Measles immunity in a population of healthcare workers.
To evaluate measles seroprevalence among cohorts of new employees and to evaluate vaccine responses of susceptible adult healthcare workers. New employees were screened for measles susceptibility as part of employee evaluations. Anti-IgG measles antibody tests were completed on 2,473 workers. Demographic, measles history, and measles vaccination information was collected using a short questionnaire. Susceptible workers were vaccinated and screened for vaccine responses following vaccination. Ninety-three workers (4%) were seronegative, and 56 (2%) were equivocal. Individuals in the youngest cohort (born after 1956) were significantly more likely to be susceptible than those in the middle cohort (born 1951 to 1956) and those in the oldest cohort (born before 1951) (P < 0.01). The middle cohort included eight (5%) of the 149 seronegative or equivocal workers. Among the members of the youngest cohort, those from the United States were more likely to be susceptible (P < 0.01) than those from outside the United States. Of the 106 vaccinated susceptible workers whose follow-up serologies were determined, 90 (85%) developed positive IgG serologies, six had equivocal results, and 10 were seronegative. Eleven of the 16 non- or hyporesponders were revaccinated and re-evaluated; nine developed low positive IgG antimeasles levels, one exhibited an equivocal response, and one failed to respond. A small but important proportion of healthcare workers are susceptible to measles. Whenever feasible, measles immunity programs for healthcare workers should include workers born before 1957. Of workers born after 1956, those from outside the United States are more likely to be immune than workers from inside the United States. Using the currently available vaccine, revaccination of initial non- or hyporesponders appears to be effective.


Ring-Opening of Indoles: An Unconventional Route for the Transformation of Indoles to 1 H-Pyrazoles Using Lewis Acid.
An unusual transformation of indoles to pyrazoles via an aromatic ring-opening strategy has been developed. The salient feature of this strategy involves the C2-N1 bond opening and concomitant cyclization reaction of the C2═C3 bond of the indole moiety with the tosylhydrazone, which proceeds under transition-metal and ligand free conditions. This ring-opening functionalization of indoles provides a wide scope of differently substituted pyrazoles.


5-Fluorouracil augmented needle revision of trabeculectomy: does the location of outflow resistance make a difference?
To determine whether the outcome of needle revision of trabeculectomy is influenced by the presumed anatomic location of resistance to aqueous outflow. Retrospective case note review. Thirty-four eyes of 30 consecutive patients undergoing their first needle revision of trabeculectomy. We compared 2 types of needle revision: "type-1 needling," limited to breaking down fibrosis in the subconjuctival-subtenon space, and "type-2 needling," which additionally involved needling underneath the scleral flap. Unqualified success was defined as a postneedling intraocular pressure (IOP) >4 mm Hg and ≤21 mm Hg at the most recent follow-up without further surgery, medications, or repeat needling. Qualified success was defined as a successful patient who required medications or repeat needling. The mean follow-up period was 2.1 ± 0.1 years (range, 1.0 to 3.8 y). Sixteen type-1 and 18 type-2 procedures were performed at a median of 124 days (22 d to 14 y) after trabeculectomy. IOP decreased from a mean of 28.2±1.3 mm Hg (19 to 52 mm Hg) preneedling to 6.7±0.8 mm Hg (2 to 22 mm Hg) on the first postoperative visit and 15.1±0.7 mm Hg (8 to 27 mm Hg) at the most recent follow-up. The overall success rate was 82.4% (47.1% unqualified and a further 35.3% qualified). There was no significant difference in the success rates between type-1 (14/16) and type-2 (14/18) needle revisions (Fisher exact test, P=0.66). Similar proportions of eyes undergoing type-1 and type-2 needling underwent a second needling procedure. There was no significant difference in the IOP reduction between type-1 and type-2 needling (Mann-Whitney U test, P=0.78). Needle revision is an effective technique for trabeculectomy bleb remodeling and can result in a sustained reduction in IOP. The location of the obstruction did not influence outcome, with type-1 and type-2 needle revisions equally likely to succeed.


Comparative study of lyophilized human dura mater and lyophilized bovine pericardium as dural substitutes in neurosurgery.
In a prospective, controlled randomized study either lyophilized bovine pericardium or lyophilized human dura mater have been used as a patch for the closure of the dura in 102 patients. The aim of this investigation was to compare both materials in terms of immunogenic response of the patients. The rate of post-operative complications was comparably low in both groups (wound infection in 1/51 patients each). In regard of workability, thickness of the material and flexibility the pericardium patches were judged to be by far superior. Neither signs of a cellular nor of an intesified humoral response could be detected in patients who received the pericardium implants. Thus, lyophilized bovine pericardium seems to be a superior alternative for the surgical repair of dural defects.


Partial Reprogramming of Pluripotent Stem Cell-Derived Cardiomyocytes into Neurons.
Direct reprogramming of somatic cells has been demonstrated, however, it is unknown whether electrophysiologically-active somatic cells derived from separate germ layers can be interconverted. We demonstrate that partial direct reprogramming of mesoderm-derived cardiomyocytes into neurons is feasible, generating cells exhibiting structural and electrophysiological properties of both cardiomyocytes and neurons. Human and mouse pluripotent stem cell-derived CMs (PSC-CMs) were transduced with the neurogenic transcription factors Brn2, Ascl1, Myt1l and NeuroD. We found that CMs adopted neuronal morphologies as early as day 3 post-transduction while still retaining a CM gene expression profile. At week 1 post-transduction, we found that reprogrammed CMs expressed neuronal markers such as Tuj1, Map2, and NCAM. At week 3 post-transduction, mature neuronal markers such as vGlut and synapsin were observed. With single-cell qPCR, we temporally examined CM gene expression and observed increased expression of neuronal markers Dcx, Map2, and Tubb3. Patch-clamp analysis confirmed the neuron-like electrophysiological profile of reprogrammed CMs. This study demonstrates that PSC-CMs are amenable to partial neuronal conversion, yielding a population of cells exhibiting features of both neurons and CMs.


Convolutional neural network based on photoplethysmography signals for sleep apnea syndrome detection.
The current method of monitoring sleep disorders is complex, time-consuming, and uncomfortable, although it can provide scientifc guidance to ensure worldwide sleep quality. This study aims to seek a comfortable and convenient method for identifying sleep apnea syndrome. In this work, a one-dimensional convolutional neural network model was established. To classify this condition, the model was trained with the photoplethysmographic (PPG) signals of 20 healthy people and 39 sleep apnea syndrome (SAS) patients, and the influence of noise on the model was tested by anti-interference experiments. The results showed that the accuracy of the model for SAS classifcation exceeds 90%, and it has some antiinterference ability. This paper provides a SAS detection method based on PPG signals, which is helpful for portable wearable detection.


Identification of insulin-like growth factor (IGF) and glucose transporter-1 and -3 mRNA in CNS tumors.
Glucose metabolism is increased in CNS tumors and correlates with malignant grade. We have previously investigated the role of IGFs in regulating CNS tumor growth and metabolism. In the present study we examined total cellular RNA from human CNS tumors for the presence for glucose transporter (Glut) and IGF mRNA. Human meningiomas and gliomas were frozen in liquid nitrogen at the time of surgery and then stored at -80 degrees C. Total cellular RNA was prepared by acid-guanidinium phenol-chloroform extraction and 20 micrograms of RNA was loaded for agarose-formaldehyde gel electrophoresis and transfer. RNA integrity in 5 meningiomas and 2 gliomas was confirmed by ethidium bromide staining of 28S and 18S ribosomal RNA and hybridization with a cDNA probe for beta-actin. For analysis, membranes were hybridized to radioactively labeled human Glut-1, Glut-3, IGF-I, and IGF-II cDNA probes, and mRNA transcripts were identified by autoradiography. All 7 tumors expressed Glut-1 and Glut-3 mRNA and Glut-3 appeared to be more abundant in meningiomas. IGF-II mRNA was detected in 2 of 6 meningiomas and in both gliomas. IGFs may play an important role in the regulation of glucose metabolism in CNS tumors. IGFs and specific glucose transporters may prove useful as markers of malignancy and potential targets for future therapy.


A study of eleven cutaneous malignant melanomas in adults with small-cell morphology: emphasis on diagnostic difficulties and unusual features.
To describe the clinicopathological and immunohistochemical features of cutaneous malignant melanomas with a pure or mixed small-cell pattern in 11 adult patients, and to discuss the diagnostic difficulties encountered. Haematoxylin and eosin-stained sections of each case of cutaneous small-cell malignant melanoma, together with locally recurrent skin lesions and, where available, metastatic deposits, were re-examined. Available immunohistochemical sections were evaluated. Clinical follow-up data were obtained in each case. One patient presented with metastatic disease, the others presented with cutaneous lesions. Suggested initial diagnoses included malignant melanoma, non-Hodgkin's lymphoma, Merkel cell carcinoma and sarcoma. All the tumours were in the vertical growth phase. Nine had a junctional component, often inconspicuous. The lesions showed either a pure small-cell pattern or a mixed pattern with more conventional areas. In one case, there was colonization of a basal cell carcinoma by invasive malignant melanoma. Variable retention of small-cell morphology in local recurrences and metastases was observed, although in some cases more typically pleomorphic cells were present. In the cases tested, there was strong immunostaining for S100 protein and NKI-C3, and variable immunostaining for HMB45 and Melan-A. Non-melanocytic markers were negative. The possibility of a small-cell malignant melanoma should be considered in the assessment of cutaneous and non-cutaneous small-cell neoplasms. The correct diagnosis requires careful evaluation for junctional activity, melanin production and the use of a panel of melanocytic markers.


E-Cigarette Use and Subsequent Cigarette Initiation and Sustained Use Among Youth, U.S., 2015-2017.
Using cross-sectional data, we measured the association between electronic cigarette (e-cigarette) use and subsequent initiation and sustained use of cigarettes among U.S. youth. Data were pooled from the 2015-2017 National Youth Tobacco Survey, a school-based survey of U.S. students in grades 6-12. Questions on current age and age of first use of different tobacco products (cigarettes, e-cigarettes, cigars, and smokeless tobacco) were used to ascertain the temporal sequence of tobacco product use. The pooled study population was 52,579 youth who 5 years before the survey had never smoked cigarettes. E-cigarette users were defined as those who used e-cigarettes before or without ever smoking cigarettes. Cigarette smoking was assessed with the following measures: ever smoking a cigarette at any time within the past 5 years and sustained smoking (smoked ≥1 year ago and within past 30 days). Adjusted odds ratios (AORs) were calculated, controlling for other tobacco product use and sociodemographics. Among never cigarette smokers as of 5 years before the survey, 17.4% used e-cigarettes, and 15.6% first smoked within the past 5 years. Compared with those who did not use e-cigarettes, those who used e-cigarettes had higher odds of ever smoking cigarettes within the past 5 years (AOR = 2.73) and had higher odds of sustained smoking (AOR = 1.55; all p < .05). E-cigarette use is associated with subsequent initiation and sustained use of cigarettes among youth. Efforts are warranted to reduce youth use of all tobacco products, including e-cigarettes.


Long-term effects of phacoemulsification and intraocular lens implantation in a patient with pathologic myopia and extremely long axial length: A case report.
To report a rare case of phacoemulsification cataract surgery and intraocular lens implantation that improved visual acuity and capsular stability in a patient with pathologic myopia and axial length >38 mm. A 51-year-old Chinese man with high myopia since childhood who had lost sight in his left eye at the age of 25 due to retinal detachment. He was referred for ophthalmological assessment due to decreased vision in the right eye, in which the best-corrected visual acuity at distance was hand motion. The patient was diagnosed with cataract, high myopia, subluxated lens, and loose zonules in the right eye. The left eyeball showed atrophy. The patient underwent uneventful phacoemulsification. An intraocular lens (Sensar AR40M) and capsular tension ring were implanted within the capsular bag. After surgery, the patient was given eye drops containing tobramycin and dexamethasone eye drops for 1 month and eye drops containing 0.1% sodium diclofenac for 2 months. There were no postoperative complications. During 1-year follow-up, uncorrected visual acuity was 20/80 and the manifest refraction was -2.50DS/-1.00DC*80, with corrected distance visual acuity of 20/60. Cataract surgery maintained adequate vision for daily living. Implantation of specific lens and capsular tension ring as well as prolonged use of non-steroidal anti-inflammatory drugs may help prevent capsular contraction and posterior capsule opacification in patients with pathologic myopia and extremely long axial length.


Stupid statistics!
The method of least squares is probably the most powerful data analysis tool available to scientists. Toward a fuller appreciation of that power, this work begins with an elementary review of statistics fundamentals, and then progressively increases in sophistication as the coverage is extended to the theory and practice of linear and nonlinear least squares. The results are illustrated in application to data analysis problems important in the life sciences. The review of fundamentals includes the role of sampling and its connection to probability distributions, the Central Limit Theorem, and the importance of finite variance. Linear least squares are presented using matrix notation, and the significance of the key probability distributions-Gaussian, chi-square, and t-is illustrated with Monte Carlo calculations. The meaning of correlation is discussed, including its role in the propagation of error. When the data themselves are correlated, special methods are needed for the fitting, as they are also when fitting with constraints. Nonlinear fitting gives rise to nonnormal parameter distributions, but the 10% Rule of Thumb suggests that such problems will be insignificant when the parameter is sufficiently well determined. Illustrations include calibration with linear and nonlinear response functions, the dangers inherent in fitting inverted data (e.g., Lineweaver-Burk equation), an analysis of the reliability of the van't Hoff analysis, the problem of correlated data in the Guggenheim method, and the optimization of isothermal titration calorimetry procedures using the variance-covariance matrix for experiment design. The work concludes with illustrations on assessing and presenting results.


A study of gene expression in the living human brain.
A goal of medical research is to determine the molecular basis of human brain health and illness. One way to achieve this goal is through observational studies of gene expression in human brain tissue. Due to the unavailability of brain tissue from living people, most such studies are performed using tissue from postmortem brain donors. An assumption underlying this practice is that gene expression in the postmortem human brain is an accurate representation of gene expression in the living human brain. Here, this assumption - which, until now, had not been adequately tested - is tested by comparing human prefrontal cortex gene expression between 275 living samples and 243 postmortem samples. Expression levels differed significantly for nearly 80% of genes, and a systematic examination of alternative explanations for this observation determined that these differences are not a consequence of cell type composition, RNA quality, postmortem interval, age, medication, morbidity, symptom severity, tissue pathology, sample handling, batch effects, or computational methods utilized. Analyses integrating the data generated for this study with data from earlier landmark studies that used tissue from postmortem brain donors showed that postmortem brain gene expression signatures of neurological and mental illnesses, as well as of normal traits such as aging, may not be accurate representations of these gene expression signatures in the living brain. By using tissue from large cohorts living people, future observational studies of human brain biology have the potential to (1) determine the medical research questions that can be addressed using postmortem tissue as a proxy for living tissue and (2) expand the scope of medical research to include questions about the molecular basis of human brain health and illness that can only be addressed in living people (e.g., "What happens at the molecular level in the brain as a person experiences an emotion?").


Effect of monosaccharides and ethyleneglycol on the interaction between Escherichia coli bacteria and Octyl-Sepharose.
Combined effects of monosaccharides and reduced surface tension of the medium were studied in relation to the hydrophobic binding of Escherichia coli bacteria, with and without mannose-specific structures. Hydrophobic binding was analyzed by hydrophobic interaction chromatography on Octyl-Sepharose. The results showed that ethyleneglycol, as well as mannose, reduced the hydrophobic interaction of the bacteria with mannose-specific structures. This effect was potentiated by combining ethyleneglycol and mannose. No other monosaccharides tested (galactose and fucose) had any effect on the hydrophobic interaction of bacteria with mannose-specific structures. These results further strengthen the hypothesis that the mannose-specific interaction of Escherichia coli bacteria is, at least in part, mediated by hydrophobic forces.


Endometriosis in para-aortic lymph node resembling a malignancy: a case report and literature review.
Endometriosis is a common benign gynecological disease characterized by growing-functioning endometrial tissue outside the uterus. Extra-pelvic endometriosis, which accounts for approximately 12% of endometriosis, is more challenging to diagnose because of its distance from the pelvic organs. Halban's theory of benign metastasis indicates that endometrial cells can appear in extra-pelvic organs via lymphatic and blood vessels, but endometrial lymph node metastasis cases are still rare. We report a case of endometriosis in a para-aortic lymph node whose clinical behavior mimicked a malignancy. A 52-year-old perimenopausal woman underwent laparoscopic hysterectomy plus bilateral salpingectomy (the patient insisted on the preservation of her ovaries) at a local hospital 2 years earlier because of adenomyosis. The patient presented with a complaint of low back pain to the gastrointestinal outpatient department of our hospital. The carbohydrate antigen 125 (CA125) was abnormally elevated at 5280.20 U/ml, human epididymis 4 (HE4) was 86.0 pmol/L, while other tumor markers were normal. Serum female hormone results were in the postmenopausal range, and her gastroenteroscopy showed no abnormalities. Moreover, both enhanced magnetic resonance imaging and positron emission tomography-computed tomography showed a high possibility of a retroperitoneal malignant lymph node (metastasis possible, primary site unknown). One week after admission, she underwent laparoscopic exploratory surgery, during which we observed normal shape and size of both ovaries while the left ovary was cystic-solid. After opening the retroperitoneal space, an enlarged lymph node-like tissue measuring 8 × 4 × 3 cm3 was found near the abdominal aorta. When the surrounding adhesions were separated, lymph node-like tissue was poorly demarcated from the abdominal aorta and renal artery. Some lymph node samples and left ovary were sent for intraoperative frozen section, which revealed benign lesions, similar to endometrial tissue. The lymph node tissue was then excised as much as possible, and the second set of intraoperative frozen sections showed high probability of endometrial tissue. The final histopathology and immunohistochemistry staining reached a diagnosis of para-aortic lymph node endometriosis. Gonadotropin-releasing hormone antigen treatment was recommended every 28 days because of the high preoperative CA125 and imaging-based suspicion of malignancy. The serum CA125 subsequently decreased to normal levels, and no para-aortic lesions were detected on abdominal enhancement CT. She is being followed up regularly. It is known that the incidence of lymph node metastasis in pelvic endometriosis is relatively rare. Our report shows that endometriotic tissue can metastasize via the lymphatic route and suggests that endometriotic tissue has the characteristics of invasion and metastasis.


Effect of restricted suckling on the onset of follicular dynamics and body condition score in Brahman cattle raised under tropical conditions.
With the aim of evaluating the effect of restricted suckling on the onset of follicular dynamics and body condition, multiparous Bos indicus cows were distributed in two groups. One group (RS=36) was subjected to a scheme of restricted suckling starting at 21 days postpartum. Calves were allowed to suckle once per day for a period of two h whilst the control group (C=18) remained with their dams at all times. At calving, body condition score, back fat thickness and body weight had similar values (p>0.05) for both groups. By day 85 postpartum both groups had recorded losses in body weight. The cows in the continuous group formed a greater (p<0.05) number of follicles of class size <6mm in both periods before and after synchronization. The proportion of cows showing estrus and ovulation before 45 days, was not different (p>0.05). The number of cows that exhibited estrus after 45 days, was greater (p<0.05) in RS than C group, 72.2% and 55.5%, respectively. Same situation (p<0.05) occurred in cows that ovulated, 88.8 and 66.7%, for groups RS and C, respectively. The subset in the intensive observations showed that the size of the bigger follicle was larger (p<0.05) for RS cows than C cows from 36 h after CIDR withdrawal. At 57 h, the size of the biggest follicle recorded was not different between groups (p>0.05). A regime of restricted suckling favors the earlier growth of follicles and the prompt restoration of ovarian activity.


A novel magnetic device for laparoscopic cholangiojejunostomy.
Laparoscopic cholangiojejunostomy (LCJ) with hand-sewn technique is technically difficult and requires a long time to master. The purpose of this study was to assess the feasibility of LCJ using a novel magnetic compression device (MCD) in dogs. The concept of the purse-string technique of the circular stapler was used to design a novel MCD for LCJ. To test the feasibility of this MCD in a more clinically relevant situation, four dogs were subjected to bile duct ligation. When the diameter of their bile ducts reached 10 mm, LCJ using MCD was performed. The anastomotic time and expelling time of the magnets were assessed. In the clinically relevant model of bile duct obstruction in dogs, LCJ created with this MCD yielded patent anastomoses. The LCJ procedure using this novel MCD was simple, and the mean anastomotic time was 12.9 ± 1.73 min. All animals recovered smoothly after the operation without complications. All magnets spontaneously passed through the rectum in 14.5 ± 2.08 d after LCJ. LCJ in dogs using this novel MCD is feasible.


Prevention of Radiation Therapy Treatment Deviations by a Novel Combined Biometric, Radiofrequency Identification, and Surface Imaging System.
To evaluate the impact of Varian Identify, a novel combined radiofrequency identification, biometric and surface-matching technology, on its potential for patient safety and prevention of radiation therapy treatment deviations. One hundred eight radiation therapy treatment deviation reports at our facility over the past 8 years were analyzed. Three major categories were defined based on the time point of occurrence: physician order deviations (19.4%), treatment-planning deviations (24.1%), and machine treatment deviations (56.5%). The impact of Identify on potential prevention of machine treatment deviations was analyzed. A failure mode and effects analysis was performed on the 5 most frequently occurring errors preventable with Identify. Safety analysis of the Identify system was reported based on 3.5 years of clinical data post-Identify system installation on 3 treatment vaults. Of the 61 machine treatment deviations, 47 (77%) were interpreted as being preventable by using Identify. Our failure mode and effects analysis showed reductions in all risk priority numbers post-Identify application. Safety analysis of the Identify system from our direct observation that for approximately 7 cumulative years of Identify use in 3 different treatment vaults, where 9 deviations would have been expected to occur over this combined period, zero machine treatment events occurred. The combination of Identify biometric, radiofrequency identification, and surface-matching technologies was observed to enable an effective process for enhancing safety and efficiency of radiation therapy treatment. A significant reduction in machine-related deviations was observed.


Microfluidics in systems biology-hype or truly useful?
Systems biology often relies on large-scale measurements and model-building to understand how complex biological systems function. Microfluidic technology has been touted as a tool for high-throughput experiments and has been a valuable tool to some systems biology research. This review focuses on applications where microfluidics can enhance experimental sensitivity and throughput, particularly in recent development in single-cell analyses and analyses on multi-cellular or complex biological entities. We conclude that microfluidics is not necessarily always useful for systems biology, but when used appropriately can greatly enhance experimentalists' ability to measure and control, and thereby enhance the understanding of and expand the utility of biological systems.


A time series and geographical analysis of population dynamics of the red-backed vole in Hokkaido, Japan.
A time series and geographical analysis of the long term (25-years and 16-years) census data of the red-backed vole, Clethrionomys rufocanus bedfordiae, populations in Hokkaido, Japan was carried out. Eighty seven populations from all over Hokkaido were grouped into the following 4 types according to their flucturation patterns: type A: low density-constant type; type B: medium density-gradual increase type; type C: medium density-wavy change type; type D: high density-large amplitude type. The border between type B and type C was not clear. Although the distribution of the fluctuation types did not show any geographical cline, the high density type (type D) occurred in limited areas where the winter was severe and spring came later and almost all the populations in the Oshima peninsula were the low density type (type A). The most common type of population in Hokkaido, type C, greatly fluctuated from year to year with the maximum density level/the minimum one being over 10. The periodicity of the peak years was not statistically significant, although peaks often occurred at 3 or 4 year intervals. The population grew from spring to autumn in almost all years so that the pattern of the seasonal change was qualitatively constant. The population density levels in spring were not significantly different between peak years and others, while those in autumn were greatly different between them, so that the population growth rates from spring to autumn were variable from year to year. This differential pattern was also found between high and low density areas.


Interaction between a 3-nitrobenzothiazolo (3,2-a) quinolinium antitumour drug and deoxyribonucleic acid.
The interaction of 3-nitrobenzothiazolo (3,2-a) quinolinium (NBQ) perchlorate with DNA was studied by u.v.-visible and fluorescence spectrophotometry as well as by hydrodynamic methods. On binding to DNA, the absorption spectrum underwent bathochromic and hypochromic shifts, and the fluorescence was quenched. Binding parameters, determined from spectrophotometric measurements by Scatchard analysis according to an excluded-site model, indicated a binding constant of 2.4 X 10(5)M-1 for calf thymus DNA at ionic strength 0.01. The interaction was markedly suppressed by increasing the salt concentration. Binding to the GC-rich DNA of Micrococcus lysodeikticus was weaker than the binding to calf thymus DNA at ionic strength 0.01 NBQ increased the viscosity of sonicated rod-like DNA fragments, producing a calculated increment in length of 2.4 A/bound drug molecule. It removed and reversed the supercoiling of closed circular duplex plasmid pBR322 DNA by virtue of a helix-unwinding angle estimated as approximately 13 degrees/bound ligand molecule. We conclude that the binding of NBQ to DNA occurs by a mechanism of intercalation, which probably accounts for its reported antitumor activity.


Ingestion and toxic impacts of weathered polyethylene (wPE) microplastics and stress defensive responses in whiteleg shrimp (Penaeus vannamei).
Weathered plastic litter is recognized as hazardous secondary microplastics(MPs) in the coastal and marine ecosystems, which are of high concern due to their greater impact on the environment. The present study aims to elucidate the impacts of environmentally weathered polyethylene (wPE) MPs on ingestion, growth and enzymatic responses in Penaeus vannamei. The Penaeus vannamei was chronically exposed to five varying concentration (0.1 mg-0.5 mg) of wPE particles in the size range between 43 and 32 μm for a period of 25days, followed by 5days depuration. At the end of exposure, a considerable number of wPE particles were observed from <2 to 14 per individual organism. However, around 60% of the wPE particles were removed after the depuration phase. The toxic exposure on P. vannamei resulted in significant changes in the enzymatic and growth responses with increasing concentration and duration. In addition, growth assessment confirmed that wPE exposure inhibited the growth of organism, and the effect was particularly evident at increasing concentrations and prolonged exposure. Also observed an elevated levels of lipid peroxidation, glutathione-S-transferases, whereas lower levels of reduced-glutathione and catalase at all exposed concentrations. This study confirmed that the ingestion of wPE was completely influenced by exposure duration, rather than the concentrations of administered. The present biomarker assay might act as an appropriate oxidative stress index for wPE toxicity. Findings of this study is useful in providing the basic biological information for environmental risk assessments of MPs, which are of high concern due to the rising input of microplastics into the environment.


Monodispersed NiO nanoflowers with anomalous magnetic behavior.
Nickel oxide (NiO) nanoflowers, prepared by thermal decomposition, exhibit anomalous magnetic properties far below the blocking temperature, i.e., a cusp in both the zero-field-cooled and field-cooled curves at about 21 K. Detailed characterization discloses that the individual NiO nanoflower consists of porous crystals with holes (1.0-1.5 nm in size) inside. We believe that the low temperature magnetic feature observed here could be a new kind of spin transition for the uncompensated spins around the holes and will trigger more studies in other nanostructured antiferromagnetic materials.


[The opinion on care of patients with cancer undergoing palliative treatment in day care].
To study the care utilisation and unmet care needs of patients receiving palliative treatment at the day care clinic of the Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital. Descriptive. During the periods 1 April-31 July 2000 and 1 April-31 May 2001 adult cancer patients were interviewed regarding their complaints and symptoms as a result of the disease and the treatment and regarding the problems that they had with the provision of care. There were 155 patients who agreed to participate: 56 men and 99 women, with an average age of 57.5 years. On average, they had 3.2 'severe' complaints. According to the patients, 65% of these 'severe' complaints were known by the specialists, 38% by the general practitioners, 24% by the day care nurses and 83% by the next of kin. Again according to the patients, 17% of the reported severe complaints received insufficient attention. About 25% of patients felt that they had received insufficient information about their disease, treatment, side effects and/or complications. The day care centre did not seem to be optimally equipped to meet the needs of patients receiving chemotherapy on an outpatient basis. According to the patients, the specialists were relatively the best informed of all the care providers about their complaints and problems.


Multiple tendon ruptures of unknown etiology.
Tendon ruptures are common findings in foot and ankle practice. The etiology of tendon ruptures tends to be multifactorial-usually due to a combination of trauma, effects of systemic diseases, adverse effects of medications, and obesity. We present an unusual case of right Achilles tendinitis, left Achilles tendon rupture, bilateral peroneus longus tendon rupture, and left peroneus brevis tendon rupture of unknown etiology. This case report highlights the need for research for other possible, lesser known etiologies of tendon pathology. Therapeutic, Level IV, Case Study.


Conformational study of the threonine-rich C-terminal pentapeptide of peptide T.
The conformation of the synthetic pentapeptide Thr-Thr-Asn-Tyr-Thr, the C-terminal part of peptide T has been studied using 2D NMR experiments. The nuclear Overhauser effects (NOESY) and the low temperature coefficients for two particular NH chemical shifts allow the proposal for two distinct beta-turn arrangements. This conformation is not in accordance with recent reports but is consistent with observed beta-bends in two sequences of ribonuclease A. The semi-rigid conformation found in the pentapeptide in which the hydroxyl groups are exposed at the periphery of the molecule could be a crucial feature to explain the ability of peptide T to bind to a specific receptor and to correlate with the observed biological activity against HIV.


Constitutional complex chromosomal rearrangements in a klinefelter patient: case report and review of literature.
While XXY aneuploidy is the most common disorder of sex chromosomes in men, complex chromosomal rearrangements (CCRs) are rare in humans. Here we describe clinical and cytogenetic findings in a male referred to our cytogenetic laboratory by an infertility clinic. The patient's age was 35 at the time of referral. Total azoospermia was confirmed on semen analysis. The karyotype of peripheral blood showed 47,XXY,t(1;3;5)(p22;q29;q22). The mother had the same CCRs. To our best of our knowledge this is the first case of 47,XXY with CCRs. We think it is important to report such a unique chromosomal occurrence.


Analysis of Functional NMDA Receptors in Astrocytes.
Neuronal N-methyl-D-aspartate (NMDA) receptors are well known for their pivotal role in memory formation. Originally, they were thought to be exclusive to neurons. However, numerous studies revealed their functional expression also on various types of glial cells in the nervous system. Here, the methodology how to study the physiology of NMDA receptors selectively on astrocytes will be described in detail. Astrocytes are the main class of neuroglia that control transmitter and ion homeostasis, which link cerebral blood flow and neuronal energy demands, but also affect synaptic transmission directly.


Autoimmune pancreatitis in a patient presenting with obstructive jaundice and pancreatic mass.
Autoimmune pancreatitis (AIP) is a rare cause of chronic pancreatitis. A case of obstructive jaundice with pancreatic mass mimicking malignancy is described. Recognition of the disease by its typical radiological and serological findings permits trial of steroid therapy and may avoid resection.


Abnormal magnesium levels and their impact on death and acute kidney injury in critically ill children.
The prevalence of magnesium imbalance in critically ill children is very high. However, its significance in the development of acute kidney injury (AKI) and mortality remains unknown. In this retrospective observational study from 2010 to 2018, the pediatric-specific intensive care database was analyzed. We included critically ill children aged > 3 months and those without chronic kidney disease. Patients were diagnosed with AKI, according to the Kidney Disease Improving Global Outcomes (KDIGO) study. We calculated the initial corrected magnesium levels (cMg) within 24 h and used a spline regression model to evaluate the cut-off values for cMg. We analyzed 28-day mortality and its association with AKI. The interaction between AKI and magnesium imbalance was evaluated. The study included 3,669 children, of whom 105 died within 28 days, while 1,823 were diagnosed with AKI. The cut-off values for cMg were 0.72 and 0.94 mmol/L. Both hypermagnesemia and hypomagnesemia were associated with 28-day mortality (odds ratio [OR] = 2.99, 95% confidence interval [CI] = 1.89-4.71, p < 0.001; OR = 2.80, 95% CI = 1.60-4.89, p < 0.001). Hypermagnesemia was associated with AKI (OR = 1.52, 95% CI = 1.27-1.82, p < 0.001), while neither hypermagnesemia nor hypomagnesemia interacted with the AKI stage on the 28-day mortality. Abnormal magnesium levels were associated with 28-day mortality in critically ill children. AKI and hypermagnesemia had a strong association. "A higher resolution version of the Graphical abstract is available as Supplementary information".


Interactions between year classes in the benthic amphipod Monoporeia affinis: effects on juvenile survival and growth.
The effect of 1-year-old Monoporeia (=Pontoporeia) affinis on the survival and growth of young of the year was studied in laboratory experiments. Amphipods were kept in jars with sediment and a continuous supply of cooled water for 3 months. Adults or juveniles were added to a control density of juveniles. Juvenile mortality increased at higher total densities, and was greater when adults were present. The mean length and dry weight of juveniles decreased at higher densities, but adults did not have a greater effect than juveniles. These density-dependent effects are probably caused by competition for food within and between year classes. Thus, a high abundance of juveniles or adults could reduce the recruitment of juveniles into the adult year-class the following year, and the suppression of juvenile growth could lower fecundity. The results of this experiment support the hypothesis, inferred from field data from the Baltic Sea and Swedish lakes, that intraspecific interactions contribute to fluctuations in the abundance of populations of M. affinis.


The extracellular signal-regulated kinase pathway may play an important role in mediating antidepressant-stimulated hippocampus neurogenesis in depression.
Understanding the reasons for the delayed action of antidepressants in patients with depression is an important step in the effort to understand the etiology and course of this disabling condition. Researches using animal models of depression find that depression is associated with impaired neurogenesis and structural plasticity in specific regions of the brain. Chronic treatment with antidepressants increases neurogenesis and reduces animal behaviors that are associated with depression. Other studies suggests that neurogenesis is an important component of the mechanism of action of both antidepressants and mood stabilizers. Moreover, the time course of increased neurogenesis is parallel to that of the behavioral effects, and animals with higher baseline hippocampus neurogenesis have a more rapid response to antidepressants. However, the molecular mechanisms that link antidepressants, neurogenesis and behavioral changes remain unknown. Previous research has shown that the extracellular signal-regulated kinase (ERK) signaling pathway plays an important role in regulating neurogenesis and synaptic plasticity in the brain and is activated by antidepressants and mood stabilizers. We hypothesize that the ERK pathway is the mechanism by which antidepressants regulate neurogenesis in the hippocampus and, thus, should be considered a potential target for the development of new antidepressants.


The role of the ventromedial hypothalamic area in periprandial glucoregulation.
There is a great deal of evidence that the ventromedial hypothalamic area (VMH) plays a significant role in glucoregulation. The present review synthesizes new and existing data in a coherent model of a hypothalamic glucoregulatory control system whose function is to stabilize blood glucose levels in the face of discontinuous exogenous supply attendant upon meal-feeding. Evidence is arrayed which suggest the VMH is critical in initiating the anticipatory insulin secretion in advance of the meal-related rise in blood-borne nutrients; that insulin rise acts as a messenger to the brain to reduce both CNS glucose utilization and endogenous glucose production in anticipation of the prandial glucose rise; that the VMH suppresses the reactive phase of insulin secretion which occurs in response to rising blood borne nutrients and finally that the VMH acts to restore endogenous production postprandially to ensure a smooth transition from use of exogenous, meal-derived energy back to endogenous stores. The net effect of this VMH modulation would be minimal periprandial glycemic perturbation. Implications of the model for diabetes and weight regulation are discussed.


Time course of efficacy of ubrogepant for the acute treatment of migraine: Clinical implications.
The full utility of an acute treatment requires examination of the entire time course of effect during a migraine attack. Here the time course of effect of ubrogepant is evaluated. ACHIEVE-I and -II were double-blind, single-attack, Phase 3 trials. Adults with migraine were randomised 1:1:1 to placebo or ubrogepant (50mg or 100mg, ACHIEVE-I; 25 mg or 50 mg, ACHIEVE-II). Pain freedom, absence of most bothersome symptom, and pain relief were assessed at various timepoints. Samples were collected for pharmacokinetic analysis. Data were pooled for this post-hoc analysis. Participants' (n = 912 placebo, n = 887 ubrogepant 50 mg, pooled analysis population) mean age was 41 years, with a majority female and white. Pain relief separated from placebo by 1 h (43% versus 37% [OR, 95% CI: 1.30, 1.0-1.59]), absence of most bothersome symptom by 1.5 h (28% versus 22% [1.42, 1.14-1.77]), and pain freedom by 2 h (20% vs. 13% [1.72, 1.33-2.22]). Efficacy was sustained from 2-24 h (pain relief: 1.71, 1.1-2.6; pain freedom: 1.71, 1.3-2.3) and remained separated at 48 h (pain relief: 1.7, 1.1-2.6; pain freedom: 1.31, 1.0-1.7). Pharmacokinetic analysis demonstrated maximum plasma concentrations were achieved at 1 h, with pharmacologically active concentrations reached within 11 min and remaining above the EC90 for nearly 12 h. Evaluation of the time course of effect of ubrogepant showed pain relief as the most sensitive and earliest measure of clinical effect, followed by absence of most bothersome symptom, and pain freedom. Efficacy was demonstrated out to 48 h, providing evidence of the long-lasting effect of ubrogepant. This evaluation supports the role of examining the entire time course of effect to understand fully the utility of an acute treatment for migraine.Trial registration: ACHIEVE I (ClinicalTrials.gov, NCT02828020) and ACHIEVE II (ClinicalTrials.gov, NCT02867709).


Imaging features of radiation-induced lung disease and its relationship with clinical and dosimetric factors in breast cancer patients.
The aim is to extensively evaluate imaging features of radiation induced lung disease in breast cancer patients and to determine the relationship of imaging alterations with dosimetric parameters and patient related characteristics. A total of 76 breast cancer patients undergoing radiotherapy (RT) were studied retrospectively by case notes, treatment plans, dosimetric parameters, and chest computed tomography (CT) scans. Time intervals, that chest CT scans were acquired, were grouped as 1-6 months, 7-12 months, 13-18 months and more than 18 months after RT. Chest CTs (one or more for each patient) were assessed for the presence of ground glass opacity, septal thickening, consolidation/patchy pulmonary opacity/alveolar infiltrates, subpleural air cyst, air bronchogram, parenchymal bands, traction bronchiectasis, pleural/subpleural thickening and pulmonary volume loss. These alterations were scored by applying a system devised by Nishioka et al. Nishioka scores were analyzed for the relationship with clinical and dosimetric factors. IBM SPSS Statistics for Windows, version 22.0 (IBM Corp., Armonk, N.Y., USA) was used to analyze data. Median follow-up time was 49 months. Advanced age and aromatase inhibitor intake were correlated with higher Nishioka scores for 1-6 months' period. However, both were found nonsignificant in multivariate analysis. Nishioka scores of CT scans acquired more than 12 months after RT were positively correlated with mean lung dose, V5, V20, V30, and V40. Receiver operating characteristic analysis revealed that V5 for ipsilateral lung was the most robust dosimetric parameter predicting chronic lung injury. V5 >41% indicates the development of radiological lung changes. Keeping V5 ≤41% for ipsilateral lung could provide avoiding chronic lung sequelae.


[Epidemiologic characteristics and serologic findings in erythema migrans].
Our three-year research covered 417 patients with erythema migrans, of both sexes and all age groups. Among them 87.3% had a history of tick bite. Average attachment of tick to a patients skin was two days. Diameter of erythematous lesions was 1-50 cm (with an average of 15.1 cm). Magnitude of the lesion does not correlate with the further development of the Lyme disease. IFA test detected antibodies against Borreliae burgdorferi in 27.0% of our patients.


Tocotrienol-rich fraction from annatto ameliorates expression of lysyl oxidase in human osteoblastic MG-63 cells.
Lysyl oxidase (LOX) is required for the formation of bone collagen cross-links. Inactivation of the LOX gene in osteoblasts by DNA methylation and JAK signaling has been reported to cause loss of cross-links and an increased risk of fractures. Tocotrienols (T3s) have proven benefits on bone strength, but their potential effects on LOX remain largely unknown. Thus, the present study investigates the in vitro effects of T3s on LOX expression in human osteoblastic MG-63 cells. Results indicated that Tocotrienol-Rich Fraction (TRF), the δ-T3 rich oil extracted from Annatto was the most effective and significantly increased LOX expression. TRF treatment decreased de-novo methyltransferases (DNMTs), DNMT3A and DNMT3B levels. In addition, TRF significantly inhibited JAK2 activation and decreased expression of Fli1, a transcription factor of DNMTs. We conclude that TRF induced an increase in LOX expression via inhibition of de-novo methylation and reduction of Fli1 expression by the inactivation of JAK2.Abbreviations: CpG: cytosine-guanine dinucleotide; DNMT: DNA methyltransferase; Fli1: friend leukemia virus integration 1; JAK: janus kinase; LOX: lysyl oxidase; PCR: polymerase chain reaction; STAT: signal transducers and activators of transcription; T3s: tocotrienols; TPs: tocopherols; TRF: Tocotrienol-Rich Fraction.


Predicting undesirable drug interactions with promiscuous proteins in silico.
Although computational tools have been used to predict toxic responses resulting from molecules binding either as substrates or inhibitors to proteins, there are complications to be resolved. Some proteins appear promiscuous in their ability to bind a diverse array of hydrophobic molecules. This promiscuity arises from the binding site simultaneously accommodating more than one molecule, multiple separate binding sites, protein flexibility, or a combination of all these properties. With the availability of more crystal structures for these non-target proteins, we should be able to predict binding in silico with a greater accuracy, thus avoiding or managing toxic side effects, therefore ultimately improving the success of drug discovery.


Transthoracic and transesophageal echocardiographic assessment of mitral regurgitation severity: usefulness of qualitative and semiquantitative techniques.
In this report, we review the advantages, limitations, and optimal utilization of various transthoracic and transesophageal echocardiographic (TTE and TEE) methods used for assessing mitral regurgitation (MR) as published in full-length, peer-reviewed articles since the color Doppler era began in 1984. In addition, comparison is made to other imaging modalities including catheter-based, magnetic resonance and surgical assessment of MR. Although left ventricular (LV) angiography has been traditionally used for validation of various TTE methods and is time-honored, its considerable limitations preclude it from being a real "gold standard." Based on the reviewed literature, no clear "gold standard" for the assessment of MR can be identified at present, but newly emerging TTE and TEE techniques, such as three-dimensional color Doppler, may have the potential to overcome some of the limitations of the two-dimensional methods.


Regulation of conventional protein kinase C isozymes by phosphoinositide-dependent kinase 1 (PDK-1).
Phosphorylation critically regulates the catalytic function of most members of the protein kinase superfamily. One such member, protein kinase C (PKC), contains two phosphorylation switches: a site on the activation loop that is phosphorylated by another kinase, and two autophosphorylation sites in the carboxyl terminus. For conventional PKC isozymes, the mature enzyme, which is present in the detergent-soluble fraction of cells, is quantitatively phosphorylated at the carboxy-terminal sites but only partially phosphorylated on the activation loop. This study identifies the recently discovered phosphoinositide-dependent kinase 1, PDK-1, as a regulator of the activation loop of conventional PKC isozymes. First, studies in vivo revealed that PDK-1 controls the amount of mature (carboxy-terminally phosphorylated) conventional PKC. More specifically, co-expression of the conventional PKC isoform PKC betaII with a catalytically inactive form of PDK-1 in COS-7 cells resulted in both the accumulation of non-phosphorylated PKC and a corresponding decrease in PKC activity. Second, studies in vitro using purified proteins established that PDK-1 specifically phosphorylates the activation loop of PKC alpha and betaII. The phosphorylation of the mature PKC enzyme did not modulate its basal activity or its maximal cofactor-dependent activity. Rather, the phosphorylation of non-phosphorylated enzyme by PDK-1 triggered carboxy-terminal phosphorylation of PKC, thus providing the first step in the generation of catalytically competent (mature) enzyme. We have shown that PDK-1 controls the phosphorylation of conventional PKC isozymes in vivo. Studies performed in vitro establish that PDK-1 directly phosphorylates PKC on the activation loop, thereby allowing carboxy-terminal phosphorylation of PKC. These data suggest that phosphorylation of the activation loop by PDK-1 provides the first step in the processing of conventional PKC isozymes by phosphorylation.


Noninvasive diagnosis of coronary artery fistula by Doppler color flow mapping.
Sixteen patients with coronary artery fistula proved by coronary angiography or surgery were studied using two-dimensional echocardiography and Doppler color flow mapping. The coronary artery fistula drained into the right atrium in 4 patients, the right ventricle in 2 and the pulmonary artery in 10. The dilated coronary artery was visualized in 7 of the 16 patients with a fistula, as compared with none of the 40 control subjects. These 7 patients included 5 of 6 patients with a fistula draining into the right atrium or right ventricle and only 2 of 10 patients with a fistula draining into the pulmonary artery. Abnormal flow signals in the dilated coronary artery were visualized with Doppler color flow mapping in five of these seven patients. Color flow imaging visualized abnormal flow signals with mosaic appearance in the pulmonary artery in eight patients, the right atrium in four and the right ventricle in two. The chamber in which abnormal signals were detected corresponded with the entry site of the fistula by angiography. Intraoperative imaging during surgical repair was needed in two cases to confirm ligation of all arteries feeding into the fistula network. In conclusion, Doppler color flow imaging is diagnostically useful to visualize shunt flows originating from the opening or exit of a coronary artery fistula. Furthermore, intraoperative use of this technique may provide confirmation of successful surgical ligation of the fistula.


A metabolic pathway assembled by enzyme selection may support herbivory of leaf-cutter ants on plant starch.
Mutualistic associations shape the evolution in different organism groups. The association between the leaf-cutter ant Atta sexdens and the basidiomycete fungus Leucoagaricus gongylophorus has enabled them to degrade starch from plant material generating glucose, which is a major food source for both mutualists. Starch degradation is promoted by enzymes contained in the fecal fluid that ants deposit on the fungus culture in cut leaves inside the nests. To understand the dynamics of starch degradation in ant nests, we purified and characterized starch degrading enzymes from the ant fecal fluid and from laboratory cultures of L. gongylophorus and found that the ants intestine positively selects fungal α-amylase and a maltase likely produced by the ants, as a negative selection is imposed to fungal maltase and ant α-amylases. Selected enzymes are more resistant to catabolic repression by glucose and proposed to structure a metabolic pathway in which the fungal α-amylase initiates starch catalysis to generate byproducts which are sequentially degraded by the maltase to produce glucose. The pathway is responsible for effective degradation of starch and proposed to represent a major evolutionary innovation enabling efficient starch assimilation from plant material by leaf-cutters.


Sufficient penetration of peracetic acid into drilled human femoral heads.
Chemical sterilisation methods for musculoskeletal transplants have the problem of penetration into all tissue strata. The present study examined if a peracetic acid/ethanol solution penetrated to a sufficient extent into specifically prepared femoral heads. To this effect, 10 femoral heads have been provided with drillings (diameter 2 mm, depth 10 mm) at a distance of 15 mm (series B) and placed in a diffusion chamber with sterilisation solution. From an additional central drilling at the femoral neck junction, the sample drawing was made after 30 min each over a period of 4 h for the iodometric determination of peracetic acid (PAA) concentration. Ten femoral heads, which did contain only the central drilling, served as controls (series A). In 9 of the examined femoral heads of series A the defined minimum concentration of PAA of 0.2% (inactivation of bacteria, spores, fungi) has been clearly exceeded over the complete period of measurement. About 0.8% PAA (inactivation of viruses) was achieved within 4 h only with six femoral heads. Nine out of the 10 examined femoral heads in series B show a clearly improved penetration behaviour which was expressed in smaller standard deviations, a faster increase in concentration, as well as in higher starting and final concentrations (approx. 0.9%) of PAA. Previous drying in air leads to a faster penetration into the centre of the bone. Standardised drilling of de-cartilaged femoral heads creates favourable conditions for the penetration of the PAA sterilisation solution into the whole tissue and guarantees a sufficient inactivation of microorganisms.


Do clinicians conceptualize DSM-IV disorders hierarchically?
All classification systems of psychopathology use hierarchical categories. The purpose of the two studies in this article was to test whether clinicians think hierarchically about mental disorders. Seventy six clinicians were asked to sort 67 diagnostic categories into groups using different instruction sets, either to make progressively larger and smaller groups of diagnoses (Study 1) or to place similar groups next to each other (Study 1 and Study 2). Clinicians' sortings of mental disorders had a hierarchical structure regardless of the methodology, profession, expertise, and instructional set used. Given that all modern diagnostic systems have been hierarchical, it is important to know that clinicians' thinking is also hierarchical.


Opioid receptor selectivity profile change via isosterism for 14-O-substituted naltrexone derivatives.
Isosterism is commonly used in drug discovery and development to address stability, selectivity, toxicity, pharmacokinetics, and efficacy issues. A series of 14-O-substituted naltrexone derivatives were identified as potent mu opioid receptor (MOR) antagonists with improved selectivity over the kappa opioid receptor (KOR) and the delta opioid receptor (DOR), compared to naltrexone. Since esters are not metabolically very stable under typical physiological conditions, their corresponding amide analogs were thus synthesized and biologically evaluated. Unlike their isosteres, most of these novel ligands seem to be dually selective for the MOR and the KOR over the DOR. The restricted flexibility of the amide bond linkage might be responsible for their altered selectivity profile. However, the majority of the 14-N-substituted naltrexone derivatives produced marginal or no MOR stimulation in the (35)S-GTP[γS] assay, which resembled their ester analogs. The current study thus indicated that the 14-substituted naltrexone isosteres are not bioisosteres since they have distinctive pharmacological profile with the regard to their opioid receptor binding affinity and selectivity.


Multicentric papillary renal carcinoma in renal allograft.
A renal transplant recipient with 13 years of excellent allograft function was found incidentally to have a malignant mass in his transplanted kidney. After resection, pathological analysis showed 29 separate lesions of renal cell carcinoma. All tumors were confined within the renal capsule. The majority of tumors (21 of 29 tumors) were chromophil basophilic carcinoma with papillary architecture, 5 tumors were clear cell, 2 tumors were mixed cell type, and 1 tumor was chromophil eosinophilic papillary carcinoma. These histological findings are similar to those reported in hereditary papillary renal carcinoma. To our knowledge, this is the first case of multicentric papillary renal carcinoma occurring in the renal allograft. We speculate that the allograft in this case is predisposed to malignant changes because of preexisting genetic mutations, as well as prolonged immunosuppression.


Medical Record Linkage of Anonymous Registries without Validated Sample Linkage of the Dutch Perinatal Registries.
This paper describes the linkage of data from three Dutch Perinatal Registries: the Dutch National Midwife Registry, the Dutch National Obstetrics Registry and the Dutch National Pediatrics Registry, for the year of 2001. All these registries are anonymous and lack a common identifier. We used probabilistic and deterministic record linkage techniques to combine data from the mother, delivery and child involving to the same pregnancy. Records of singleton and twin pregnancies were linked separately. We have developed a probabilistic close method based on maximum likelihood methods to estimate the weights of individual linking variables and the threshold value for the overall weight. Probabilistic linkage identified 80% more links than a full deterministic linkage approach. External validation revealed an error rate of less than 1%. Our method is a flexible and powerful method to link anonymous registries in the absence of a gold standard.


Mechanism and isotherm modeling of effective adsorption of malachite green as endocrine disruptive dye using Acid Functionalized Maize Cob (AFMC).
Cationic Malachite green has been identified as a candidate for the endocrine disruptive compound found in the environment. In this study, the mechanism and isotherm modeling of effective adsorption of cationic malachite green dye onto acid-functionalized maize cob (AFMC) was investigated by batch technique. The operational parameters such as initial concentration (100-600 mg/L); contact time (10-120 min) and pH (3-10) influenced the removal efficiency and quantity adsorbed. A maximum of 99.3% removal efficiency was obtained at optimum conditions. AFMC physicochemical properties (surface area 1329 m2/g and particle size 300 μm < Ф < 250 μm) enhanced its efficiency. Based on R2 > 0.97 and consistently low values of adsorption statistical error functions (ASEF), equilibrium data were best fitted to Freundlich isotherm. Kinetic data were best described by a pseudo-second-order model with consistent R2 > 0.98 and validated by ASEF. The mechanism of the process was better described by intraparticle diffusion. Evidence of the adsorption process was confirmed by the change in morphology via Scanning Electron Microscopy (SEM) and surface chemistry by Fourier Transform infrared (FTIR). The performance of AFMC enlisted it as a sustainable and promising low-cost adsorbent from agro-residue for treatment of endocrine disruptive dye polluted water.


'O-Acyl isopeptide method' for the efficient preparation of amyloid beta peptide 1-42 mutants.
Novel water-soluble isopeptides of Abeta1-42 mutants, '26-O-acyl isoAbeta1-42 (26-AIAbeta42) mutants', which were efficiently converted to intact Abeta1-42 mutants with no byproduct formation under physiological conditions, were synthesized. These isopeptides provide a new system useful for investigating the biological function of Abeta1-42 mutants.


Risky business? Investigating outcomes of patients undergoing urgent laparoscopic appendectomy on antithrombotic therapy.
The literature regarding outcomes in patients on irreversible antithrombotic therapy (IAT) undergoing urgent laparoscopic appendectomy is limited. The aim of this multicenter retrospective study was to examine the impact of prehospital IAT on outcomes in this population. From 2010 to 2014, seven institutions from the Southwest Surgical Multicenter Trials (SWSC MCT) group conducted a retrospective study to evaluate the clinical course of all patients on IAT who underwent urgent/emergent laparoscopic appendectomy. The IAT+ group was subdivided into IAT+ (Aspirin only) and IAT+ (Aspirin-Plavix). These groups were matched 1:1 to controls. The primary outcomes were estimated blood loss (EBL) and transfusion requirement. Secondary outcomes included infections (SSI - Surgical Site Infection, DSI - Deep Space Infection, and OSI - Organ Space Infection), hospital length of stay (HLOS), complications, 30-day readmissions, and mortality. Out of the 2903 patients included in the study, 287 IAT+ patients were identified and matched in a 1:1 ratio to 287 IAT-patients. In the IAT+ vs IAT-analysis, no significant differences in EBL (p = 1.0), transfusion requirement during the preoperative (p = 0.5), intraoperative (p = 0.3) or postoperative periods (p = 0.5), infectious complications (SSI; p = 1.0, DSI; p = 1.0, and OSI; p = 0.1), overall complications (p = 0.3), HLOS (p = 0.7), 30-day readmission (p = 0.3), or mortality (p = 0.1) were noted. Similarly, outcomes in the IAT+ (Aspirin only) and IAT+ (Aspirin-Plavix) subgroups failed to demonstrate any significant differences when compared to controls. Our analysis suggests that IAT is not associated with worse outcomes in urgent/emergent laparoscopic appendectomy. Prehospital use of IAT should not be used to delay laparoscopic appendectomy.


Concurrent palliative chemoradiation leads to survival and quality of life benefits in poor prognosis stage III non-small-cell lung cancer: a randomised trial by the Norwegian Lung Cancer Study Group.
The palliative role of chemoradiation in the treatment of patients with locally advanced, inoperable non-small-cell lung cancer stage III and negative prognostic factors remains unresolved. Patients not eligible for curative radiotherapy were randomised to receive either chemoradiation or chemotherapy alone. Four courses of intravenous carboplatin on day 1 and oral vinorelbin on days 1 and 8 were given with 3-week intervals. Patients in the chemoradiation arm also received radiotherapy with fractionation 42 Gy/15, starting at the second chemotherapy course. The primary end point was overall survival; secondary end points were health-related quality of life (HRQOL) and toxicity. Enrolment was terminated due to slow accrual after 191 patients from 25 Norwegian hospitals were randomised. Median age was 67 years and 21% had PS 2. In the chemotherapy versus the chemoradiation arm, the median overall survival was 9.7 and 12.6 months, respectively (P<0.01). One-year survival was 34.0% and 53.2% (P<0.01). Following a minor decline during treatment, HRQOL remained unchanged in the chemoradiation arm. The patients in the chemotherapy arm reported gradual deterioration during the subsequent months. In the chemoradiation arm, there were more hospital admissions related to side effects (P<0.05). Chemoradiation was superior to chemotherapy alone with respect to survival and HRQoL at the expense of more hospital admissions due to toxicity.


Irregular-shaped platinum nanoparticles as peroxidase mimics for highly efficient colorimetric immunoassay.
Enzyme-linked immunosorbent assay (ELISA) methods based on natural enzyme-labeled probes have been applied in the immunoassays, but most have some inevitable limitations (e.g. harsh preparation, purification and storage) and are unsuitable for routine use. Herein we synthesized a new class of irregular-shaped platinum nanoparticles (ISPtNP) with a mean length of 7.0 nm and a narrowing width from 2.0 to 5.0 nm along the longitudinal axes, which were utilized as peroxidase-like mimics for the development of colorimetric immunoassays. Compared with bioactive horseradish peroxidase (HRP), the synthesized ISPtNP exhibited a low Km value (~0.12 mM) and a high Kcat value (~2.27×10(4)s(-1)) for 3,3',5,5'-tetramethylbenzidine (TMB) with strong thermal stability and pH tolerance. The catalytic mechanism of the ISPtNP toward TMB/H2O2 was for the first time discussed and deliberated in this work. Based on a sandwich-type assay format, two types of colorimetric immunoassay protocols were designed and developed for the detection of rabbit IgG (RIgG, as a model) by using the synthesized ISPtNP and conventional HRP as the labeling of detection antibodies, respectively. Similar detection limits (LODs) of 2.5 ng mL(-1) vs. 1.0 ng mL(-1) were obtained toward RIgG with the ISPtNP labeling compared to HRP format. Intra- and inter-assay coefficients of variation were less than 13%. Importantly, the ISPtNP-based assay system could be suitable for use in a mass production of miniaturized lab-on-a-chip devices and open new opportunities for protein diagnostics and biosecurity.


Solitary Testicular Myofibroma in a Rabbit.
Myofibromas are mesenchymal tumours of myofibroblastic origin that occur in solitary or multicentric forms. Solitary benign myofibromas mainly occur on the head and neck, especially in the subcutaneous region. They rarely occur in visceral organs in humans, but visceral myofibroma has not been reported in animals. We now report a case of testicular myofibroma in a 6-year-old rabbit in which orchiectomy revealed an enlarged testis with a multinodular surface. The cut surface of the testis showed a thick, homogeneous white-yellow mass surrounding the testicular parenchyma. Histopathologically, the mass was composed of collagen and eosinophilic fascicles of spindle cells that were immunopositive for α-smooth muscle actin but not desmin, S-100 or von Willebrand factor. These features distinguished the myofibroma from other spindle cell tumours. To the best of our knowledge, this is the first report of solitary testicular myofibroma in any animal species.


[Induction of bacterial translocation in rats with minimal doses of endotoxin].
To determine whether a non lethal dose of intramuscular endotoxin in rats causes a physical disruption of the mucosal barrier and promotes the translocation of bacteria from gut to visceral organs. Prospective randomized trial. Experimental laboratory university medical center. 60 male wistar rats, weighing 250 g. six hours and twenty-four hours after endotoxin (8 mg/kg) or saline (control group) given intramuscularly, rats were sacrificed and mesenteric lymph nodes, spleen and some segments of the ileum were removed. Lymph nodes and spleen were cultured for translocating bacteria while ileum segments were observed by light microscopy. Incidence of bacterial translocation increases from 6 hours (40% p < 0.05) to 24 hours (60%, p < 0.01) after endotoxin administration. Histologic evaluation of the ileum demonstrated that a mucosal injury occurred only at the 24 an hour and that it was characterized by an evident pronounced interstitial edema with focal breaks in the basal membranes of villous and glands. It appears that microorganisms and microbial products contained in the gut can cross the mucosal barrier and spread into other visceral organs also after a low dose of intramuscular endotoxin.


Pain in Patients With Type 2 Diabetes-Related Polyneuropathy Is Associated With Vascular Events and Mortality.
Type 2 diabetes-related polyneuropathy (DPN) is associated with increased vascular events and mortality, but determinants and outcomes of pain in DPN are poorly understood. We sought to examine the effect of neuropathic pain on vascular events and mortality in patients without DPN, DPN with pain (DPN + P), and DPN without pain (DPN-P). A retrospective cohort study was conducted within a large health system of adult patients with type 2 diabetes from January 1, 2009 through December 31, 2016. Using an electronic algorithm, patients were classified as no DPN, DPN + P, or DPN-P. Primary outcomes included number of vascular events and time to mortality. Independent associations with DPN + P were evaluated using multivariable negative binomial and Cox proportional hazards regression models, adjusting for demographics, socioeconomic characteristics, and comorbidities. Of 43 945 patients with type 2 diabetes (age 64.6 ± 14.0 years; 52.1% female), 13 910 (31.7%) had DPN: 9104 DPN + P (65.4%) vs 4806 DPN-P (34.6%). Vascular events occurred in 4538 (15.1%) of no DPN patients, 2401 (26.4%) DPN + P, and 1006 (20.9%) DPN-P. After adjustment, DPN + P remained a significant predictor of number of vascular events (incidence rate ratio [IRR] = 1.55, 95% CI, 1.29-1.85), whereas no DPN was protective (IRR = 0.70, 95% CI, 0.60-0.82), as compared to DPN-P. Compared to DPN-P, DPN + P was also a significant predictor of mortality (hazard ratio = 1.42, 95% CI, 1.25-1.61). Our study found a significant association between pain in DPN and an increased risk of vascular events and mortality. This observation warrants longitudinal study of the risk factors and natural history of pain in DPN.


[Histochemical and ultrastructural investigations on the activity of methylglyoxal (bis)-guanylhydrozan (methyl-GAG) on organ cultures of malignant tumors (author's transl)].
Methyl-GAG was tested in organotypic cultures of malignant tumors of human and mice. In 3 cases, a reduction of the activity of two oxydoreductases (lactate dehydrogenase and NADH-diaphorase) after treatment with methyl-GAG was observed whereas in 19 other cultivated tumors no change of enzyme activity was induced by methyl-GAG. Electronmicroscopy revealed only minor structural alterations of tumor cells after application of methyl-GAG as compared with control cultures.


Neuropeptide substance P: A promising regulator of wound healing in diabetic foot ulcers.
In the past, neuropeptide substance P (SP) was predominantly recognized as a neuroinflammatory factor, while its potent healing activity was overlooked. This paper aims to review the regulatory characteristics of neuropeptide SP in both normal and diabetic wound healing. SP actively in the regulation of wound healing-related cells directly and indirectly, exhibiting robust inflammatory properties, promoting cell proliferation and migration and restoring the activity and paracrine ability of skin cells under diabetic conditions. Furthermore, SP not only regulates healing-related cells but also orchestrates the immune environment, thereby presenting unique and promising application prospects in wound intervention. As new SP-based preparations are being explored, SP-related drugs are poised to become an effective therapeutic intervention for diabetic foot ulcers (DFU).


Transplantation of the fetal occipital cortex to the third ventricle of SCN-lesioned rats induces a diurnal rhythm in drinking behavior.
Fetal hypothalamic transplants which include the suprachiasmatic nuclei (SCN), were shown previously to be capable of restoring circadian rhythmicity as manifested by both diurnal and free-running rhythms in drinking behavior in rats rendered arrhythmic by SCN lesions. The question arises as to whether the transplant must be homologous tissue or whether any other fetal brain tissue can produce similar effects. In this study rats with a lesion of the SCN and with clear loss of drinking rhythms received grafts of fetal occipital cortex placed into the third ventricle. Following the graft, animals were placed in LD conditions for 8 weeks and then in DD for another 8 weeks. The results indicate that the cortical graft induced recovery of a drinking rhythm under LD lighting conditions but that under DD the rhythm was lost again. These results suggest that non-hypothalamic tissue can mediate recovery of a diurnal rhythm but that hypothalamic tissue including the SCN is required to restore circadian function with maintenance of free-running rhythms.


An unusual case of benign reflex myoclonic epilepsy of infancy.
A previously healthy one-year-old boy, the youngest child of unrelated parents, presented with a four-week history of episodes of myoclonus triggered only by tactile stimulation to his head. There had been no loss of developmental skills. The electroencephalogram (EEG) revealed generalised polyspike wave activity both with and without clinical correlate. The infant was started on sodium valproate, which resulted in cessation of the myoclonic episodes one week after starting therapy. At subsequent follow-up (at 18 months) the infant was seizure free and a repeat EEG was normal. This case of non-progressive reflex myoclonic epilepsy of infancy triggered only by head tapping (and not by acoustic stimuli) is an extremely rare phenomenon. Reflex myoclonic epilepsy of infancy represents a distinct subtype of myoclonic epilepsy in infancy. It should be considered as an age-dependent idiopathic generalised epileptic syndrome with an apparently good prognosis.


Mapping the RNA-binding domain on the DpCPV VP4.
The RNA-binding properties of VP4 protein of Dendrolimus punctatus cytoplasmic polyhedrosis virus (DpCPV) VP4 were analyzed. VP4 was expressed in E. coli and assayed for RNA binding activity by gel mobility shift assay. VP4 was found to bind RNA (ssRNA and dsRNA) in a sequence-independent manner, but did not interact with DNA. To identify the domain(s) of the protein important for RNA binding, a number of deletions were made and tested by gel mobility shift assays and northwestern blot. The central region of VP4 from amino acid residues 77 to 155 was found to contain the RNA binding domain.


Reduced hypoxia tolerance and survival at elevated temperatures may limit the ability of Amazonian fishes to survive in a warming world.
The Amazon basin contains more than 20% of the world's freshwater fishes, many of ecological and economical importance. An increase in temperature of 2.2 to 7 °C is predicted to occur within the next century in the worst-case scenario of climate change predictions, which will likely be associated with an increase in the prevalence and duration of reduced water oxygen levels (hypoxia). Furthermore, there is an increasing frequency of heat waves in the Amazon basin, which exacerbates issues related to temperature and hypoxia. Increases in temperature and hypoxia both constrain an organism's ability to supply oxygen to metabolizing tissues, thus the ability to cope with thermal and hypoxic stress may be correlated. Here, we reveal a positive correlation between acute thermal tolerance and acute hypoxia tolerance amongst 37 Amazonian fish species at the current river temperatures of 28-31 °C. The effects of long-term (10 days or 4 weeks) increases in temperature were investigated in a subset of 13 species and demonstrated that 2 species failed to acclimate and survive at 33 °C, 9 species failed at 35 °C, and only 2 species survived up to 35 °C. Of those that survived long-term exposure to 33 or 35 °C, the majority of the species demonstrated only an improvement in acute thermal tolerance. In contrast, hypoxia tolerance was reduced following acute- and long-term exposure to 33, 35 or 37 °C in all species investigated. The results of this study suggest that many of the fish species that inhabit the Amazon may be at risk during both short- and long-term temperature increases and these risks are exacerbated by the associated environmental hypoxia.


Effectiveness of psychoeducation interventions in reducing negative psychological outcomes and improving coping skills in caregivers of children with cancer: A systematic review and meta-analysis.
Psychoeducation interventions (PEIs) have been used as an adjunct treatment for negative psychological outcomes in caregivers of children with cancer. This systematic review and meta-analysis aimed to evaluate the evidence on the effectiveness of PEIs in reducing anxiety and depressive symptoms and improving health-related quality of life (HRQoL) and coping skills in caregivers of children with cancer. Ten English databases were searched to identify studies on PEIs for caregivers of children with cancer. Studies inclusion criteria were as follows: (1) participants who were caregivers of children with cancer receiving treatment; (2) psychoeducational interventions assessing anxiety, depressive symptoms, HRQoL, and coping outcomes; and (3) usual care, waitlist, or active control as a control group. Meta-analysis and narrative synthesis were used to analyse data. Fourteen randomised control trials were included. PEIs have a beneficial effect on anxiety levels (SMD: -0.59, 95% CI [-0.92, -0.25], p = 0.0007), quality of life (SMD: -0.31, 95% CI [-0.00, -0.61], p = 0.05) and depressive symptoms (SMD: -1.18, 95% CI [-2.08, -0.28], p = 0.01) immediately post-intervention. The effect of PEIs was maintained at long-term follow-up on depressive symptoms (SMD: -0.52, 95% CI [-1.54, -0.36], p = 0.0004). Similarly, the synthesised data suggest that PEIs are effective in improving coping skills. The review provides evidence that PEIs effectively reduce negative psychological outcomes and improve coping skills in caregivers of children with cancer. However, due to methodological flaws and heterogeneity of the interventions evaluated, more research is needed to determine the most effective PEI design and improve the quality of evidence.


Molecular and negative ion production by a standard electron cyclotron resonance ion source.
Molecular and negative ion beams, usually produced in special ion sources, play an increasingly important role in fundamental and applied atomic physics. The ATOMKI-ECRIS is a standard ECR ion source, designed to provide highly charged ion (HCI) plasmas and beams. In the present work, H(-), O(-), OH(-), O(2)(-), C(-), C(60)(-) negative ions and H(2)(+), H(3)(+), OH(+), H(2)O(+), H(3)O(+), O(2)(+) positive molecular ions were generated in this HCI-ECRIS. Without any major modification in the source and without any commonly applied tricks (such as usage of cesium or magnetic filter), negative ion beams of several μA and positive molecular ion beams in the mA range were successfully obtained.


Effects of resveratrol supplementation on nitric oxide-mediated vascular outcomes in hypertension: A systematic review.
Hypertension is associated with endothelial dysfunction and decreased nitric oxide (NO). It has been proposed that decreasing oxidative stress may help regulate blood pressure by increasing NO concentration. Therefore, the purpose of this systematic review was to determine whether the antioxidant resveratrol effects NO-mediated vascular outcomes in hypertension. A comprehensive literature search of PubMed and EBSCOhost databases was conducted using the terms: "resveratrol" and "nitric oxide or NO" and "hypertension or high blood pressure." Searches were not restricted for year of publication or study design but limited to full-text studies from scholarly, peer-reviewed journals. Ten animal studies published between 2005 and 2017 were identified. Human studies did not meet criteria and were not included. Articles were critically assessed using the Academy of Nutrition and Dietetics' Evidence Analysis Library Quality Criteria Worksheet. All studies evaluated resveratrol supplementation and at least one NO outcome measure including: circulating NO metabolites, endothelial nitric oxide synthase (eNOS) expression, eNOS phosphorylation, and eNOS uncoupling. All but one study assessed blood pressure. Nine of ten studies reported positive significant results of resveratrol supplementation on NO outcomes, and in all but one study, this was seen concomitantly with decreases in blood pressure. Resveratrol supplementation shows promise for improving NO-mediated vascular outcomes and improving blood pressure. Translation to human studies is warranted, with dose of resveratrol considered, as the human equivalency doses are not consistent amongst animal studies. Additionally, a standard battery of tests examining NO-mediated vascular outcomes is needed to ensure generalizability among studies to determine dose-duration effects.


Measuring Substance Use and Misuse via Survey Research: Unfinished Business.
This article reviews unfinished business regarding the assessment of substance use behaviors by using survey research methodologies, a practice that dates back to the earliest years of this journal's publication. Six classes of unfinished business are considered including errors of sampling, coverage, non-response, measurement, processing, and ethics. It may be that there is more now that we do not know than when this work began some 50 years ago.


Comparison of ongoing compound field potentials in the brains of invertebrates and vertebrates.
(1) Ongoing compound field potential fluctuations of higher brain centers (the micro-EEG of some authors) are considered as a biological phenomenon, a sign of the activity in the organized assemblage of cells. Such activity has been compared in several taxa with quite different brain structure to look for possible evolution in the form of the field potentials and for possible explanations of differences and similarities. (2) Recordings were made with semimicroelectrodes in the neuropile of the cerebral ganglion of the mollusc, Aplysia, with comparative observations on Helix, and the arthropods Limulus, Melanoplus, and Cambarus, and in or on the cerebral cortex and optic tectum of rays, cats and rabbits, with comparative observations on sharks, bony fish, turtles and geckos in unstimulated resting or generalized arousal states. Manipulations of state did not alter the main findings. (3) Power spectra in the cerebral ganglia of various higher invertebrates are similar; activity is fast and spikey (with the exception of Octopus). Integrated energy above 50 Hz exceeds that from 2-50 Hz and falls slowly with frequency; in Aplysia the power spectrum falls less than 10 dB between 10 and 300 Hz. In vertebrates from fish to mammals activity is similar in being mainly slow (less than 40 Hz); it commonly falls greater than 20 dB between 10 and 50 Hz. (4) Amplitude is low in invertebrates and lower vertebrates. RMS voltage in Aplysia (3-300 Hz, reference electrode remote) is typically less than 10 microV; in the ray optic tectum less than 25 microV (2-50 Hz); in the dorsal cortex of the gecko less than 30 microV, in the cat cortex greater than 85 microV. In the vertebrates amplitude does not change greatly with small shifts in electrode position, as it does in invertebrates. (5) Coherence decline with distance, measured tangentially at different electrode separations in the millimeter range, is used as an estimator of synchrony. Averaged coherence between loci 1 mm apart is negligible in Aplysia in any band from 3 to 100 Hz; in the ray tectum it is low, 0.25-0.5 between 3 and 16 Hz. In the turtle dorsal pallium it is higher, at 2 mm, 0.6-0.75 in this band. In the rabbit cortex coherence is even higher, typically greater than 0.7 at 1 mm, and greater than 0.3 at 4 mm in this band. (6) Band-pass filtered electrograms, ca. one octave wide, in all species show constant waxing and waning in each band; amplitude is not maintained even for a second. (ABSTRACT TRUNCATED AT 400 WORDS)


Causes, effects, and clinical implications of perturbed patterns within the cancer epigenome.
Somatic mutations accumulating over a patient's lifetime are well-defined causative factors that fuel carcinogenesis. It is now clear, however, that epigenomic signature is also largely perturbed in many malignancies. These alterations support the transcriptional program crucial for the acquisition and maintenance of cancer hallmarks. Epigenetic instability may arise due to the genetic mutations or transcriptional deregulation of the proteins implicated in epigenetic signaling. Moreover, external stimulation and physiological aging may also participate in this phenomenon. The epigenomic signature is frequently associated with a cell of origin, as well as with tumor stage and differentiation, which all reflect its high heterogeneity across and within various tumors. Here, we will overview the current understanding of the causes and effects of the altered and heterogeneous epigenomic landscape in cancer. We will focus mainly on DNA methylation and post-translational histone modifications as the key regulatory epigenetic signaling marks. In addition, we will describe how this knowledge is translated into the clinic. We will particularly concentrate on the applicability of epigenetic alterations as biomarkers for improved diagnosis, prognosis, and prediction. Finally, we will also review current developments regarding epi-drug usage in clinical and experimental settings.


Otolaryngology in the COVID-19 pandemic era: the impact on our clinical practice.
To give an overview of the current knowledge about COVID-19 pandemic and its impact on otolaryngology clinical practice. Recent findings about SARS-CoV-2 virus and the COVID-19 infection it causes are reviewed. In addition to international databases and in the absence of hard scientific data, literature search included reports published online from scientific societies and other institutions. The role of anosmia as a COVID-19-related symptom is presented. Further, considerations about steroid administration in ENT-related conditions are also discussed. Due to the close work with mucosa surfaces of the upper aerodigestive tract, otolaryngologists and surrounding staff are considered high risk for coronavirus transmission. Hence, staff protection measures for ENT examinations, surgeries and other procedures during COVID-19 pandemic are recommended. Knowledge and evidence about the impact of COVID-19 infection on otolaryngology clinical practice are accumulating rapidly. Additionally to patient's management, safety of health care professionals should be a main goal right now by following strict safety guidelines.


Studies on the interaction between Streptomyces pepsin inhibitor and several acid proteinases by means of a zinc(II)-dye complex as a probe.
The zinc(II) complex of pyridine-2-azo-p-dimethylaniline is bound to several acid proteinases, at pH 5.0, accompanied by a change is the visible absorption spectrum. Streptomyces pepsin inhibitor, which was discovered by Satoi and Murao (Satoi, S. and Murao, S. (1970) Agric. Biol. Chem. 34, 1265-1267 and Satoi, S. and Murao, S. (1971) Agric. Biol. Chem. 35, 1482-1487), is also bound to acid proteinases. Spectrophotometric studies with ten acid proteinases from different sources have revealed that in several acid proteinases, zinc(II)-pyridine-2-azo-p-dimethylaniline is released from the enzyme by the inhibitor, while some acid proteinase forms a quaternary complex, zinc(II)-pyridine-2-azo-p-dimethylaniline-inhibitor-enzyme. It is speculated that zinc(II)-pyridine-2-azo-p-dimethylaniline is bound to two catalytic carboxylate groups in the active site of the acid proteinases and the inhibitor is bound mainly to the substrate-binding site of the enzymes. The binding of the inhibitor may overlap the catalytic site completely or partially. The degree of overlapping is characteristic of the kind of acid proteinases.


Laser bronchoscopy in respiratory failure from malignant airway obstruction.
To examine the value of laser bronchoscopy in patients with inoperable carcinoma of the lung who required ventilatory assistance for acute respiratory failure. Retrospective review of the medical records of all patients undergoing laser bronchoscopy. The Lahey Clinic Medical Center, a tertiary referral center. The medical records of 311 patients undergoing laser bronchoscopy at the Lahey Clinic Medical Center between 1982 and 1990 were reviewed. The 17 patients who required mechanical ventilation at the time of laser surgery formed the study group. All patients underwent neodymium:yttrium-aluminum-garnet laser bronchoscopy through a rigid bronchoscope in the operating room with use of jet ventilation and general anesthesia throughout the procedure. Postoperative care was directed by the same physician for all patients. The following data were extracted from medical records: age and sex of patient, cell type and location of tumor, length of time between diagnosis and laser therapy, treatment before and after laser therapy, number of days receiving mechanical ventilation before and after laser therapy, medical and operative complications, survival, and cause of death. The patients were divided into two groups on the basis of clinical improvement that permitted elective discontinuation of mechanical ventilation. Group 1 included patients who experienced clinical improvement permitting endotracheal extubation. Group 2 was composed of patients who died while still receiving mechanical ventilatory support or who were extubated before institution of comfort measures. The two groups were compared using nonparametric tests of significance, including the Mann-Whitney test. No significant differences were apparent between groups 1 and 2 regarding clinical characteristics before laser treatment. Patients in group 1 had significantly (p = .03) shorter requirements for mechanical ventilation after laser treatment than patients in group 2 (1 vs. 6 days). Similarly, patients in group 1 were more likely to receive additional treatment after laser therapy than patients in group 2 (seven of nine patients vs. two of eight patients; p = .048). Patients in group 1 had significantly (p = .0038) longer survival than patients in group 2 (98 vs. 8.5 days). A greater endobronchial component to airway obstruction appeared to exist in patients in group 1 (nine of nine patients) vs. patients in group 2 (three of eight patients; p = .009). Extrinsic compression and submucosal tumor were more commonly seen in patients in group 2. In addition, patients in group 2 appeared to have a greater number of postoperative medical complications than patients in group 1. Operative complications were minor in both groups. In nine of 17 patients, laser bronchoscopy appeared to improve the clinical status, permitting removal of mechanical ventilation and extubation and provided the opportunity for further treatment modalities in seven of the nine patients. Survival was improved in this subgroup, and requirement for mechanical ventilatory support was shortened. The improved outcome after laser therapy was related to the presence of obstructing endobronchial tumor as the cause of the respiratory insufficiency. Patients with inoperable carcinoma of the lung and respiratory failure should be evaluated for the presence of an endobronchial lesion that might be responsive to laser bronchoscopy.


A comparison of nutrient uptake efficiency and growth rate between different macrophyte growth forms.
Aquatic macrophytes grow abundantly in many lowland streams and play a key role in ecosystem functioning, such as nutrient retention. In this study, we performed a microcosm experiment to quantify and compare the contribution of two freshwater macrophyte growth forms to nutrient cycling. We measured and compared inorganic nitrogen (NH4-N and NO3-N) and phosphorus (PO4-P) uptake kinetic parameters (Vmax and Cmin) in 12 submerged and seven amphibious plant species. We tested whether relative growth rate (RGR) was related to high Vmax and low Cmin, and quantified changes in nutrient uptake kinetic in a subset of six out of 19 plants species during the growth season. Uptake rates of NH4-N were higher in submerged compared to amphibious plants, whereas uptake rates of NO3-N were significantly higher in amphibious species; PO4-P uptake kinetics were not significantly different between the two growth forms. There were also significant seasonal differences in Vmax NH4-N rate among both submerged and amphibious species and in Vmax NO3-N among amphibious species. Highest uptake rates were observed in summer for both submerged and amphibious species. Overall, we found that nutrient uptake kinetics differed between the two growth forms within and between seasons. Consequently, the presence of both growth forms should extend the period of nutrient uptake across the year and enhance nutrient uptake within seasons. We conclude that higher functional diversity enhances annual nutrient uptake in streams and that stream restoration efforts should consider increasing the niche space available for both submerged and amphibious species.


A simulation study on the influence of energy migration and relative interaction strengths of homo- and hetero-FRET on the net FRET efficiency.
Förster resonance energy transfer (FRET) is a powerful method for probing biomolecular conformations and dynamics in bulk as well as at a single-molecule level. FRET utilizes non-radiative mechanisms to transfer energy between fluorophores, donor and acceptor when placed in close proximity. The FRET efficiency has a strong distance dependence and serves as a direct read-out for molecular interaction. In case of a significant overlap of donor emission and absorption spectra, the excited state energy can be exchanged between the identical donors in close proximity, which eventually migrates back and forth until it gets dissipated. This form of energy transfer is called energy migration or homo-FRET. Here, we have simulated FRET efficiency by considering the donor-donor interaction strength (ξDD) and donor-acceptor interaction strength (ξDA) under conditions of non-uniform distribution of molecules. Our earlier studies indicate that energy migration modulate the FRET efficiency for various values of ξDD and ξDA. We, therefore, determined the limiting values of acceptor concentration (CLA) that will allow the determination of FRET efficiency in the absence and presence of energy migration. Taken together, our study optimizes the conditions for meaningful FRET efficiency for a given FRET pair for better reporting of molecular interactions.


A genetic linkage map for azuki bean [Vigna angularis (Willd.) Ohwi & Ohashi].
To make progress in genome analysis of azuki bean (Vigna angularis) a genetic linkage map was constructed from a backcross population of (V. nepalensis x V. angularis) x V.angularis consisting of 187 individuals. A total of 486 markers-205 simple sequence repeats (SSRs), 187 amplified fragment length polymorphisms (AFLPs) and 94 restriction fragment length polymorphisms (RFLPs) -were mapped onto 11 linkage groups corresponding to the haploid chromosome number of azuki bean. This map spans a total length of 832.1 cM with an average marker distance of 1.85 cM and is the most saturated map for a Vigna species to date. In addition, RFLP markers from other legumes facilitated finding several orthologous linkage groups based on previously published RFLP linkage maps. Most SSR primers that have been developed from SSR-enriched libraries detected a single locus. The SSR loci identified are distributed throughout the azuki bean genome. This moderately dense linkage map equipped with many SSR markers will be useful for mapping a range of useful traits such as those related to domestication and stress resistance. The mapping population will be used to develop advanced backcross lines for high resolution QTL mapping of these traits.