The seventh London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.
The 7th London-Innsbruck Colloquium on Status Epilepticus was held in London on 7-9 April 2019, with a faculty of 47 clinicians and scientists from 16 countries and a total of 401 delegates from 41 countries. This paper is an introduction to the proceedings of the colloquium, and outlines the recent developments in status epilepticus which formed the core of colloquium program in the areas of 1. basic science; 2. clinical description, etiology, and investigation; and 3. treatment. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".


Views on the wisdom of using antioxidant vitamin supplements.
In the Forum that follows, four authorities in nutrition and vitaminology present their divergent views on the use of antioxidant vitamin supplements. In this introduction, the basic dilemma between setting RDAs that insure an absence of deficiency symptoms and those that insure optimal health is discussed, as well as other factors that must be considered to reach a consensus on this controversial topic.


Differential effects of spinal motor neuron-derived and skeletal muscle-derived Rspo2 on acetylcholine receptor clustering at the neuromuscular junction.
We recently reported that R-spondin 2 (Rspo2), a secreted activator of Wnt/β-catenin signaling, promotes acetylcholine receptor (AChR) clustering and neuromuscular junction (NMJ) formation via its receptor, Lgr5. Rspo2 is expressed highly in spinal motor neurons (SMNs) and marginally in the skeletal muscle, but the origin of Rspo2 at the NMJ remains elusive. We rescued Rspo2-deficient (Rspo2-/-) mice by specifically expressing Rspo2 in the skeletal muscle and SMNs. SMN-specific Rspo2 mitigated or over-corrected abnormal features of the NMJs and AChR clusters observed in Rspo2-/- mice including (i) abnormal broadening of enlarged AChR clusters, (ii) three of six abnormal ultrastructural features, and (iii) abnormal expression of nine genes in SMNs and the diaphragm. In contrast, muscle-specific Rspo2 normalized all six abnormal ultrastructural features, but it had no effect on AChR clustering and NMJ formation at the light microscopy level or on abnormal gene expression in SMNs and the diaphragm. These results suggest that SMN-derived Rspo2 plays a major role in AChR clustering and NMJ formation in the postsynaptic region, and muscle-derived Rspo2 also plays a substantial role in juxtaposition of the active zones and synaptic folds.


Correlation between clinical manifestations of nocturnal enuresis and attentional performance in children with attention deficit hyperactivity disorder (ADHD).
Children with attention deficit hyperactivity disorder (ADHD) tend to be more vulnerable to various forms of voiding dysfunction and nocturnal enuresis (NE). We attempt to compare the clinical manifestations and attentional performance between ADHD children with NE and those without NE. We consecutively enrolled children diagnosed with ADHD in child and adolescent psychiatric clinics. The questionnaires for evaluation of ADHD symptoms and voiding dysfunction symptoms were administered to all study participants. All participants also received the Test Battery for Attention Performance (TAP) for assessment of attentional function. A total of 53 children were enrolled in this study, comprising 47 boys and six girls. The prevalence rate of NE was 28.3%. Children in the NE group had statistically significant higher dysfunctional voiding symptom score (5.40 ± 3.66 vs.3.16 ± 2.74; p = 0.018) and two subscales of "When I wet myself, my underwear is soaked" (p < 0.001) and "I miss having a bowel movement every day" (p = 0.047). There were no significant differences with regard to all psychiatric evaluations between the NE and non-NE groups. In the TAP test, the NE group showed a significantly shorter reaction time in the domain of inhibitory control, working memory, and auditory sustained attention than the non-NE group. Children with ADHD have a high prevalence of NE. ADHD children with NE had a significantly higher dysfunctional voiding symptom score and shorter reaction time in most domains of the TAP test. Further study is needed to discern the impact of NE on the neuropsychological function of ADHD children.


The antidiabetic and hepatoprotective effects of myricitrin on aged mice with D-galactose.
The present study aims to evaluate the effects of antidiabetic and hepatoprotective of myricitrin in the aged mice induced by D-galactose (D-gal). Aging occurs during a person's life; there has been no way to stop the aging process, but antioxidant and changing lifestyles can delay it. In this experimental study, 72 female adult mice (weighing30-35g) were randomly divided into six groups: 1: control, 2: D-gal at 500mg/kg/d, 3-5: D-gal+ Myricitrin at 5, 10 and 20mg/kg/d 6: D-gal+ Vitamin E at 100mg/kg/d. Aging induced by D-gal for 45 days via intraperitoneal. Myricitrin and Vitamin E administrated orally by gavage for the last 28 days. The blood glucose, insulin level, β-cell function, insulin resistance, hepatic enzymes, lipid profile, and histology of the liver, and pancreas were evaluated. D-gal injection increased the glucose (p<0.001) and insulin levels (p<0.01) compared to control group. Myricitrin (p<0.01) and Vitamin E (p<0.001) increased insulin and decreased blood glucose levels compared to D-gal group. Myricitrin had a similar impact on insulin levels to vitamin E. Insulin resistance induced in the D-gal group (p<0.001). Myricitrin reduced insulin resistance and increased β-cell function (p<0.01) compared to D-gal group. D-gal elevated (p<0.01) cholesterol, LDL and triglyceride level, myricitrin (p<0.001), and Vitamin E (p<0.05) were reduced. D-gal-induced aging causes the accumulation of RBCs, inflammation in the liver, and changes in the number and diameter of Langerhans islets in the pancreas. Myricitrin improved these D-gal effects. Myricitrin had the anti-diabetic and hepatoprotective effects on the aged mice induced by D-galactose.


Disparities in Colorectal Cancer Screening Practices in a Midwest Urban Safety-Net Healthcare System.
Although colorectal cancer screening (CRC) using stool-based test is well-studied, evidence on fecal immunochemical test (FIT) patterns in a safety-net healthcare system utilizing opportunistic screening is limited. We studied the FIT completion rates and adenoma detection rate (ADR) of positive FIT-colonoscopy (FIT-C) in an urban safety-net system. We performed a retrospective cross-sectional chart review on individuals ≥ 50 years who underwent CRC screening using FIT or screening colonoscopy, 09/01/2017-08/30/2018. Demographic differences in FIT completion were studied; ADR of FIT-C was compared to that of screening colonoscopy. Among 13,427 individuals with FIT ordered, 7248 (54%) completed the stool test and 230 (48%) followed up a positive FIT with colonoscopy. Increasing age (OR 1.01, CI 1.01-1.02), non-Hispanic Blacks (OR 0.87, CI 0.80-0.95, p = 0.002), current smokers (OR 0.84, CI 0.77-0.92, p < 0.0001), those with Medicaid (OR 0.86, CI 0.77-0.96, p = 0.006), commercial insurance (OR 0.85, CI 0.78-0.94, p = 0.002), CCI score ≥ 3 (OR 0.82, CI 0.74-0.91, p < 0.0001), orders by family medicine providers (OR 0.87, CI 0.81-0.94, p < 0.0001) were associated with lower completion of stool test. Individuals from low median household income cities had lower follow-up of positive FIT, OR 0.43, CI 0.21-0.86, p = 0.017. ADR of FIT-C was higher than that of screening colonoscopy. Adherence to CRC screening is low in safety-net systems employing opportunistic screening. Understanding demographic differences may allow providers to formulate targeted strategies in high-risk vulnerable groups.


Building functional materials for health care and pharmacy from microfluidic principles and Flow Focusing.
In this review, we aim at establishing a relationship between the fundamentals of the microfluidics technologies used in the Pharmacy field, and the achievements accomplished by those technologies. We describe the main methods for manufacturing micrometer drops, bubbles, and capsules, as well as the corresponding underlying physical mechanisms. In this regard, the review is intended to show non-specialist readers the dynamical processes which determine the success of microfluidics techniques. Flow focusing (FF) is a droplet-based method widely used to produce different types of fluid entities on a continuous basis by applying an extensional co-flow. We take this technique as an example to illustrate how microfluidics technologies for drug delivery are progressing from a deep understanding of the physics of fluids involved. Specifically, we describe the limitations of FF, and review novel methods which enhance its stability and robustness. In the last part of this paper, we review some of the accomplishments of microfluidics when it comes to drug manufacturing and delivery. Special attention is paid to the production of the microencapsulated form because this fluidic structure gathers the main functionalities sought for in Pharmacy. We also show how FF has been adapted to satisfy an ample variety of pharmaceutical requirements to date.


Detection of JC virus by polymerase chain reaction in cerebrospinal fluid from two patients with progressive multifocal leukoencephalopathy.
The polymerase chain reaction (PCR) was used to identify JC virus (JCV) in the cerebrospinal fluid of two patients with progressive multifocal leukoencephalopathy confirmed by brain biopsy. In addition, JCV viremia was demonstrated by PCR in one case. JCV detection in spinal fluid by PCR may be the first non-invasive technique available for the diagnostic confirmation of progressive multifocal leukoencephalopathy.


Myocardial strain pattern progress in patients with Coarctation of the Aorta undergoing aortic stenting.
Ventricular function evaluation in coarctation of the aorta (CoA) has become more sophisticated and precise with speckle tracking, revealing subclinical changes. However, CoA stenting treatment effects in on myocardial strain are still controversial. This study aimed to estimate the extent to which changes in left ventricular global longitudinal strain (LV GLS) occur in patients with CoA who undergo stenting. The study included 21 patients with CoA (median age: 15 years [8-39]) and 21 healthy individuals matched by age and gender. Clinical and echocardiographic evaluations were performed 1 day before, 6 months, and 1 year after stenting. Correlations between LV GLS and arm-leg gradient, isthmus gradient on echocardiogram, age at intervention, left ventricular mass, and ejection fraction were tested. Before treatment, patients with CoA had lower LV GLS than the control group (-18.4% ± 1.96 vs -21.5% ± 1.37; P < .01), showing significant increase to -19.4% ± 2.1 at 6 months and -20.7% ± 2.19 at 1 year, P < .001. Only 28.5% (6 patients) had preserved GLS before treatment, improving to 80.9% (17 patients) in 1 year. The only variable correlated with low LV GLS values before treatment was age at intervention (Spearman's index = -0.571; P = .007). Percutaneous therapy showed significant LV GLS improvement 12 months after aortic stenting. Older patients have lower GLS, suggesting that early intervention may have positive effects on preservation of LV systolic function.


Identification of ETV6-RUNX1-like and DUX4-rearranged subtypes in paediatric B-cell precursor acute lymphoblastic leukaemia.
Fusion genes are potent driver mutations in cancer. In this study, we delineate the fusion gene landscape in a consecutive series of 195 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP ALL). Using RNA sequencing, we find in-frame fusion genes in 127 (65%) cases, including 27 novel fusions. We describe a subtype characterized by recurrent IGH-DUX4 or ERG-DUX4 fusions, representing 4% of cases, leading to overexpression of DUX4 and frequently co-occurring with intragenic ERG deletions. Furthermore, we identify a subtype characterized by an ETV6-RUNX1-like gene-expression profile and coexisting ETV6 and IKZF1 alterations. Thus, this study provides a detailed overview of fusion genes in paediatric BCP ALL and adds new pathogenetic insights, which may improve risk stratification and provide therapeutic options for this disease.


Combination treatment with hypofractionated radiotherapy plus IL-2/anti-IL-2 complexes and its theranostic evaluation.
Immunogenic radiotherapy (RT) can act synergistically with immune checkpoint blockers (ICBs). However, alternatives are needed for non-responding patients and those with pre-existing or ICB-induced autoimmune symptoms. Combination of RT with IL-2 could be an alternative. But IL-2 has a short half-life, and, by binding to its high-affinity receptor, it strongly stimulates immunosuppressive CD4+ Tregs and seems to promote potentially life-threatening vascular leakage. IL-2/anti-IL-2 complexes (IL-2c), which bind to the low-affinity receptor, have been reported to circumvent these disadvantages but they have not yet been thoroughly tested in conjunction with radiotherapy. We evaluated, in three mouse models, the antitumoral effects induced by hypofractionated RT (hRT) plus IL-2c. We also used non-invasive imaging with a newly developed PET tracer based on therapeutically active IL-2c and a PD-L1 PET tracer for the theranostic evaluation of the treatment and its side effects. Treatment of mice bearing established B16 melanomas with hRT + IL-2c was superior to hRT + uncomplexed IL-2 or hRT alone; IL-2c alone was not effective. hRT + IL-2c was also synergistic in mice bearing C51 colon carcinomas or 4T1 mammary carcinomas. The better antitumor response correlated with increased tumor-specific CD8+ T cells and NK cells, but not CD4+ Tregs, in the irradiated tumor and in lymphoid organs. With the new PET tracer, we visualized the whole-body distribution of IL-2c and the bound receptors in naïve mice and tumor-bearing mice. Surprisingly, the tumor uptake was non-specific and only moderate. This prompted experiments demonstrating that specific IL-2c binding in the tumor is limited by IL-2 secreted by tumor-resident effector cells and that extratumorally expanded T and NK cells can infiltrate the irradiated tumor, which suggests that systemic immune activation considerably contributed to the reduction of tumor growth. Lastly, we show that a side effect of IL-2c treatment - a quite dramatic non-specific expansion of CD8+ T and NK cells - is only transient, and we visualized the associated splenomegaly as well as side effects on liver and lung by contrast-enhanced CT and PD-L1 PET. Our results show that the combination of immunogenic RT with IL-2c that are directed towards the low-affinity IL-2 receptor can be synergistic and more effective than the combination with uncomplexed IL-2. In addition, our theranostic evaluation provided insights into the mechanism of action and the side effects of IL-2c treatment.


Astonishing diversity of natural surfactants: 4. Fatty acid amide glycosides, their analogs and derivatives.
FA amide glycosides are of great interest, especially for the medicinal and pharmaceutical industries. These biologically active natural surfactants are good prospects for future chemical preparation of compounds useful as antibiotics, anticancer agents, or for industry. More than 200 unusual and interesting natural surfactants, including their chemical structures and biological activities, are described in this review article.


"You felt like a prisoner in your own self, trapped": the experiences of Aboriginal people with acquired communication disorders.
Aboriginal Australians are under-represented in brain injury rehabilitation services despite a high incidence of both stroke and traumatic brain injury in this population. This study aimed to explore the experiences of Aboriginal Australian adults with acquired communication disorders (ACDs) after brain injury for the first time to inform the development of accessible and culturally secure service delivery models. Semi-structured interviews were undertaken with 32 Aboriginal people who had experienced a brain injury resulting in ACDs (aged 35-79 years) and 18 family members/carers across Western Australia. Thematic analysis identified common themes across participants. Overall themes related to communication (both related to the communication disorder and general healthcare interactions), health and social contexts, recovery, and support, being away from family and country, knowledge and beliefs about brain injury, and follow-up. An increase in healthcare staff's appreciation of the health and social contexts of Aboriginal people after brain injury is needed in order to improve communication with Aboriginal patients and the ability to offer accessible rehabilitation services. Ongoing support is required, with cultural identity noted as key to ensuring cultural security and ultimately recovery. Involvement of family and other Aboriginal people in recovery processes, as well as access to relevant Aboriginal languages and proximity to ancestral lands is central.Implications for rehabilitationAcknowledgment of cultural identity and strengths through involvement of extended family and Aboriginal Hospital Liaison Officers, access to language and proximity to country all central to rehabilitation planning for Aboriginal people after brain injury.Cultural security training for rehabilitation staff is recommended focusing on clear two-way communication skills to make medical information accessible for Aboriginal patients and to listen to patients' concerns in a way that respects cultural context.Information regarding practical support and implications for ongoing management of life after brain injury (for the person and their family) is essential, and should supplement the medical-related information provided.Follow-up post discharge from hospital best facilitated through establishing contact with local Aboriginal community through Aboriginal community controlled health services, community elders, and Aboriginal health workers across organisations.


Forward masking in the medial nucleus of the trapezoid body of the rat.
Perception of acoustic stimuli is modulated by the temporal and spectral relationship between sound components. Forward masking experiments show that the perception threshold for a probe tone is significantly impaired by a preceding masker stimulus. Forward masking has been systematically studied at the level of the auditory nerve, cochlear nucleus, inferior colliculus and auditory cortex, but not yet in the superior olivary complex. The medial nucleus of the trapezoid body (MNTB), a principal cell group of the superior olive, plays an essential role in sound localization. The MNTB receives excitatory input from the contralateral cochlear nucleus via the calyces of Held and innervates the ipsilateral lateral and medial superior olives, as well as the superior paraolivary nucleus. Here, we performed single-unit extracellular recordings in the MNTB of rats. Using a forward masking paradigm previously employed in studies of the inferior colliculus and auditory nerve, we determined response thresholds for a 20-ms characteristic frequency pure tone (the probe), and then presented it in conjunction with another tone (the masker) that was varied in intensity, duration, and frequency; we also systematically varied the masker-to-probe delay. Probe response thresholds increased and response magnitudes decreased when a masker was presented. The forward suppression effects were greater when masker level and masker duration were increased, when the masker frequency approached the MNTB unit's characteristic frequency, and as the masker-to-probe delay was shortened. Probe threshold shifts showed an exponential decay as the masker-to-probe delay increased.


Nursing Students and Nurses' Recommendations Aiming at Improving the Development of the Humanistic Caring Competency.
Most nursing education programs prepare their students to embody humanism and caring as it is expected by several regulatory bodies. Ensuring this embodiment in students and nurses remains a challenge because there is a lack of evidence about its progressive development through education and practice. This manuscript provides a description of nursing students' and nurses' recommendations that can foster the development of humanistic caring. Interpretive phenomenology was selected as the study's methodological approach. Participants (n = 26) were recruited from a French-Canadian university and an affiliated university hospital. Data was collected through individual interviews. Data analysis consisted of an adaptation of Benner's (1994) phenomenological principles that resulted in a five-stage interpretative process. The following five themes emerged from the phenomenological analysis of participants' recommendations: 1) pedagogical strategies, 2) educators' approach, 3) considerations in teaching humanistic caring, 4) work overload, and 5) volunteerism and externship. The findings suggest the existence of a challenge when using mannikins in high-fidelity simulations with the intention of developing humanistic caring. The findings also reaffirm the importance of giving concrete and realistic exemplars of humanistic caring to students in order to prevent them from making "communication" synonymous to "humanization of care".


[Lunocapitate shortening arthrodesis after scaphoid and triquetrum resection: treatment of Watson stage III advanced scaphoid periarthrosis].
Between 1993 and 2000, 16 patients with scaphoid periarthrosis (Watson stage III) were treated by lunocapitate shortening arthrodesis after resection of the scaphoid and triquetrum. These patients were reviewed to evaluate outcome. Thirteen patients had antecedent trauma with scaphoid nonunion (SNAC, n=9) or scapholunate advanced collapse (SLAC, n=4). The remaining three patients had chondrocalcinosis. Clinical and radiological results were encouraging at a mean follow-up of 3 years (1-7 years). Fourteen patients were very satisfied and two experienced partial improvement. Persistent pain relief as well as 11% improved muscle power was achieved. Mean improvement of joint motion was 12 degrees. This technique has shown better global results than 4-corner arthrodesis. It can be applied if capitate arthrodesis is performed. Results are comparable to those of proximal row carpectomy.


Rebleeding of an angiographically healed aneurysm.
An angiographically "healed" aneurysm, which rebled, is reported. Although the angiographic control was negative, the patient was operated upon, and the aneurysmal sac was patent.


What Are the Short-term Benefits and Potential Harms of Therapeutic Modalities for the Management of Overactive Bladder Syndrome in Women? A Review of Evidence Under the Auspices of the European Association of Urology, Female Non-neurogenic Lower Urinary Tract Symptoms Guidelines Panel.
Overactive bladder syndrome (OAB) is highly prevalent among women and has a negative impact on their quality of life. The current available treatments for OAB symptoms include conservative, pharmacological, or surgical modalities. To provide an updated contemporary evidence document regarding OAB treatment options and determine the short-term effectiveness, safety, and potential harms of the available treatment modalities for women with OAB syndrome. The Medline, Embase, and Cochrane controlled trial databases and clinicaltrial.gov were searched for all relevant publications up to May 2022. The risk of bias assessment followed the recommended tool in the Cochrane Handbook for Systematic Reviews of Interventions, and quality of evidence was assessed using the modified Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. A meta-analysis was performed where appropriate. Antimuscarinics and beta-3 agonists were significantly more effective than placebo across most outcomes, with beta-3 agonists being more effective at reducing nocturia episodes and antimuscarinics causing significantly higher adverse events. Onabotulinumtoxin-A (Onabot-A) was more effective than placebo across most outcomes, but with significantly higher rates of acute urinary retention/clean intermittent self-catheterisation (six to eight times) and urinary tract infections (UTIs; two to three times). Onabot-A was also significantly better than antimuscarinics in the cure of urgency urinary incontinence (UUI) but not in the reduction of mean UUI episodes. Success rates of sacral nerve stimulation (SNS) were significantly higher than those of antimuscarinics (61% vs 42%, p = 0.02), with similar rates of adverse events. SNS and Onabot-A were not significantly different in efficacy outcomes. Satisfaction rates were higher with Onabot-A, but with a higher rate of recurrent UTIs (24% vs 10%). SNS was associated with 9% removal rate and 3% revision rate. Overactive bladder is a manageable condition, with first-line treatment options including antimuscarinics, beta-3 agonists, and posterior tibial nerve stimulation. Second-line options include Onabot-A bladder injections or SNS. The choice of therapies should be guided by individual patient factors. Overactive bladder is a manageable condition. All patients should be informed and advised on conservative treatment measures in the first instance. The first-line treatment options for its management include antimuscarinics or beta-3 agonists medication, and posterior tibial nerve stimulation procedures. The second-line options include onabotulinumtoxin-A bladder injections or sacral nerve stimulation procedure. The therapy should be chosen based on individual patient factors.


Dopamine-dependent interactions between limbic and prefrontal cortical plasticity in the nucleus accumbens: disruption by cocaine sensitization.
The prefrontal cortex and the hippocampus exhibit converging projections to the nucleus accumbens and have functional reciprocal connections via indirect pathways. As a result, information processing between these structures is likely to be bidirectional. Using evoked potential measures, we examined the interactions of these inputs on synaptic plasticity within the accumbens. Our results show that the direction of information flow between the prefrontal cortex and limbic structures determines the synaptic plasticity that these inputs exhibit within the accumbens. Moreover, this synaptic plasticity at hippocampal and prefrontal inputs selectively involves dopamine D1 and D2 activation or inactivation, respectively. Repeated cocaine administration disrupted this synaptic plasticity at hippocampal and prefrontal cortical inputs and goal-directed behavior in the spatial maze task. Thus, interactions of limbic-prefrontal cortical synaptic plasticity and its dysfunction within the accumbens could underlie complex information processing deficits observed in individuals following psychostimulant administration.


Do patients with intake of drugs labelled as sleep disturbing really sleep worse? A population based assessment from the Heinz Nixdorf Recall Study.
The sleep disturbing effect of many drugs is derived from clinical trials with highly selected patient collectives. However, the generalizability of such findings to the general population is questionable. Our aim was to assess the association between intake of drugs labelled as sleep disturbing and self-reported nocturnal sleep disturbances in a population-based study. We used data of 4221 participants (50.0% male) aged 45 to 75 years from the baseline examination of the Heinz Nixdorf Recall Study in Germany. The interview provided information on difficulties falling asleep, difficulties maintaining sleep and early morning arousal. We used the summary of product characteristics (SPC) for each drug taken and assigned the probability of sleep disturbances. Thereafter, we calculated cumulative probabilities of sleep disturbances per subject to account for polypharmacy. We estimated prevalence ratios (PR) using log Poisson regression models with robust variance. The adjusted PRs of any regular nocturnal sleep disorder per additional sleep disturbing drug were 1.01 (95% confidence interval (CI) 0.97, 1.06) and 1.03 (95% CI 1.00, 1.07) for men and women, respectively. Estimates for each regular nocturnal sleep disturbance were similarly close to 1. PRs for regular nocturnal sleep disturbances did not increase with rising cumulative probability for drug-related sleep disturbances. SPC-based probabilities of drug-related sleep disturbances showed barely any association with self-reported regular nocturnal sleep disturbances. We conclude that SPC-based probability information may lack generalizability to the general population or may be of limited data quality.


Pollution evaluation and source identification of heavy metals in soil around steel factories located in Lanshan District, Rizhao City, eastern China.
More than 40 enterprises have settled in the constructed steel-supporting industrial park adjacent to the Yellow Sea in Lanshan District, Rizhao City, eastern China. The concentration of heavy metals in the soil around steel factories often exceeds the limit specified by the national environmental agency. In this study, nine metals (Cu, Zn, Pb, Cd, Cr, Ni, Mn, Fe, and Mg) in the soil around the steel-supporting industrial park were examined, and 100 soil samples were analyzed. The pollution characteristics and sources of these heavy metals were obtained via pollution index analysis, potential ecological risk evaluation, geostatistical analysis, and multivariate statistical analysis combined with a positive matrix factorization (PMF) model. The results indicated that the heavy metals showed varying accumulation levels, among which Cd, Ni, and Pb were the major heavy metals greatly influencing the soil quality. The area around the steel factories exhibited heavy pollution and a high ecological risk, and Ni and Cd were the main risk factors. The soil at the steel factories and that in the southeastern and southwestern parts of the study area attained higher heavy metal element contents than those in the soil in other parts. PMF analysis confirmed that Cu, Pb, and Cd originated from mixed agricultural and traffic sources. Mn was related to natural sources. Cr and Ni likely resulted from atmospheric deposition, and Zn, Cd, Fe, and Mg were mainly associated with industrial materials, with these four sources accounting for 32.68%, 12.2%, 27.57%, and 27.54%, respectively, of the total metal content. This study could facilitate the investigation, evaluation, and source identification of soil heavy metal pollution in industrial regions and surrounding areas of Lanshan District, Rizhao City.


A reminder reduces urinary catheterization in hospitalized patients.
Indwelling urinary catheters are placed in up to 25% of hospitalized patients and are a leading cause of hospital-acquired infection. Duration of catheterization is the dominant risk factor for hospital-acquired urinary tract infection. Physicians are often unaware that their patients have a urinary catheter, and these "forgotten" catheters are frequently unnecessary. A controlled trial, using a pretest-posttest design, was conducted on four hospital wards at an academic medical center. A simple written reminder was designed to aid the hospitalized patient's team in remembering that the patient had a urinary catheter. Two of the four wards were assigned to the intervention group, and two served as controls. A research nurse monitored the urethral catheter status of each patient daily. A total of 5,678 subjects were evaluated. After adjusting for age, sex, and length of stay, the average proportion of time patients were catheterized increased by 15.1% in the control group but decreased by 7.6% in the intervention group in the intention-to-treat analysis (p = .007). There was no significant difference in urethral recatheterizations between intervention and control groups. The hospital cost savings provided by the intervention offset the necessary costs of this nurse-based intervention. CONCLUSIORN: In the approximately 90% of U.S. hospitals currently without computerized order-entry systems, a written reminder should be considered as one method for improving the safety of hospitalized patients.


The effects of myostatin mutation on the tibia bone quality in female Japanese quail before and after sexual maturation.
In the modern layer industry, improvement of bone quality is one of the prior tasks to solve from economic and welfare standpoints. In addition to nutritional and environmental factors, genetic factors have been considered major factors regulating bone quality in layers but are yet to be fully investigated due to limitations on available animal models. Initially, the myostatin (MSTN) gene was genetically edited in quail to investigate the effect of MSTN mutation on economic traits in meat producing poultry species. In the current study, the function of the MSTN gene on regulation of bone quality in layers was investigated using MSTN mutant female quail as an animal model. Tibia bones were collected from wild-type (WT) and MSTN mutant female quail at 5 wk old and 4 mo old, representing prelaying and actively laying stages, respectively. Left tibia bones were analyzed by microcomputed tomography scanning to evaluate the architectural characteristics, while bone breaking strength (BBS) was measured using right tibia bones. At 5 wk of age, MSTN mutant female quail showed higher BBS and values on parameters related to bone quality such as bone mineral contents (BMC), bone mineral density (BMD), bone volume (BV), and/or trabecular bone thickness in whole diaphysis, whole metaphysis, and metaphyseal trabecular bone, compared to WT female quail. Although BBS and BMD became similar between the 2 groups at 4 mo of age, higher TV and TS in whole metaphysis and higher BMC and TV in whole diaphysis of MSTN mutant group compared to those of WT group suggested that the improved tibia bone quality by MSTN mutation before sexual maturation lasted to a certain degree even after sexual maturation. The use of the MSTN mutant female model provided new insights into genetic regulation on female quail bone quality depending on physiological changes.


Inhibitory control in trauma-exposed youth: A systematic review.
The aim of this systematic review was to provide insight in inhibitory control (prepotent response inhibition and interference control) in trauma-exposed youth from a developmental perspective and exploring the effects of prolonged stress. A systematic search was conducted, resulting in 1722 abstracts. Of those, 33 studies met inclusion criteria. Twelve studies measured prepotent response inhibition (Go/no-go and Stop-signal task), 20 studies measured interference control (Flanker and Stroop task), and one measured both. Some studies indeed found evidence for prolonged trauma exposure impeding both subcomponents of inhibitory control, although others did not. At a later age, inhibitory control problems on task performance seem to disappear. However, distinct patterns of brain activity may suggest that those individuals employ compensation strategies. Together, the findings may suggest that non-specific inhibitory control problems occur after prolonged trauma exposure, with older youth possibly employing compensation strategies on the tasks. Future studies may provide a clearer picture of the compensation strategies and the circumstances in which they become visible.


Binding ability of Clostridium botulinum neurotoxin to the synaptosome upon treatment of various kinds of the enzymes.
The binding ability of Cl. botulinum neurotoxin to synaptosomes upon treatment with various enzymes (neuraminidase, trypsin, and beta-bungarotoxin containing phospholipase A2 activity) was studied. When synaptosomes were treated with neuraminidase, their ability to bind toxin decreased; trypsin and beta-bungarotoxin had slightly week or no effect. The decrease in toxin-binding ability of synaptosomes was paralleled by a release of sialic acid from the synaptosomes by the neuraminidase treatment. The toxin-binding ability of synaptosomes treated with neuraminidase was lower than untreated ones at a high concentration of sodium chloride. The binding of the toxin to synaptosomes occurred at least at the two types of structural sites, one site which contained sialic acid, and other site which was sensitive to high ionic strength. It may be possible that another binding state except these is present at the synapse.


Unusual 'spike-wave stupor' in a patient with manic-depressive psychosis treated with amitriptyline.
'Spike-wave stupor' was observed in a 58-year-old male patient with manic-depressive psychosis. Almost continuous atypical spike-wave activity was seen in conjunction with a stuporous episode with stereotyped automatism. Intravenous diazepam ended both the electroencephalographic epileptiform discharges and the clinical stupor. Before and during this episode the patient was treated with an average-dose amitriptyline monotherapy. There was no family history of epileptic seizures. The patient had had electroconvulsive therapy. The history suggests that the analeptic property of amitriptyline induced the 'spike-wave stupor' in this patient.


Hypoxia activates the cyclin D1 promoter via the Jak2/STAT5b pathway in breast cancer cells.
Hypoxia, a common consequence of solid tumor growth in breast cancer or other cancers, serves to propagate a cascade of molecular pathways which include angiogenesis, glycolysis, and various cell-cycle control proteins. As we have shown previously, hypoxia activates STAT5 (signal transducer and activator of transcription 5) and increases its binding activity to the GAS element in mammary epithelial cells. In this study we attempted to elucidate the mechanism by which cyclin D1 is regulated by the STAT5 protein under hypoxic conditions. Our data demonstrate that hypoxia (2% O(2)) or desferrioxamine (DFO) induces tyrosine and serine phosphorylation of STAT5 in human breast cancer cells (MCF-7) and mammary epithelial cells (HC11). Imunoprecipitation and subsequent Western analysis showed that Jak2 leads to the tyrosine phosphorylation and activation of STAT5a or STAT5b under hypoxic conditions. Using a transfected COS-7 cell model system, we demonstrate that the activity of a cyclin D1 promoter-luciferase construct increased under hypoxic conditions or DFO treatment. The activity of the STAT5b/cyclin D1 promoter increased significantly by 12 h of hypoxia, whereas the activity of the STAT5a/cyclin D1 promoter was unaffected under hypoxic conditions. These increases in promoter activity are predominantly mediated by the Jak2/STAT5b signaling pathway. We have shown by EMSA that hypoxia induces STAT5 to bind to the cyclin D1 promoter (GAS-1) in MCF-7 and HC11 cells. These data suggest that STAT5b may mediate the transcriptional activation of cyclin D1 after hypoxic stimulation.


Efficient enzymatic synthesis of α-keto acids by redesigned substrate-binding pocket of the l-amino acid deaminase (PmiLAAD).
In our previous study, we produced α-keto acids by using an L-amino acid deaminase PmiLAAD (wide-type) from Proteus mirabilis, however, the catalytic efficiency was low due to its low substrate affinity. In this study, protein engineering of PmiLAAD was performed to improve the α-keto acid production. PmiLAAD was engineered by iterative CASTing to improve its catalytic performance. The four mutant PmiLAAD-SAVS (PmiLAAD-Phe93Ser-Pro186Ala- Met394Val-Phe184Ser) with 6.6 -fold higher specific activity compared with that of wild-type PmiLAAD has been obtained by high-throughput screening. Comparative kinetics analysis showed that the four mutant PmiLAAD-SAVS had a higher substrate-binding affinity and catalytic efficiency than that of PmiLAAD wild-type. The Km, kcat, and kcat/Km values of the PmiLAAD(SAVS) variant was better (-42.7%, 75.11%, and 85.79%, respectively) than the corresponding values of PmiLAAD wild type. Finally, the whole cell biocatalyst E. coli-pETDuet-1-PmiLAAD(SAVS) has been applied to α-keto acids production. The conversion rate of L-phenylalanine reached 99% by whole-cell biocatalyst E. coli-pETDuet-1-PmiLAAD(SAVS). The conversion of (D/L)-4-phenylalanine was reached 49.5% after 7 h by whole-cell biocatalyst E. coli-pETDuet-1-PmiLAAD(SAVS), while the conversion of E. coli-pETDuet-1-PmiLAAD (wild type) was only 18% after an extension of the reaction time (24 h). This study has developed a robust whole-cell E. coli biocatalyst for α-keto acids production by protein engineering, and this strategy may be useful for the construction of other biotransformation biocatalysts.


Optimising wheat straw alkali-organosolv pre-treatment to enhance hemicellulose modification and compatibility with reinforcing fillers.
Hemicellulose acetylation, filler compatibility and film hydrophobicity were enhanced by optimising alkali-catalysed organosolv treatment conditions for wheat straw before hemicellulose extraction. Two optimum (OPT) conditions were established by varying organosolv components' concentrations [ethanol (EC) (50-80%) and NaOH (1-13%)], and time (2-6 h), in a Box-Behnken experimental design. The OPT1 (1% NaOH/50% EC/6h) that enhanced acetylation and filler compatibility, and OPT2 (13% NaOH/80% EC/5h) that enhanced hydrophobicity by minimising degree of acetylation (DS), uronic acid content and arabinose/xylose ratio. The films made from OPT2 hemicellulose had higher water contact angle (68.1°) than OPT1 hemicellulose (39.90°). However, OPT1 hemicellulose had a higher DS (1.7 vs 0.4), and their acetylated nanocellulose reinforced films had higher tensile strength (10.59 vs 4.87 MPa) and Young modulus (590.15 vs 323.64 MPa) than OPT2 hemicellulose. Therefore, hemicellulose acetylation, hydrophobicity and filler interaction can be engineered by manipulating the organosolv treatment conditions.


Practice patterns among oncologists participating in the oncology care model after three years.
The Oncology Care Model (OCM) incentivized care coordination and cost-efficiency and has been associated with short-term care reductions, but its multi-year associations are less well-studied. We used monthly provider-level claims data spanning nearly five years between July 1 st, 2014 and May 30th, 2019 from a large community oncology practice network where roughly half of the practices participated in the OCM. The key outcome measures were monthly mean office visits, costs, and buy-and-bill drug costs among prostate, colon, breast, and lung cancers. We conducted two quasi-experimental analyses: an event study, which measures the monthly association of providing care in an OCM relative to a non-participating practice, and a difference-in-differences model, which summarizes the event study results into post-launch average estimates. We controlled for mean differences between practices, providers, and patient. The event study analysis shows similar pre-period estimates and trends for each cancer. The difference-in-differences estimates for office visits are statistically significant for each cancer: 33 percentage point reductions in prostate cancer (95 % CI: -0.66 to 0.00; p = 0.05), 22 percentage point reductions in colon cancer (95 % CI: -0.48 to 0.04; p = 0.09), 21 percentage point reductions in breast cancer (95 % CI: -0.45 to 0.02; p = 0.08), and 24 percentage point reductions in lung cancer (95 % CI: -0.49 to 0.00; p = 0.05). Monthly prostate cancer costs also reduced by $505 (95 % CI: -$1108 to $99; p = 0.10). Our results suggest that the OCM was associated with relative reductions in office visits and, for prostate cancer, in overall costs too. These associations generally decreased within the first year of launch and sustained through roughly two years. Novel payment models that incentivize care coordination and cost-efficiency like the OCM may modestly yet sustainably reduce office visits and overall costs.


Minor anomalies: can they predict specific major defects? A study based on 23 major and 14 minor anomalies in over 25,000 newborns with birth defects.
Minor anomalies (mAs) are morphological features with little clinical relevance that have been mentioned as possible predictors of major defects (MDs). To identify the preferential associations between selected MDs and mAs and to establish if mAs can serve as predictors for specific MDs. Information of newborns with birth defects was obtained from the ECLAMC (Latin American Collaborative Study of Congenital Malformations) database. The sample consisted of 27,247 live- and stillborn newborns with multiple malformations that included at least one of the selected MDs or mAs. The odds ratio and predictive values were calculated for significant associations, and concurrence rates in first degree relatives. A total of 33 significant minor-major associations were identified. Single umbilical artery (SUA) and preauricular tags were the most frequent mAs; the former was associated with 10 MDs, the latter only with microtia. The highest positive predictive value was shown by SUA for anal atresia. Newborns with preauricular tags had significantly more relatives with microtia than expected. No new relevant associations between MDs and mAs were identified and few mAs seem to serve as predictors for specific MDs in the same newborn. However, preauricular tags can predict the occurrence of microtia in other family members.


Synthesis and fluorescent study of 5-phenyl furocoumarin derivatives as vasodilatory agents.
Two series of 5-phenyl furocoumarin derivatives were designed and prepared based on our previous research. All new compounds were characterized by (1)H NMR, (13)C NMR and mass spectra. Furthermore, they were screened for their vasodilatory activity on the mesenteric artery of Sprague-Dawley rats, and they all presented with moderate vasodilatory activity. Fluorescent properties of the target compounds were tested in methanol. The fluorescence variation of 4a was investigated in different solvents, various pH and the migration time was determined. All results indicated that this type of fluorescent compound can be used as vasodilatory agents and probes simultaneously after further structural modifications.


Tools for the cryo-EM gold rush: going from the cryo-EM map to the atomistic model.
As cryo-electron microscopy (cryo-EM) enters mainstream structural biology, the demand for fitting methods is high. Here, we review existing flexible fitting methods for cryo-EM. We discuss their importance, potential concerns and assessment strategies. We aim to give readers concrete descriptions of cryo-EM flexible fitting methods with corresponding examples.


Abnormal low density lipoproteins in children with familial hypercholesterolemia--effect of polyanion exchange resins.
In 20 children and adolescents with familial Type II a hyperlipoproteinemia, serum lipids and lipoproteins were examined before and during treatment with polyanion exchange resins. The composition of LDL was compared to that of helthy siblings. The patients were given Colestyramine (0.6 g/kg body weight) and Colestipol (0.5 g/kg body weight) in a cross-over study for 8 weeks each, after they had been under dietary treatment for at least 12 months. In 6 children, drug treatment had to be stopped due to side-effects. The most common complaints were gastrointestinal discomfort and constipation. Cholesterol, triglycerides and phopholipids were measured in whole serum and cholesterol, triglycerides and Apolipoprotein-B in isolated lipoprotein fractions after ultracentrifugation. Apo-B was determined by radial immunodiffusion. The Apo-B: cholesterol ratio in whole serum and in the LDL fraction was identical in the patients and in the controls. The LDL triglyceride: Apo-B ratio, however, was about 50% lower in the patients. This abnormal LDL composition was not altered by therapy with polyanion exchange resins. HDL cholesterol levels were significantly lower in the patients than in healthy children, and remained low during therapy. The decrease of total and LDL cholesterol (25%) and Apo-B (20%) was similar under both Colestipol and Colestyramine. Triglycerides and phospholipids showed no significant changes in therapy.


Scopolamine-induced muscarinic supersensitivity in normal man: changes in sleep.
Scopolamine (6 microgram/kg) was administered on 3 consecutive mornings to normal human subjects. Sleep recordings obtained at night (when the central anticholinergic effect of the morning scopolamine was no longer present) indicated a significant reduction in latency to REM-sleep onset on the nights following the second and third injections. This effect is opposite to the direct pharmacological action of nighttime administration of scopolamine (i.e., prolongation of REM latency). In addition, total sleep time and sleep efficiency were reduced, and sleep latency was increased. Furthermore, scopolamine pretreatment on 2 consecutive mornings also potentiated the REM-inducing effect of arecoline, a central muscarinic agonist. These data are consistent with the development of cholinergic supersensitivity following cholinergic blockade.


Targeting PI3K/AKT/mTOR pathway to enhance the anti-leukemia efficacy of venetoclax.
The treatment of acute myeloid leukemia (AML) is developing towards "targeted therapy", which faces challenges such as low sensitivity and drug resistance. Therefore, targeted drugs need to be used in combination with other drugs to overcome clinical problems. AML cells and animal models were used to determine the synergistic anti-leukemic effect of Dactolisib (BEZ235) and Venetoclax (ABT199) and explore its mechanism. In vitro experiments, we used cell counting kit-8 (CCK8), flow cytometry, real-time quantitative PCR (qPCR), and Western blot to detect the anti-leukemic effects of ABT199 and BEZ235. In vivo experiments, female nude mice were injected subcutaneously with THP-1 cells to form tumors, evaluate the combined effect of ABT199 and BEZ235 by indicators such as tumor size, tumor weight, Ki67 and cleaved-Caspase3 staining. The mice's body weight and HE staining were used to evaluate the liver injury and adverse drug reactions. The combination of BEZ235 and ABT199 has a synergistic effect through promoting apoptosis and inhibiting proliferation. The BEZ235 increased the drug sensitivity of ABT199 by reducing the MCL-1 protein synthesis and promoted the degradation of MCL-1 protein, which is considered as the mechanism of reversing ABT199 resistance. Furthermore, the BEZ235 and ABT199 can synergistically enhance the inhibition of PI3K/AKT/mTOR pathway. The combination of BEZ235 and ABT199 exhibits a synergistic anti-tumor effect in AML by down-regulating MCL-1 protein.


Reducing blood sample hemolysis in the emergency department using S-Monovette® in aspiration mode.
Blood sample hemolysis continues to be a significant problem in clinical practice. In vitro hemolysis rates up to 77% have been reported in literature. The use of manual aspiration techniques for blood sampling has previously been shown to reduce the burden of erythrocyte injury in the pre-analytical phase compared to the vacuum collection technique. This study compares the hemolysis rates between two blood sampling methods: 5.0 ml BD Vacutainer® SST™ (BDV) and 4.9 ml S-Monovette® serum gel tubes in aspiration mode (SMA). This was a prospective randomised controlled study conducted in an Emergency department (ED). A convenience sample of 191 adult patients, aged 18-90 years old, presenting at the ED and requiring blood samples for serum electrolyte was included in the study. Paired blood samples were obtained through an intravenous cannula from each patient with randomised order of blood draw using SMA or BDV. Patient data was obtained and hemolysis index (HI), serum lactate dehydrogenase (LDH), and serum potassium (K) levels measured. The adjusted mean HI (35.2 vs 21.5 mg/dL, p < 0.001), serum K (4.38 vs 4.16 mmol/L, p < 0.001) and LDH levels (259.6 vs 228.4 U/L, p < 0.001) were significantly higher in blood samples taken using BDV compared to SMA. The frequency of severely hemolyzed (>150 mg/dL) samples was also higher in blood collected using BDV (16.2%) compared to SMA (0%). The burden of hemolysis in blood samples taken from IV cannulae can be effectively reduced with the use of manual aspiration using the S-Monovette® blood collection system as compared to BD-Vacutainer.


The accuracy of outcome prediction models for childhood-onset epilepsy.
Two large prospective cohort studies of childhood epilepsy (Nova Scotia and the Netherlands) each developed a statistical model to predict long-term outcome. We sought to evaluate the accuracy of a prognostic model based on the two studies combined. Analyses with classification tree models and stepwise logistic regression produced predictive models for the combined dataset and the two separate cohorts. The resulting models were then externally validated on the opposite cohort. Remission was defined as no longer receiving daily medication for any length of time at the end of follow-up. The combined cohorts yielded 1,055 evaluable patients. At the end of follow-up (>or=5 years in >96%), 622 (59%) were in remission. By using the combined data, the classification tree model and the logistic regression model predicted the outcome correctly in approximately 70%. The classification tree model split the data on epilepsy type and age at first seizure. Predictors in the logistic regression model were: seizure number before treatment, age at first seizure, absence seizures, epilepsy types of symptomatic generalized and symptomatic partial, preexisting neurologic signs, intelligence, and the combination of febrile seizures and cryptogenic partial epilepsy. When the prediction models from each cohort were cross-validated on the opposite cohort, the outcome was predicted slightly less accurately than did the model from the combined data. Based on currently available clinical and EEG variables, predicting the outcome of childhood epilepsy may be difficult and appears to be incorrect in about one of every three patients.


A Clinical Genomics-Guided Prioritizing Strategy Enables Selecting Proper Cancer Cell Lines for Biomedical Research.
Selecting appropriate cell lines to represent a disease is crucial for the success of biomedical research, because the usage of less relevant cell lines could deliver misleading results. However, systematic guidance on cell line selection is unavailable. Here we developed a clinical Genomics-guided Prioritizing Strategy for Cancer Cell Lines (CCL-cGPS) and help to guide this process. Statistical analyses revealed CCL-cGPS selected cell lines were among the most appropriate models. Moreover, we observed a linear correlation between the drug response and CCL-cGPS score of cell lines for breast and thyroid cancers. Using RT4 cells selected by CCL-GPS, we identified mebendazole and digitoxin as candidate drugs against bladder cancer and validate their promising anticancer effect through in vitro and in vivo experiments. Additionally, a web tool was developed. In conclusion, CCL-cGPS bridges the gap between tumors and cell lines, presenting a helpful guide to select the most suitable cell line models.


Risk factors predicting upper urinary tract deterioration in children with spinal cord injury.
The aim of this study is to determine the risk factors predicting upper urinary tract (UUT) deterioration in children with spinal cord injury (SCI). The medical records of 108 children with SCI who were referred to our unit between 1996 and 2018 were retrospectively reviewed. The data included general patient demographics, SCI characteristics, bladder management methods, presence of urinary tract infection, radiological evaluation of the UUT and lower urinary tract (LUT), and videourodynamic findings. The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff values of the maximum detrusor pressure during filling and the bladder volume ratio (BVR) for predicting UUT deterioration. Multivariate analyses were used to determine the risk factors predicting UUT deterioration. Complete data were available for 76 children. The median patient age was 15 years (2-17). The leading causes of SCI were motor vehicle accidents (44%) and fall (33%). UUT deterioration was identified in 33 patients (43%). Iatrogenic SCI etiology, abnormal radiological LUT findings, and detrusor pressures greater than 70 cmH2 O were found to be independent risk factors for UUT deterioration using regression analysis. In addition, ROC analysis revealed that a BVR less than 0.7 was the cutoff value for UUT deterioration in children with SCI. Abnormal radiological LUT findings, iatrogenic SCI etiology, detrusor pressure greater than 70 cmH2 O, and a BVR less than 0.7 were independent risk factors for UUT deterioration in children with SCI.


Transgenic expression of CECR1 adenosine deaminase in mice results in abnormal development of heart and kidney.
Cat eye syndrome is a rare developmental defect associated with duplication of chromosome 22q11. The patients demonstrate specific abnormalities of heart, kidney, and eye. Here we attempted to produce a model for this defect by expressing CECR1 adenosine deaminase, a gene duplicated in cat eye syndrome patients, in mice. The transgenic mice expressed CECR1 under the control of either beta-actin promoter for ubiquitous expression or myosin heavy chain for heart-specific expression. The transgenics expressing CECR1 in the heart demonstrated high rate of embryonic and neonatal lethality. The mice from all the lines examined showed enlargement of the heart. Abnormalities of the kidney and eye were also detected in mice expressing CECR1 under control of the actin promoter.


Effect of treatment time on outcome of radiotherapy for oral tongue carcinoma.
To investigate the importance of total treatment time on the outcome of external beam radiotherapy (EBRT) followed by internal brachytherapy for the treatment of oral tongue carcinoma. Ninety-four patients with T1-T2N0 squamous cell carcinoma of the oral tongue were treated using 35-40 Gy EBRT followed by 35-40 Gy interstitial (137)Cs brachytherapy between 1985 and 1995. The interval between the end of EBRT and the start of interstitial treatment varied for numerous unavoidable reasons, with a mean of 25.3 days and standard deviation of 3.5 days. The median follow-up period was 59.1 months (range 6-146). The actuarial survival rate of all cases was 78.4% at 5 years. The 5-year local control rate for those with T1 and T2 was 92.8% and 62.7%, respectively (p < 0.05). The local control rate of the primary tumor in patients with a total treatment time >43 days was statistically lower than that of patients with a total treatment time < or =43 days in all patients (p < 0.05) and in the subgroup of Stage T2 patients (p < 0.05). Multivariate analysis revealed that the local control rates in all cases were significantly related to the T stage (T2 or not), total treatment time (>43 days or not), and location of disease (posterior or not). Regression analysis for 5-year local control as a function of treatment duration showed a 2% loss of local control per day of treatment extension >30 days (r = 0.94, p < 0.01). The total treatment time was associated with the local control rate in the RT of oral tongue carcinoma. The loss in local control was estimated to be 2.0% per additional day in our series for oral tongue carcinoma.


A nonenzymatic electrochemical glucose sensor based on molecularly imprinted polymer and its application in measuring saliva glucose.
Diabetes mellitus (DM) is often diagnosed by invasive or enzymatic methods being progressively somewhat undesirable. If salivary glucose (SG) level correlates with blood glucose (BG), it could be useful for early DM detection. In this work, a molecular imprinted polymer (MIP) approach was used to develop an electrochemical non-enzymatic sensor to determine SG in micro-molar levels. The MIP based Screen printed gold electrode (Au-SPE) was prepared by electropolymerizing Acrylamide/Bis-Acrylamide (AAM/NNMBA) in the presence of glucose (G) as a template. The Cyclic voltammetry (CV), differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS) techniques were employed for the electrochemical measurements with Ferri/Ferrocyanide as redox probe in phosphate buffer saline. Morphological characterizations of the elaborated sensors were performed by using atomic force microscopy (AFM) and scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM-EDS). Important parameters influencing the MIP sensor performances such as extraction, incubation time, potential range and number of CV cycles, were studied and optimized. Under optimum conditions, the sensor could effectively detect glucose avoiding interferences of structural similar substances like lactose and sucrose. In a working range from 0.5 to 50 μg/mL, it exhibits a detection and quantification limits of 0.59 μg/mL and 1.9 μg/mL, respectively. Additionally, the real saliva glucose determination was compared to those of finger prick blood with satisfactory results (R2 = 0.99) by using partial least squares (PLS) statistical technique. Correspondingly, this work has demonstrated a cheap, simple and effective sensing platform for non-enzymatic glucose detection thus making it a promising tool for future evolution of accurate and reliable non-invasive DM diagnosis.


Destruction of Opportunistic Pathogens via Polymer Nanoparticle-Mediated Release of Plant-Based Antimicrobial Payloads.
The synthesis of antimicrobial thymol/carvacrol-loaded polythioether nanoparticles (NPs) via a one-pot, solvent-free miniemulsion thiol-ene photopolymerization process is reported. The active antimicrobial agents, thymol and carvacrol, are employed as "solvents" for the thiol-ene monomer phase in the miniemulsion to enable facile high capacity loading (≈50% w/w), excellent encapsulation efficiencies (>95%), and elimination of all postpolymerization purification processes. The NPs serve as high capacity reservoirs for slow-release and delivery of thymol/carvacrol-combination payloads that exhibit inhibitory and bactericidal activity (>99.9% kill efficiency at 24 h) against gram-positive and gram-negative bacteria, including both saprophytic (Bacillus subtilis ATCC 6633 and Escherichia coli ATCC 25922) and pathogenic species (E. coli ATCC 43895, Staphylococcus aureus RN6390, and Burkholderia cenocepacia K56-2). This report is among the first to demonstrate antimicrobial efficacy of essential oil-loaded nanoparticles against B. cenocepacia - an innately resistant opportunistic pathogen commonly associated with debilitating respiratory infections in cystic fibrosis. Although a model platform, these results point to promising pathways to particle-based delivery of plant-derived extracts for a range of antimicrobial applications, including active packaging materials, topical antiseptics, and innovative therapeutics.


[Regulation of thyroid hormones of the interaction of mitochondria with low-molecular weight cytoplasmic mediators, induced by phosphate- dependent transport of K+ and H+ ions through the mitochondrial inner membrane].
In vivo thyroid hormones control the binding to mitochondria of low molecular weight water-soluble cytoplasmic mediators that are capable to induce oxidative phosphorylation uncoupling, by increasing the sensitivity of mitochondria to the effects of these mediators. In hyperthyroid rat liver mitochondria cytoplasmic mediators stimulate the phosphate-dependent transport of K+ and H+ in a greater degree than in liver mitochondria of control rats. The increase in the oxidative phosphorylation uncoupling by cytoplasmic mediators is one of mechanisms of thermogenesis stimulation by thyroid hormones.


Social network centrality and hormones: The interaction of testosterone and cortisol.
In this study we tested whether testosterone and cortisol interacted in predicting social network centrality within a male rugby team. Using social network analysis (SNA), three measures of centrality were investigated: popularity (i.e., the number of incoming ties a participant receives), gregariousness (i.e., the number of ties leaving from a participant and reaching out to others), and betweenness (i.e., the number of times a person lies between two other individuals). In line with the idea that testosterone and cortisol jointly regulate the emergence of social status, we found that individuals with high basal testosterone and low basal cortisol were more popular and more likely to act as connectors among other individuals (i.e., betweenness). The same hormonal profile was not predictive of gregariousness. However, in line with the small literature on the topic, we found that cortisol was inversely correlated with gregariousness. Despite the cross-sectional and correlational nature of our research design, these findings represent the first empirical evidence that testosterone and cortisol interact to predict complex measures of social hierarchy position derived from social network analyses.


Seroprevalence of VZV IgG antibody in kidney transplant recipients: A systematic and meta-analysis review.
Varicella-zoster virus (VZV) is a human neurotropic virus, that becomes latent in nerve ganglia. VZV infection rarely occurs after kidney transplantation but causes severe clinical features and is associated with higher mortality rates. This study was performed to survey the reports on the seroprevalence of VZV IgG antibodies in kidney transplant recipients. Relevant studies were obtained by an online review of international databases (Web of Science, PubMed, Scopus, Science Direct, and Google scholar), and suitable studies were selected. The NOS checklist was used for the quality assessment of the selected studies. Heterogeneity assay among the primary studies was conducted by Cochran's Q test and I2 index (significance level 50%). Statistical analysis was performed using the Comprehensive Stata software (Version 14 package). Seroprevalence of VZV IgG in transplant recipients has been reported in ten studies. After combining the results of preliminary studies using a random effect model, the overall estimate of IgG positivity to VZV in transplant recipients was obtained equal to 98%. In this study, our results demonstrated that VZV is a prevalent infectious agent in kidney transplant recipients. A prophylactic vaccine may provide an effective strategy for preventing VZV in renal transplant recipients and also provide prophylaxis against the occurrence of post-herpetic neuralgia in immunocompetent patients.


Postweaning exposure to lanthanum alters neurological behavior during early adulthood in rats.
Lanthanum is a rare-earth element that has been used in various fields including medicine, agriculture and industry. Previously, in utero lanthanum exposure to dams was shown to alter neurobehavior and neurotransmitter levels in rat offspring; however, the effects of postweaning exposure to lanthanum on neurological behavior is still limited. The purpose of this study was to investigate the effects of postweaning exposure to lanthanum on neurological behavior during early adulthood in rats. Rats were orally exposed to 0, 2, 20, 60 mg/kg BW of lanthanum nitrate from postnatal day (PND) 24 to PND60. Our results indicated that lanthanum treatment significantly decreased body weight and food intake. Morris water maze test results showed that lanthanum significantly decreased escape latency and travel distance. Lanthanum treatment also significantly decreased grip strength, hindlimb strength, and running time & distance in motor activity test. Further results showed that lanthanum treatment significantly decreased plasma neurotransmitter levels of acetylcholine and norepinephrine as well as the number of neurons in the CA1 area of the hippocampus. These results suggest that postweaning exposure to lanthanum have adverse effects on neurobehaviors and the central nervous system, with no-observed-adverse-effect level at 2 mg/kg BW and benchmark dose lower confidence limit at 1.7 mg/kg BW.


Long non-coding RNA LOC554202 modulates chordoma cell proliferation and invasion by recruiting EZH2 and regulating miR-31 expression.
Chordoma is a rare malignant bone tumour arising from notochordal remnants. Long non-coding RNA LOC554202, as the host gene of miR-31, contributes to various cancer developments. However, little is known about the biological function of LOC554202 in chordoma. Here, the relationship between LncRNA LOC554202, miR-31 and EZH2 was elucidated in chordoma. The levels of LOC554402, miR-31, EZH2, RNF144B, and epithelial-mesenchymal transition (EMT) markers were measured in chordoma tissues and the chordoma cell lines via quantitative real-time PCR (qRT-PCR) or Western blot. FISH assay demonstrated the LOC554402 expression in chordoma tissues. The chordoma cell lines, U-CH1 and JHC7, were transfected with siRNA or miRNA mimics and analysed for cell proliferation ability, apoptosis, cell migration, and invasion. RNA pull down, RIP assay, and Luciferase Reporter Assay were used to analyze the interaction between LOC554202 and EZH2. Animal tumour xenografts were generated, and qRT-PCR was performed to investigate EZH2, miR-31, and RNB144B expression on tumour growth in vivo. We found elevated expression of LOC554202 was associated with a decreased level of miR-31 in cancer tissues. Knockdown of LOC554202 or overexpression of miR-31 suppressed the proliferation, migration, and invasion of chordoma cells. Unexpectedly, EZH2 as a binding protein of LOC554202, and it was positively regulated by LOC554202, leading to the reduced expression of miR-31. Furthermore, the impaired function of miR-31 restored expression of the oncogene RNF144B and maintained the metastasis-promoting activity in vitro. The results in vivo confirmed the anti-tumour effects of knockdown of LOC554202, which inhibited EZH2/miR-31 to activate the oncogene RNF144B. Our results suggest that LOC554202 may play an important role in the progression of chordoma by the direct upregulation of EZH2 and indirect promotion of RNF144B via miR-31.


Genetic basis of SMARCB1 protein loss in 22 sinonasal carcinomas.
SMARCB1-deficient sinonasal carcinoma (SNC) is an aggressive malignancy characterized by INI1 loss mostly owing to homozygous SMARCB1 deletion. With the exception of a few reported cases, these tumors have not been thoroughly studied by massive parallel sequencing (MPS). A retrospective cohort of 22 SMARCB1-deficient SNCs were studied by light microscopy, immunohistochemistry, fluorescence in situ hybridization (n = 9), targeted exome MPS (n = 12), and Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) (n = 10), a bioinformatics pipeline for copy number/zygosity assessment. SMARCB1-deficient SNC was found in 13 (59%) men and 9 (41%) women. Most common growth patterns were the basaloid pattern (59%), occurring mostly in men (77%), and plasmacytoid/eosinophilic/rhabdoid pattern (23%), arising mostly in women (80%). The former group was significantly younger (median age = 46 years, range = 24-54, vs 79 years, range = 66-95, p < 0.0001). Clear cell, pseudoglandular, glandular, spindle cell, and sarcomatoid features were variably present. SMARCB1-deficient SNC expressed cytokeratin (100%), p63 (72%), neuroendocrine markers (52%), CDX-2 (44%), S-100 (25%), CEA (4/4 cases), Hepatocyte (2/2 cases), and aberrant nuclear β-catenin (1/1 case). SMARCB1 showed homozygous deletion (68%), hemizygous deletion (16%), or truncating mutations associated with copy neutral loss of heterozygosity (11%). Coexisting genetic alterations were 22q loss including loss of NF2 and CHEK2 (50%), chromosome 7 gain (25%), and TP53 V157F, CDKN2A W110∗, and CTNNB1 S45F mutations. At 2 years and 5 years, the disease-specific survival and disease-free survival were 70% and 35% and 13% and 0%, respectively. SMARCB1-deficient SNCs are phenotypically and genetically diverse, and these distinctions warrant further investigation for their biological and clinical significance.


Brain-stem auditory evoked potentials in the rat: effects of gender, stimulus characteristics and ethanol sedation.
Rat BAEPs varied significantly as a function of gender and ethanol sedation as well as stimulus intensity and repetition rate. All BAEP wave latencies decreased and amplitudes increased with increasing stimulus intensity. Contrary to the prevailing view, the I-IV interpeak latency changed significantly as a function of stimulus intensity. In terms of repetition rate, all BAEP wave latencies increased and amplitudes decreased with increasing repetition rate. Male rats, compared to females, had significantly longer latencies for several BAEP components and interpeak latencies as well as smaller wave II amplitudes across a broad range of stimulus intensities. Males, compared to females, also had longer BAEP wave IV latencies and I-IV interpeak latencies at a slow stimulus repetition rate (8 clicks/sec) but shorter wave IV and I-IV latencies at a fast repetition rate (120 clicks/sec). These gender-dependent differences indicate that male and female rat BAEP data should not be combined indiscriminantly. Ethanol sedation had a statistically significant effect on the I-IV interpeak latency that was judged to be largely independent of core temperature changes. This finding suggests that while sedatives and anesthetics used to immobilize animals may have apparently minor temperature-independent effects on BAEP latencies, these effects can be statistically significant.


Chaotic synchronization of two optical cavity modes in optomechanical systems.
The synchronization of the motion of microresonators has attracted considerable attention. In previous studies, the microresonators for synchronization were studied mostly in the linear regime. While the important problem of synchronizing nonlinear microresonators was rarely explored. Here we present theoretical methods to synchronize the motions of chaotic optical cavity modes in an optomechanical system, where one of the optical modes is strongly driven into chaotic motion and transfers chaos to other weakly driven optical modes via a common mechanical resonator. This mechanical mode works as a common force acting on each optical mode, which, thus, enables the synchronization of states. We find that complete synchronization can be achieved in two identical chaotic cavity modes. For two arbitrary nonidentical chaotic cavity modes, phase synchronization can also be achieved in the strong-coupling small-detuning regime.


Influence of dietary and physical activity restriction on pediatric adenotonsillectomy postoperative care in Brazil: a randomized clinical trial.
Although culturally food and physical activity restriction are part of the routine postoperative care of many Brazilian surgeons, current evidences from other countries support no such recommendations. To determine whether dietary and physical restriction effectively lead to a decrease on postoperative complications of adenotonsillectomy in children when compared to no restriction. We have designed a randomized clinical trial comparing two intervention: no specific counseling on diet or activity (Group A), and restriction recommendations on diet and physical activities (Group B). Caregivers completed a questionnaire on observed pain, diet and activity patterns, and medications administered. Parameters were compared at the 3rd and at the 7th postoperative day between intervention groups. We have enrolled a total of 95 patients, 50 in Group A and 45 in Group B. Fourteen patients were lost to follow up. Eventually, 41 patients in group A and 40 in Group B were available for final analysis. Mean age in months (A=79.5; SD=33.9/B=81.1; SD=32.6) and sex (A=58% male; B=64.4% male) were equivalent between groups. Pain, evaluated through visual analog scale in the 3rd (A=2.0; IQR 1-6/B=4.5; IQR 2-6; p=0.18) and in the 7th (A=1.0; IQR 1.0-4.5/B=2.0; IQR 1.0-4.7; p=0.29) postoperative days, was not different between groups, as was the amount of analgesics administered. Dietary and physical activity patterns also showed no statistically significant differences between groups. Dietary and activity restriction after adenotonsillectomy does not seem to affect patients' recovery. Such information may impact considerably on the social aspects that involve a tonsillectomy, reducing the working days lost by parents and accelerating the return of children to school.


Alpine vegetation in the context of climate change: A global review of past research and future directions.
Climate change is causing extensive alterations to ecosystems globally, with some more vulnerable than others. Alpine ecosystems, characterised by low-temperatures and cryophilic vegetation, provide ecosystems services for billions of people but are considered among the most susceptible to climate change. Therefore, it is timely to review research on climate change on alpine vegetation including assessing trends, topics, themes and gaps. Using a multicomponent bibliometric approach, we extracted bibliometric metadata from 3143 publications identified by searching titles, keywords and abstracts for research on 'climate change' and 'alpine vegetation' from Scopus and Web of Science. While primarily focusing on 'alpine vegetation', some literature that also assessed vegetation below the treeline was captured. There has been an exponential increase in research over 50 years, greater engagement and diversification in who does research, and where it is published and conducted, with increasing focus beyond Europe, particularly in China. Content analysis of titles, keywords and abstracts revealed that most of the research has focused on alpine grasslands but there have been relatively few publications that examine specialist vegetation communities such as snowbeds, subnival vegetation and fellfields. Important themes emerged from analysis of keywords, including treelines and vegetation dynamics, biodiversity, the Tibetan Plateau as well as grasslands and meadows. Traditional ecological monitoring techniques were important early on, but remote sensing has become the primary method for assessment. A key book on alpine plants, the IPCC reports and a few papers in leading journals underpin much of the research. Overall, research on this topic is increasing, with new methods and directions but thematic and geographical gaps remain particularly for research on extreme climatic events, and research in South America, in part due to limited capacity for research on these rare but valuable ecosystems.


A mass shooting at Port Arthur, Tasmania, Australia: a study of its impact on early pregnancy losses using a conception time-based methodology.
Does an acute calamity in a community cause early miscarriage and is this association the same for male and female fetuses? Estimated losses of 29.5% of first trimester pregnancies in the affected region could be associated with an acute calamity, with no statistically significant difference in estimated losses by fetal sex. There are very few studies on the impact of a calamity on early pregnancy loss and its differential effects on male and female fetuses. A decline in the human sex ratio at birth associated with the events of 9/11 in New York has been documented. This is a retrospective descriptive study of birth register data in Tasmania, Australia, from 1991 to 1997, covering the period in which the calamity occurred. The register contains data on all pregnancies that proceeded to >20 weeks gestation. The conception date was calculated by subtracting gestational age from birth date. We estimated that 40 318 pregnancies were conceived in the period 1991-1996 inclusive. These were aggregated to 4-weekly blocks classified by region and sex. The acute calamity was at Port Arthur, Tasmania, Australia. On 28 April 1996, a gunman opened fire on visitors and staff in a tourist cafe. A very stressful 20 h period, ended with 35 people dead and 22 injured. A negative binomial regression model was used to assess the association between this calamity and pregnancy loss. This loss is evidenced by a shortfall in the registration of pregnancies that were in their first trimester at the time of the calamity. We estimated a shortfall of 29.5% or 229 registered pregnancies among those in the first trimester at the time of the calamity (P < 0.001), in the region surrounding the calamity site. There was no sex effect in this shortfall (P = 0.911). There was no corresponding shortfall in other parts of Tasmania (P = 0.349). The study is descriptive and cannot produce causal inferences. These first trimester miscarriages are estimated statistically and it is understood that gestational age is an estimate. The use of maternal residential postcodes at birth as a surrogate for geographic area or space assumes that the mother has not moved into the postcode area after the calamity and before the reporting of a birth. The results of this study suggest that calamities bring about significant pregnancy loss affecting both sexes. The methodology presented of inferring conception date from birth date and using this for analysis, provides a more accurate assessment of first trimester pregnancy losses than raw birth data or sex ratio at birth.


Catching the waves: following the leading edge of elongating RNA polymerase II.
By precisely tracking the waves of elongating RNA polymerase II (Pol II) during gene activation, Danko et al. (2013), in this issue of Molecular Cell, discovered a surprising diversity of elongation rates among and along human genes.


Who volunteers for phase I clinical trials? Influences of anxiety, social anxiety and depressive symptoms on self-selection and the reporting of adverse events.
To investigate the influence of anxiety, social anxiety and depressive symptoms on the willingness of healthy subjects to volunteer for phase I studies and to report adverse events. A group of healthy subjects who had never participated in a clinical trial ("Naïve Subjects") were invited to participate in a phase I study. All subjects were assessed for trait anxiety (State-Trait Anxiety Inventory, STAI-T), social anxiety (Social Avoidance and Distress, SAD, and Fear of Negative Evaluation, FNE) and depressive symptomatology (Beck Depression Inventory, BDI-II). Subjects who accepted the invitation to participate were compared with those who refused. The personality traits of a group of "Actual Participants" were examined, and the relation of these traits to adverse events reported during participation was evaluated. A significant inverse correlation was found between the STAI-T (R = -0.203, p < 0.05) and SAD (R = -0.204, p < 0.05) scores and the willingness to participate. Naïve Subjects who refused the invitation to participate showed higher scores on STAI-T (Z = -2.600, p < 0.01) and SAD (Z = -2.524, p < 0.05) inventories. Logistic regression using BDI-II, STAI-T, SAD and FNE as covariates also showed that the only unique predictors of participation were the STAI-T (p < 0.05) and SAD (p < 0.01) scores. Significant positive correlations were found between trait anxiety and reporting of adverse events. Participants in phase I studies are a self-selected sample defined by low trait-anxiety and social avoidance behaviors. This self-selection bias may affect the study results because less anxious subjects tend to report fewer adverse events. The characterization of a participant's personality traits may be important in phase I studies.


Phthalates in the environment: characteristics, fate and transport, and advanced wastewater treatment technologies.
Phthalates are well-known emerging contaminants that harm human health and the environment. Therefore, this review aims to discuss about the occurrence, fate, and phthalates concentration in the various environmental matrices (e.g., aquatic, sediment, soil, and sewage sludge). Hence, it is necessary to treat sources containing phthalates before discharging them to aqueous environment. Various advanced wastewater treatments including adsorption process (e.g., biochar, activated carbon), advanced oxidation processes (e.g., photo-fenton, ozonation, photocatalysis), and biological treatment (membrane bioreactor) have been successfully to address this issue with high removal efficiencies (70-95%). Also, the degradation mechanism was discussed to provide a comprehensive understanding of the phthalate removal for the reader. Additionally, key factors that influenced the phthalates removal efficiency of these technologies were identified and summarized with a view towards pilot-scale and industrial applications.


Spontaneously hypertensive (SHR) rats choose more impulsively than Wistar-Kyoto (WKY) rats on a delay discounting task.
Indications of Attention Deficit Hyperactivity Disorder (ADHD) in the spontaneously hypertensive rat (SHR) are not consistent across different tests of impulsivity, questioning the SHR's validity as a rodent model of ADHD. This study used a concurrent-chains procedure to examine possible differences in impulsive choice between SHRs and control-normotensive Wistar Kyoto (WKY) rats. The aim was to extend the generality of findings showing regularities between the hyperbolic-decay model and the generalized matching law fitting delay discounting data from nonhuman animals. The objectives were to: (1) examine differences in impulsive choice between SHRs and WKYs; (2) add evidence suggesting that the SHR is a suitable model of ADHD; (3) demonstrate that concurrent-chains procedures requiring locomotion detect differences in impulsive choice between SHRs and WKYs; (4) support the idea that impulsivity in nonhuman animals increases with training. The initial link used two non-independent random interval schedules arranging entries to the terminal links, where one fixed-time (FT) schedule delayed 1-food pellet and the other FT 4-food pellets. The FT delaying the former was kept constant at 0.1s and that delaying the latter changed after every 10 food deliveries, defining six delay components (0.1, 5, 10, 20, 40, and 80s) presented in random order each session. Results showed that the SHRs choose more impulsively than the WKYs, adding to the body of evidence suggesting that the SHR may be a suitable model of ADHD. Both models of choice fitted the impulsive choices of the SHRs and WKYs well; positive correlations between estimates of parameters k and s suggested compatibility between models of choice showing that impulsivity increases with training.


Effects of surfactant and temperature on biotransformation kinetics of anthracene and pyrene.
The biotransformation and mineralization of a mixture of two polycyclic aromatic hydrocarbons (PAHs), anthracene and pyrene, which are known contaminants of soil and groundwater, by an enrichment culture in the presence or absence of 100 mg l(-1) Tergitol NP-10, a non-ionic surfactant, and at temperatures of 10 degrees C and 25 degrees C were investigated. The overall biotransformation of 2 mg l(-1) total PAHs with free cell suspensions in batch culture was greater than 97.2% at both examined temperatures. At 25 degrees C, the overall mineralization of anthracene was 48.8% and that of pyrene was 66.1%. However, the decrease of temperature to 10 degrees C had a negative effect on the mineralization of PAHs and reduced it to 18.5% and 61.5% for anthracene and pyrene, respectively. Using a higher PAHs concentration of 20 mg l(-1) at 25 degrees C, the overall biotransformation of anthracene was 80.7% and that of pyrene was 100%, where only 17.3% anthracene and 7.6% pyrene were mineralized to carbon dioxide and water. The addition of surfactant at 25 degrees C increased the overall mineralization of anthracene and pyrene to 33.0% and 27.6%, respectively. However, the addition of surfactant at 10 degrees C had a negative impact on the overall biotransformation of anthracene and pyrene, reducing them to 20.6% and 14.0%, respectively. These results have significant implications in the bioremediation of PAHs-contaminated sites.


Identification and degradation characterization of hexachlorobutadiene degrading strain Serratia marcescens HL1.
A bacterium (strain HL1) capable of growing with hexachlorobutadiene (HCBD) as sole carbon and energy sources was isolated from a mixture of soil contaminated with HCBD and activated sludge obtained from petrochemical plant wastewater treatment plant by using enrichment culture. Biochemical characteristics and phylogenetic analysis based on 16S rDNA sequence indicate that strain HL1 clearly belongs to Serratia marcescens sp. Resting cells of strain HL1 were found to remove HCBD from culture fluids with the concomitant release of chloride ion under aerobic conditions. The ranges of pH value and temperature for satisfactory growth of strain HL1 cells were from 7.0 to 8.0 and 25 to 30 degrees C, respectively. Capability of resting cells to degrade HCBD was induced by HCBD in the culture fluids. HCBD (20mg/l) was removed from culture fluids by resting cells in 4 d without lag phase, but for 50mg/l and 80mg/l HCBD 7 days were needed with lag phase. Growth of strain HL1 cells was inhibited by HCBD at the concentration up to 160mg/l. First order kinetics could be fitted to the biodegradation of HCBD by HL1 cells after lag phase at initial concentrations of 20, 50, and 80mg/l. Strain HL1 also showed strong capacity to degrade chloroprene, trichloroethylene, tetrachloroethylene, and vinyl chloride at solely initial concentration of 50mg/l. Results could offer useful information for the application of strain HL1 in bioremediation or control of HCBD-polluted environment.


Safe administration of high-dose methotrexate with minimal drug level monitoring: Experience from a center in north India.
High-dose methotrexate (HDMTX) is recommended to be administered with serial monitoring of methotrexate (MTX) levels, which may not be universally feasible in resource-limited settings. In this study, we evaluated the overall experience of administration of HDMTX at our center by monitoring a single drug level at 54 h from the start of MTX infusion. This retrospective study was performed at a tertiary level hospital in north India, over a 5-year period (2011-2015). All patients <18 years of age with newly diagnosed acute lymphoblastic leukemia (ALL) and T-non-Hodgkin lymphoma (T-NHL) were enrolled in the study. Details of HDMTX and all significant toxicities requiring prolonged or repeat hospitalization were retrieved from the medical records. All eligible patients received HDMTX as per the recommendations followed by at least three doses of leucovorin rescue, before drug levels were sent at 54 h. Subsequent leucovorin doses were adjusted accordingly. The records of 598 cycles of HDMTX in 184 patients were reviewed. A total of 531 of 598 cycles (88.7%) were managed with monitoring only a single plasma drug level at 54 h from the beginning of infusion. Delayed MTX clearance was seen in 260 of 598 cycles (43.5%). Only three episodes (0.5%) were associated with significant toxicity. There were no deaths. The strategy of monitoring MTX concentration at 54 h was safe in our cohort. Although recommended, dynamic monitoring of plasma drug levels may not always predict toxicity.


Fully independent external validation of the Transcatheter Aortic Valve Replacement 30-day (TAVR-30) hospital readmission model.
Early and late readmissions after Transcatheter Aortic Valve Replacement (TAVR) are common and associated with worse outcome. A risk prediction model (TAVR-30) was recently developed using readily available clinical variables to identify patients at risk for hospital readmission within 30 days after TAVR. We performed an independent external validation of the TAVR-30 model. The Swedish TAVR-registry, linked together with other mandatory national registries was used to identify all TAVR procedures, variables from the original model, hospitalizations and deaths between the years 2008 to 2021. A total of 8459 patients underwent TAVR, 7693 patients had complete data and were included in the analysis. Out of these, 928 patients experienced a readmission within 30 days. Using the estimates from the original model, a concordance (c)-index of 0.51, a calibration slope of 0.07 and intercept of -0.62 were obtained respectively, overall implying poor model performance. This independent external validation indicates poor performance of the TAVR-30 model in a Swedish setting. Further research is needed to develop more reliable tools for predicting the risk of early hospital readmission after TAVR, as well as, for providing a deeper understanding of how to develop risk models that performs well in patients with multiple underlying comorbidities.


Massive iliac artery bleeding in patients receiving intraoperative radiation therapy for advanced rectal cancer: report of two cases.
Multimodality treatment for advanced rectal cancer, including intraoperative radiation therapy, is associated with significant complications. Unfortunately, because of the high local recurrence rates and mortality in these patients, the treatment regimen of external beam radiation therapy, chemotherapy, extensive resection, and intraoperative radiation therapy is one of the few potentially curative options available. Here we report two cases of massive iliac artery bleeding after multimodality treatment for advanced rectal cancer, which included intraoperative radiation therapy.


Vertically acquired community methicillin-resistant Staphylococcus aureus dacryocystitis in a neonate.
Methicillin-resistant Staphylococcus aureus (MRSA) infections are becoming increasingly common in the community, especially among children.(1) Community MRSA differs from the more familiar nosocomial MRSA in having a distinct epidemiology and a broader antibiotic-susceptibility profile.(2) Community MRSA can infect the eye and orbit.(3,4) Cases have been reported in otherwise-healthy children, including chronic dacryocystitis in an 8-month-old infant and orbital cellulitis in a 16-month-old child.(5,6) I report a case of perinatally acquired community MRSA dacryocystitis and periorbital cellulitis associated with bacteremia in a 12-day-old previously healthy, full-term neonate.


Effect of jute yarn on the mechanical behavior of concrete composites.
The objective of the study is to investigate the effect of introducing jute yarn on the mechanical properties of concrete. Jute fibre is produced abundantly in Bangladesh and hence, very cheap. The investigation on the enhancement of mechanical properties of concrete with jute yarn as reinforcement, if enhanced, will not only explore a way to improve the properties of concrete, it will also explore the use of jute and restrict the utilization of polymer which is environmentally detrimental. To accomplish the objective, an experimental investigation of the compressive, flexural and tensile strengths of Jute Yarn Reinforced Concrete composites (JYRCC) has been conducted. Cylinders, prisms and cubes of standard dimensions have been made to introducing jute yarn varying the mix ratio of the ingredients in concrete, water cement ratio, length and volume of yarn to know the effect of parameters as mentioned. Compressive, flexural and tensile strength tests had been conducted on the prepared samples by appropriate testing apparatus following Standards of tests. Mechanical properties of JYRCC were observed to be enhanced for a particular range of lengths of cut (10, 15, 20 and 25 mm) and volume content of jute yarn (0.1, 0.25, 0.5 and 0.75 %). The maximum increment of compressive, flexural and tensile strengths observed in the investigation are 33, 23 and 38 %, respectively with respect to concrete without jute yarn.


In vitro anti-human immunodeficiency virus (HIV) activity of the chromanone derivative, 12-oxocalanolide A, a novel NNRTI.
The three chromanone derivatives, (+)-, (-)-, and (+/-)-12-oxocalanolide A (2), were evaluated for in vitro antiviral activities against HIV and simian immunodeficiency virus (SIV). The compounds were determined to be inhibitors of HIV-1 reverse transcriptase (RT) and exhibited activity against a variety of viruses selected for resistance to other HIV-1 nonnucleoside RT inhibitors. They are the first reported calanolide analogues capable of inhibiting SIV.


Morbidity and mortality of red foxes (Vulpes vulpes) and gray foxes (Urocyon cinereoargenteus) admitted to the Wildlife Center of Virginia, 1993-2001.
The medical records of 48 red foxes (Vulpes vulpes) and 35 gray foxes (Urocyon cinereoargenteus) examined at the Wildlife Center of Virginia (Waynesboro, Virginia, USA) from 1993 to 2001 were reviewed. The most common diagnosis in red foxes was orphaned (33%), followed by trauma (27%), undetermined diagnosis (23%), and sarcoptic mange (17%). Trauma (46%) was the most frequent cause of morbidity and mortality in gray foxes followed by orphaned (23%), undetermined (20%), toxoplasmosis (6%), presumptive canine distemper (3%), and rabies (3%). One gray fox had concurrent toxoplasmosis and presumptive canine distemper (3%). Similar diseases were detected in previous studies at a diagnostic laboratory; however in this study, trauma and orphaned animals were more common than infectious diseases. The lack of diagnostic information on some cases limited the usefulness of this study, and more emphasis should be placed on performing postmortem examinations of wildlife presented to wildlife rehabilitation centers.


The neural correlates of anhedonia in major depressive disorder.
Anhedonia is a relative lack of pleasure in response to formerly rewarding stimuli. It is an important diagnostic feature of major depressive disorder (MDD), and predicts antidepressant efficacy. Understanding its neurobiological basis may help to target new treatments and predict treatment outcomes. Using a novel paradigm, we aimed to explore the correlations between anhedonia severity and magnitude of neural responses to happy and sad stimuli in regions previously implicated in studies of human reward processing and depressive anhedonia. Neural responses to happy and sad emotional stimuli (autobiographical prompts and mood congruent facial expressions) were measured using blood oxygen level dependent (BOLD) functional magnetic resonance imaging in twelve MDD individuals with varying degrees of anhedonia. In response to happy stimuli, anhedonia, but not depression severity per se, was positively and negatively correlated with ventromedial prefrontal cortex (VMPFC) and amygdala/ventral striatal activity, respectively. State anxiety independently contributed to a VMPFC-subcortical dissociation of response to happy (but not sad) stimuli, which was similar, but different, to anhedonia. These findings suggest that anhedonia and state anxiety are associated with dysfunction within neural systems underlying the response to, and assessment of, the rewarding potential of emotive stimuli in MDD, and highlight the importance of employing a symptom-dimension-based approach in the examination of the neurobiology of depression.