levels would be desirable additions to the currently available therapeutic options.


2-Chloro-6-fluoro-benzoic acid.
The title compound, C(7)H(4)ClFO(2), is a twofold halogenated derivative of benzoic acid. The C-C-C angles within the aromatic moiety cover a range 116.11 (14)-123.96 (15)°, with the maximum and the minimum value next to each other. In the crystal, O-H⋯O hydrogen bonds form carb-oxy-lic acid dimers, which are further connected by C-H⋯F contacts into undulating sheets perpendicular to the a axis.


[How much is lung function affected by smoking and occupation? Dichotomy of continuous variables can change the results].
Data from a cross-sectional study of 1045 men comprising a random population sample (768 men) and a sample of cement workers (277 men) were analyzed in order to examine the effects of smoking and occupation on forced expiratory volume in one second (FEV1). The continuous FEV1 variable and five dichotomous FEV1 variables based on % of predicted were analyzed. Differences between the "relative importance" of smoking and occupation were found to depend on the choice of the FEV1 variable. The effects of occupation compared with the effects of smoking varied considerably with different FEV1 variables, continuous or dichotomized at different cut-off levels. We conclude that comparison of surveys utilizing different FEV1 variables must be made with caution.


Highly diversified mitochondrial genomes provide new evidence for interordinal relationships in the Arachnida.
Arachnida is an exceptionally diverse class in the Arthropoda, consisting of 20 orders and playing crucial roles in the terrestrial ecosystems. However, their interordinal relationships have been debated for over a century. Rearranged or highly rearranged mitochondrial genomes (mitogenomes) were consistently found in this class, but their various extent in different lineages and efficiency for resolving arachnid phylogenies are unclear. Here, we reconstructed phylogenetic trees using mitogenome sequences of 290 arachnid species to decipher interordinal relationships as well as diversification through time. Our results recovered monophyly of ten orders (i.e. Amblypygi, Araneae, Ixodida, Mesostigmata, Opiliones, Pseudoscorpiones, Ricinulei, Sarcoptiformes, Scorpiones and Solifugae), while rejecting monophyly of the Trombidiformes due to the unstable position of the Eriophyoidea. The monophyly of Acari (subclass) was rejected, possibly due to the long-branch attraction of the Pseudoscorpiones. The monophyly of Arachnida was further rejected because the Xiphosura nested within arachnid orders with unstable positions. Mitogenomes that are highly rearranged in mites but less rearranged or conserved in the remaining lineages point to their exceptional diversification in mite orders; however, shared derived mitochondrial (mt) gene clusters were found within superfamilies rather than interorders, confusing phylogenetic signals in arachnid interordinal relationships. Molecular dating results show that arachnid orders have ancient origins, ranging from the Ordovician to the Carboniferous, yet have significantly diversified since the Cretaceous in orders Araneae, Mesostigmata, Sarcoptiformes, and Trombidiformes. By summarizing previously resolved key positions of some orders, we propose a plausible arachnid tree of life. Our results underline a more precise framework for interordinal phylogeny in the Arachnida and provide new insights into their ancient evolution.


Objective detection of faking on role-play tests of assertion: gender differences.
The validity of role-play tests of assertiveness can be reduced by the effects of faking. Kern demonstrated that faking could be detected using assessors' global judgements. The present analysis is based on Kern's 1994 videotapes, examining the effectiveness of more objective measures. Undergraduates who were low in assertiveness and instructed to fake high assertiveness on the Idiographic Role-play Test (n = 23) emitted more statements indicative of social-evaluative concerns than the veridically highly assertive testees (n = 27). Significant gender differences in the detectability of faking were also obtained. Whereas 24 female fakers and nonfakers were differentiated via verbalizations of likability, 26 male fakers and nonfakers were differentiated via empathic-assertive statements. The implications and limitations of this method to detect faking are discussed.


Interfacial Curvature as a Potential Index for Prognosis of Colon Adenocarcinoma.
Tumor invasion and metastasis are complex interfacial mechanical processes between the tumor and its surrounding tissue, with the interfacial curvature of tumor playing an important role in cancer progression. In this study, the potential role of interfacial curvature in the prognosis of patients with colon adenocarcinoma is investigated. The front edge interfacial curvature of adenocarcinoma from biopsies of patients in different tumor, lymph node, and metastasis (TNM) stages are calculated and compared, and prognosis assessment is conducted using Kaplan-Meier and Cox proportional hazards regression analyses. Results reveal that patients with larger interfacial curvature of adenocarcinoma are more likely to belong to higher TNM stages. Concomitantly, in the same TNM stage, patients with increased adenocarcinoma interfacial curvature show worse prognosis with higher recurrence and lower survival rates. Besides, interfacial curvature is an independent prognostic factor for cause-specific survival and relapse-free survival among all selected patients. Mechanical models of colon adenocarcinoma invasion and metastasis are established to better understand the close association between interfacial curvature and tumor progression. The results together with hematoxylin and eosin staining indicate that metastasis in stages T3N0M0 and T3N1M0 may be linked to large interfacial curvatures. Therefore, interfacial curvature may serve as a potential index for predicting prognosis in patients with colon adenocarcinoma.


How and When to Screen for Atrial Fibrillation after Stroke: Insights from Insertable Cardiac Monitoring Devices.
The introduction of insertable cardiac monitoring devices has dramatically altered our understanding of the role of intermittent atrial fibrillation in cryptogenic stroke. In this narrative review we discuss the incidence, timing and relationship between atrial fibrillation and cryptogenic stroke, how to select patients for monitoring and the value and limitations of different monitoring strategies. We also discuss the role of empirical anticoagulation, and atrial fibrillation burden as a means of tailoring anticoagulation in patients at high risk of bleeding.


Apoptotic cell death induced by physarumin (hemagglutinin from myxomycete, Physarum polycephalum).
Physarumin, a carbohydrate-binding protein (hemagglutinin or lectin), was isolated from the plasmodium of Physarum polycephalum. Physarumin agglutinated not only several species of erythrocytes but also tumor cells such as AH109A ascites hepatoma cells, sarcoma 180 ascites cells and mouse leukemia P388 cell lines. Physarumin had tumor cell growth-inhibitory activity, and induced the apoptosis of P388 cell lines. Physarumin-induced apoptosis required binding to a 68 kDa counter-receptor on the P388 cell surface. Since the agglutinating and antiproliferative activities of physarumin were inhibited by asialofetuin and thyroglobulin, respectively, it is suggested that physarumin reacts with the galactose moiety of carbohydrate chains of physarumin receptor.


Differential effects of a GTP-restricted mutant of Sar1p on segregation of cargo during export from the endoplasmic reticulum.
Export of cargo from the endoplasmic reticulum (ER) is the first membrane trafficking step in the secretory pathway. To date, all cargo proteins appear to use a common set of machinery for the initial stages of export, namely the COPII coat complex. Recent data from both yeast and mammalian systems have emerged suggesting that specific cargoes could be sorted from one another at the point of exit from the endoplasmic reticulum or immediately afterwards. Here, we have examined the mechanisms used for export of different types of cargo molecule from the endoplasmic reticulum. All cargoes examined utilise the COPII machinery, but specific differences are seen in the accumulation of cargo into ER-derived pre-budding complexes following expression of a GTP-restricted mutant of the Sar1p GTPase. Glycosylphosphatidylinositol (GPI)-anchored GFP is seen to be restricted to the ER under these conditions whereas other cargoes, including ts045-G and lumFP accumulate in pre-budding complexes. Following exit, GPI-FP, lumFP and ts045-G-FP all travel to the Golgi in the same vesicular tubular clusters (VTCs). These data show a differential requirement for efficient GTP hydrolysis by the Sar1p GTPase in export of cargo from the ER.


[An overview of the revised international classification of headache disorders (ICHD -II)].
The International Headache Society (IHS) revised The International Classification of Headache published in 1988. Old version has facilitated epidemiological and multinational clinical trials. Fifteen years after its original publication, a revised International Classification of Headache Disorders 2nd Edition(ICHD-II) has been unveiled in 2004. Modifications are small but significant. A lot of knowledge and evidences were added to the new version. A revised classification classifies headaches in 14 groups and categorized headache groups into four parts; part 1: primary headache, part 2: secondary headache, part 3: neuralgias and facial pain, and appendix. Physicians should continue to consult the IHS criteria to ensure accurate diagnosis and management for headache.


Gallium-67 citrate localization in the heart secondary to constrictive pericarditis with myocardial fibrosis.
Scintigraphy has demonstrated gallium-67 accumulation within the heart in pericarditis and cardiomyopathies of various kinds. We present a case report of a 63-yr-old man with multisystem disease who showed extensive myocardial uptake of Ga-67 by scintigraphy. At autopsy, constrictive pericarditis with myocardial fibrosis was found. Gallium-67 localization has not been documented previously in myocardial fibrosis accompanying constrictive pericarditis.


Development and validation of a tool to appraise guidelines on SARS-CoV-2 infection control strategies in healthcare workers.
Clinical guidelines on infection control strategies in healthcare workers (HCWs) play an important role in protecting them during the severe acute respiratory syndrome coronavirus 2 pandemic. Poorly constructed guidelines that are incomprehensive and/or ambiguous may compromise HCWs' safety. The objective of this study was to develop and validate a tool to appraise guidelines on infection control strategies in HCWs based on the guidelines published early in the coronavirus disease 2019 pandemic. A three-stage, web-based, Delphi consensus-building process among a panel of diverse HCWs and healthcare managers was performed. The tool was validated by appraising 40 international, specialty-specific, and procedure-specific guidelines along with national guidelines from countries with a wide range of gross national income. Overall consensus (≥75%) was reached at the end of three rounds for all six domains included in the tool. The Delphi panel recommended an ideal infection control guideline should encompass six domains: general characteristics (domain 1), engineering recommendations (domain 2), personal protective equipment (PPE) use (domain 3), and administrative aspects (domain 4-6) of infection control. The appraisal tool performed well across the six domains, and the inter-rater agreement was excellent for the 40 guidelines. All included guidelines performed relatively better in domains 1-3 than in domains 4-6, and this was more evident in guidelines originating from lower income countries. The guideline appraisal tool was robust and easy to use. Engineering recommendations aspects of infection control, administrative measures that promote optimal PPE use, and HCW wellbeing were generally lacking in assessed guidelines. This tool may enable health systems to adopt high-quality HCW infection control guidelines during the severe acute respiratory syndrome coronavirus 2 pandemic and may also provide a framework for future guideline development.


Vegetated Treatment Systems for Removing Contaminants Associated with Surface Water Toxicity in Agriculture and Urban Runoff.
Urban stormwater and agriculture irrigation runoff contain a complex mixture of contaminants that are often toxic to adjacent receiving waters. Runoff may be treated with simple systems designed to promote sorption of contaminants to vegetation and soils and promote infiltration. Two example systems are described: a bioswale treatment system for urban stormwater treatment, and a vegetated drainage ditch for treating agriculture irrigation runoff. Both have similar attributes that reduce contaminant loading in runoff: vegetation that results in sorption of the contaminants to the soil and plant surfaces, and water infiltration. These systems may also include the integration of granulated activated carbon as a polishing step to remove residual contaminants. Implementation of these systems in agriculture and urban watersheds requires system monitoring to verify treatment efficacy. This includes chemical monitoring for specific contaminants responsible for toxicity. The current paper emphasizes monitoring of current use pesticides since these are responsible for surface water toxicity to aquatic invertebrates.


Impacts of the Great East Japan Earthquake on diabetic patients.
We investigated impacts of the Great East Japan Earthquake on diabetic patients and characterized those with disaster-susceptible diabetes. We enrolled 497 diabetic patients who had been followed at hospitals in devastated areas. We collected metabolic parameters prospectively, 1 and 3 months after the earthquake, and retrospectively for pre-earthquake time-points. Questionnaire surveys were carried out regarding earthquake-related damage and post-earthquake lifestyle alterations. Available data were analyzed to examine associations with post-earthquake glycosylated hemoglobin alterations. The mean glycosylated hemoglobin level of the participants was not elevated at 1 month, and was significantly decreased at 3 months as compared with the pre-earthquake glycosylated hemoglobin. There were no significant differences in earthquake-related damage or lifestyle alterations between the improved and worsened glycemic control groups according to the data obtained from the questionnaire survey. As reported, fasting serum C-peptide levels were significantly lower in the worsened glycemic control group (P < 0.05). Notably, plasma noradrenaline levels were significantly higher in the worsened glycemic control group (P < 0.05). Furthermore, at 1 month after the earthquake, the plasma noradrenaline level was significantly higher in the low C-peptide group (fasting serum C-peptide <1.0 ng/mL) than in the high C-peptide group (fasting serum C-peptide ≥1.0 ng/mL), but this difference had disappeared by 3 months after the earthquake. These findings show that post-earthquake plasma noradrenaline levels were temporarily increased in the low C-peptide group. Sympathetic nerve activation might be elicited more easily in subjects with lower endogenous insulin secretory capacity, and could be involved in the mechanism underlying post-earthquake worsening of glycemic control.


Effects of a curriculum and inservice program on the quantity and quality of elementary physical education classes.
The primary responsibility for engaging children in opportunities to be physically active and learn physical skills rests with school physical education. This study evaluated the effects of a combined health-related curriculum and inservice program on the quantity and quality of elementary school physical education lessons. Seven schools (N = 28 fourth-grade classes) in one district were randomly assigned to one of three conditions: 10 classes were taught in their usual manner by classroom teachers (Control [CO]); 10 classes were taught by trained classroom teachers (TT) who received inservice training and follow-up consultations; and 8 classes were taught by physical education specialists (PES) hired by the research project. Student activity level, curriculum context, and teacher behavior were directly observed and coded during a sample of 112 lessons over an 8-month period. Results indicated significant differences in both the frequency and mean length of classes (PES, 26.7 min; TT, 23.4 min; CO, 18.9 min). Additionally, the curriculum and inservice program equipped trained classroom teachers to provide significantly better classes than were provided by controls in terms of student activity engagement, lesson context, and active instructional behavior, though their classes did not match the quality of those taught by the physical education specialists. This study is unique in its use of direct observation of lessons to assess a curriculum and inservice intervention.


Hybrid Prepectoral Breast Reconstruction: A Surgical Approach that Combines the Benefits of Autologous and Implant-Based Reconstruction.
The advantages of hybrid breast reconstruction (i.e., the combination of free tissue transfer with simultaneous implant placement) are well known. In an attempt to further minimize morbidity and simplify the procedure, the authors have modified their approach in that a prepectoral approach is now routinely chosen. A retrospective analysis of patients who underwent immediate microsurgical breast reconstruction with simultaneous prepectoral implant placement was performed. Clinical outcomes and postoperative complications were examined. A total of 23 patients with a mean age of 46.6 years (range, 26 to 72 years) and mean body mass index of 25.8 kg/m (range, 21.4 to 32.1 kg/m) underwent reconstruction with 46 free flaps with simultaneous prepectoral silicone gel implant placement. The most common implant volume was 210 cc (range, 150 to 255 cc). Postoperative complications included hematoma [n = 1 (4.3 percent)], mastectomy skin flap necrosis [n = 5 (21.7 percent)], fat necrosis [n = 3 (13 percent)], and delayed wound healing at the flap donor site [n = 4 (17.4 percent)]. No case of implant malposition, implant infection, flap loss, or "red breast" syndrome was encountered during a mean follow-up of 8.4 months (range, 2 to 17 months). Prepectoral hybrid breast reconstruction is a safe procedure that combines the benefits of autologous and implant-based reconstruction. Although the transfer of well-vascularized soft tissue allows reconstruction of natural breast ptosis, the addition of an implant provides the desired projection, but without being associated with complications such as rippling or animation deformity. Therapeutic, IV.


Lipopolysaccharides induce Smad2 phosphorylation through PI3K/Akt and MAPK cascades in HSC-T6 hepatic stellate cells.
Endotoxemia and its pro-fibrogenic signaling play a significant role in the development of hepatic fibrosis. This study investigated whether lipopolysaccharide (LPS) directly activate cultured HSC-T6 hepatic stellate cells (HSCs) through triggering Smad-dependent pro-fibrogenic signaling pathway. Direct cell counting and assays for cell proliferation and migration were used to measure the effects of LPS on HSC behaviors. Quantitative PCR, Western blot, and gelatin zymography were used to quantify the molecular effects of LPS on expression of HSC activation markers and signaling activity. Long-term exposure to LPS exhibited moderately stimulatory effect on HSC cell growth. A wound-healing cell migration assay showed that LPS suppressed HSC-T6 cell migration. qPCR and Western blotting detection indicated that LPS treatment induced upregulation of type I and IV collagens, α-smooth muscle actin (α-SMA), and matrix metalloproteinase-9 (MMP-9). Gelatin zymography confirmed that LPS elevated MMP-9, but not MMP-2 gelatinolytic activity. Moreover, LPS immediately stimulated Akt, EKR1/2, JNK, p38 MAPK, and Smad2 hyperphosphorylation, supporting that LPS directly triggers pro-fibrogenic Smad signaling cascade without TGF-β1 stimulation. Kinase blockade experiments demonstrated the involvement of PI3K/Akt, JNK, p38 MAPK, but not ERK1/2 signaling activation in the LPS-elicited Smad2 phosphorylation as well as the overexpression of type I collagen and α-SMA in HSC-T6 cells. These findings demonstrate that LPS exerts pro-fibrogenic effect through activation and transformation of HSCs. The tissue-remodeling effect of LPS may be attributable to its ability to activate non-canonical Smad pathway through PI3K/Akt and MAPK signaling cascades.


Pigmented basal cell carcinoma: Cytological diagnosis and differential diagnoses.
Pigmented basal cell carcinoma is a rare cutaneous neoplasm with only a few cases reported so far. Review of the literature yielded only an occasional fine-needle aspiration report of the cytologic features of the tumor.We report a rare case of pigmented basal cell carcinoma occurring on the thigh of a 55-year-old woman. The cytological features are described with discussion over the possible differential diagnoses.


Modeling current density distributions during transcutaneous cardiac pacing.
We developed a two-dimensional finite element model of a cross-section of the human thorax to study the current density distribution during transcutaneous cardiac pacing. The model comprises 964 nodes and 1842 elements and accounted for the electrical properties of eight different tissues or organs and also simulated the anisotropies of the intercostal muscles. The finite element software employed was a version for electrokinetics problems of Finite Element for Heat Transfer (FEHT) and we assessed the effects upon the efficacy of transcutaneous cardiac pacing of several electrode placements and sizes. To minimize pain in the chest wall and still be able to capture the heart, we minimized the ratio, R, between the current density in the thoracic wall (which causes pain) and the current density in the heart wall (which captures the heart). The best placement of the negative electrode was over the cardiac apex. The best placement of the positive electrode was under the right scapula, although other placements were nearly as good. The efficiency of pacing increased as electrode size increased up to 70 cm2 and showed little improvement for larger areas. Between different configurations of the precordial electrodes V1, V2, ..., V6 the most efficient configuration to pace with was V1 and V2 positive and V5 and V6 negative. A more efficient configuration uses an auxiliary electrode located at the right subscapular region.


Attitudes toward in-vehicle advanced alcohol detection technology.
Efforts are underway to develop advanced alcohol detection technologies suitable for use in all vehicles to prevent driving with an illegal blood alcohol concentration (BAC). Attitudes toward having this technology in all vehicles were assessed. A nationally representative sample of people 18 and older was interviewed by telephone. Eighty-four percent of survey respondents supported requiring alcohol ignition interlocks in the vehicles of convicted driving while intoxicated (DWI) offenders. Sixty-four percent said having advanced alcohol detection technology in all vehicles is a good or a very good idea, assuming the technology is reliable; 30 percent said it is a bad idea. Most people in favor said that it would prevent alcohol-impaired driving, save lives, or prevent crashes. Among respondents who said it is a bad/very bad idea, one third cited concerns about privacy or government interference; 20 percent said not all drivers need screening. Support was highest among respondents who do not drink, but it also was favored by the majority of respondents who drink, respondents who have driven within 2 hours of consuming alcohol, and respondents who may have driven when they were above the legal limit for alcohol. Forty-two percent of respondents who drive said they would want an advanced alcohol detection device in their next vehicles if it were available as an option at a reasonable price. Of the 54 percent who said they would not want a device, 44 percent said they do not drink alcohol so it would not be useful. Most people said a price less than $500 would be reasonable. It appears that the majority of the U.S. population is receptive to the idea of having advanced alcohol detection devices in all vehicles to prevent people from driving with an illegal BAC, although less than half say they would purchase a device in their next vehicles.


A new diterpenoid from Rhizophora apiculata.
A new diterpenoid, 15(S)-isopimar-7-en-1-oxo-15,16-diol (1), was isolated from the stems of mangrove plant Rhizophora apiculata. The structure of the new compound was elucidated by MS, IR, 1D, and 2D NMR techniques, including HMQC, HMBC, and NOESY correlations. In addition, seven known constituents were isolated from this plant for the first time.


Experimental investigation of factors affecting the absolute recovery coefficients in iodine-124 PET lesion imaging.
The use of recovery coefficients (RCs) in (124)I PET lesion imaging is a simple method to correct the imaged activity concentration (AC) primarily for the partial-volume effect and, to a minor extent, for the prompt gamma coincidence effect. The aim of this phantom study was to experimentally investigate a number of various factors affecting the (124)I RCs. Three RC-based correction approaches were considered. These approaches differ with respect to the volume of interest (VOI) drawn, which determines the imaged AC and the RCs: a single voxel VOI containing the maximum value (maximum RC), a spherical VOI with a diameter of the scanner resolution (resolution RC) and a VOI equaling the physical object volume (isovolume RC). Measurements were performed using mainly a stand-alone PET scanner (EXACT HR(+)) and a latest-generation PET/CT scanner (BIOGRAPH mCT). The RCs were determined using a cylindrical phantom containing spheres or rotational ellipsoids and were derived from images acquired with a reference acquisition protocol. For each type of RC, the influence of the following factors on the RC was assessed: object shape, background activity spill in and iterative image reconstruction parameters. To evaluate the robustness of the RC-based correction approaches, the percentage deviation between RC-corrected and true ACs was determined from images acquired with a clinical acquisition protocol of different AC regimes. The observed results of the shape and spill-in effects were compared with simulation data derived from a convolution-based model. The study demonstrated that the shape effect was negligible and, therefore, was in agreement with theoretical expectations. In contradiction to the simulation results, the observed spill-in effect was unexpectedly small. To avoid variations in the determination of RCs due to reconstruction parameter changes, image reconstruction with a pixel length of about one-third or less of the scanner resolution and an OSEM 1 x 32 algorithm or one with somewhat higher number of effective iterations are recommended. Using the clinical acquisition protocol, the phantom study indicated that the resolution- or isovolume-based recovery-correction approaches appeared to be more appropriate to recover the ACs from patient data; however, the application of the three RC-based correction approaches to small lesions containing low ACs was, in particular, associated with large underestimations. The phantom study had several limitations, which were discussed in detail.


Mother-child emotion dialogues: the disrupting effect of maternal history of communal sleeping.
The study examined associations between mothers' upbringing background (kibbutz vs. home) and maternal-sensitive guidance of emotional conversations with their preschool children; children's cooperation and exploration; and the coherence of their conversations. Using a quasi-experimental design, 112 children and their mothers (72 kibbutz raised, 40 home) completed the Autobiographical Emotional Event Dialogue. We hypothesized that maternal kibbutz upbringing would be associated to lower levels of mothers' sensitive guidance of the conversations, children's lower cooperation and exploration, and lower overall coherence. Results showed no upbringing-related differences for the mothers, but significant differences were found for the children, with children of kibbutz-raised mothers showing less cooperation and exploration, and lower levels of coherence for these dyads. The role of maternal background in shaping the interaction with their child is discussed.