Correlation of serum Anti-Müllerian hormone concentrations on day 3 of the in vitro fertilization stimulation cycle with assisted reproduction outcome in polycystic ovary syndrome patients.
To investigate whether serum Anti- Müllerian hormone (AMH) on day 3 could predict controlled ovarian stimulation and reproductive outcomes in women with polycystic ovary syndrome. A total of 164 PCOS patients undergoing their first IVF treatment cycle were prospectively included. Serum AMH levels on cycle day 3 was measured. The controlled ovarian stimulation and clinical outcomes for the study population were divided according to the <25th, 25 to 75th, or >75th percentile of serum day-3 AMH. Estradiol levels on hCG day and the number of retrieved oocytes significantly increased with increasing serum AMH levels, while total consumption of gonadotropin dose showed a significant decrease (P < 0.05). Fertilization rate and the number of good quality embryos were comparable among the low, average and high groups (P > 0.05). Embryo implantation rates in the high AMH group was significantly inferior to those with low and average AMH concentration (27 versus 48.8 and 50%, P < 0.01). Clinical pregnancy rates was lower in the high AMH group than that of the low and average group (45.9 versus 65 and 66.7%, P = 0.09), but this difference was only close to statistical significance. In addition, ordinal regression analysis indicated that LH level was the only independent predictor of embryo implantation rates (P = 0.017). In PCOS women, AMH levels on day 3 of the IVF stimulation cycle positively predict ovarian response to gonadotrophins. However, the women with high AMH levels had a significantly decreased IR, which may be due to remarkably increased LH concentrations.


Amplitude spectrum area measured in real-time during cardiopulmonary resuscitation - How does this technology work?
Amplitude spectrum area (AMSA) is one of the most accurate predictors of defibrillation outcome. Details on functioning and use of the available technology to measure AMSA during cardiopulmonary resuscitation (CPR) in the real clinical scenario are described. During chest compression (CC) pauses for ventilations, AMSA is promptly calculated and values displayed through a modified defibrillator. In addition, real-time AMSA analysis has the additional promise to monitor CPR quality, being AMSA threshold values contingent on CC depth. Future larger studies employing this new technology are now needed to demonstrate the impact of AMSA on survival of cardiac arrest.


Dose related inhibitor effect of enrofloxacin on in vitro feline spontaneous myometrial contractility.
Enrofloxacin is one of the most widely used antibacterial drugs in feline medicine. This study investigated the effects of enrofloxacin on in vitro feline spontaneous myometrial contractility at different sexual stages. Uterine samples of the 20 queen cats at different sexual periods were placed in a tissue bath, and in vitro spontaneous stretch-induced myometrial contractions were recorded for 10 min. The tissue bath was adjusted for cumulative enrofloxacin concentrations of 0.25 mM, 0.50 mM, 1.00 mM, and 2.00 mM, respectively. Myometrial contractions were recorded for 10 min after each dose was adjusted in the tissue bath. It was observed that enrofloxacin caused a significant decrease in the peak amplitude and area under curve, while causing an increase the frequency of stretch-induced myometrial contractions in a dose dependent manner in vitro at all sexual stages. The current preliminary study concluded that enrofloxacin has an inhibitory effect on in vitro feline uterine myometrial activity at all sexual stages. It is recommended to take this medical effect into consideration and apply enrofloxacin and uterotonics together in treatment of uterine infections in feline medicine.


Breast osteosarcoma originating from a malignant phyllodes tumor: A case report of a rare neoplasm.
Malignant phyllodes tumors with osteosarcomatous transformation are exceedingly rare. The clinical manifestations are similar to those associated with benign giant calcification, resulting in nonspecific and complex clinical symptoms. A 59-year-old woman presented with a firm, painless, movable, 5.0 × 4.0 cm lump in the lower inner quadrant of the left breast that she had detected 1 month prior. Breast osteosarcoma originating from a malignant phyllodes tumor was confirmed by histopathologic and immunohistochemical evaluation. The patient underwent a wide local excision. The patient recovered uneventfully and was discharged after the operation. The 6-month postoperative follow-up assessment revealed no evidence of recurrence. Diagnosing malignant phyllodes tumors with osteosarcomatous transformation requires a high level of suspicion and awareness by both surgeons and pathologists. They should be aware of the extent of such disease, which might be mistaken as benign giant calcification. Medical history and imaging findings are important for accurate diagnosis. Phyllodes tumor with an osteosarcomatous component is an aggressive neoplasm associated with distant metastasis. Delayed diagnosis and insufficient excision might negatively impact both treatment and survival.


Real-World, Multicenter Case Series of Patients Treated with Oral Omadacycline for Resistant Gram-Negative Pathogens.
Antibiotic-resistant Gram-negative bacteria have been associated with substantial morbidity and mortality and have limited treatment options available. Omadacycline (OMC) is an aminomethylcycline antibiotic that has been shown to exhibit broad in vitro activity against antibiotic-resistant Gram-negative bacteria. Given the lack of real-world data, the primary objective of our report was to describe early experience with OMC for the treatment of resistant Gram-negative infections. This was a real-world, multicenter, observational cases series/pilot study conducted in the USA. Inclusion criteria included any adult patient aged ≥ 18 years who received OMC for ≥ 72 h either in the inpatient and/or outpatient setting. Clinical success was defined as a composite of 90-day survival from initiation of OMC, lack of alteration in treatment/addition of other antibiotic due to concerns of OMC failure, and lack of microbiologic recurrence within 30 days from the end of therapy. Oral OMC was used in nine cases primarily for multidrug-resistant (MDR)/extensively drug-resistant (XDR) Gram-negative bacterial infections (55.6% XDR and/or carbapenem-resistant Acinetobacter baumannii [CRAB]). The majority of infections were of bone/joint (55.6%) origin, followed by intra-abdominal (33.3%) origin. Clinical success occurred in 66.7% of cases, with 80.0% success each in infections of bone/joint origin or those caused by CRAB. One patient experienced an adverse effect that was not treatment limiting while on therapy (gastrointestinal). The use of oral OMC in MDR/XDR Gram-negative infections exhibited a relatively high success rate with minimal adverse effects. Real-world studies with larger case numbers are needed to confirm our initial findings.


Data for "Social-evaluative threat: Stress response stages and influences of biological sex and neuroticism".
This Data In Brief article contains supplementary materials to the article "Social-evaluative threat: stress response stages and influences of biological sex and neuroticism" [1], and describes analysis results of an open dataset [2]. Additional information is provided regarding the methods, particularly: the analysis of individual stress response peak times per stress system, and the statistical analysis. Importantly, correlation tables are presented between the different stress systems, both for baseline stress levels as well as for stress responses, and significant associations are displayed in scatter plots.


Rational engineering NiMoO4nanosheets or Mn3O4nanowires on Fe2O3microdiscs as novel hierarchical anodes for high-performance lithium-ion batteries.
Since current graphite-based lithium-ion battery anode has a low theoretical capacity, the development of high-performance lithium-ion battery is severely restricted. Here, novel hierarchical composites composing of microdisc and the secondarily grown nanosheets and nanowires are developed, taking NiMoO4nanosheets and Mn3O4nanowires growing on Fe2O3microdiscs as demonstrating examples. The growth processes of the hierarchical structures have been investigated by adjusting a series of preparation conditions. The morphologies and structures have been characterized by using scanning electron microscopy, transmission electron microscope and x-ray diffraction. Fe2O3@Mn3O4composite-based anode displays a capacity of 713 mAh g-1after 100 cycles at 0.5 A g-1with a high Coulombic efficiency. A good rate-performance is also achieved. Fe2O3@NiMoO4anode delivers 539 mAh g-1after 100 cycles at 0.5 A g-1, which is obviously higher than that of pure Fe2O3. The hierarchical structure is conducive to improve the transport of electrons and ions, and provide numerous active sites, thus significantly enhancing the electrochemical performance. Moreover, the electron transfer performance is investigated by using density functional theory calculations. It is expected the findings presented here and the rational engineering of nanosheets/nanowires on microdiscs would be applicable for developing many other high-performance energy-storage composites.


Intraoperative blood transfusion is a major risk factor for coronary artery bypass grafting in women.
Women have been found to have greater mortality from coronary artery bypass grafting than men. Uncertainty exists regarding the causes of the differences in outcomes between men and women after coronary artery bypass grafting. From a database of 2,569 patients having coronary bypass grafting we have determined factors that contribute to poorer outcomes in women compared with men. Women were found to have greater mortality, postoperative bleeding, and postoperative pulmonary failure than men (p < 0.05). There was no significant difference between men and women in postoperative renal failure, postoperative infection, postoperative stroke, or intraaortic balloon pump (p = not significant). Patient factors other than sex accounted for all the significant predictors (stepwise logistic regression) of mortality, postoperative bleeding, postoperative renal failure, postoperative pulmonary failure, postoperative stroke, need for intraaortic balloon pump, and postoperative infection (p < 0.05). Poorer outcomes in women are associated with greater need for transfusion during operation. Diabetes is predictive of renal failure and stroke. Mortality and morbidity is less in men despite their higher preoperative creatinine level, greater incidence of reoperation, lower ejection fraction, and more common atherosclerosis of the ascending aorta.


Effect of di(2-ethylhexyl)phthalate (DEHP) on hepatic mixed function oxidases in different animal species.
Administration of 2000 mg/kg of di(2-ethylhexyl)phthalate (DEHP) for a period of 7 or 15 days in rats, mice, guinea pigs and rabbits produced a differential effect as judged by alterations in body weight gain, liver weight and activities of mixed function oxidases. DEHP exposure for 7 days caused an increase in the activity of aniline hydroxylase, arylhydrocarbon hydroxylase and ethylmorphine N-demethylase in rats, mice and guinea pigs, but a decrease in that of rabbits. However, exposure for 15 days produced a smaller degree of increase in the activity of these enzymes in rats and mice and even produced a decrease in the activity of these enzymes in guinea pigs. This differential response of DEHP in various animal species suggests a species difference in the toxicity of the plasticizer.


The function of groups of neurons changes from moment to moment.
Modern techniques that enable identification and targeted manipulation of neuron groups are frequently used to bolster theories that attribute specific behavioral functions to specific neuron types. These same techniques can also be used, however, to highlight limitations of such attribution, and to develop the argument that the question "what is the function of these neurons?" is ill-posed in the absence of temporal and network constraints. Here we do this, first reviewing evidence that neural responses are dynamic at multiple time scales, making the point that such changes in firing rates imply changes in what the neuron is doing. Studies involving brief perturbations of neural populations confirm this point, showing that the functions in which these populations participate change across seconds and even milliseconds. Based on these studies, we suggest that it is inappropriate to assign function to sets of neurons without contextualizing that assignment to specific times and network conditions.


Effect of water activity on growth and enterotoxin D production of Staphylococcus aureus.
Four enterotoxin D-producing strains of Staphylococcus aureus, were cultured at 37 degrees C in brain heart infusion broth adjusted to various water activity (aw) levels by means of NaCl. For high cell inocula growth of all strains and enterotoxin D production were observed within 6 days at aw levels down to 0.86.


Distribution of caprine arthritis encephalitis virus provirus, RNA, and antigen in the reproductive tract of one naturally and seven experimentally infected bucks.
Caprine arthritis encephalitis is a worldwide, multisystemic disease caused by a small ruminant lentivirus. Although the main route of transmission is oral, detection of proviral DNA of the caprine arthritis encephalitis virus (CAEV) in caprine semen has been previously described. However, the presence of viral antigens in the male reproductive tract has apparently never been reported. The objective was to study lesions in the buck reproductive system and to detect, in these tissues, the presence of proviral DNA, viral RNA and CAEV antigens. Tissues from eight CAEV-infected bucks (one naturally and seven experimentally infected) were analyzed by histopathology, nested polymerase chain reaction, reverse transcriptase-polymerase chain reaction, and immunohistochemistry. Interstitial pneumonia, synovitis, and lesions in the male reproductive tract were detected in some of the bucks. Proviral DNA was detected in the lungs and joints as well as in the reproductive systems of all animals, whereas viral RNA was detected only in the genital tract of the naturally infected buck. Viral antigens were immunostained in most of the organs of the male reproductive tract. This report was apparently the first to clearly demonstrate CAEV antigen expression in the male reproductive tract, which indicates the possibility of venereal transmission of CAEV.


The effect of a brief mindfulness-based stress reduction program on strengthening awareness of medical errors and risks among nursing students.
Healthcare professionals' awareness of medical errors and risks results in effective medical error reporting and patient safety. Mindfulness has positive effects on strengthening attention and awareness. However, little is known about the use of mindfulness in patient safety education among nursing students. This study aimed to examine if a brief mindfulness-based stress reduction program would have a beneficial impact on (a) medical error attitudes, (b) the number of medical errors and risks in a simulation environment, and (c) self-confidence and satisfaction among nursing students. A quasi-experimental design with a control group was conducted with 78 third-year nursing students at a private, accredited, nursing program in Istanbul, Türkiye. There was a statistically significant improvement in the intervention group between the pre-test and post-test for medical error attitudes (p < 0.001), and the number of medical errors and risks in a simulation environment (p < 0.001). There was no statistical difference in the intervention and control groups for self-confidence and satisfaction (p > 0.05). These results suggest that a brief mindfulness-based stress reduction program positively strengthens nursing students' awareness of medical errors and risks.


Andrographolide protects rat hepatocytes against paracetamol-induced damage.
Andrographolide, the active constituent isolated from the plant Andrographis paniculata, showed a significant dose dependent (0.75-12 mg/kg p.o. x 7) protective activity against paracetamol-induced toxicity on ex vivo preparation of isolated rat hepatocytes. It significantly increased the percent viability of the hepatocytes as tested by trypan blue exclusion and oxygen uptake tests. It completely antagonized the toxic effects of paracetamol on certain enzymes (GOT, GPT and alkaline phosphatase) in serum as well as in isolated hepatic cells. Andrographolide was found to be more potent than silymarin, a standard hepatoprotective agent.


'Providing good and comfortable care by building a bond of trust': nurses views regarding their role in patients' perception of safety in the intensive care unit.
To describe and understand intensive care unit (ICU) nurses' views regarding their role in ICU patients' perception of safety. Feeling safe is an important issue for ICU patients. Not feeling safe may result in adverse effects including traumatic experiences, having nightmares and feeling depressed. Nursing care plays a major role in patients' perception of safety. However, it is unknown whether ICU nurses are aware of this role. A grounded theory approach following Corbin and Strauss. A total of 13 participants were included in the study following maximum variation sampling, by selecting ICU nurses who differed in gender, age, work experience as registered ICU nurse, and were employed in different IC units. In-depth interviews were performed using open-ended questions guided by a topic list with broad question areas. Data collection and analysis were executed during an iterative process. The core category, building a bond of trust to provide good and comfortable care, arose from four main categories: explaining and informing ICU patients, using patients' family bond, ICU nurses' attitudes and expertise, and creating physical safety. The ICU nurses stated that they were not explicitly aware of ICU patients' perception of safety, but that they strived to provide good and comfortable care, through building a bond of trust with their patients. According to the nurses, a bond of trust is essential for patients to feel safe in the ICU. The importance of feeling safe in ICU patients should be addressed within the education and clinical practice of ICU nurses, to ensure that they become aware of ICU patients' perception of safety.


Performance of children with social communication disorder on the Happé Strange Stories: Physical and mental state responses and relationship to language ability.
This study investigated whether a modified scoring method was useful for examining the ability of children with social communication disorder (CwSCD) to understand non-literal language and use mental state responses on the Happé Strange Stories (HSS) task. CwSCD and a control group of children with typical language development (CwTLD) completed 10 of the original HSS. CwSCD scored significantly lower on the HSS task than did CwTLD and were much less likely to produce mental state responses. There was a high level of inter-rater reliability (Weighted Kappa=0.907) across data from both groups. HSS performance and language ability correlated significantly for CwSCD. A regression model with age, nonverbal intelligence, receptive and expressive language as predictors explained 55.2% of the variance in HSS ability for CwSCD. The results suggest that the HSS have potential to be used as a clinical assessment to investigate high-level language and ability to infer intent in CwSCD. Readers will be able to describe a modified scoring method for the Happé Strange Stories task. Readers will be able to identify areas of impairment for children with social communication disorder. Readers will identify how these areas of impairment have an effect on ability to understand non-literal language and produce mental state responses on the Happé Strange Stories task.


New acylated flavonols identified in Vitis vinifera grapes and wines.
Flavonols are a class of polyphenol compounds whose importance for wine quality has increased as their structures and properties have become better understood. Here, the acetylated and p-coumaroylated derivatives of the flavonol 3-O-glucosides of isorhamnetin, laricitrin and syringetin have been identified for the first time in Vitis vinifera grape skins and wines. First, the MS2 fragmentation patterns of the new flavonol derivatives showed a main signal attributable to the expected flavonol aglycone. In the p-coumaroylated derivatives, the signal corresponding to the intermediate loss of the phenolic acid was also observed. The structures of the aglycones were confirmed by their respective MS3 experiments that matched with those obtained from authentic standards of the aglycones. In addition, the fragmentation signals corresponding to the aglycone radical ions generated through homolytic cleavage assisted identification, and could support future studies of flavonoid compounds by ESI-MS. Using an HPLC-ESI-Q-ToF system, the observed m/z values of the compounds being studied were successfully matched with the expected formula. Surprisingly, just the minority methoxylated flavonol glucosides presented acylation, suggesting a high substrate specificity of the acyltransferases implicated in their synthesis. These findings show higher diversity of grape and wine flavonols. Additional studies and isolation strategies need to be followed to further characterize these metabolites as to test their presence in other grape varieties and it wines.


Age-related characteristics of uterine cancer mortality in Japan.
Several studies have proved that uterine cancer mortality has decreased in Japan over the past 50 years, but the age demographics in this regard are not clear. This study investigated the change pattern of age characteristics for this cancer. Cause-specific mortality was identified in the population of Japan and Ireland in the years 1950-2000. Time trends of age-specific mortality rate were assessed by fitting linear regression. The change rates between 1950 and 2000 were calculated in comparison with Ireland. The contribution of death from uterine cancer was estimated using cause-elimination life tables. The mortality rate of uterine cancer decreased 59% from 1950 (19.7 per 100,000 women) to 2000 (8.14 per 100,000 women). Age-specific rates for women younger than 70 decreased around 80%, whereas that for women over 85 increased 105% during the same period. Correspondingly, the age of 70 years was the median age for the negative contribution of uterine cancer to life expectancy. Younger than that age, the trend of negative contribution decreased, over that age, it was increased. Mortality from uterine cancer tended toward the aging in Japan. The general mortality reduction trend was attributed to younger people and adults. These age characteristics can be explained by the increase in life expectancy during the 50-year period.


Impact of Iron-Deficiency Management on Quality of Life in Patients with Cancer: A Prospective Cohort Study (CAMARA Study).
Iron deficiency (ID) is very common in patients with solid tumors and may cause symptoms such as fatigue. However, its impact on clinical outcomes is poorly described. The aim of this prospective monocentric cohort study was to evaluate the evolution of quality of life (QoL) of these patients after iron supplementation. We included patients treated for a solid tumor, which were diagnosed with a functional (ferritin <800 ng/mL) or absolute (ferritin <300 ng/mL) ID (transferrin saturation coefficient <20%). The primary endpoint was patients' QoL evolution between baseline and intermediate visit, 15-30 days after initial intravenous iron supplementation, assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) scale. Secondary endpoints were the same assessment between baseline, intermediate, and final visit at 6 months and the evolution of functional capacities. From 02/2014 to 12/2016, 248 patients were enrolled, of whom 186 were included in the analyses, including 140/186 (75.3%) with absolute ID. Anemia was detected in 141/174 (81.0%) patients at baseline. The FACT-An scores improved significantly between inclusion and intermediate visit (P = .001) and also between the 3 times of evaluation (P < .001). The most improved dimensions were those assessing physical, emotional well-being, and fatigue. Patients who performed the functional tests in all 3 phases had a significant improvement in performance on the majority of tests. The supplementation of ID was associated with an improvement of the QoL and functional capacities in patients with cancer. A randomized control trial is necessary to confirm our results. Our findings underline the importance of supportive care, including screening for ID, in oncology. NCT03625661.


Cost-effectiveness analysis of Vaborem in Carbapenem-resistant Enterobacterales (CRE) -Klebsiella pneumoniae infections in Italy.
Vaborem is a fixed dose combination of vaborbactam and meropenem with potent activity against target Carbapenem-resistant Enterobacterales (CRE) pathogens, optimally developed for Klebsiella pneumoniae carbapenemase (KPC). The study aims to evaluate the cost-effectiveness of Vaborem versus best available therapy (BAT) for the treatment of patients with CRE-KPC associated infections in the Italian setting. A cost-effectiveness analysis was conducted based on a decision tree model that simulates the clinical pathway followed by physicians treating patients with a confirmed CRE-KPC infection in a 5-year time horizon. The Italian National Health System perspective was adopted with a 3% discount rate. The clinical inputs were mostly sourced from the phase 3, randomised, clinical trial (TANGO II). Unit costs were retrieved from the Italian official drug pricing list and legislation, while patient resource use was validated by a national expert. Model outcomes included life years (LYs) and quality adjusted life years (QALYs) gained, incremental costs, incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). Deterministic and probabilistic sensitivity analyses were also performed. Vaborem is expected to decrease the burden associated with treatment failure and reduce the need for chronic renal replacement therapy while costs related to drug acquisition and long-term care (due to higher survival) may increase. Treatment with Vaborem versus BAT leads to a gain of 0.475 LYs, 0.384 QALYs, and incremental costs of €3549, resulting in an ICER and ICUR of €7473/LY and €9246/QALY, respectively. Sensitivity analyses proved the robustness of the model and also revealed that the probability of Vaborem being cost-effective reaches 90% when willingness to pay is €15,850/QALY. In the Italian setting, the introduction of Vaborem will lead to a substantial increase in the quality of life together with a minimal cost impact, therefore Vaborem is expected to be a cost-effective strategy compared to BAT.


Treatment for Positive Urine Cultures in Hospitalized Adults: A Survey of Prevalence and Risk Factors in 3 Medical Centers.
Antibiotic treatment for asymptomatic bacteriuria (ASB) is prevalent but often contrary to published guidelines. To evaluate risk factors for treatment of ASB. Retrospective observational study. A tertiary academic hospital, county hospital, and community hospital. Hospitalized adults with bacteriuria. Patients without documented symptoms of urinary tract infection per Infectious Diseases Society of America (IDSA) criteria were classified as ASB. We examined ASB treatment risk factors as well as broad-spectrum antibiotic usage and quantified diagnostic concordance between IDSA and National Healthcare Safety Network criteria. Among 300 patients with bacteriuria, ASB was present in 71% by IDSA criteria. By National Healthcare Safety Network criteria, 71% of patients had ASB; within-patient diagnostic concordance with IDSA was moderate (kappa, 0.52). After excluding those given antibiotics for nonurinary indications, antibiotics were given to 38% (62/164) with ASB. Factors significantly associated with ASB treatment were elevated urine white cell count (65 vs 24 white blood cells per high-powered field, P<.01), hospital identity (hospital C vs A, odds ratio, 0.34 [95% CI, 0.14-0.80], P =.01), presence of leukocyte esterase (5.48 [2.35-12.79], P<.01), presence of nitrites (2.45 [1.11-5.41], P=.03), and Escherichia coli on culture (2.4 [1.2-4.7], P=.01). Of patients treated for ASB, broad-spectrum antibiotics were used in 84%. ASB treatment was prevalent across settings and contributed to broad-spectrum antibiotic use. Associating abnormal urinalysis results with the need for antibiotic treatment regardless of symptoms may drive unnecessary antibiotic use.


Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial.
Vascular dementia is the second commonest form of dementia, and vascular factors contribute to the development of dementia in many patients with Alzheimer's disease. Galantamine amplifies the acetylcholine response by inhibiting acetylcholinesterase and modulating nicotinic receptors. It has shown broad, sustained benefits in patients with Alzheimer's disease. We investigated the effects of galantamine in patients with a diagnosis of probable vascular dementia or Alzheimer's disease combined with cerebrovascular disease. Eligible patients were randomly assigned galantamine 24 mg/day (n=396) or placebo (n=196) in a multicentre, double-blind, 6-month trial. Primary endpoints were cognition (Alzheimer's disease assessment scale, cognitive subscale [ADAS-cog]) and global functioning (clinician's interview-based impression of change plus caregiver input [CIBIC-plus]). Secondary endpoints included assessments of activities of daily living and behavioural symptoms. Patients were monitored for adverse events. Analyses were on the basis of observed case or last observation carried forward. Galantamine showed greater efficacy than placebo on ADAS-cog (galantamine change -1.7 [SE 0.4] vs placebo 1.0 [0.5]; treatment effect 2.7 points; p<0.0001) and CIBIC-plus (213 [74%] vs 95 [59%] patients remained stable or improved, p=0.0001). Activities of daily living and behavioural symptoms were also significantly improved compared with placebo (p=0.002 and p=0.016, respectively). Galantamine was well tolerated. Galantamine showed a therapeutic effect on all key areas of cognitive and non-cognitive abilities in this group of dementia patients.


Functional coupling of transcription and splicing.
The tightly regulated process of precursor messenger RNA (pre-mRNA) alternative splicing is a key mechanism to increase the number and complexity of proteins encoded by the genome. Evidence gathered in recent years has established that transcription and splicing are physically and functionally coupled and that this coupling may be an essential aspect of the regulation of splicing and alternative splicing. Recent advances in our understanding of transcription and of splicing regulation have uncovered the multiple interactions between components from both types of machinery. These interactions help to explain the functional coupling of RNAPII transcription and pre-mRNA alternative splicing for efficient and regulated gene expression at the molecular level. Recent technological advances, in addition to novel cell and molecular biology approaches, have led to the development of new tools for addressing mechanistic questions to achieve an integrated and global understanding of the functional coupling of RNAPII transcription and pre-mRNA alternative splicing. Here, we review major milestones and insights into RNA polymerase II transcription and pre-mRNA alternative splicing as well as new concepts and challenges that have arisen from multiple genome-wide approaches and analyses at the single-cell resolution.


Sparser spiking activity can be better: Feature Refine-and-Mask spiking neural network for event-based visual recognition.
Event-based visual, a new visual paradigm with bio-inspired dynamic perception and μs level temporal resolution, has prominent advantages in many specific visual scenarios and gained much research interest. Spiking neural network (SNN) is naturally suitable for dealing with event streams due to its temporal information processing capability and event-driven nature. However, existing works SNN neglect the fact that the input event streams are spatially sparse and temporally non-uniform, and just treat these variant inputs equally. This situation interferes with the effectiveness and efficiency of existing SNNs. In this paper, we propose the feature Refine-and-Mask SNN (RM-SNN), which has the ability of self-adaption to regulate the spiking response in a data-dependent way. We use the Refine-and-Mask (RM) module to refine all features and mask the unimportant features to optimize the membrane potential of spiking neurons, which in turn drops the spiking activity. Inspired by the fact that not all events in spatio-temporal streams are task-relevant, we execute the RM module in both temporal and channel dimensions. Extensive experiments on seven event-based benchmarks, DVS128 Gesture, DVS128 Gait, CIFAR10-DVS, N-Caltech101, DailyAction-DVS, UCF101-DVS, and HMDB51-DVS demonstrate that under the multi-scale constraints of input time window, RM-SNN can significantly reduce the network average spiking activity rate while improving the task performance. In addition, by visualizing spiking responses, we analyze why sparser spiking activity can be better. Code.


Intraoperative MRI electrical noise and monitor ECG filters affect arrhythmia detection and identification.
Most electrical equipment in the modern operating room (OR) radiates electrical noise (EN) that can interfere with patient monitors. We have described the EN that an intraoperative magnetic resonance imaging (iMRI) system emits and have shown that this high-energy EN diminishes the quality of the ECG waveform during iMRI scans in our neurosurgical OR. We have also shown that the ECG signal filters in our iMRI-compatible patient monitor reduce this interference but, in the process, disturb the true morphology of the displayed waveform. This simulation study evaluates how iMRI-generated EN affects the ability of the anesthetist to detect and identify ECG arrhythmias and whether the patient monitor's ECG signal filters can improve arrhythmia recognition. Using an ECG simulator, we generated Lead II and V5 ECG signal segments that contained either no arrhythmia or one of four common cardiac arrhythmias. We filtered the ECG segments with four filters available on our iMRI-compatible monitor (Veris MR, MEDRAD Inc., Indianola, PA USA). We then digitized the segments and mixed simulated iMRI EN into the resultant tracings. With institutional approval and written informed consent, board-certified anesthesiologists reviewed the tracings, determined if an arrhythmia was present and identified the arrhythmia. We conducted the study anonymously. We reported the data as percent correct arrhythmia detection and correct arrhythmia identification. Thirty-one anesthesiologists completed the study. Overall, the participants correctly detected 79.5% (95% CI: 77.2, 81.7%) of the arrhythmias and correctly identified 62.5% (95% CI: 59.8, 65.3%) of the arrhythmias, regardless of EN presence. Although the proportions among monitor noise filters studied were not significant, the manufacturer-designated MR5 Veris MR filter optimized arrhythmia detection and arrhythmia identification for our participants, regardless if EN was present in the ECG tracings. In the neurosurgical OR, the anesthetist must be able to effectively monitor a patient in the presence of iMRI-generated EN. Depending on the OR design, the patient may be out of the anesthetist's direct view during a scan procedure. The anesthetist must rely on monitored physiologic parameters to assess patient status during this time. He/she should be familiar with his/her monitor's filtering capabilities and routinely adjust the ECG filters to achieve the best compromise between minimized EN effects and maximized displayed ECG signal quality.


Exploring the impact of COVID-19 on individual's travel mode choice in China.
Travel activities and travel behaviors have been greatly affected by the outbreak of Covid-19. Facing the change of individuals' travel choices, policymakers have to make an appropriate response to mitigate negative consequences. This paper aims to explore how the COVID-19 would impact travel mode choice and the intention of car purchase. The data was collected from a large-scale survey conducted in June 2020 after the highest point. Random utility maximization (RUM), random regret minimization (RRM) and generalized regret minimization (GRRM) are employed to examine the effects of various factors on mode choice behaviors. The estimation results reveal that regret aversion psychology doesn't have a dominant proportion of decision choices, even if the congested condition of the mass mobility plays a significant role in the consideration of decision-making. Combined with the statistical results from the official departments, we concluded that public transport displays a great propensity on the long trip, and meanwhile, the industry of ride-hailing services has shocked sharply. In terms of the intention of traffic tool purchase, carless people prefer to buy electric two-wheel vehicles rather than automobiles. The research findings and the contribution to policy implications give assistance to authority in understanding citizens' travel mode preferences under the impact of COVID-19.


Effects of a Responsiveness-Focused Intervention in Family Child Care Homes on Children's Executive Function.
Caregiver responsiveness has been theorized and found to support children's early executive function (EF) development. This study examined the effects of an intervention that targeted family child care provider responsiveness on children's EF. Family child care providers were randomly assigned to one of two intervention groups or a control group. An intervention group that received a responsiveness-focused online professional development course and another intervention group that received this online course plus weekly mentoring were collapsed into one group because they did not differ on any of the outcome variables. Children (N = 141) ranged in age from 2.5 to 5 years (mean age = 3.58 years; 52% female). At pretest and posttest, children completed delay inhibition tasks (gift delay-wrap, gift delay-bow) and conflict EF tasks (bear/dragon, dimensional change card sort), and parents reported on the children's level of attention problems. Although there were no main effects of the intervention on children's EF, there were significant interactions between intervention status and child age for delay inhibition and attention problems. The youngest children improved in delay inhibition and attention problems if they were in the intervention rather than the control group, whereas older children did not. These results suggest that improving family child care provider responsive behaviors may facilitate the development of certain EF skills in young preschool-age children.


Hepatitis A virus-encoded miRNAs attenuate the accumulation of viral genomic RNAs in infected cells.
The establishment of persistent infection with hepatitis A virus (HAV) is the common result of most HAV/cell culture systems. Previous observations show that the synthesis of viral RNAs is reduced during infection. However, the underlying mechanism is poorly understood. We characterized three HAV-encoded miRNAs in our previous study. In this study, we aim to investigate the impact of these miRNAs on the accumulation of viral RNAs. The results indicated that the synthesis of viral genomic RNAs was dramatically reduced (more than 75 % reduction, P < 0.05) when transfected with one or two viral miRNA mimics. Conversely, they were significantly increased (more than 3.3-fold addition, P < 0.05) when transfected with one or two viral miRNA inhibitors. The luciferase reporter assay of miRNA targets showed that viral miRNAs were fully complementary to specific sites of the viral plus or minus strand RNA and strongly inhibited their expressions. Further data showed that the relative abundance of viral genomic RNA fragments that contain miRNA targets was also dramatically reduced (more than 80 % reduction, P < 0.05) when viral miRNAs were overexpressed with miRNA mimics. In contrast, they were significantly increased (approximately 2-fold addition, P < 0.05) when viral miRNAs were inhibited with miRNA inhibitors. In conclusion, these data suggest a possible mechanism for the reduction of viral RNA synthesis during HAV infection. Thus, we propose that it is likely that RNA virus-derived miRNA could serve as a self-mediated feedback regulator during infection.


Targeted effects of retinoic acid signaling upon photoreceptor development in zebrafish.
Retinoic acid (RA) is a signaling molecule important for photoreceptor development in vertebrates. The purpose of this study was to examine the mechanisms of the effects of RA upon developing rod and cone photoreceptors in the embryonic zebrafish. Exposure to exogenous RA increased the number of photoreceptors expressing rod opsin and red cone opsin, and decreased the number of photoreceptors expressing the blue and UV cone opsins, suggesting targeted effects of RA on photoreceptor development. RA exposure also increased opsin expression in individual rods and red cones, but decreased opsin expression in individual blue and UV cones, as indicated by differences in the strength of opsin hybridization in identified photoreceptors. RA exposure did not, however, significantly alter quantitative measures of photoreceptor pattern in a manner expected for changes in photoreceptor fate. These observations collectively indicate that RA treatment does not affect photoreceptor fate, but rather differentially influences opsin transcription in determined photoreceptors. An enzyme involved in RA synthesis, RALDH2, was immunocytochemically localized to retinal progenitor cells and the retinal pigmented epithelium (RPE), suggesting the presence of RA in the vicinity of developing photoreceptors. However, expression of an RA response element-driven transgene was restricted to the RPE, retinal progenitors, and a small population of neurons in ventral retina, suggesting that the endogenous RA signaling system is spatially limited within the eye.


Expression and characterization of codon-optimized Crimean-Congo hemorrhagic fever virus Gn glycoprotein in insect cells.
Crimean-Congo hemorrhagic fever virus (CCHFV) is a major cause of tick-borne viral hemorrhagic disease in the world. Despite of its importance as a deadly pathogen, there is currently no licensed vaccine against CCHF disease. The attachment glycoprotein of CCHFV (Gn) is a potentially important target for protective antiviral immune responses. To characterize the expression of recombinant CCHFV Gn in an insect-cell-based system, we developed a gene expression system expressing the full-length coding sequence under a polyhedron promoter in Sf9 cells using recombinant baculovirus. Recombinant Gn was purified by affinity chromatography, and the immunoreactivity of the protein was evaluated using sera from patients with confirmed CCHF infection. Codon-optimized Gn was successfully expressed, and the product had the expected molecular weight for CCHFV Gn glycoprotein of 37 kDa. In time course studies, the optimum expression of Gn occurred between 36 and 48 hours postinfection. The immunoreactivity of the recombinant protein in Western blot assay against human sera was positive and was similar to the results obtained with the anti-V5 tag antibody. Additionally, mice were subjected to subcutaneous injection with recombinant Gn, and the cellular and humoral immune response was monitored. The results showed that recombinant Gn protein was highly immunogenic and could elicit high titers of antigen-specific antibodies. Induction of the inflammatory cytokine interferon-gamma and the regulatory cytokine IL-10 was also detected. In conclusion, a recombinant baculovirus harboring CCHFV Gn was constructed and expressed in Sf9 host cells for the first time, and it was demonstrated that this approach is a suitable expression system for producing immunogenic CCHFV Gn protein without any biosafety concerns.


Exacerbation of hepatic encephalopathy by chronic renal failure: response to maintenance hemodialysis.
The consequences of chronic renal insufficiency relevant to hepatic failure are not well appreciated. We describe a patient with chronic cirrhosis and marked porto-systemic shunting who, after the onset of chronic renal failure, developed intractable encephalopathy which improved markedly during an eight month period of maintenance hemodialysis.


Systemic treatment for prostate cancer.
Prostate cancer is a leading cause of cancer mortality in adult men. The majority of patients have subclinical systemic disease at diagnosis and will eventually require systemic therapy for palliation of symptoms. Recent development of new hormonal treatment options (e.g., gonadotropin-releasing hormone analogues and estramustine) has yet to demonstrate potential for improving the therapeutic index or for lengthening survival over results achieved with traditional modalities (i.e., supplemental estrogens or castration). Chemotherapeutic agents have demonstrated palliative efficacy and are being tested in multidrug regimens and in combination with hormones. At the present time, the optimal use of cytotoxic drugs remains undefined, since recently published studies have shown neither that combination chemotherapy is superior to single agents nor that chemo-hormonal therapy produces more favorable results than hormonal treatment alone.


Involvement of GABAergic, glutamatergic, opioidergic, and brain-derived neurotrophic factor systems in the trigeminal neuropathic pain process.
Trigeminal neuropathic pain (TNP) is an intense pain condition characterized by hyperalgesia and allodynia; however, its neural mechanisms are not completely understood. Its management is complex, and studies that investigate its biochemical mechanisms are important for improving clinical approaches. This study aimed to evaluate the involvement of GABAergic, glutamatergic, and opioidergic systems and brain-derived neurotrophic factor (BDNF) levels in the TNP process in rats. TNP is induced by chronic constriction injury of the infraorbital nerve (CCI-ION). Nociceptive responses were evaluated using the facial von Frey test before and after the administration of GABAergic and opioidergic agonists and glutamatergic antagonists. The rats were divided into vehicle-treated control (C), sham-surgery (SS), and CCI-ION groups, and then subdivided into the vehicle (V)-treated SS-V and CCI-ION-V groups, SS-MK801 and CCI-ION-MK801, treated with the N-methyl-d-aspartate receptor selective antagonist MK801; SS-PB and CCI-ION-PB, treated with phenobarbital; SS-BZD and CCI-ION-BZD, treated with diazepam; SS-MOR and CCI-ION-MOR, treated with morphine. BDNF levels were evaluated in the cerebral cortex, brainstem, trigeminal ganglion, infraorbital branch of the trigeminal nerve, and serum. CCI-ION induced facial mechanical hyperalgesia. Phenobarbital and morphine reversed the hyperalgesia induced by CCI-ION, and the CCI-BZD group had an increased nociceptive threshold until 60 min. CCI-ION-GLU increased the nociceptive threshold at 60 min. Cerebral cortex and brainstem BDNF levels increased in the CCI-ION and SS groups. Only the CCI group presented high levels of BDNF in the trigeminal ganglion. Our data suggest the involvement of GABAergic, glutamatergic, and opioidergic systems and peripheral BDNF in the TNP process.


Polyamines enhance calcium mobilization in fMet-Leu-Phe-stimulated phagocytes.
Spermidine and putrescine (50 microM-1 mM), found in exudates from infection sites, significantly enhance fMet-Leu-Phe-induced Ca2+ mobilization in differentiated HL-60 cells and polymorphonuclear leukocytes (PMNs) by delaying the return to basal cytosolic Ca2+ levels. This enhancement by polyamines is associated with inhibition of Ca2+ efflux across the plasma membrane. In parallel with their effects on Ca2+ signaling, polyamines also significantly prolong the kinetics of fMet-Leu-Phe-induced protein kinase C translocation. Thus, polyamines may play a novel role in modulating regulatory events in phagocytes.


Esophageal atresia: primary results of 500 consecutively treated patients.
During 1947-1978, 500 patients with esophageal atresia and/or tracheoesophageal fistula were treated at the Children's Hospital, University of Helsinki. The proportion of different types of anomaly followed the usual distribution, the commonest being the type with distal fistula (88.2%). For analysis, the patients were divided into five phases, each consisting of 100 consecutively treated patients. The hospital mortality decreased from 81% in the first phase to 15% in the last phase. No patients were excluded, not even those cases with lethal associated anomalies. Many more severe cases were treated in the last two phases than in the first three. Patients with distal fistula were examined separately as were the patients without a fistula and those with only a tracheoesophageal fistula. With time, early diagnosis and early referral for treatment became a rule. This led to the policy that nearly all patients in the last phase had an early operation without staging. Gastrostomy was not considered necessary when early anastomosis was possible. In the last phase, only the transpleural approach was used and single-layer end-to-end anastomosis was favored. As a whole, the type of approach or anastomosis did not have significant effect on the results, except that the Sulamaa-type end-to-side anastomosis had the highest frequency for refistula. With time there was only a slight decrease in the incidence of anastomotic leak, but significant improvement in its management. Refistula as an early complication was seen only once in the last phase. As all anastomoses were routinely dilated, severe strictures were uncommon; there were only six in the series. The factor that probably improved the prognosis the most was better pulmonary care. The improved prognosis was also due to earlier referral, modern anesthesia, and intensive care. Postoperative pulmonary complications dropped from 92% in the first phase to 40% in the last. They were the most common single cause of death in the early series but caused no deaths among the last 100 patients with no associated anomalies. Low birth weight was an important prognostic factor early in the series but in the last phase the survival rate of under-2500-gm infants with no associated anomalies was 88%. The presence of severe associated anomalies remains the most important single cause of death of an esophageal atresia patient today. Some patients (eg, trisomy 18) are beyond the possibilities of surgical treatment. To improve the prognosis of the others, efforts in the treatment of their associated (especially cardiovascular) anomalies must be made. In the treatment of esophageal atresia itself, improvement may still be achieved in the number of patients using their own esophagus without replacement procedures. Finally, a new prognostic classification of esophageal atresia patients is suggested, excluding pneumonia as an index factor in the Waterston classification.


Effect of self-assembling peptide, chondrogenic factors, and bone marrow-derived stromal cells on osteochondral repair.
The goal of this study was to test the ability of an injectable self-assembling peptide (KLD) hydrogel with or without chondrogenic factors (CF) and allogeneic bone marrow stromal cells (BMSCs) to stimulate cartilage regeneration in a full-thickness, critically-sized, rabbit cartilage defect model in vivo. We used CF treatments to test the hypotheses that CF would stimulate chondrogenesis and matrix production by cells migrating into acellular KLD (KLD+CF) or by BMSCs delivered in KLD (KLD+CF+BMSCs). Three groups were tested against contralateral untreated controls: KLD, KLD+CF, and KLD+CF+BMSCs, n=6-7. Transforming growth factor-β1 (TGF-β1), dexamethasone, and insulin-like growth factor-1 (IGF-1) were used as CF pre-mixed with KLD and BMSCs before injection. Evaluations included gross, histological, immunohistochemical and radiographic analyses. KLD without CF or BMSCs showed the greatest repair after 12 weeks with significantly higher Safranin-O, collagen II immunostaining, and cumulative histology scores than untreated contralateral controls. KLD+CF resulted in significantly higher aggrecan immunostaining than untreated contralateral controls. Including allogeneic BMSCs+CF markedly reduced the quality of repair and increased osteophyte formation compared to KLD-alone. These data show that KLD can fill full-thickness osteochondral defects in situ and improve cartilage repair as shown by Safranin-O, collagen II immunostaining, and cumulative histology. In this small animal model, the full-thickness critically-sized defect provided access to the marrow, similar in concept to abrasion arthroplasty or spongialization in large animal models, and suggests that combining KLD with these techniques may improve current practice.


Repeated subarachnoid administrations of allogeneic human umbilical cord mesenchymal stem cells for spinal cord injury: a phase 1/2 pilot study.
Stem cell transplantation is a potential treatment for intractable spinal cord injury (SCI), and allogeneic human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising candidate because of the advantages of immune privilege, paracrine effect, immunomodulatory function, convenient collection procedure and little ethical concern, and there is an urgent need to develop a safe and effective protocol regarding their clinical application. A prospective, single-center, single-arm study in which subjects received four subarachnoid transplantations of hUC-MSCs (1 × 106 cells/kg) monthly and were seen in follow-up four times (1, 3, 6 and 12 months after final administration) was conducted. At each scheduled time point, safety and efficacy indicators were collected and analyzed accordingly. Adverse events (AEs) were used as a safety indicator. American Spinal Injury Association (ASIA) and SCI Functional Rating Scale of the International Association of Neurorestoratology (IANR-SCIFRS) total scores at the fourth follow-up were determined as primary efficacy outcomes, whereas these two indicators at the remaining time points as well as scores of pinprick, light touch, motor and sphincter, muscle spasticity and spasm, autonomic system, bladder and bowel functions, residual urine volume (RUV) and magnetic resonance imaging (MRI) were secondary efficacy outcomes. Subgroup analysis of primary efficacy indicators was also performed. Safety and efficacy assessments were performed on 102 and 41 subjects, respectively. Mild AEs involving fever (14.1%), headache (4.2%), transient increase in muscle tension (1.6%) and dizziness (1.3%) were observed following hUC-MSC transplantation and resolved thoroughly after conservative treatments. There was no serious AE. ASIA and IANR-SCIFRS total scores revealed statistical increases when compared with the baselines at different time points during the study, mainly reflected in the improvement of pinprick, light touch, motor and sphincter scores. Moreover, subjects showed a continuous and remarkable decrease in muscle spasticity. Regarding muscle spasm, autonomic system, bladder and bowel functions, RUV and MRI, data/imaging at final follow-up showed significant improvements compared with those at first collection. Subgroup analysis found that hUC-MSC transplantation improved neurological functions regardless of injury characteristics, including level, severity and chronicity. The authors' present protocol demonstrates that intrathecal administration of' allogeneic hUC-MSCs at a dose of 106 cells/kg once a month for 4 months is safe and effective and leads to significant improvement in neurological dysfunction and recovery of quality of life.


Operational safety issues in MRI.
The clinical usefulness of a diagnostic modality is weighed by considering its potential diagnostic benefit against its potential risk for a patient in question. Magnetic resonance imagining appears to offer both high efficacy and safety under most circumstances. Our understanding of the conditions under which MRI is safe and effective has undergone continual refinement with technological advances and clinical experience. The early emphasis on safety issues of MR focussed on consideration of bioeffects of RF and magnetic fields. More recently, hundreds of operating clinical MR sites, performing hundreds of thousands of clinical examinations to date, have provided a greater awareness of operational safety issues. Much of this experience is summarized in device labeling provided by manufacturers of MR devices, summaries prepared by regulatory agencies, and case reports in the medical literature. The purpose of this article is to review a broad range of safety considerations involved in the operation of MR imagers. The discussion is in two parts: (1) a short update of reported incidents and (2) an analysis of safety issues.


The effects of enriched CO2 atmospheres on plant-insect herbivore interactions: growth responses of larvae of the specialist butterfly, Junonia coenia (Lepidoptera: Nymphalidae).
Little is known about the effects of enriched CO2 environments, which are anticipated to exist in the next century, on natural plant-insect herbivore interactions. To begin to understand such effects on insect growth and survival, I reared both early and penultimate instar larvae of the buckeye, Junonia coenia (Lepidoptera: Nymphalidae), on leaves from one of their major hostplants, plantain, Plantago lanceolata (Plantaginaceae), grown in either ambient (350 PPM) or high (700 PPM) CO2 atmospheres. Despite consuming more foliage, early instar larvae experienced reduced growth on high CO2-grown compared to ambient CO2-grown leaves. However, survivorship of early instar larvae was unaffected by the CO2 treatment. Larval weight gain was positively correlated with the nitrogen concentration of the plant material and consumption was negatively correlated with foliar nitrogen concentration, whereas neither larval weight gain nor consumption were significantly correlated with foliar water or allelochemical concentrations. In contrast, penultimate instar larvae had similar growth rates on ambient and high CO2-grown leaves. Significantly higher consumption rates on high CO2-grown plants enabled penultimate instar larvae to obtain similar amounts of nitrogen in both treatments. These larvae grew at similar rates on foliage from the two CO2 treatments, despite a reduced efficiency of conversion of ingested food (ECI) on the low nitrogen, high CO2-grown plants. However, nitrogen utilization efficiencies (NUE) were unaffected by CO2 treatment. Again, for late instar larvae, consumption rates were negatively correlated with foliar nitrogen concentrations, and ECI was also very highly correlated with leaf nitrogen; foliar water or allelochemical concentrations did not affect either of these parameters. Differences in growth responses of early and late instar larvae to lower nitrogen, high-CO2 grown foliage may be due to the inability of early instar larvae to efficiently process the increased flow of food through the gut caused by additional consumption of high CO2 foliage.


Environmentally driven shift between alternative female morphotypes in the mottled shore crab.
Precocious maturity is an important life history trait and might be advantageous if the juvenile habitat is risky. Larvae of the mottled shore crab Pachygrapsus transversus settle to the benthic habitat at a very large size, undergo a brief juvenile development and mature within a few months at a size about a fourth of the asymptotic maximum size for this species. This strategy may rely on the capacity of this species to molt to a juvenile-like morphotype (mI) in which reproduction is suppressed. In the laboratory, winter temperature triggered the puberty molt for a large proportion of juveniles, and still allowed high growth rates if combined with long photoperiod. This would result in a large number of juvenile crabs to join the adult reproductive stock in spring, at the beginning of the breeding season. Adult morphs (mII) grow faster under winter conditions, and therefore might be able to direct resources to reproduction during summer. Yet, females held in captivity without any interaction with conspecifics failed to maintain their reproductive status and often reversed to mI stages. In contrast, when a potential mate was presented, all crabs held their mII status, regardless of whether interaction involved visual, visual + chemical, or visual + chemical + tactile cues. Males discriminate female morphs, and physical interactions, including the inspection of mate receptivity and copulation, took longer when they were interacting with mII females. More than a trade-off between growth and reproduction, sustaining a breeding condition in P. transversus females is apparently a bet for successful mating in the presence of a suitable male conspecific.


Heterocyclic steroids-part VIII: Studies on the total synthesis of racemic 2-phenyl-7-methyl-3-oxa-A-nor-14 beta-estra-1,5(10),6,8-tetraen-17 alpha-ol.
2-Phenyl-6-methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran (II) is converted into racemic 2-phenyl-7-methyl-3-oxa-A-nor-14 beta-estra-1,5(10),6,8-tetraen-17 alpha-ol (VIII).


Alpha-mercaptoketone based histone deacetylase inhibitors.
In an effort to discover novel non-hydroxamic acid histone deacetylase (HDAC) inhibitors, a novel alpha-mercaptoketone was identified in a high-throughput screen. Lead optimization of the screening hit, led to a number of potent HDAC inhibitors. In particular, alpha-mercaptoketone 19y (KD5150) exhibited nanomolar in vitro activity and inhibition of tumor growth in vivo.


Comparative effects of insulin and refeeding on DNA synthesis, HMP shunt and cholesterogenesis in diabetic and fasted rats.
DNA synthesis, cholesterogenesis and the enzymes of the hexosemonophosphate (HMP) shunt pathway were investigated in liver of diabetic rats treated with insulin and in fasted/re-fed rats. Both insulin and refeeding were found to induce liver cell proliferation, accompanied by a remarkable increase in cholesterogenesis. An enhancement of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (G6PD) activities was also found in insulin-treated diabetic rats and in re-fed rats, supporting the concept that these two enzymes are involved in the proliferative process. Since insulin did not exert the same biochemical effects in a non replicating cell population, such as in insulin-treated normal rats, these studies provide new evidence of a close correlation between DNA, cholesterol synthesis and HMP shunt enzymes during cell proliferation.


Studies of a contaminated brackish marsh in the Hackensack Meadowlands of northeastern New Jersey: an assessment of natural recovery.
Eight-Day Swamp is known to be contaminated with heavy metals, especially mercury. Sediment cores were collected to approximately 32 cm at 17 sites on four transects and analyzed at 1 or 2 cm intervals for seven metals and organic matter. Very high metal levels were found throughout the site. Long and Morgan's "effects range-median" (ER-M) was exceeded in more than 50% of slices for all elements except As. Hg had the highest concentration relative to ER-M; median Hg concentration was 72 times its ER-M. On the marsh plain, all metals showed enrichment at 14-20 cm depth of 10-40X over surficial sediments. 137Cs analysis showed sedimentation rates ranging from 0.33 to 0.50 cm yr(-1) over the last approximately 40 yr. These rates indicate that metal contamination peaks occurred in sediments deposited in the early 1960s. Thus, newer, less contaminated sediments are burying older, more contaminated layers and peak levels of contaminants are becoming less available to benthos.


Scope of the Problem and Perception by Owners and Veterinarians.
Obesity is a common disease of modern dogs and cats. Dog and cat owners often do not realize their animal is affected. Some pet owners are skeptical of the diagnosis or rationalize the overweight condition of their pets. Animal-related factors associated with obesity in dogs and cats include breed, neuter status, age, and gender, whereas owner-related factors include diet choice, feeding method, and provision of exercise. Owner characteristics, such as age and income, are also potential risk factors for pet obesity. Identifying such risk factors for both animals and owners may help provide targets for prevention or interventional tools.


NR4A1 promotes TNF‑α‑induced chondrocyte death and migration injury via activating the AMPK/Drp1/mitochondrial fission pathway.
Nuclear receptor subfamily 4 group A member 1 (NR4A1)‑induced chondrocyte death plays a critical role in the development of osteoarthritis through poorly defined mechanisms. The present study aimed to investigate the role of NR4A1 in regulating chondrocyte death in response to tumor necrosis factor‑α (TNF‑α) and cycloheximide (CHX) treatment, with a focus on mitochondrial fission and the AMP‑activated protein kinase (AMPK) signaling pathway. The results demonstrated that NR4A1 was significantly upregulated in TNF‑α and CHX exposed chondrocytes. Increased NR4A1 triggered mitochondrial fission via the AMPK/dynamin‑related protein 1 (Drp1) pathway, resulting in mitochondrial dysfunction, and mitochondrial permeability transition pore (mPTP) opening‑related cell death. Furthermore, excessive mitochondrial fission impaired chondrocyte migration through imbalance of F‑actin homeostasis. Inhibiting NR4A1 attenuated TNF‑α and CHX‑induced mitochondrial fission and, thus, reduced mitochondrial dysfunction in chondrocytes, mPTP opening‑related cell death and migration injury. Altogether, the present data confirmed that mitochondrial fission was involved in NR4A1‑mediated chondrocyte injury via regulation of mitochondrial dysfunction, mPTP opening‑induced cell death and F‑actin‑related migratory inhibition.


The responsiveness of the Manchester Chronic Obstructive Pulmonary Disease Fatigue Scale to pulmonary rehabilitation.
We examined the responsiveness of the Manchester Chronic Obstructive Pulmonary Disease (COPD) Fatigue Scale (MCFS) in patients with COPD following 8 weeks of pulmonary rehabilitation (PR). Patients (n = 273) with clinically stable COPD completed 8 weeks of outpatient multidisciplinary PR, comprising 2 h (1 h exercise and 1 h education) weekly. Anxiety, exercise capacity, quality of life, dyspnea, fatigue were measured pre- and post-PR, utilizing the Anxiety Inventory for Respiratory Disease (AIR), Incremental Shuttle Walk Test (ISWT), St. George's Respiratory Questionnaire (SGRQ), and modified Medical Research Council (mMRC) scale and MCFS, respectively. The mean (SD) age of participants was 72 (8) years, and 50% were women. Total MCFS score fell after PR mean (95% confidence interval) -4.89 (-7.90 to -3.79) as did domain scores: physical -1.89 (-2.33 to -1.46), cognition -1.37 (-1.65 to -1.09), and psychosocial -1.62 (-2.00 to -1.62). Total MCFS effect size (ES) was 0.55; and for domains, physical was 0.52, cognition was 0.59, and psychosocial was 0.51. The ES for AIR was 0.30, mMRC was 0.38, SGRQ was 0.66, and ISWT was 1.19. MCFS changes correlated with changes in both SGRQ (p < 0.002) and AIR (p < 0.004), but not ISWT (p = 0.30) or mMRC (p = 0.18). The AIR, SGRQ, mMRC, and ISWT all improved after PR (all, p < 0.001). The MCFS scale is a valid and responsive scale to measure fatigue in patients with COPD after pulmonary rehabilitation.


Language differences as a barrier to quality and safety in health care: the Joint Commission perspective.
Effective communication with patients is critical to the safety and quality of care. Barriers to this communication include differences in language, cultural differences, and low health literacy. Evidence-based practices that reduce these barriers must be integrated into, rather than just added to, health care work processes.


Incremental value of endoscopic brush cytology in response assessment after chemo-irradiation for Esophageal cancer.
Response assessment after chemo-radiotherapy (CTRT) in locally advanced esophageal cancer is usually performed using a PET-CT scan, an upper GI endoscopy (UGIE) and histological correlation with biopsy or cytology. We aim to study the incremental value of brush cytology in addition to PET-CT for response assessment. In this retrospective analysis, 40 patients with Stage II- IV carcinoma esophagus treated with radical intent between June 2015 and August 2019 were included. Patients were treated with either upfront concurrent CTRT or neo-adjuvant chemotherapy followed by CTRT. All patients underwent PET-CT and UGIE for initial staging and response assessment on follow-up. Patients with esophageal stricture (disease related or treatment induced) had brush cytology done during UGIE. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of brush cytology were calculated considering serial clinical follow-up as gold standard. Twenty-three male (57.5%) and 17 (42.5%) female patients with median age of 57 years (range: 27 - 79 years) were analyzed. Concurrent CTRT was delivered in 52.5%; 75% patients were treated with intensity-modulated radiotherapy (IMRT); median RT dose was 63 Gy (range- 41.4 to 64 Gy). At a median follow-up of 16 months (range 6- 54 months), 20 patients (55.5%) were clinically controlled, 9 (25%) had local recurrence, 5 (13.8%) had loco-regional recurrence and 2 had distant metastasis. Considering clinical follow-up as the gold standard, sensitivity, PPV and NPV of PET-CT combined with brush cytology improved compared to PET-CT alone and was found to be 75%, 90%, 85.7% and 81.8% respectively. We found that brush cytology on endoscopy is a simple tool with high specificity which adds value to the findings of response assessment PET-CT scan and thereby can increase the confidence of the treating oncologist in making clinical decisions.


Prevalence, patterns, and determinants of gender-based violence among women and girls in IDP camps, Mogadishu-Somalia.
Gender-based violence (GBV) against women and girls, is a global pandemic that affects 1 in 3 women in their lifetime. Somalia is one of the leading countries in human rights violations and has one of the highest rates of sexual and gender-based violence (SGBV) worldwide. Such violence is more prevalent among women and girls in internally displaced persons (IDP) camps who lack livelihood and civil protections. Therefore, this study was designed to identify the prevalence and the determinants of gender-based violence in IDP camps in Deynile district, Somalia. This is a cross-sectional study design conducted in IDP camps in Deynile District from August 1 to September 30, 2022. A total of three hundred eighty-four women and girls aged 18 years and above living in the selected IDP camps were involved in the study. The camps were selected randomly while households and participants were selected systematic random sampling. The recall period was set at 12 months (August 2021 to July 2022). Participants were interviewed by well-trained research assistants using pre-tested structured questionnaire. Data was entered into and analyzed with SPSS 25.0. Logistic regression was used, and the significance level was set at p value ≤ 0.05. The study revealed that gender-based violence was quite common in the IDP camps in Mogadishu's Deynile area. Physical abuse was the most prevalent type of GBV, which was primarily committed by intimate partners, parents, and other family members. The main factors associated with gender-based violence were young age (OR=4.77, 95% CI: 1.96-11.63, p<0.001), extended family structure (OR=7.89, 95% CI: 4.30-14.47, p<0.001), household size >5 individuals (OR=1.86, 95% CI:1.04-3.30, p<0.005), employment (OR=1.57, 95% CI: 1.0.41-2.32, p<0.05), substance misuse (OR=3.25, 95% CI: 1.57-6.73, p<0.05), a long distance to the nearest police station (OR=2.75, 95% CI:1.51-5.00, p<0.005), and camp safety protection (OR=1.94, 95% CI:1.24-3.30, p<0.005). There was a high prevalence of gender-based violence in the IDP camps in Mogadishu's Deynile area. The most common form of GBV was physical violence mainly perpetuated by intimate partners. The study recommends improving some of the modifiable factors that were strongly associated with gender-based violence.


Preliminary evidence that estrogen protects against age-related hippocampal atrophy.
Few studies have examined gender differences in hippocampal volumes, and the potential effect of estrogen on these measures has not been well studied. We used MRI to measure hippocampal volumes in elderly Mexican American men and women subjects in order to determine if there were gender differences and if estrogen replacement therapy (ERT) had an effect on hippocampal volume in postmenopausal women. MRI measures of hippocampal volumes (normalized to intracranial volume) were compared in 59 women and 38 men. Further comparisons were made between men subjects, women subjects taking ERT, and women subjects not taking ERT. There were no significant effects of gender on normalized hippocampal volumes. However, women subjects taking ERT had larger right hippocampal volumes than women subjects not taking ERT and larger anterior hippocampal volumes than men subjects and women subjects not taking ERT. These findings suggest a neuroprotective effect of estrogen.


Botryosphaeriaceae species associated with dieback and canker disease of bay laurel in northern California with the description of Dothiorella californica sp. nov.
Members of the Botryosphaeriaceae are cosmopolitan fungi that may exist as seemingly innocuous endophytes or as destructive pathogens of numerous woody hosts, including fruit and nut crops, urban ornamental trees and shrubs, and forest trees. Surveys of bay laurel in northern California have revealed symptoms of dieback and branch canker of unknown aetiology. The goals of this study were to identify and clarify the species of Botryosphaeriaceae associated with these symptoms and to confirm their pathogenicity. To understand the role of members of the Botryosphaeriaceae in the dieback and canker disease of bay laurel, 23 isolates were isolated from symptomatic wood. Phylogenetic analyses of ITS, translation elongation factor 1-α, and beta-tubulin revealed three species: Botryosphaeria dothidea, Neofusicoccum nonquaesitum, and the newly described and typified species Dothiorella californica sp. nov. When select isolates were inoculated to 2- to 3-year-old branches of Umbellularia californica in a natural forest, both B. dothidea and N. nonquaesitum were pathogenic with N. nonquaesitum producing the largest lesions at 12- and 18-months post inoculation, respectively, while Do. californica did not cause wood lesions significantly greater than the mock-inoculated controls. This study represents the first attempt to identify and test the pathogenicity of Botryosphaeriaceae species associated with dieback and canker disease of bay laurel in a northern California forest.


Imaging of rectus femoris proximal tendinopathies.
The rectus femoris is the most commonly injured muscle of the anterior thigh among athletes, especially soccer players. Although the injury pattern of the muscle belly is well documented, less is known about the anatomy and specific lesions of the proximal tendons. For each head, three distinctive patterns may be encountered according to the location of the injury, which can be at the enthesis, within the tendon, or at the musculotendinous junction. In children, injuries correspond most commonly to avulsion of the anteroinferior iliac spine from the direct head and can lead to subspine impingement. Calcific tendinitis and traumatic tears may be encountered in adults. Recent studies have shown that traumatic injuries of the indirect head may be underdiagnosed and that injuries of both heads may have a surgical issue. Finally, in the case of tears, functional outcome and treatment may vary if the rupture involves one or both tendons and if the tear is partial or complete. Thus, it is mandatory for the radiologist to know the different ultrasound and magnetic resonance imaging (MRI) patterns of these lesions in order to provide accurate diagnosis and treatment. The purpose of this article is to recall the anatomy of the two heads of rectus femoris, describe a reliable method of assessment with ultrasound and MRI and know the main injury patterns, through our own experience and literature review.


Pioglitazone prevents corporal veno-occlusive dysfunction in a rat model of type 2 diabetes mellitus.
To determine whether corporal veno-occlusive dysfunction (CVOD), corporal smooth muscle (SM) loss, fibrosis and oxidative stress occur in a rat model of type 2 diabetes, and whether these are counteracted by pioglitazone, as pioglitazone is vasculoprotective, and corporal SM is an extension of arterial SM. Male obese Zucker fa/fa rats were fed chow containing 0%, 0.001% or 0.02% pioglitazone for 2 or 5 months, using untreated lean Zucker and Fischer 344 rats as controls. Functional changes were determined by dynamic-infusion cavernosometry. Histological changes were assessed by histochemistry and immunohistochemistry followed by quantitative image analysis and/or quantitative Western blot. CVOD was detected at 4.5 months of diabetes, accompanied by a lower corporal SM/collagen ratio, and increases in collagen, collagen III/I ratio, apoptotic index, and systemic and tissue oxidative stress. In the short-term treatment, high-dose pioglitazone normalized glycaemia and ameliorated fibrosis and oxidative stress, but induced CVOD, whereas the effects with the low dose were not significant. However, low-dose pioglitazone for 5 months corrected all alterations. Type 2 diabetes in Zucker fa/fa rats was associated with penile corporal fibrosis, oxidative stress, and CVOD, which were ameliorated by long-term low-dose pioglitazone, suggesting that this drug might protect the SM, independently from its antidiabetic effect.


Changing patterns of binocular visual connections in the intertectal system during development of the frog, Xenopus laevis. II. Abnormalities following early visual deprivation.
During normal metamorphic and post-metamorphic growth of the frog, Xenopus laevis, there is a major and orderly remodelling of the pattern of neuronal connections in the intertectal system. These changes preserve the spatial registration of binocular visual inputs to each optic tectum in the face of continuous changes in relative eye alignment (Grant and Keating 1989). We suggested that visual experience might be utilised by the intertectal system to effect the maturational remodelling of its connections, with particular involvement in maintaining binocular visual registration. To investigate this suggestion we studied the development of the intertectal system in animals that had been reared in total darkness from before the onset of function in the system. Visual deprivation did not affect the developmental ocular migration that normally occurs in Xenopus, nor did it affect the maturation of the contralateral visuotectal projection. Abnormalities were, however, observed in the ipsilateral visuotectal projection of all dark-reared animals studied, reflecting perturbation of the underlying intertectal system. The abnormalities included disorder and deficits in the projection, which became more marked with age. Quantitative analyses of the spatial registration of binocular visual inputs to the optic tectum revealed that, in all dark-reared animals studied, registration was both significantly poorer and systematically shifted compared to normal controls. Analysis of maturational changes in the pattern of intertectal connections in visually-deprived animals led to the conclusion that intrinsic developmental processes generate an initially well-organised intertectal system and programme much of its continuous expansion with age. Visual experience, however, is necessary for the large scale and orderly remodelling of the system which, during normal maturation, preserves binocular visual registration despite changes in interocular alignment.


Root Dentin Translucency and Forensic International Dental Database: Methodology for estimation age-at-death in adults using single-rooted teeth.
Estimation of the age-at-death in adults is essential when the identification of deceased persons with unknown identity is required in both humanitarian and judicial contexts. However, the methodologies and the results obtained can be questioned. Various efforts have been developed to adjust procedures to specific populations, always seeking the precision and accuracy of the methodologies. It is known that the estimation of the age-at-death in adults coexists with wide margins of error, due to several reasons, including but not limited to statistical problems, the size of the sample or the physiological process of aging. This research focuses on a degenerative indicator of the dentin (Root Dentin Translucency) and its combination with Periodontal Height (PH) following the Lamendin's technique for estimation of the age-at-death in adults. The main objective of this research was to demonstrate the applicability of a Bayesian model based on a Forensic International Dental Database (FIDB) that include Root Translucency Height (RTH) and PH as a method to age-at-death in adults. The conclusion of this research was that the combined both indicators become a generalizable age-at-death in adults model for all human populations, where the Bayesian method would offer optimal results in any population. In this way, those populations that do not have had the possibility of validating a specific procedure, now have the opportunity to apply a valid method for estimating age-at-death in adults to global scope.


Structure of the O-specific galactan from the lipopolysaccharide of the reference strain for Serratia marcescens serogroup O24.
The putative O-specific polysaccharide for Serratia marcescens serogroup O24 is a galactan with a branched, trisaccharide repeating-unit of the structure shown. The structure of the backbone is identical to that of the linear galactans isolated from the reference strains for S. marcescens serogroups O16 and O20, presumably accounting for the serological cross-reactions observed. (Formula: see text)


Torsion of an undescended testis located in the inguinal canal.
Torsion of undescended testis located within the inguinal canal is a rare finding in the emergency department (ED). This diagnosis can present as undifferentiated abdominal or groin pain, and a full genitourinary examination is essential to making this diagnosis. We present this case to increase awareness among emergency physicians regarding torsion of undescended testis. A 5-year-old boy presented to the ED with abdominal pain and a mass in his right groin. Physical examination and Doppler ultrasound were used to diagnose torsion of undescended testis. In a patient with undescended testis, torsion must be considered as a cause of abdominal or groin pain. Full genitourinary examination is essential to making this diagnosis.


New trend in artificial intelligence-based assistive technology for thoracic imaging.
Although there is no solid agreement for artificial intelligence (AI), it refers to a computer system with intelligence similar to that of humans. Deep learning appeared in 2006, and more than 10 years have passed since the third AI boom was triggered by improvements in computing power, algorithm development, and the use of big data. In recent years, the application and development of AI technology in the medical field have intensified internationally. There is no doubt that AI will be used in clinical practice to assist in diagnostic imaging in the future. In qualitative diagnosis, it is desirable to develop an explainable AI that at least represents the basis of the diagnostic process. However, it must be kept in mind that AI is a physician-assistant system, and the final decision should be made by the physician while understanding the limitations of AI. The aim of this article is to review the application of AI technology in diagnostic imaging from PubMed database while particularly focusing on diagnostic imaging in thorax such as lesion detection and qualitative diagnosis in order to help radiologists and clinicians to become more familiar with AI in thorax.


Validation of patient symptom diary in acute posterior vitreous detachment.
The purpose of the study is to determine the validity of an original patient symptom diary in recording symptoms of posterior vitreous detachment (PVD). In this prospective cohort study, all patients presenting to the Hotel Dieu hospital emergency eye clinic between September 2008 and July 2009 diagnosed with acute PVD were offered enrollment in the study. Patients were given the Queen's University posterior vitreous detachment patient diary at the initial visit after detailed eye examination, assessment of risk factors for retinal tears and detachments and a thorough explanation of their presenting complaints to record their symptoms related to PVD. At a random point during their six-week follow up, the patients were verbally asked the same questions being recorded in the diary over the phone. At the six-week follow up visit, the diaries were collected and the verbal results were compared with the written results. There was substantial to near perfect agreement between the verbal questions and written answers. Cohen's kappa scores for flash frequency, flash intensity, floater frequency, and floater type were 0.6229, 0.6389, 0.6495, and 0.8603, respectively. The Queen's University posterior vitreous detachment patient diary is a useful tool for investigating the quantity, quality and change in symptoms of patients presenting with PVD in the first 6 weeks of initial presentation.


The role of human dopamine transporter in NeuroAIDS.
HIV-associated neurocognitive disorder (HAND) remains highly prevalent in HIV infected individuals and represents a special group of neuropathological disorders, which are associated with HIV-1 viral proteins, such as transactivator of transcription (Tat) protein. Cocaine abuse increases the incidence of HAND and exacerbates its severity by enhancing viral replication. Perturbation of dopaminergic transmission has been implicated as a risk factor of HAND. The presynaptic dopamine (DA) transporter (DAT) is essential for DA homeostasis and dopaminergic modulation of the brain function including cognition. Tat and cocaine synergistically elevate synaptic DA levels by acting directly on human DAT (hDAT), ultimately leading to dysregulation of DA transmission. Through integrated computational modeling and experimental validation, key residues have been identified in hDAT that play a critical role in Tat-induced inhibition of DAT and induce transporter conformational transitions. This review presents current information regarding neurological changes in DAT-mediated dopaminergic system associated with HIV infection, DAT-mediated adaptive responses to Tat as well as allosteric modulatory effects of novel compounds on hDAT. Understanding the molecular mechanisms by which Tat induces DAT-mediated dysregulation of DA system is of great clinical interest for identifying new targets for an early therapeutic intervention for HAND.


Potential Transfer of Polyglutamine and CAG-Repeat RNA in Extracellular Vesicles in Huntington's Disease: Background and Evaluation in Cell Culture.
In Huntington's disease (HD) the imperfect expanded CAG repeat in the first exon of the HTT gene leads to the generation of a polyglutamine (polyQ) protein, which has some neuronal toxicity, potentially mollified by formation of aggregates. Accumulated research, reviewed here, implicates both the polyQ protein and the expanded repeat RNA in causing toxicity leading to neurodegeneration in HD. Different theories have emerged as to how the neurodegeneration spreads throughout the brain, with one possibility being the transport of toxic protein and RNA in extracellular vesicles (EVs). Most cell types in the brain release EVs and these have been shown to contain neurodegenerative proteins in the case of prion protein and amyloid-beta peptide. In this study, we used a model culture system with an overexpression of HTT-exon 1 polyQ-GFP constructs in human 293T cells and found that the EVs did incorporate both the polyQ-GFP protein and expanded repeat RNA. Striatal mouse neural cells were able to take up these EVs with a consequent increase in the green fluorescent protein (GFP) and polyQ-GFP RNAs, but with no evidence of uptake of polyQ-GFP protein or any apparent toxicity, at least over a relatively short period of exposure. A differentiated striatal cell line expressing endogenous levels of Hdh mRNA containing the expanded repeat incorporated more of this mRNA into EVs as compared to similar cells expressing this mRNA with a normal repeat length. These findings support the potential of EVs to deliver toxic expanded trinucleotide repeat RNAs from one cell to another, but further work will be needed to evaluate potential EV and cell-type specificity of transfer and effects of long-term exposure. It seems likely that expanded HD-associated repeat RNA may appear in biofluids and may have use as biomarkers of disease state and response to therapy.


Optimal packaging of dispersion-compensating fibers for matched nonlinear compensation and reduced optical noise.
A method of packaging dispersion-compensating fibers (DCFs) is discussed that achieves optimal nonlinearity compensation and a good signal-to-noise ratio simultaneously. An optimally packaged dispersion-compensating module (DCM) may consist of portions of DCFs with higher and lower loss coefficients. Such optimized DCMs may be paired with transmission fibers to form scaled translation-symmetric lines that could effectively compensate for signal distortions due to dispersion and nonlinearity, with or without optical phase conjugation.


Risk perceptions and COVID-19 protective behaviors: A two-wave longitudinal study of epidemic and post-epidemic periods.
We investigated how perceived risk and protective behaviors changed as the coronavirus epidemic progressed. A longitudinal sample of 538 people responded to a COVID-19 risk perception questionnaire during the outbreak and post-epidemic periods. Using Structural Equation Modeling (SEM), we examined the mean level change of selected constructs and differences in their relationships. We tested a risk perception pathway in which affective attitude, informed by experience, shaped risk perceptions and protective behaviors. The model also postulated a social pathway in which cultural worldviews, like individualism and hierarchy, predicted risk perceptions and protective behaviors through social norms. Latent mean difference analyses revealed a decrease in social distancing behaviors and an increase in hygiene-cleanliness, corresponding to a reduction in risk perceptions and social norms and a rise in direct and indirect experience, while affective attitude remained substantially stable. Cross-sectional and longitudinal path analyses showed that affective risk perception, primarily informed by affective attitude, and social norms promoted behavior consistency regardless of epidemic contingencies. Instead, analytic risk perceptions were linked to protective behaviors only during the outbreak. Although risk perceptions dropped over time, analytic risk perceptions dropped more steeply than affective risk perceptions. Our findings supported the distinction between affective and deliberative processes in risk perception, reinforcing the view that affective reactions are needed to deploy analytic processes. Our study also supports the claim that perceived social norms are essential to understanding cultural worldview-related protective behaviors variability.


Simultaneous radio- and chemotherapy of inoperable brain tumours.
Between January 1980 and May 1985, 102 patients (68 men, 34 women, median age 47 years) with malignant brain tumours (35% glioblastoma multiforme, 30% astrocytoma grade III, 21% oligodendroglioma grade III) have been treated in our clinic. All tumours were inoperable because of their size and/or location. The diagnosis was confirmed histopathologically (stereotactic biopsy or subtotal resection). Seventy-five patients without previous radiotherapy received three courses of a concomitant radio- and chemotherapy with free intervals of 5 weeks between the courses of the therapy. Using lateral opposing fields the whole brain was irradiated with 60Co in daily fractions of 1.5 Gy up to 15 Gy per course of the treatment. Simultaneously, all patients received ifosfamide on five consecutive days in a dosage of 1.2 g/sqm body surface each day i.v. On days 1, 3 and 5, BCNU was given additionally in a daily dosage of 30 mg/sqm body surface i.v. After three courses, a total radiation dose of 45 Gy was administered to the whole brain. Directly after the last cycle of the combined treatment the primary tumour was boosted up to 50-60 Gy using smaller portals. Seventy-one of the 75 patients were amenable to statistical analysis. The overall tolerance was good. No severe haematological or gastrointestinal complications occurred. According to the criteria of the UICC, 12 complete remissions (CR) (i.e. 16.9%) and 35 partial remissions (PR) (i.e. 49.3%) were achieved. In 21 cases (i.e. 29.6%), the progression of the tumour could be stopped. Depending on the histopathological classification of the malignancies survival rates between 64.3% and 87.5% were achieved for one year.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro potentiation of human natural killer cell activity by a streptococcal preparation, OK-432: interferon and interleukin-2 participation in the stimulation with OK-432.
Inasmuch as human natural killer (NK) cell activity was markedly augmented by a streptococcal immunopotentiator, OK-432, both in vivo and in vitro, the mechanism in which OK-432 augmented human NK cell activity was analyzed. Culture supernatants of nonadherent lymphocytes stimulated with OK-432 significantly augmented NK cell activity. Significant activity of both interferon (IFN) (both alpha- and gamma-types) and interleukin-2 (IL-2) was detected in the culture supernatants from nonadherent lymphocytes. Concomitant treatment of supernatants with anti-IFN-alpha antiserum and pH-2 glycine-HCI buffer or the absorption of supernatants with an IL-2-dependent cell line completely abrogated the NK-augmenting activity, whereas the treatment with either one of these resulted in only partial elimination of the activity. These results indicate that OK-432 stimulates human nonadherent lymphocytes to produce IFN and IL-2 and that both factors are primarily responsible for the NK augmentation by OK-432.


[Synthesis and pharmacological activity of 1,2,3-triazole derivatives of naphthalene, quinoline and pyridine].
The preparation of three series of 1,2,3-triazol derivatives, with a naphthalene, quinoline or pyridine ring in 1 position, is described. Preliminary pharmacological screening of some of these compounds showed no appreciable activity.


Type III Interferons in Antiviral Defenses at Barrier Surfaces.
Barrier surfaces such as the epithelium lining the respiratory and gastrointestinal (GI) tracts, the endothelium comprising the blood-brain barrier (BBB), and placental trophoblasts provide key physical and immunological protection against viruses. These barriers utilize nonredundant mechanisms to suppress viral infections including the production of interferons (IFNs), which induce a strong antiviral state following receptor binding. However, whereas type I IFNs control infection systemically, type III IFNs (IFN-λs) control infection locally at barrier surfaces and are often preferentially induced by these cells. In this review we focus on the role of IFN-λ at barrier surfaces, focusing on the respiratory and GI tracts, the BBB, and the placenta, and on how these IFNs act to suppress viral infections.


In vivo effect of the Syndets Idet 5L and Swanic 6L ON ATPase activity in the teleost, Channa punctatus.
Channa punctatus were exposed to various sub-lethal concentrations of Idet 5L and Swanic 6L for 25 and 50 days. Brain and gill homogenates were analyzed for enzyme activity from treated and untreated fish. Enzyme inhibitions were highest in oligomycin-insensitive Mg++ ATPase, with pronounced effects (over 65% inhibition) after 50 days exposure of fish to 7.5 mg/L concentration of Swanic 6L. Fish exposed to lowest concentrations of syndets showed an insignificant activation of Na+-K+ and oligomycin-sensitive Mg++ ATPases in the gill.


Photocontrol of spatial orientation and DNA cleavage activity of copper(II)-bound dipeptides linked by an azobenzene derivative.
Copper(II) ion-bound CysGly dipeptides linked by an azobenzene derivative were photoisomerized between the trans and cis forms. The two copper(II) ion centers were positioned close to each other in the cis form, whereas they were far away from each other in the trans form. The copper complex in the cis form exhibited DNA cleavage activity, whereas the activity in the trans form was negligible. The DNA cleavage activity of the cis form is attributed to the cooperation of the closely located copper(II) centers. The present results show the photocontrol of the cooperation of metal ions for DNA cleavage.