Smoking is an independent risk factor for complications following open rotator cuff repair.
Objectives: Smoking has been associated with poor cuff healing and worse long-term outcomes in patients undergoing rotator cuff repair. The effects of smoking on short-term complications following open rotator cuff repair are not well defined. The purpose of this study is to analyze the effects of smoking on 30-day outcomes following open rotator cuff repair. Methods: The American College of Surgeons National Surgical Quality Improvement Program was used to identify patients who underwent open rotator cuff repair from 2011 to 2016. Patients who were current smokers (within 1 year prior to surgery) were identified and compared with nonsmokers. Demographic data and postoperative complications within 30 days were analyzed. Multivariable logistic regression was used to isolate the effect of smoking on complications after surgery. Results: We identified 5,157 patients who underwent open rotator cuff repair, of which 18% (946 patients) were current smokers (within 1 year of surgery). Smokers were younger (54.4 years versus 61.5 years, P < 0.001) and were more likely to be male (60.8% versus 56.9%, P = 0.03). Compared with nonsmokers, smokers had a similar rate of comorbidities (P = 0.35) and similar preoperative functional status (P = 0.53), but had higher mean American Society of Anesthesiologists (ASA) class (P < 0.001). Logistic regression revealed that smoking was an independent predictor for any complication (OR 1.9, P = 0.03), any venous thromboembolic event (OR 4.6, P = 0.01), and pulmonary embolism (OR 6.4, P = 0.02). Conclusion: Patients who smoke are at increased risk for short-term complications after open rotator cuff repair. Smoking is independently associated with increased rate of postoperative venous thromboembolic events such as pulmonary embolism. This further highlights the importance of preoperative smoking cessation in patients undergoing open rotator cuff repair.


Molecular pathogenesis of triple-negative breast cancer based on microRNA expression signatures: antitumor miR-204-5p targets AP1S3.
Triple-negative breast cancer (TNBC) is an aggressive type of cancer associated with a poor prognosis. Identification of novel therapeutic targets in TNBC is urgently needed. Here, we investigated the microRNA (miRNA) expression signature of TNBC using clinical specimens. In total, 104 miRNAs (56 upregulated and 48 downregulated) were significantly dysregulated in TNBC tissues; miR-204-5p showed the most dramatic downregulation. We then examined the antitumor roles of miR-204-5p in breast cancer (BC) cells. Notably, cancer cell migration and invasion were significantly reduced by ectopic expression of miR-204-5p in BC cells. Genome-wide gene expression analysis and in silico database search revealed that 32 genes were putative miR-204-5p targets. High expression of AP1S3, RACGAP1, ELOVL6, and LRRC59 was significantly associated with poor prognosis in patients with BC, and adaptor-related protein complex 1 sigma 3 subunit (AP1S3) was directly regulated by miR-204-5p, as demonstrated by luciferase reporter assays. AP1S3 overexpression was detected in TNBC clinical specimens and enhanced cancer cell aggressiveness. We further analyzed downstream RNA networks regulated by AP1S3 in BC cells. Overall, this miRNA signature is expected to be an effective tool for identification of miRNA-mediated molecular mechanisms of TNBC pathogenesis.


Potential uptake of Escherichia coli O157:H7 from organic manure into crisphead lettuce.
To investigate the potential transfer of Escherichia coli O157:H7 from contaminated manure to fresh produce, lettuce seedlings were transplanted into soil fertilized with bovine manure which had been inoculated with approximately 10(4) CFU g(-1) E. coli O157:H7. The lettuce was grown for approximately 50 days in beds in climate-controlled rooms in a greenhouse. As the bacterium was not detected in the edible parts of the lettuce, the outer leaves of the lettuce, or the lettuce roots at harvest it was concluded that transmission of E. coli O157:H7 from contaminated soil to lettuce did not occur. The pathogen persisted in the soil for at least 8 weeks after fertilizing but was not detected after 12 weeks. Indigenous E. coli was detected only sporadically on the lettuce at harvest, and enterococci were not detected at all. The numbers of enterococci declined more rapidly than those of E. coli in the soil. Pseudomonas fluorescens, which inhibited growth of E. coli O157:H7 in vitro, was isolated from the rhizosphere.


Development and validation of the Terminal Delirium-Related Distress Scale to assess irreversible terminal delirium.
There is no tool to appropriately assess terminal delirium, including the natural terminal course. The objective of this study was to develop an evaluation scale to assess distress from irreversible terminal delirium and to examine the validity of the scale. Based on previous qualitative analysis and systematic literature searches, we carried out a survey regarding the views of bereaved families and developed a questionnaire. We extracted items that bereaved families regarded as important and constructed an evaluation scale of terminal delirium. Then, we applied the questionnaire in a cross-sectional questionnaire survey of bereaved relatives of cancer patients who were admitted to a hospice or a palliative care unit. We developed the Terminal Delirium-Related Distress Scale (TDDS), a 24 item questionnaire consisting of five subscales (support for families and respect for a patient, ability to communicate, hallucinations and delusions, adequate information about the treatment of delirium, and agitation and restlessness). Two hundred and eighty-one bereaved relatives participated in the validation phase. The construct validity was shown to be good by repeated factor analysis. Convergent validity, confirmed by the correlation between the TDDS and the Care Evaluation Scale (r = 0.651, P < 0.001), was also good. The TDDS had good internal consistency (Cronbach's alpha coefficient for all 24 items = 0.84). This study showed that the TDDS is a valid and feasible measure of irreversible terminal delirium.


The Medici Project first anthropological and paleopathological results of the exploration of the Medici tombs in Florence.
Within the framework of the Medici Project, a paleopathological team of experts from the University of Pisa, the University of Florence and the Superintendence for Florentine Museums, is carrying out a study on 49 tombs of some of the Medici family members (16th-18th centuries) housed in the so-called Basilica of San Lorenzo in Florence. The project involves disciplines such as paleopathology, funerary archeology, physical anthropology, paleonutrition, parasitology, histology, histochemistry, immuno-histochemistry, electron microscopy, molecular biology, and identification of ancient pathogens. The most recent biomedical imaging technologies have been employed to obtain as much information as possible about the genetic make-up, eating habits, life styles and diseases of these important rulers of Renaissance Florence. The first anthropological and paleopathological results are presented here.


Reinfection of yearling calves with Ascaris suum.
Naturally occuring outbreaks of Ascaris suum infection in calves have usually beeen found in animals nine to 12 months of age. The circumstances surrounding these outbreaks suggest that yearling calves are either particularly susceptible to a primary exposure to A. suum or react strongly to A. summ after sensitization early in life to this or some related ascarid. To determine the effect of reinfection with A. suum nine to 12 months after varying levels of exposure to this nematode, six calves were inoculated with 200,000 to 9,000,000 eggs. Neither death nor, in general, severe clinical signs resulted from reinfection. All calves were examined 15 days after reinfection with pathological changes noted only in the lungs and consisting of emphysema, alveolar wall thickening as well as accumulations of fibrin, eosinophils and hemorrhage in the lumina of alveoli. The findings suggested that exposure to A. suum early in life is not a factor in the development of disease in calves infected at one year of age. It was also found that the eosinophilia that develops following a primary infection with A. suum evidently persists for at least one year.


[Transportation of the critical newborn infant and child].
Advance in the science and technology of neonatal and pediatric critical care have resulted in improved outcome for high risk newborn and children. Effective interhospital transport programmes are necessary for the appropriate use of resources and has become an integral component of regionalized perinatal care. It is now well established that use of an organized neonatal and pediatric transport team results in a fall in mortality and morbidity of infant. The American College of Obstetrician and Gynecologist and, recently, American Academy of Pediatrics published guidelines and recommendations for safe interhospital transfer of neonates, infants and children. Training of personnel, selection of equipment, organization and communication between hospitals are critical elements of a successful transport system. We present an overview of the role, principles and operating procedures of such neonatal-pediatric transport team and the basis of clinical stabilization before and during transfer. We also discuss data of the first 17 month experience of the Neonatal-Pediatric Transport Service of the Department of Pediatrics, University of Padua.


Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor.
Hsp90 is an essential molecular chaperone responsible for the folding and activation of hundreds of 'client' proteins, including the glucocorticoid receptor (GR). Previously, we revealed that Hsp70 and Hsp90 remodel the conformation of GR to regulate ligand binding, aided by co-chaperones. In vivo, the co-chaperones FKBP51 and FKBP52 antagonistically regulate GR activity, but a molecular understanding is lacking. Here we present a 3.01 Å cryogenic electron microscopy structure of the human GR:Hsp90:FKBP52 complex, revealing how FKBP52 integrates into the GR chaperone cycle and directly binds to the active client, potentiating GR activity in vitro and in vivo. We also present a 3.23 Å cryogenic electron microscopy structure of the human GR:Hsp90:FKBP51 complex, revealing how FKBP51 competes with FKBP52 for GR:Hsp90 binding and demonstrating how FKBP51 can act as a potent antagonist to FKBP52. Altogether, we demonstrate how FKBP51 and FKBP52 integrate into the GR chaperone cycle to advance GR to the next stage of maturation.


[Effect of heart tablets on cardiac hemodynamics and myocardial oxygen consumption in anesthetized dogs].
To observe the pharmacological effects of Heart tablets on cardiac function and its mechanism, the effects on cardiac hemodynamics and myocardial oxygen consumption in anesthetized dogs were observed. Observe the effect of Heart tablets on coronary blood flow, cardiac output, myocardial oxygen consumption and other indicators in normal anesthetized dogs. The Heart tablets can increase femoral arterial blood pressure, while no effect is found on the heart rate, standard II ECG PR interval, QRS interval, QT interval, T wave and other parameters. The tablets can expand coronary artery and peripheral vessel, increase coronary blood flow, lower coronary resistance and increase cardiac blood supply capacity, improve left ventricular function, ameliorate cardiovascular adaptability, increase dp/dt(max), enhance myocardial activity and have a positive regulatory role in heart. At the meantime raise the cardiac output and stroke volume were raised, so that blood pressure can be increased, while the total peripheral resistance was decreased. The coronary vein sinus oxygen content were significantly increased and myocardial oxygen consumption index and myocardial oxygen utilization were reduced. The tablets can adjust and improve the cardiovascular system.


Inhibition of protein tyrosine kinases impairs axon extension in the embryonic optic tract.
The role of protein tyrosine kinase (PTK) activity in the development of the retinal projection was examined in vivo by applying inhibitors of cytoplasmic PTKs, herbimycin A and lavendustin A, to intact brain preparations of Xenopus embryos. The inhibitors were present during the period when retinal ganglion cell axons first navigate through the optic tract to reach their target, the optic tectum. A majority of inhibitor-treated retinal axons stalled at the beginning of the optic tract, leading to an 80% reduction in projection length at the highest doses. All inhibitor-treated axons that did extend into the optic tract exhibited normal pathfinding behavior. Tyrosine kinase assays of inhibitor-treated brains demonstrated that at doses at which retinal axon extension was severely impaired, PTK activity, including that of src family proteins, was reduced by 50-60%. Consistent with the in vivo findings, PTK inhibitors reduced neurite outgrowth from cultured retinal neurons by 70-80%. This contrasts with the strong enhancement of outgrowth induced by the same inhibitors in cultured chick ciliary ganglion neurons and suggests that the mediation of outgrowth by PTK activity may vary in different neuronal types. Inhibitor-treated growth cones cultured on laminin were larger than normal, suggesting that tyrosine phosphorylation can modulate growth cone-substrate adhesive interactions. Our results in vivo and in vitro provide complementary evidence that retinal axon outgrowth is inhibited by pharmacological blockers of PTK activity and indicate that inhibitor-sensitive PTKs normally play a role in promoting retinal neurite extension.


Dehydroepiandrosterone modulates endothelial nitric oxide synthesis via direct genomic and nongenomic mechanisms.
Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are the major circulating steroid hormones in humans, and their levels progressively decline with age. Epidemiological studies suggest that DHEA/DHEAS concentrations may be inversely related to cardiovascular risk, but disagreement exists on this issue. Preliminary studies show that DHEA regulates vascular function, but few data have been published on the mechanisms. We show that DHEA administration to human endothelial cells triggers nitric oxide synthesis, due to enhanced expression and stabilization of endothelial nitric oxide synthase (eNOS). Additionally, DHEA rapidly activates eNOS, through a nontranscriptional mechanism that depends on ERK1/2 MAPK, but not on phosphatidylinositol 3-kinase/Akt. DHEA is not converted to estrogens or androgens by endothelial cells, and its genomic and nongenomic effects are not blocked by antagonists of the estrogen, progesterone, glucocorticoid, or androgen receptors, suggesting that DHEA acts through a specific receptor. Oral DHEA administration to ovariectomized Wistar rats dose-dependently restores aortic eNOS levels and eNOS activity, confirming the effects of DHEA in vivo. Our present data suggest that DHEA may have direct genomic and nongenomic effects on the vascular wall that are not mediated by other steroid hormone receptors, leading to eNOS activation and induction.


Integrative EEG biomarkers predict progression to Alzheimer's disease at the MCI stage.
Alzheimer's disease (AD) is a devastating disorder of increasing prevalence in modern society. Mild cognitive impairment (MCI) is considered a transitional stage between normal aging and AD; however, not all subjects with MCI progress to AD. Prediction of conversion to AD at an early stage would enable an earlier, and potentially more effective, treatment of AD. Electroencephalography (EEG) biomarkers would provide a non-invasive and relatively cheap screening tool to predict conversion to AD; however, traditional EEG biomarkers have not been considered accurate enough to be useful in clinical practice. Here, we aim to combine the information from multiple EEG biomarkers into a diagnostic classification index in order to improve the accuracy of predicting conversion from MCI to AD within a 2-year period. We followed 86 patients initially diagnosed with MCI for 2 years during which 25 patients converted to AD. We show that multiple EEG biomarkers mainly related to activity in the beta-frequency range (13-30 Hz) can predict conversion from MCI to AD. Importantly, by integrating six EEG biomarkers into a diagnostic index using logistic regression the prediction improved compared with the classification using the individual biomarkers, with a sensitivity of 88% and specificity of 82%, compared with a sensitivity of 64% and specificity of 62% of the best individual biomarker in this index. In order to identify this diagnostic index we developed a data mining approach implemented in the Neurophysiological Biomarker Toolbox (http://www.nbtwiki.net/). We suggest that this approach can be used to identify optimal combinations of biomarkers (integrative biomarkers) also in other modalities. Potentially, these integrative biomarkers could be more sensitive to disease progression and response to therapeutic intervention.


Ethnic Differences in the Quality of the Interview Process and Implications for Survey Analysis: The Case of Indigenous Australians.
Comparable survey data on Indigenous and non-Indigenous Australians are highly sought after by policymakers to inform policies aimed at closing ethnic socio-economic gaps. However, collection of such data is compromised by group differences in socio-economic status and cultural norms. We use data from the Household, Income and Labour Dynamics in Australia Survey and multiple-membership multilevel regression models that allow for individual and interviewer effects to examine differences between Indigenous and non-Indigenous Australians in approximate measures of the quality of the interview process. We find that there are both direct and indirect ethnic effects on different dimensions of interview process quality, with Indigenous Australians faring worse than non-Indigenous Australians in all outcomes ceteris paribus. This indicates that nationwide surveys must feature interview protocols that are sensitive to the needs and culture of Indigenous respondents to improve the quality of the survey information gathered from this subpopulation.


Ambient NH3 synthesis via electrochemical reduction of N2 over cubic sub-micron SnO2 particles.
Electrochemical N2-to-NH3 fixation under ambient conditions is emerging as a promising alternative to the energy-intensive and CO2-emitting Haber-Bosch process. However, this process involves difficulty in N2 activation, underlining the demand of electrocatalysts for the N2 reduction reaction (NRR). In this work, cubic sub-micron SnO2 particles on carbon cloth (SnO2/CC) are proposed as an efficient NRR electrocatalyst for ambient N2 conversion to NH3 with excellent selectivity. Electrochemical tests reveal that SnO2/CC attains a large NH3 yield of 1.47 × 10-10 mol s-1 cm-2 at -0.8 V vs. reversible hydrogen electrode (RHE) and a high Faradaic efficiency of 2.17% at -0.7 V vs. RHE in 0.1 M Na2SO4, outperforming most reported aqueous-based NRR electrocatalysts. Notably, it also shows strong electrochemical stability.


Internet addictive behavior in adolescence: a cross-sectional study in seven European countries.
A cross-sectional school-based survey study (N=13,284; 53% females; mean age 15.8±0.7) of 14-17-year-old adolescents was conducted in seven European countries (Greece, Spain, Poland, Germany, Romania, the Netherlands, and Iceland). The aim of the study was to investigate the prevalence of Internet addictive behavior (IAB) and related psychosocial characteristics among adolescents in the participating countries. In the study, we distinguish two problematic groups: adolescents with IAB, characterized by a loss of control over their Internet use, and adolescents "at risk for IAB," showing fewer or weaker symptoms of IAB. The two groups combined form a group of adolescents with dysfunctional Internet behavior (DIB). About 1% of adolescents exhibited IAB and an additional 12.7% were at risk for IAB; thus, in total, 13.9% displayed DIB. The prevalence of DIB was significantly higher among boys than among girls (15.2% vs. 12.7%, p<0.001) and varied widely between countries, from 7.9% in Iceland to 22.8% in Spain. Frequent use of specific online activities (e.g., gambling, social networking, gaming) at least 6 days/week was associated with greater probability of displaying DIB. Multiple logistic regression analysis indicated that DIB was more frequent among adolescents with a lower educational level of the parents, earlier age at first use of the Internet, and greater use of social networking sites and gaming sites. Multiple linear regression analysis showed that externalizing (i.e., behavioral) and internalizing (i.e., emotional) problems were associated with the presence of DIB.


The slippery slope: lubricant use and rectal sexually transmitted infections: a newly identified risk.
Use of lubricant products is extremely common during receptive anal intercourse (RAI) yet has not been assessed as a risk for acquisition of sexually transmitted infections (STIs). Between 2006 and 2008, a rectal health and behavior study was conducted in Baltimore and Los Angeles as part of the University of California, Los Angeles Microbicide Development Program (NIAID IPCP# #0606414). Participants completed questionnaires, and rectal swabs were tested for Neisseria gonorrhoeae and Chlamydia trachomatis with the Aptima Combo 2 assay, and blood was tested for syphilis (for RPR and TPHA with titer) and HIV. Of those reporting lubricant use and RAI, STI results were available for 380 participants. Univariate and multivariate regressions assessed associations of lubricant use in the past month during RAI with prevalent STIs. Consistent lubricant use during RAI in the past month was reported by 36% (137/380) of participants. Consistent past month lubricant users had a higher prevalence of STI than inconsistent users (9.5% vs. 2.9%; P = 0.006). In a multivariable logistic regression model, testing positive for STI was associated with consistent use of lubricant during RAI in the past month (adjusted odds ratio: 2.98 95% confidence interval: 1.09, 8.15) after controlling for age, gender, study location, HIV status, and numbers of RAI partners in the past month. Findings suggest some lubricant products may increase vulnerability to STIs. Because of wide use of lubricants and their potential as carrier vehicles for microbicides, further research is essential to clarify if lubricant use poses a public health risk.


Assessing international alcohol consumption patterns during isolation from the COVID-19 pandemic using an online survey: highlighting negative emotionality mechanisms.
The COVID-19 pandemic has required drastic safety measures to control virus spread, including an extended self-isolation period. Stressful situations increase alcohol craving and consumption in alcohol use disorder (AUD) and non-AUD drinkers. Thus, we assessed how COVID-19 related stress may have affected drinking behaviours in the general population. We developed an online cross-sectional survey, Habit Tracker (HabiT), which measured changes in drinking behaviours before and during COVID-19 quarantine. We also assessed psychiatric factors such as anxiety, depression (Hospital Anxiety and Depression Scale) and impulsivity (Short-Impulsive Behavior Scale). Lastly, we related drinking behaviours to COVID-19 specific stress factors. HabiT was released internationally, with individuals from 83 countries participating. Participants were included if they were 18 years of age or older and confirmed they were proficient in English. The survey was completed by 2873 adults with 1346 usable data (46.9% accurately completed). Primary outcome measures were change in amount and severity of drinking behaviours before and during quarantine, and current drinking severity during quarantine. Although drinking behaviours decreased overall during quarantine, 36% reported an increase in alcohol use. Those who increased alcohol use during quarantine were older individuals (95% CI 0.04 to 0.1, p<0.0001), essential workers (95% CI -0.58 to -0.1, p=0.01), individuals with children (95% CI -12.46 to 0.0, p=0.003), those with a personal relationship with someone severely ill from COVID-19 (95% CI -2 to -0.38, p=0.01) and those with higher depression (95% CI 0.67 to 1.45, p<0.0001), anxiety (95% CI 0.61 to 1.5, p=0.0002), and positive urgency impulsivity (95% CI 0.16 to 0.72, p=0.009). Furthermore, country-level subsample analyses indicated that drinking amount (95% CI 9.36 to 13.13, p=0.003) increased in the UK during quarantine. Our findings highlight a role for identifying those vulnerable for alcohol misuse during periods of self-isolation and underscore the theoretical mechanism of negative emotionality underlying drinking behaviours driven by stress. Limitations include a large degree of study dropout (n=1515). Future studies should assess the long-term effects of isolation on drinking behaviours.


Adherence of surgeons to antimicrobial prophylaxis guidelines in a tertiary general hospital in a rapidly developing country.
Objectives. To assess the standard practice of care of surgeons regarding surgical antibiotic prophylaxis, to identify gaps, and to set recommendations. Methods. A retrospective analysis of data obtained from different surgical units in a single center in Qatar over a 3-month period in 2012. A total of 101 patients who underwent surgery and followed regimes for surgical prophylaxis as per hospital guidelines were included in the study. Results. The overall use of antibiotic was 89%, whereas the current practice did not match the recommended hospital protocols in 53.5% of cases. Prolonged antibiotics use (59.3%) was the commonest reason for nonadherence followed by the use of an alternative antibiotic to that recommended in the protocol (31.5%) and no prophylaxis was used in 9.2% of cases. The rate of compliance was significantly higher among clean surgery than clean contaminated group (P = 0.03). Forty-four percent of clean and 65% of clean-contaminated procedures showed noncompliance with the recommended surgical antimicrobial prophylaxis hospital guidelines. Conclusion. Lack of adherence to hospital protocols is not uncommon. This finding remains a challenge to encourage clinicians to follow hospital guidelines appropriately and to consistently apply the surgical antibiotic prophylaxis. The role of clinical pharmacist may facilitate this process across all surgical disciplines.


Spatial and temporal demographic variation drives within-season fluctuations in sexual selection.
Our understanding of selection in nature stems mainly from whole-season and cross-sectional estimates of selection gradients. These estimates suggest that selection is relatively constant within, but fluctuates between seasons. However, the strength of selection depends on demographics, and because demographics can vary within seasons, there is a gap in our understanding regarding the extent to which seasonal fluctuations in demographics may cause variation in selection. Here we use two populations of the golden orb-web spider (Nephila plumipes) that differ in density to examine how demographics change within a season and whether there are correlated shifts in selection. We demonstrate that there is within-season variation in sex ratio and density at multiple spatial and temporal scales. This variation led to changes in the competitive challenges that males encountered at different times of the season and was correlated with significant variation in selection gradients on male size and weight between sampling periods. We highlight the importance of understanding the biology of the organism under study to correctly determine the relevant scale in which to examine selection. We also argue that studies may underestimate the true variation in selection by averaging values, leading to misinterpretation of the effect of selection on phenotypic evolution.


Outcome of genetic evaluation of patients with kidney cancer referred for suspected hereditary cancer syndromes.
To analyze patients with kidney cancer referred for evaluation at a high-volume genetics service at a comprehensive cancer center and identify factors associated with positive tests for hereditary cancer syndromes. A retrospective review of patients referred to the Clinical Genetics Service at Memorial Sloan-Kettering Cancer Center was performed, and patients with a personal history of kidney cancer were identified. Patient and disease characteristics were reviewed. In all, 4 variables including age at diagnosis of kidney tumor, presence of syndromic manifestations, family history of kidney cancer, and number of primary malignancies were evaluated for association with positive test results in 2 groups: patients tested for renal cell carcinoma syndromes and Lynch syndrome. Guidance for genetic testing strategy in patients with kidney cancer is provided. Between 1999 and 2012, 120 patients with a history of kidney cancer were evaluated by the Clinical Genetics Service. The mean age at kidney cancer diagnosis was 52 years (interquartile range: 42-63), with 57% being women. A family history of kidney cancer was reported by 39 patients (33%). Time between diagnosis of first cancer and genetic consultation was <1 year in 54%, 2 to 5 years in 23%, and>5 years in the remaining 23%. Overall, 95 patients were tested for genetic abnormalities with 27 (28%) testing positive. Testing for renal cell carcinoma (RCC)-related syndromes was performed on 43 patients, with 13 testing positive (30%). Lynch syndrome testing was positive in 9 patients (32%) after 28 were tested. In RCC-associated syndromes, young age of diagnosis was associated with positive test results. Conversely, syndromic manifestations and increasing number of primary malignancies were associated with positive Lynch testing. The discovery of inherited kidney cancer syndromes has provided a unique opportunity to identify patients at increased risk for cancer. Factors associated with positive genetic testing are unique to different syndromes. These data suggest that in kidney cancer patients evaluated for hereditary cancer syndromes, young age is associated with diagnosis of RCC syndromes, whereas syndromic manifestations and multiple primaries are found in Lynch syndrome. These results, along with clinical awareness, may be useful for practicing urologists to select patients with kidney cancer to refer for genetic counseling.


From mass vaccination to personalized vaccinology? The COVID-19 case. Commentary.
In recent times, especially as a result of the experience gained worldwide with the COVID19 pandemic vaccination campaigns, the personalization of vaccination strategies is becoming increasingly important. This does not yet mean bringing precision medicine and genomics approaches into immunization campaigns, but where there is more than one vaccine against the same disease, there is a need to identify criteria for personalizing vaccination.Vaccination strategies based on prescription appropriateness - whenever is possible - can lead to more effective immune response, reduced rates of adverse events, increased public confidence in vaccination and higher vaccination coverage, contributing to a decrease of morbidity and mortality related to preventable diseases.


Posttraumatic Reactions to Psychosis: A Qualitative Analysis.
The current study aimed to evaluate the potentially traumatic aspects of psychotic symptoms and psychiatric treatment of psychosis using qualitative methods. Participants included 63 people with first episode psychosis or multiple psychotic episodes recruited from an inpatient psychiatric unit and an urban state psychiatric hospital in the North East region of the United States. Quasi-structured interviews were used to explore those aspects of symptoms and treatment that were perceived as traumatic Emotional reactions to the most traumatic aspect of symptoms and treatment, during and after the event, were also examined. Participants described a number of traumatogenic aspects of psychotic symptoms, including frightening hallucinations; suicidal thought/attempts, thoughts/attempts to hurt others; paranoia/delusions and bizarre/disorganized behavior or catatonia. Traumatic aspects of psychosis elicited emotions including anger, sadness and confusion, anxiety, and numbness at the time of event. Furthermore, many participants found aspects of treatment to be traumatic, including: being forced to stay in the hospital for a long time; experiencing upsetting side-effects; coercive treatments, including involuntary hospitalization, use of restraints, and forced medication; being exposed to aggressive patients; and mistreatment by professionals. These experiences elicited emotions of anger, sadness, distrust, and a sense of helplessness. Study findings suggest that the experiences both of psychotic symptoms and psychiatric treatment, potentially traumatic, can be a powerful barrier to engaging people in mental health services and facilitating recovery. Clinical implications were discussed.


Oxidative stress and antioxidant defenses after prolonged starvation in Dentex dentex liver.
The aim of this work was to evaluate the effects of prolonged starvation and refeeding on antioxidant status and some metabolic-related parameters in common dentex (Dentex dentex) liver. Fish deprived of food for 5 weeks showed a significant increase in lipid peroxidation, measured as malondialdehyde (MDA) levels. The activity of the antioxidative enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) in starved fish significantly increased (by 42%, 22%, and 52%, respectively), whereas glutathione reductase (GR) activity was significantly depressed by 53% compared to controls. No qualitative changes in the SOD isoenzymatic pattern were detected by nondenaturing PAGE analysis, but the isoforms corresponding to CuZn-SOD I and II were enhanced in starved fish. The activity of the enzymes indicative of oxidative metabolism, beta-hydroxyacyl CoA dehydrogenase (HOAD) and citrate synthase (CS), significantly increased (by 123% and 28%, respectively), and that of glucose-6-phosphate dehydrogenase (G6PDH) was inhibited by 56%. Oxidative damage under these circumstances is reversible since all biomarkers assayed returned to control values after refeeding. Our results show that prolonged starvation leads to a pro-oxidant situation and oxidative stress despite activation of antioxidant defense mechanisms, and that inhibition of G6PDH activity might be responsible for this failure in cellular antioxidant defenses.


The anatomy of missed breast cancers.
Missed breast cancer continues to account for the highest percentage of medical malpractice cases in the United States. A retrospective, computer-aided study was performed to investigate the mechanisms of missed breast carcinomas, missed either by mammography or by clinical exam. In a consecutive series of 509 breast cancers found in patients registered at a University Comprehensive Breast Cancer Clinic, no tumour that was 5 mm or less in maximal diameter was clinically palpable. This subgroup consisted of seven in situ and 32 invasive carcinomas. The incidence of palpable tumours in 5 mm increments increased so that when a tumour was between 11 and 15 mm in size, 48% of the lesions were palpable, and with tumours greater than 20 mm in size, 84% were palpable. There was a good correlation between size of the tumour as judged by mammography and the eventual size determined by histologic examination. Smaller breast cancers were detected by mammography than by physical examination. In a separate analysis of 553 consecutive cases of breast cancer examined by mammography, there were 50 (9%) cases in which the cancer was not read from the mammogram. In retrospect, 10 of these mammograms were abnormal for a misinterpretation rate of 1.8%. Cancers associated with false negative mammograms occurred more often in younger women and in dense breast parenchyma than cancers detected by mammography. Cancers missed by mammography were smaller than palpable cancers detected by mammography, more often had negative nodes and presented with a lower stage of disease. Breast augmentation implants were associated more frequently with missed breast cancers, with 5/8 clinically detected breast carcinomas being undetected by mammography. An asymmetric mass was more often associated with cancers missed by mammography, accounting for the sole sign of malignancy in 3% of all cancers, but was the source of 14% of false negative exams. Architectural distortion, ill-defined or well circumscribed masses or calcifications as mammographic signs of malignancy were not associated with an increased frequency of missed cancers. Three 'interval' breast cancers occurred in this series and are included in the false negative mammograms. It is concluded that the threshold of clinically detected breast cancers is 6 mm and experienced clinicians do not detect the majority of breast cancers until the lesions are greater than 16 mm. Mammography has a defined misinterpretation and false negative rate. Likewise, asymmetric mammographic densities that are greater than 16 mm and are not palpable may be followed, since most breast cancers are palpable in this range.


More Poop, More Precision: Improving Epidemiologic Surveillance of Soil-Transmitted Helminths with Multiple Fecal Sampling using the Kato-Katz Technique.
Soil-transmitted helminths, or parasitic intestinal worms, are among the most prevalent and geographically widespread parasitic infections in the world. Accurate diagnosis and quantification of helminth infection are critical for informing and assessing deworming interventions. The Kato-Katz thick smear technique, the most widely used laboratory method to quantitatively assess infection prevalence and infection intensity of helminths, has often been compared with other methods. Only a few small-scale studies, however, have considered ways to improve its diagnostic sensitivity. This study, conducted among 4,985 school-age children in an area of rural China with moderate prevalence of helminth infection, examines the effect on diagnostic sensitivity of the Kato-Katz technique when two fecal samples collected over consecutive days are examined and compared with a single sample. A secondary aim was to consider cost-effectiveness by calculating an estimate of the marginal costs of obtaining an additional fecal sample. Our findings show that analysis of an additional fecal sample led to increases of 23%, 26%, and 100% for Ascaris lumbricoides, Trichuris trichiura, and hookworm prevalence, respectively. The cost of collecting a second fecal sample for our study population was approximately USD4.60 per fecal sample. Overall, the findings suggest that investing 31% more capital in fecal sample collection prevents an underestimation of prevalence by about 21%, and hence improves the diagnostic sensitivity of the Kato-Katz method. Especially in areas with light-intensity infections of soil-transmitted helminths and limited public health resources, more accurate epidemiological surveillance using multiple fecal samples will critically inform decisions regarding infection control and prevention.


Formulary conversion from glipizide to glyburide: a cost-minimization analysis.
Economic pressure prompted us to search for and implement cost-saving strategies at Bronx Municipal Hospital. This paper describes a cost-minimization analysis of the impact of formulary substitution of glyburide for glipizide on glycemic control, safety, and costs. In 76 patients with computerized prescription records, switching from a mean daily glipizide dose of 19 mg to a mean daily glyburide dose of 10.2 mg did not affect glycemic control. A subset of 33 elderly patients experienced only three drug-related adverse events during the 2-year observation period. The conversion program yielded a 51% reduction in overall expenditures for oral hypoglycemic agents between 1991 and 1993. These findings indicate that our conversion program was successful, which has led to its becoming a model for other New York City municipal outpatient pharmacies.


Genes associated with T helper 17 cell differentiation and function.
Interleukin-17 (IL-17)-producing T helper cells (Th17 cells) constitute a lineage of CD4 effector T helper cells that is distinct from the Th1 and Th2 CD4 phenotypes. In humans, Th17 differentiation is induced in the presence of the cytokines IL-1 beta, IL-6 and TGF beta, whereas IL-23 maintains Th17 survival. Effector human Th17 cells express several cytokines and cell surface markers, including IL-17A, IL-17F, IL-22, IL-26, CCR6 and TNFalpha. Studies on human cells have revealed that the RORC2 transcription factor plays an effective role in Th17 differentiation. Th17 cells contribute to the host immune response by involving various pathologies, including rheumatoid arthritis, multiple sclerosis and Crohn's disease. However, the full extent of their contribution to diseases is being investigated. The differentiation of Th17 cells is controlled by many transcription factors, including ROR gammat, IRF4, RUNX1, BATF, and STAT3. This review covers the general principles of CD4 T helper differentiation and the known transcription factors that play a role in the recently discovered Th17 cells.


Postoperative Rehabilitation Following Thumb Base Surgery: A Systematic Review of the Literature.
To provide an overview of rehabilitation for patients who underwent first carpometacarpal joint (CMC-1) arthroplasty, with emphasis on early active mobilization. PubMed/MEDLINE, Embase, CINAHL, and Cochrane were searched. Articles written in English that described the postoperative regimen (including immobilization period/method and/or description of exercises/physical therapy, follow-up 6wk) on CMC-1 arthroplasty were included. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used as guidance in this review, and methodological quality was assessed using the Effective Public Health Practice Project quality assessment tool. Randomized studies were additionally scored using the Physiotherapy Evidence Database scale. Twenty-seven studies were included consisting of 1015 participants, in whom 1118 surgical procedures were performed. A summary of the components of postoperative rehabilitation used in the included studies of CMC-1 osteoarthritis is presented for different surgical interventions. We found that early active recovery (including short immobilization, early initiation of range of motion and strength exercises) provides positive outcomes for pain, limitations in activities of daily living, and grip and pinch strength, but comparative studies are lacking. Furthermore, 3 postoperative exercises/therapy phases were identified in the literature-the acute phase, the unloaded phase, and the functional phase-but again comparative studies are lacking. Early active recovery is used more often in the literature and does not lead to worse outcomes or more complications. This systematic review provides guidance for clinicians in the content of postoperative rehabilitation for CMC-1 arthroplasty. The review also clearly identifies the almost complete lack of high-quality comparative studies on postoperative rehabilitation after CMC-1 arthroplasty.


Efferent pathways modulate hyperactivity in inferior colliculus.
Animal models have demonstrated that mild hearing loss caused by acoustic trauma results in spontaneous hyperactivity in the central auditory pathways. This hyperactivity has been hypothesized to be involved in the generation of tinnitus, a phantom auditory sensation. We have recently shown that such hyperactivity, recorded in the inferior colliculus, is still dependent on cochlear neural output for some time after recovery (up to 6 weeks). We have now studied the capacity of an intrinsic efferent system, i.e., the olivocochlear system, to alter hyperactivity. This system is known to modulate cochlear neural output. Anesthetized guinea pigs were exposed to a loud sound and after 2 or 3 weeks of recovery, single-neuron recordings in inferior colliculus were made to confirm hyperactivity. Olivocochlear axons were electrically stimulated and effects on cochlear neural output and on highly spontaneous neurons in inferior colliculus were assessed. Olivocochlear stimulation suppressed spontaneous hyperactivity in the inferior colliculus. This result is in agreement with our earlier finding that hyperactivity can be modulated by altering cochlear neural output. Interestingly, the central suppression was generally much larger and longer lasting than reported previously for primary afferents. Blockade of the intracochlear effects of olivocochlear system activation eliminated some but not all of the effects observed on spontaneous activity, suggesting also a central component to the effects of stimulation. More research is needed to investigate whether these central effects of olivocochlear efferent stimulation are due to central intrinsic circuitry or to coactivation of central efferent collaterals to the cochlear nucleus.


[Double inlet left ventricle. Morphopathology and surgical anatomy].
Because of the possibility of surgical treatment of double inlet left ventricle, its basic morphologic features of surgical and imaging importance are analyzed. Seventeen hearts were studied with the segmental sequential system. The situs was solitus in thirteen; dextroisomerism in three and levoisomerism in one. The atrioventricular valves were separated in nine; there was a common atrioventricular valve in eight; straddling of the atrioventricular valve in seven and stenosis in two. The rudimentary right ventricle was to the right side in twelve hearts and to the left side in five. The discordant ventriculoarterial connection was the most frequent (seven), followed by the concordant one (five) and double outlet right ventricle (five). There was pulmonary stenosis in five. The ventricular septum did not reach the crux cordis. The ventricular septal defect was bigger in straddling atrioventricular valves than in valves completely open into the left ventricle, being restrictive in ventriculoarterial concordance. Surgical treatment varies as the complexity of this cardiopathy does, from cardiac septation to palliation procedures. The morphologic knowledge of this cardiac malformation is basic to interpret correctly the diagnostic imaging.


Anakinra for the Treatment of Hemophagocytic Lymphohistiocytosis: 21 Cases.
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening cytokine storm syndrome. There are no definitive guidelines for the management of secondary HLH (sHLH). A recent report by a National Health Service (NHS) clinical panel has recommended anakinra as a treatment option. We aimed to analyse the efficacy and safety of anakinra for the treatment of all-cause sHLH. We conducted a multicentric retrospective study in two French University hospitals and included all patients who had a diagnosis of sHLH and who received anakinra. Among 21 patients (median age, 45 years), 13 were men. Anakinra was used as first-line therapy in 10 patients, and as monotherapy in 5 patients. We found that anakinra was effective in 19/21 patients (90.5%), with fever resolution in 19 patients (90.5%) within a median of 1.0 day (1, 2). At the Day 7 assessment, the mean CRP concentration decreased significantly (p < 0.001), as did the mean ferritin (p = 0.011). Anakinra was generally safe and well tolerated and was discontinued for side effects in only three patients (14.3%). Anakinra is an efficient and safe treatment to control sHLH of various causes. These data, together with the recent report of the NHS panel, call for the rapid conduct of prospective randomized clinical trials.


Inpatient mortality and healthcare resource utilization of nontraumatic intracerebral hemorrhage complications in the US.
Nontraumatic, primary intracerebral hemorrhage (ICH) accounts for 2 million strokes worldwide annually and has a 1-year survival rate of 50%. Recent studies examining functional outcomes from ICH evacuation have been performed, but limited work has been done quantifying the incidence of subsequent complications and their healthcare economic impact. The purpose of this study was to quantify the incidence and healthcare resource utilization (HCRU) for major complications that can arise from ICH. The IBM MarketScan Research databases were used to retrospectively identify patients with ICH from 2010 to 2015. Complications examined included cerebral edema, hydrocephalus, venous thromboembolic events (VTEs), pneumonia, urinary tract infections (UTIs), and seizures. For each complication, inpatient mortality and HCRU were assessed. Of 25,322 adult patients included, 10,619 (42%) developed complications during the initial admission of ICH: 22% had cerebral edema, 11% hydrocephalus, 10% pneumonia, 6% UTIs, 5% seizures, and 5% VTEs. The inpatient mortality rates at 7 and 30 days for each complication of ICH ranked from highest to lowest were hydrocephalus (24% and 32%), cerebral edema (15% and 20%), pneumonia (8% and 18%), seizure (7% and 13%), VTE (4% and 11%), and UTI (4% and 8%). Hydrocephalus had the highest total cost (median $92,776, IQR $39,308-$180,716) at 7 days post-ICH diagnosis and the highest cumulative total cost (median $170,839, IQR $91,462-$330,673) at 1 year post-ICH diagnosis. This study characterizes one of the largest cohorts of patients with nontraumatic ICH in the US. More than 42% of the patients with ICH developed complications during initial admission, which resulted in high inpatient mortality and considerable HCRU.


A review of the toxicity of chemical dispersants.
Chemical dispersants are a mixture of various surfactants and solvents. Most dispersants are proprietary, and the complete composition is not often public knowledge. Chemical dispersants used for the cleanup and containment of crude oil toxicity became a major concern after the 2010 Deepwater Horizon oil crisis in the Gulf of Mexico. During the crisis, millions of liters of chemical dispersants (Corexit 9527 and 9500) were used--the largest known application of dispersants in the field. As of February 2011, 38 peer-reviewed articles were available on the toxicity of 35 different chemical dispersants. Nalco, BP, Shell, and Total Special Fluids manufacture a variety of chemical dispersants. Most notably, Nalco manufactures Corexit 9527 and 9500, and 19 miscellaneous dispersants are manufactured by others. Most studies examined the lethality of the dispersants. Several nonlethal end points were considered, including the effect on predator/prey recognition, enzyme activity changes, effects on hatchability, and the threshold for bradycardia. The animals studied included Daphnia (small planktonic crustaceans), anemones, corals, crustaceans, starfish, mollusks, fish, birds, and rats. Studies in birds and mammals are distinctly lacking. The variety of chemical dispersants, the variability in test methods, and the lack of distinct species overlap between studies make it difficult to compare and deduce which dispersant is most toxic and which is least. Here, we offer some attempt at comparing Corexit 9527 and 9500 (because these have had the largest field application), but significantly more research is needed before clear conclusions can be drawn.


DNA adducts in human pancreatic tissues and their potential role in carcinogenesis.
Pancreas cancer is the fourth and fifth leading cause of cancer death for men and women, respectively, in the United States. Although the etiology of this cancer is poorly understood, smoking and dietary fat have been implicated by epidemiological studies. To test the hypothesis that DNA damage derived from carcinogen exposure and diet is involved in pancreatic carcinogenesis, aromatic and lipid peroxidation-related DNA adducts in 13 normal tissues adjacent to tumor and 20 tumors from pancreatic cancer patients were analyzed by 32P-postlabeling. Normal pancreatic tissues from 5 nonpancreatic cancer patients and 19 healthy organ donors served as controls. To correlate the DNA adduct level with patients' characteristics, information on age, sex, body mass index, and smoking status of pancreatic cancer patients were collected from medical records. A significantly higher level of total DNA adducts was detected in pancreatic cancer patients as compared with controls. The mean level of adducts/10(8) nucleotides in adjacent normal pancreatic tissues from pancreatic cancer patients (A tissues) was 102 +/- 21 compared with 39 +/- 6 and 13 +/- 1 in pancreatic tumor tissues (T tissues) and normal pancreatic tissues from controls (C tissues), respectively. Among the adducts observed, one single aromatic adduct (spot 1) was present in 100, 90, and 0% of the A, T, and C tissues, respectively. Two novel clusters of adducts (spots 2 and 3) were observed in 11 of 13, 12 of 20, and 2 of 24 of A, T, and C tissues, respectively, and the presence of these adducts was positively correlated with smoking status. In addition, the previously defined smoking-related diagonal radioactive zone was detected in three A samples only, although 50% (10 of 20) of the patients with pancreatic cancers in this study were ever smokers. Putative lipid peroxidation-related adducts were detected in all samples examined and were significantly higher in A than in T and C samples. Multiple regression analyses showed that body mass index was positively correlated to the levels of spot 1 and the lipid peroxidation-related adducts in A tissues and the total aromatic adducts in tumors. Smoking was also positively correlated to the level of total adducts. These observations are consistent with previous epidemiological findings and support the hypothesis that DNA damage related to carcinogen exposure and lipid peroxidation is involved in human pancreatic carcinogenesis.


Endoscopic thoracic microdiscectomy.
The purpose of this investigation was to evaluate surgical and neurological outcomes in thoracic disc surgery in a prospective fashion. Quantifiable outcome data such as operating time, blood loss, duration of chest tube drainage, narcotic drug use, length of hospital stay (LOS), and long-term follow up of neurological function and pain-related symptoms were collected prospectively. In patients with myelopathy there was an improvement of two Frankel grades in the thoracoscopic discectomy group and one Frankel grade in the patients treated with thoracotomy; however, patients in the thoracotomy group were significantly worse preoperatively. None of the patients experienced worsened pain, and pain related to radiculopathy was improved by 75% in the thoracoscopic group. Thoracoscopic discectomy yields acceptable surgical results and has several distinct advantages, with reduced postoperative pain, morbidity, and LOS.


A common neuronal code for perceptual processes in visual cortex? Comparing choice and attentional correlates in V5/MT.
In the past two decades, sensory neuroscience has moved from describing response properties to external stimuli in cerebral cortex to establishing connections between neuronal activity and sensory perception. The seminal studies by Newsome, Movshon and colleagues in the awake behaving macaque firmly link single cells in extrastriate area V5/MT and perception of motion. A decade later, extrastriate visual cortex appears awash with neuronal correlates for many different perceptual tasks. Examples are attentional signals, choice signals for ambiguous images, correlates for binocular rivalry, stereo and shape perception, and so on. These diverse paradigms are aimed at elucidating the neuronal code for perceptual processes, but it has been little studied how they directly compare or even interact. In this paper, I explore to what degree the measured neuronal signals in V5/MT for choice and attentional paradigms might reflect a common neuronal mechanism for visual perception.


Physical Activity Counseling Promotes Physical and Psychological Resilience in Older Veterans with Posttraumatic Stress Disorder.
Individuals with posttraumatic stress disorder (PTSD) have elevated rates of morbidity, and a sedentary lifestyle can cause and aggravate the physical health needs of adults with PTSD. The primary aim of this paper was to explore the impact of physical activity (PA) counseling (vs. usual care) on physical and psychological outcomes among individuals with PTSD. A secondary aim was to compare these arm effects between those with and without PTSD. Older (>60 years) overweight veterans with impaired glucose tolerance were randomly assigned to an intervention or a usual care control arm. Of the 302 participants who underwent randomization, 67 (22%) had PTSD. Participants in the intervention arm received one in-person activity counseling session followed by regular PA telephone counseling over 12 months. Physical and psychological outcomes were assessed at baseline, 3, and 12 months. Primary Aim (intervention vs. usual care among those with PTSD): PA increased on average from 80 minutes/week to 161 minutes/week among participants in the intervention arm (p=0.01). Large, clinically meaningful improvements in six-minute walk test and psychological health were observed over the course of the intervention (p<0.01). Secondary Aim (PTSD/No PTSD, intervention/usual care): participants with PTSD responded equally well to the intervention compared to participants without PTSD, though we observed significantly greater improvements in vitality and six-minute walk compared to participants without PTSD (p<0.05). Given the epidemic of comorbid psychological illness and lifestyle-related disease among persons with PTSD, our findings support development and implementation of targeted PA interventions in this high-risk population.


Inhibition of return in discrimination tasks.
Although inhibition of return is known to affect a wide range of detection tasks, it has not been found consistently in discrimination tasks. To examine this issue, 5 experiments were conducted in which participants discriminated between a visual target and a distractor. The responses were not inhibited if, before the onset of stimuli, attention had been overtly oriented (i.e., an eye movement was made) to the future target location and the stimulus at that location was the same symbol as the upcoming target. However, if attention was covertly oriented (i.e., no eye movement was made) to the future location of the target, or if the stimulus at the earlier attended location was a symbol different from the target, responses to the target were inhibited. Overall, the findings provide insights into the relation between movements of attention and discrimination judgments and support the notion that inhibition of return is an attentional phenomenon.


Subcutaneous exposure of calves to Myobacterium paratuberculosis compared with intravenous and oral exposures.
Three groups of calves, 21 days of age, were exposed to Mycobacterium paratuberculosis by oral, intravenous, and subcutaneous routes. Fecal cultural examination and intradermal tests were made, and at 150 days after exposure, the calves were euthanatized and tissues were collected for histopathologic and bacteriologic cultural examination. Calves in the 3 groups were infected. Those exposed intravenously had significantly higher colony counts than did either of the other groups. There was no significant difference between colony counts of cultures from tissues of calves exposed orally and those of calves exposed subcutaneously.


A sodium-channel mutation causes isolated cardiac conduction disease.
Cardiac conduction disorders slow the heart rhythm and cause disability in millions of people worldwide. Inherited mutations in SCN5A, the gene encoding the human cardiac sodium (Na+) channel, have been associated with rapid heart rhythms that occur suddenly and are life-threatening; however, a chief function of the Na+ channel is to initiate cardiac impulse conduction. Here we provide the first functional characterization of an SCN5A mutation that causes a sustained, isolated conduction defect with pathological slowing of the cardiac rhythm. By analysing the SCN5A coding region, we have identified a single mutation in five affected family members; this mutation results in the substitution of cysteine 514 for glycine (G514C) in the channel protein. Biophysical characterization of the mutant channel shows that there are abnormalities in voltage-dependent 'gating' behaviour that can be partially corrected by dexamethasone, consistent with the salutary effects of glucocorticoids on the clinical phenotype. Computational analysis predicts that the gating defects of G514C selectively slow myocardial conduction, but do not provoke the rapid cardiac arrhythmias associated previously with SCN5A mutations.


Identifying and Responding to Delirium in Acute Stroke: Clinical Team Members' Understandings.
Delirium is associated with increased mortality, morbidity, and length of hospital stay. In the acute stroke setting, delirium identification is challenging due to the complexity of cognitive screening in this patient group. The aim of this study was to explore how members of interprofessional stroke-unit teams identified and responded to a potential delirium in a patient. Online focus groups and interviews utilizing case vignettes were conducted with 15 participants: nurses, occupational therapists, speech and language therapists, and physiotherapists working in acute stroke services. Participants' understandings of delirium varied, most participants did not identify the symptoms of a possible hypoactive delirium, and nearly all participants discussed delirium symptoms in tentative terms. Aspects of interprofessional working were discussed through the expression of distinct roles around delirium identification. Although participants demonstrated an ethos of person-focused care, there are ongoing challenges involved in early identification and management of delirium in stroke survivors.


The Listeria monocytogenes gene ctpA encodes a putative P-type ATPase involved in copper transport.
A Tn917 transposon derivative was used to construct a lacZ transcriptional fusion mutant in Listeria monocytogenes DRDC8 that displayed increased beta-galactosidase activity in response to cation stress. A 4.3 kb fragment of L. monocytogenes chromosomal DNA flanking the lacZ fusion was cloned and sequenced. A 1962 bp open reading frame was identified, and designated ctpA. Analysis of the deduced 653 amino acid sequence revealed significant similarity to the family of ATP-dependent enzymes involved in copper transport in prokaryotes and eukaryotes. CtpA is distinctive by virtue of an N-terminal truncation in the domain responsible for cation binding. Growth of ctpA insertion mutants was restricted by the copper-chelating agent 8-hydroxyquinoline. DNA/RNA hybridisation studies revealed that levels of ctpA mRNA were increased following growth in media containing low and high copper concentrations. These results suggest the isolation of a region of DNA that encodes a novel copper-transporting system in L. monocytogenes.


Chronic haloperidol effects on oral movements and radial-arm maze performance in rats.
Rats were examined for the development of adverse motor and cognitive effects during and after 24 weeks of chronic haloperidol (HAL) administration using an 8-arm maze and a computerized apparatus for measuring spontaneous oral movements. In the maze, HAL caused a significant decline in choice accuracy only during the first week of administration, whereas it caused a significant decline in locomotor speed throughout drug administration. There were no effects of HAL on maze behavior after withdrawal. Haloperidol reduced the number of mouth movements during drug administration, but after withdrawal there was a significant increase. This replicated a previous finding from our lab. The oral movements which did occur in the HAL-treated rats were slower than normal. The timing of the HAL-induced cognitive dysfunction was similar to the Parkinson-like disorder shown by patients given chronic neuroleptics, whereas the timing of the increase in oral movements after the withdrawal of HAL was more related to the appearance of tardive dyskinesia. There was evidence in both tests of a persisting sedation during chronic neuroleptic administration.


Self-start HIV postexposure prophylaxis (PEPSE), to reduce time to first dose and increase efficacy.
Effectiveness of HIV postexposure prophylaxis (PEPSE) correlates with speed of uptake following HIV exposure. Time to first dose has not improved in the UK for over 10 years. On-demand pre-exposure prophylaxis (PrEP) has shown that people can self-start medication for HIV prevention.We hypothesised that advanced provision of PEPSE (HOME PEPSE) for men who have sex with men (MSM) to self- initiate would reduce time to first dose following HIV exposure. Phase IV, randomised, prospective, 48-week, open-label study was carried out. MSM at medium risk of acquiring HIV were randomised (1:1) to immediate or deferred standard of care (SOC) HOME PEPSE. Every 12 weeks, participants self-completed mental health/risk behaviour surveys and had HIV/sexually transmitted infection (STI) testing.HOME PEPSE comprised a 5-day pack of emtricitabine/tenofovir disoproxil fumarate/maraviroc 600 mg once daily initiated following potential exposure to HIV. If taken, participants completed a risk survey; PEPSE continuation was physician directed. Primary outcome was time from potential exposure to HIV to first PEPSE dose. 139 participants randomised 1:1; 69 to immediate HOME PEPSE and 70 to deferred HOME PEPSE. Median age 30 years (IQR 26-39), 75% white, 55% UK born and 72% university educated. 31 in HOME PEPSE and 15 in SOC arm initiated PEPSE. Uptake of HOME PEPSE was appropriate in 27/31 cases (87%, 95% CI: 71% to 95%). Median time from exposure to first dose was 7.3 hours (3.0, 20.9) for HOME PEPSE and 28.5 hours (17.3, 34.0) for SOC (p<0.01). HOME PEPSE was well tolerated with no discontinuations.No significant differences in missed opportunities for PEPSE uptake, sexual behaviour or bacterial STI infections between treatment arms. HOME PEPSE reduced the time from exposure to first-dose PEPSE by 21+ hours, with no impact on safety. This significantly improves the efficacy of PEPSE and provides an option for people declining PrEP.


Prospective Phycocompounds for Developing Therapeutics for Urinary Tract Infection.
Antibiotic resistance of bacteria is causing clinical and public health concerns that are challenging to treat. Infections are becoming more common in the present era, and patients admitted to hospitals often have drug-resistant bacteria that can spread nosocomial infections. Urinary tract infections (UTIs) are among the most common infectious diseases affecting all age groups. There has been an increase in the proportion of bacteria that are resistant to multiple drugs. Herein is a comprehensive update on UTI-associated diseases: cystitis, urethritis, acute urethral syndrome, pyelonephritis, and recurrent UTIs. Further emphasis on the global statistical incidence and recent advancement of the role of natural products in treating notorious infections are described. This updated compendium will inspire the development of novel phycocompounds as the prospective antibacterial candidate.


Treatment with anticoagulants in cerebral events (TRACE).
90 patients with acute stroke and a concomitant cardiac embolism source or a symptomatic high-grade stenosis of an extra-or intracranial vessel received in a mulitcenter, randomized, controlled study either Enoxaparin 1 mg/kg BW s.c. b.i.d. or i.v. heparin aPTT-adjusted daily for 8 +/- 2 days as secondary prophylaxis. There were no significant differences between the two groups regarding cerebral and systemic embolic events, bleeding complications, length of hospital stay, number of diagnostic and therapeutic measures and outcome after three months. This suggests that Enoxaparin, which is easier to administer and monitor, is a safe drug in patients with acute cerebral events.


Involvement of sphingosine-1-phosphate in glutamate secretion in hippocampal neurons.
Neuronal activity greatly influences the formation and stabilization of synapses. Although receptors for sphingosine-1-phosphate (S1P), a lipid mediator regulating diverse cellular processes, are abundant in the central nervous system, neuron-specific functions of S1P remain largely undefined. Here, we report two novel actions of S1P using primary hippocampal neurons as a model system: (i) as a secretagogue where S1P triggers glutamate secretion and (ii) as an enhancer where S1P potentiates depolarization-evoked glutamate secretion. Sphingosine kinase 1 (SK1), a key enzyme for S1P production, was enriched in functional puncta of hippocampal neurons. Silencing SK1 expression by small interfering RNA as well as SK1 inhibition by dimethylsphingosine resulted in a strong inhibition of depolarization-evoked glutamate secretion. Fluorescence recovery after photobleaching analysis showed translocation of SK1 from cytosol to membranes at the puncta during depolarization, which resulted in subsequent accumulation of S1P within cells. Fluorescent resonance energy transfer analysis demonstrated that the S1P(1) receptor at the puncta was activated during depolarization and that depolarization-induced S1P(1) receptor activation was inhibited in SK1-knock-down cells. Importantly, exogenously added S1P at a nanomolar concentration by itself elicited glutamate secretion from hippocampal cells even when the Na(+)-channel was blocked by tetrodotoxin, suggesting that S1P acts on presynaptic membranes. Furthermore, exogenous S1P at a picomolar level potentiated depolarization-evoked secretion in the neurons. These findings indicate that S1P, through its autocrine action, facilitates glutamate secretion in hippocampal neurons both by secretagogue and enhancer actions and may be involved in mechanisms underlying regulation of synaptic transmission.


Creatine kinase isoenzymes in bovine tissue.
Brain, heart, liver, kidney, spleen, lungs, rumen, abomasum, small intestine, skeletal muscle, and urinary bladder from healthy cattle were analyzed for creatine kinase isoenzymes as a possible aid in the diagnosis of myocardial disease. Creatine kinase was detected in all organs evaluated. In addition, 6 different fluorescing bands were detected by isoenzyme analysis. Large quantities of the same isoenzymes were in cardiac and skeletal muscle, but not in other organs. Creatine kinase isoenzyme analysis does not necessarily indicate cardiac damage, but may narrow the range of tissue damage possibilities to be included in the differential diagnosis.


Fluorescence recovery kinetic analysis of gamma-tubulin binding to the mitotic spindle.
Fluorescence recovery after photobleaching has been widely used to study dynamic processes in the cell, but less frequently to analyze binding interactions and extract binding constants. Here we use it to analyze gamma-tubulin binding to the mitotic spindle and centrosomes to determine the role of gamma-tubulin in microtubule nucleation in the spindle. We find rapid gamma-tubulin turnover in mitotic spindles of Drosophila early embryos, characterized by diffusional interactions and weak binding, differing from centrosomes with tight binding interactions. The diffusion coefficient of gamma-tubulin is consistent with a major species existing in the cytoplasm as the less efficiently nucleating gamma-tubulin small complex (gammaTuSC) or gamma-tubulin, rather than gamma-tubulin ring complex (gammaTuRC). The fluorescence recovery kinetics we observe implies that gamma-tubulin functions by binding weakly to spindle microtubules. gamma-Tubulin may interact transiently with the spindle, nucleating microtubules very rapidly, differing from centrosomes, where gamma-tubulin binds tightly to nucleate microtubules.


Catalase-negative Escherichia coli isolated from blood.
A catalase-negative variant of Escherichia coli was isolated from the blood of a patient with acute leukemia who had been treated with various antibiotics and gentamicin. This small-colony variant grew almost as actively under anaerobic conditions as its large-colony revertant or E. coli NIHJ JC-2. The variant was resistant to gentamicin, in contrast with the revertant. Streptomycin and hemin stimulated growth of the variant slightly. With repeated subculturing the variant tended to increase slightly in colony size with coincident recovery of weak catalase production. The possibility that such a variant may have been induced by gentamicin was indicated.


Wedged AFM-cantilevers for parallel plate cell mechanics.
The combination of atomic force microscopy (AFM) and optical microscopy has gained popularity for mechanical analysis of living cells. In particular, recent AFM-based assays featuring tipless cantilevers and whole-cell deformation have yielded insights into cellular function, structure, and dynamics. However, in these assays the standard ≈10° tilt of the cantilever prevents uniaxial loading, which complicates assessment of cellular geometry and can cause cell sliding or loss of loosely adherent cells. Here, we describe an approach to modify tipless cantilevers with wedges and, thereby, achieve proper parallel plate mechanics. We provide guidance on material selection, the wedge production process, property and geometry assessment, and the calibration of wedged cantilevers. Furthermore, we demonstrate their ability to simplify the assessment of cell shape, prevent lateral displacement of round cells during compression, and improve the assessment of cell mechanical properties.


Isotope fractionation associated with the direct photolysis of 4-chloroaniline.
Compound-specific isotope analysis is a useful approach to track transformations of many organic soil and water pollutants. Applications of CSIA to characterize photochemical processes, however, have hardly been explored. In this work, we systematically studied C and N isotope fractionation associated with the direct photolysis of 4-Cl-aniline used as a model compound for organic micropollutants that are known to degrade via photochemical processes. Laboratory experiments were carried out at an irradiation wavelength of 254 nm over the pH range 2.0 to 9.0 as well as in the presence of Cs(+) as a quencher of excited singlet 4-Cl-aniline at pH 7.0 and 9.0. We observed considerable variation of C and N isotope enrichment factors, ϵC and ϵN, between -1.2 ± 0.2‰ to -2.7 ± 0.2‰ for C and -0.6 ± 0.2‰ to -9.1 ± 1.6‰ for N, respectively, which could not be explained by the speciation of 4-Cl-aniline alone. In the presence of 1 M Cs(+), we found a marked increase of apparent (13)C-kinetic isotope effects ((13)C-AKIE) and decrease of 4-Cl-aniline fluorescence lifetimes. Our data suggest that variations of C and N isotope fractionation originate from heterolytic dechlorination of excited triplet and singlet states of 4-Cl-aniline. Linear correlations of (13)C-AKIE vs (15)N-AKIE were distinctly different for these two reaction pathways and may be explored further for the identification of photolytic aromatic dechlorination reactions.


Heparin-Induced Thrombocytopenia in COVID-19: A Systematic Review.
It has been more than a year since the whole world is struggling with COVID-19 pandemic and may experience resurgences in the near future. Along with severe pneumonia, this disease is notorious for extensive thromboembolic manifestations. That is why experts advocated aggressive anticoagulation as a part of the therapy since the beginning. However, from May 2020 onwards, cases of heparin-induced thrombocytopenia (HIT) are being reported. HIT in itself is an autoimmune entity leading to life-threatening thrombosis in the setting of thrombocytopenia. Continuation of heparin can have disastrous consequences in case of unrecognized HIT. Hence, timely recognition of HIT is of utmost value to modify the anticoagulation strategy and salvaging lives. We performed a systemic review trying to find all reported cases of HIT in COVID-19. It involved extensive search of the databases including PubMed, Google Scholar, Scopus, and Embase in an attempt to find all reported literature in the last 1 year (November 1, 2019-December 25, 2020) using keywords in various combinations. Literature search resulted in a total of 27 articles and 12 articles were finally selected based on the study design and their relevance pertaining to the intervention done and the outcome of interest. A total of 35 patients were included (mean age 56.7 ± 12.8 years, male-to-female ratio = 2:1). The most frequent comorbidity was hypertension. Fifty-seven percent of cases were with low-molecular weight heparin and the rest with unfractionated heparin. Confirmatory functional assay was done in 85.7% of cases (67% by serotonin-release assay [SRA] and 33% by heparin-induced platelet aggregation [HIPA]). All cases tested with HIPA were positive, while with SRA, only 30% were positive. The most common alternate anticoagulation used was argatroban infusion. The new arterial thrombotic event was seen in only 5.7% of cases as repeat myocardial infarction, stroke, and splenic infarction, while clinically significant bleeding was seen in 17.1% of cases. Fifty percent of bleeding episodes were seen where conventional doses of argatroban were used, while no mortality was seen with low-dose argatroban infusion. However, only 45.7% of patients were discharged, 31.4% of patients died, while the outcome was pending for 23% of patients. Severe endotheliitis and immune dysregulation giving rise to HIT antibodies and antiphospholipid antibodies have been demonstrated in COVID-19 and modifying our therapy becomes indispensable when it is pathogenic with potentially fatal consequences. In the light of interim results of REMAP-CAP study in severe COVID-19 cases where heparin does not improve the outcome, the present anticoagulation strategy needs re-evaluation. Unrecognized HIT can be catastrophic and close clinical monitoring is required for patients on heparin therapy.


Martian Residents: Mass Media and Ramsar High Background Radiation Areas.
Considering current controversies regarding the health effects of low doses of ionizing radiation, study of the high background radiation areas such as Ramsar, Iran can help scientists better evaluate the validity of linear no-threshold (LNT) hypothesis. Ramsar is a coastal city in northern Iran with some areas known to have the highest levels of natural background radiation in the world. The mean annual dose of the residents of high background radiation areas (HBRAs) of Ramsar is 10 times higher than the public dose limit recommended by the ICRP (1 mSv/year) and a proportion of the residents receive annual doses as large as 260 mSv (13 times higher than the occupational dose limit recommended by the ICRP). A report published in Popular Science proclaims that background radiation in Ramsar approaches that of the Martian surface. However, estimates show that the maximum annual radiation dose in HBRAs of Ramsar can be much higher than that of the Martian surface (260 mGy/y vs 76 mGy/y). Furthermore, a Guardian report introduces Talesh Mahalleh, a district in Ramsar, as an inhabited area with the highest levels of natural radioactivity in the world and C Net claims that the best Mars colonists may come from places like Iran and Brazil. In spite of current concerns, nearly all residents still live in their paternal dwellings and there are not consistent reports on any detrimental effects. It is worth noting that, due to small sample size, to draw a firm conclusion about the health effects of high level natural radiation in Ramsar, in particular about the cancer risk, current information is not sufficient and further studies are needed.


Topological friction strongly affects viral DNA ejection.
Bacteriophages initiate infection by releasing their double-stranded DNA into the cytosol of their bacterial host. However, what controls and sets the timescales of DNA ejection? Here we provide evidence from stochastic simulations which shows that the topology and organization of DNA packed inside the capsid plays a key role in determining these properties. Even with similar osmotic pressure pushing out the DNA, we find that spatially ordered DNA spools have a much lower effective friction than disordered entangled states. Such spools are only found when the tendency of nearby DNA strands to align locally is accounted for. This topological or conformational friction also depends on DNA knot type in the packing geometry and slows down or arrests the ejection of twist knots and very complex knots. We also find that the family of (2, 2k+1) torus knots unravel gradually by simplifying their topology in a stepwise fashion. Finally, an analysis of DNA trajectories inside the capsid shows that the knots formed throughout the ejection process mirror those found in gel electrophoresis experiments for viral DNA molecules extracted from the capsids.


Increased vascular responsiveness to bradykinin in kidneys of spontaneously hypertensive rats. Effect of N omega-nitro-L-arginine.
We investigated the role of nitric oxide (NO)-dependent and NO-independent mechanisms in mediation of renal vasodilatory responses to bradykinin in spontaneously hypertensive rats (SHR), rats with angiotensin II-induced hypertension (200 ng/min i.p. for 6 days) and the corresponding normotensive control Wistar-Kyoto (WKY) rats and sham-infused rats. To this end, we contrasted the effects of arterial injections of bradykinin and other vasodilators, acetylcholine and sodium nitroprusside, on perfusion pressure and output of cyclic GMP in isolated kidneys perfused with Krebs bicarbonate buffer containing phenylephrine, both with and without N omega-nitro-L-arginine (L-NOARG) (50 microM), an inhibitor of NO synthetase. In kidneys perfused without L-NOARG, all agonists increased the output of cyclic GMP and reduced perfusion pressure, indicative of vasodilation. In kidneys perfused with L-NOARG, vasodilatory responses to bradykinin and acetylcholine were attenuated, and associated effects on output of cyclic GMP were abolished, suggesting dependency on NO synthesis. Irrespective of whether kidneys were perfused with or without L-NOARG, kidneys of SHR were more responsive than kidneys of WKY rats with regard to bradykinin-induced vasodilation. In contrast, vasodilatory responsiveness to bradykinin was nearly equal in perfused kidneys of rats with angiotensin II-induced hypertension and in normotensive controls. Also, vasodilatory responsiveness to acetylcholine and sodium nitroprusside was similar in kidneys of normotensive and hypertensive rats. These data suggest that the renal vasculature of SHR is uniquely and selectively hyperresponsive to bradykinin, with regard to both the NO-dependent and NO-independent vasodilatory actions.


Reinnervation of extraocular muscles by facial-to-oculomotor nerve anastomosis in rats: anatomic nuclear changes.
Oculomotor nerve palsy greatly impairs the patient's daily life. After oculomotor nerve injury, when the central nerve stump is not available, neurotization of the distal nerve stump with a donor nerve may be performed. Here, we present an experimental anatomic study in rats related to the motor nuclear organization after facial-to-oculomotor nerve anastomosis. In adult rats, the right oculomotor nerve was transected at the skull base. Then, the ipsilateral facial nerve was exposed at the stylomastoid foramen and connected side-to-end to one extremity of a peroneal nerve autograft. The other extremity of the nerve autograft was connected end-to-end to the distal stump of the transected oculomotor nerve. Twelve weeks later, axonal regeneration in the autograft and brainstem somatotopic representation of the reinnervated extraocular muscles were investigated by use of histological and retrograde axonal tracing techniques. The autograft was reinnervated by a large number of small axons, 1 to 5 microm in diameter. After tracer injection into the superior rectus and medial rectus muscles, retrogradely labeled neurons were seen not only in the ipsilateral facial nucleus (16%) but also in the contralateral nucleus (8%). Labeled neurons were also seen in the ipsilateral abducens (12%), motor trigeminus (7%), trochlear (23%), and contralateral trochlear (34%) nuclei. In normal rats, the extraocular muscles are innervated by unilateral-ipsilateral brainstem motor nuclei, except for the superior rectus and superior oblique muscles, which are innervated by bilateral, primarily contralateral, nuclei. The central rearrangement of the extraocular muscle nuclei after facial-to-oculomotor nerve anastomosis represents an original example of plasticity. Functional studies are needed to demonstrate whether this procedure might serve to restore some degree of eye motility.


Functional Connectivity Analysis in Multi-channel EEG for Emotion Detection with Phase Locking Value and 3D CNN.
The noise-assisted multivariate Empirical mode decomposition (NA-MEMD) is applied to multi-channel EEG signals to obtain narrow-band scale-aligned intrinsic mode functions (IMFs) upon which functional connectivity analysis is performed. The connectivity pattern in relation to inherent functional activity of brain is estimated with the phase locking value (PLV). Instantaneous phase difference among different EEG channels gives PLV that is used to build the functional connectivity map. The connectivity map yields spatial-temporal feature representation which is taken as input of the proposed emotion detection system. The spatial-temporal features can be learned with a 3D convolutional neural network for classifying emotion states. The proposed system is evaluated on two publicly available DEAP and SEED dataset for binary and multi-class emotion classification. On detecting low versus high level in the valence and arousal dimensions, the attained accuracy values are 97.37% and 96.26% respectively. Meanwhile, this system yields 94.78% and 99.54% accuracy on multi-class task on DEAP and SEED, which outperform previously reported systems with other deep learning models and conventional EEG features.


H2B (Ser10) phosphorylation is induced during apoptosis and meiosis in S. cerevisiae.
The nucleosome, composed of an octamer of highly conserved histone proteins and associated DNA, is the fundamental unit of eukaryotic chromatin. How arrays of nucleosomes are folded into higher-order structures, and how the dynamics of such compaction are regulated, are questions that remain largely unanswered. Our recent studies demonstrated that phosphorylation of histone H2B is necessary to induce cell death that exhibits phenotypic hallmarks of apoptosis including DNA fragmentation and chromatin condensation in yeast (serine 10)1 and in mammalian cells (serine 14)2. In this article, we extend these findings by uncovering a role for H2B phosphorylation at serine 10 (Ser10) in another biological event that is associated with dramatic alterations in higher-order chromatin structure, meiosis. Our data show strong staining, indicative of H2B (Ser10) phosphorylation, during the pachytene stage of yeast meiotic prophase. These data broaden the use of this phosphorylation mark in chromatin remodeling that closely correlates with chromatin compaction. How phosphorylation marks are translated into meaningful downstream events during processes as diverse as apoptosis and meiosis remain a challenge for future studies.


Histidine at position 61 and its adjacent amino acid residues are critical for the ability of SLAM (CD150) to act as a cellular receptor for measles virus.
Signalling lymphocyte activation molecule (SLAM, also known as CD150), a membrane glycoprotein involved in lymphocyte activation, has two extracellular immunoglobulin superfamily domains, V and C2. It has been shown previously that human SLAM is a cellular receptor for measles virus (MV) and that its V domain is necessary and sufficient for receptor function. Although mouse SLAM has functional and structural similarity to human SLAM, it hardly acts as a receptor for MV. By producing human/mouse chimeric molecules and assessing their receptor function with a vesicular stomatitis virus pseudotype assay, the region at amino acid positions 58-67 was found to be critically responsible for the difference in MV receptor function between human and mouse SLAMs. Exchange of this region allowed mouse SLAM to act as a receptor for MV, almost comparable to human SLAM. Among three amino acid differences (positions 60, 61 and 63) in this region, histidine 61 present in human SLAM was most significant, but combined substitutions with this residue and one or both of isoleucine 60 and valine 63 increased further the receptor activity of mouse SLAM. On the other hand, converse substitution at position 61 compromised receptor function of human SLAM. Thus, histidine 61 and its adjacent residues at positions 60 and 63 are critical for SLAM to act as a receptor for MV. Notably, the pseudotype assay indicated that residues at these three positions are also critical for the function of SLAM as a receptor for canine distemper virus.


An optical method for three-dimensional dosimetry.
Accurate determination of the spatial distribution of the absorbed dose of ionising radiation plays an important role in radiotherapy, industrial radiation processing and many other applications. Computer calculations have frequently been used to estimate three-dimensional (3D) dose distributions in complex geometries and it becomes important to validate these by accurate 3D measurements. For this purpose we have been investigating the use of gelatin gels loaded with a modified Fricke solution which are pale orange in appearance and which, upon irradiation, become increasingly purple when viewed in normal light. This ferrous sulphate xylenol orange in gelatin gel (FXG) system displays very good properties, such as sensitivity, linearity and dynamic range, that make it suitable for 3D dosimetry applications. A high-speed optical tomography readout technique has been developed enabling two-dimensional projections of optical absorption data to be recorded rapidly. From these data the 3D absorbed dose distribution can quickly be derived with minimal degradation due to ion diffusion.


Rhythmic Auditory Cueing in Motor Rehabilitation for Stroke Patients: Systematic Review and Meta-Analysis.
Given the increasing evidence demonstrating the effects of rhythmic auditory cueing for motor rehabilitation of stroke patients, this synthesized analysis is needed in order to improve rehabilitative practice and maximize clinical effectiveness. This study aimed to systematically analyze the literature on rhythmic auditory cueing for motor rehabilitation of stroke patients by highlighting the outcome variables, type of cueing, and stage of stroke. A systematic review with meta-analysis of randomized controlled or clinically controlled trials was conducted. Electronic databases and music therapy journals were searched for studies including stroke, the use of rhythmic auditory cueing, and motor outcomes, such as gait and upper-extremity function. A total of 10 studies (RCT or CCT) with 356 individuals were included for meta-analysis. There were large effect sizes (Hedges's g = 0.984 for walking velocity; Hedges's g = 0.840 for cadence; Hedges's g = 0.760 for stride length; and Hedges's g = 0.456 for Fugl-Meyer test scores) in the use of rhythmic auditory cueing. Additional subgroup analysis demonstrated that although the type of rhythmic cueing and stage of stroke did not lead to statistically substantial group differences, the effect sizes and heterogeneity values in each subgroup implied possible differences in treatment effect. This study corroborates the beneficial effects of rhythmic auditory cueing, supporting its expanded application to broadened areas of rehabilitation for stroke patients. Also, it suggests the future investigation of the differential outcomes depending on how rhythmic auditory cueing is provided in terms of type and intensity implemented.


Evolutionary morphology of the rattlesnake style.
The rattlesnake rattling system is an evolutionary novelty that includes anatomical, behavioral, and physiological modifications of the generalized pitviper tail. One such modification, the formation of a bony clublike style at the terminal region of the caudal vertebrae, has not previously been examined in a phylogenetic context. Here we used skeletal material, cleared and stained preparations, and radiographs of whole preserved specimens to examine interspecific variation in style morphology among 34 rattlesnake species. Evolutionary Principal Components Analysis revealed an inverse relationship between caudal segmental counts and style size, supporting the hypothesis that bone from caudal vertebral elements was reallocated to style formation during the evolution of this structure. Most of the basal rattlesnake species have small styles consisting of few compacted vertebral elements; however, early in the rattlesnake radiation there appears to have been two independent transitions to relatively large, pronged styles consisting of multiple coalesced vertebrae (once in Sistrurus catenatus, and once in Crotalus following the divergence of the Mexican long-tailed rattlesnakes). In terms of style shape, the two most divergent species, C. catalinensis and C. ericsmithi, provide insight into the possible relationship between style and rattle matrix morphology and lineage-specific evolutionary strategies for retaining rattle segments. The considerable interspecific variation in rattle morphology appears to correspond to variation in the bony style. We hypothesize that style morphology evolves indirectly as an integrated module responding to adaptive evolution on matrix morphology.


Transesophageal echocardiography for the diagnosis of pulmonary vein stenosis after catheter ablation of atrial fibrillation: a systematic review.
Pulmonary vein (PV) stenosis is a potentially serious complication of catheter ablation of atrial fibrillation (AF). The optimal method for diagnosis of PV stenosis has not been established. We undertook a systematic review of the literature to investigate the diagnostic performance of transesophageal echocardiography (TEE) for the detection of PV stenosis after catheter ablation of AF. We searched MEDLINE and EMBASE databases for studies evaluating the diagnostic performance of TEE for the detection of PV stenosis after catheter ablation of AF, compared to a reference standard of PV angiography, magnetic resonance imaging (MRI), or computed tomography (CT). Study quality was assessed using the QUADAS tool. A total of seven studies that included 344 patients (1,344 PVs) met the selection criteria. Of these, three studies used PV angiography as the reference standard, while MRI and CT were used in two studies each. Compared to PV angiography, TEE had sensitivity between 82% and 100% and specificity between 98% and 100%. Compared to MRI, TEE sensitivity was 100% in both studies, while the specificity ranged between 98% and 99%. Compared to CT, TEE had sensitivity between 86% and 100% and specificity of 95%. Quality of the reviewed studies was somewhat limited by the retrospective design in most of the studies. TEE has a high sensitivity and specificity in detecting PV stenosis. Given its wide availability and favorable side effect profile, these data suggest that TEE is very useful tool for the diagnosis of PV stenosis after catheter ablation of AF.


A spectroscopic and electrochemical approach to the study of the interactions and photoinduced electron transfer between catechol and anatase nanoparticles in aqueous solution.
We have combined in situ photoelectrochemical and spectroscopic techniques (Attenuated Total Reflection Infrared, ATR-IR, and Resonance Raman Spectroscopy) for the study of the charge-transfer complex formed upon adsorption of catechol on anatase nanoparticles in contact with aqueous acidic solutions. Vibrational spectroscopies reveal the existence of at least two adsorbate configurations: catecholate in a chelate configuration and molecularly adsorbed catechol, with apparent values of -12.3 and -10.5 kJ mol(-1), respectively. These values are significantly less negative than the values reported for anatase colloidal dispersions. The adsorption of both catechol species on the nanoparticulate anatase thin films follows the Freundlich isotherm. As revealed by resonance Raman spectroscopy, only the adsorbed chelating catecholate forms the charge-transfer complex. The electron transfer from the adsorbate to the anatase nanoparticles has been evidenced by the development of a negative photopotential upon 514.5 or 632.8 nm laser illumination of an anatase nanostructured thin film electrode in contact with a catechol solution. The time evolution of the Raman spectra shows an increasing fluorescence indicating that, upon electron injection, catechol polymerization occurs on the TiO2 surfaces. This conclusion is confirmed by in situ ATR-IR measurements, which show a progressive broadening of the catecholate bands together with the appearance of new signals. This study illustrates the benefits of combining electrochemical, infrared, and Raman techniques for the elucidation of processes occurring at the semiconductor/solution interface. Finally, evidence is given on the different adsorption and reactivity behavior found for suspensions and nanoporous thin films under equivalent experimental conditions.