Longitudinal Associations of Adherence to the Dietary World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) and Dutch Healthy Diet (DHD) Recommendations with Plasma Kynurenines in Colorectal Cancer Survivors after Treatment.
The tryptophan-kynurenine pathway has been linked to cancer aetiology and survivorship, and diet potentially affects metabolites of this pathway, but evidence to date is scarce. Among 247 stage I-III CRC survivors, repeated measurements were performed at 6 weeks, 6 months, and 1 year post-treatment. Adherence to the World Cancer Research Fund/ American Institute for Cancer Research (WCRF) and Dutch Healthy Diet (DHD) recommendations was operationalized using seven-day dietary records. Plasma kynurenines of nine metabolites were analysed. Longitudinal associations of adherence to these dietary patterns and plasma kynurenines were analysed using confounder-adjusted linear mixed-models. In general, higher adherence to the dietary WCRF/AICR and DHD recommendations was associated with lower concentrations of kynurenines with pro-oxidative, pro-inflammatory, and neurotoxic properties (3-hydroxykynurenine (HK) and quinolinic acid (QA)), and higher concentrations of kynurenines with anti-oxidative, anti-inflammatory, and neuroprotective properties (kynurenic acid (KA) and picolinic acid (Pic)), but associations were weak and not statistically significant. Statistically significant positive associations between individual recommendations and kynurenines were observed for: nuts with kynurenic-acid-to-quinolinic-acid ratio (KA/QA); alcohol with KA/QA, KA, and xanthurenic acid (XA); red meat with XA; and cheese with XA. Statistically significant inverse associations were observed for: nuts with kynurenine-to-tryptophan ratio (KTR) and hydroxykynurenine ratio; alcohol with KTR; red meat with 3-hydroxyanthranilic-to-3-hydroxykynurenine ratio; ultra-processed foods with XA and KA/QA; and sweetened beverages with KA/QA. Our findings suggest that CRC survivors might benefit from adhering to the dietary WCRF and DHD recommendations in the first year after treatment, as higher adherence to these dietary patterns is generally, but weakly associated with more favourable concentrations of kynurenines and their ratios. These results need to be validated in other studies.


Low response rate to ATG-based immunosuppressive therapy in very severe aplastic anaemia - A Swedish nationwide cohort study.
Antithymocyte globulin (ATG)-based immunosuppression remains a cornerstone in aplastic anaemia (AA) treatment. However, most ATG studies are not population-based and knowledge about real-world results concerning response and outcome could offer important information for treating physicians. We have recently performed a nationwide retrospective cohort study on all AA patients diagnosed in Sweden in 2000-2011 and now present treatment and outcome data on patients receiving first-line ATG. In total, 158 patients showed a 47.0% response rate which was similar in all age groups (range 41.5%-51.7%) with no difference regarding ATG formulation. The response was significantly associated with severity grade-especially at time of treatment initiation: very severe (VSAA) 22.7%; severe (SAA) 54.5% (P < .001); and non-severe 88.5% (P < .001). A logistic regression-based predictive model indicated that VSAA patients with an absolute reticulocyte count <25 × 109 /L had only a 19% probability of response. In a multivariable analysis, age and VSAA at the time of treatment were the independent factors for inferior survival. Real-world VSAA patients respond poorly to ATG which indicates the need for a different treatment approach. Our findings suggest that age alone should not be a discriminating factor for administering ATG treatment.


Three-dimensional spiral fMRI technique: a comparison with 2D spiral acquisition.
A comparison study was performed of 3D and 2D spiral k-space fMRI techniques using BOLD contrast with a 4.25-min finger-tapping task paradigm. The 3D sequence uses the conventional 2D spiral technique in conjunction with Fourier phase encoding in the slice select direction. Characteristics that were compared included image appearances, signal-to-noise ratio (SNR), fluctuation noise, functional contrast-to-noise ratio (fCNR), detected activation areas, inflow effect, and large vessel involvement. The results showed that, with constant total scan time, the 3D spiral acquisition has higher SNR and fCNR despite its slightly higher fluctuation noise. The capability for thin-slice incoherent averaging is a further advantage of 3D over 2D. With these advantages as well as its intrinsic ability for contiguous slices and image reformatting, the 3D spiral fMRI technique may be superior to its 2D counterpart.


Sonographic evaluation of renal appearance in 665 adult volunteers. Correlation with age and obesity.
The purpose of this study was to investigate the sonographic appearance of the normal adult kidney. Parenchymal echogenicity, pyramid visibility, and transverse pelvis diameter of the kidneys were prospectively determined in an age- and sex-stratified random sample of 665 volunteers 30, 40, 50, 60, and 70 years old. Furthermore, incidences of kidney stones and split sinus echo were determined. The relation between obesity and above-mentioned parameters was evaluated. In the 30-year-old age group the right kidney was isoechoic as compared to the liver in 1/3, and had clearly or faintly visible pyramids in 2/3 of the cases. These rates decreased gradually with increasing age. Transverse diameter of renal pelvis > or = 10 mm was observed in 13% of participants. Renal stones were observed in 2.1%. The incidence of split sinus echo was 3.6%. Obese participants showed lower incidences of isoechogenicity, pyramid visibility, pelvic ectasia, and split sinus echo. Isoechoic parenchyma, clearly visible pyramids, and transverse pelvis diameter > or = 10 mm are not uncommon sonographic findings in normal adult kidneys and should not be used as indicators of renal pathology.


The prognostic effect of cigarette smoking on stroke severity, disability, length of stay in hospital, and mortality in a cohort with cerebrovascular disease.
The aim of this study was to determine the prognostic influence of cigarette smoking on stroke severity, disability, length of stay (LOS) in hospital, and mortality in different stroke types. A cohort separated by smoking status from the Registry of the Canadian Stroke Network was analyzed using logistic regression while controlling for key outcomes and clinical and demographic characteristics. There were 20,523 patients that were included for this study from July 2003 to March 2008. Multivariable analyses revealed that, in general, long-time smoking had a negative effect on functional outcome at discharge, mortality at 1 year, and LOS in hospital. In general, former smoking had a positive impact in reducing the risk of severe stroke, mortality risk at 30 days, and the LOS in hospital. Significant differences in clinical and demographics were found between smokers, nonsmokers, and former smokers with cerebrovascular disease. On average, smokers had an earlier initial stroke presentation of cerebrovascular disease. Our results provide empirical evidence regarding the prognostic influence of cigarette smoking on stroke severity, disability, and LOS in hospital and mortality, but the magnitude of the effect varied by stroke type.


[Perfusion imaging of acute ischemic stroke].
Multi-modal imaging in acute ischemic stroke includes structural imaging, perfusion imaging and angiographic assessment of brain arteries. Perfusion imaging discriminates brain tissue that is critically hypo-perfused but salvageable (ischemic penumbra) from irreversibly injured tissue (ischemic core). In acute reperfusion therapies (intravenous or endovascular), patients who have substantial penumbra and a small core (target mismatch pattern) are most likely to have a good clinical outcome. Patient selection based on multi-modal imaging is not proven mandatory for acute treatment in patients admitted within the established time-window. Multi-modal image-based patient selection may be promising tool to identify candidates for acute treatment beyond the established time-window.


Incremental value of natriuretic peptide measurement in acute decompensated heart failure (ADHF): a systematic review.
The aim of this systematic review was to determine whether B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) independently add incremental value for predicting mortality and morbidity in patients with acute decompensated heart failure (ADHF). Medline(®), Embase™, AMED, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and CINAHL were searched from 1989 to June 2012. We also searched reference lists of included articles, systematic reviews, and the gray literature. Studies were screened for eligibility criteria and assessed for risk of bias. Data were extracted on study design, population demographics, assay cutpoints, prognostic risk prediction model covariates, statistical methods, outcomes, and results. From 183 citations, only seven studies (5 BNP and 2 NT-proBNP) considered incremental value in ADHF subjects admitted to acute care centers. Admission assay levels and length of follow-up varied for BNP studies (31 days to 12 months) and for NT-proBNP studies (25-82 months). All studies presented at least one estimate of incremental value of BNP/NT-proBNP relative to the base prognostic model. Using discrimination or likelihood statistics, these studies consistently showed that BNP or NT-proBNP increased model performance. Three studies used reclassification and model validation computations to establish incremental value; these studies showed less consistency with respect to added value. In conclusion, the literature assessing incremental value of BNP/NT-proBNP in ADHF populations is limited to seven studies evaluating only mortality outcomes and at moderate risk of bias. Although there were differences in the base risk prediction models, assay cutpoints, and lengths of follow-up, there was consistency in BNP/NT-proBNP adding incremental value in prediction models in ADHF patients.


The Selectivity of Polymers Imprinted with Amines.
One of the main reasons for making molecularly imprinted polymers (MIPs) has been that MIPs interact selectively with a specific target compound. This claim is investigated here with the example of a widely used type of noncovalent MIP, the MIP for the beta blocker propranolol. Adsorption isotherms of this MIP and of a nonimprinted control polymer (NIP), respectively, have been measured with a series of compounds in the porogen solvent acetonitrile. The results, visualized as "selectivity ladders", show that the MIP binds propranolol and many other amines better than the NIP does, but the selectivity of the MIP is actually inferior to that of the NIP. The selectivity of either polymer for propranolol is modest against many amines, but is remarkable with respect to other compounds. The contribution of imprinting towards selectivity can be better appreciated when three MIPs, made with different amine templates, are compared among themselves. Each MIP is seen to bind its own template slightly better than the other two MIPs do. In media different from the porogen, the selectivity patterns may change substantially. Propranolol seems to have properties that make it stand high on the selectivity scale in different solvents, albeit for different reasons.


[Forensic-medical aspects of injuries inflicted by nonlethal arms].
Special literature (surgical, forensic-medical and criminalistic) is reviewed on classification, mechanisms of a harmful action and characteristics of injuries inflicted by non-lethal arms. Some details of such arms construction and damaging action are given.


Myotonic dystrophy kinase modulates skeletal muscle but not cardiac voltage-gated sodium channels.
Altered modulation of skeletal muscle voltage-gated sodium channels by myotonic dystrophy kinase (DMPK) has been proposed as a possible mechanism underlying myotonia in this disease. We examined the effect of a recombinant mouse DMPK on the functional properties of human skeletal muscle (hSkM1) and cardiac (hH1) voltage-gated sodium channels in the Xenopus oocyte expression system. Co-expression of DMPK with hSkM1 in oocytes resulted in significantly lower peak sodium current amplitude as compared to cells expressing hSkM1 alone in agreement with a previous report. By contrast, DMPK had no effect on the level of expressed sodium current in cells expressing hH1. Similarly, there were no measurable effects of the kinase on the kinetics or steady-state properties of activation or inactivation. Our findings support the previous observations made with rat muscle sodium channels and demonstrate that the effect of DMPK on sodium channels is isoform specific despite conservation of a putative phosphorylation site between the two isoforms.


Status of strains that contravene Rules 27 (3) and 30 of the International Code of Nomenclature of Bacteria. Opinion 81.
Based on a list of 205 names proposed in original articles in the International Journal of Systematic and Evolutionary Microbiology or cited in Validation Lists from January 2001 that are not in accordance with Rules 27(3) and 30 of the International Code of Nomenclature of Bacteria (the Code), the Judicial Commission rules that names contained in lists 2-4 are to be considered to be validly published and that deposit in more than one collection in different countries is documented. Names included in list 1 are only to be considered validly published if evidence is presented that the strains have been deposited in additional collections, as laid down by Rules 27 (3) and 30 of the Code.


Monoclonal antibodies selective for α-synuclein oligomers/protofibrils recognize brain pathology in Lewy body disorders and α-synuclein transgenic mice with the disease-causing A30P mutation.
Inclusions of intraneuronal alpha-synuclein (α-synuclein) can be detected in brains of patients with Parkinson's disease and dementia with Lewy bodies. The aggregation of α-synuclein is a central feature of the disease pathogenesis. Among the different α-synuclein species, large oligomers/protofibrils have particular neurotoxic properties and should therefore be suitable as both therapeutic and diagnostic targets. Two monoclonal antibodies, mAb38F and mAb38E2, with high affinity and strong selectivity for large α-synuclein oligomers were generated. These antibodies, which do not bind amyloid-beta or tau, recognize Lewy body pathology in brains from patients with Parkinson's disease and dementia with Lewy bodies and detect pathology earlier in α-synuclein transgenic mice than linear epitope antibodies. An oligomer-selective sandwich ELISA, based on mAb38F, was set up to analyze brain extracts of the transgenic mice. The overall levels of α-synuclein oligomers/protofibrils were found to increase with age in these mice, although the levels displayed a large interindividual variation. Upon subcellular fractionation, higher levels of α-synuclein oligomers/protofibrils could be detected in the endoplasmic reticulum around the age when behavioral disturbances develop. In summary, our novel oligomer-selective α-synuclein antibodies recognize relevant pathology and should be important tools to further explore the pathogenic mechanisms in Lewy body disorders. Moreover, they could be potential candidates both for immunotherapy and as reagents in an assay to assess a potential disease biomarker.


Doing it for themselves.
There is a cornucopia of writing about clinical supervision, with assertions about how important it is and how it ensures safe practice. There have been recommendations from the Allitt inquiry about its introduction, yet there is only the sketchiest information about how to do it and introduce it effectively within a trust to the satisfaction of both professional clinical staff and managers with an eye to the financial bottom line.


Foreign body granuloma formation secondary to silicone injection.
Injectable silicone has been used extensively over the last 40 years for soft tissue augmentation. Although considered biologically inert, this material has been implicated in a variety of adverse reactions including granulomas, disfiguring nodules, and lymphedema, sometimes with latent periods of decades. Often these complications are a result of the use of industrial grade products injected by unlicensed or unskilled practitioners. Here we report a case of foreign body granuloma in the thigh secondary to silicone injection in the buttocks. Initially the patient did not disclose a cosmetic contouring procedure administered by a nonprofessional nine months earlier, making diagnosis difficult. We remind clinicians to include foreign body granulomas in the differential diagnosis of apparent cellulitis and to question patients about the use of injectable fillers.


Cortical bone histomorphometry in male femoral neck: the investigation of age-association and regional differences.
Low bone volume and changes in bone quality or microarchitecture may predispose individuals to fragility fractures. As the dominant component of the human skeleton, cortical bone plays a key role in protecting bones from fracture. However, histological investigations of the underlying structural changes, which might predispose to fracture, have been largely limited to the cancellous bone. The aim of this study was to investigate the age-association and regional differences of histomorphometric properties in the femoral neck cortical bone. Undecalcified histological sections of the femoral neck (n = 20, aged 18-82 years, males) were cut (15 μm) and stained using modified Masson-Goldner stain. Complete femoral neck images were scanned, and cortical bone boundaries were defined using our previously established method. Cortical bone histomorphometry was performed with low (×50) and high magnification (×100). Most parameters related to cortical width (Mean Ct.Wi, Inferior Ct.Wi, Superior Ct.Wi) were negatively associated with age both before and after adjustment for height. The inferior cortex was the thickest (P < 0.001) and the superior cortex was the thinnest (P < 0.008) of all cortical regions. Both osteonal size and pores area were negatively associated with age. Osteonal area and number were higher in the antero-inferior area (P < 0.002) and infero-posterior area (P = 0.002) compared to the postero-superior area. The Haversian canal area was higher in the infero-posterior area compared to the postero-superior area (P = 0.002). Moreover, porosity was higher in the antero-superior area (P < 0.002), supero-anterior area (P < 0.002) and supero-posterior area (P < 0.002) compared to the infero-anterior area. Eroded endocortical perimeter (E.Pm/Ec.Pm) correlated positively with superior cortical width. This study describes the changes in cortical bone during ageing in healthy males. Further studies are needed to investigate whether these changes explain the increased susceptibility to femoral neck fractures.


Factors influencing antenatal care service utilization in hadiya zone.
In Ethiopia, the levels of maternal and infant morbidity and mortality are among the highest in the world. This is attributed to, among other factors, none use of modern health care services by women in Ethiopia. According to the 2005 Ethiopian Demographic Health Survey, more than seven in ten mothers did not receive antenatal care at all. Therefore, the objective of this study was to explore factors influencing antenatal care services utilization in Southern Ethiopia. A community-based cross sectional study was conducted in Hadiya Zone of Southern Ethiopia from January to February 2009. A multi stage sampling technique was used to select the study population in one urban and five rural kebeles. Analysis was done using SPSS for windows version 16. This study revealed that antenatal care service utilization in the study area was 86.3%. However, from those who attended antenatal care service 406 (68.2%) started antenatal care visit during the second trimester of pregnancy and significant proportion 250 (42%) had less than four visits. Maternal age, husband attitude, family size, maternal education, and perceived morbidity were major predictors of antenatal care service utilization. Though the antenatal care service utilization is high in the study population, four in ten of the mothers did not have the minimum number of visits recommended by World Health Organization. Promoting information, education and communication in the community is recommended to favorably affect the major predictors of antenatal care service utilization.


Pharmacognostical Sources of Popular Medicine To Treat Alzheimer's Disease.
A large number of classical and recently discovered plants are indicated in preventing and/or treating Alzheimer's disease (AD). Name of plants with their anti-AD effects are important for their further use and investigation. A short overview of AD is given; anti-Alzheimer plants are given in a Table. Various medicinal plants are listed here as sources of popular medicines to be used in cases when patients are afraid of developing and/or suffer from AD. Some of these plants have been used for centuries. The major sources in the literature, over one hundred of references are given for plants that show beneficial effect on the progress of AD. Plant extracts are widely used addition to the synthetic drugs approved by various administrative authorities to stop/slow down the progress of symptoms of AD.


Host range, replicative, and cytopathic properties of human immunodeficiency virus type 1 are determined by very few amino acid changes in tat and gp120.
Human immunodeficiency virus type 1 (HIV-1) isolates display differences in a variety of in vitro biological properties, including the ability to infect different cell types, the kinetics of replication, and cytopathicity in the infected cells. Studies with isolates obtained from the same individual over time have shown that these in vitro properties of the viral isolates correlate with pathogenicity in the host. The later isolates, recovered when disease has developed, display a wider cellular host range, replicate rapidly and to high titers in the infected cells, and induce syncytia in these cells. In the present studies, the genomic determinants of these biological properties were defined with recombinant viruses generated between two HIV-1 isolates recovered sequentially from the same individual. The results show that the rate of HIV-1 replication in the HUT 78 T-cell line is controlled by the first coding exon of tat. Infection of T-cell and monocytic cell lines is determined by two specific regions in the envelope gp120, one of which also confers the ability of an isolate to induce syncytia. Amino acid sequence comparison of the regions identified revealed minor differences between the two viral isolates: 2 amino acids in the tat gene product and 10 and 12 amino acids in the two regions of envelope gp120. These data suggest that small changes in the tat and env proteins can have dramatic effects on the pathogenic potential of HIV-1.


Cross-linking of glycoprotein oligomers during herpes simplex virus type 1 entry.
Herpes simplex virus (HSV) has 10 glycoproteins in its envelope. Glycoprotein B (gB), gC, gD, gH, and gL have been implicated in virus entry. We previously used chemical cross-linking to show that these five glycoproteins were close enough to each other to be cross-linked into homodimeric and hetero-oligomeric forms; hetero-oligomers of gB-gC, gC-gD, gD-gB, gH-gL, gC-gL and gD-gL were found in purified virions. To better understand the roles of these glycoproteins in viral entry, we have modified a standard HSV penetration assay to include cross-linkers. This allowed us to examine changes in associations of viral glycoproteins during the entry process. HSV-1(KOS) was adsorbed at 4 degrees C to human neuroblastoma cells (SY5Y). The temperature was raised to 37 degrees C and cells were treated with cross-linker at various times after the temperature shift. Cytoplasmic extracts were examined by Western blotting (immunoblotting) for viral glycoproteins. We found that (i) as in virus alone, the length and concentration of the cross-linking agent affected the number of specific complexes isolated; (ii) the same glycoprotein patterns found in purified virions were also present after attachment of virions to cells; and (iii) the ability to cross-link HSV glycoproteins changed as virus penetration proceeded, e.g., gB and gD complexes which were present during attachment disappeared with increasing time, and their disappearance paralleled the kinetics of penetration. However, this phenomenon appeared to be selective since it was not observed with gC oligomers. In addition, we examined the cross-linking patterns of gB and gD in null viruses K082 and KOSgD beta. Neither of these mutants, which attach but cannot penetrate, showed changes in glycoprotein cross-linking over time. We speculate that these changes are due to conformational changes which preclude cross-linking or spatial alterations which dissociate the glycoprotein interactions during the penetration events.


The Prognostic Value of Preoperative Naples Prognostic Score in Upper Tract Urothelial Carcinoma Patients after Radical Nephroureterectomy.
This study aims to determine the prognostic value of preoperative Naples prognostic score (NPS) on survival outcomes in upper tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). We conducted a retrospective study about UTUC patients at West China Hospital from January 2015 to June 2019. The X-Tile program was used to identify the optimal cutoff value of NPS. Overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) were the endpoints of interest. Kaplan-Meier curves were used to estimate survival and Cox proportional hazard model was used for risk assessment. A total of 237 UTUC patients after RNU were identified and the threshold of NPS was determined to be 2. Preoperative high-NPS was associated with inferior OS (p = 0.004), CSS (p = 0.002) and PFS (p = 0.008), especially in locally advanced UTUC patients. Preoperative NPS was an independent predictor for OS (HR: 1.78; 95% CI: 1.08, 2.93), CSS (HR: 1.87; 95% CI: 1.11, 3.14) and PFS (HR: 1.60; 95% CI: 1.02, 2.50). The addition of NPS into the predictive model consisting of predictors from multivariate Cox regression resulted in better prediction performance. Preoperative NPS was a novel and reliable predictor for survival in UTUC patients after RNU, and should be further explored.


Acute Effects of Plyometric Intervention—Performance Improvement and Related Changes in Sprinting Gait Variability.
The purpose of this study was to examine the effect of a short high-intensity plyometric program on the improvement of explosive power of lower extremities and sprint performance as well as changes in sprinting stride variability in male sprinters. Fourteen healthy male sprinters (mean ± SD: age: 18.07 ± 0.73 years, body mass: 73 ± 9.14 kg, height: 180.57 ± 8.16 cm, and best 100 m: 10.89 ± 0.23) participated in the experiment. The experimental protocol included vertical jumping such as squat jump, countermovement jump, and horizontal jumps; standing long jump and standing triple jumps to assess lower-body power, maximal running velocity; a 20-m flying start sprint that evaluated variability of 10 running steps and 60-m starting block sprint. All analyzed parameters were obtained using the new technology of OptoJump-Microgate (OptoJump, Italy). The short-term plyometric training program significantly increased the explosive power of lower extremities, both vertical and horizontal jumping improvement. However, the vertical jumps increased much more than the horizontal. The 20-m improvements were derived from an increase of stride frequency from 4.31 to 4.39 Hz because of a decrease of ground contact time from 138 to 133 milliseconds. This did not translate into step length changes. Therefore, the significantly increased frequency of stride (1.8%), which is a specific expression of ground contact time reduction during support phase, resulted in an increase of speed. The training volume of 2 weeks (with 6 sessions) using high-intensity (between 180 and 250 jumps per session) plyometric exercises can be recommended as the short-term strategy that will optimize one's probability of reaching strong improvements in explosive power and sprint velocity performance.


Enhanced efficiency of light-trapping nanoantenna arrays for thin-film solar cells.
We suggest a new type of efficient light-trapping structures for thin-film solar cells based on arrays of planar nanoantennas operating far from their plasmon resonances. The operation principle of our structures relies on the excitation of collective modes of the nanoantenna arrays whose electric field is localized between the adjacent metal elements. We calculate a substantial enhancement of the short-circuit photocurrent for photovoltaic layers as thin as 100-150 nm. We compare our light-trapping structures with conventional anti-reflecting coatings and demonstrate that our design approach is more efficient. We show that it may provide a general background for different types of broadband light-trapping structures compatible with large-area fabrication technologies for thin-film solar cells.


Brain potassium ion homeostasis, anoxia, and metabolic inhibition in turtles and rats.
Microelectrode measurements of tissue oxygen tension (PtO2) and extracellular potassium ion concentration ([K+]o) and dual wavelength spectrophotometric measurements of the reduction/oxidation state of cytochrome aa3 were used to compare the resistance of turtle and rat brain to anoxia in vivo. In both species, respiration with 100% N2 resulted in a decrease of tissue oxygen tension to near 0 mmHg and reduction of cytochrome aa3. However, N2 respiration resulted in only moderate elevation of [K+]o in turtle bran while [K+]o in rat brain was elevated to levels greater than 50 mM. In addition, N2 respiration in turtles had no effect on the rate of recovery of [K+]o, which was elevated by direct electrical stimulation of the brain. Electrocorticographic activity (ECoG) of the turtle brain was only moderately depressed during N2 respiration for up to 4 h whereas the ECoG of rat brain became isoelectric within 1 min. Inhibition of glycolysis with iodoacetate (IAA) resulted in rapid elevation of [K+]o in turtle brain during anoxia, but IAA had little effect on [K+]o during normoxia. These results indicate that the remarkable resistance of the diving turtle to anoxia does not result from continued provision of oxygen to the brain either by redistribution of systemic blood flow or from blood O2 storage. In addition, the turtle brain does not rely on cellular stores of high-energy compounds for maintenance of ionic homeostasis. We conclude that potassium ion homeostasis in the anoxic turtle brain must result from increased glycolytic ATP production and from decreased energy utilization.


HuR uses AUF1 as a cofactor to promote p16INK4 mRNA decay.
In this study, we show that HuR destabilizes p16(INK4) mRNA. Although the knockdown of HuR or AUF1 increased p16 expression, concomitant AUF1 and HuR knockdown had a much weaker effect. The knockdown of Ago2, a component of the RNA-induced silencing complex (RISC), stabilized p16 mRNA. The knockdown of HuR diminished the association of the p16 3' untranslated region (3'UTR) with AUF1 and vice versa. While the knockdown of HuR or AUF1 reduced the association of Ago2 with the p16 3'UTR, Ago2 knockdown had no influence on HuR or AUF1 binding to the p16 3'UTR. The use of EGFP-p16 chimeric reporter transcripts revealed that p16 mRNA decay depended on a stem-loop structure present in the p16 3'UTR, as HuR and AUF1 destabilized EGFP-derived chimeric transcripts bearing wild-type sequences but not transcripts with mutations in the stem-loop structure. In senescent and HuR-silenced IDH4 human diploid fibroblasts, the EGFP-p16 3'UTR transcript was more stable. Our results suggest that HuR destabilizes p16 mRNA by recruiting the RISC, an effect that depends on the secondary structure of the p16 3'UTR and requires AUF1 as a cofactor.


Resident learning curve for minimal-access transforaminal lumbar interbody fusion in a military training program.
Minimal-access transforaminal lumbar interbody fusion (TLIF) has gained popularity as a method of achieving interbody fusion via a posterior-only approach with the aim of minimizing injury to adjacent tissue. While many studies have reported successful outcomes, questions remain regarding the potential learning curve for successfully completing this procedure. The goal of this study, based on a single resident's experience at the only Accreditation Council for Graduate Medical Education-approved neurosurgical training center in the US military, was to determine if there is in fact a significant learning curve in performing a minimal-access TLIF. The authors retrospectively reviewed all minimal-access TLIFs performed by a single neurosurgical resident between July 2006 and January 2008. Minimal-access TLIFs were performed using a tubular retractor inserted via a muscle-dilating exposure to limit approach-related morbidity. The accuracy of screw placement and operative times were assessed. A single resident/attending team performed 28 minimal-access TLIF procedures. In total, 65 screws were placed at L-2 (1 screw), L-3 (2 screws), L-4 (18 screws), L-5 (27 screws), and S-1 (17 screws) from the resident's perspective. Postoperative CTs were reviewed to determine the accuracy of screw placement. An accuracy of 95.4% (62 of 65) properly placed screws was noted on postoperative imaging. Two screws (at L-5 in the patient in Case 17 and at S-1 in the patient in Case 9) were lateral, and no revision was needed. One screw (at L-4 in Case 24) was 1 mm medial without symptoms or the need for revision. In evaluating the operative times, 2 deformity cases (Grade III spondylolisthesis) were excluded. The average operating time per level in the remaining 26 cases was 113.25 minutes. The average time per level for the first 13 cases was 121.2 minutes; the amount of time decreased to 105.3 minutes for the second group of 13 cases (p = 0.25). In summary, minimal-access TLIF can be safely performed in a training environment without a significant complication rate due to the expected learning curve.


Cell cycle sensitivity of HL-60 cells to the differentiation-inducing effects of 1-alpha,25-dihydroxyvitamin D3.
A recently described system for monocyte-like differentiation of HL-60 cells was utilized to determine if the initiation of this pathway can be linked to a set of replicative cellular events. The standard induction system consisted of a 4-h exposure to 100 nM 1-alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] followed by determination of nonspecific esterase and phagocytic activity 24 h later. The cell cycle status was ascertained by the incorporation of [3H]thymidine and autoradiography. Studies in which cell cycle block in the G1/S phase boundary region was produced by a partial inhibition of DNA synthesis with thymidine, or sodium butyrate, showed that the exposure of such semisynchronous cultures to 1,25(OH)2D3 resulted in an increased proportion of differentiated cells. Conversely, blocking the cell cycle with vinblastine (G2/M block) or theobromine (mid-G1 block) inhibited the initiation of differentiation by 1,25(OH)2D3. Experiments in which the differentiated cells were examined for the cell cycle position at the time of the exposure to 1,25(OH)2D3 by [3H]thymidine labeling and autoradiography confirmed that the late G1 and early S phase cells are those which predominate in the differentiated fraction of 1,25(OH)2D3-treated HL-60 cultures. These results link pre- and early replicative cellular events to the induction of monocytic differentiation by 1,25(OH)2D3.


Opposing immunoregulatory functions of CD8+ lymphocytes: a requirement for monocytes in suppressor cell induction.
We have found that the induction of suppressor T cell (Ts) function in pokeweed mitogen (PWM)-stimulated cultures of peripheral blood mononuclear cels (PBMC) depends on the concentration of monocytes in inductive cultures. When cultured for 7 to 8 days in a physiologic concentration of monocytes (10 to 15%) suppressor cells differentiated with the surface phenotype CD8+ DR+ Leu-7- Leu-8+ Tp44-. Suppressor function, as assessed in secondary cultures of fresh PWM-stimulated CD4+ cells, was partially radiosensitive, and its induction could be partially inhibited by treatment with indomethacin. Culture supernatants of PWM-pulsed CD4+ cells could induce CD8+ suppressor cells only when monocytes were included in cultures for supernatant production. In marked contrast, if the monocyte concentration of PWM-stimulated T cells was reduced to less than 5%, CD8+ cells harvested from such cultures substantially augmented proliferation of PWM-stimulated CD4+ cells in assay cultures. Amplifier cells from monocyte-depleted cultures, were also DR+Tp44-. Suppressive activity of the CD8+ subset was restored simply by addition of monocytes to purified T cells, reconstituting the concentration present among unfractionated PBMC. Addition of IL 1 could not replace the requirement of monocytes for suppressor cell induction either in PWM-stimulated primary cultures or in culture supernatants. The data thus demonstrate that the regulatory activity of CD8+ lymphocytes is critically dependent on the conditions of cellular activation; at concentrations of monocytes normally present in peripheral blood, PWM stimulation induced potent suppressor activity, whereas under conditions of moderate monocyte depletion the regulatory activity of the same phenotypic subset of CD8+ cells was reversed. The experiments thus suggest that the functional consequences of an activating stimulus may depend on regulatory effects of monocytes in CD8+ suppressor cell induction.


Cation recognition by self-assembled monolayers of oriented helical peptides having a crown ether unit.
Cation recognition of self-assembled monolayers (SAMs) of helical peptides having a crown ether unit was investigated by the impedance spectroscopy and cyclic voltammetry. Lipo-(Ala-Aib)8-Ala-Cr and Boc-Glu(Cr)-(Ala-Aib)8-Lipoa (Lipo, Lipoa, and Cr represent lipoic acid, lipoamide, and amidobenzo-18-crown-6, respectively) were synthesized and the helix SAMs were prepared. The peptides having a crown ether unit formed SAMs oriented nearly vertically to the substrate. The capacitance of the Lipo-(Ala-Aib)(8)-Ala-Cr SAM changed specifically with the addition of cations, and the binding constants of the SAM were larger than those of the crown ether in aqueous solution because of a large dipole moment of the helical peptide. In the case of the Boc-Glu(Cr)-(Ala-Aib)8-Lipoa SAM, the cation binding to the SAM showed a drastic decrease in the peak current of the cyclic voltammetry around 10(-5)M of K+ ion. In either capacitance measurement or cyclic voltammetry, the helical peptide SAM played an important role in the sensitive response to cations.


Defining the dynamin-based ring organizing center on the peroxisome-dividing machinery isolated from Cyanidioschyzon merolae.
Organelle division is executed through contraction of a ring-shaped supramolecular dividing machinery. A core component of the machinery is the dynamin-based ring conserved during the division of mitochondrion, plastid and peroxisome. Here, using isolated peroxisome-dividing (POD) machinery from a unicellular red algae, Cyanidioschyzon merolae, we identified a dynamin-based ring organizing center (DOC) that acts as an initiation point for formation of the dynamin-based ring. C. merolae contains a single peroxisome, the division of which can be highly synchronized by light-dark stimulation; thus, intact POD machinery can be isolated in bulk. Dynamin-based ring homeostasis is maintained by the turnover of the GTP-bound form of the dynamin-related protein Dnm1 between the cytosol and division machinery via the DOC. A single DOC is formed on the POD machinery with a diameter of 500-700 nm, and the dynamin-based ring is unidirectionally elongated from the DOC in a manner that is dependent on GTP concentration. During the later step of membrane fission, the second DOC is formed and constructs the double dynamin-based ring to make the machinery thicker. These findings provide new insights to define fundamental mechanisms underlying the dynamin-based membrane fission in eukaryotic cells.


Automated Spatial Pattern Analysis for Identification of Foot Arch Height From 2D Foot Prints.
Arch height is an important determinant for the risk of foot pathology, especially in an aging population. Current methods for analyzing footprints require substantial manual processing time. The current research investigated automated determination of foot type based on features derived from the Gabor wavelet utilizing digitized footprints to allow timely assessment of foot type and focused intervention. Two hundred and eighty footprints were collected, and area, perimeter, curvature, circularity, 2nd wavelet moment, mean bending energy (MBE), and entropy were determined using in house developed MATLAB codes. The results were compared to the gold standard using Spearman's Correlation coefficient and multiple linear regression models with significance set at 0.05. The proposed approach found MBE combined with foot perimeter to give the best results as shown by ANOVA (F(2,211) = 10.18, p < 0.0001) with the mean ±SD of low, normal, and high arch being, respectively, 0.26 ± 0.025,.24 ± 0.021, and 0.23 ± 0.024. A clinical review of the new cut off values, as set by the first and the third quartiles of our sample, lead to reliability up to 87%. Our results suggest that automated wavelet-based foot type classification of 2D binary images of the plantar surface of the foot is comparable to current state-of-the-art methods providing a cost and time effective tool suitable for clinical diagnostics.


When Fiction Is Just as Real as Fact: No Differences in Reading Behavior between Stories Believed to be Based on True or Fictional Events.
Experiments have shown that compared to fictional texts, readers read factual texts faster and have better memory for described situations. Reading fictional texts on the other hand seems to improve memory for exact wordings and expressions. Most of these studies used a "newspaper" vs. "literature" comparison. In the present study, we investigated the effect of reader's expectation to whether information is true or fictional with a subtler manipulation by labeling short stories as either based on true or fictional events. In addition, we tested whether narrative perspective or individual preference in perspective taking affects reading true or fictional stories differently. In an online experiment, participants (final N = 1,742) read one story which was introduced as based on true events or as fictional (factor fictionality). The story could be narrated in either 1st or 3rd person perspective (factor perspective). We measured immersion in and appreciation of the story, perspective taking, as well as memory for events. We found no evidence that knowing a story is fictional or based on true events influences reading behavior or experiential aspects of reading. We suggest that it is not whether a story is true or fictional, but rather expectations toward certain reading situations (e.g., reading newspaper or literature) which affect behavior by activating appropriate reading goals. Results further confirm that narrative perspective partially influences perspective taking and experiential aspects of reading.


Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems.
We developed a scoring system for the assessment of perinatal asphyxia as depicted on MR images. Four scoring systems were derived to evaluate MR images obtained in asphyxiated neonates: the basal ganglia (BG) score, the watershed (W) score, the combined basal ganglia/watershed (BG/W) score, and the sum of the BG and W scores, the summation (S) score. In addition, three MR sequences, T1-weighted, first-echo T2-weighted, and second-echo T2-weighted, were assessed for each patient for each scoring system. Neuromotor examinations were performed at ages 3 and 12 months, and cognitive development was tested at age 12 months. Statistical analysis was then performed to test the relationship between the MR scores and the outcome scores. The BG/W score, obtained with the first-echo T2-weighted sequence, was the most useful overall score for predicting neuromotor outcome at 3 and 12 months and cognitive outcome at 12 months. T1-weighted and first-echo T2-weighted sequences showed a stronger association with outcome in patients imaged during the first postnatal week, whereas second-echo T2-weighted sequences showed a stronger association with outcome in patients imaged during the second postnatal week. It appears that, with the use of the BG/W score, MR imaging discriminates accurately between patients with good and poor neuromotor and cognitive outcome at 3 and 12 months. In terms of our scoring systems, the first-echo T2-weighted sequence appears to discriminate best between patients with good and poor 3- and 12-month outcomes. Proper use of the imaging sequences and scoring systems described in this article can increase the knowledge base upon which treatment decisions are made in asphyxiated neonates.


High-Resolution Structural Proteomics of Mitochondria Using the 'Build and Retrieve' Methodology.
The application of integrated systems biology to the field of structural biology is a promising new direction, although it is still in the infant stages of development. Here we report the use of single particle cryo-EM to identify multiple proteins from three enriched heterogeneous fractions prepared from human liver mitochondrial lysate. We simultaneously identify and solve high-resolution structures of nine essential mitochondrial enzymes with key metabolic functions, including fatty acid catabolism, reactive oxidative species clearance, and amino acid metabolism. Our methodology also identified multiple distinct members of the acyl-CoA dehydrogenase family. This work highlights the potential of cryo-EM to explore tissue proteomics at the atomic level.


Changes in quality of life after short and long term follow-up of Roux-en-Y gastric bypass for morbid obesity.
It is unclear whether health-related quality of life (HRQL) is sustained in a long-term follow-up of morbidly obese patients who underwent Roux-en-Y gastric bypass (RYGB). Objective This study aims to analyze the HRQL changes following RYGB in short and long-term follow-up. We compared the health-related quality of life among three separate patient groups, using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Group A - 50 preoperative morbidly obese patients; Group B - 50 RYGB patients 1-2 years post-surgery; Group C - 50 RYGB patients more than 7 years post-surgery. The groups were similar for gender, age and body mass index before surgery. We observed that physical functioning, social function, emotional role functioning and mental health scales did not vary between the three groups. The physical role functioning scale was unchanged in the short-term and decreased compared to the preoperative scale in the long-term follow-up. Bodily pain improved after the operation but returned to the initial level after 7 years. The vitality and general health perceptions improved after the operation and maintained these results after 7 years compared with the preoperative perceptions. RYGB improved health-related quality of life in three SF-36 domains (bodily pain, general health perceptions and vitality) in the short-term and two SF-36 domains (general health perceptions and vitality) in the long-term.


Spatial bias in figure placement in representational drawing: Associations with handedness and script directionality.
Spatial biases in graphomotor production tasks such as figure drawing may reflect biological (cerebral lateralization), biomechanical (limb movement), and/or cultural (reading/writing direction) influences. The present study examined sources of bias in the placement in graphic space of a symmetrical drawn figure (a tree). A previous study using a child sample found an overall leftward placement bias, independent of participants' reading/writing direction experience [Picard & Zarhbouch, 2014. Leftward spatial bias in children's drawing placement: Hemispheric activation versus directional hypotheses. Laterality: Asymmetries of Body, Brain and Cognition, 19(1), 96-112]; moreover, the left-side bias was greater in right handers. Using an adult sample, the present study also found an overall left placement bias. This effect was significantly greater in right-handed than left-handed participants. Importantly, a left placement bias was significantly greater in left-to-right readers (English) than in participants whose first learned language was from right-to-left (Urdu, Arabic or Farsi). The fact that script directionality is associated with figure placement in our study but not in the previous study suggests that a certain threshold of experience in reading/writing in a given direction may be needed for scanning biases to exert a demonstrable effect on representational drawing. These findings suggest that biomechanical and cultural factors offer a more parsimonious account of spatial biases in drawing.


[Comparison of different laryngeal preservation strategies based on chemoradiotherapy in locally advanced hypopharyngeal carcinoma].
Objective:This study aimed to evaluate the clinical features and treatment outcomes of the value of response-adapted treatment following radiotherapy and induction chemotherapy follwing subsequent comprehensive therapy in patients with resectable locally advanced hypopharyngeal carcinoma. Methods:This cohort study was conducted from September 2010 to September 2020 in our hospital, 231 patients pathologically confirmed stage Ⅲ and ⅣB resectable locally advanced hypopharyngeal carcinoma included. For the IC-directed ART strategy, IC is used to select good candidates to receive radical RT or CCRT, and others undergo surgery. He response-adapted strategy was determined based on the primary tumor response, which was evaluated at a dose of 50 Gy. If the response reached complete response or partial response(more than 80% tumor regression), patients received radical RT or CCRT; otherwise, they received surgery, if possible, at 4 to 6 weeks after RT. The end points of the study were OS(overall survival), progression free survival(PFS), locoregional recurrence-free survival(LRRFS) and LDFS. Results:In IC-directed group, 75.0%(57/76) patients reached PR after 2 cycles of induction chemotherapy. While in RT-directed group, 70.3%(109/155) patients reached large PR at dose of 50 Gy. The median interquartile range follow-up period of the whole cohort was 63.8 months. The 5-year OS, PFS, LRRFS and SFL of the whole cohort were 47.9%、39.6%、44.3% and 36.2%, respectively. In evaluations based on the different treatment strategies, the 5-year OS and SFL were 51.3% versus 37.0%(HR 0.67; 95%CI 0.43-1.05; P=0.07) and 27.8% versus 39.8%(HR 0.68; 95%CI 0.46-0.99; P=0.04) between IC-directed and RT-directed groups. In additional, surgery complications did not significantly differ between these two groups. Conclusion:In this cohort study, the response-adapted strategy based on an early RT response facilitated better treatment tailoring, and higher laryngeal preservation compared with IC-directed strategies. This approach could provide a feasible laryngeal preservation strategy in patients with resectable locally advanced hypopharyngeal carcinoma.


Comparison of the efficacy and safety of different formulations of omeprazole-based triple therapies in the treatment of Helicobacter pylori-positive peptic ulcer.
Little is known about the efficacy and safety of different formulations of omeprazole-based triple therapy regimens for the treatment of Helicobacter pylori-positive peptic ulcer. We compared the efficacy and safety of two formulations of omeprazole used in triple therapies in patients with H. pylori-positive active peptic ulcer. Seventy-four patients with endoscopically proven H. pylori-positive active peptic ulcer were randomized to two groups, each with 37 patients, to receive either OAC-I (6 weeks of "A" formulation of omeprazole [20 mg twice daily] plus 2 weeks of amoxicillin [1.0 g twice daily] and clarithromycin [500 mg twice daily] or OAC-II (6 weeks of "B" formulation of omeprazole [20 mg twice daily] plus 2 weeks of the same antibiotics. The H. pylori and ulcer healing status were assessed at the baseline and at the 6-week endpoint of therapy. Gastrointestinal symptoms, documentation of adverse events, and standard laboratory examinations were assessed at each visit. Eradication of H. pylori (intention to treat [n = 74]/per protocol [n = 66]) and healing of the ulcer were successful in 83.8%/96.9% and 93.8%, respectively, of the OAC-I group patients, and in 91.9%/100% and 97.1%, respectively, of the OAC-II group patients (P = 0.477; P = 0.608). The OAC-I group experienced rapid resolution of symptoms, but no significant differences were found between the two groups for number of days taken for resolution of gastrointestinal symptoms, adverse events, and laboratory findings. The two different formulations of omeprazole used in triple therapy regimens produced similar efficacy and safety results after 6 weeks of treatment in patients with H. pylori-positive active peptic ulcer.


Always on call: thoughts from a neophyte physician.
This commentary describes a new physician who encountered a patient in crisis in a nonmedical environment. It discusses professional obligations, ethical principles, errors committed, and reasoning behind such errors. Unusual circumstances, uncertainty about how to properly identify oneself as a physician, self-doubt, and discomfort with practicing outside one's scope of training are recognized as reasons behind these errors. Medical students should be reminded of their ethical obligation to offer emergency care within their limitations, instructed how to identify themselves, and guided to become competent team leaders. Resident doctors should continue to receive instruction as they internalize ethical principles and identify their scopes of practice. Practicing physicians should be competent in offering basic emergency care if needed.


Fabrication and Mechanical Performance of Non-Crimp Unidirectional Jute-Yarn Preform-Based Composites.
This work developed novel jute-yarn, non-crimp, unidirectional (UD) preforms and their composites, with three different types of warp jute yarns of varying linear densities and twists in the dry UD preforms, in order to present a possible solution to the detrimental effects of higher yarn twists and crimp at the warp-weft yarn interlacements of traditional, woven, preform-based composites on their mechanical properties. In the developed UD preforms, warp jute yarns were placed in parallel by using a wooden picture-frame pin board, with the minimal number of glass weft yarns to avoid crimp at the warp-weft yarns interlacements, which can significantly enhance the load-bearing ability of UD composites compared to traditional, woven, preform composites. It was found that an optimal combination of jute warp yarn linear densities and twists in the UD preforms is important to achieve the best possible mechanical properties of newly developed UD composites, because it encourages a proper polymer-matrix impregnation on jute fibres, leading to excellent fibre-matrix interface bonding. Composites made from the 25 lb/spindle jute warp yarn linear density (UD25) exhibited higher tensile and flexural properties than other UD composites (UD20, UD30). All the UD composites showed a much better performance compared to the traditional woven preform composites (W20), which were obviously related to the higher crimp and yarn interlacements, less load-carrying capacity, and poor fiber-matrix interfaces of W20 composites. UD25 composites exhibited a significant enhancement in tensile modulus by ~232% and strength by ~146%; flexural modulus by 138.5% and strength by 145% compared to W20 composites. This reveals that newly developed, non-crimp, UD preform composites can effectively replace the traditional woven composites in lightweight, load-bearing, complex-shaped composite applications, and hence, this warrants further investigations of the developed composites, especially on long-term and dynamic-loading mechanical characterizations.


Reconstruction of the inferior alveolar nerve with bioabsorbable polyglycolic acid nerve conduits.
Iatrogenic injury to the inferior alveolar nerve can result in debilitating anesthesia, dysesthesia, and allodynia. The authors report their experience with polyglycolic acid nerve tubes in inferior alveolar nerve reconstruction. Five patients with iatrogenically injured inferior alveolar nerves underwent reconstruction with polyglycolic acid nerve tubes performed by the senior author (A.P.T.). Patient charts were reviewed retrospectively. Resolution of pain, narcotic medication use, neuropathic pain medication use, and patient satisfaction with surgery were assessed by means of patient surveys. Sensation recovery was assessed with the Ten Test. Costs of surgery were calculated and adjusted to 2010 U.S. dollars using the consumer price index. Survey response rate was 100 percent. All patients suffered from preoperative pain and sensation loss. Preoperatively, 80 percent of patients used prescription narcotic and 100 percent of patients used neuropathic pain medications. Average time from injury to reconstruction was 14 months. Operative time averaged 240 minutes, and total surgical costs averaged $8177. At average follow-up of 47.8 months, Ten Test results averaged 3.3. Average time to maximum recovery of sensation and reduction of pain was 8 months and 7 months, respectively. One hundred percent of patients experienced pain relief, with an average 46 percent reduction in pain. Postoperatively, 100 percent of patients discontinued all narcotic and neuropathic pain medications. The use of polyglycolic acid nerve tubes in the reconstruction of iatrogenically injured inferior alveolar nerves achieves diminution of pain and variable sensory recovery. This technique is cost effective and carries no donor-site morbidity. : Therapeutic, IV.


Robust graphene-based molecular devices.
One of the main challenges to upscale the fabrication of molecular devices is to achieve a mechanically stable device with reproducible and controllable electronic features that operates at room temperature1,2. This is crucial because structural and electronic fluctuations can lead to significant changes in the transport characteristics at the electrode-molecule interface3,4. In this study, we report on the realization of a mechanically and electronically robust graphene-based molecular junction. Robustness was achieved by separating the requirements for mechanical and electronic stability at the molecular level. Mechanical stability was obtained by anchoring molecules directly to the substrate, rather than to graphene electrodes, using a silanization reaction. Electronic stability was achieved by adjusting the π-π orbitals overlap of the conjugated head groups between neighbouring molecules. The molecular devices exhibited stable current-voltage (I-V) characteristics up to bias voltages of 2.0 V with reproducible transport features in the temperature range from 20 to 300 K.


Palladium in the Chemical Synthesis and Modification of Proteins.
The field of site-specific modification of proteins has drawn significant attention in recent years owing to its importance in various research areas such as the development of novel therapeutics and understanding the biochemical and cellular behaviors of proteins. The presence of a large number of reactive functional groups in the protein of interest and in the cellular environment renders modification at a specific site a highly challenging task. With the development of sophisticated chemical methodologies it is now possible to target a specific site of a protein with a desired modification, however, many challenges remain to be solved. In this context, transition metals in particular palladium-mediated C-C bond-forming and C-O bond-cleavage reactions gained great interest owing to the unique catalytic properties of palladium. Palladium chemistry is being explored for protein modifications in vitro, on the cell surface, and within the cell. Very recently, palladium complexes have been applied for the rapid deprotection of several widely utilized cysteine protecting groups as well as in the removal of solubilizing tags to facilitate chemical protein synthesis. This Minireview highlights these advances and how the accumulated knowledge of palladium chemistry for small molecules is being impressively transferred to synthesis and modification of chemical proteins.


A hybrid microfluidic platform for cell-based assays via diffusive and convective trans-membrane perfusion.
We present a novel 3D hybrid assembly of a polymer microfluidic chip with polycarbonate track-etched membrane (PCTEM) enabling membrane-supported cell culture. Two chip designs have been developed to establish either diffusive or convective reagent delivery using the integrated PCTEM. While it is well suited to a range of cell-based assays, we specifically employ this platform for the screening of a common antitumor chemotoxic agent (mitomycin C - MMC) on the HL60 myeloid leukemia cell line. The toxic activity of MMC is based on the generation of severe DNA damage in the cells. Using either mode of operation, the HL60 cells were cultured on-chip before, during, and after exposure to MMC at concentrations ranging from 0 to 50 μM. Cell viability was analysed off-chip by the trypan blue dye exclusion assay. The results of the on-chip viability assay were found to be consistent with those obtained off-chip and indicated ca. 40% cell survival at MMC concentration of 50 μM. The catalogue of capabilities of the here described cell assay platform comprises of (i) the culturing of cells either under shear-free conditions or under induced through-membrane flows, (ii) the tight time control of the reagent exposure, (iii) the straightforward assembly of devices, (iv) the flexibility on the choice of the membrane, and, prospectively, (v) the amenability for large-scale parallelization.


How distressing is it to participate in medical research? A calibration study using an everyday events questionnaire.
To investigate how distressing participating in medical research is perceived to be, compared to everyday events. Anonymous questionnaire. Scotland and New Zealand. One hundred members of the Scottish general public, 94 University of Auckland students, 22 New Zealand Ministry of Health ethics committee members. Distress ratings made on a 0-10 scale for everyday events and common medical research procedures. Both general population and student samples generally rated the distress caused by participating in various medical research procedures as low or very low. Most research procedures were rated less than the distress caused by not being able to find a car park at a supermarket. In contrast, the ethics committee members rated the distress caused by most of the medical research procedures at a significantly higher level than the ratings of the student and general population samples. Ethics committee members overestimated the distress caused by interview or questionnaire assessments (M = 203.31%, SE = 11.42, 95% CI [179.79, 226.83]) more than medical testing for research (M = 158.06%, SE = 12.33, 95% CI [132.66, 183.46], p = 0.04) and everyday events (M = 133.10%, SE = 7.80, 95% CI [117.03, 149.16], p < 0.001). Common medical research procedures are not rated as particularly distressing by the general public, and ethics committees may be adopting an over-protective role when evaluating research applications that involve the use of questionnaire or survey methodology.


Geometric pumping induced by shear flow in dilute liquid crystalline polymer solutions.
We investigate nonlinear rheology of dilute liquid crystalline polymer solutions under time dependent two-directional shear flow. We analyze the Smoluchowski equation, which describes the dynamics of the orientation of a liquid crystalline polymer, by employing technique of the full counting statistics. In the adiabatic limit, we derive the expression for time integrated currents generated by a Berry-like curvature. Using this expression, it is shown that the expectation values of the time-integrated angular velocity of a liquid crystalline polymer and the time-integrated stress tensor are generally not zero even if the time average of the shear rate is zero. The validity of the theoretical calculations is confirmed by direct numerical simulations of the Smoluchowski equation. Nonadiabatic effects are also investigated by means of simulations and it is found that the time-integrated stress tensor depends on the speed of the modulation of the shear rate if we adopt the isotropic distribution as an initial state.


Performance of a fire detector based on a compact laser spectroscopic carbon monoxide sensor.
In this paper we show the suitability of a miniaturized tunable diode laser spectroscopy (TDLS)-based carbon-monoxide (CO) sensor for fire detection applications. The sensor utilizes a vertical-cavity surface-emitting laser (VCSEL) and inherent calibration scheme with reference gas filled in the photodetector housing. The fire-detection experiments are carried out under realistic conditions as described in the European standard EN54. The CO generation of all class C fires (according to EN54) could be well resolved. The cross-sensitivity to other substances was found to be very low: the maximum CO false response from cigarette smoke, hairspray and general aerosols reaches a low value of a few μL/L and only if the substance is directly applied into the sensor gas inlet. Therefore this sensor overcomes the disadvantage of high false alarm rate given by smoke detectors and is also in small size which is suitable for household and industrial applications. Hence, the VCSEL-based TDLS sensor is shown to have sufficient performance for fire-detection. It has advantages such as capability for fail-safe operation and, low cross-sensitivities as compared to existing point fire detector technology which is presently limited by these factors.


Structural pathology is not related to patient-reported pain and function in patients undergoing meniscal surgery.
The relationship between meniscal tears and other joint pathologies with patient-reported symptoms is not clear. We investigated associations between structural knee pathologies identified at surgery with preoperative knee pain and function in patients undergoing arthroscopic meniscal surgery. This study included 443 patients from the Knee Arthroscopy Cohort Southern Denmark (KACS), a prospective cohort following patients 18 years or older undergoing arthroscopic meniscal surgery at 4 hospitals between 1 February 2013 and 31 January 2014. Patient-reported outcomes, including the Knee Injury and Osteoarthritis Outcome Score (KOOS), were obtained by online questionnaires prior to surgery. Knee pathology was assessed by the operating surgeons using a modified version of the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) classification of meniscal tears questionnaire, supplemented with information extracted from surgery reports. Following hypothesis-driven preselection of candidate variables, backward elimination regressions were performed to investigate associations between patient-reported outcomes and structural knee pathologies. Regression models only explained a small proportion of the variability in self-reported pain and function (adjusted R2=0.10-0.12) and this association was mainly driven by age, gender and body mass index. Specific meniscal pathology and other structural joint pathologies found at meniscal surgery were not associated with preoperative self-reported pain and function in patients with meniscal tears questioning inferences made about a direct relationship between these. Our findings question the role of arthroscopic surgery to address structural pathology as a means to improve patient-reported outcomes in patients having surgery for a meniscal tear.


Cyanobacterial poisoning in livestock, wild mammals and birds--an overview.
Poisoning of livestock by toxic cyanobacteria was first reported in the 19th century, and throughout the 20th century cyanobacteria-related poisonings of livestock and wildlife in all continents have been described. Some mass mortality events involving unrelated fauna in prehistoric times have also been attributed to cyanotoxin poisoning; if correct, this serves as a reminder that toxic cyanobacteria blooms predate anthropogenic manipulation of the environment, though there is probably general agreement that human intervention has led to increases in the frequency and extent of cyanobacteria blooms. Many of the early reports of cyanobacteria poisoning were anecdotal and circumstantial, albeit with good descriptions of the appearance and behaviour of cyanobacteria blooms that preceded or coincided with illness and death in exposed animals. Early necropsy findings of hepatotoxicity were subsequently confirmed by experimental investigations. More recent reports supplement clinical and post-mortem findings with investigative chemistry techniques to identify cyanotoxins in stomach contents and tissue fluids.


Efficacy of Particulated Juvenile Cartilage Allograft Transplantation for Osteochondral Lesions of the Talus.
Particulated juvenile cartilage allograft transplantation (PJCAT) is a novel treatment option for osteochondral lesions of the talus (OLTs). It is typically employed as a salvage procedure after initial debridement and microfracture has failed as it is theorized to deliver viable hyaline cartilage. We hypothesized that PJCAT would be a safe and effective treatment option for OLTs. This is a retrospective case-control study of patients who underwent PJCAT for the treatment of OLTs at a single academic institution. Failure of the procedure was defined as no change or worsening of symptoms and/or the need for a subsequent cartilage restoration procedure. Variables recorded included preoperative magnetic resonance imaging (MRI) area and volume, intraoperative size, etiology, lesion location, sex, age, body mass index (BMI), history of prior surgery, American Orthopaedic Foot & Ankle Society score, and foot and ankle outcome score. Fifteen patients completed a minimum of 12 months of follow-up (mean, 34.6 months). The failure rate of PJCAT in this series was 40% (6/15). Preoperative MRI area and intraoperative OLT size along with male sex were predictive of failure ( P < .05). Age, BMI, etiology, technique (open vs arthroscopic), history of prior surgery, and location of lesion were not predictors of failure in this limited series ( P > .05). Patients with lesions greater than 125 mm2 area had a significant increased risk of clinical failure ( P < .05). Functional outcome scores were significantly better at final follow-up in the patients who had undergone successful treatment vs those who did not. These findings demonstrate the association of preoperative MRI lesion area, intraoperative lesion size, and male sex as risk factors for failure of PJCAT setting of an already difficult to treat pathology. Level IV, retrospective case series.


The role of meat in strategies to achieve a sustainable diet lower in greenhouse gas emissions: A review.
Food consumption is responsible for a considerable proportion of greenhouse gas emissions (GHGE). Hence, individual food choices have the potential to substantially influence both public health and the environment. Meat and animal products are relatively high in GHGE and therefore targeted in efforts to reduce dietary emissions. This review first highlights the complexities regarding sustainability in terms of meat consumption and thereafter discusses possible strategies that could be implemented to mitigate its climatic impact. It outlines how sustainable diets are possible without the elimination of meat. For instance, overconsumption of food in general, beyond our nutritional requirements, was found to be a significant contributor of emissions. Non-voluntary and voluntary mitigation strategies offer potential to reduce dietary GHGE. All mitigation strategies require careful consideration but on-farm sustainable intensification perhaps offers the most promise. However, a balance between supply and demand approaches is encouraged. Health should remain the overarching principle for policies and strategies concerned with shifting consumer behaviour towards sustainable diets.


Long-term survival of patients given hormonal therapy for metastatic endometrial stromal sarcoma.
Endometrial stromal sarcoma (ESS) is a rare neoplasm, mainly observed in premenopausal women. We describe two women 44 and 34 years old at the time ESS diagnosis, who developed lung metastases 3 and 6 years, respectively, after initial treatment: hysterectomy without (case 1) or with oophorectomy (case 2), followed by hormone replacement therapy (HRT) for the latter. Their estrogen (ER) and progesterone receptors (PR) were analyzed biochemically in metastatic lung tissue, yielding respective concentrations of ER 242 and 184, and PR 910 and 100 fmol/mg of cytosol protein. Both patients started treatment with the aromatase inhibitor aminoglutethimide (500 mg qid) after surgery for the first patient and after stopping HRT for the second. Under aromatase-inhibitor therapy, both patients achieved a complete response, patient 1 remains disease- free with 14+ years of follow-up, and patient 2 with 7+ years. Our data suggest that an aromatase inhibitor may be an effective treatment for ESS. Furthermore, routine ER and PR analyses could be useful to predict the response to hormonal therapy in ESS.


An additional suture secures against pitfalls in delta-shaped gastroduodenostomy after laparoscopic distal gastrectomy.
Laparoscopic gastrectomy is widely used as a minimally invasive surgery for gastric cancer. Laparoscopic distal gastrectomy must be followed by either a gastroduodenostomy or gastrojejunostomy to restore continuity of the alimentary tract. The intraabdominal delta-shaped gastroduodenostomy using endoscopic linear staplers, which was developed by Kanaya et al., is one of the feasible reconstructive procedures. However, the clinical results still remain uncertain. In 71 patients treated between February 2008 and February 2009, we found that anastomotic failure occurred in six patients and there was an intraabdominal abscess around the anastomosis in two patients, findings which might be associated with technical pitfalls in the procedure. After considering the mechanisms underlying these unfavorable complications, we developed a modification of the procedure to successfully overcome these complications by reinforcement of the anastomosis using simple suturing at the closed common channel on the greater curvature. This modified Kanaya's procedure will be safer and should provide a better intracorporeal gastroduodenostomy after laparoscopic distal gastrectomy.


Comparative breeding characteristics of fusion and fast reactors.
Expressions are developed to allow ready comparison of a hybrid fission-fusion plant and a fast breeder with respect to the number of thermal reactors that their fissile production could support, both for their feed requirements and for the new inventory needs of an expanding industry. These relations are expressed in terms of the neutron multiplication factor obtained in the fusion blanket, and the analogous quantities represented by the conversion ratios of the fast and thermal fission associated with the comparison. Results are presented graphically both for the steady state and for industries of arbitrary growth rate, and include the influence of tritium production requirements. Even a modest blanket neutron multiplication factor could enable the hybrid fusion system greatly to outperform the fast breeder on this simple basis of material balances.


Inhibition by long-term fermented miso of induction of pulmonary adenocarcinoma by diisopropanolnitrosamine in Wistar rats.
The present study was designed to investigate the effects of fermented miso in the diet on the development of lung tumors initiated by diisopropanolnitrosamine (BHP) in male Slc:Wistar rats. A total of 63 animals, 6 weeks of age, were divided into 4 groups and given BHP (2000 ppm) in their drinking water for 10 weeks. After the carcinogen treatment the rats were fed a normal control MF solid diet, or the same diet containing 10% long-term or short-term fermented miso for 12 weeks. The long-term fermented miso significantly reduced the number of lung tumors, adenocarcinomas and PCNA strongly positive tumors as compared with the short-term fermented miso. The present results thus indicate that dietary supplementation with long-term fermented miso could exert chemopreventive effects on lung carcinogenesis.


UDP-glucuronosyltransferase (UGT) 2B15 pharmacogenetics: UGT2B15 D85Y genotype and gender are major determinants of oxazepam glucuronidation by human liver.
Oxazepam is a commonly used 1,4-benzodiazepine anxiolytic drug that is polymorphically metabolized in humans. However, the molecular basis for this phenomenon is currently unknown. We have previously shown that S-oxazepam glucuronide, the major oxazepam metabolite, is selectively formed by UDP-glucuronosyltransferase (UGT) 2B15, whereas the minor R-oxazepam glucuronide is produced by multiple UGTs other than UGT2B15. Phenotype-genotype studies were conducted using microsomes and DNA prepared from the same set of 54 human livers. Sequencing of the UGT2B15 gene revealed three nonsynonymous polymorphisms, D85Y, T352I, and K523T, with variant allele frequencies of 0.56, 0.02, and 0.40, respectively. D85Y genotype showed a significant effect (p = 0.012) on S-oxazepam glucuronidation with lower median activities in 85Y/Y livers (49 pmol/min/mg protein) compared with 85D/D livers (131 pmol/min/mg), whereas 85D/Y livers were intermediate in activity (65 pmol/min/mg). There was also a significant trend (p = 0.049) for higher S-oxazepam activities in the two 352T/I livers (135 and 210 pmol/min/mg) compared with the remaining 352T/T livers (median, 64 pmol/min/mg). Conversely, K523T genotype had no apparent effect on oxazepam glucuronidation (p > 0.05). Donor gender also significantly influenced S-oxazepam glucuronidation with higher median activities in male (65 pmol/min/mg) compared with female (39 pmol/min/ mg) livers (p = 0.042). R-Oxazepam glucuronidation was not affected by either genotype or gender (p > 0.05). In conclusion, gender and D85Y genotype are identified as major determinants of S-oxazepam glucuronidation by human liver and may explain in part polymorphic oxazepam glucuronidation by human subjects.


The impact of smoking in developing countries with special reference to Africa.
The health effects of smoking have been well documented in developed countries. This article highlights the impact of smoking and tobacco production on health and agricultural production in Africa. It shows that smoking represents an important current and future health risk to people in Africa, which will place stresses on the development of their health services. Tobacco production is shown to be associated with food imports, deforestation, and an economic dependence on transnational corporations. Possible solutions are proposed.


Colon injury following percutaneous endoscopic gastrostomy tube insertion.
Percutaneous endoscopic gastrostomy (PEG) is used to provide a safe route for enteral feeding. However, serious complications may occur during the procedure, such as transverse colon injuries. It can be difficult to diagnose a colon injury after the procedure in a patient with cobormidities. Herein, we present a case of transverse colon injury following insertion of a PEG tube, discuss the possible complications of PEG, and review the recent literature. This case demonstrates the importance of careful PEG tube insertion and close follow-up of the patient's clinical status after a PEG procedure.


Ewing Sarcoma-Derived Extracellular Vesicles Impair Dendritic Cell Maturation and Function.
Ewing sarcoma (EwS) is an aggressive pediatric cancer of bone and soft tissues characterized by scant T cell infiltration and predominance of immunosuppressive myeloid cells. Given the important roles of extracellular vesicles (EVs) in cancer-host crosstalk, we hypothesized that EVs secreted by EwS tumors target myeloid cells and promote immunosuppressive phenotypes. Here, EVs were purified from EwS and fibroblast cell lines and exhibited characteristics of small EVs, including size (100-170 nm) and exosome markers CD63, CD81, and TSG101. Treatment of healthy donor-derived CD33+ and CD14+ myeloid cells with EwS EVs but not with fibroblast EVs induced pro-inflammatory cytokine release, including IL-6, IL-8, and TNF. Furthermore, EwS EVs impaired differentiation of these cells towards monocytic-derived dendritic cells (moDCs), as evidenced by reduced expression of co-stimulatory molecules CD80, CD86 and HLA-DR. Whole transcriptome analysis revealed activation of gene expression programs associated with immunosuppressive phenotypes and pro-inflammatory responses. Functionally, moDCs differentiated in the presence of EwS EVs inhibited CD4+ and CD8+ T cell proliferation as well as IFNγ release, while inducing secretion of IL-10 and IL-6. Therefore, EwS EVs may promote a local and systemic pro-inflammatory environment and weaken adaptive immunity by impairing the differentiation and function of antigen-presenting cells.


Multifocal glioma of the brain. Case report.
A case is presented in which two separate concurrent astrocytomas of the brain in the same patient were successfully operated on. The patient has been followed for 3 years and remains well. The authors believe that the diagnosis of multifocal tumors can be established on clinical grounds when the tumors are remote from each other, and when there has been no recurrence of neoplasm between the lesions after a long follow-up period. It is felt that a more optimistic approach to the treatment of multifocal tumors may yield good results.


Predictors of opiate drug abuse during a 90-day methadone detoxification.
The behavioral circumstances related to opiate drug use were examined during a 90-day out-patient methadone detoxification. Seventy-one subjects (55 male and 16 female) were followed from the day of intake to treatment termination. Data were collected by means of a weekly structured interview. Questions were asked about each occasion of opiate use in the previous week with respect to time, source, cost, social circumstance, etc. Monitored urine samples were tested x 3/week to verify verbal reports. The study demonstrated beneficial effects of the detoxification treatment by showing dramatic decreases in rates and amounts of opiate drug use during treatment. The study also identified race (p less than .0008; t = -3.522; beta = -0.366), gender (p less than .0243; t = 2.305; beta = 0.222), and the number of opiate use episodes/week at baseline (p less than .0013; t = -3.364; beta = -0.338) as significant and independent predictors of treatment outcome. Current duration of regular and continuous opiate use was also found to be marginally significant. The overall regression was highly significant (p less than .0001; F = 9.176; df = 4,66). A second regression analysis with race, age, and gender excluded as independent variables was conducted in order to derive indices which were related to behavioral and environmental characteristics versus global physical/cultural identification. With race and gender removed, the overall regression was still highly significant, although less than a fifth of the variance was accounted for. The number of opiate use episodes/week at baseline and the total number of drug-related stimulus cue exposures at baseline were found to be independently significant variables in the analysis. Knowledge of the impact of such behavioral factors on the treatment process may enable us to better understand the role of environmental contributors to opiate use. Such information may also help us to direct our limited resources and to better focus our treatment interventions.


Hormonal and hemodynamic responses to vena caval obstruction in fetal sheep.
To test the hypothesis that ACTH and vasopressin responses are quantifiable as functions of induced changes in central venous or arterial pressures, we produced various degrees of vena caval obstruction in fetal sheep (118--134 days gestation). In seven experiments, vena caval obstruction increased heart rate 18 +/- 7 beats/min and carotid arterial oxygen saturation 8.4 +/- 2.1%, but did not alter any measured vascular pressure or hormones. More severe vena caval obstruction (n = 10) decreased mean arterial pressure 13 +/- 2 mmHg, central venous pressure 1.3 +/- 0.3 mmHg, and heart rate 47 +/- 12 beats/min, and increased fetal plasma ACTH 1,047 +/- 448 pg/ml, cortisol 4.4 +/- 2.2 ng/ml, and vasopressin 47.9 +/- 24.2 pg/ml, but did not alter 11-deoxycortisol. The stimulus increased plasma cortisol (radioimmunoassay after chromatography) 100% and "corticosteroids" (radiotransinassay without chromatography) 20%, demonstrating the nonlinear relationship between these two variables. End-inflation plasma ACTH and vasopressin concentrations were significantly related to the induced decreases in mean arterial and central venous pressures, suggesting that the hormonal responses to vena caval obstruction were mediated by cardiovascular mechanoreceptors. Plasma vasopressin concentrations were linearly related to plasma ACTH concentrations (4 = 0.94; P less than 0.001), suggesting parallel release of the two hormones.


The Budget Impact of Monoclonal Antibodies Used to Treat Metastatic Colorectal Cancer in Minas Gerais, Brazil.
Biological medicines have increased the cost of cancer treatments, which also raises concerns about sustainability. In Brazil, three monoclonal antibodies (mAbs)-bevacizumab, cetuximab, and panitumumab-are indicated for the treatment of metastatic colorectal cancer (mCRC) but not currently funded by the Unified Health System (SUS). However, successful litigation has led to funding in some cases. Our objective was to evaluate the budgetary impact of including the mAbs bevacizumab, cetuximab, and panitumumab in standard chemotherapy for the treatment of mCRC within the SUS of Minas Gerais (MG), Brazil. A budget impact analysis of incorporating mAbs as first-line treatment of mCRC in MG was explored. The perspective taken was that of the Brazilian SUS, and a 5-year time horizon was applied. Data were collected from lawsuits undertaken between January 2009 and December 2016, and the model was populated with data from national databases and published sources. Costs are expressed in $US. In total, 351 lawsuits resulted in funding for first-line treatment with mAbs for mCRC. The three alternative scenarios analyzed resulted in cost increases of 348-395% compared with the reference scenario. The use of panitumumab had a budgetary impact of $US103,360,980 compared with the reference scenario over a 5-year time horizon, and bevacizumab and cetuximab had budgetary impacts of $US111,334,890 and 113,772,870, respectively. The use of the anti-epidermal growth factor receptor (EGFR) mAbs (cetuximab and panitumumab) is restricted to the approximately 41% of patients with KRAS mutations, so the best cost alternative for incorporation would be the combination of panitumumab and bevacizumab, with a cost of approximately $US106 million. These results highlight the appreciable costs for incorporating bevacizumab, cetuximab, and panitumumab into the SUS. Appreciable discounts are likely to be necessary before incorporation of these mAbs is approved.


Identification and characterisation of tobacco microRNA transcriptome using high-throughput sequencing.
MicroRNAs (miRNAs) are post-transcriptional regulators that are involved in numerous biological processes in plants. In this study, we investigate miRNAs in Honghua Dajinyuan, an agronomically important species of tobacco in China. Here, we report a comprehensive analysis of miRNA expression profiles in the leaf, stem and root using a high-throughput sequencing approach. A total of 165 miRNAs, representing 55 conserved families, and 50 novel miRNAs, representing 19 families, were identified in three libraries. In addition, 12 miRNAs were randomly selected from a differentially expressed conserved miRNA family in three libraries with expression alterations and subjected to qRT-PCR validation. Of these, the expression level of nta-miR167d is highly enriched in the leaf tissue. In addition, the expression level of nta-miR319a is prominently enriched in the stem, while nta-miR160c is highly enriched in the root. Moreover, the target prediction showed that most of the targets coded for transcription factors that are involved in cellular and metabolic processes. GO analysis showed that most of the targets were involved in organelle function, served binding functions, and take part in cellular and metabolic processes. This study helps shed new light on understanding the role of miRNAs in different parts of the tobacco plant and adds a significant number of novel miRNAs to the tobacco miRNA transcriptome.


Pretibial mucin. Histologic patterns and clinical correlation.
We identified several patients with a histologic diagnosis of pretibial myxedema in whom thyroid disease was not found. The purpose of this study was to investigate if histologic characteristics can distinguish between pretibial mucinosis secondary to Graves' disease and that unassociated with thyroid disease. Biopsy specimens interpreted as compatible with pretibial myxedema were reviewed; these included 12 cases of pretibial mucinosis with documented Graves' disease, and six cases of pretibial mucinosis without evidence of Graves' disease. Ten specimens interpreted as compatible with stasis dermatitis were also evaluated for histologic characteristics, including the possible presence of mucin. Features that distinguish between pretibial mucinosis associated with Graves' disease and pretibial mucinosis without Graves' disease included preservation of a zone of normal-appearing collagen in the superficial papillary dermis (12/12 with Graves' disease, 0/6 without), mucin deposition in the reticular dermis (12/12 with Graves' disease, 0/6 without), lack of mucin deposition in the superficial papillary dermis (11/12 with Graves' disease, 1/6 without), angioplasia (2/12 with Graves' disease, 6/6 without), and the presence of hemosiderin (2/12 with Graves' disease, 6/6 without). Mucin deposition in the papillary dermis was found in six of 10 specimens interpreted as stasis dermatitis. There are patients with pretibial mucinosis in whom there is no thyroid disease. Specimens from patients without Graves' disease have features of stasis dermatitis in addition to mucinosis. We conclude that pretibial mucinosis may result from stasis or Graves' disease and that histologic differences allow for accurate differentiation.


Effect of infliximab on inflammatory bowel disease with Takayasu arteritis: case series and review of the literature.
Takayasu arteritis (TA) and inflammatory bowel disease (IBD) are chronic inflammatory disorders. The mechanisms underlying these diseases are not precisely known, but tumor necrosis factor alpha (TNF-α) is considered to have an important role in the pathophysiology of both TA and IBD. Simultaneous occurrence of both TA and IBD is rare. Our first case was a 42-year-old woman with TA and inflammatory bowel disease unclassified. The patient was refractory to treatment with an immunomodulator, and infliximab (IFX) was started. After starting IFX, clinical remission was achieved and maintained for 2 years. The second case was a 34-year-old woman with TA accompanied by Crohn's disease. Because her abdominal symptoms relapsed despite treatment with an immunomodulator, IFX was started. Both diseases were well controlled for 2 years by scheduled maintenance therapy with IFX. Relapse of the TA required increased doses of IFX at shorter intervals, which relieved her symptoms. Overall, we identified nine cases for which IFX was effective, including our 2 cases. They may demonstrate the efficacy of IFX for IBD with TA and emphasize the role of TNF-α in the pathophysiology.


Implementing Infection Control and Quality of Life Best Practices in Nursing Homes With Project ECHO: Protocol for a Patient-Centered Randomized Controlled Trial.
Nursing homes in the United States were devastated by COVID-19, with 710,000 cases and 138,000 deaths nationally through October 2021. Although facilities are required to have infection control staff, only 3% of designated infection preventionists have taken a basic infection control course prior to the COVID-19 pandemic. Most research has focused on infection control in the acute care setting. However, little is known about the implementation of infection control practices and effective interventions in nursing homes. This study utilizes Project ECHO (Extension for Community Health Outcomes), an evidence-based telementoring model, to connect Penn State University subject matter experts with nursing home staff and administrators to proactively support evidence-based infection control guideline implementation. Our study seeks to answer the research question of how evidence-based infection control guidelines can be implemented effectively in nursing homes, including comparing the effectiveness of two ECHO-delivered training interventions on key patient-centered outcomes such as reducing the number of residents with a COVID-19 diagnosis. A stratified cluster randomized design was utilized. Using a 1:1 ratio, we randomly assigned 136 nursing homes to ECHO or ECHO Plus arms. Randomization was stratified by geographic location, baseline COVID-19 infection rate, and facility capacity. The study had two phases. In phase one, completed in July 2021, nursing homes in both study arms received a 16-week infectious disease and quality improvement training intervention via real-time, interactive videoconferencing and the ECHO learning model. Phase one sessions were up to 90 minutes in duration. In phase two, completed in November 2021, the ECHO group was offered optional 60-minute office hours for 9 weeks and the ECHO Plus group received 9 weeks of 60-minute sessions on emerging topics and an additional 8-session refresher series on infection control. A total of 290 nursing home facilities were assessed for eligibility, with 136 nursing homes recruited and randomly assigned to ECHO or ECHO Plus. Guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework, we will simultaneously evaluate the study's effectiveness and implementation outcomes at baseline (intervention start date), and at 4, 6, 12, and 18 months. The primary outcome is the COVID-19 infection rate in nursing homes. Secondary outcomes include COVID-19 hospitalizations and deaths, flu-like illness, and quality of life. Surveys and interviews with participants will also provide data as to the adoption, implementation, and maintenance of best practices taught throughout ECHO sessions. A multipronged approach to improving infection control and emergency preparedness in nursing homes is important, given the toll that the COVID-19 pandemic has taken on residents and staff. The ECHO model has significant strengths when compared to traditional training, as it allows for remote learning delivered by a multidisciplinary team of experts, and utilizes case discussions that match the context and capacity of nursing homes. ClinicalTrials.gov NCT04499391; https://clinicaltrials.gov/ct2/show/NCT04499391.


Same Chemotherapy Regimen Leads to Different Myelotoxicity in Different Malignancies: A Comparison of Chemotherapy-Associated Myelotoxicity in Patients With Advanced Ovarian and Non-Small-Cell Lung Cancer.
Carboplatin-paclitaxel chemotherapy combination is the standard first-line treatment of advanced ovarian cancer and is the most commonly used treatment combination shown to be effective in advanced non-small-cell lung cancer (NSCLC). The most important dose-limiting side effect is hematologic toxicity. In this study, the severity of treatment-related myelotoxicity is compared in patients with advanced ovarian and lung cancers who received same schedule of carboplatin-paclitaxel. The study was prospectively performed from February 2009 to July 2011 and involved 103 patients with stages Ic-IV ovarian (n = 51) and advanced NSCLC (n = 52) who were administered a maximum of 6 cycles of carboplatin-paclitaxel as a first-line treatment. Full blood counts were measured before treatment, before each chemotherapy cycle during therapy, and at the first and sixth month after therapy. The median ages were 59 years (range, 35-77 years) for patients with NSCLC and 56 years (range, 38-75 years) for patients with ovarian cancer. The frequencies of anemia were 17% and 28.6% before the initiation of chemotherapy, 39.2% and 68.0% at the third cycle of treatment, and 44.2% and 45.2% at the sixth cycle of treatment in patients with NSCLC and ovarian cancer, respectively. Initial leukopenia rates were 3.4% and 0%; at the third cycle 46.0% and 41.2%; and at the sixth cycle 41.9% and 48.8% in patients with NSCLC and ovarian cancer, respectively. At the third cycle, 2.5% of the patients with NSCLC and 10.4% of the patients with ovarian cancer had thrombocytopenia, and at the sixth cycle, 23.3% of the patients with NSCLC and 25% of the patients with ovarian cancer had thrombocytopenia. Hemoglobin, leukocyte, and platelet values at the third cycle were significantly lower than those at admission in both cancer groups. Declines in hemoglobin levels in patients with NSCLC and in platelets in patients with ovarian cancer at the sixth cycle were statistically significant compared with the third cycle. In conclusion, the same schedule of chemotherapy may lead to different myelotoxicities in different types of cancer. These results should be taken into consideration in terms of supportive care and management of toxicity.