Nurse cell polytene chromosomes of Drosophila melanogaster otu mutants: morphological changes accompanying interallelic complementation and position effect variegation.
Combinations of certain mutant alleles of the ovarian tumor gene permit the production of viable eggs. Two alleles that behave in this way are otu7 and otu11. Females homozygous for either allele are sterile, and their ovarian nurse cells (NC) contain giant polytene chromosomes of various morphologies. Fertile flies (otu+/otu+, otu+/otu7, otu+/otu11) have endopolyploid nurse cells with typical dispersed chromosomes. Fertile hybrids (otu7/otu11) produce large numbers of polytene chromosomes comparable to, and often larger than, classic salivary gland (SG) chromosomes. Therefore, these otu hybrids provide a unique system for studying, at the chromosomal level, the activation and expression of genes functioning during oogenesis. The otu gene encodes a long and a short isoform. The normal long isoform appears to be responsible for the dispersion of chromosomes during the endomitolic DNA replications occurring in ovarian NCs. The genetic inactivation of euchromatic genes placed next to pericentric heterochromatin by a chromosomal rearrangement is accompanied by the compaction of corresponding chromosome regions. A comparative study of the manifestation of position-effect variegation for the polytene chromosomes of SG cells and NCs was made using the Dp(1;1)pn 2b and Dp(1;f)1337 rearrangements. The percentage frequencies of block formation in the SG and NC nuclei for Dp(1;1)pn 2b rearrangement were 92.6% vs. 15.8%, respectively; for Dp(1;f) 1337, these values were 56.8% vs. 9.7%. Therefore heterochromatin belonging to germ line chromosomes is in a configuration that is far less likely to inactivate inserted segments of euchromatin than is heterochromatin from somatic chromosomes.


Effect of nano-oxide concentration on the mechanical properties of a maxillofacial silicone elastomer.
Contemporary silicone-based elastomeric prostheses tend to degrade over time because of the effect of mechanical loading. Little has been reported on how the mechanical properties of a maxillofacial prosthetic elastomer may be affected by the addition of nanosized oxide particles used as an opacifier. The purpose of this study was to evaluate the effect of different concentrations of nanosized oxides of various composition on the mechanical properties of a commercially available silicone elastomer. Nanosized oxides (Ti, Zn, or Ce) were added in various concentrations (0.5%, 1.0%, 1.5%, 2.0%, 2.5%, or 3.0% by weight) to a commercial silicone elastomer (A-2186), commonly used for fabricating extraoral maxillofacial prostheses. Silicone elastomer A-2186 without nanosized oxides served as a control group. Specimens (n=5) were polymerized according to manufacturer's recommendations and tested for tensile strength (ASTM D412) and tear strength (ASTM D624), and percent elongation in a universal testing machine. Uniformity of particle dispersion within the processed elastomer was assessed using scanning electron microscopic imaging. For each property, a 2-way ANOVA was performed evaluating the effect of oxide type and strength, and Fisher's PLSD test was used for pairwise comparisons (alpha=.05). SEM examination indicated that all 3 nanosized oxides distribute evenly throughout the silicone specimens, except for the 3.0% group, which are partly agglomerated. The 2.0% and 2.5% groups of all nanosized oxides demonstrated significantly higher tensile and tear strengths and percent elongation (P<.001) than the control group. CeO(2) had significantly lower tensile strength than TiO2 and ZnO (P<.05). The ZnO group had significantly higher tear strength than TiO(2) and CeO(2) (P <.05). Most of specimens became somewhat harder when compared with the control group. CeO(2) group had significantly higher Shore A hardness than TiO(2) and ZnO (P<.001). There was no significant difference of percent elongation among the type of nanosized oxides. Incorporation of Ti, Zn, or Ce nano-oxides at concentrations of 2.0% and 2.5% improved the overall mechanical properties of the silicone A-2186 maxillofacial elastomer.


Perfluoroalkylation of Unactivated Alkenes with Acid Anhydrides as the Perfluoroalkyl Source.
An efficient perfluoroalkylation of unactivated alkenes with perfluoro acid anhydrides was developed. Copper salts play a crucial role as a catalyst to achieve allylic perfluoroalkylation with the in situ generated bis(perfluoroacyl) peroxides. Furthermore, carboperfluoroalkylation of alkene bearing an aromatic ring at an appropriate position on the carbon side chain was found to proceed under metal-free conditions to afford carbocycles or heterocycles bearing a perfluoroalkyl group. This method, which makes use of readily available perfluoroalkyl sources, offers a convenient and powerful tool for introducing a perfluoroalkyl group onto an sp(3) carbon to construct synthetically useful skeletons.


Augmentation by bacterial lipopolysaccharide of antitumor potency of murine recombinant interferon-gamma against Lewis lung adenocarcinoma.
Stimulation by recombinant murine interferon-gamma (rMuIFN-gamma) of host defenses against the growth of Lewis lung adenocarcinoma, cell line 3LL, in the lung was examined. 3LL cells were resistant to in vitro antiproliferative activities of rMuIFN-gamma. On the other hand, rMuIFN-gamma augmented the killer activities of the non-adherent population of spleen cells and peripheral blood mononuclear cells (PBMC) in vivo, and the IFN also stimulated the cytostatic activities of peritoneal and splenic macrophages, but not alveolar macrophages. The combination of rMuIFN-gamma with LPS synergistically activated macrophages from the lung, as well as the peritoneal cavity and the spleen, to become both cytostatic and cytolytic against 3LL cells. The macrophages activated in vitro by simultaneous incubation with these agents markedly suppressed the growth of 3LL cells in vivo. The growth in the lung of 3LL cells implanted iv was significantly (P less than 0.05) suppressed by combination therapy with rMuIFN-gamma and LPS, but not by either agent alone. These results indicate that the potency of rMuIFN-gamma action against 3LL cells can be augmented by combination with LPS, mainly through synergistic macrophage activation.


Discovery and optimization of pyrimidone indoline amide PI3Kβ inhibitors for the treatment of phosphatase and tensin homologue (PTEN)-deficient cancers.
Compelling molecular biology publications have reported the implication of phosphoinositide kinase PI3Kβ in PTEN-deficient cell line growth and proliferation. These findings supported a scientific rationale for the development of PI3Kβ-specific inhibitors for the treatment of PTEN-deficient cancers. This paper describes the discovery of 2-[2-(2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (7) and the optimization of this new series of active and selective pyrimidone indoline amide PI3Kβ inhibitors. 2-[2-(2-Methyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one (28), identified following a carefully designed methyl scan, displayed improved physicochemical and in vitro pharmacokinetic properties. Structural biology efforts enabled the acquisition of the first X-ray cocrystal structure of p110β with the selective inhibitor compound 28 bound to the ATP site. The nonplanar binding mode described herein is consistent with observed structure-activity relationship for the series. Compound 28 demonstrated significant in vivo activity in a UACC-62 xenograft model in mice, warranting further preclinical investigation. Following successful development, compound 28 entered phase I/Ib clinical trial in patients with advanced cancer.


Autosomal recessive spastic ataxia of Charlevoix-Saguenay: compound heterozygotes for nonsense mutations of the SACS gene.
Mutations of the SACS gene have been reported in patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay from Canada (Quebec), Tunisia, Japan, Turkey, Belgium, Italy, Spain, the Netherlands, and Germany. Features that distinguish autosomal recessive spastic ataxia of Charlevoix-Saguenay from other recessive ataxias include sensory motor polyneuropathy and hypermyelinated retinal nerve fibers. We describe the clinical, electrophysiological, and radiological features in 2 white American siblings diagnosed with autosomal recessive spastic ataxia of Charlevoix-Saguenay. The 2 affected children are compound heterozygotes for nonsense mutations of the SACS gene (c. 3484 G>T, p. E 1162 X; and c. 11,707 C>T, p. R 3903 X). We have measured allele-specific SACS mRNA abundance in peripheral blood and show that these specific mutant mRNAs are not degraded. We suggest that in children with early onset cerebellar ataxia and spasticity, ophthalmological examination and nerve conduction testing may guide genetic testing.


Efficacy of Coral Sand for Removal of and Bacteriophage under Saturated Flow Conditions.
Knowledge of how effectively microbes are transported through porous media is useful for water resource/wastewater management. Despite much research having been done to characterize microbial contaminant transport through various sedimentary materials, very little study has been made on coral sand, such as constitutes the primary substrate of many Pacific atolls. We conducted a set of laboratory column experiments as a preliminary examination of how effective coral sand is at attenuating model pathogens J6-2 and MS2 bacteriophage (phage) under saturated flow conditions mildly representative of field conditions at the Bonriki freshwater lens, South Tarawa, Kiribati. The very poorly sorted gravelly sand coral substrate tested proved very effective at attenuating the bacterial tracer, and spatial removal rates of between 0.02 and 0.07 log cm were determined for J6-2. The ability to determine precise removal rates for MS2 phage was compromised by the use of a plastic apparatus, although the evidence weights toward coral sand being less effective at attenuating MS2 phage than it is . Further research is required to fully assess the ability of coral sand to remove pathogens and to explore how this medium could be engineered into cost-effective water/wastewater treatment solutions on Pacific atolls. The phage data from this work highlight the limitations of using plastic apparatus in experiments targeted at characterizing the fate and transport of viruses.


[Work process of nurses' aides and nursing technicians in primary health care].
This research had as its object the practice of nurses' aides and nursing technicians in service of Primary Health Care of the city of Ribeirão Preto-SP, Brazil. The aims were: characterize the work process of these agents, analyze his concepts on the constituent elements of working process and identify and analyze the difficulties and facilities in developing the work process from the perspective of integrality. It was descriptive and qualitative. To collect the data were used participant observation and the semi-structured interview and the data were dealt with thematic analysis. It was found the predominance of the organization of the work process to assist people with the need to deal with diseases/health problems and met potential for development of the work process for integrality health care. It is suggested the practice of permanent education, the qualification to listening and new training policies for these workers.


The effectiveness of the treatment of octreotide on chylous ascites after liver cirrhosis.
Octreotide is a crucial drug used for treating patients with chylous ascites; however, there have been few reports related to octreotide that are being used in cirrhotic patients. Thus, this thesis is designed to determine the effects of octreotide on patients with chylous ascites after liver cirrhosis. Eight patients were diagnosed with chylous ascites, on the basis of laboratory findings on ascites samples, between January 2003 and May 2008. Octreotide was given to the six patients, while the remaining two were treated as a control. All patients had persistent peritoneal drainage with the quantity and quality of the drainage fluid observed once every other day. All the necessary care was individually given to the patients during the therapy. All patients properly received combined therapy including a low-fat and low-sodium diet, and diuretic and peritoneal drainage. The volume of the peritoneal drainage was reduced to zero in one of the six patients who received octreotide therapy, while the other five had the drainage volumes decreased from 2,000 to 50 ml with a clear appearance and negative qualitative analysis of chyle. For those two patients who did not receive octreotide therapy, the conditions of peritoneal drainage seldom changed both from the qualitative and quantitative aspects. In conclusion, Octreotide, along with combined therapy, can rapidly relieve portal hypertension and reduce triglyceride levels in ascites. It appears to be an effective therapy available for the treatment of chylous ascites caused by liver cirrhosis.


Health impacts of caregiving for older adults with functional limitations: results from the Singapore survey on informal caregiving.
To estimate the health impact, in terms of depression, self-rated health, and health services utilization, of providing care to older adults (75+) requiring human assistance in at least one activity of daily living (ADL) limitation. Data from 1,077 caregivers and 318 noncaregivers, interviewed in the Singapore Survey on Informal Caregiving, was used to examine differences in depressive symptoms, self-rated health, and number of outpatient visits in the last 1 month between caregivers and noncaregivers. Multivariate models for the outcomes, adjusting for characteristics of the caregiver/noncaregiver and care-recipient/potential care recipient, were run. Caregivers were more depressed, had poorer self-rated health, and had a higher rate of outpatient visits in the past month compared to noncaregivers. The study indicates the need for support services to family caregivers of older adults with ADL limitations.


An oxygen-independent and membrane-less glucose biobattery/supercapacitor hybrid device.
Enzymatic biofuel cells can generate electricity directly from the chemical energy of biofuels in physiological fluids, but their power density is significantly limited by the performance of the cathode which is based on oxygen reduction for in vivo applications. An oxygen-independent and membrane-less glucose biobattery was prepared that consists of a dealloyed nanoporous gold (NPG) supported glucose dehydrogenase (GDH) bioanode, immobilised with the assistance of conductive polymer/Os redox polymer composites, and a solid-state NPG/MnO2 cathode. In a solution containing 10mM glucose, a maximum power density of 2.3µWcm-2 at 0.21V and an open circuit voltage (OCV) of 0.49V were registered as a biobattery. The potential of the discharged MnO2 could be recovered, enabling a proof-of-concept biobattery/supercapacitor hybrid device. The resulting device exhibited a stable performance for 50 cycles of self-recovery and galvanostatic discharge as a supercapacitor at 0.1mAcm-2 over a period of 25h. The device could be discharged at current densities up to 2mAcm-2 supplying a maximum instantaneous power density of 676 μW cm-2, which is 294 times higher than that from the biobattery alone. A mechanism for the recovery of the potential of the cathode, analogous to that of RuO2 (Electrochim. Acta 42(23), 3541-3552) is described.


Influence of collaborative customer service by service robots and clerks in bakery stores.
In recent years, various service robots have been deployed in stores as recommendation systems. Previous studies have sought to increase the influence of these robots by enhancing their social acceptance and trust. However, when such service robots recommend a product to customers in real environments, the effect on the customers is influenced not only by the robot itself, but also by the social influence of the surrounding people such as store clerks. Therefore, leveraging the social influence of the clerks may increase the influence of the robots on the customers. Hence, we compared the influence of robots with and without collaborative customer service between the robots and clerks in two bakery stores. The experimental results showed that collaborative customer service increased the purchase rate of the recommended bread and improved the impressions of the robot and store experience of the customers. Because the results also showed that the workload required for the clerks to collaborate with the robot was not high, this study suggests that all stores with service robots may demonstrate high effectiveness in introducing collaborative customer service.


Examining the patterns of uncertainty across clinical reasoning tasks: effects of contextual factors on the clinical reasoning process.
Objectives Uncertainty is common in clinical reasoning given the dynamic processes required to come to a diagnosis. Though some uncertainty is expected during clinical encounters, it can have detrimental effects on clinical reasoning. Likewise, evidence has established the potentially detrimental effects of the presence of distracting contextual factors (i.e., factors other than case content needed to establish a diagnosis) in a clinical encounter on clinical reasoning. The purpose of this study was to examine how linguistic markers of uncertainty overlap with different clinical reasoning tasks and how distracting contextual factors might affect physicians' clinical reasoning process. Methods In this descriptive exploratory study, physicians participated in a live or video recorded simulated clinical encounter depicting a patient with unstable angina with and without contextual factors. Transcribed think-aloud reflections were coded using Goldszmidt's clinical reasoning task typology (26 tasks encompassing the domains of framing, diagnosis, management, and reflection) and then those coded categories were examined using linguistic markers of uncertainty (e.g., probably, possibly, etc.). Results Thirty physicians with varying levels of experience participated. Consistent with expectations, descriptive analysis revealed that physicians expressed more uncertainty in cases with distracting contextual factors compared to those without. Across the four domains of reasoning tasks, physicians expressed the most uncertainty in diagnosis and least in reflection. Conclusions These results highlight how linguistic markers of uncertainty can shed light on the role contextual factors might play in uncertainty which can lead to error and why it is essential to find ways of managing it.


Transmission of bovine viral diarrhea virus to adult goats from persistently infected cattle.
The transmission of bovine viral diarrhea virus (BVDV) from persistently infected (PI) heifers to adult seronegative goats was examined in this study. Ten seronegative adult goats were exposed to 4 PI heifers. None of the goats developed any clinical signs but all goats seroconverted by 42 days after exposure to the PI cattle. Results indicate that goats are susceptible to BVDV infection when housed with PI cattle.


[Neurologic and neurophysiologic studies of impotent patients].
A multispeciality approach of impotent patients are necessary to establish the cause of impotence. Neurological history and examination are very important and must be completed by neurophysiological investigations. Bulbo-cavernosus reflex, conduction velocity of the dorsal nerve of penis and pudendal evoked potentials seems the most interesting tests. Urodynamics, perineal EMG, penile vibratory sensibility test can help determination of some peripheral neuropathies. Single potential analysis of cavernous electric activity may be useful in diagnosis of pudendal autonomic dysfunction.


Cell based therapy for osteoarthritis in a sheep model: gross and histological assessment.
This study was to determine if autologous bone marrow mesenchymal stem cells (BMSCs) cultured in chondrogenic medium could repair surgically induced osteoarthritis. Sheep BMSCs were cultured in medium containing 5ng/ml TGFbeta3 + 50ng/ml IGF-1 for three weeks. The cultured cells were then suspended at density of 2x10(6) cell/ml and injected intraarticularly into the osteoarthritic knee joint. After six weeks, the distal head of the femur and the proximal tibial plateau were removed and stained with H&E. The results indicated that knee joints treated with autologous BMSCs cultured in chondrogenic medium showed clear evidence of articular cartilage regeneration in comparison with other groups.


Squamous cell carcinoma of the oral tongue: a 25-year, single institution experience.
To report the characteristics, prognostic factors and treatment outcomes of 102 patients with squamous cell carcinoma of the oral tongue treated and followed up at a single institution over a 25-year period. This retrospective study was carried out by auditing the medical records of 102 patients diagnosed with squamous cell carcinoma of the oral tongue and treated at our institution between 1982 and 2007. Patient follow up ranged from nine to 310 months (median 35 months). Fifty per cent of the patients were treated with surgery followed by a combination of chemotherapy and radiotherapy (43.1 per cent received concurrent chemoradiation and 6.9 per cent received sequential chemotherapy and radiotherapy), whereas 29.4 per cent received surgery followed by adjuvant radiotherapy alone. The remaining patients (20.6 per cent) did not undergo surgery and were treated with definitive radiotherapy with or without chemotherapy. There were 48 men and 54 women. The age at presentation was 19-85 years (median 57 years). The peak incidence was observed between 60 and 70 years. Resection margins were clear in 75 per cent of patients and involved in 25 per cent. Stage I disease was found in 11.8 per cent of patients, stage II in 34.3 per cent, stage III in 22.5 per cent and stage IV in 31.4 per cent. The five-year disease-free survival and overall survival were 65.7 and 72.5 per cent, respectively. Thirty-five patients suffered recurrence after treatment, 74.0 per cent of them at the site of initial cervical nodal involvement. Univariate analysis for overall survival revealed the following as prognostic factors: treatment schedule (surgical vs non-surgical; p < 0.001); age (<60 years vs >or=60 years; p = 0.038); extent of cervical lymph node involvement (p = 0.015); primary tumour stage (p < 0.001); node stage (p = 0.034); and disease stage (p = 0.013). However, on multivariate analysis, only non-surgical treatment (p = 0.001) and advanced disease stage (p = 0.05) were found to have a negative influence on survival. Our limited data suggest that, in Iran, squamous cell carcinoma of the oral tongue tends to present at a locally advanced stage, with a high frequency of locoregional failure and a poor outcome. Combined modality therapy should be considered for the majority of patients with squamous cell carcinoma of the tongue.


Study of Glycated Haemoglobin (HbA1c) In Non-Diabetic Subjects with Subclinical Hypothyroidism.
India has the higher prevalence of prediabetes, diabetes and hypothyroidism. Subclinical Hypothyroidism (SH) is more prevalent in the females than in the males. Studies have shown the elevated HbA1c in the non-diabetic hypothyroid patients. SH is defined by normal serum triiodothyronine (T3), thyroxine (T4) levels and serum Thyroid Stimulating Hormone (TSH) level falling between 4.2 to 10 mU/L. To study the HbA1c level in the non-diabetic SH patients and to compare the HbA1c level with the controls. This case-control study was conducted on 200 subjects. A total of 100 subjects of the SH without diabetes were selected on the basis of the serum TSH (> 4.2 to < 10 mU/L), Fasting Blood Sugar (FBS) (< 110 mg/dl) level and another 100 age and sex matched normal healthy individuals were selected as the control. The HbA1c levels were measured using Immunoturbidimetry method in the Cobas Integra 400 plus. An independent t-test is applied to find out the statistically significant difference in the level of HbA1c in the case and the control groups. Subjects with the non-diabetic SH had a significant higher level (5.70±0.35 %) of the HbA1c than the controls (5.26±0.17 %) (p<0.0001). There was no significant difference between the cases and the controls for the age, sex, FBS, vitamin D3, Haemoglobin (Hb), serum T3 and serum T4 levels. Our data suggest that the non-diabetic subjects with SH show misleadingly high levels of the HbA1c. Therefore, the effect of altered levels of the serum TSH on the HbA1c must be considered when interpreting the HbA1c for the diagnosis of diabetes in the SH patients.


[Cardiac transplantation: role of echocardiography in the diagnosis of rejection].
Sixteen patients surviving orthotopic cardiac transplantation were studied by M-Mode and two dimensional echocardiography (ECHO) on the same day of cardiac biopsy during (n = 138) a mean follow-up of 6.2 +/- 4 months (range 1-4 months). The following parameters were measured: right ventricular end diastolic internal diameter (RVdD) left ventricular end diastolic internal diameter (LVdD), interventricular septum (IVS) and posterior wall (PW) diastolic thickness, myocardial mass (MM); LV cross sectional area (CSA) and ejection fraction (EF). LV and RV wall motion, pericardial effusion and myocardial echogenicity (brightness) were evaluated by inspection. Every ECHO was compared with the previous one for qualitative and quantitative changes. In the absence of rejection, analysis of the data during the first postoperative week showed the following results: mean EF = 51 +/- 6.8%, dilated overloaded RV (30.4 +/- 4.8 mm), various amount of pericardial effusion; FE increased significantly (55.3 +/- 4%; p less than 0.001) and RVdD decreased (26.6 +/- 5mm; p less than 0.001) after the 2nd week and remained stable thereafter, while pericardial effusion decreased or disappeared. The mean values of the remaining ECHO parameters did not very significantly during the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)


Potential value for new diagnostic markers in the early recognition of acute coronary syndromes.
The diagnostic approach to acute coronary syndromes (ACS) remains one of the most difficult and controversial challenges facing emergency physicians. In recent years, cardiac troponins have emerged as the biochemical "gold standard" for diagnosis of patients with acute chest pain, enhancing our ability to recognize ACS. Early diagnosis and treatment of myocardial ischemia improve patient outcomes, but conventional markers are often nondiagnostic at the time of arrival at the emergency department. Promising new biomarkers, which appear earlier after the onset of ischemia, are being studied and integrated into clinical practice. Some are markers of myocyte necrosis, but others, including ischemia-modified albumin and natriuretic peptides, detect myocardial ischemia and myocardial dysfunction. The aim of the present article is to review the diagnostic approach to ACS, focusing on recent literature describing novel biochemical markers. If ongoing and future studies confirm their role in probability-based models risk assessment, a new era in the diagnostic approach to ACS may be dawning.


Effect of fuel properties on mutagenic activity in extracts of heavy-duty diesel exhaust particulate.
The effect of varying fuel properties on the emission of mutagenic materials was studied in diesel exhaust particles from a heavy duty engine run under transient speed and load conditions while using nine fuels varying in aromatics, sulfur and boiling point. Mutagenic activity of the soluble organic fraction (SOF) of the particulate was determined using the Ames Salmonella test system with strain TA98 with and without S9 activation. Increasing mutagenic activity relative to fuel consumed (mutants/lb fuel) or to engine work output (mutants/hp-h) was correlated with increasing fuel aromatics (p less than 0.05), but not with fuel sulfur. Increased fuel sulfur levels were correlated with increased amounts of SOF but with decreasing mutagenic activity of the SOF (mutants/microgram SOF) (p less than 0.05). As a result, mutants/hp-h were essentially the same for high- and low-sulfur fuels with high aromatics. No association was found between the fuels' boiling points and the mutagenic activity of the SOF. Mutagenic activity with S9 was generally lower than without, but the correlations were not changed.


The state of evidence for social and emotional learning: A contemporary meta-analysis of universal school-based SEL interventions.
This article provides a systematic review and meta-analysis of the current evidence for universal school-based (USB) social and emotional learning (SEL) interventions for students in kindergarten through 12th grade available from 2008 through 2020. The sample includes 424 studies from 53 countries, reflecting 252 discrete USB SEL interventions, involving 575,361 students. Results endorsed that, compared to control conditions, students who participate in USB SEL interventions experienced significantly improved skills, attitudes, behaviors, school climate and safety, peer relationships, school functioning, and academic achievement. Significant heterogeneity in USB SEL content, intervention features, context, and implementation quality moderated student experiences and outcomes. Strengths and limitations of this evidence and implications for future USB SEL research, policy, and practice are discussed.


Response of polymorphonuclear leukocytes to topical leukotriene B4 in healthy and psoriatic skin.
The in situ infiltration of polymorphonuclear leukocytes following the topical application of leukotriene B4 to the clinically uninvolved skin of psoriatic patients and the skin of normal controls has been quantified using elastase as a marker enzyme. The magnitude of this response in the psoriatic patients proved to be significantly diminished compared with the response in the controls. The time course of the response was similar in both groups, maximum elastase activity being seen about 18 h after application of the LTB4.


An evaluation and recommendation of the optimal methodologies to detect RET gene rearrangements in papillary thyroid carcinoma.
To recommend a reliable and clinically realistic RET/PTC rearrangement detection assay for papillary thyroid carcinoma (PTC), we compared multiplex quantitative polymerase chain reaction (qPCR), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). RET/PTC rearrangement was detected using either RET break-apart FISH followed by multicolor FISH to confirm CCDC6/RET or NCOA4/RET fusions, or by multiplex qPCR to detect 14 RET/PTC subtypes with simultaneous RET mRNA expression. RET protein expression was detected by IHC. The specificity and sensitivity of multiplex qPCR and IHC were calculated using break-apart FISH as a reference. Among 73 PTC patients with sufficient tissue available for FISH and multiplex qPCR, 10 cases were defined as RET/PTC positive by both assays, including eight CCDC6/RET and two NCOA4/RET fusions with relatively high RET mRNA. In addition, multiplex qPCR identified another two CCDC6/RET fusion positive cases, but with low RET mRNA expression. IHC staining identified 11 RET positive cases among 39 patients with available samples. In comparison to FISH, multiplex qPCR displayed 100% sensitivity and 97% specificity to detect RET/PTC fusions, while IHC was neither sensitive nor specific. Our data reveal that both multiplex qPCR and FISH assays are equally applicable for detection of RET/PTC rearrangements. Break-apart FISH methodology is highly recommended for the wider screening of RET rearrangements (regardless of partner genes), while multiplex qPCR is preferred to identify all known fusion types using one assay, provided mRNA expression is also measured. IHC analysis could potentially provide an additional method of fusion detection dependent on further optimization of assay conditions and scoring cutoffs.


Acute side effects of surfactant treatment.
There is increasing evidence from studies on animals and humans that surfactant administration may have a great impact on cerebral perfusion. These effects may result from direct pulmonary or hemodynamic changes (or a combination of both), but may also be due to rapid alterations of blood gases. Type of surfactant and mode of administration seem to play an important role. Results from the pertinent literature are summarised with a special emphasis on how to avoid potentially harmful side effects of surfactant therapy in preterm infants.


Common variation at 6p21.31 (BAK1) influences the risk of chronic lymphocytic leukemia.
We performed a meta-analysis of 3 genome-wide association studies to identify additional common variants influencing chronic lymphocytic leukemia (CLL) risk. The discovery phase was composed of genome-wide association study data from 1121 cases and 3745 controls. Replication analysis was performed in 861 cases and 2033 controls. We identified a novel CLL risk locus at 6p21.33 (rs210142; intronic to the BAK1 gene, BCL2 antagonist killer 1; P = 9.47 × 10(-16)). A strong relationship between risk genotype and reduced BAK1 expression was shown in lymphoblastoid cell lines. This finding provides additional support for polygenic inheritance to CLL and provides further insight into the biologic basis of disease development.


(Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease.
Chronic inflammation represents one of the most consistent biologic features of aging. However, the precise etiology of persistent low-grade increases in inflammation remains unclear. Recent evidence suggests that the gut microbiome may play a key role in age-related inflammation. Indeed, several studies have indicated that older adults display an altered composition of the gut microbiota, and early evidence indicates that this dysbiosis is associated with the presence of several key circulating inflammatory analytes. The present review summarizes knowledge on age-related inflammation and discusses how potential relationships with gut dysbiosis may lead to novel treatment strategies in the future."The pattern of disease is an expression of the response of man to his total environment (physical, biological, and social); this response is, therefore, determined by anything that affects man himself or his environment." - Rene Dubos, 1961.


The Impact of Parameter Selection and Setup Conditions on Image Quality of an On-Board Helical Kilovoltage Computed Tomography System.
Purpose To evaluate the imaging performance of an on-board helical kilovoltage computed tomography (kVCT) system mounted on a helical tomotherapy unit for various imaging parameters and setup conditions. Methods Images of a commonly used computed tomography (CT) image quality phantom were acquired while varying the selection of available parameters (anatomy, mode, body size) as well as phantom positioning and size. Image quality metrics (IQM) including noise, uniformity, contrast, CT number constancy, and spatial resolution were compared for parameter and setup variations. Results The use of fine mode improved noise and contrast metrics by 20-30% compared to normal mode and by nearly a factor of two compared to the coarse mode for otherwise identical protocols. Uniformity, CT number constancy, and spatial resolution were also improved for fine mode. Thorax and pelvis anatomy protocols improved noise, uniformity, and contrast metrics by 10-20% compared to images acquired with head protocols. No significant differences in CT number constancy or spatial resolution were observed regardless of anatomy choice. Increasing body size (milliampere second (mAs)/rotation) improved each image quality metric. Vertical and lateral phantom shifts of up to ±6 cm degraded noise and contrast metrics by up to 30% relative to the isocenter while also worsening uniformity and CT number constancy. IQM were also degraded substantially with the use of annuli to increase the phantom diameter (32 cm vs. 20 cm). Despite variations in image characteristics among the investigated changes, most metrics were within manufacturer specifications when applicable. Conclusion This work demonstrates the dependence of image quality on parameter selection and setup conditions for a helical kVCT system utilized in image-guided and adaptive helical tomotherapy treatments. While the overall image quality is robust to variations in imaging parameters, care should be taken when selecting parameters as patient size increases or positioning moves from the isocenter to ensure adequate image quality is still achieved.


Expediting Discharge in Hospitalized, Adult Patients with Skin and Soft Tissue Infections Who Received Empiric Vancomycin Therapy with Oritavancin: Description of Findings from an Institutional Pathway.
An internal quality assurance review at AtlantiCare Regional Medical Center (ARMC) revealed that patients admitted with skin and soft tissue infections (SSTIs) remained in hospital post-resolution of acute symptoms and demonstrated a delayed transition to step-down oral antibiotic therapy. A non-mandatory institutional pathway was developed and implemented in 2016 to expedite hospital discharge in hemodynamically stable SSTI patients by utilizing oritavancin. To describe the outcomes associated with use of single-dose oritavancin therapy to expedite hospital discharge in hemodynamically stable inpatients with SSTIs. A retrospective, descriptive cohort was evaluated for outcomes of patients with SSTIs who received either oritavancin to expedite discharge or were discharged on oral step-down antibiotics. Patients were included in this analysis if they were: ≥ 18 years old; hospitalized; received empiric vancomycin; not pregnant or nursing; hemodynamically stable at the time of assessment; and received either oritavancin or oral step-down antibiotics to facilitate discharge. The primary outcomes were index hospital length of stay (LOS), 30-day SSTI-related readmissions, and 30-day SSTI progression. Overall, 199 patients met the study criteria (oritavancin = 99 and oral step-down antibiotics = 100). Groups were well matched at baseline. Patients who received oritavancin had a shorter mean index hospital LOS than those in the oral step-down antibiotic group (3.5 days vs. 5.6 days). Patients receiving oritavancin also had lower SSTI 30-day readmission and SSTI-progression rates. An institutional pathway that used oritavancin to expedite hospital discharge of hemodynamically stable SSTI patients resulted in shorter hospital LOS, less 30-day SSTI-related hospital readmissions, and decreased SSTI progression relative to those discharged on conventional oral step-down therapy.


Efficient killing of radioresistant breast cancer cells by cytokine-induced killer cells.
Recurrence of breast cancer after radiotherapy may be partly explained by the presence of radioresistant cells. Thus, it would be desirable to develop an effective therapy against radioresistant cells. In this study, we demonstrated the intense antitumor activity of cytokine-induced killer cells against MCF-7 and radioresistant MCF-7 cells, as revealed by cytokine-induced killer-mediated cytotoxicity, tumor cell proliferation, and tumor invasion. Radioresistant MCF-7 cells were more susceptible to cytokine-induced killer cell killing. The stronger cytotoxicity of cytokine-induced killer cells against radioresistant MCF-7 cells was dependent on the expression of major histocompatibility complex class I polypeptide-related sequence A/B on radioresistant MCF-7 cells after exposure of cytokine-induced killer cells to sensitized targets. In addition, we demonstrated that cytokine-induced killer cell treatment sensitized breast cancer cells to chemotherapy via the downregulation of TK1, TYMS, and MDR1. These results indicate that cytokine-induced killer cell treatment in combination with radiotherapy and/or chemotherapy may induce synergistic antitumor activities and represent a novel strategy for breast cancer.


Interstitial fluid: exchange of macromolecules between plasma and skin interstitium.
Fluid was collected from blisters developed by suction on the abdominal skin in ten normal volunteers. During the same study the transcapillary escape rate of intravenously injected 131I-albumin and 125I-IgG together with the accumulation of these tracers in the blister fluid was measured. The ratios between the concentrations of endogenous albumin, transferrin, IgG and alpha 2-macroglobulin in the blister fluid (Cb) and serum (Cs) correlated directly with the free diffusion coefficients indicating that the sieving properties of the vascular endothelium remained intact during the suction. The ratios of intravascular to total masses of the four endogenous proteins calculated from plasma volume, Cs, Cb and extracellular fluid volume determined with inulin and Cb were very similar to those obtained in long-term metabolic turnover studies. The ratio between the accumulated IgG and albumin tracers in the blister fluid (0.80) was identical with the Cb/Cs ratio between endogenous IgG and albumin (0.78) but higher than the ratio between the IgG and albumin escape rates from the total microvasculature (0.58). From the protein tracer determinations it cannot be definitely excluded that suction increases the microvascular escape rates. If the distribution volume of inulin equates that of albumin in steady-state it can, however, be concluded from the data given on the endogenous plasma protein, that blister fluid from the abdominal skin corresponds to average interstitial tissue fluid.


The appearance of acetylcholinesterase in the dorsal root neuroblast of the rabbit embryo. A study by electron microscope cytochemistry and microgasometric analysis with the magnetic diver.
In the nine day old embryo, acetylcholinesterase (AChE) is found in the reticulum, i.e. the nuclear envelope, endoplasmic reticulum, and Golgi complex, of a few cells in the neural crest. When the neurite first enters the neural tube, reticulum-bound enzyme is present also in the varicosity of the growth cone of the bipolar neuroblast. At later stages, AChE in the neuroblast has a dual distribution; in addition to the reticulum, activity also appears at the axolemmal surface. The axolemmal activity is found initially on the distal portions of axons in the posterior fasciculus and then progressively appears along the nerve roots in a distal to proximal direction. Very little reticulum-bound enzyme is present within the axon proper. After the 13th day the levels of AChE activity in the posterior fasciculus greatly exceed those in the dorsal root or in the ganglion. Enzymatic activity in the dorsal root equals or exceeds that in the posterior fasciculus by day 16, and both areas are considerably more active than the ganglion.


Mechanistic Modeling Based PAT Implementation for Ion-Exchange Process Chromatography of Charge Variants of Monoclonal Antibody Products.
Process chromatography is typically used to remove product related impurities and variants that have very similar physicochemical properties to the product. Baseline separation may not be achieved in most cases due to high protein loading and thus, pooling of the elution peak can be challenging for maximizing yield and achieving consistency in product quality. Batch-to-batch variability in quality of the feed material also occurs in commercial manufacturing. Mechanistic modeling of process chromatography, though non-trivial, can be an enabler for implementation of Process Analytical Technology. This paper presents one such application involving prediction of the impact of variability in feed quality and in gradient shape on separation of charge variants by cation exchange process chromatography and thereby facilitating feed forward control. Five batches having different compositions of charge variants have been used to demonstrate the proposed pooling strategy based on simulated chromatograms and the outcome has been compared to offline pooling based on fractionation. For all the conditions examined and for the desired target of main product (67%), the proposed approach resulted in remarkable consistency in product quality (67 ± 2%) while delivering a yield of greater than 90%.


Pharmacokinetics and pharmacokinetic/dynamic relationship of rocuronium bromide in humans.
The existing human pharmacokinetic studies have been reviewed and compared with data derived from animals. The earliest study confirms the similarity of rocuronium to vecuronium with respect to the variables derived from the plasma concentration decay curves and the proportion excreted renally. Other studies led to the conclusion that concurrent administration of volatile anaesthetics did not significantly influence rocuronium pharmacokinetics and that the potentiation must be due to an increased sensitivity of the neuromuscular junction. These studies do not provide an explanation for the clinical observation of a more rapid onset of action. One possible explanation was the finding of a more rapid onset of block in the laryngeal muscles than in the adductor pollicis. However, no pharmacokinetic explanation for this observation has emerged. Alternative concepts need to be modelled. There is a need for comparative pharmacokinetic studies which focus on the period immediately following administration of rocuronium and vecuronium.


Suicide and suicidality in contemporary serving and ex-serving Australian Defence Force personnel.
The risk of suicide in contemporary serving and ex-serving Australian Defence Force personnel is an area of significant concern, driving government-directed inquiries, community campaigns and most recently, the establishment of a permanent National Commissioner for Defence and Veteran Suicide Prevention. This concern is mirrored in international militaries and despite investment in prevention programmes, suicide is a leading cause of death in military populations. This review seeks to summarise recent findings from Australian research regarding the magnitude and factors associated with suicide and suicidality in contemporary serving and ex-serving Australian Defence Force populations and discusses research findings, implications and future opportunities. Initial review of the prevalence of suicide and suicidality in the general community and military populations is presented, followed by review of recent research findings pertaining to suicides and suicidal thoughts, plans and attempts in contemporary serving and ex-serving Australian Defence Force personnel. Key findings are presented from the 2010 Australian Defence Force Mental Health and Wellbeing Prevalence Study and the 2015 Transition and Wellbeing Research Programme. Differences between serving and ex-serving Australian Defence Force cohorts were observed, with rates of completed suicide in ex-serving Australian Defence Force males more than double that of serving Australian Defence Force males, and increased risk for suicidality observed among those who had recently transitioned out of full-time Australian Defence Force service. Risk for increased suicidality and completed suicide is particularly evident for younger males of lower ranks, and those who have been medically discharged. The findings provide insight into career phases and groups that should be followed-up and targeted for prevention and early intervention programmes, including prior to and several years following transition out of full-time military service. Further research to better understand the factors that influence those who develop suicidal ideation, and those who progress to plans and attempts, will inform a more sophisticated approach to suicide prevention programmes.


Electromyographic and pressure studies in the canine bladder.
The dog is unable to void until funnelling of the bladder neck occurs, even when the bladder is stressed with a large volume and with parasympathomimetic drugs. Nil or very little pressure rise occurs just prior to micturition. Well-coordinated voiding is associated with simultaneous electrical activity in either the upper urethra and bladder neck or these two areas plus the fundus, with predominance of electrical activity (frequency and amplitude) in the bladder neck in both circumstances. In cooordinate electrical activity is seen in bladder fundus, bladder neck, and upper urethra with incoordinate voiding.


A randomized phase II study of pemetrexed in combination with cisplatin or carboplatin as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer.
Pemetrexed plus cisplatin was approved for first-line treatment of non-small-cell lung cancer (NSCLC) in patients with nonsquamous histology after initiation of this study. This phase II study evaluated pemetrexed plus cisplatin and pemetrexed plus carboplatin as first-line treatments for stage IIIB/IV NSCLC. The patients were randomized (1:1) to 2 parallel arms: pemetrexed (500 mg/m(2)) plus cisplatin (75 mg/m(2)) or pemetrexed (500 mg/m(2)) plus carboplatin (area under the curve 6) day 1 every 3 weeks (maximum, 6 cycles). Progression-free survival (PFS) was the primary objective; secondary objectives included overall survival (OS), 1-year survival, and safety. Sixty-five patients were randomized to each treatment arm. The patients treated with pemetrexed plus cisplatin had a median age of 64 years and were predominantly men (42 [64.6%]) with nonsquamous histology (53 [81.5%]), stage IV (61 [92.4%]) disease, and a performance status of 0 (40 [61.5%]). Median PFS was 6.0 months, 6-month PFS rate was 50.5%, median OS was 11.7 months, and 1-year survival rate was 47.5%. Drug-related grade 3/4 toxicities included neutropenia (11 [16.9%]), anemia (5 [7.7%]), thrombocytopenia (2 [3.1%]), and nausea (3 [4.6%]). Patients treated with pemetrexed plus carboplatin had a median age of 63 years, were predominantly men (46 [70.8%]) with nonsquamous histology (52 [80.0%]), stage IV (58 [86.6%]) disease, and a performance status of 0 (45 [69.2%]). The median PFS was 4.7 months, the 6-month PFS rate was 34.9%, median OS was 8.9 months, and 1-year survival rate was 39.2%. Drug-related grade 3/4 toxicities included neutropenia (17 [26.2%]), thrombocytopenia (11 [16.9%]), anemia (7 [10.8%]), and nausea (5 [7.7%]). Both the pemetrexed plus cisplatin and pemetrexed plus carboplatin arms met their primary endpoints and demonstrated efficacy and tolerability as first-line therapy in patients with advanced NSCLC. http://ClinicalTrials.gov: NCT00402051.


Probabilistic model of altitude decompression sickness based on mechanistic premises.
To develop a predictive equation and to test ideas about the mechanisms involved in hypobaric decompression sickness, we performed statistical analyses on published results of 7,023 exercising O2-breathing men subjected to one-step decompressions in altitude chambers. The dependent variable was signs or symptoms so severe that the person's trial was terminated (forced descent). The three independent variables were 1) duration of 100% O2 breathing at ground level (prebreathing), 2) atmospheric pressure after ascent, and 3) exposure duration. The best model, chosen from trial-and-error combinations of premises about bubble behavior, indicates that decompression sickness outcome depends on 1) prebreathing time, but with an unexpectedly long washout half time for N2; 2) time at altitude, as if bubbles grow; and 3) the estimated difference, raised to the fifth power, between the partial pressure of N2 in tissue before and that in bubbles after decompression, perhaps an index of the number of bubbles generated. We expect the model to provide accurate predictions for decompressions matching those of the bulk of the data; the mechanistic cues should be considered hypotheses for further investigation.


Levels of Surgical Patients' Education Related to Surgical Interventions Among Patients in Saudi Arabia.
Patient education and counseling should simplify and clarify the condition, surgery, postoperative care, and potential complications. This study aimed to determine the levels of surgical patients' education regarding surgical interventions among patients in Saudi Arabia. This was an online survey study that was conducted between January and May 2023 to determine the levels of surgical patients' education regarding surgical interventions among patients in Saudi Arabia. The study population was patients who underwent surgeries (elective and emergency) living in Saudi Arabia. The questionnaire tool used in this study was developed based on an extensive literature review in the field of patients' education regarding surgical interventions. Binary logistic regression analysis was used to identify predictors of satisfaction with the callouts and the surgeon-consultant's communication quality. A total of 1360 participants were involved in this study. Around 40.5% of the participants reported that they met the surgeon after diagnosing and recommending the issue. Almost 70.0% of research participants reported that the consultant surgeon personally explained a diagnosis or strategy to attain it and the surgical technique, method, and purpose before signing the informed consent. The majority of study participants reported that the consulting surgeon or a member of his surgical team explained the stages of reaching a diagnosis and the steps he/she will take to diagnose their condition (83.2%), discussed the diagnosis with them and how certain they are of the diagnosis (88.1%), described the surgery clearly and simply (85.5%), informed them of alternatives to surgical intervention (63.1%), and discussed the entire postoperative treatment plan (81.8%), informed them of possible postoperative complications (79.6%), used additional callout during the discussion (81.3%), and spoke to them after the surgery and before they left the hospital (69.2%). After a conversation with their doctors, 36.3% of study participants said they did not require an outside source to understand the diagnosis, operation, probable problems, treatment plan, and follow-up. Discussion "Just talk," sketching, and pictograms were the most popular callouts during patient education, with 78.3%, 22.3%, and 17.9%, respectively. Saudi participants were more likely to be satisfied with the quality of communication by the surgeon-consultant (p<0.05). At the same time, participants who live in the Southern area were less likely to be satisfied with the quality of communication by the surgeon-consultant (p<0.05). This study highlights the crucial role of surgeons in preoperative patient education as well as the significance of surgical team participation in this process. In order to increase patient knowledge, facilitate treatment decisions, and assure informed consent, it is necessary to establish guidelines and roles to improve surgeon-patient communication, increase patient and surgeon awareness, nurture patient concern expression, and encourage non-medical patient participation.


Earthquake impacts on microcrustacean communities inhabiting groundwater-fed springs alter species-abundance distribution patterns.
Earthquakes are important natural events, yet their impacts on animal communities are poorly known. Understanding earthquake impacts on groundwater communities is essential to assess their resilience and hence to perform conservation actions. We investigated how a 6.3 Mw earthquake that occurred in 2009 altered the community structure (diversity, evenness, dominance, species abundance distributions and beta-diversity) of microcrustaceans (Crustacea Copepoda) inhabiting springs fed by the Gran Sasso Aquifer (Central Italy). Sampling was done in low-discharge (1997), high-discharge (2005), and post-seismic (2012) hydrological years. Stygobites (obligate groundwater species) and non-stygobites (non-obligate groundwater species) showed different patterns. A high-water discharge in 2005 altered abundance patterns of non-stygobites. The earthquake re-established former abundance patterns. Stygobites were less affected by high-water discharge in 2005, and showed strong increases in diversity and evenness after the earthquake. This effect was due to the fact that the earthquake induced a strong population decline of previously dominant stygobites (especially of Nitocrella pescei) in the aquifer, and subsequently at the main spring outlets, thus allowing a more equitable species-abundance distribution. These results highlight the importance of considering species ecology to understand the effects of a significant earthquake event on animal communities.


Utilizing patient-nurse verbal communication in building risk identification models: the missing critical data stream in home healthcare.
In the United States, over 12 000 home healthcare agencies annually serve 6+ million patients, mostly aged 65+ years with chronic conditions. One in three of these patients end up visiting emergency department (ED) or being hospitalized. Existing risk identification models based on electronic health record (EHR) data have suboptimal performance in detecting these high-risk patients. To measure the added value of integrating audio-recorded home healthcare patient-nurse verbal communication into a risk identification model built on home healthcare EHR data and clinical notes. This pilot study was conducted at one of the largest not-for-profit home healthcare agencies in the United States. We audio-recorded 126 patient-nurse encounters for 47 patients, out of which 8 patients experienced ED visits and hospitalization. The risk model was developed and tested iteratively using: (1) structured data from the Outcome and Assessment Information Set, (2) clinical notes, and (3) verbal communication features. We used various natural language processing methods to model the communication between patients and nurses. Using a Support Vector Machine classifier, trained on the most informative features from OASIS, clinical notes, and verbal communication, we achieved an AUC-ROC = 99.68 and an F1-score = 94.12. By integrating verbal communication into the risk models, the F-1 score improved by 26%. The analysis revealed patients at high risk tended to interact more with risk-associated cues, exhibit more "sadness" and "anxiety," and have extended periods of silence during conversation. This innovative study underscores the immense value of incorporating patient-nurse verbal communication in enhancing risk prediction models for hospitalizations and ED visits, suggesting the need for an evolved clinical workflow that integrates routine patient-nurse verbal communication recording into the medical record.


Efficacy of intermittent hypoxic training on hemodynamic function and exercise performance in competitive swimmers.
Hemodynamic function is a parameter indicating oxygen delivery and utilization capacity and is an important determinant of exercise performance. The present study aimed to determine whether intermittent hypoxic training (IHT) ameliorates hemodynamic function and exercise performance in competitive swimmers. Twenty competitive swimmers (10 men, 10 women) volunteered to participate in the study. Participants were divided into the normoxic training (NT) group and the hypoxic training (HT) group and were subjected to training in a simulated altitude of 3000 m. We evaluated hemodynamic function profiles over 30 min of submaximal exercise on a bicycle and exercise performance before and after 6 weeks of training, which involved continuous exercise at 80% maximal heart rate (HRmax) for 30 min and interval exercise at 90% of HRmax measured before training for 30 min (ten rounds comprising 2 min of exercise followed by 1 min of rest each round). Significant changes in oxygen consumption (decrease) and end-diastolic volume (increase) were observed only in the HT group. Heart rate (HR), cardiac output (CO), and ejection fraction (EF) were significantly reduced in both groups, but the reduction rates of HR and CO were greater in the HT group than in the NT group. Exercise performance measures, including maximal oxygen consumption and 400-m time trial, were significantly increased only in the HT group. Our findings suggested that 6 weeks of IHT, which involved high-intensity continuous and interval exercise, can effectively improve exercise performance by enhancing hemodynamic function in competitive swimmers.


Contraplacental hypogastrinemic effect of gastrin infusion in sheep.
Infusion of gastrin, G-17I, at 0.4 microgram/min into either the maternal or fetal venous circulation of six late gestation sheep was associated with increases in serum gastrin concentration in the infused circulation and reciprocal decreases in the serum gastrin concentration in the other circulation (contraplacental) that perfused the placenta. Pentagastrin infusion at 0.4 microgram/min was associated with an increase in C-terminal specific gastrin immunoreactivity in both the infused and the contraplacental circulations. These observations suggest that biologically active fragments of gastrin, but not the intact molecule, may cross the ovine placenta. An alternative explanation for our results is that gastrin infusion into either the maternal or fetal circulation which perfuses the placenta may result in the release of an inhibitor (i.e., somatostatin) into the other circulation. Of broad importance, these observations indicate that although intact polypeptide hormones may not traverse the placenta, their concentrations in maternal and fetal sera may not be as independent as previously believed. Serum gastrin half-life values in late gestation sheep fetuses, lambs, and ewes were determined to be 13.7 +/- 1.9, 16.7 +/- 2.6, and 15.2 +/- 2.8 min, respectively. These similar values indicate that the relatively high serum gastrin concentrations observed in near-term sheep fetuses are not the result of prolonged half-life in the fetus.


Improved molecular diagnostics of idiopathic short stature and allied disorders: quantitative polymerase chain reaction-based copy number profiling of SHOX and pseudoautosomal region 1.
Short stature has an incidence of three in 100 in children. Reliable molecular genetic testing may be crucial in the context of beneficial disease management. Deletions spanning or surrounding the SHOX gene account for a significant proportion of patients with idiopathic short stature (ISS) and allied disorders, such as Leri-Weill dyschondrosteosis. Several shortcomings of current strategies for copy number profiling of the SHOX region prompted us to develop an improved test for molecular diagnostics of the SHOX region. We introduced a quantitative PCR (qPCR)-based copy number profiling test, consisting of 11 amplicons targeting clinically relevant regions, i.e. the SHOX gene and regulatory regions. To ensure an optimal sensitivity and specificity, this test was validated in 32 controls and 18 probands with previously identified copy number changes. In addition, 152 probands with SHOX-associated phenotypes were screened, revealing 10 novel copy number changes. This highly validated qPCR test supersedes other approaches for copy number screening of the SHOX region in terms of reliability, accuracy, and cost efficiency. In addition, another strong point is the fact that it can be easily implemented in any standard equipped molecular laboratory. Our qPCR-based test is highly recommended for molecular diagnostics of idiopathic short stature and allied disorders.


Orbital rhabdomyosarcomas and related tumors in childhood: relationship of morphology to prognosis--an Intergroup Rhabdomyosarcoma study.
Children and adolescents who develop rhabdomyosarcoma (RMS) and related sarcomas in the orbit and treated on Intergroup Rhabdomyosarcoma protocols have had an extremely high cure rate. This study evaluates the possible relationship between their tumor morphologic subtypes and this high cure rate. The histology of tumors was re-reviewed from 229 of the 264 patients with tumors of the orbit, conjunctiva, and eyelids treated on Intergroup Rhabdomyosarcoma Studies (IRS I, II, III, and IV pilot protocols, and followed through July, 1992. Immunohistochemistry was applied in selected cases. Clinical correlations were done on all 264 cases including both the re-reviewed cases and those reviewed only by the IRS Pathology committee. The 5-year survival rate of 24 children with alveolar RMS was 74% (p < .001). All five infants diagnosed to have an alveolar RMS died before the age of one. Two hundred and twenty-one patients (84%) had embryonal RMS. About three-fourths of the re-reviewed embryonal RMS tumors showed only minimal rhabdomyoblastic differentiation. Thirty-one had a spindle cell RMS, two were anaplastic variants. The 5-year survival rate for patients with embryonal RMS subtypes combined was 94%, and 97% for the 144 patients with poorly differentiated embryonal RMS. In contrast, 90 of 432 IRS II patients treated for poorly differentiated embryonal RMS located in extraocular sites had a 66% survival estimate.


Three-Fold Scholl-Type Cycloheptatriene Ring Formation around a Tribenzotriquinacene Core: Toward Warped Graphenes.
A nonplanar polycyclic aromatic compound 6 bearing a tribenzotriquinacene (TBTQ) core merged with an o,p,o,p,o,p-hexaphenylene belt was prepared and characterized by NMR spectroscopy and X-ray crystallography. The key synthesis step involves three Scholl-type cycloheptatriene ring formation steps of the 1,4,8-tris(3',4'-dimethoxyphenyl)-TBTQ derivative 5. The bridging of each of the three TBTQ bays by 1,2-phenylene units in compound 6 gives rise to an unusual wizard hat shaped structure, which represents a promising key intermediate for the construction of nonplanar nanographene molecules bearing a TBTQ core.


[The electrolyte composition of liver preservation solutions for hepatocytes in a model of in vitro preservation and reoxygenation].
The cation and anion content in liver preservation solutions have been investigated in order to justify the use of "intracellular" or "extracellular" electrolyte compositions. Various concentrations of sodium and potassium with chloride or lactobionate as anions and with added calcium and/or magnesium were made up as preservation solutions and incubated with in vitro adherent cultures of pig hepatocytes. In vitro hypoxia and hypothermia (4 degrees C, PO2 < 0.1 mmHg) for 24 h, with reoxygenation for 3 h, in standard culture medium was used as a model for preservation. Measurements of cell viability and detachment rate by light microscopy and of LDH and GOT liberation were used as parameters of cell damage. Cell swelling was estimated in suspension cultures of isolated hepatocytes. When chloride was used as the anion, significant cell toxicity from potassium concentrations over 75 mM was found within 6 h of preservation. Enzyme liberation decreased with increasing content of sodium cations in the preservation solution. Calcium ions had a protective effect at a concentration of 0.8 mM. Addition of magnesium to an "intracellular" ion composition minimized the toxic effect of potassium cations. Using lactobionate as an impermeant anion, there was no difference between the sodium and the potassium salt and the choice of cation had no effect on enzyme leakage or cell volume. An "extracellular" solution with high sodium chloride content and 0.8 mM calcium resulted in better preservation than was obtained with lactobionate solutions. With chloride as the anion, a significant increase in cell swelling was found when potassium replaced sodium in the solutions. Cell swelling decreased with increasing concentration of sodium cations.(ABSTRACT TRUNCATED AT 250 WORDS)


Who are the young victims of violence?
Although young victims of intentional violence are commonly cared for in emergency departments, minimal information exists regarding the characteristics of these young people. This study fills that knowledge gap. The assessment tool was administered on all consenting consecutive victims of interpersonal violence. A statistical analysis was performed on the data using SPSS to obtain descriptive information, frequencies, correlations, and regressions. The setting was the emergency department of an inner-city level 1 pediatric and adult trauma center with approximately 43,000 visits per year. Patients, aged 10 to 24, who were victims of interpersonal violence (excluding child abuse, sexual assault, and domestic violence), were interviewed using an assessment tool to determine their characteristics. The tool was an extensive evaluation questionnaire containing the following constructs: background information, stress, coping skills, parental involvement, peers, delinquency, peer delinquency, future plans, and expectations. The results of this study were compared with national, state, or Chicago area data for the same noted problems. A total of 188 victims of interpersonal violence were interviewed. Of those, 82.5% were male; 65.4% were African Americans, and 31.4% were Hispanic. The study showed that 46.8% of the subjects admitted to having carried a hidden weapon in the past, and 28.9% to having attacked someone with a weapon. Forty-one percent witnessed someone being shot or killed in the past year, many in the last year (41.2%). In terms of home environment, 27.7% stated they live with only their mother, 23.4% live with both parents. Over half (51.1%) were members of a gang, and 50.8% had been arrested or detained in the past year. Regarding drug abuse, 75.5% reported using marijuana or hashish, 14.4% used cocaine, and 4.3% used crack during the past year. The study demonstrated that the levels of weapon carrying, fighting, and marijuana and cocaine use were higher in relation to the comparative data, whereas the level of alcohol use was similar. Young persons who are victims of interpersonal violence have a high rate of delinquency and drug abuse than nonvictimized youth. Physicians caring for these youth need to be cognizant of the special psychosocial issues of these victims.


Muscle phenotype and mutation load in 51 persons with the 3243A>G mitochondrial DNA mutation.
Mitochondrial disorders are generally not associated with a clear phenotype-genotype relationship, which complicates the understanding of the disease and genetic counseling. To investigate the relationship between the muscle and blood mitochondrial DNA mutation load and phenotype. Survey. The Neuromuscular Research Unit, Rigshospitalet, Copenhagen, Denmark. Fifty-one persons with the 3243A>G point mutation of mitochondrial DNA, and 20 healthy control subjects. We recorded the maximal oxygen uptake (Vo(2)max), maximal workload, resting and peak-exercise plasma lactate levels, muscle and blood mutation load, muscle morphology, and presence of diabetes mellitus and hearing impairment in all subjects. Muscle mutation load (mean +/- SE, 50% +/- 5%; range, 2%-95%) correlated with Vo(2)max and resting plasma lactate level (P<.001; R>/=0.64). All persons except 5 with a muscle mutation load above 50% had abnormal Vo(2)max and morphology on muscle biopsy findings. Persons with hearing impairment and diabetes mellitus had a muscle mutation load above 65%. The mutation load in blood (mean +/- SE, 18% +/- 3%; range, 0%-61%) did not correlate with Vo(2)max, resting plasma lactate levels, or presence of hearing impairment or diabetes mellitus. This study demonstrates a close relationship between the muscle mutation load and phenotype in persons carrying the 3243A>G mutation. The lack of correlation between the mutation load in blood and symptoms from other tissues emphasizes the importance of assessing phenotype-genotype correlations in the same tissue in mitochondrial disease. The results indicate that the threshold of muscle mutation load at which oxidative impairment occurs can be as low as 50%, which is as much as 40% lower than that suggested by in vitro studies.


Molecular genetics of tetrahydrobiopterin (BH4) deficiency in the Maltese population.
Deficient activity of the Dihydropteridine Reductase enzyme (DHPR; EC 18.104.22.168; OMIM 261630) is due to mutations in the Quinoid Dihydropteridine Reductase gene on 4p15.3 (QDPR; RefSeq NM_000320). It results in defective recycling of tetrahydrobiopterin (BH(4)) and homozygotes have a rare form of atypical Hyperphenylalaninaemia and Phenylketonuria (aPKU). The heterozygote frequency in the Maltese population is high at 3.3%. The more recently described and rarer type of BH(4) deficiency due to Sepiapterin Reductase enzyme deficiency (SR; EC 184.108.40.206; OMIM 182125), which presents as an atypical form of Dopa Responsive Dystonia (DRD) [L. Bonafe, B. Thony, J.M. Penzien, B. Czarnecki, N. Blau, Mutations in the sepiapterin reductase gene cause a novel tetrahydrobiopterin-dependent monoamine-neurotransmitter deficiency without hyperphenylalaninemia, Am. J. Hum. Genet. 69 (2001) 269-277; B.R.G. Neville, R. Parascandalo, S. Attard Montalto, R. Farrugia, A.E. Felice, A congenital dopa responsive motor disorder: a Maltese variant due to sepiapterin reductase deficiency, Brain 128 (Pt10) (2005) 2291-2296.] has also been identified at high frequency (4.6%) in this population. Two mutations, the c.68G>A in QDPR (p.G23D), and the new SPR, IVS2-2A>G mutation at the splice site consensus sequence in intron 2 of the Sepiapterin Reductase gene (SPR; RefSeq NM_003124) on 2p14-p12, were found to be the sole causative mutations in all the patients with DHPR deficiency and SR deficiency studied. All parents were heterozygotes for the corresponding mutation and showed no clinical symptoms. Three polymorphisms, c.96C>T (p.A32A), c. 345G>A (p.S115S) and c. 396G>A (p.L132L), have also been identified in the QDPR gene, defining four wild-type frameworks, useful in molecular epidemiology studies. The c. 68G>A mutation in QDPR was found only on framework I, suggesting a founder effect. In contrast no additional sequence diversity was found in the SPR gene whether in wild-type or mutant alleles which is also consistent with a founder effect.


Micro-RNAs as potential new molecular biomarkers in oncology: have they reached relevance for the clinical imaging sciences?
Minimally invasive biomarkers for early cancer detection and monitoring of personalized therapies are of high importance to further improve prognosis in oncological disease. MicroRNAs (miRNAs) are small regulatory RNAs in humans and play a key role in carcinogenesis. In recent years they have emerged as promising biomarkers in oncology. miRNA profiling has demonstrated its capacity for sub-classifying tumors and monitoring of therapeutic effects. Different expression profiles of miRNAs in cancer and the stability of circulating miRNAs potentially provide a clinically accessible molecular monitoring tool of malignant tissues and its response to therapies. Clinical imaging including the modalities PET/CT and MRI is well established for characterizing tumor tissue and sub-classifying morphological, metabolic or vascular treatment response in cancer. Sophisticated clinical imaging biomarkers for cancer detection and monitoring should now been correlatively applied to further validate the potential of miRNAs as oncologic biomarkers for the clinic.


Docetaxel does not impair cardiac autonomic function in breast cancer patients previously treated with anthracyclines.
The effects of docetaxel treatment on autonomic cardiac function was studied with 24-h ECG recordings in breast cancer patients pretreated with anthracyclines. Twenty-four women were evaluated before docetaxel treatment and after 3-4 courses of docetaxel 100 mg/m(2). The heart rate, cardiac extrasystoles and heart rate variability (HRV) in both the time and frequency domain were assessed from 24-h ECG recordings. The acute effects of docetaxel were calculated from 1-h recordings immediately prior to, during and after infusion. Long-term effects were evaluated from 24-h recordings performed before treatment and after 3-4 courses of docetaxel. There was no increase in the number of cardiac extrasystoles during docetaxel infusion. The number of ventricular extrasystoles decreased from 14 (23) to 7 (14) during and 5 (10) after the first infusion (p=0.02). The heart rate, HRV and extrasystoles were similar before and after 3-4 courses of docetaxel. The treatment did not abolish circadian variability of the heart rate. Docetaxel did not deteriorate autonomic cardiac function. In conclusion, our findings suggest that docetaxel does not have harmful cumulative effects on autonomic control of the heart and is therefore unlikely to be cardiotoxic.


INTENSE NATURAL SELECTION ON BODY SIZE AND WING AND TAIL ASYMMETRY IN CLIFF SWALLOWS DURING SEVERE WEATHER.
Extreme climatic disturbances provide excellent opportunities to study natural selection in wild populations because they may cause measurable directional shifts in character traits. Insectivorous cliff swallows (Petrochelidon pyrrhonota) in the northern Great Plains must often endure periods of cold weather in late spring that reduce food availability, and if cold spells last four or more days, mortality due to starvation may result. We analyzed morphological shifts associated with viability selection, and how patterns of bilateral symmetry were affected by survival selection, during a four-day period of cold weather in 1992 and a six-day period in 1996 in southwestern Nebraska. Birds that died during the cold were compared to those still alive when the severe weather ended. The event in 1992 killed relatively few birds, but the cold spell in 1996 killed thousands of cliff swallows and reduced their population by about 53%. Climatological records suggest that mortality events comparable to that of 1996 have occurred in only one other year since 1875. Larger birds were favored in the 1996 event. Selection was more intense in 1996 than in 1992 because of more stressful conditions in 1996. Directional selection gradient analysis showed that measures of skeletal body size (tarsus length, culmen width and length) and wing length were targets of selection in 1996. Survivors had lower wing and outer tail asymmetry, and wing and tail asymmetry were targets of selection in both events. Mortality patterns did not differ by sex, but older birds suffered heavier mortality; morphological traits generally did not vary with age. Nonsurvivors were not in poorer apparent condition prior to the weather event than survivors, suggesting that selection acted directly on morphology independent of condition. Selection on body size in cliff swallows was more intense than in studies of body size evolution in other bird species. Larger swallows were probably favored in cold weather due to the thermal advantages of large size and the ability to store more fat. Swallows with low asymmetry were favored probably because low asymmetry in wing and tail made foraging more efficient and less costly, conferring survival advantages during cold weather. This population of cliff swallows may have undergone relatively recent body size evolution.


Deformable biomechanical models: application to 4D cardiac image analysis.
This article describes a methodology for creating a generic volumetric biomechanical model from different image modalities and segmenting time series of medical images using this model. The construction of such a generic model consists of three stages: geometric meshing, non-rigid deformation of the mesh in images of various modalities, and image-to-mesh information mapping through rasterization. The non-rigid deformation stage, which relies on a combination of global and local deformations, can then be used to segment time series of images, e.g. cine MRI or gated SPECT cardiac images. We believe that this type of deformable biomechanical model can play an important role in the extraction of useful quantitative local parameters of cardiac function. The biomechanical model of the heart will be coupled with an electrical model of another collaborative project in order to simulate and analyze a larger class of pathologies.


Oral contraceptives and cardiovascular risk in women with polycystic ovary syndrome.
Because women affected by polycystic ovary syndrome (PCOS) present an increased cardiovascular risk, the safety of estroprogestin treatment is debated and contrasting data have been reported. However, cardiovascular risk is not the same in all PCOS women and individual cardiovascular risk should be assessed before staring any estroprogestin treatment. The available data show that products containing both 2nd-generation and 3rd-generation progestins (including drospirenone and cyproterone acetate) represent a safe treatment in PCOS patients with regular cardiovascular risk. In PCOS patients with increased cardiovascular risk, a careful choice of estroprogestin product is needed and cardiovascular risk should be monitored during treatment. In obese PCOS patients with normal glucose tolerance and lipid profile, products containing 2nd-generation progestins may be preferred because of lower venous thromboembolism risk. In PCOS patients with altered lipid profile or glucose intolerance, 3rd-generation progestins should be used but, during treatment, cardiovascular risk should be periodically re-assessed. In special situations, metformin or statins may be added to estroprogestin treatment.


Diagnostic accuracy of three sensory tests for diagnosis of sensory disturbances.
Clinical diagnosis of sensory disturbances is extremely challenging, partly because the utility of sensory tests is questionable. Transection of C7 nerve root provides an objective assessment model to determine the diagnostic accuracy of sensory tests. The purpose of this study was to investigate the diagnostic accuracy of Semmes-Weinstein Monofilaments (SWM; Sammons Preston, Bolingbrook, IL), static two-point discrimination (s2PD), and current perception threshold (CPT) tests in patients with contralateral C7 nerve root transfer. The contralateral index finger of patients was tested preoperatively and 6 weeks postoperatively, including the Revised Short-Form McGill Pain Questionnaire (SF-MPQ-2), SWM, s2PD, and CPT tests. The SF-MPQ-2 was used as a gold standard for sensory disturbances. A total of 38 patients were included in the study. The likelihood probability ratio of SWM and CPT tests generated small shifts in probability, whereas the s2PD test did not show any capacity to detect sensory disturbances. The areas under the curves (AUC) for SWM and CPT tests were 0.724 and 0.697, respectively. Based on different positive test standards, the AUCs for s2PD (≥ 6 mm) and s2PD (≥ 7 mm) tests were 0.632 and 0.658, respectively. When CPT and SWM tests were combined as a measure, the AUC increased to 0.763. The SWM and CPT tests show a small capacity to detect sensory disturbances, whereas the s2PD test does not show any diagnostic capacity. To better understand sensory disturbances, a comprehensive testing protocol including valid measures of physical impairment and symptom-specific measurement tools should be adopted.


Standalone Sensors System for Real-Time Monitoring of Cutting Emulsion Properties with Adaptive Integration in Machine Tool Operation.
This paper presents a novel cutting fluid monitoring sensor system and a description of an algorithm framework to monitor the state of the cutting emulsion in the machine tool sump. One of the most frequently used coolants in metal machining is cutting emulsion. Contamination and gradual degradation of the fluid is a common occurrence, and unless certain maintenance steps are undertaken, the fluid needs to be completely replaced, which is both un-economical and non-ecological. Increasing the effective service life of the cutting emulsion is therefore desired, which can be achieved by monitoring the parameters of the fluid and taking corrective measures to ensure the correct levels of selected parameters. For this purpose, a multi-sensor monitoring probe was developed and a prototype device was subsequently created by additive manufacturing. The sensor-carrying probe was then placed in the machine tool sump and tested in operation. The probe automatically takes measurements of the selected cutting emulsion properties (temperature, concentration, pH, level height) in set intervals and logs them in the system. During the trial run of the probe, sensor accuracy was tracked and compared to reference measurements, achieving sufficiently low deviations for the purpose of continuous operation.


Analysis of Characteristic Factors of Nursing Safety Incidents in ENT Surgery by Deep Learning-Based Medical Data Association Rules Method.
It is of great significance to explore the characteristic factors of postoperative nursing safety events in patients with otolaryngology surgery and to understand the characteristics of postoperative nursing safety events in otolaryngology surgery patients. This paper carried out preoperative safety protection for 385 inpatients, and the results showed that there were 52 cases of postoperative safety nursing events. This experiment found that the coinfected lesions (P = 0.001, HR = 14.283, 95.0% C1: 9.365~21.038), the treatment period (P = 0.001, HR = 13.716, 95.0% CI: 7.147~20.275), during hospital treatment (P = 0.002, HR = 15.208, 95.0% CI: 8.918-24.237), antibiotic use (P = 0.001, HR = 14.054, 95.0% CI: 8.163-21.739), and hypertension (P = 0.001, HR = 13.976, 95.0% CI: 7.926-22.385) are the important factors affecting postoperative care; using the association rule method to control and analyze the main risk factors of postoperative infection and bleeding in ENT patients can significantly improve the prognosis.


Generation of three induced pluripotent stem cell lines from a patient with KCNQ2 developmental and epileptic encephalopathy as a result of the pathogenic variant c.881C > T; p.Ala294Val (NUIGi059-A, NUIGi059-B, NUIGi059-C) and 3 healthy controls (NUIGi060-A, NUIGi060-B, NUIGi060-C).
Developmental and epileptic encephalopathies (DEEs) are a group of severe, early-onset epilepsies which are often caused by genetic mutations in ion channels. Mutations in KCNQ2, which encodes the voltage-gated potassium channel Kv7.2, is known to cause DEE. Here, we generated three iPSC lines from dermal fibroblasts of a 5 year-old male patient with the KCNQ2 c.881C > T (p.Ala294Val) pathogenic heterozygous variant and three iPSC lines from a healthy sibling control. These iPSC lines have been validated by SNP karyotyping, STR analysis, expression of pluripotent genes, the capacity to differentiate into three germ layers and confirmation of the mutation in the patient.


Dynamics of Fukuoka Criteria and Patient Management in Pancreatic Intraductal Papillary Mucinous Neoplasms (IPMNs) During Follow-Up.
BACKGROUND Pancreatic intraductal papillary mucinous neoplasms (IPMNs) present a clinical challenge. Evidence-based guidelines are lacking. The so-called "Fukuoka criteria" were developed to assess the risk of malignancy in IPMNs upon imaging. However, little is known about their diagnostic value and the natural course of IPMNs. Thus, the aim of this study was the assessment of Fukuoka criteria and patient management in pancreatic IPMNs -during follow-up. MATERIAL AND METHODS IPMNs were identified via retrospective survey of endoscopic ultrasound (EUS) examinations. Fukuoka criteria were assessed on EUS findings and additional imaging (CT, MRI, ultrasound). Patients' symptoms and comorbidities were recorded. Dynamics of Fukuoka criteria and patient management were compared at first presentation and during follow-up. RESULTS We screened 1324 EUS examinations. Sixty-five patients (male/female, 14/37; mean age, 68.8 years; range, 48-85 years) with IPMNs were identified (57 branch duct (BD-)IPMNs, 3 main duct (MD-) IPMNs, 5 mixed-type (MT)-IPMNs). Seven patients received surgical resection (4 BD-IPMNs, 2 MD-IPMNs, 1 MT-IPMN). Nine BD-IPMNs had neither surgery nor follow-up. Fifty-one patients (44 BD-IPMNs, 2 MD-IPMNs, 5 MT-IPMNs) underwent follow-up (mean duration, 18.7 months; range, 3-139 months). There were 15/51 patients who were initially Fukuoka-positive. One MD-IPMN, 4/5 MT-IPMNs, and 13/44 BD-IPMNs showed progressive changes but were not resected due to patients' refusal or comorbidities. Four BD-IPMNs converted to Fukuoka-positive. CONCLUSIONS Evidence-based guidelines for non-invasive dignity assessment of IPMNs are lacking. In our study, MD-IPMNs displayed greater dynamics than BD-IPMNs and MT-IPMNs concerning Fukuoka criteria. Prospective long-term studies are needed to clarify prognostic significance of the single Fukuoka criteria and sensible duration of follow-up.


Human papillomavirus and head and neck cancer: epidemiology and molecular biology.
Human papillomaviruses (HPV) are known to cause cancers of the cervix and other anogenital tract sites. Molecular biology has provided some evidence as to the specific mechanisms involved in the HPV-related carcinogenesis. Epidemiologic and molecular biology studies have also suggested that HPV infection may be associated with cancers of the head and neck. This review summarizes the biology of HPV and its potential etiologic role in head and neck cancer. Published reports were used to determine the prevalence of HPV in benign, precancerous, and neoplastic lesions of the oral cavity, pharynx, and larynx. The prevalence was also examined by head and neck site, HPV type, and method of HPV detection. In addition, the occurrence of HPV in normal head and neck tissue, epidemiologic factors related to HPV infection, and clinical implications are discussed. Overall, the frequency of HPV in benign and precancerous lesions ranged from 18.5% to 35.9%, depending upon the detection methodology. Based upon the most sensitive method of detection, polymerase chain reaction (PCR), the overall prevalence of HPV in head and neck tumors was 34.5% (416 of 1205 tumors). The majority of HPV-positive tumors contained the "high risk" HPV types 16 (40.0%) and 18 (11.9%). Among head and neck sites, HPV was most often detected in tumors of the oral cavity (59%), followed by the pharynx (43%), and larynx (33%). The frequency of HPV positivity in oral samples from healthy individuals ranged from 1% to 60%. A limited number of descriptive and analytic epidemiologic studies have indicated that age (<60 years) and sex (male) were associated with the presence of HPV in the tumor, whereas tobacco and alcohol use were not. The relationship between HPV and survival is unclear, with few comprehensive studies currently available. The prevalence of HPV, particularly the high-risk types, suggests a potential etiologic role for the virus in head and neck cancer. Molecular biology has provided important data on the interaction of the HPV oncoproteins with genes important in cell cycle control. Nonetheless, more basic research is needed to describe the physical state of the virus in a variety of cell types and the interaction with other genes. In addition, epidemiologic research is required to further understand the association between HPV and demographic and other risk factors as well as possible routes of transmission. Finally, much work is warranted to provide a definitive assessment of the prognostic significance of HPV in head and neck cancer.


Effect of Fufang Huangqi Decoction on the Gut Microbiota in Patients With Class I or II Myasthenia Gravis.
To investigate the effect of Fufang Huangqi Decoction on the gut microbiota in patients with class I or II myasthenia gravis (MG) and to explore the correlation between gut microbiota and MG (registration number, ChiCTR2100048367; registration website, http://www.chictr.org.cn/listbycreater.aspx; NCBI: SRP338707). In this study, microbial community composition and diversity analyses were carried out on fecal specimens from MG patients who did not take Fufang Huangqi Decoction (control group, n = 8) and those who took Fufang Huangqi Decoction and achieved remarkable alleviation of symptoms (medication group, n = 8). The abundance, diversity within and between habitats, taxonomic differences and corresponding discrimination markers of gut microbiota in the control group and medicated group were assessed. Compared with the control group, the medicated group showed a significantly decreased abundance of Bacteroidetes (P < 0.05) and significantly increased abundance of Actinobacteria at the phylum level, a significantly decreased abundance of Bacteroidaceae (P < 0.05) and significantly increased abundance of Bifidobacteriaceae at the family level and a significantly decreased abundance of Blautia and Bacteroides (P < 0.05) and significantly increased abundance of Bifidobacterium, Lactobacillus and Roseburia at the genus level. Compared to the control group, the medicated group had decreased abundance, diversity, and genetic diversity of the communities and increased coverage, but the differences were not significant (P > 0.05); the markers that differed significantly between communities at the genus level and influenced the differences between groups were Blautia, Bacteroides, Bifidobacterium and Lactobacillus. MG patients have obvious gut microbiota-associated metabolic disorders. Fufang Huangqi Decoction regulates the gut microbiota in patients with class I or II MG by reducing the abundance of Blautia and Bacteroides and increasing the abundance of Bifidobacterium and Lactobacillus. The correlation between gut microbiota and MG may be related to cell-mediated immunity.


First-in-human phase I study of the liposomal RNA interference therapeutic Atu027 in patients with advanced solid tumors.
Atu027 is a novel liposomal RNA interference therapeutic that includes a short-interfering RNA (siRNA), which silences expression of protein kinase N3 in the vascular endothelium. Atu027 has previously been shown to inhibit local tumor invasion as well as lymph node and pulmonary metastasis in mouse cancer models. This first-in-human study aimed to assess the safety, tolerability, and pharmacokinetics of Atu027 while evaluating therapeutic effects on both primary tumors and metastatic lesions. Thirty-four patients with advanced solid tumors received 10 escalating doses of Atu027 without premedication, as one single followed by eight intravenous infusions twice per week during a 28-day cycle. Response was monitored by computed tomography/magnetic resonance imaging at baseline, at the end of treatment (EoT), and at final follow-up (EoS), and was assessed according to RECIST. Atu027 was well tolerated up to dose levels of 0.336 mg/kg; most adverse events (AEs) were low-grade toxicities (grade 1 or 2). No maximum tolerated dose was reached. Plasma levels of siRNA strands and lipids were dose proportional, peaking during 4-hour infusion. Disease stabilization was achieved in 41% of patients at EoT (n = 14 of 34 treated patients); eight patients had stable disease at EoS, and some experienced complete or partial regression of metastases. sFLT1 (soluble variant of vascular endothelial growth factor receptor-1) decreased from pretreatment levels in most patients after dose levels 04 to 10. Atu027 was safe in patients with advanced solid tumors, with 41% of patients having stable disease for at least 8 weeks. In view of these results, further clinical trials have been initiated, and sFLT1 will be investigated as a potential biomarker.


Super silyl stereo-directing groups for complete 1,5-syn and -anti stereoselectivities in the aldol reactions of beta-siloxy methyl ketones with aldehydes.
In this communication, we report that substrate-controlled 1,5-syn and -anti stereoinduction in the aldol reaction of beta-tris(trialkylsilyl)siloxy methyl ketones can be achieved with high diastereoselectivities. Tris(trialkylsilyl)silyl groups are easily prepared and play an important role in the selectivities of these reactions. Furthermore, all of the 1,3,5-triol stereoisomers can easily be prepared from beta-siloxy methyl ketones in no more than three steps.


Description of a second species of the genus Moronius Grossi Vaz-de-Mello, 2015 (Coleoptera: Scarabaeidae: Rutelinae: Rutelini).
Moronius Grossi Vaz-de-Mello, 2015 (Coleoptera: Scarabaeidae: Rutelinae: Rutelini) is the latest genus described within the subtribe Areodina (Grossi Vaz-de-Mello 2015). Areodina consists of 11 genera distributed throughout the New World (10 genera) and Africa (one genus) (Jameson 1990; Grossi Vaz-de-Mello 2015). Moronius is distinguished from other genera of Areodina by: 1) the pentagonal clypeal shape with the apex strongly reflexed, and 2) the hind wings with the anterior margin near RA1+2, RA1+3, and apical hinge setose. The South American genera of Areodina form a distinct clade (Jameson 1990) composed of Oplognathus MacLeay, 1819, Areoda MacLeay, 1819, and Byrsopolis Burmeister, 1844. Oplognathus and Areoda are differentiated by the presence of a forward-projecting mesoventral process, which is absent in both Byrsopolis and Moronius. These two latter genera are similar according to the characters presented in the Jameson (1990) phylogeny and are differentiated by habitus colour, shape of clypeus, and antennal club length (Grossi Vaz-de-Mello 2015).


Distribution functions for filaments under tension.
We develop a biased Monte Carlo simulation technique to measure the distribution functions of the extension and the end-to-end distance of fluctuating filaments stretched by external force. The method is applicable for arbitrary ratio of the persistence length to the contour length and for arbitrary forces, and also for the case of steric constraints, such as an external wall. The fundamental idea underlying the algorithm is to account explicitly for the length-scale dependence of the effective elastic moduli. We find that orientational fluctuations and wall effects produce non-Gaussian distributions for nearly rigid filaments in the small to intermediate force regime. The simulation results are tested against analytic expressions for the force-extension curves, both in the semiflexible and nearly stiff limits.


Choledochal cyst and duodenal atresia: a rare combination.
A rare case of congenital duodenal atresia (DA) associated with a choledochal cyst (CC) is reported. At 38 weeks of gestation, a 1,610-g girl was born by cesarean section with a prenatal diagnosis of DA. After the disorder was confirmed by X-ray, she underwent a duodenoduodenostomy for a complete separation of the duodenum with an annular pancreas. Thirty-two months after the initial operation, she developed upper abdominal pain and acholic stools. Abdominal ultrasonography demonstrated a CC and dilatated intrahepatic bile ducts. Magnetic resonance cholangiopancreatography showed an anomalous arrangement of the choledochus and main pancreatic duct. A diffusely dilatated extrahepatic bile duct was resected, and a hepaticoduodenostomy was performed after cholecystectomy. The patient was discharged without complications. We could not find a similar case report in the English literature. Although it is not reported that there is a close relationship in embryologic development of DA and CC, one should be aware of the possibility of this combination.