Hearing Sensation Changes When a Warning Predicts a Loud Sound in the False Killer Whale (Pseudorca crassidens).
Stranded whales and dolphins have sometimes been associated with loud anthropogenic sounds. Echolocating whales produce very loud sounds themselves and have developed the ability to protect their hearing from their own signals. A false killer whale's hearing sensitivity was measured when a faint warning sound was given just before the presentation of an increase in intensity to 170 dB. If the warning occurred within 1-9 s, as opposed to 20-40 s, the whale showed a 13-dB reduction in hearing sensitivity. Warning sounds before loud pulses may help mitigate the effects of loud anthropogenic sounds on wild animals.


[Screening and identification of phage-displayed polypeptides specifically binding to human gastric cancer with high metastatic potential to peritoneum].
By means of phage-display technique, to screen polypeptides that specifically bind to human gastric cancer with high metastatic potential to peritoneum. Two human gastric cancer cell lines were used: GC9811-P with high metastatic potential to peritoneum and its wild type parental GC9811, to carry out subtractive screening with a phage display-12 peptide library. After three rounds of screening, 40 phage clones bond to GC9811-P cells were randomly selected. When injected into the peritoneal cavity of nude mice, 6 of the 40 clones did not bind to mouse peritoneum as examined by immunohistochemical staining. They were considered to be capable of binding specifically to GC9811-P cells. Sequence analysis revealed two different exogenous peptides: TLNINRLILPRT and SMSI(X)SPYI(XXX). Two peptides have been obtained that specifically bind to a gastric cancer cell variant GC9811-P, which easily disseminates to the peritoneum. Whether or not they could block GC9811-P metastasis to peritoneum in vivo remains to be determined.


Initial report of KSCC0803: feasibility study of capecitabine as adjuvant chemotherapy for stage III colon cancer in Japanese patients.
A prospective feasibility study was planned to clarify the proportion of compliance and adverse events in the administration of capecitabine as adjuvant chemotherapy for colon cancer in Japanese patients. We aimed initially to register 92 cases of R0 stage III colon cancer. Capecitabine (2,500 mg/m(2)/day) was given orally on days 1-14 every 3 weeks for 8 cycles. The proportion of treatments completed as planned was selected as the primary endpoint. Ninety-seven cases were registered and treated between September 2008 and August 2009. The proportion of treatments completed in the full analysis set was 64/97 [66.0%; 95% confidence interval (CI), 55.7-75.3%] and in the per protocol set was 64/91 (70.3%; 95% CI, 59.8-79.5%). Adverse events which led to treatment discontinuation included hand-foot syndrome (HFS) (7), haematotoxicity (5) and increased hepatic damage (4). The proportions of patients with major grade 3/4 adverse events were HFS 22.7%, neutropenia 7.2%, diarrhoea 2.1%, and increased bilirubin 0.0%. This collaborative multi-facility study, the first of its kind in Japan, presented results of a safety confirmation experiment on capecitabine as adjuvant chemotherapy for stage III colon cancer. The results suggest that capecitabine may be administered safely to Japanese patients.


Curative and preventive treatment of uncomplicated malaria in public health institutions in Cameroon.
Chloroquine-resistant Plasmodium strains are found in certain foci in Cameroon. We do not know what contribution drug prescriptions and drug pressure had in bringing this about. We contacted 66 persons (39 doctors and 27 nurses) who prescribe antimalarial drugs in Cameroon regarding their prescription habits; 46 (69.7%) responded. The three most prescribed drugs for uncomplicated malaria were quinine (84.4%), chloroquine (80.4%) and amodiaquine (80.4%). The most common reason for prescribing the drugs was availability. The drug of choice for the treatment of uncomplicated malaria was chloroquine with amodiaquine and quinine being second best for doctors and nurses, respectively. The form of treatment preferred by most doctors (ie 46%) was tablets while most nurses (42%) preferred injections. Prophylatic antimalarials were prescribed by 73% of the doctors and by 83% of the nurses. Doctors prescribed mainly to children and pregnant women while nurses prescribed to everyone. The drugs used were chloroquine, amodiaquine, quinine and pyrimethamine. Ten doctors and four nurses had encountered at least one case of drug resistant malaria. The most common evidence on which the diagnosis had been based was the absence of improvement on the treatment prescribed. The implicated drugs were chloroquine, amodiaquine and quinine. There was evidence of major differences in the practice of the respondents regarding treatment, prophylaxis and the diagnosis of drug resistance. These results indicate an urgent need for a national antimalarial drug policy in Cameroon.


Differential expression of serum proteins before 20 weeks gestation in women with hypertensive disorders of pregnancy: A potential role for SH3BGRL3.
The objective of this study was to explore serum levels of differentially abundant proteins between women with hypertensive disorders of pregnancy (HDP) and women with normal-term pregnancy, and to explore the contribution of SH3BGRL3 to the pathogenesis of HDP. At 6-20 weeks gestation 48 pregnant women who later developed HDP (HDP group) and 48 women with normal-term pregnancy (normal group) were recruited based on maternal age and gestational age at a 1:1 ratio. Total serum protein was extracted, denatured, deoxidized, and subjected to enzymolysis. The sample was labeled with Tandem Mass Tags and analyzed via mass spectroscopy to identify differentially abundant proteins. The role of SH3BGRL3 in trophoblast invasion, proliferation and apoptosis was examined using the HTR-8/SVneo cell line and primary isolates of extravillous trophoblast (EVT) cells. In the proteomic profiling analysis, there were 19 proteins that showed significant differential abundance (P < 0.05). Among them, 13 proteins were more abundant and 6 proteins were less abundant in the serum from the HDP group compared with the normal group. The function of one of the more abundant proteins, SH3BGRL3, in trophoblast cell invasion, proliferation and apoptosis was investigated. Treatment of the EVT cells or the HTR-8/SVneo cell line with anti-SH3BGRL3 inhibited proliferation, but stimulated both apoptosis and invasion. MMP2 and p-ERK levels were also decreased in EVT after anti-SH3BGRL3 treatment. The SH3BGRL3 protein can regulate various aspects of trophoblast biology, and may be useful in the clinical diagnosis of HDP.


The shape of the glucose response curve during an oral glucose tolerance test heralds β-cell function in a large Chinese population.
The shape of the glucose response curve during an oral glucose tolerance test (OGTT) can predict β-cell function and insulin resistance. However, there have been few studies conducted on Chinese people. Thus, we aimed to verify the usefulness of the glucose response curve in a large Chinese population. A total of 9059 OGTT (3-h tests) were categorized into either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, the Matsuda Index, the insulinogenic index, and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. The shape of the OGTT glucose response curve was monophasic in 87.3% and multiphasic in 12.7% of participants. Individuals in the multiphasic group were younger compared to those in the monophasic group (38.6 ± 13.6 vs. 35.4 ± 13.5, P < 0.001). Individuals in the monophasic group had significantly higher fasting plasma glucose (FPG 5.6 ± 13.5 vs. 5.2 ± 0.6, P < 0.001), fasting insulin (FINS 14.8 ± 8.7 vs. 13.5 ± 7.9, P < 0.01), and homeostasis model assessment of insulin resistance (HOMA-IR 3.8 ± 2.6 vs. 3.1 ± 2.0, P < 0.001) and impaired β-cell function (disposition index 12.7 ± 14.1 vs. 16.6 ± 17.8, P < 0.001) compared to those in the multiphasic group. The monophasic OGTT glucose response curve could reflect impaired β-cell function in a large Chinese population.


High-performance vector bending and orientation distinguishing curvature sensor based on asymmetric coupled multi-core fibre.
Fibre optic technology is rapidly evolving, driven mainly by telecommunication and sensing applications. Excellent reliability of the manufacturing processes and low cost have drawn ever increasing attention to fibre-based sensors, e.g. for studying mechanical response/limitations of aerospace composite structures. Here, a vector bending and orientation distinguishing curvature sensor, based on asymmetric coupled multi-core fibre, is proposed and experimentally demonstrated. By optimising the mode coupling effect of a seven core multi-core fibre, we have achieved a sensitivity of - 1.4 nm/° as a vector bending sensor and - 17.5 nm/m-1 as a curvature sensor. These are the highest sensitivities reported so far, to the best of our knowledge. In addition, our sensor offers several advantages such as repeatability of fabrication, wide operating range and small size and weight which benefit its sensing applications.


How to Review a Surgical Scientific Paper: A Guide for Critical Appraisal.
It is important for surgeons to participate in the peer-review process of scientific literature. As the number of published manuscripts continues to increase, there is a great need for volunteerism in this arena. However, there is little formal or informal training, which can help surgeons provide unbiased and meaningful reviews. Therefore, it is critical to provide more resources and guidelines to aid surgeons during the review process. The purpose of this paper is to provide a structured guide for a quality review of a surgical paper. This review represents the work of the Association of Women Surgeons Publications Committee.


Functional specialization of CK2 isoforms and characterization of isoform-specific binding partners.
In mammals, protein kinase CK2 has two isozymic forms of its catalytic subunit, designated CK2alpha and CK2alpha'. CK2alpha and CK2alpha' exhibit extensive similarity within their catalytic domains but have completely unrelated C-terminal sequences. To systematically examine the cellular functions of each CK2 isoform in mammalian cells, we have generated human osteosarcoma U2-OS cell lines with the expression of active or inactive versions of each CK2 isoform under the control of an inducible promoter. Examination of these cell lines provides evidence for functional specialization of CK2 isoforms at the cellular level in mammals with indications that CK2alpha' is involved in the control of proliferation and/or cell survival. To understand the molecular basis for functional differences between CK2alpha and CK2alpha', we have undertaken studies to identify proteins that interact specifically with each isoform of CK2 and could contribute to the regulation of their independent functions. A novel pleckstrin-homology domain containing protein, designated CK2-interacting protein 1 (i.e. CKIP-1) was isolated using the yeast two hybrid system as a protein that interacts with CK2alpha but not CK2alpha'. When expressed in cells as a fusion with green fluorescent protein, CKIP-1 localizes to the cell membrane and to the nucleus. In this study, we present evidence from deletion analysis of CKIP-1 suggesting that a C-terminal region containing a putative leucine zipper has a role in regulating its nuclear localization. Collectively, our data supports a model whereby CKIP-1 is a non-enzymatic regulator of CK2alpha that regulates the cellular functions of CK2alpha by targeting or anchoring CK2alpha to specific cellular localization or by functioning as an adapter to integrate CK2alpha-mediated signaling events with components of other signal transduction pathways.


Backbone and side-chain 13C and 15N signal assignments of the alpha-spectrin SH3 domain by magic angle spinning solid-state NMR at 17.6 Tesla.
The backbone and side-chain 13C and 15N signals of a solid 62-residue (u-13C,15N)-labelled protein containing the alpha-spectrin SH3 domain were assigned by two-dimensional (2D) magic angle spinning (MAS) 15N-13C and 13C-13C dipolar correlation spectroscopy at 17.6 T. The side-chain signal sets of the individual amino acids were identified by 2D 13C-13C proton-driven spin diffusion and dipolar recoupling experiments. Correlations to the respective backbone nitrogen signals were established by 2D NCACX (CX=any carbon atom) experiments, which contain a proton-nitrogen and a nitrogen-carbon cross-polarisation step followed by a carbon-carbon homonuclear transfer unit. Interresidue correlations leading to sequence-specific assignments were obtained from 2D NCOCX experiments. The assignment is nearly complete for the SH3 domain residues 7-61, while the signals of the N- and C-terminal residues 1-6 and 62, respectively, outside the domain boundaries are not detected in our MAS spectra. The resolution observed in these spectra raises expectations that receptor-bound protein ligands and slightly larger proteins (up to 20 kDa) can be readily assigned in the near future by using three-dimensional versions of the applied or analogous techniques.


First theophylline-based ratiometric fluorescent synthetic receptor for selective recognition of dihydrogenphosphate and biological phosphate ions.
We have developed a new ratiometric fluorescent chemosensor 1 based on xanthine alkaloid theophylline moiety for the detection of dihydrogen phosphate and ATP. The chemosensor 1 selectively recognizes tetrabutylammonium dihydrogen phosphate in CH(3)CN/H(2)O (9:1) by exhibiting a significant decrease in the emission of naphthalene and its sensing properties regarding ATP and other related phosphate species were evaluated. The anion binding properties of 1 were evaluated by (1)H NMR, UV-vis, and fluorescence spectroscopic methods.


Rapid and persistent loss of TXNIP in HT22 neuronal cells under carbonyl and hyperosmotic stress.
Thioredoxin interacting protein (TXNIP) binds to thioredoxin thereby limiting its activity, but it also promotes internalization of glucose transporters, participates in inflammasome activation, and controls autophagy. Published data and this work demonstrate that TXNIP responds to a number of apparently unrelated stresses, such as serum deprivation, pH change, and oxidative, osmotic and carbonyl stress. Interestingly, we noticed that hyperosmotic (NaCl) and carbonyl (methylglyoxal, MGO) stresses in HT22 neuronal cells produced a rapid loss of TXNIP (half-life ∼12 min), prompting us to search for possible mechanisms controlling this TXNIP loss, including pH change, serum deprivation, calcium metabolism and inhibition of the proteasome and other proteases, autophagy and MAPKs. None of these routes stopped the TXNIP loss induced by hyperosmotic and carbonyl stress. Besides transcriptional, translational and microRNA regulation, there is evidence indicating that mTOR and AMPK also control TXNIP expression. Indeed, AMPK-deficient mouse embryonic fibroblasts failed to respond to phenformin (AMPK activator) and compound C (AMPK inhibitor), while rapamycin induced a marked increase in TXNIP levels, confirming the known AMPK/mTOR control over TXNIP. However, the TXNIP loss induced by NaCl or MGO were observed even in AMPK deficient MEFs or after mTOR inhibition, indicating AMPK/mTOR does not participate in this rapid TXNIP loss. These results suggest that rapid TXNIP loss is a general and immediate response to stress that can improve energy availability and antioxidant protection, eventually culminating in better cell survival.


Fast determination of 24 steroid hormones in river water using magnetic dispersive solid phase extraction followed by liquid chromatography-tandem mass spectrometry.
The easiness-to-handle of the magnetic dispersive solid phase extraction (Mag-dSPE) procedure was developed for preconcentration of 24 steroid hormones in river water. Ethylenediamine-functionalized magnetic carbon nanotubes (EDA@Mag-CNTs) were synthesised by a simple one-pot reaction and were used as sorbent in Mag-dSPE procedure. The properties of the EDA@Mag-CNTs were characterized by transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). An ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) method for determination of 24 steroid hormones in river water at nanograms per liter had been developed with pretreatment of the samples by Mag-dSPE. The obtained results demonstrated the higher extraction capacity of EDA@Mag-CNT Mag-dSPE with recoveries between 82.1 and 113%. The limits of quantification (LOQs) for the steroid hormone were between 0.020 and 1.00 ng/L. The developed method had been successfully applied to 60 river water samples, and it was confirmed that EDA@Mag-CNT Mag-dSPE was a highly effective extraction method for the steroid hormone analyses.


An unconventional vertical fluidic-controlled wearable platform for synchronously detecting sweat rate and electrolyte concentration.
Epidermal microfluidic devices with long microchannels have been developed for continuous sweat analysis, which are crucial to assess personal hydration status and underlying health conditions. However, the flow resistance in long channels and the ionic concentration variation significantly affect the accuracy of both the sweat rate and electrolyte concentration measurements. Herein, we present a novel fluidic-controlled wearable platform for synchronously dropwise-detecting the sweat rate and total electrolyte concentration. The unconventional platform consisting of a vertically shortened channel, a pair of embedded electrodes and an absorption layer, is designed to minimize the flow resistance and transform sweat fluidics into uniform micro-droplets for chronological and dropwise detection. Real-time sweat conductance is decoupled from a square-wave-like curve, where the sweat rate and electrolyte concentration can be derived from the interval time and peak value, respectively. Flexible and wearable band devices are demonstrated to show their potential application for hydration status assessment during exercises.


Poly(propylene fumarate)/(calcium sulphate/beta-tricalcium phosphate) composites: preparation, characterization and in vitro degradation.
This study aimed to prepare a poly(propylene fumarate)/(calcium sulphate/beta-tricalcium phosphate) (PPF/(CaSO(4)/beta-TCP)) composite. We first examined the effects of varying the molecular weight of PPF and the N-vinyl pyrrolidinone (NVP) to PPF ratio on the maximum cross-linking temperature and the composite compressive strength and modulus. Then the in vitro biodegradation behaviour of PPF/(CaSO(4)/beta-TCP) composites was investigated. The effects of varying the molecular weight of PPF, the NVP/PPF ratio and the CaSO(4)/beta-TCP molar ratio on the weight loss and the composite compressive strength and modulus were examined. The cross-linking temperature, which increased with increasing molecular weight of PPF and NVP/PPF ratio, ranged from 41 to 43 degrees C for all formulations. The mechanical properties were increased by a decrease in the NVP/PPF ratio. For all formulations, the compressive strength values fell between 12 and 62 MPa, while the compressive modulus values fell between 290 and 1149 MPa. The weight loss decreased either with increasing molecular weight of PPF or with decreasing NVP/PPF ratio and CaSO(4)/beta-TCP molar ratio during degradation. The compressive strength and modulus increased with decreasing NVP/PPF ratio or decreasing CaSO(4)/beta-TCP ratio. The greatest weight loss over 6 weeks was 14.72%. For all formulations, the compressive modulus values fell between 57 and 712 MPa and the compressive strength fell between 0.5 and 21 MPa throughout 6 weeks degradation. Scanning electron microscopy and X-ray diffraction analysis of the PPF/(CaSO(4)/beta-TCP) composites demonstrated that hydroxyapatite was deposited on the surface of CaSO(4)/beta-TCP granules during degradation.


Differential regulation of the estrogen receptor mRNA by estradiol in the trout hypothalamus and pituitary.
In an attempt to understand the molecular mechanisms by which steroids can modulate brain functions in fish, we first localized the cells which produce estrogen receptor mRNA in the rainbow trout forebrain (Salbert et al., 1991). We now report how estradiol itself can alter the estrogen receptor mRNA content of these cells in a sterile strain of female rainbow trout. We also examined liver and pituitary levels of the estrogen receptor mRNA under the same estrogenic treatment. As revealed by slot blot and in situ hybridisations, a single injection (1.5 mg/kg) of estradiol can induce a strong increase (about five-fold) in the estrogen receptor mRNA levels in the liver, as well as a moderate increase (about two-fold) in two nuclei of the hypothalamus/preoptic area: the nucleus lateralis tuberis and the nucleus preopticus periventricularis. Conversely, no modifications of these levels were observed in the pars intermedia and the proximal pars distalis of the pituitary. Moreover, a comparison between estrogen receptor mRNA levels in the brain of sexually active female trout and in the brain of these sterile animals revealed that, in these latter, estrogen receptor mRNA levels are lower but can be increased by a single estradiol injection and reached the levels observed in mature females.


[The consensus of the Portuguese Society of Andrology, Sexual Medicine and Reproduction on Male HPV: diagnosis].
HPV infection affects about 50% of sexually active individuals at least once in a lifetime. Diagnosis is made on careful inspection of the genital area and can be divided into benign lesions (genital warts or condyloma acuminatum) and pre-malignant lesions (intraepithelial neoplasia) that can lead to cancer (invasive neoplasia). Diagnostic recommendations are reviewed in Male, Female, Couple and in the immunocompromised host. Recent histological concepts are also discussed.


Apigenin suppresses mycoplasma-induced alveolar macrophages necroptosis via enhancing the methylation of TNF-α promoter by PPARγ-Uhrf1 axis.
Mycoplasma-associated pneumonia is characterized by severe lung inflammation and immunological dysfunction. However, current anti-mycoplasma agents used in clinical practice do not prevent dysfunction of alveolar macrophages caused by the high level of the cytokine tumor necrosis factor-α (TNF-α) after mycoplasma infection. Apigenin inhibits the production of TNF-α in variet inflammation associated disease. This study aimed to investigate apigenin's effect on mycoplasma-induced alveolar immune cell injury and the mechanism by which it inhibits TNF-α transcription. In this study, we performed a mouse model of Mycoplasma hyopneumoniae infection to evaluate the effect of apigenin on reducing mycoplasma-induced alveolar immune cell injury. Furthermore, we carried out transcriptome analysis, RNA interference assay, methylated DNA bisulfite sequencing assay, and chromatin immunoprecipitation assay to explore the mechanism of action for apigenin in reducing TNF-α. We discovered that M. hyopneumoniae infection-induced necroptosis in alveolar macrophages MH-S cells and primary mouse alveolar macrophages, which was activated by TNF-α autocrine. Apigenin inhibited M. hyopneumoniae-induced elevation of TNF-α and necroptosis in alveolar macrophages. Apigenin inhibited TNF-a mRNA production via increasing ubiquitin-like with PHD and RING finger domains 1 (Uhrf1)-dependent DNA methylation of the TNF-a promotor. Finally, we demonstrated that apigenin regulated Uhrf1 transcription via peroxisome proliferator activated receptor gamma (PPARγ) activation, which acts as a transcription factor binding to the Uhrf1 promoter and protected infected mice's lungs, and promoted alveolar macrophage survival. This study identified a novel mechanism of action for apigenin in reducing alveolar macrophage necroptosis via the PPARγ/ Uhrf1/TNF-α pathway, which may have implications for the treatment of Mycoplasma pneumonia.


[Treatment of sixty-one patients with coronary slow flow phenomenon by yiqi huoxue recipe combined Western drugs: a clinical research].
To observe the clinical efficacy of treating patients with coronary slow flow phenomenon by Yiqi Huoxue Recipe (YHR) combined Western drugs, thus providing clinical evidence for further studies. Totally 61 patients with coronary slow flow phenomenon were randomly assigned to the treatment group (31 cases) and the control group (30 cases). Patients in the control group were treated with basic treatment of Western medicine, while those in the treatment group were treated with basic treatment of Western medicine and YHR. The therapeutic course for all was two months. Clinical symptoms were observed, and electrocardiogram examinations taken, and left ventricular ejection fraction (LVEF) were evaluated before treatment and at two months after treatment. Patients' clinical symptoms and electrocardiogram examinations were significantly improved in the treatment group. Its effective rate of improved symptoms was 90.32% in the treatment group, superior to that in the control group (76.67%, P < 0.05). The effective rate of electrocardiogram examinations was 87.10% in the treatment group, superior to that in the control group (73.33%, P < 0.05). But there was no statistical difference in LVEF between the two groups (P > 0.05). YHR combined Western drugs could improve clinical symptoms and electrocardiographic ischemia in patients with coronary slow flow phenomenon.


Use of the Endoscopic Clipping Over the Scope Technique to Treat Acute Severe Lower Gastrointestinal Bleeding in the Colon and Anal Transition Zone.
Endoscopic treatment of lower gastrointestinal bleeding can be challenging. This article reports on the use of the endoscopic clipping over the scope technique to treat acute severe lower gastrointestinal bleeding. In particular, it describes the approaches and outcomes of using the technique for acute severe bleeding in the colon and the anal transition zone. The following synopsis is the one that you supplied, but lightly copyedited. Please confirm OK. Please note that the synopsis will appear in PubMed: Endoscopic treatment of lower gastrointestinal bleeding can be challenging. This article reports on the use of the endoscopic clipping over the scope technique to treat acute severe lower gastrointestinal bleeding. In particular, it describes the approaches and outcomes of using the technique for acute severe bleeding in the colon and the anal transition zone.


Strategies for New Skill Acquisition by Practicing Surgeons.
To understand how practicing surgeons utilize available training methods, which methods are perceived as effective, and important barriers to using more effective methods. Online survey designed to characterize surgeon utilization and perception of available training methods. Two large Midwestern academic health centers. 150 faculty surgeons. Nominal values were compared using a McNemar's Test and Likert-like values were compared using a paired t-test (IBM SPSS Statistics v. 21.0; New York, NY). Survey response rate was 81% (122/150). 98% of surgeons reported learning a new procedure or technology after formal training. Many surgeons reported scrubbing in expert cases (78%) and self-directed study (66%), while few surgeons (6%) completed a mini-fellowship. The modalities used most commonly were scrubbing in expert cases (34%) and self-directed study (27%). Few surgeons (7%) believed self-directed study would be most effective, whereas 31% and 16% believed operating under supervision and mini-fellowships would be most effective, respectively. Surgeons believed more effective methods "would require too much time" or they had "confidence in their ability to implement safely." Practicing surgeons use a variety of training methods when learning new procedures and technologies, and there is disconnect between commonly used training methods and those deemed most effective. Confidence in surgeon's ability was cited as a reason for this discrepancy; and surgeons found time associated with more effective methods to be prohibitive.


Ultrastructure of the ascospores of the new yeast genus Sporopachydermia Rodrigues de Miranda.
Development of the ascospores of Sporopachydermia lactativora and S. cereana was studied in ultrathin sections. The spores have a very thick wall consisting of a thin dark outer layer and a double light inner layer the outer part of which is very wide and often irregular. During germination, this part disappears, the outer dark layer breaks up and the inner part of the light layer remains around the protoplast during development to a vegetative cell.


Inter-institution preference-based variability of ejection fraction and volumes using quantitative gated SPECT with 99mTc-tetrofosmin: a multicentre study involving 106 hospitals.
Inter-institution reproducibility of gated SPECT quantification based on institutional preferences was evaluated. This sort of variability is crucial for a multicentre study when many hospitals are involved. A total of 106 institutes participated in this study and were grouped according to their use of five workstation types. Fifteen sets of 99mTc-tetrofosmin gated projection images with normal ejection fraction (EF) (approximately 70%, group A, n = 5), borderline low EF (approximately 50%, group B, n = 5) and low EF with large perfusion defects (approximately 30%, group C, n = 5) were prepared. The projection images were processed by QGS software in each institute based on its own routine settings. Based on 318 QGS results, the reproducibility of EF and volumes was analysed for each group and workstation. The reproducibility of EF was good in 14 of 15 cases, showing a standard deviation (SD) of <3.6%, and the coefficient of variance of the end-diastolic volume (EDV) was <9.3% in all cases. When the deviation from the average value was analysed, the difference between EF at each institute and the average EF of the workstation (dEF) showed an SD of 2.2-3.7% for each group. The ratio of the EDV divided by the average EDV (rEDV) showed an SD of 0.061-0.069 for each group. One case in group C that had a large anterior defect with low EF showed bimodal EF distribution in one of the five workstations. The SD of EF was workstation dependent, owing to the SPECT reconstruction conditions. The reproducibility in EF and volumes within a workstation was good, even though the gated SPECT preferences varied. This reproducibility study supports the use of gated SPECT as a standard of ventricular function in multicentre studies.


Outcome of Combined Mitral and Aortic Valve Replacement in Adults With Mucopolysaccharidosis (the Hurler Syndrome).
We describe 2 adult sisters with type I mucopolysaccharidosis (MPS) who underwent combined mitral and aortic valve replacement for mitral and aortic valve stenosis. One died early postoperatively and the other survived but had a repeat double-valve replacement 1 month after the first. We analyzed previously reported patients with MPS and valve replacement to learn of their outcomes. The study of our 2 patients and those previously reported suggests that valve replacement in patients with MPS should be viewed with extreme caution.


Collagen-related gene expression level predicts the prognosis and immune therapy response.
Gastric cancer patients responded differently to the same treatment strategy and had various prognoses for the lack of biomarkers to guide the therapy choice. RNA data of a local gastric cancer cohort with 103 patients were processed and used to explore potential treatment guiding factors. Cluster analysis was performed by non-negative matrix factorization. The expression level of collagen-related genes was evaluated by ssGSEA named collagen score (CS). Data from TCGA, ACRG, and an immune therapy cohort were utilized to explore prognosis and efficacy. Prognostic predictive power of CS was assessed using the nomogram. In our study, local RNA data were processed by cluster analysis, and it was found that cluster 2 contained a worse tumor infiltration status. The GSEA result showed that collagen-related pathways were differentially activated in two clusters. In TCGA and ACRG cohorts, the CS can be used as an independent prognostic factor (TCGA OS: p = 0.018, HR = 3.5; ACRG OS: p = 0.014, HR = 4.88). An immunotherapy cohort showed that the patients with higher CS had a significantly worse ORR (p = 0.0025). The high CS group contained several cell death pathways down-regulated and contained the worse tumor microenvironment. The nomogram demonstrated the survival prediction capability of collagen score. CS was verified as an independent prognostic factor and potentially reflected the therapeutic effect of immunotherapy. The CS could provide a new way to evaluate the clinical prognosis and response information helping develop the collagen-targeted treatment.


Effect of 4-hydroxynonenal, a product of lipid peroxidation, on NK susceptibility of human K562 target cells.
4-Hydroxynonenal (HNE) is one of the major breakdown products generated by lipid peroxidation of cellular membranes. The level of lipid peroxidation and the concentration of its products are inversely related to the rate of cell proliferation and directly related to the level of cell differentiation. It has been reported that HNE inhibits DNA synthesis, ornithine decarboxylase (ODC) activity and c-myc expression in different leukemic cells lines. It has also been demonstrated that HNE inhibits proliferation and induces differentiation in HL60 cell line. In the present study the effects of HNE, at concentrations close to those found in the normal tissues, on the NK susceptibility of human K562 target cells were analyzed. Repeated treatments at 45 minutes intervals with 1 microM HNE were performed to maintain the cells in the presence of the aldehyde for 12 hours. The effect of HNE was compared with that obtained in Haemin-treated cells. HNE causes a strong inhibition of cells growth (53% vs. 34% with Haemin) without affecting cell viability. We further investigated the NK susceptibility of K562 cell line upon in vitro treatment with HNE. Cytotoxic activity of mononuclear cells (MNC) from peripheral blood of healthy donors was determined by 4 hours Cr51-release assay. The results obtained, expressed in terms of percentage of specific lysis at different E:T ratios and in terms of KC (10(6)) at the E:T ratio of 50:1, show that HNE treatment of K562 cells leads to a marked reduction of susceptibility to NK cells; this decrease is very close to that found in the K562 cells treated with Haemin used as inducer. Similar results were obtained using MNC pre-treated with beta-interferon (IFN) as effector cells. MNC show a reduced capacity to lyse HNE-treated cells also under the enhancing cytolytic effect of IFN. These results are in line with data obtained with several common inducers of differentiation such as DMSO, retinoic acid or others.


Enteropeptidase levels in duodenal juice of normal subjects and patients with gastrointestinal disease.
Enteropeptidase, trypsin, and chymotrypsin activity in basal and secretin-stimulated duodenal juice of 20 normal adult volunteers and 15 patients with gastrotestinal disease were determined. All enzyme concentrations showed skew distributions, but fluctuations in the secretin-stimulated juices were less pronouced than in the basal secretions. Secretin administration had no influence on the release of enteropeptidase from human duodenal mucosa, but resulted in a very small increase in secretion of pancreatic enzymes. Six out of seven patients with chronic alcoholic pancreatitis or cancer of the pancreas exhibited highly significant elevations of enteropeptidase in their basal as well as secretin-stimulated duodenal juice. It is suggested that raised luminal enteropeptidase activity may be the result of pancreatic insufficiency or elevated blood glucagon concentrations.


Telomere length dynamics in human memory T cells specific for viruses causing acute or latent infections.
Declining telomere length (TL) is associated with T cell senescence. While TL in naïve and memory T cells declines with increasing age, there is limited data on TL dynamics in virus-specific memory CD4+ T cells in healthy adults. We combined BrdU-labeling of virus-stimulated T cells followed with flow cytometry-fluorescent in situ hybridization for TL determination. We analyzed TL in T cells specific for several virus infections: non-recurring acute (vaccinia virus, VACV), recurring-acute (influenza A virus, IAV), and reactivating viruses (varicella-zoster virus, VZV, and cytomegalovirus, CMV) in 10 healthy subjects. Additionally, five subjects provided multiple blood samples separated by up to 10 years. VACV- and CMV-specific T cells had longer average TL than IAV-specific CD4+ T cells. Although most virus-specific cells were CD45RA-, we observed a minor population of BrdU+ CD45RA+ T cells characterized by long telomeres. Longitudinal analysis demonstrated a slow decline in average TL in virus-specific T cells. However, in one subject, VZV reactivation led to an increase in average TL in VZV-specific memory T cells, suggesting a conversion of longer TL cells from the naïve T cell repertoire. TLs in memory CD4+ T cells in otherwise healthy adults are heterogeneous and follow distinct virus-specific kinetics. These findings suggests that the distribution of TL and the creation and maintenance of long TL memory T cells could be important for the persistence of long-lived T cell memory.


Ultrasound, CT, and MRI comparison in primary and secondary tumors of the liver.
Thirty-five patients with surgically removed or percutaneous biopsy-proven tumors were examined by ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). This retrospective study describes the appearance of the primary tumors and metastases and compares the sensitivity and specificity of the 3 imaging methods. Ultrasound, CT, and MRI examinations as well as clinical, operative, and/or histologic data were available for all 35 patients. Paramagnetic contrast agent gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) was used in 23 patients and a short TI inversion recovery MRI sequence was used in 23 patients, in addition to various spin echo MRI sequences. Thirteen patients were examined using both Gd-DTPA and the short TI inversion recovery sequence. Our comparative study--based on the following criteria: detection, size, location of the tumor, and portal vein involvement and bile duct dilatation--demonstrated an advantage of MRI over ultrasound in 16 of 35 cases, equal results in 17 of 35 cases and a disadvantage of MRI compared to ultrasound in 2 of 35 cases. With the identical criteria, MRI proved to be more informative than CT in 10 of 35 cases, equal in 21 of 35 cases, and less informative in 4 of 35 cases.


The role of histamine H(1) receptors in late-phase reaction of allergic conjunctivitis.
The role of histamine H(1) receptors in the late-phase reaction of allergic conjunctivitis was studied using histamine H(1) receptor-deficient mice. To clarify the eosinophil infiltration, which is a reliable indicator of late-phase reaction, eosinophil peroxidase activity in the conjunctiva was measured. Mice were actively immunized with ovalbumin, and conjunctivitis was induced by topical instillation of ovalbumin. A significantly high eosinophil peroxidase level in the conjunctiva was observed in sensitized wild-type mice, whereas sensitized histamine H(1) receptor-deficient mice showed no significant increase in the conjunctival eosinophil peroxidase level. In addition, the elevation of eosinophil peroxidase level observed in sensitized wild-type mice was significantly antagonized by pretreatment with anti-P-selectin antibody. From these findings, it was concluded that eosinophil infiltration into the conjunctival tissue in late-phase reaction of allergic conjunctivitis is mediated by P-selectin stored in endothelial cells via histamine H(1) receptors.


Region- and age-dependent alterations of glial-neuronal metabolic interactions correlate with CNS pathology in a mouse model of globoid cell leukodystrophy.
Globoid cell leukodystrophy (GLD) or Krabbe disease is a lysosomal storage disorder caused by genetic defects in the expression and activity of galactosylceramidase, a key enzyme in the catabolism of myelin-enriched sphingolipids. While there are several histologic, biochemical, and functional studies on GLD, correlations between morphologic and biochemical alterations in central nervous system (CNS) tissues during disease progression are lacking. Here, we combined immunohistochemistry and metabolic analysis using (1)H and (13)C magnetic resonance (MR) spectra of spinal cord, cerebellum, and forebrain to investigate glial-neuronal metabolic interactions and dysfunction in a GLD murine model that recapitulates the human pathology. In order to assess the temporal- and region-dependent disease progression and the potential metabolic correlates, we investigated CNS tissues at mildly symptomatic and fully symptomatic stages of the disease. When compared with age-matched controls, GLD mice showed glucose hypometabolism, alterations in neurotransmitter content, N-acetylaspartate, N-acetylaspartylglutamate, and osmolytes levels. Notably, age- and region-dependent patterns of metabolic disturbances were in close agreement with the progression of astrogliosis, microglia activation, apoptosis, and neurodegeneration. We suggest that MR spectroscopy could be used in vivo to monitor disease progression, as well as ex vivo and in vivo to provide criteria for the outcome of experimental therapies.


PET amyloid ligand [11C]PIB uptake and cerebrospinal fluid beta-amyloid in mild cognitive impairment.
In mild cognitive impairment (MCI), Alzheimer's disease (AD)-type cerebrospinal fluid (CSF) biomarker profiles predict rapid progression and conversion to AD. An increased brain amyloid burden in AD and MCI has been demonstrated with PET using [(11)C]PIB (Pittsburgh compound B). Little is known about the relationship between these biomarkers in MCI. We studied 15 patients with amnestic MCI and 22 controls with PET using [(11)C]PIB. In MCI patients, CSF levels of Abeta42, pTAU, totalTAU and the Abeta42/pTAU ratio were measured. In MCI patients, CSF Abeta42 was abnormal in 53% of patients, totalTAU in 67%, pTAU in 64% and the Abeta42/pTAU ratio in 64%. A composite neocortical [(11)C]PIB uptake score was increased in 87% of the MCI patients. Only 54% of [(11)C]PIB-positive subjects showed AD-type Abeta42 values. During a 2-year follow-up, 6 MCI patients converted to AD, all of them had increased neocortical PIB scores at the MCI stage. Abnormal CSF Abeta42 was found in 3 patients, pTAU in 3 patients and Abeta42/pTAU ratio in 4 patients. Follow-up studies are needed to confirm whether [(11)C]PIB uptake might be more sensitive than CSF Abeta42 concentration in detecting increased amyloid burden in MCI, as suggested by the results of this study.


Identification of supraventricular tachycardia mechanisms with surface electrocardiograms using a convolutional neural network.
It remains difficult to definitively distinguish supraventricular tachycardia (SVT) mechanisms using a 12-lead electrocardiogram (ECG) alone. Machine learning may identify visually imperceptible changes on 12-lead ECGs and may improve ability to determine SVT mechanisms. We sought to develop a convolutional neural network (CNN) that identifies the SVT mechanism according to the gold standard of SVT ablation and to compare CNN performance against experienced electrophysiologists among patients with atrioventricular nodal re-entrant tachycardia (AVNRT), atrioventricular reciprocating tachycardia (AVRT), and atrial tachycardia (AT). All patients with 12-lead surface ECG during sinus rhythm and SVT and had successful SVT ablation from 2013 to 2020 were included. A CNN was trained using data from 1505 surface ECGs that were split into 1287 training and 218 test ECG datasets. We compared the CNN performance against independent adjudication by 2 experienced cardiac electrophysiologists on the test dataset. Our dataset comprised 1505 ECGs (368 AVNRT, 304 AVRT, 95 AT, and 738 sinus rhythm) from 725 patients. The CNN areas under the receiver-operating characteristic curve for AVNRT, AVRT, and AT were 0.909, 0.867, and 0.817, respectively. When fixing the specificity of the CNN to the electrophysiologist adjudicators' specificity, the CNN identified all SVT classes with higher sensitivity: (1) AVNRT (91.7% vs 65.9%), (2) AVRT (78.4% vs 63.6%), and (3) AT (61.5% vs 50.0%). A CNN can be trained to differentiate SVT mechanisms from surface 12-lead ECGs with high overall performance, achieving similar performance to experienced electrophysiologists at fixed specificities.


The SIU medical curriculum: systemwide objectives-based instruction.
The Southern Illinois University School of Medicine has completed a five-year experience applying an objectives-based approach to an entire curriculum in a medical school setting. Approximately 250 students have worked and studied within the system, and three classes have been graduated. This paper describes the instructional system and the procedures for monitoring, maintaining, and improving it and provides available outcome data.


Further evidence for association of variants in the AKT1 gene with schizophrenia in a sample of European sib-pair families.
Involvement of AKT signaling pathways in schizophrenia has been recently suggested, on the basis of several lines of evidence. In addition to impairment of protein-levels and phosphorylation levels in the pathway, association of DNA sequence variants in the AKT1 gene with schizophrenia has been detected in a family sample. We investigated the reported association of DNA sequence variants in the AKT1 gene in a sample of 79 sib-pair families with schizophrenia using the five single nucleotide polymorphisms (SNPs) of the original study and two additional SNPs in the neighborhood of the SNP for which association had been reported. We obtained statistical significance for single markers (p = .002) and multilocus haplotypes (p = .0013) located in the same region as has been reported in the previous study. The replication of association of variants in the AKT1 gene in a family sample with similar ethnical background as in the original study adds further evidence for involvement of AKT1 in development of schizophrenic disorders.


Loss of HOXB3 correlates with the development of hormone receptor negative breast cancer.
The homeobox gene family, encoding a specific nuclear protein, is essential for embryonic development, differentiation, and homeostasis. The role of the HOXB3 protein varies in different tumors. This study aims to explore the role of the HOXB3 gene in breast cancer. Differentially expressed genes were screened by analyzing metastatic breast cancer gene chip data from TCGA and GEO databases. The function of the selected HOXB3 gene was also analyzed in different databases and through molecular biology methods, such as qRT-PCR, western blot and IF to verify bioinformatics findings. Both bioinformatics analyses and western blot showed that HOXB3 was lost in breast cancer compared to normal breast tissue. Survival analysis also showed that lower expression of HOXB3 was associated with poor prognosis. Bioinformatics analyses further showed that HOXB3 was positively correlated with hormone receptors. Metascape for GO analysis of GEO data provided possible mechanisms that HOXB3 could positively regulate cell adhesion, inhibit cell proliferation and activate immune response in breast cancer; moreover, GSEA included several cancer-associated pathways. In summary, HOXB3 expression was decreased in breast cancer, and it was associated with poor prognosis. It might become a new biomarker to predict prognosis of breast cancer.


Targeted heritable mutation and gene conversion by Cas9-CRISPR in Caenorhabditis elegans.
We have achieved targeted heritable genome modification in Caenorhabditis elegans by injecting mRNA of the nuclease Cas9 and Cas9 guide RNAs. This system rapidly creates precise genomic changes, including knockouts and transgene-instructed gene conversion.


Intermittent microalbuminuria in children with type 1 diabetes mellitus without clinical evidence of nephropathy.
Microalbuminura (MA) was determined in 127 children and adolescents (age 3-21 years) with type 1 (insulin-dependent) diabetes mellitus. Patients with clinical evidence of long-term complications or macroproteinuria were excluded. Urinary albumin excretion was measured in a nocturnal 12-h collection and correlated with the albumin/creatinine ratio of a urine sample freshly voided on the morning immediately following the collection. The patients were divided into group A (n = 83, age less than 16 years, duration of diabetes 1-13 years, mean 4.4) and group B (n = 44, age greater than 16 years, duration of diabetes 1-19 years, mean 8.7) and compared with appropriate controls. MA above 15 micrograms/min was present in 11 of 83 (13.3%) patients in group A and in 7 of 44 (15.9%) in group B. In a repeat urine collection at least 3 months later elevated MA persisted in 1 of 11 (group A) and in 4 of 7 (group B) patients. There was no correlation between increased MA in a 12-h urine collection and the albumin/creatinine ratio in a subsequently voided urine sample. MA was not strictly dependent on age, sex, duration of diabetes, haemoglobin A1, mean arterial blood pressure, plasma creatinine, creatinine clearance or serum beta-2-microglobulin. Further systematic studies and careful follow up are necessary to appraise whether intermittent MA is indeed an early manifestation of incipient kidney disease in children with type 1 diabetes.


Picomolar zinc binding modulates formation of Bcl10-nucleating assemblies of the caspase recruitment domain (CARD) of CARD9.
The caspase recruitment domain-containing protein 9 (CARD9)-B-cell lymphoma/leukemia 10 (Bcl10) signaling axis is activated in myeloid cells during the innate immune response to a variety of diverse pathogens. This signaling pathway requires a critical caspase recruitment domain (CARD)-CARD interaction between CARD9 and Bcl10 that promotes downstream activation of factors, including NF-κB and the mitogen-activated protein kinase (MAPK) p38. Despite these insights, CARD9 remains structurally uncharacterized, and little mechanistic understanding of its regulation exists. We unexpectedly found here that the CARD in CARD9 binds to Zn2+ with picomolar affinity-a concentration comparable with the levels of readily accessible Zn2+ in the cytosol. NMR solution structures of the CARD9-CARD in the apo and Zn2+-bound states revealed that Zn2+ has little effect on the ground-state structure of the CARD; yet the stability of the domain increased considerably upon Zn2+ binding, with a concomitant reduction in conformational flexibility. Moreover, Zn2+ binding inhibited polymerization of the CARD9-CARD into helical assemblies. Here, we also present a 20-Å resolution negative-stain EM (NS-EM) structure of these filamentous assemblies and show that they adopt a similar helical symmetry as reported previously for filaments of the Bcl10 CARD. Using both bulk assays and direct NS-EM visualization, we further show that the CARD9-CARD assemblies can directly template and thereby nucleate Bcl10 polymerization, a capacity considered critical to propagation of the CARD9-Bcl10 signaling cascade. Our findings indicate that CARD9 is a potential target of Zn2+-mediated signaling that affects Bcl10 polymerization in innate immune responses.


Low-dose radiotherapy for COVID-19 pneumonia treatment: case report, procedure, and literature review.
The COVID-19 pandemic outbreak has set the emergency services in developing countries on major alert, as the installed response capacities are easily overwhelmed by the constantly increasing high demand. The deficit of intensive care unit beds and ventilators in countries like Peru is forcing practitioners to seek preventive or early interventional strategies to prevent saturating these chronically neglected facilities. A 64-year-old patient is reported after presenting with COVID-19 pneumonia and rapidly progressing to deteriorated ventilatory function. Compassionate treatment with a single 1‑Gy dose to the bilateral whole-lung volume was administered, with gradual daily improvement of ventilatory function and decrease in serum inflammatory markers and oxygen support needs, including intubation. No treatment-related toxicity developed. Procedures of transport, disinfection, and treatment planning and delivery are described. Whole-lung low-dose radiotherapy seems to be a promising approach for avoiding or delaying invasive respiratory support. Delivered low doses are far from meeting toxicity ranges. On-going prospective trials will elucidate the effectiveness of this approach.


Connectomics: a new paradigm for understanding brain disease.
In recent years, pathophysiological models of brain disorders have shifted from an emphasis on understanding pathology in specific brain regions to characterizing disturbances of interconnected neural systems. This shift has paralleled rapid advances in connectomics, a field concerned with comprehensively mapping the neural elements and inter-connections that constitute the brain. Magnetic resonance imaging (MRI) has played a central role in these efforts, as it allows relatively cost-effective in vivo assessment of the macro-scale architecture of brain network connectivity. In this paper, we provide a brief introduction to some of the basic concepts in the field and review how recent developments in imaging connectomics are yielding new insights into brain disease, with a particular focus on Alzheimer's disease and schizophrenia. Specifically, we consider how research into circuit-level, connectome-wide and topological changes is stimulating the development of new aetiopathological theories and biomarkers with potential for clinical translation. The findings highlight the advantage of conceptualizing brain disease as a result of disturbances in an interconnected complex system, rather than discrete pathology in isolated sub-sets of brain regions.


Creatine kinase B suppresses ferroptosis by phosphorylating GPX4 through a moonlighting function.
Activation of receptor protein kinases is prevalent in various cancers with unknown impact on ferroptosis. Here we demonstrated that AKT activated by insulin-like growth factor 1 receptor signalling phosphorylates creatine kinase B (CKB) T133, reduces metabolic activity of CKB and increases CKB binding to glutathione peroxidase 4 (GPX4). Importantly, CKB acts as a protein kinase and phosphorylates GPX4 S104. This phosphorylation prevents HSC70 binding to GPX4, thereby abrogating the GPX4 degradation regulated by chaperone-mediated autophagy, alleviating ferroptosis and promoting tumour growth in mice. In addition, the levels of GPX4 are positively correlated with the phosphorylation levels of CKB T133 and GPX4 S104 in human hepatocellular carcinoma specimens and associated with poor prognosis of patients with hepatocellular carcinoma. These findings reveal a critical mechanism by which tumour cells counteract ferroptosis by non-metabolic function of CKB-enhanced GPX4 stability and underscore the potential to target the protein kinase activity of CKB for cancer treatment.


Auditory screening.
Hearing screening is one of the most viable techniques in the health screening arena. The procedures are sufficiently valid and flexible to meet the requisite goals at any age level. The yields are easily great enough to justify the relatively small expenditures for screening programs. When one considers that the proper identification of hearing loss can create fulfillment in life that would not otherwise have been possible, it is evident that these programs should be implemented universally.


Sudden death in athletes.
Competitive sports activity is associated with an increased risk of sudden cardiovascular death (SCD) in adolescents and young adults with clinically silent cardiovascular disorders. While in middle-aged/senior athletes atherosclerotic coronary artery disease accounts for the vast majority of SCDs, in young athletes the spectrum of substrates is wider and includes inherited (cardiomyopathies) and congenital (anomalous origin of coronary arteries) structural heart diseases. Inherited ion channel diseases have been implicated in SCDs occurring with an apparently normal heart at autopsy. Screening including the ECG allows identification of athletes affected by heart muscle diseases at a pre-symptomatic stage and may lead to reduction of the risk of SCD during sports. The use of modern criteria for interpretation of the ECG in the athlete offers the potential to improve the screening accuracy by reducing the number of false positives. Screening with exercise testing middle aged/senior athletes engaged in leisure sports activity is likely to be effective in patients with significant coronary risk factors, while it is not useful in low-risk subgroups. The availability of automated external defibrillator on the athletic field provides a "back-up" preventive strategy for unpredictable arrhythmic cardiac arrest, mostly occurring in patients with coronary artery diseases.


[Continuous local wound infusion with local anesthetics : For thoracotomy and major abdominal interventions].
Wound infusion with local anesthetics is a nearly 100 years old proven and secure analgesic method. Recently special wound infusion catheters have become available which can be placed intraoperatively into the wound under direct supervision of the surgeon to infuse local anesthetics and optimize postoperative analgesia. For thoracotomy this method was modified to improve its efficacy and the catheters are used to establish a continuous paravertebral intercostal nerve block (PVB). Many studies have confirmed the analgesic power of PVB which results in a pain reduction comparable to thoracic epidural analgesia (TEA) but without TEA-specific side-effects, in particular hypotension. The efficacy of continuous local wound infusion (CLWI) is less obvious for laparotomy. If fundamental preconditions for this loco-regional method are considered (indications, choice of catheter, local anesthetic dose) the laparotomy wound could also be suitable for the use of CLWI. According to the literature currently available CLWI is not associated with an increased risk of wound infections.


Electrophysiologic drug testing in symptomatic ventricular arrhythmias after repair of tetralogy of Fallot.
Nine patients with symptomatic ventricular arrhythmias were evaluated a mean interval of 16 years after surgical repair of tetralogy of Fallot. The clinical arrhythmia was sustained ventricular tachycardia (VT) in 4 patients (group I) and premature ventricular contractions in 5 (group II). All patients underwent cardiac catheterization and electrophysiologic studies. Ventricular tachycardia was induced at electrophysiologic study in all patients in group I and in 3 patients in group II. Six patients with inducible sustained monomorphic VT underwent chronic drug testing based on electrophysiologic study. A mean of 3.3 drugs per patient was tested. Patients with right ventricular systolic hypertension did not respond to any drug tested, and underwent surgery. Five patients received drug treatment based on the results of electrophysiologic study. During a mean follow-up period of 2.2 years, no patient in either group had recurrent episodes of VT or syncope. In the postoperative patient with tetralogy of Fallot with symptomatic ventricular arrhythmias, it is concluded that electrophysiologic study is useful in reproducing clinical episodes of VT and in selecting effective antiarrhythmic medication; a small number of patients with ventricular premature complexes alone will have inducible sustained VT during electrophysiologic study; prognosis of these patients may be improved by treatment that results in prevention of VT induction; and in patients with right ventricular hypertension, VT is likely to be refractory to drug treatment.


Implications and reflections on the 2010 Supreme Court ruling on Canada's AHR Act.
In December, 2010, Canada's 6 year old Assisted Human Reproduction Act was successfully challenged in the Supreme Court of Canada. There may be important implications for public health and the evolution of reproductive technologies in this country.


Vitamin D deficiency induces cardiac hypertrophy and inflammation in epicardial adipose tissue in hypercholesterolemic swine.
Vitamin D is a sectosteroid that functions through Vitamin D receptor (VDR), a transcription factor, which controls the transcription of many targets genes. Vitamin D deficiency has been linked with cardiovascular diseases, including heart failure and coronary artery disease. Suppressor of cytokine signaling (SOCS)3 regulates different biological processes such as inflammation and cellular differentiation and is an endogenous negative regulator of cardiac hypertrophy. The purpose of this study was to test the hypothesis that vitamin D deficiency causes cardiomyocyte hypertrophy and increased proinflammatory profile in epicardial adipose tissue (EAT), and this correlates with decreased expression of SOCS3 in cardiomyocytes and EAT. Eight female Yucatan miniswine were fed vitamin D-sufficient (900 IU/d) or vitamin D-deficient hypercholesterolemic diet. Lipid profile, metabolic panel, and serum 25(OH)D levels were regularly measured. After 12 months animals were euthanized and histological, immunohistochemical and qPCR studies were performed on myocardium and epicardial fat. Histological studies showed cardiac hypertrophy, as judged by cardiac myocyte cross sectional area, in the vitamin D-deficient group. Immunohistochemical and qPCR analyses showed significantly decreased mRNA and protein expression of VDR and SOCS3 in cardiomyocytes of vitamin D-deficient animals. EAT from vitamin D-deficient group had significantly higher expression of TNF-α, IL-6, MCP-1, and decreased adiponectin in association with increased inflammatory cellular infiltrate. Interestingly, EAT from vitamin D-deficient group had significantly decreased expression of SOCS3. These data suggest that vitamin D deficiency induces hypertrophy in cardiomyocytes which is associated with decreased expression of VDR and SOCS3. Vitamin D deficiency is also associated with increased inflammatory markers in EAT. Activity of VDR in the body is controlled through regulation of vitamin D metabolites. Therefore, restoration of VDR function by supplementation of VDR ligands in vitamin D-deficient population might be helpful in reducing inflammation and cardiovascular risk.


[Effects of diethyldithiocarbamate on ejaculatory inhibition and change in monoamine levels of accessory glands (author's transl)].
Effects of diethyldithiocarbamate(DDC) on erection and ejaculation were investigated and monoamine levels in central nervous system, gonad and accessory glands were determined in dogs. Intraperitoneal administration of 50, 75 and 100 mg/kg of DDC suppressed ejaculation 1 hour after administration, although penial erection did occur. This suppression of ejaculation was recovered to some extent 3 hours after DDC and completely recovered 24 hours after DDC. One hour after the administration of 100 mg/kg of DDC, noradrenaline (NA) level in the caudate and serotonin (5-HT) level in the posterior hypothalamus decreased significantly, as compared with the control. However, there were no significant changes in the regions of anterior hypothalamus and hippocampus which are known to play an important role in sexual behavior. In the epididymis, NA and adrenaline levels decreased significantly, though 5-HT levels increased, as compared with those of the control. In the prostate and posterior urethra, NA levels decreased significantly, as compared with the control. The seminal emission induced by hypogastric nerve stimulation induced a gradual rise in the posterior urethral pressure. When the pressure reached the maximum level, rhythmic alterations of the pressure considered to be a phenomenon associated with ejaculation occurred. DDC (100 mg/kg) abolished both seminal emission and rhythmic alterations of the posterior urethral pressure. These findings indicate that the sperm transport may be inhibited by decrease of NA level in accessory glands.


Interinstitutional agreement of individual functional independence measure (FIM) items measured at two sites on one sample of SCI patients.
Individual items of the Functional Independence Measure (FIM) were analyzed for interinstitutional agreement using a sample of 57 spinal cord injured (SCI) patients at discharge from an acute care rehabilitation setting (ACRS) and at admission to an ongoing rehabilitation setting (ORS). The two FIM ratings were performed within 6 days of each other. The reliability coefficient for total FIM scores was good: 0.83. Individual items were classified into four groups: (1) above average reliability coefficient, above average proportion agreement, which included the feeding items and items from the mobility category; (2) above average reliability coefficient, below average agreement, which included the majority of items in the selfcare category; (3) below average reliability coefficient, above average agreement, which included items in the sphincter control and communication categories; and (4) below average reliability coefficient, below average agreement, which included items in the social cognition category. Patients received significantly higher ratings on most selfcare items in the ACRS, and significantly higher ratings on social cognition items in the ORS. Implications of these results are discussed in terms of using individual FIM items for research purposes. Reliability coefficients were acceptably high for subgroups of complete and incomplete paraplegics and for complete quadriplegics, ranging from 0.74 to 0.87, but low for incomplete quadriplegics, r = 0.49. However, these sample sizes were small, ranging from 9 to 17 patients. Data collection will continue in order to increase sample size and permit further analysis of these subgroups.


Second primary cancer after liver transplantation in hepatocellular carcinoma: a nationwide population-based study.
The aim of this study is to evaluate prevalence of second primary cancer (SPC) among hepatocellular carcinoma (HCC) patients after liver transplantation (LT) by using nationwide claims data from South Korea. The nationwide cohort included patients who were diagnosed with HCC and received LT from 1 January 2010 to 31 December 2014. We analyzed frequency and standardized incidence ratios (SIRs) to estimate the risk of SPC in HCC patients after LT. A total of 2462 patients who were diagnosed with HCC and received LT were confirmed. Of these patients, 103 (4.2%) developed SPC after LT; the most common cancer site was lung (16.5%). Patients with HCC receiving LT had high risk of SPC [SIR 2.79, 95% confidence interval (CI) 2.27-3.38], particularly lymphoma (SIR 9.26), myeloma (SIR 10.60), and bladder cancer (SIR 7.19). The 12-, 24-, 36-, and 48-month overall survival for patients with HCC after LT was 92.7, 87.8, 84.6, and 82.1%, respectively. HCC patients with LT had longer life expectancy and higher risk for SPC compared with the general population. Therefore, close surveillance for SPC is important in patients with HCC receiving LT.


[Salter and Harris type-II distal femoral physeal fracture-separations at adolescent age: a new therapeutic approach (preliminary study)].
The prognosis of distal femoral physeal fracture-separation is poor in children. In adolescents, more than half of the cases are classified as Salter and Harris type-II. The gold-standard treatment for a displaced fracture combines anatomic reduction with internal fixation with a pin or screw, preserving the growth cartilage. Despite this treatment, the rate of mid- and long-term complications has been high in the literature, most problems being related to leg length discrepancy and misalignments (genu valgum and genu varum). In order to avoid these problems, for adolescents, we propose and osteosynthesis system which bridges the entire growth cartilage with a blade-plate. Depending on the bone age, puberty and thus potential for further growth, we combine this osteosynthesis with a contralateral distal femoral epiphysiodesis to prevent invalidating leg length discrepancy. We reviewed retrospectively the cases of 21 patients aged 11 to 15 years treated between 1990 and 2005 for Salter and Harris type-II distal femoral physeal fracture- separation. Clinical and radiographic outcome was compared between the 16 patients treated with the classical internal fixation system or cast immobilization and the five patients treated with a blade-plate. A complete physical examination was available for the follow-up in all cases. A full stance view was used for the radiographic analysis. The mean follow-up was 6.7 years (range 2-17), minimal two years. In patients treated with the classical fixation system or a plaster cast, four of 16 (25 %) developed frontal misalignment of more than 5 degrees and five of 16 (32 %) leg length discrepancy of more than 2cm. No misalignment or leg length discrepancy (>2cm) was observed among the five patients treated with a blade-plate. The results observed in our patients treated with the classical fixation systems are comparable with those reported by others. Our patients treated with the blade-plate system constitute the only series with no cases of frontal misalignment or invalidating leg length discrepancy after this type of fracture. We used contralateral distal femoral epiphysiodesis in all patients whose predictable leg length discrepancy at the end of growth was greater than 2cm, that is 11-3.5 years (bone age) in girls and 13-14.5 years in boys. Internal fixation techniques bridging the growth cartilage are the only techniques used for Salter and Harris type-II distal femoral physeal fracture-separation in adolescents which have been able to prevent posttraumatic knee misalignment (genu valgum or genu varum). Leg length discrepancy can be prevented by a contalateral distal femoral epiphysiodesis when the fracture occurs in a child or early puberty.


The impact of brachytherapy boost for anal canal cancers in the era of de-escalation treatments.
To analyze clinical outcomes of high-dose-rate (HDR) interstitial brachytherapy boost (ISBT) after external beam radiation therapy (EBRT) or chemoradiotherapy (CRT) for the treatment of anal canal cancers (ACC). A total of 78 patients with ACC were treated at our institution by ISBT. Local Control (LC), disease-free survival (DFS), overall survival (OS), colostomy-free survival (CFS) and toxicity rates were analyzed. With a median followup (FU) of 59.8 months (95% CI [55.8-64.2]), six (7.7%) local recurrences with 2 patients (2.6%) having persistent disease at 3 months were observed. The 5-year rate of LC for the entire population was 92% [83-96%]. The 5-year DFS rate was 86% [76-93%]. The 5-year OS was 96% [88-99%]. In the univariate analysis, chemotherapy was significantly associated with morbidity grade ≥2. Late digestive toxicity grade ≥3 was reported in 8.9% patients, 1 patient underwent colostomy due to toxicity. The 5-year CFS rate was 88% [79-94%]. HDR interstitial brachytherapy boost provide excellent rates of tumor control and colostomy-free survival with a favorable profile of GI toxicity. Continence in anal cancer survivors is a challenge and the boost technique must be discussed in a multidisciplinary approach as part of de-escalation treatments.


Computed tomography of adrenal abscess.
We present a patient with a progressively enlarging adrenal mass detected by CT which extended to the renal hilum and inferior vena cava. Pathologic evaluation revealed an adrenal abscess containing purulent debris.


Prophylactic consequences of sodium salicylate nanoparticles in cisplatin-mediated hepatotoxicity.
Unintended side effects linked to the antineoplastic drug cisplatin are a major drawback in its clinical application. The underlying source of these side effects include the generation of reactive oxygen species which are toxic and damaging to tissues and organs. In the present study the anti-inflammatory and antioxidant potential of sodium salicylate was assessed against cisplatin-induced hepatotoxicity in albino rats. Sodium salicylate was used as a model drug and loading into hollow structured porous silica using ultrasound-assisted sol-gel method to produce a nanoemulsion. Transmission Electron Microscopy and Dynamic Light scattering analysis were employed to assess the structural properties and stability of this model. Liver function was assessed by measuring biomarkers including ALT, AST & GGT and oxidant/antioxidant markers including MDA, NO, PON, GSH, MCP1 & AVP in serum or liver tissue. Additionally, blood leukocyte DNA damage was evaluated. Cisplatin significantly altered the normal levels of all biomarkers confirming its hepatotoxic effects. In contrast, treatment with sodium salicylate-loaded silica nanoemulsion significantly restored the levels of these markers. The finding suggests the protective effects of this model drug in preventing cisplatin-induced hepatotoxicity, and therefore may have implications in attenuating cisplatin-induced hepatotoxicity.


Size-dependent long-term weathering converting floating polypropylene macro- and microplastics into nanoplastics in coastal seawater environments.
In this study, we systematically developed the long-term photoaging behavior of different-sized polypropylene (PP) floating plastic wastes in a coastal seawater environment. After 68 d of laboratory accelerated UV irradiation, the PP plastic particle size decreased by 99.3 ± 0.15%, and nanoplastics (average size: 435 ± 250 nm) were produced with a maximum yield of 57.9%, evidencing that natural sunlight irradiation-induced long-term photoaging ultimately converts floating plastic waste in marine environments into micro- and nanoplastics. Subsequently, when comparing the photoaging rate of different sized PP plastics in coastal seawater, we discovered that large sized PP plastics (1000-2000 and 5000-7000 μm) showed a lower photoaging rate than that of small sized PP plastic debris (0-150 and 300-500 μm), with the decrease rate of plastic crystallinity as follow: 0-150 μm (2.01 d-1) > 300-500 μm (1.25 d-1) > 1000-2000 μm (0.780 d-1) and 5000-7000 μm (0.900 d-1). This result can be attributed to the small size PP plastics producing more reactive oxygen species (ROS) species, with the formation capacity of hydroxyl radical •OH as follows: 0-150 μm (6.46 × 10-15 M) > 300-500 μm (4.87 × 10-15 M) > 500-1000 (3.61 × 10-15 M) and 5000-7000 μm (3.73 × 10-15 M). The findings obtained in this study offer a new perspective on the formation and ecological risks of PP nanoplastics in current coastal seawater environments.


Assessing context suitability (generalizability, external validity, applicability or transferability) of findings in evidence syntheses in healthcare-An integrative review of methodological guidance.
Evidence syntheses provide the basis for evidence-based decision making in healthcare. To judge the certainty of findings for the specific decision context evidence syntheses should consider context suitability (ie, generalizability, external validity, applicability or transferability). Our objective was to determine the status quo and to provide a comprehensive overview of existing methodological recommendations of Health Technology Assessment (HTA) and Systematic Review (SR) producing organizations in assessing context suitability of evidence on effectiveness of health care interventions. Additionally, we analyzed similarities and differences between the recommendations. In this Integrative Review we performed a structured search for methods documents from evidence synthesis producing organizations that include recommendations on appraising context suitability in effectiveness assessments. Two reviewers independently selected documents according to predefined eligibility criteria. Data were extracted in standardized and piloted tables by one reviewer and verified by a second reviewer. We performed a thematic analysis to identify and summarize the main themes and categories regarding recommended context suitability assessments. We included 14 methods documents of 12 organizations in our synthesis. Assessment approaches are very heterogeneous both regarding the general concepts (eg, integration in the evidence synthesis preparation process) and the content of assessments (eg, assessment criteria). Some heterogeneity seems to be justified because of the need to tailor the assessment to different settings and medical areas. However, most differences were inexplicable. More harmonization is desirable and appears possible.


The relationship between retinal layers and brain areas in asymptomatic first-degree relatives of sporadic forms of Alzheimer's disease: an exploratory analysis.
Two main genetic risks for sporadic Alzheimer's disease (AD) are a family history and ɛ4 allele of apolipoprotein E. The brain and retina are part of the central nervous system and share pathophysiological mechanisms in AD. We performed a cross-sectional study with 30 participants without a family history of sporadic AD (FH-) and noncarriers of ApoE ɛ4 (ApoE ɛ4-) as a control group and 34 participants with a family history of sporadic AD (FH+) and carriers of at least one ɛ4 allele (ApoE ɛ4+). We analyzed the correlations between macular volumes of retinal layers and thickness of the peripapillary retinal nerve fiber layer (pRNFL) measured by optical coherence tomography (OCT) with the brain area parameters measured by magnetic resonance imaging (MRI) in participants at high genetic risk of developing AD (FH+ ApoE ɛ4+). We observed a significant volume reduction in the FH+ ApoE ɛ4+ group compared with the control group in some macular areas of (i) macular RNFL (mRNFL), (ii) inner plexiform layer (IPL), (iii) inner nuclear layer (INL), and (iv) outer plexiform layer (OPL). Furthermore, in the FH+ ApoE ɛ4+ group, the retinal sectors that showed statistically significant volume decrease correlated with brain areas that are affected in the early stages of AD. In the same group, the peripapillary retinal nerve fiber layer (pRNFL) did not show statistically significant changes in thickness compared with the control group. However, correlations of these sectors with the brain areas involved in this disease were also found. In cognitively healthy participants at high genetic risk of developing sporadic forms of AD, there are significant correlations between retinal changes and brain areas closely related to AD such as the entorhinal cortex, the lingual gyrus, and the hippocampus.


Hypothesis: fetal movement influences fetal and infant bone strength.
Infants who present with multiple unexplained fractures in which there is no prior trauma, no radiographic evidence of metabolic bone disease, and no biochemical evidence of metabolic bone disease are almost always diagnosed as victims of child abuse, even though parents and caregivers deny wrongdoing. Such a diagnosis has far reaching implications for the infant and family. This article describes the clinical features of 65 such infants with multiple unexplained fractures in which the parents and caregivers deny wrongdoing and in which child abuse was diagnosed. These infants have the phenotype of temporary brittle bone disease that was described by Paterson. A striking observation in these young infants is the pregnancy history of decreased fetal movement. A hypothesis is suggested as an alternative explanation for the mechanism of these fractures in these infants--namely temporary brittle bone disease from fetal immobilization. This hypothesis states that fetal bone loading through fetal movement is essential for the formation of bones of normal strength. This hypothesis is an application of Frost's mechanostat/bone-loading model of bone physiology to the prenatal period of bone formation. This hypothesis explains many of the other observations about temporary brittle bone disease including the early onset of the fractures in the first several months of life, the lack of bruising, the lack of other internal organ injury, and the low risk profile of many of the parents for committing child abuse.


Modulation of inhibitory post-synaptic currents (IPSCs) in mouse cerebellar Purkinje and basket cells by snake and scorpion toxin K+ channel blockers.
Using an in vitro mouse cerebellar slice preparation and whole-cell electrophysiological recording techniques we have characterized Purkinje and basket cell inhibitory post-synaptic currents (IPSCs), and examined the effects of a number of selective peptidergic K+ channel blockers. Spontaneous IPSC amplitude ranged from approximately 10 pA up to approximately 3 nA for both cell types [mean values: Purkinje cells -122.8+/-20.0 pA (n = 24 cells); basket cells -154.8+/-15.9 pA (n = 26 cells)]. Frequency varied from approximately 3 up to approximately 40 Hz, [mean values: basket cells 14.9+/-1.7 Hz (n=26 cells); Purkinje cells 17.9+/-2.2 Hz (n=24 cells)]. 5 microM bicuculline eliminated virtually all spontaneous currents. IPSC rise times were fast (approximately 0.6 ms) and the decay phase was best fit with the sum of two exponential functions (tau1 and tau2: approximately 4 ms and approximately 20 ms, n=40; for both cell types). The snake toxins alpha-dendrotoxin (alpha-DTX) and toxin K greatly enhanced IPSC frequency and amplitude in both cell types; the closely related homologues toxin I and gamma-dendrotoxin (gamma-DTX) produced only marginal enhancements (all at 200 nM). Two scorpion toxins, margatoxin (MgTX) and agitoxin-2 (AgTX-2) had only minor effects on IPSC frequency or amplitude (both at 10 nM). Low concentrations of tetraethylammonium (TEA; 200 microM) had no overall effect on cerebellar IPSCs, whilst higher concentrations (10 mM) increased both the frequency and amplitude. The results suggest that native K+ channels, containing Kv1.1 and Kv1.2 channel subunits, play an influential role in controlling GABAergic inhibitory transmission from cerebellar basket cells.


Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease.
To compare the diagnostic accuracy of CSF biomarkers and amyloid PET for diagnosing early-stage Alzheimer disease (AD). From the prospective, longitudinal BioFINDER study, we included 122 healthy elderly and 34 patients with mild cognitive impairment who developed AD dementia within 3 years (MCI-AD). β-Amyloid (Aβ) deposition in 9 brain regions was examined with [18F]-flutemetamol PET. CSF was analyzed with INNOTEST and EUROIMMUN ELISAs. The results were replicated in 146 controls and 64 patients with MCI-AD from the Alzheimer's Disease Neuroimaging Initiative study. The best CSF measures for identifying MCI-AD were Aβ42/total tau (t-tau) and Aβ42/hyperphosphorylated tau (p-tau) (area under the curve [AUC] 0.93-0.94). The best PET measures performed similarly (AUC 0.92-0.93; anterior cingulate, posterior cingulate/precuneus, and global neocortical uptake). CSF Aβ42/t-tau and Aβ42/p-tau performed better than CSF Aβ42 and Aβ42/40 (AUC difference 0.03-0.12, p<0.05). Using nonoptimized cutoffs, CSF Aβ42/t-tau had the highest accuracy of all CSF/PET biomarkers (sensitivity 97%, specificity 83%). The combination of CSF and PET was not better than using either biomarker separately. Amyloid PET and CSF biomarkers can identify early AD with high accuracy. There were no differences between the best CSF and PET measures and no improvement when combining them. Regional PET measures were not better than assessing the global Aβ deposition. The results were replicated in an independent cohort using another CSF assay and PET tracer. The choice between CSF and amyloid PET biomarkers for identifying early AD can be based on availability, costs, and doctor/patient preferences since both have equally high diagnostic accuracy. This study provides Class III evidence that amyloid PET and CSF biomarkers identify early-stage AD equally accurately.


Cryptocurrency as a new method for participant compensation in research.
Public health research relies heavily on participant involvement. Investigators have examined factors that affect participation and found that altruism enables engagement. At the same time, time commitment, family concerns, multiple follow-up visits, and potential adverse events are barriers to engagement. Thus, investigators may need to find new methods to attract and motivate participants to participate, including new compensation methods. As cryptocurrency is being increasingly used and accepted to pay and reimburse people for work activities, this currency should be similarly explored as an option for research participants to attempt to incentivize them to participate in studies and offer new possibilities for study reimbursement. This paper explores the potential use of cryptocurrency as a form of compensation in public health research studies and discusses the pros and cons of its use. Although few studies have used cryptocurrency to compensate participants, cryptocurrency may be used as a reward for various research tasks, including filling out surveys, participating in in-depth interviews or focus groups, and/or completing interventions. Using cryptocurrencies to compensate participants in health-related studies can provide benefits such as anonymity, security, and convenience. However, it also poses potential challenges, including volatility, legal and regulatory challenges, and the risk of hacking and fraud. Researchers must carefully weigh the benefits against the potential downsides before using them as a compensation method in health-related studies.


A survey regarding the organizational aspects and quality systems of in-house 3D printing in oral and maxillofacial surgery in Germany.
The aim of the study was to get a cross-sectional overview of the current status of specific organizational procedures, quality control systems, and standard operating procedures for the use of three-dimensional (3D) printing to assist in-house workflow using additive manufacturing in oral and maxillofacial surgery (OMFS) in Germany. An online questionnaire including dynamic components containing 16-29 questions regarding specific organizational aspects, process workflows, quality controls, documentation, and the respective backgrounds in 3D printing was sent to OMF surgeons in university and non-university hospitals as well as private practices with and without inpatient treatment facilities. Participants were recruited from a former study population regarding 3D printing; all participants owned a 3D printer and were registered with the German Association of Oral and Maxillofacial Surgery. Sixty-seven participants answered the questionnaires. Of those, 20 participants ran a 3D printer in-unit. Quality assurance measures were performed by 13 participants and underlying processes by 8 participants, respectively. Standard operating procedures regarding computer-aided design and manufacturing, post-processing, use, or storage of printed goods were non-existent in most printing units. Data segmentation as well as computer-aided design and manufacturing were conducted by a medical doctor in most cases (n = 19, n = 18, n = 8, respectively). Most participants (n = 8) stated that "medical device regulations did not have any influence yet, but an adaptation of the processes is planned for the future." The findings demonstrated significant differences in 3D printing management in OMFS, especially concerning process workflows, quality control, and documentation. Considering the ever-increasing regulations for medical devices, there might be a necessity for standardized 3D printing recommendations and regulations in OMFS.


Impact of directed movement on invasive spread in periodic patchy environments.
To address the effect of taxis of invasive animals on their spreading speed in heterogeneous environments, we deal with an advection-diffusion-reaction equation (ADR) in a periodic patchy environment. Two-types of advection that spatially vary depending on environmental heterogeneity are taken into consideration: a stepwise taxis function and a saw-like taxis function. We first analyze the ADR with the stepwise taxis advection, and derive an invasion criterion. When the invasion criterion holds, an initially localized population evolves to a traveling periodic wave (TPW). The asymptotic speed of the TPW is found to be equal to the minimal speed of the TPW analytically derived. Thus, we examine how the minimal speed is influenced by the taxis. The major results are: (1) As the magnitude of the taxis toward favorable patches increases, invasion becomes more feasible. However, the spreading speed increases at first, and then decreases to show a one-humped curve against the magnitude of the taxis; (2) As the scale of fragmentation in the patchy environment is increased, the spreading speed increases when the magnitude of the taxis is small, while it decreases when the magnitude of the taxis becomes sufficiently large. These characteristic features qualitatively apply to the ADR model with the saw-like taxis function.


Regulation of presynaptic neurotransmission by macroautophagy.
mTOR is a regulator of cell growth and survival, protein synthesis-dependent synaptic plasticity, and autophagic degradation of cellular components. When triggered by mTOR inactivation, macroautophagy degrades long-lived proteins and organelles via sequestration into autophagic vacuoles. mTOR further regulates synaptic plasticity, and neurodegeneration occurs when macroautophagy is deficient. It is nevertheless unknown whether macroautophagy modulates presynaptic function. We find that the mTOR inhibitor rapamycin induces formation of autophagic vacuoles in prejunctional dopaminergic axons with associated decreased axonal profile volumes, synaptic vesicle numbers, and evoked dopamine release. Evoked dopamine secretion was enhanced and recovery was accelerated in transgenic mice in which macroautophagy deficiency was restricted to dopaminergic neurons; rapamycin failed to decrease evoked dopamine release in the striatum of these mice. Macroautophagy that follows mTOR inhibition in presynaptic terminals, therefore, rapidly alters presynaptic structure and neurotransmission.


Bio-conversion of apple pomace into ethanol and acetic acid: Enzymatic hydrolysis and fermentation.
Enzymatic hydrolysis of cellulose present in apple pomace was investigated using process variables such as enzyme activity of commercial cellulase, pectinase and β-glucosidase, temperature, pH, time, pre-treatments and end product separation. The interaction of enzyme activity, temperature, pH and time had a significant effect (P<0.05) on release of glucose. Optimal conditions of enzymatic saccharification were: enzyme activity of cellulase, 43units; pectinase, 183units; β-glucosidase, 41units/g dry matter (DM); temperature, 40°C; pH 4.0 and time, 24h. The sugars were fermented using Saccharomyces cerevisae yielding 19.0g ethanol/100g DM. Further bio-conversion using Acetobacter aceti resulted in the production of acetic acid at a concentration of 61.4g/100g DM. The present study demonstrates an improved process of enzymatic hydrolysis of apple pomace to yield sugars and concomitant bioconversion to produce ethanol and acetic acid.


The effect of rim-off deep lateral orbital decompression on the lateral rectus shape and oculomotor balance.
The purpose of the study was to measure the effect of rim-off deep lateral decompression for Graves orbitopathy on the lateral rectus muscle path and oculomotor balance. Retrospective analysis of the medical records and pre- and postoperative computed tomography scans of 34 orbits of 23 patients who underwent deep lateral decompression alone. The oculomotor balance of these 23 patients was measured with the alternate cover test and prisms before and after surgery. Bezier functions were used to measure the postoperative path of the lateral rectus in all decompressed orbits. Deep lateral decompression induced a curvilinear deformation of the lateral rectus. There was no significant correlation between the position of the point of maximum muscle displacement and the size of the residual lateral wall. The changes in the lateral rectus path had no adverse effects on the oculomotor balance of the patients. The location of the curvilinear deformation of the lateral rectus does not depend on the residual segment of the lateral wall. The changes of the lateral rectus path have no deleterious effect on the oculomotor balance.


Discovery of GS-9451: an acid inhibitor of the hepatitis C virus NS3/4A protease.
The discovery of GS-9451 is reported. Modification of the P3 cap and P2 quinoline with a series of solubilizing groups led to the identification of potent HCV NS3 protease inhibitors with greatly improved pharmacokinetic properties in rats, dogs and monkeys.


Spinal c-fos induction by sensory stimulation in neonatal rats.
C-fos immunocytochemistry was used to investigate the functional connectivity between primary afferent nociceptive fibres and second-order neurons in the spinal cord of the anaesthetised neonatal rat. Subcutaneous injection of 50 mg/kg capsaicin potently induced c-fos in the spinal cord on the first postnatal day (P1), whilst plantar injection of dilute formalin was much less effective until P3. In contrast with the adult, there was no c-fos response of the neonatal rat spinal cord to cutaneous application of the C-fibre irritant, mustard oil. It is concluded that spinal c-fos expression induced by noxious sensory stimulation can occur before the development of mature functional synaptic contact with first-order neurones.


[Prasiquantel treatment of patients under ambulatory conditions in an opisthorchiasis focus in the Komi-Permyak autonomous area].
90 Opisthorchis felineus invaded patients were subjected to prasiquantel treatment. Single doze of the drug (40 mg/kg) was administered under ambulatory conditions. Treatment efficacity 6 months after administration attained 85.9%. Side-effects were observed in 89.7% of patients, the neurotropic effects' rate being 85.4%. Lower side-effects' rate was established in case of prasiquantel administration with milk. Positive clinical effect of prasiquantel treatment was observed in 69.3% patients.


Development and effects of an internet-based family resilience-promoting program for parents of children with cancer: A randomized controlled trial.
The diagnosis of cancer in children can negatively impact their parents, owing to the complex treatment processes. Families with high levels of resilience can overcome these difficulties and thus perform higher family functions. We aimed to develop an internet-based family resilience-promoting program for parents of children with cancer and evaluate its effect on the levels of family resilience, depression, and family function. This prospective, parallel-group, randomized-controlled study that was conducted at Yonsei Cancer Center from June to October 2021 included 41 parents of children with cancer. In total, four sessions of the internet-based family resilience-promoting program, led by a nurse, were conducted individually for parents. Levels of family resilience, depression, and family function were measured before, immediately after, and 4 weeks after the program. The data were analyzed using the linear mixed-effect model, and program satisfaction was evaluated through an internet-based questionnaire and interview. The experimental group (the family resilience-promoting program participants) differed more significantly from the control group in the level of change in family resilience (β = 13.214, p = 0.003, effect size = 0.374) and family function (β = 1.256, p = 0.018, effect size = 0.394). However, there was no significant difference between the groups in the level of depression (β = 2.133, p = 0.187, effect size = 0.416). All the program participants showed a high program satisfaction score of 4.75 out of 5.00 points overall. The applicability of the internet-based family resilience-promoting program as an appropriate nursing intervention was verified. Its application can help the families of children with cancer adapt to the stressful situation of their children's cancer diagnosis and treatment.


Quantitative autoradiography of M2 muscarinic receptors in the rat brain identified by using a selective radioligand [3H]AF-DX 116.
Muscarinic receptors of the M2 type have been studied in the rat brain using quantitative autoradiography with the selective ligand, [3H]AF-DX 116. High specific binding of [3H]AF-DX 116 was found in areas such as laminae IV and V of the parietal cerebral cortex, thalamus and hypothalamus and dentate gyrus. Intermediate [3H]AF-DX 116 binding was found in the frontal cortex, hippocampus, caudate-putamen, nucleus accumbens, and claustrum as well as in certain brainstem nuclei such as the nucleus of the solitary tract and the dorsal motor nuclei of the vagus. In contrast, the accessory olfactory nucleus, globus pallidus and cerebellum contained very low concentrations of M2 receptors. The present study demonstrates a unique regional distribution of M2 receptors in the rat brain.


A model of the generation of the cochlear microphonic with nonlinear hair cell transduction and nonlinear basilar membrane mechanics.
A phenomenological model of the generation of the cochlear microphonic of the guinea pig is presented which incorporates sharp tuning and nonlinear growth of the vibration of the cochlear partition, and nonlinear transduction of this response by a single linear array of hair cells (assumed to be the outer hair cells). The contribution to the microphonic potential from each hair cell generator is also assumed to decay exponentially with distance from the hair cell. Using experimentally obtained estimates for the parameters a good agreement between the theoretical microphonic tuning curves and growth functions was obtained without recourse to complex micromechanical motion of the cochlear partition, electrical tuning of the hair cells or a contribution from the inner hair cells of the cochlea.