Patients' Perspectives on the Psychological Impact of Inflammatory Arthritis and Meeting the Associated Support Needs: Open-Ended Responses in a Multi-Centre Survey.
Psychological support for inflammatory arthritis is recommended in rheumatology treatment guidelines. Previous research found that high numbers of patients would access such support but that provision is often inconsistent and inadequate. The present study explored patients' perspectives on the nature of the psychological impact of inflammatory arthritis and how to meet the associated support needs. A cross-sectional survey was conducted, using questionnaires which included three open-ended questions about helpful and unhelpful psychological support. The questionnaires were administered to 1,080 patients at six regional rheumatology units across England, and 1,200 members of a national patient charity. A total of 1,210 (53%) patients completed the questionnaire, with 779 (64%) responding to the open-ended questions: 80% female; mean age 59 years (12.6); disease duration <5 years (40%), 5-10 years (20%), >10 years (40%). Data were analysed using a hybrid content analysis. Four categories emerged: challenges of an altered life course (negative emotions, isolation and loneliness, a dysfunctional body, loss, strained relationships, and fears for the future); poor communication (feeling unheard, clinicians' reluctance to address psychological issues, a lack of help to manage pain and fatigue, and struggling to ask for help); understood by others (sharing with people who have arthritis, supportive family and friends, whole team support, and understanding from clinicians); and acquiring strategies (ways of coping). Psychological distress was commonplace, and often attributed to fatigue and pain. In addition to peers and family, patients looked to the rheumatology team for validation and support. Further research will address the skills training needs of rheumatology teams to meet patients' psychological support requirements.


Meta-analysis of robotic and laparoscopic surgery for treatment of rectal cancer.
To conduct a meta-analysis to determine the relative merits of robotic surgery (RS) and laparoscopic surgery (LS) for rectal cancer. A literature search was performed to identify comparative studies reporting perioperative outcomes for RS and LS for rectal cancer. Pooled odds ratios and weighted mean differences (WMDs) with 95% confidence intervals (95% CIs) were calculated using either the fixed effects model or random effects model. Eight studies matched the selection criteria and reported on 661 subjects, of whom 268 underwent RS and 393 underwent LS for rectal cancer. Compared the perioperative outcomes of RS with LS, reports of RS indicated favorable outcomes considering conversion (WMD: 0.25; 95% CI: 0.11-0.58; P = 0.001). Meanwhile, operative time (WMD: 27.92, 95% CI: -13.43 to 69.27; P = 0.19); blood loss (WMD: -32.35, 95% CI: -86.19 to 21.50; P = 0.24); days to passing flatus (WMD: -0.18, 95% CI: -0.96 to 0.60; P = 0.65); length of stay (WMD: -0.04; 95% CI: -2.28 to 2.20; P = 0.97); complications (WMD: 1.05; 95% CI: 0.71-1.55; P = 0.82) and pathological details, including lymph nodes harvested (WMD: 0.41, 95% CI: -0.67 to 1.50; P = 0.46), distal resection margin (WMD: -0.35, 95% CI: -1.27 to 0.58; P = 0.46), and positive circumferential resection margin (WMD: 0.54, 95% CI: 0.12-2.39; P = 0.42) were similar between RS and LS. RS for rectal cancer is superior to LS in terms of conversion. RS may be an alternative treatment for rectal cancer. Further studies are required.


Gabapentin monotherapy in patients with chronic radiculopathy: the efficacy and impact on life quality.
The purpose of this, open-label, non-comparative study, was to evaluate the efficacy on quality of life and the efficacy of gabapentin monotherapy in patients with chronic radiculopathy. Thirty-five patients with radicular pain and diagnosed as L4, L5 or S1 radiculopathy were treated with oral gabapentin from a total of 300 mg per day once up to a total of 1800 mg per day divided in 3 doses for eight-week trial period. Quality of life, functional disability and psychological mood of the patients were assessed using the Nottingham Healthy Profile (NHP), Oswestry Low Back Pain Disability Questionnaire (ODQ) and Beck Depression Inventory (BDI). Of the patients (n = 35), 25 were females and 10 were males (mean age: 41.8 +/- 10.4, range: 24-60 years); mean radiculopathy duration was 16.4 +/- 14.2 months (range: 3-48 months). The pain intensity at rest, quality of life, functional disability and depression scores were determined significantly improved after treatment and 4 months compared to baseline scores (p < 0.001). 1.5 points compared to baseline for at pain rest and 15 points improvement on the ODQ were obtained. Gabapentin may provide benefits in terms of alleviation of pain and overall quality of life in patients with chronic radiculopathy.


Aluminum and Alzheimer's disease: perspectives for a cytoskeletal mechanism.
A considerable volume of literature has accumulated concerning the association of aluminum with Alzheimer's disease. The pathogenic mechanisms resulting in Alzheimer's disease remain unknown, but recent investigations have focused on cytoskeletal abnormalities as perhaps the key lesion in Alzheimer's disease and related neurological disorders. The diversity of neuronal functions that are dependent on cytoskeletal integrity suggests that subtle effects on polymerization, assembly, transcription, or processing of cytoskeletal elements may have significant and far-reaching neurological effects. That aluminum may participate in the development of neuropathological lesions characteristic of Alzheimer's disease is suggested by evidence that aluminum is a potent cytoskeletal toxin, produces cognitive deficits in laboratory animals, and can be detected within abnormal neurons isolated from brain tissue from Alzheimer's disease patients. In this review, a critical look will be taken at the enigmatic role aluminum has played in Alzheimer's disease research, the possibility of its pathogenicity, and its use as a tool for the investigation of cytoskeletal changes that may result in the biochemical and, ultimately, clinical manifestations of Alzheimer's disease.


[Changes in the structural components of the thymus gland with different degrees of adaptation of the body to physical loads].
The thymus has been studied by means of histological and morphometrical methods in 167 male white rats subjected to various regimens of physical loadings. The physical loading is accompanied with certain changes in relationship of the thymus structural components. These changes are slightly depended on the loading regimen, but essentially vary in animals that differently adapt to the loading. When adaptation is sufficient, the areas occupied by the thymus connective tissue components decrease, while the part of the cortical substance increases. This demonstrates certain activation of immune processes in these animals. An insufficient adaptation produces an acceleration of age involution of the thymus and results in decreasing immunological reactions of the organism.


Severe pulmonary arterial hypertension due to toxic oil syndrome: a new cause of plexogenic arteriopathy.
Ten patients with severe pulmonary hypertension due to Toxic Oil Syndrome (TOS) (3 men, 7 women; mean age 27.9 +/- 11.23 yrs.) are presented. The pulmonary vessels were examined with a micromorphometric technique. All patients had intimal fibrosis of the arteries and veins. Seven also had a thrombus in different stages. All arteries were shown to have medial hypertrophy. Plexiform lexions were found in eight cases. It is concluded that TOS can produce severe pulmonary hypertension histologically undistinguishable from the primary form. TOS can be added to the list of diseases causing plexogenic arteriopathy.


Sexual rehabilitation after treatment for prostate cancer.
Although there is little evidence that sexual behavior causes prostate cancer, men with prostate cancer often have sexual dysfunction before the cancer diagnosis is made. Each treatment for prostate cancer increases the prevalence of sexual problems. After nerve-sparing radical prostatectomy, the chance of recovering erections is better for men who are younger and in whom both neurovascular bundles can be spared. Definitions of "potency" after nerve-sparing surgery have not specified the rigidity of the erections achieved. Thus, some men classified as "potent" may wish additional sexual rehabilitation. The chance that definitive radiation therapy will cause erectile dysfunction probably has been overestimated. The prevalence rate may be closer to 25% of men with new problems compared with the 50% often cited in the literature. Men are more at risk to have erection problems after radiation therapy if the quality of erections before treatment was borderline. Hormonal therapy has an impact on the central mechanisms mediating sexual desire and arousability. Therefore, with most treatment methods, only approximately 20% of men remain sexually functional. Newer antiandrogenic drugs interfere less with sexual function, but their long-term ability to control prostate cancer is still under investigation. Sexual rehabilitation should be addressed by the primary care team. Sexual partners should be included in brief sexual counseling, even when a mechanical treatment for erectile dysfunction is prescribed.


Lymphatics - not just a chylomicron conduit.
Lymphatics are known to have active, regulated pumping by smooth muscle cells that enhance lymph flow, but whether active regulation of lymphatic pumping contributes significantly to the rate of appearance of chylomicrons (CMs) in the blood circulation (i.e., CM production rate) is not currently known. In this review, we highlight some of the potential mechanisms by which lymphatics may regulate CM production. Recent data from our lab and others are beginning to provide clues that suggest a more active role of lymphatics in regulating CM appearance in the circulation through various mechanisms. Potential contributors include apolipoproteins, glucose, glucagon-like peptide-2, and vascular endothelial growth factor-C, but there are likely to be many more. The digested products of dietary fats absorbed by the small intestine are re-esterified and packaged by enterocytes into large, triglyceride-rich CM particles or stored temporarily in intracellular cytoplasmic lipid droplets. Secreted CMs traverse the lamina propria and are transported via lymphatics and then the blood circulation to liver and extrahepatic tissues, where they are stored or metabolized as a rich energy source. Although indirect data suggest a relationship between lymphatic pumping and CM production, this concept requires more experimental evidence before we can be sure that lymphatic pumping contributes significantly to the rate of CM appearance in the blood circulation.


Quercetin improves gut dysbiosis in antibiotic-treated mice.
The diversity and activity of the gut microbiota residing in humans and animals are significantly influenced by the diet. Quercetin, one of the representative polyphenols in human diets, possesses a wide range of biological properties. The aim of this study was to investigate the prebiotic effects of quercetin in antibiotic-treated mice. Gut dysbiosis was successfully induced in mice by treatment with an antibiotic cocktail. Gas chromatography and 16S rDNA high-throughput sequencing techniques were used to investigate short-chain fatty acid content and gut microbial diversity and composition. The results showed that quercetin supplementation significantly improved the diversity of the gut bacterial community in antibiotic-treated mice (P < 0.05). Meanwhile, intestinal barrier function was also recovered remarkably as indicated by a decrease in the content of serum d-lactic acid and the activity of serum diamine oxidase (P < 0.05). The length of intestinal villi and mucosal thickness were also significantly increased in response to quercetin treatment (P < 0.05). Furthermore, the production of butyrate in faeces was enhanced significantly in quercetin-treated mice (P < 0.05). In conclusion, quercetin is effective in recovering gut microbiota in mice after antibiotic treatment and may act as a prebiotic in combatting gut dysbiosis.


Efficacy of 1st-line bismuth-containing quadruple therapies with levofloxacin or clarithromycin for the eradication of Helicobacter pylori infection: A 1-week, open-label, randomized trial.
The aim of the present open-label, randomized control trial was to determine the clinical efficacy and safety of two 1-week bismuth-containing quadruple regimens and 1 levofloxacin-based triple regimen for the eradication of Helicobacter pylori infection in treatment-naive patients. The influence of susceptibility and host CYP2C19 polymorphisms on the efficacy was also evaluated. Eligible patients were randomly to receive esomeprazole and colloidal bismuth pectin along with clarithromycin and amoxicillin (EBCA), esomeprazole and colloidal bismuth pectin along with levofloxacin and amoxicillin (EBLA), or esomeprazole along levofloxacin and amoxicillin (ELA) for 1 week. The primary outcome was the eradication rate in the intention-to-treat (ITT) and per-protocol (PP) analyses. Overall, 270 patients were randomized. The eradication rates in the above 3 groups were 80.25%, 89.66%, and 81.93% in PP analysis and 72.22%, 86.66%, and 75.56% in ITT analysis, respectively. The eradication rate of EBLA was significantly higher than that of EBCA (P = 0.016) in ITT analysis. No significant differences were found among these groups in terms of adverse effects and compliance. The efficacy was significantly affected by levofloxacin resistance for EBLA (P = 0.01) and ELA (P = 0.04), but not by polymorphisms of CYP2C19 gene for any of the 3 groups. All 1-week bismuth-containing quadruple therapies and levofloxacin-based triple therapy can obtain an acceptable eradication rate, and levofloxacin-based quadruple regimen exhibits the highest eradication rate. The antibiotic resistant rate of levofloxacin was associated with the eradication rate.


Notification of relapse and other previously treated tuberculosis in the 52 health districts of South Africa.
OBJECTIVE: To investigate the extent to which relapse and other previously treated tuberculosis (TB) contribute to the notified TB burden in South Africa.DESIGN: We conducted an ecological analysis at the level of the 52 South African health districts using national electronic TB register data. We included all bacteriologically confirmed TB cases treated for presumed drug-susceptible TB in 2011. Treatment history information was based on recorded patient categories (new vs. retreatment).RESULTS: Relapse and other previously treated TB cases constituted between 7.6% and 40% (median 17%, interquartile range 12-22) of all bacteriologically confirmed TB cases in the 52 South African districts. Multivariable analysis suggested that districts with higher proportions of previously treated TB cases had higher TB case notification rates (P < 0.001), lower estimates of antenatal human immunodeficiency virus (HIV) prevalence in the district population (P < 0.001) as well as lower HIV co-infection rates (P < 0.001) among new TB cases.CONCLUSION: Relapse and other previously treated TB cases contributed substantially to the notified TB burden in several South African health districts, particularly those with high case notification rates and lower antenatal HIV prevalence. Additional efforts to prevent TB among previously treated people, such as strengthening treatment monitoring and/or secondary preventive therapy, should be considered.


Acute effects of alpha-1 adrenoceptor antagonist, doxazosin on circulating vasoactive hormones.
The acute effects of doxazosin, a new selective alpha-1 adrenergic blocking agent, on blood pressure, heart rate, and on some circulating vasoactive hormones, such as plasma renin activity, catecholamines, serotonin and endothelin-1 in ten healthy normotensive volunteers and eight moderate-severe essential hypertensives were studied. Two milligrams doxazosin was administered orally in randomised fashion as compared to placebo and the acute effects were evaluated one half to four hours later. Doxazosin did not reduce blood pressure and did not increase heart rate in normotensive subjects as compared to placebo. A significant decrease in blood pressure was found in hypertensives after doxazosin (p < 0.01), without change in heart rate. Simultaneously, doxazosin did not modify plasma renin activity, catecholamines, serotonin and endothelin-1 concentrations both in normotensive and hypertensive subjects when compared with placebo administration. Thus, it appears that doxazosin does not influence local and systemic vasopressor hormones involving in the regulation of blood pressure. In conclusion, the lack of effects on plasma vasoactive factors confirms the selective alpha-1 postsynaptic antagonism of doxazosin and an effective antihypertensive action in the treatment of essential hypertension.


Base pair specificity and energetics of binding of the phenazinium molecules phenosafranine and safranine-O to deoxyribonucleic acids: a comparative study.
The base specificity and energetics of DNA binding of the phenazinium dyes phenosafranine and safranine-O have been studied using various biophysical tools. The guanine-cytosine base specificity of both compounds was established from binding affinity values and competition dialysis results and also from circular dichroism, thermal melting, and calorimetric studies. Both dyes bind to DNA with affinity of the order of 10(5) M(-1), but the values are significantly higher for the guanine-cytosine rich DNAs over adenine-thymine rich ones and for phenosafranine over safranine-O. Calorimetric studies revealed that the binding reactions were exothermic and favoured by negative enthalpy as well as predominantly large positive entropy contributions. The temperature dependence of enthalpy changes yielded negative heat capacity values, which were higher for phenosafranine, compared to safranine-O, suggesting substantial contribution from hydrophobic forces in the binding process. Enthalpy-entropy compensation behaviour was also observed for the binding of both dyes to DNAs, revealing the molecular aspects of the interaction. Taken together, the spectroscopic and calorimetric data reflect clearly the guanine-cytosine base specificity of these molecules and a stronger DNA binding of PSF over SO. The results also provide some insights into the role of a bulkier substituent in the phenazinium ring in the binding process.


Nonlinear optical limiting property and carrier dynamics in tin phthalocyanine porous organic frameworks.
The nonlinear optical limiting (OL) property of tin phthalocyanine porous organic frameworks (Sn-Pc-POFs) dispersion in the nanosecond regime was studied, which showed excellent dispersibility and stability as well as a low OL threshold. To clarify the nonlinear optical response mechanisms in the material, the energy level structure of Sn-Pc-POFs was simulated using the density functional theory calculation, and the photoinduced carrier dynamics was studied using femtosecond time-resolved transient absorption spectroscopy. The results indicated that the large absorption cross section and long lifetime of the excited state were responsible for the excellent OL property of the material.


MLN8237 ( alisertib ) and its role in peripheral T-cell lymphoma.
Peripheral T-cell lymphomas (PTCL) are a diverse group of rare non-Hodgkin lymphomas (NHL) that carry a poor prognosis and are in need of effective therapies. A greater understanding of how these tumours proliferate as well as how best to exploit these processes should lead to more durable tumour regression and better clinical outcomes for patients. New approaches include the histone deacetylase inhibitors, antifolates, fusion proteins, nucleoside analogues and agents targeting the immune system, which are being investigated either as single agents or as a combination. The authors review the evidence for the orally administered aurora A kinase inhibitor MLN8237 ( alisertib ) in T-cell lymphoma. No significant association between clinical response and AAK expression has been observed but inhibition of this enzyme in a Phase II study has demonstrated tumour regression in 27% of heavily pretreated B- and T-cell NHL, with 50% of PTCL patients responding and 3 of 4 patients achieving durable responses. A Phase III trial in relapsed PTCL is recruiting patients comparing MLN8237 against single agent comparators. With regards to the data; the response rate of MLN8237 in refractory NHL is promising. The authors believe that further preclinical work identifying the best combinations to take through into clinical trials is important, particularly as this agent is used in earlier lines of therapy.


A combined score of pro- and anti-inflammatory interleukins improves mortality prediction in severe sepsis.
Identification of patients at increased risk of death is dramatically important in severe sepsis. Cytokines have been widely assessed as potential biomarkers in this disease, but none of the cytokines studied has evidenced a sufficient specificity or sensitivity to be routinely employed in clinical practice. In this pilot study, we profiled 17 immune mediators in the plasma of 29 consecutively recruited patients with severe sepsis or septic shock, during the first 24h following admission to the ICU, by using a Bio-Plex Human Cytokine 17-Plex Panel (Bio-Rad). Patients were 66.1year old in average. Twelve patients of our cohort died during hospitalization at the ICU, eight of them in the first 72h due to multiorganic dysfunction syndrom (MODS). Levels in plasma of three pro-inflammatory mediators (IL-6, IL-8, MCP-1) and of an immunosuppressive one (IL-10) were higher in those patients with fatal outcome. We developed a combined score with those cytokines showing to better predict mortality in our cohort based on the results of Cox regression analysis. This way, IL-6, IL-8 and IL-10 were included in the score. Patients were split into two groups based on the percentile 75 (P75) of the plasma levels of these three interleukins. Those patients showing at least one interleukin value higher than P75 were given the value "1". Those patients showing IL-6, IL-8, IL-10 levels below P75 were given the value "0". Hazard ratios for mortality at day 3 and day 28th obtained with the combined score were 2-3-fold higher than those obtained with the individual interleukins values. In conclusion, we have described a combined cytokine score associated with a worse outcome in patients with sepsis, which may represent a new avenue to be explored for guiding treatment decisions in this disease.


A critique of elective pediatric supraglottic airway devices.
In 1988, when the Laryngeal Mask Airway-Classic (Intavent Orthofix, Maidenhead, UK), was introduced there were only two choices of airway management: tracheal tube or facemask. The supraglottic airway, as we now understand the term, did not exist. Yet, 20 years later, we are faced with an ever increasing choice of supraglottic airway devices (SAD). For many SADs, with the exception of the LMA-Classic and LMA-Proseal (Intavent Orthofix, Maidenhead, UK), there is a lack of high quality data of efficacy. The best evidence requires a randomized controlled trial comparing a new device against an established alternative, properly powered to detect clinically relevant differences in clinically important outcomes. Such studies in children are very rare. Safety data is even harder to establish particularly for rare events such as aspiration. Therefore, most safety data comes from extended use rather than high quality evidence which inevitably biases against newer devices. For reason of these factors, claims of efficacy and particularly safety must be interpreted cautiously. This narrative review aims to present the evidence surrounding the use of currently available pediatric SADs in routine anesthetic practice.


Safety and Seropositivity after Live Attenuated Vaccine in Adult Patients Receiving Hematopoietic Stem Cell Transplantation.
Vaccination against vaccine-preventable diseases (VPDs) is highly recommended for hematopoietic stem cell transplantation (HSCT) recipients by several guidelines; however, the safety and seropositivity after live attenuated vaccines remain unclear in adult HSCT recipients. We analyzed titers of antibodies against measles, rubella, mumps, and varicella zoster virus (VZV) from Japanese adult patients who underwent allogeneic HSCT (allo-HSCT) (n = 74), autologous HSCT (auto-HSCT) (n = 39), or chemotherapy (n = 93). The seropositive rates for measles, rubella, mumps, and VZV in allo-HSCT recipients were 20.2%, 36.4%, 5.4%, and 55.4%, respectively. These rates were equivalent to those in auto-HSCT recipients but were significantly lower than those in patients receiving chemotherapy. Antibody titers tended to gradually decrease with time. Twenty-nine allo-HSCT recipients and 8 auto-HSCT recipients received live attenuated vaccines against VPDs for which they tested seronegative. The titers of antibodies against measles, rubella, and mumps significantly increased after 2 shots of vaccine, and the seropositive rate increased up to 19%, 30%, and 27%, respectively. Three patients (8.1%) experienced mild adverse events, which resolved promptly, indicating safe administration of the live attenuated vaccines. In multivariate analysis, history of chronic graft-versus-host disease was significantly associated with high seropositivity for measles as well as high seroconversion rate for measles after vaccination. Live attenuated vaccines against VPDs were safely administered in seronegative adult HSCT recipients. A further observational study is crucial to evaluate the efficacy of vaccination in seronegative HSCT patients.


Intranasal drug delivery by spray and drops.
A solution of 99mTc-labelled human serum albumin was administered into the nose as a spray and as one or three drops. The patterns of deposition and the rates of clearance in normal subjects were monitored by gamma scintigraphy. The spray was deposited mainly in the atrium, and cleared slowly into the pharynx. The single drop spread more extensively than the spray, while the three drops were sufficient to cover most of the walls of the nasal cavity. Clearance was faster following administration of the drops. These factors have implications when designing dosage regimens for drugs administered by the intranasal route.


Transport of cranberry A-type procyanidin dimers, trimers, and tetramers across monolayers of human intestinal epithelial Caco-2 cells.
A-type procyanidin oligomers in cranberries are known to inhibit the adhesion of uropathogenic bacteria. B-type procyanidin dimers and trimers are absorbed by humans. The absorption of A-type procyanidins from cranberries in humans has not been demonstrated. This study examined the transport of A-type cranberry procyanidin dimers, trimers, and tetramers on differentiated human intestinal epithelial Caco-2 cell monolayers. Procyanidins were extracted from cranberries and purified using chromatographic methods. Fraction I contained predominantly A-type procyanidin dimer A2 [epicatechin-(2-O-7, 4-8)-epicatechin]. Fraction II contained primarily A-type trimers and tetramers, with B-type trimers, A-type pentamers, and A-type hexamers being minor components. Fraction I or II in solution was added onto the apical side of the Caco-2 cell membranes. The media at the basolateral side of the membranes were analyzed using HPLC-MS(n) after 2 h. Data indicated that procyanidin dimer A2 in fraction I and A-type trimers and tetramers in fraction II traversed across Caco-2 cell monolayers with transport ratio of 0.6%, 0.4%, and 0.2%, respectively. This study demonstrated that A-type dimers, trimers, and tetramers were transported across Caco-2 cells at low rates, suggesting that they could be absorbed by humans after cranberry consumption.


Systematic review and meta-analysis appraising efficacy and safety of adrenaline for adult cardiopulmonary resuscitation.
There is a beneficial effect of adrenaline during adult cardiopulmonary resuscitation (CPR) from cardiac arrest but there is also uncertainty about its safety and effectiveness. The aim of this study was to evaluate the use of adrenaline versus non-adrenaline CPR. PubMed, ScienceDirect, Embase, CENTRAL (Cochrane Central Register of Controlled Trials) and Google Scholar databases were searched from their inception up to 1st July 2020. Two reviewers independently assessed eligibility and risk of bias, with conflicts resolved by a third reviewer. Risk ratio (RR) or mean difference of groups were calculated using fixed or random-effect models. Nineteen trials were identified. The use of adrenaline during CPR was associated with a significantly higher percentage of return of spontaneous circulation (ROSC) compared to non-adrenaline treatment (20.9% vs. 5.9%; RR = 1.87; 95% confidence interval [CI] 1.37-2.55; p < 0.001). The use of adrenaline in CPR was associated with ROSC at 19.4% and for non-adrenaline treatment - 4.3% (RR = 3.23; 95% CI 1.89-5.53; p < 0.001). Survival to discharge (or 30-day survival) when using adrenaline was 6.8% compared to non-adrenaline treatment (5.5%; RR = 0.99; 95% CI 0.76-1.30; p = 0.97). However, the use of adrenaline was associated with a worse neurological outcome (1.6% vs. 2.2%; RR = 0.57; 95% CI 0.42-0.78; p < 0.001). This review suggests that resuscitation with adrenaline is associated with the ROSC and survival to hospital discharge, but no higher effectiveness was observed at discharge with favorable neurological outcome. The analysis showed higher effectiveness of ROSC and survival to hospital discharge in non-shockable rhythms. But more multicenter randomized controlled trials are needed in the future.


Freezing of water in red-osier dogwood stems in relation to cold hardiness.
Studies of stem water in red-osier dogwood (Cornus stolonifera Michx.) using nuclear magnetic resonance spectroscopy indicated that most freezing occurs at temperatures above -30 C in cold-hardy and tender stems. Hardy and tender stems had about the same amount of unfrozen water at -40 C (0.28 gram of water per gram dry weight). When hardy stems were slowly cooled below -20 C, the temperature below which little additional freezing occurs, they survived direct immersion in liquid N(2) (-196 C). Fully hardy samples not slowly precooled to at least -15 C did not survive direct immersion in liquid N(2). The results support the hypothesis that cooling rate is an unimportant factor in tissue survival at and below temperatures where there is little freezable water.


Mast cell inflammasome activity in the meninges regulates EAE disease severity.
Inflammasomes are multiprotein complexes that assemble in response to microbial and other danger signals and regulate the secretion of biologically active IL-1β and IL-18. Although they are important in protective immunity against bacterial, viral and parasitic infections, aberrant inflammasome activity promotes chronic inflammation associated with autoimmune disease. Inflammasomes have been described in many immune cells, but the majority of studies have focused on their activity in macrophages. Here we discuss an important role for mast cell-inflammasome activity in EAE, the rodent model of multiple sclerosis, a CNS demyelinating disease. We review our evidence that mast cells in the meninges, tissues that surround the brain and spinal cord, interact with infiltrating myelin-specific T cells in early disease. This interaction elicits IL-1β expression by mast cells, which in turn, promotes GM-CSF expression by T cells. In view of the essential role that GM-CSF plays in T cell encephalitogenicity, we propose this mast cell-T cell crosstalk in the meninges is critical for EAE disease development.


At the molecular resolution with MINFLUX?
MINFLUX is purported as the next revolutionary fluorescence microscopy technique claiming a spatial resolution in the range of 1-3 nm in fixed and living cells. Though the claim of molecular resolution is attractive, I am concerned whether true 1 nm resolution has been attained. Here, I compare the performance with other super-resolution methods focusing particularly on spatial resolution claims, subjective filtering of localizations, detection versus labelling efficiency and the possible limitations when imaging biological samples containing densely labelled structures. I hope the analysis and evaluation parameters presented here are not only useful for future research directions for single-molecule techniques but also microscope users, developers and core facility managers when deciding on an investment for the next 'state-of-the-art' instrument. This article is part of the Theo Murphy meeting issue 'Super-resolution structured illumination microscopy (part 2)'.


Diacylglycerol accumulation is involved in the potentiating effect of A23187 on carbachol-stimulated amylase secretion from parotid gland.
We studied the role of sn-1, 2-diacylglycerol (DAG) accumulation in the potentiating effect of A23187 on carbachol (CCh)-stimulated amylase secretion from rat parotid acinar cells. A23187 (0.1 microM) linearly increased DAG accumulation with time for at least 30 min. At concentrations higher or lower than 0.1 microM, DAG levels increased for up to 20 min, but declined at 30 min. Dose-response curve for DAG accumulation induced by A23187 was similar to that for amylase secretion. A23187 augmented CCh-stimulated DAG accumulation and amylase secretion. These results suggest that DAG accumulation is involved in the potentiating effect of A23187 on CCh-stimulated amylase secretion.


Salivary Gland Adenoma in a North Island Brown Kiwi (Apteryx mantelli).
A 7-month-old male North Island brown kiwi (Apteryx mantelli) was transferred from a European zoological park to a North American private aviary. The bird appeared clinically normal upon arrival, but within 30 days, it developed clinical disease signs of sneezing, stridor, and increased respiratory effort. Upon examination a 1-mm yellow plaque was identified on the glottis. After 14 days of empiric treatment with enrofloxacin, meloxicam, and itraconazole, on repeat examination, the glottal plaque had increased in size to a 7-mm-diameter friable mass attached to the right laryngeal cartilage and was partially obstructing the airway. Initially, 80% of the mass was manually dislodged, but within 4 days the tissue mass had again enlarged to approximately 3 mm × 4 mm × 4 mm, prompting surgical excision. On histopathologic examination, the mass was identified as a benign salivary gland adenoma without clear margins. Approximately 3 years postexcision, there is no evidence of tumor regrowth. The successful excision of a benign salivary tumor described in this report will serve as a valuable guide for future cases of similar neoplasms diagnosed in the oral cavity of kiwis and other avian species.


Inhomogeneous magnetism in single crystalline Sr(3)CuIrO(6+delta): implications to phase-separation concepts.
The single crystalline form of an insulator, Sr(3)CuIrO(6+delta), is shown to exhibit unexpectedly more than one magnetic transition (at 5 and 19 K) with spin-glass-like magnetic susceptibility behavior. On the basis of this finding, viz., inhomogeneous magnetism in a chemically homogeneous material, we propose that the idea of "phase separation" described for manganites is more widespread in different ways. The observed experimental features enable us to make a comparison with the predictions of a recent toy model on magnetic phase separation in an insulating environment.


Myeloid differentiation of purified CD34+ cells after stimulation with recombinant human granulocyte-monocyte colony-stimulating factor (CSF), granulocyte-CSF, monocyte-CSF, and interleukin-3.
CD34+ cells isolated from bone marrow or umbilical cord blood from healthy donors were studied for proliferation and differentiation in liquid cultures in the presence of recombinant human granulocyte-monocyte colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), monocyte CSF (M-CSF), and interleukin-3 (IL-3), followed by immunophenotyping for myeloid and myeloid-associated cell surface markers. IL-3, either alone or together with GM-CSF, G-CSF, or M-CSF, induced, on average, 50-fold cell multiplication, GM-CSF five fold to 10-fold, and G-CSF and M-CSF less than fivefold. Cells from cultures stimulated with GM-CSF, G-CSF, or M-CSF alone contained cells with a "broad" myeloid profile, "broader" than observed in cultures with IL-3. However, since IL-3 induced rapid cell multiplication, high numbers of cells expressing early (CD13, CD33) and late myeloid markers (CD14, CD15) were recovered. The presence of other CSFs together with IL-3 did not alter the IL-3-induced effect on the cells. When 5,000 CD34+ cells were cultured with IL-3 alone, the cultures still contained 2,000 to 5,000 CD34+ cells after 14 days of culture, while cells cultured with GM-CSF, G-CSF, or M-CSF contained less than 1,000 CD34+ cells. Furthermore, 1,000 to 3,000 cells were positive for the megakaryocytic lineage marker CD41b after cultures with GM-CSF or IL-3, while cultures with G-CSF or M-CSF did not contain detectable numbers of CD41b+ cells. Finally, erythroid cells could also be generated from purified CD34+ cells. The results show that IL-3 and GM-CSF can induce rapid proliferation of purified CD34+ cells in vitro with differentiation to multiple myeloid lineages, while certain subsets maintain expression of CD34.


Pain in children with cerebral palsy: a cross-sectional multicentre European study.
To determine the prevalence and associations of self-reported and parent-reported pain in children with cerebral palsy (CP) of all severities. Cross-sectional design using a questionnaire; analysis using ordinal regression. Children aged 8-12 years were randomly selected from population-based registers of children with CP in eight European regions; a further region recruited 75 children from multiple sources. Outcome measures were pain in the previous week among children who could self-report and parents' perception of their child's pain in the previous 4 weeks. Data on pain were available from 490 children who could self-report and parents of 806 children (those who could and could not self-report). The estimated population prevalence of self-reported pain in the previous week was 60% (95% CI: 54-65%) and that of parent-reported pain in the previous 4 weeks was 73% (95% CI: 69-76%). In self-reporting children, older children reported more pain but pain was not significantly associated with severity of impairment. In parent reports, severity of child impairment, seizures and parental unemployment were associated with more frequent and severe pain. Pain in children with CP is common. Clinicians should enquire about pain and consider appropriate physical, therapeutic or psychological management.


Ventricular lead dysfunction and subclavian vein stenosis: when problems come in pairs.
The widespread and increasing use of cardiac devices implantation naturally augments the number of device related complications. Lead failure is a known complication associated with increased morbidity, mortality and need for reintervention.Chronic stenosis or occlusions of coronary, cephalic or subclavian veins, especially at the site of previous device implantation,can limit lead passage through the target vein, imposing great technical difficulties, especially in patients needing follow-up procedures such as lead revisions and/or system upgrades. Venous balloon angioplasty can be a valuable and safe tool for successful implantation, helping to avoid more complex and hazardous procedures. The authors report the case of a 65 years old male presenting with a "Sprint Fidelis" defibrillator lead malfunction and severe asymptomatic left subclavian vein stenosis after cardiac resynchronization defibrillator therapy. The patient was submitted to a successful percutaneous balloon venoplasty in order to regain adequate venous access and enable reimplantation of the right ventricular lead.


Efficacy of salvage radiotherapy plus 2-year androgen suppression for postradical prostatectomy patients with PSA relapse.
To determine the efficacy of a combined approach of radiotherapy (RT) plus 2-year androgen suppression (AS) as salvage treatment for prostate-specific antigen (PSA) relapse after radical prostatectomy (RP). Seventy-five patients with PSA relapse after RP were treated with salvage RT plus 2-year AS, as per a pilot, prospective study. AS started within 1 month after completion of salvage RT and consisted of nilutamide for 4 weeks and buserelin acetate depot subcutaneously every 2 months for 2 years. Relapse-free rate including freedom from PSA relapse was estimated using the Kaplan-Meier method. PSA relapse was defined as a PSA rise above 0.2 ng/mL with two consecutive increases over a minimum of 3 months. A Cox regression analysis was performed to evaluate prognostic factors for relapse. Median age of the cohort was 63 years at the time of salvage RT. Median follow-up from salvage RT was 6.4 years. All achieved initially complete PSA response (< 0.2) with the protocol treatment. Relapse-free rate including the freedom from PSA relapse was 91.5% at 5 years and 78.6% at 7 years. Overall survival rate was 93.2% at both 5 and 7 years. On Cox regression analysis, pT3 stage and PSA relapse less than 2 years after RP were significant prognostic factors for relapse. The combined treatment of salvage RT plus 2-year AS yielded an encouraging result for patients with PSA relapse after RP and needs a confirmatory study.


Language-enriched exercise plus socialization for older adults with dementia: translation to rural communities.
Interventions that stimulate and engage individuals with dementia physically, cognitively, and socially offer promise for improving health and well-being and for potentially slowing functional losses with disease progression. We describe a volunteer-based intervention that combines physical exercise, cognitive-linguistic stimulation, and social outings for older persons living with dementia in rural communities. One-year follow-up data, although clearly preliminary (n = 8), suggest stability in global cognition, mood, and aspects of physical fitness. Challenges to implementing dementia interventions in rural areas are discussed.


Using Accelerometer Data to Identify Movement Patterns in an Older Adult: Innovative Strategy for Physical Activity Promotion.
Evidence suggests a physically active lifestyle increases proportion of life lived free of disability. Unfortunately, physical activity participation in older adults is low, suggesting innovative strategies are needed. This case-report (1) examined daily activity routines from accelerometer data; and (2) utilized the movement patterns to "infuse" physical activity within the participant's normal routine. A 60 year old wore an Actigraph GT3X+ accelerometer, on 2 separate days and weeks. Movement patterns, from "raw" accelerometer data, were presented to the participant to identify areas of high and low activity, with suggestions how to increase overall activity. Results indicated activity patterns were reproducible. Physical activity infusions increased movement counts by 34%, and moderate-vigorous physical activity (MVPA) by ~82minutes. Examination of "raw" accelerometer data identified distinct movement routines. Understanding these routines allowed for health provider/participant interaction that led to physical activity "infusions" which contributed to a large increase in MVPA, without major alterations to the individual's day.


A linear relationship exists among brain diffusion eigenvalues measured by diffusion tensor magnetic resonance imaging.
Diffusion in biological tissues can be measured by magnetic resonance diffusion tensor imaging The complex nature of anisotropic diffusion in the brain has been described by a diffusion tensor which contains information about the magnitude of diffusion in different directions. Each tensor contains a set of three eigenvalues which are related to the major, intermediate, and minor axes of a diffusion ellipsoid. This investigation demonstrates that the various sets of diffusion eigenvalues from different regions of the brain lie along a line in ordered eigenvalue space. Sets of ordered diffusion eigenvalues were considered points in ordered eigenvalue space. The line which best fit the data by minimizing the total squared deviations was determined. A new coordinate system was constructed through translation and rotation which spanned ordered eigenvalue space. Eigenvalues from both monkey brain and human brain were studied. It was found that the sets of eigenvalues from both species have significant linear trends. Moreover, the same line may describe the brain eigenvalues from both species. It is likely that this linear relationship of the eigenvalues observed in an ordered eigenvalue plot is related to a combination of (1) conservation of total isotropic diffusion and (2) the degree of orientational dispersion of the microfibers within each voxel.


Global Research Trends in Tyrosine Kinase Inhibitors: Coword and Visualization Study.
Tyrosine kinase inhibitors (TKIs) have achieved revolutionary results in the treatment of a wide range of tumors, and many studies on this topic continue to be published every year. Some of the published reviews provide great value for us to understand TKIs. However, there is a lack of studies on the knowledge structure, bibliometric analysis, and visualization results in TKIs research. This paper aims to investigate the knowledge structure, hotspots, and trends of evolution of the TKIs research by co-word analysis and literature visualization and help researchers in this field to gain a comprehensive understanding of the current status and trends. We retrieved all academic papers about TKIs published between 2016 and 2020 from the Web of Science. By counting keywords from those papers, we generated the co-word networks by extracting the co-occurrence relationships between keywords, and then segmented communities to identify the subdirections of TKIs research by calculating the network metrics of the overall and local networks. We also mapped the association network topology, including the network within and between TKIs subdirections, to reveal the association and structure among varied subdirections. Furthermore, we detected keyword bursts by combining their burst weights and durations to reveal changes in the focus of TKIs research. Finally, evolution venation and strategic diagram were generated to reveal the trends of TKIs research. We obtained 6782 unique words (total frequency 26,175) from 5584 paper titles. Finally, 296 high-frequency words were selected with a threshold of 10 after discussion, the total frequency of which accounted for 65.41% (17,120/26,175). The analysis of burst disciplines revealed a variable number of burst words of TKIs research every year, especially in 2019 and 2020, such as HER2, pyrotinib, next-generation sequencing, immunotherapy, ALK-TKI, ALK rearrangement. By network calculation, the TKIs co-word network was divided into 6 communities: C1 (non-small-cell lung cancer), C2 (targeted therapy), C3 (chronic myeloid leukemia), C4 (HER2), C5 (pharmacokinetics), and C6 (ALK). The venation diagram revealed several clear and continuous evolution trends, such as non-small-cell lung cancer venation, chronic myeloid leukemia venation, renal cell carcinoma venation, chronic lymphocytic leukemia venation. In the strategic diagram, C1 (non-small-cell lung cancer) was the core direction located in the first quadrant, C2 (targeted therapy) was exactly at the junction of the first and fourth quadrants, which meant that C2 was developing; and C3 (chronic myeloid leukemia), C4 (HER2), and C5 (pharmacokinetics) were all immature and located in the third quadrant. Using co-word analysis and literature visualization, we revealed the hotspots, knowledge structure, and trends of evolution of TKIs research between 2016 and 2020. TKIs research mainly focused on targeted therapies against varied tumors, particularly against non-small-cell lung cancer. The attention on chronic myeloid leukemia and pharmacokinetics was gradually decreasing, but the focus on HER2 and ALK was rapidly increasing. TKIs research had shown a clear development path: TKIs research was disease focused and revolved around "gene targets/targeted drugs/resistance mechanisms." Our outcomes will provide sound and effective support to researchers, funders, policymakers, and clinicians.


Fundamental Understanding of Water-Induced Mechanisms in Li-O2 Batteries: Recent Developments and Perspectives.
Modern sustainability challenges in recent years have warranted the development of new energy storage technologies. Practical realization of the lithium-O2 battery holds great promise for revolutionizing energy storage as it holds the highest theoretical specific energy of any rechargeable battery yet discovered. However, the complete realization of Li-O2 batteries necessitates ambient air operations, which presents quite a few challenges, as carbon dioxide (CO2 ) and water (H2 O) contaminants introduce unwanted byproducts from side reactions that greatly affect battery performance. Although current research has thoroughly explored the beneficial incorporation of CO2 , much mystery remains over the inconsistent effects of H2 O. The presence of water in both the cathode and electrolyte has been observed to alter reaction mechanisms differently, resulting in a diverse range of effects on voltage, capacity, and cyclability. Moreover, recent preliminary research with catalysts and redox mediators has attempted to utilize the presence of water to the battery's benefit. Here, the key mechanism discrepancies of water-afflicted Li-O2 batteries are presented, concluding with a perspective on future research directions for nonaqueous Li-O2 batteries.


The relation between the internal phosphorylation potential and the proton motive force in mitochondria during ATP synthesis and hydrolysis.
Using 31P NMR and a potassium ion distribution method, the internal phosphorylation potential and the transmembrane electrical potential of intact rat liver mitochondria were measured simultaneously during ATP synthesis and ATP hydrolysis. The ATPase was shown to quickly equilibrate the internal phosphorylation potential with the proton motive force across the mitochondrial membrane. Upon oxygenation of anaerobic mitochondria, there was a very fast increase of delta pH and a quick uptake of inorganic phosphate prior to the buildup of the internal ATP. Consistent with the chemiosmotic theory, these results showed the presence of proton pumping by the respiratory system from the bulk internal aqueous phase to the bulk external aqueous phase. There was, in the measured energetic parameters, no indication of direct energy coupling or short circuiting protons between the respiratory energy input and the ATP synthesis.


[Inhibition of the in vitro interaction between hypoxia inducible factor 1alpha and p300 by mitogen-activated protein kinase phosphatase 1].
To investigate the effects of mitogen-activated protein kinase phosphatase-1 (MKP-1) on the interaction between hypoxia-inducible factor (HIF)-1alpha and coactivator p300. Prokaryotic expression vector PGEX-4T1 was constructed based on DNA recombination technology. GST fusion proteins were purified by glutathione-agarose beads and transfected into Escherichia coli BL-21. Effects of MKP-1 or PD98059 on in vitro interaction between HIF-1alpha and p300 was determined by Pull-down assay coupled with Western bloting. Effects of MKP-1 on the p300 expression level was detected using Western bloting. (1) GST fusion proteins were expressed in BL-21 Escherichia coli and purified proteins were obtained. (2) Less amount of p300 was pulled down by GST fusion protein from SGC7901-MKP-1 cells than from control cells after 12 hours of exposure to hypoxia. (3) 12 hours after hypoxia, Less amount of p300 was pulled down by GST fusion protein from PD98059 treated cells than from DMSO treated cells or SGC7901 cells. (4) There were no significant differences in p300 expression levels between recombinant MKP-1 transfected cells and control cells after 12 hours of exposure to hypoxia. MKP-1 inhibits the in vitro interaction between HIF-1alpha and p300.


Cholinergic modulation of basal and amphetamine-induced dopamine release in rat medial prefrontal cortex and nucleus accumbens.
Behavioral evidence suggests that muscarinic/cholinergic inhibition of brain dopaminergic activity may be a useful principle for developing novel antipsychotic drugs (APDs). Thus, oxotremorine, a muscarinic agonist, attenuates amphetamine-induced locomotor activity in rodents, an effect also produced by a wide variety of proven APDs, whereas scopolamine, a muscarinic antagonist, has the opposite effect. Since atypical APDs such as clozapine, olanzapine, risperidone, ziprasidone and quetiapine, increase brain acetylcholine as well as dopamine (DA) release in a region-specific manner, their effects on cholinergic and dopaminergic neurotransmission may also contribute to various actions of these drugs. Oxotremorine (0.5-1.5 mg/kg) dose-dependently and preferentially increased DA release in rat medial prefrontal cortex (mPFC), compared to the nucleus accumbens (NAC). However, S-(-)-scopolamine (0.5-1.5 mg/kg) produced similar increases in DA release in the mPFC, but the effect was much less than that of oxotremorine. Whereas a dose of S-(-)-scopolamine of 0.5 mg/kg comparably increased DA release in the mPFC and NAC, 1.5 mg/kg had no effect on DA release in the NAC. Oxotremorine-M (0.5 mg/kg), a M(1/4)-preferring agonist, also increased DA release in the mPFC, but not the NAC, an effect completely abolished by telenzepine (3 mg/kg), a M(1/4)-preferring antagonist, which by itself had no effect on DA release in either region. Oxotremorine (0.5, but not 1.5, mg/kg) attenuated amphetamine (1 mg/kg)-induced DA release in the NAC, whereas S-(-)-scopolamine did not. Oxotremorine (1.5 mg/kg) and S-(-)-scopolamine (0.5 mg/kg) modestly but significantly potentiated amphetamine (1 mg/kg)-induced DA release in the mPFC. These results suggest that stimulation of muscarinic receptors, in particular M(1/4), as indicated by the effect of oxotremorine-M and telenzepine, may preferentially increase cortical DA release and inhibit amphetamine-induced DA release in the NAC.


B-type cyclins regulate G1 progression in fission yeast in opposition to the p25rum1 cdk inhibitor.
The onset of S phase in fission yeast is regulated at Start, the point of commitment to the mitotic cell cycle. The p34cdc2 kinase is essential for G1 progression past Start, but until now its regulation has been poorly understood. Here we show that the cig2/cyc17 B-type cyclin has an important role in G1 progression, and demonstrate that p34cdc2 kinase activity is periodically associated with cig2 in G1. Cells lacking cig2 are defective in G1 progression, and this is particularly clear in small cells that must regulate Start with respect to cell size. We also find that the cig1 B-type cyclin can promote G1 progression. Whilst p25rum1 can inhibit cig2/cdc2 activity in vitro, and may transiently inhibit this complex in vivo, cig1 is regulated independently of p25rum1. Since cig1/cdc2 kinase activity peaks in mitotic cells, and decreases after mitosis with similar kinetics to cdc13-associated kinase activity, we suggest that cig2 is likely to be the principal fission yeast G1 cyclin. cig2 protein levels accumulate in G1 cells, and we propose that p25rum1 may transiently inhibit cig2-associated p34cdc2 activity until the critical cell size required for Start is reached.


The application of magnetization transfer to MR angiography with reduced total power.
Magnetization transfer (MT) techniques have been shown to significantly reduce background soft-tissue signal in time-of-flight magnetic resonance angiography. To achieve sufficient suppression, radio frequency (RF) pulses with tip angles on the order of 1000 degrees are typically used, resulting in significant RF power deposition in the patient. Although these power deposition levels do not exceed the FDA guidelines, they are significantly higher than those used in typical imaging techniques. The use of these same magnetization transfer pulses in applications at field strengths higher than 1.5 T will require MT power levels which exceed FDA safety standards. This report demonstrates that the total power deposition required to achieve background tissue suppression can be significantly reduced by the application of the saturation pulses only during the phase-encoding steps corresponding to the central portion of "k space." This technique allows equivalent soft tissue suppression with approximately 10% of the energy deposition of conventional magnetization transfer techniques.


Predictors of thromboembolism in atrial fibrillation: I. Clinical features of patients at risk. The Stroke Prevention in Atrial Fibrillation Investigators.
To identify those patients with nonrheumatic atrial fibrillation who are at high risk and those at low risk for arterial thromboembolism. Cohort study of patients assigned to placebo in a randomized clinical trial. Five hundred sixty-eight inpatients and outpatients with nonrheumatic atrial fibrillation assigned to placebo therapy at 15 U.S. medical centers from 1987 to 1989 in the Stroke Prevention in Atrial Fibrillation study. Patients were followed for a mean of 1.3 years. Clinical variables were assessed at study entry and correlated with subsequent ischemic stroke and systemic embolism by multivariate analysis. Recent (within 3 months) congestive heart failure, a history of hypertension, and previous arterial thromboembolism were each significantly and independently associated with a substantial risk for thromboembolism (greater than 7% per year; P less than or equal to 0.05). The presence of these three independent clinical predictors (recent congestive heart failure, history of hypertension, previous thromboembolism of 2.5% per year (no risk factors), 7.2% per year (one risk factor), and 17.6% per year (two or three risk factors). Nondiabetic patients without these risk factors, comprising 38% of the cohort, had a low risk for thromboembolism (1.4% per year; 95% Cl, 0.05% to 3.7%). Patients without clinical risk factors who were under 60 years of age had no thromboembolic events. Patients with atrial fibrillation at high risk (greater than 7% per year) and low risk (less than 3% per year) for thromboembolism can be identified by readily available clinical variables.


PTEN drives Th17 cell differentiation by preventing IL-2 production.
T helper 17 (Th17) cells are a CD4+ T cell subset that produces IL-17A to mediate inflammation and autoimmunity. IL-2 inhibits Th17 cell differentiation. However, the mechanism by which IL-2 is suppressed during Th17 cell differentiation remains unclear. Here, we show that phosphatase and tensin homologue (PTEN) is a key factor that regulates Th17 cell differentiation by suppressing IL-2 production. Th17-specific Pten deletion (Ptenfl/flIl17acre ) impairs Th17 cell differentiation in vitro and ameliorated symptoms of experimental autoimmune encephalomyelitis (EAE), a model of Th17-mediated autoimmune disease. Mechanistically, Pten deficiency up-regulates IL-2 and phosphorylation of STAT5, but reduces STAT3 phosphorylation, thereby inhibiting Th17 cell differentiation. PTEN inhibitors block Th17 cell differentiation in vitro and in the EAE model. Thus, PTEN plays a key role in Th17 cell differentiation by blocking IL-2 expression.


Complex carbohydrates: the science and the label.
This conference resulted in a foundation upon which consensus will be built in the future. Further, it provided a forum for the articulation of the critical need for carbohydrates in human nutrition. We have come a long way in the past 25 years in the food and nutrition sciences and this conference well illustrated that point. At the White House Conference on Nutrition in 1969, macronutrients were never even mentioned as being necessary to nutrition; only micronutrients were emphasized. In 1977 the term complex carbohydrate was used without definition in the Dietary Goals for the United States. This conference encapsulated the tremendous strides that have been made concerning the chemical, nutritional, biologic, and physiologic importance of carbohydrates in health and disease. It is fascinating to review the recommendations concerning complex carbohydrate from 1977 on. Recommendations were made by the Senate Select Committee in 1977; the Dietary Guidelines of 1980, 1985, and 1990; the Surgeon General's report of 1979 and 1988; the 10th edition of Recommended Dietary Allowances; the 1989 National Academy of Sciences Diet and Health: Implications for Reducing Chronic Disease Risk; the 1991 FDA proposal for labeling; and the 1992 Food Guide Pyramid. Indeed, as Dr. Joanne Slavin pointed out, "there is a wide range of consensus that increased complex carbohydrate is consistent with good health," and certainly as Dr. Gary Henderson said, "the term complex carbohydrate has equity with consumers." With this level of apparent clarity it is difficult at first to identify a problem for the food label. After all, if consumer health would benefit, why not simply do it? However, a problem does exist in that carbohydrates may be classified chemically in groups that are difficult to analyze and to define as to their physiologic function in the body. Indeed, complex carbohydrates defined by chain length may have molecular structures less complex than those of smaller units and may vary in solubility and digestibility. A continuum does exist in each of the chemical, analytical, and physiologic characteristics of carbohydrates. Scientists do not like a continuum and regulators probably like it even less, but such a continuum holds great promise for future consensus. This continuum provided the thoughtful alternatives presented above by Drs. Jonathan DeVries, Dennis Gordon, and Alison Stephen. Dr. DeVries suggested a scheme of complex carbohydrates, sugars, and sugar alochols, while Dr. Gordon suggested complex carbohydrates, dietary fiber, and simple carbohydrates, and Dr. Stephen suggested starch, sugar, and nonstarch polysaccharides.(ABSTRACT TRUNCATED AT 400 WORDS)


Informed consent for tracheostomy procedures in Intensive Care Unit: an Italian national survey.
Critically ill patients in Intensive Care Unit (ICU), due to their temporary or permanent incompetence, are often not capable to provide informed consent (IC), although required, for not emergency invasive procedures, like elective tracheostomy. By Italian law, a person with partially/temporarily physical/mental impairment needs a legal tutorship appointed by the court (Support Administrator, SA). We performed a national survey in Italy to investigate IC practice for elective tracheostomy procedure in critically ill conscious and unconscious patients in ICU. Questions about IC were included in a survey concerning the clinical practice of tracheostomy in ICU. The survey was approved by the Italian Society of Anesthesia, Analgesia and Intensive Care (SIAARTI, n° 434 - 28 March 2012) and sent by e-mail to all members included in its mailing list. The duration of the survey was three months from April to June 2012. All required information was referred to the year 2011. The mailed questionnaire correctly fulfilled was sent back by 131/427 (30%) national ICUs. Our data showed 1) in conscious patients, IC was obtained by 82.4% of ICUs; 2) in unconscious patients, IC was obtained in only 61.8% with different procedures not following the current Italian law, 3) for surgical tracheostomy performed in operating room, IC was obtained in conscious and unconscious patients in only 69.8% and 47.2% of ICUs, respectively, 4) risk/benefit informative document was provided in 61.1% ICUs, but available only in 47.2% of ICUs performing tracheostomy in operating room. In Italian ICUs, participating to this study, the procedures related to IC for conscious and unconscious critically ill patients requiring surgical or percutaneous tracheostomy are not in line with current legal rules and procedures.


Efficient synthesis of 2-amino-6-arylbenzothiazoles via Pd(0) Suzuki cross coupling reactions: potent urease enzyme inhibition and nitric oxide scavenging activities of the products.
In general, benzothiazole derivatives have attracted great interest due to thier pharmaceutical and biological importance. New 2-amino-6-arylbenzothiazoles were synthesized in moderate to excellent yields via Suzuki cross coupling reactions using various aryl boronic acids and aryl boronic acid pinacol esters and the antiurease and nitric oxide (NO) scavenging activity of the products were also examined. The most active compound concerning urease enzyme inhibition was 6-phenylbenzo[d]thiazole-2-amine 3e, with an IC₅₀ value of 26.35 µg/mL. Compound 3c, 6-(4-methoxyphenyl) benzo[d]thiazole-2-amine, exhibited the highest nitric oxide percentage scavenging at 100 µg/mL.


Minimum secondary structure requirements for catalytic activity of a self-splicing group I intron.
We have completed a comprehensive deletion analysis of the Tetrahymena ribozyme in order to define the minimum secondary structure requirements for phosphoester transfer activity of a self-splicing group I intron. A total of 299 nucleotides were removed in a piecewise fashion, leaving a catalytic core of 114 nucleotides that form 7 base-paired structural elements. Among the various deletion mutants are a 300-nucleotide single-deletion mutant and a 281-nucleotide double-deletion mutant whose activity exceeds that of the wild type when tested under physiologic conditions. Consideration of those structural elements that are essential for catalytic activity leads to a simplified secondary structure model of the catalytic core of a group I intron.


Interleukin-10 promotes activation-induced cell death of SLE lymphocytes mediated by Fas ligand.
Immune function in SLE is paradoxically characterized by active T cell help for autoantibody production, along with impaired T cell proliferative and cytokine responses in vitro. To reconcile these observations, we investigated the possibility that the accelerated spontaneous cell death of SLE lymphocytes in vitro is caused by an activation-induced cell death process initiated in vivo. 27 SLE patients, three patients with systemic vasculitis, seven patients with arthritis, and 14 healthy subjects were studied. Patients with clinically active SLE or systemic vasculitis had accelerated spontaneous death of PBMC with features of apoptosis at day 5 of culture. A prominent role for IL-10 in the induction of apoptosis was observed, as neutralizing anti-IL-10 mAb markedly reduced cell death in the active SLE patients by 50%, from 22.3 +/- 5.2% to 11.2 +/- 2.8%, and the addition of IL-10 decreased viability in the active SLE group, but not in the control group, by 38%. In addition, apoptosis was shown to be actively induced through the Fas pathway. The potential clinical relevance of T cell apoptosis in active SLE is supported by the correlation of increased apoptosis and IL-10 levels in vitro with low lymphocyte counts in vivo. We conclude that the spontaneous cell death observed in vitro in lymphocytes from patients with SLE and other systemic autoimmune disorders results from in vivo T cell activation, is actively induced by IL-10 and Fas ligand, and reflects pathophysiologically important events in vivo. Activation-induced cell death in vivo provides a pathogenic link between the aberrant T helper cell activation and impaired T cell function that are characteristic features of the immune system of patients with SLE.


Horizontal Gaze Palsy and Progressive Scoliosis in Dizygotic Twins.
Horizontal gaze palsy and progressive scoliosis (HGPPS) is a rare autosomal recessive disorder caused by mutations in the ROBO3 gene. Clinical presentation consists of impairment of conjugate horizontal eye movements together with a progressive scoliosis beginning in childhood. We report dizygotic twins with HGPPS that had absence of conjugate horizontal eye movements combined with divergent strabismus and synergistic divergence. One of them also had a congenital palpebral ptosis and vertical strabismus of the right eye. Onset of scoliosis occurred in childhood with rapid progression in the second decade of life. Brain imaging showed characteristic features of the disease such as hypoplasia of the pons and a midline cleft of the brainstem with a butterfly-like bifid appearance. Genetic analysis revealed a pathogenic homozygous mutation on the ROBO3 gene. These siblings and a previous report of two other individuals with the same disorder from the same small geographical region with less than 38000 inhabitants, likely represent a founder effect.


Kidney and liver biomarkers in female dry-cleaning workers exposed to perchloroethylene.
Blood and urine perchloroethylene and urine trichloroacetic acid, as markers of exposure, and serum AST, ALT, GGT and creatinine, urine total solutes and proteins, angiotensin converting enzyme, N-acetyl-ß-D-glucosaminidase and glutamine synthetase, as markers of effect, were measured in 40 dry-cleaning and 45 ironing-shop female workers. Average perchloroethylene air level in the dry-cleaning shops was 59.7 mg m(-3), i.e. three-fold lower than the current A.C.G.I.H. TLV-TWA (170 mg (m-3)). No statistically significant difference in the mean values of any of the effect markers was observed between the two groups, except for AST which was significantly higher in drycleaners. In addition, a statistically significant correlation was observed in dry-cleaners between environmental perchloroethylene and total urinary solutes (r = 0.308, p < 0.05) or urine glutamine synthetase (r= 0.469, p < 0 .01), between glutamine synthetase and blood perchloroethylene in post-shift (r= 0.406, p < 0.01) or urinary perchloroethylene in post(r= 0.571, p < 0.001) or pre-shift (r= 0.586, p < 0.001), and between urinary perchloroethylene in pre-shift and GGT (r= 0.407, p < 0.05). Interestingly, some statistically significant correlations between exposure and effect indices were found in ironing-shop workers alone, as in all subjects. Finally, transaminases, GGT and total urinary proteins were influenced by age and alcohol consumption which were significantly higher in dry-cleaners, thus providing an explanation for some of the correlations observed. In conclusion, our results show a dose-related increase of glutamine synthetase activity,a marker of damage of the pars recta of the kidney proximal tubule, in the urine of female subjects exposed to perchloroethylene concentrations in the work environment lower than current A.C.G.I.H. TLV-TWA.


Involvement of beta-COP in membrane traffic through the Golgi complex.
Non-clathrin-coated vesicles mediate membrane traffic through the Golgi complex. The proteins that constitute the coats of these vesicles have similar molecular weights to the clathrin coat proteins. A major component of the coat of non-clathrin-coated vesicles, beta-COP, has significant homology with the clathrin coat protein beta-adaptin, indicating that the coats of the two different classes of vesicles may be structurally and functionally homologous.


Lateral Trochlear Inclination Angle: Measurement via a 2-Image Technique to Reliably Characterize and Quantify Trochlear Dysplasia.
Trochlear dysplasia (TD) is a risk factor for patellar instability (PI). The Dejour classification categorizes TD but has suboptimal reliability. Lateral trochlear inclination (LTI) is a quantitative measurement of trochlear dysplasia on a single axial magnetic resonance imaging (MRI) scan. A modified LTI measurement technique using 2 different axial MRI scans that reference the most proximal aspect of the trochlear cartilage on 1 image and the fully formed posterior condyles on the second image would be as reliable as and significantly different from the single-image measurement technique for LTI. Further, the 2-image LTI would adequately represent overall proximal trochlear morphologic characteristics. Cohort study (diagnosis); Level of evidence, 2. Patients aged 9 to 18 years treated for PI between 2014 and 2017 were identified. The Dejour classification was radiographically determined. Single-image LTI was measured on a single axial MRI scan at the most proximal aspect of visible trochlear cartilage. A 2-image LTI was measured from 2 separate MRI scans: 1 at the most proximal aspect of trochlear cartilage and the second at the fully formed posterior condyles. This 2-image LTI was repeated at 3 subsequent levels (the first measurement is referred to as LTI-1; repeated measurements are LTI-2, LTI-3, and LTI-4, moving distally). In total, 65 patients met the inclusion criteria, and 30 were randomly selected for reliability analysis. Inter- and intrarater reliability trended toward more variability for single-image LTI (intraclass correlation coefficient [ICC], 0.86 and 0.88, respectively) than for 2-image LTI (ICC, 0.97 and 0.96, respectively). The Dejour classification had lower intra- and interrater reliability (ICC, 0.31 and 0.73, respectively). Average single-image LTI (9.2° ± 12.6°) was greater than average 2-image LTI-1 (4.2° SD ± 11.9°) (P = .0125). Single-image LTI classified 60% of patients with PI as having TD, whereas the 2-image LTI classified 71% as having TD. The 2-image LTI was able to capture 91% of overall proximal trochlear morphologic characteristics. LTI has higher reliability when performed using a 2-image measurement technique compared with single-image LTI and Dejour classification. The strong correlation between 2-image LTI and average LTI shows that 91% of TD is represented on the most proximal axial image. Because the single-image measurement appears to underestimate dysplasia, previously described thresholds should be reexamined using this 2-image technique to appropriately characterize TD.


Governance of science at the National Cancer Institute: perceptions and opportunities in oncogene research.
Insights from various areas of carcinogenesis can now be blended into cohesive and molecular hypotheses testable at a clinical level. One can now define new areas such as biochemical epidemiology. Whereas previously one thought of identifying individuals at high risk for cancer due to life-style or occupation, one can now propose to identify the susceptible individual at the molecular level for some cancers. Theoretically, if past exposure to carcinogens were significant, we may now be able to measure the exact sites of attack and damage in cellular DNA. We now have oncogenes as the probable targets. Treatment potential with highly specific molecular tools should not be far behind. As often cited before, the first priority of the NCl has always been basic research. The present excitement in the area of oncogenes has certainly been a shining example of research success. As is always the case in a rapidly moving field, there are optimists and pessimists. There are fears of overpromise and dangers of lack of swift application. NCl's view can be summed up this way. Oncogene research is important if only for its implications in developmental biology. It needs no other reason for support or excitement. It also will be important to our understanding of cancer; how important, we do not yet know. We believe it will lead to practical applications in diagnosis, prevention, and treatment; how practical and how soon remain unknowns. By definition then, we are clearly optimists, for which no apologies are offered. The danger of overpromise, it seems to these authors, is exceeded by the risk of failure to pursue and apply one of the most exciting areas of research that brings molecular biology to the crowded bedside of the cancer patient. A good dose of optimism seems about right to make a little room.


Remotely triggerable drug delivery systems.
Triggerable drug delivery systems enable on-demand controlled release profiles that may enhance therapeutic effectiveness and reduce systemic toxicity. Recently, a number of new materials have been developed that exhibit sensitivity to visible light, near-infrared (NIR) light, ultrasound, or magnetic fields. This responsiveness can be triggered remotely to provide flexible control of dose magnitude and timing. Here we review triggerable materials that range in scale from nano to macro, and are activated by a range of stimuli.


Power spectrum density of EEGs of sleeping epilepsy-prone El mice and their non-epileptic mother strain.
A power spectrum density (PSD) analysis was performed on electroencephalograms (EEG) of sleeping epileptic El mice and non-epileptic ddY mice. A respiratory peak at 3.13 Hz was detected in the EEGs of both categories. The PSD analysis revealed a peak at 8.59 Hz in the El mice, which was associated with interictal discharges. This peak may be helpful in diagnosing epilepsy.


Spinal cord injury and anxiety: a comprehensive review.
Although there have been past literature reviews which have addressed the psychological adjustment, consequences, and impact/reaction to spinal cord injury, as well as reviews of depression after spinal cord injury, there appears to be an absence of reviews which have focused primarily on the relationship between spinal cord injury and anxiety. The purpose of this paper is to present a comprehensive review of the relatively recent (the past 23-31 years depending on the database utilized) scientific literature as it pertains to anxiety reactions in spinal cord injured individuals. Specifically, this paper provides reviews of the prevalence/presence of anxiety reactions, as well as the correlates of anxiety, in the spinal cord injured population. Furthermore, this paper reviews the relatively few articles which have addressed the treatment of such symptomatology in spinal cord injured individuals. Methodological concerns and limitations of the existing literature and directions for future research are also provided.


Predictors of genital injury after nonconsensual intercourse.
Understanding differences in genital injuries after nonconsensual and consensual intercourse is an important element of prosecuting sexual assault cases. In order to determine if the injury patterns and total surface area of genital injuries can differentiate between the types of intercourse (consensual or non-consensual), eighty women were examined after non-consensual (retrospective chart review, n = 40) and consensual (recruited, n = 40) intercourse within 48 hours using colposcopy, toluidine blue dye, and digital photography to document genital injuries. Differences between types of injuries found in the nonconsensual and consensual groups, based on the univariate analysis, were found with the number of sites (NoS) with ecchymosis (p < 0.01) and NoS with redness (p < 0.01). Based on the logistic hierarchical regression model, 85% of the nonconsensual group and 90% of the consensual group were classified correctly by using the NoS with tears, ecchymosis, abrasions, and redness and SA of injury when controlling for time from intercourse to examination. The NoS with redness (p = 0.017), NoS with ecchymosis, and SA of injury (p = 0.039) were individually predictive. The NoS with ecchymosis were also a significant finding when addressed as an individual block (p < 0.001). In this small sample, exploratory study, while controlling for time, the injury patterns and total SA of genital injuries were able to correctly classify the nonconsensual group 85% of the time. Replication of this study with a larger sample is essential.


Patterns of particle distribution in multiparticle systems by random walks with memory enhancement and decay.
We investigate the pattern of particle distribution and its evolution with time in multiparticle systems using the model of random walks with memory enhancement and decay. This model describes some biological intelligent walks. With decrease in the memory decay exponent alpha, the distribution of particles changes from a random dispersive pattern to a locally dense one, and then returns to the random one. Correspondingly, the fractal dimension D(f,p) characterizing the distribution of particle positions increases from a low value to a maximum and then decreases to the low one again. This is determined by the degree of overlap of regions consisting of sites with remanent information. The second moment of the density rho(2) was introduced to investigate the inhomogeneity of the particle distribution. The dependence of rho(2) on alpha is similar to that of D(f,p) on alpha. rho(2) increases with time as a power law in the process of adjusting the particle distribution, and then rho(2) tends to a stable equilibrium value.


[Involvement of doctors' assistants in primary care for patients with long-term conditions. General practitioners' (GPs) perception of barriers and opportunities--a qualitative study].
Care for patients with multiple and chronic diseases is an increasing challenge. The particular demands of chronically ill patients increase the complexity of primary care. Involvement of doctors' assistants is discussed as part of comprehensive frameworks for structured care like the Chronic Care Model (CCM). The aim of this qualitative study was to reveal perceived barriers and opportunities among German general practitioners (GPs) according to the involvement of their assistants in patient care. 14 GPs were interviewed. The documents were evaluated analytically according to their content. Most GPs have a positive point of view with regard to the integration of their assistants. They claim a task-oriented training for the assistants as a precondition. Their working experience, an established patient-assistant relationship and the preparedness to take own responsibility in patient care are stated as supporting factors for the involvement of doctors' assistants in patient care. Main barrier seems to be a lack of time for additional work of their employees. There is a need for task-oriented training, in order to professionalize practice teams. Remarkably, this new approach to chronic care is already integrated into routine care. However, it seems to suit only for some distinct diseases, selected patients and a limited number of doctors' assistants. As part of further professionalization an evaluation of a new job profile for doctors' assistants should be discussed.


Rhodium(I) and Rhodium(III) complexes containing the chiral ligand 2,6-bis[4'(S)-isopropyloxazolin-2'-yl]pyridine (pybox): an unprecedented monohapto coordination of pybox.
The complex [Rh(kappa(3)-N,N,N-pybox)(CO)][PF(6)] (1) has been prepared by reaction of the precursor [Rh(mu-Cl)(eta(2)-C(2)H(4))(2)](2), 2,6-bis[4'(S)-isopropyloxazolin-2'-yl]pyridine (pybox), CO, and NaPF(6). Complex 1 reacts with monodentate phosphines to give the complexes [Rh(kappa(1)-N-pybox)(CO)(PR(3))(2)][PF(6)] (R(3) = MePh(2) (2), Me(2)Ph (3), (C(3)H(5))Ph(2) (4)), which show a previously unseen monodentate coordination of pybox. Complex 1 undergoes oxidative addition reactions with iodine and CH(3)I leading to the complexes [RhI(R)(kappa(3)-N,N,N-pybox)(CO)][PF(6)] (R = I (5); R = CH(3) (6)). Furthermore, a new allenyl Rh(III)-pybox complex of formula [Rh(CH=C=CH(2))Cl(2)(kappa(3)-N,N,N-pybox)] (7) has been synthesized by a one-pot reaction from [Rh(mu-Cl)(eta(2)-C(2)H(4))(2)](2), pybox, and an equimolar amount of propargyl chloride.


Non-Hodgkin lymphoma in Gabon and its relation to HTLV-I.
A case-control study was performed in Libreville, Gabon, to determine whether a relationship can be established between the relatively high proportion of non-Hodgkin lymphoma (NHL) among all cancer cases and the high seroprevalence rate of HTLV-I observed, and to discover whether cases of adult T-leukemia/lymphoma (ATLL) related to HTLV-I exist in Gabon. From November 1987 to April 1989, a total of 32 patients with NHL were recruited; 6 were infants with Burkitt's lymphoma and 26 were adults with NHL. Each patient was matched with 2 asymptomatic controls for age, sex and ethnic group. HTLV-I serology was done by ELISA and Western blot. Comparison of the groups was done by chi-square analysis. None of the 6 infants with Burkitt's lymphoma and none of their controls had antibodies to HTLV-I. Of the 26 patients with NHL, 7 (26.9%) had HTLV-I antibodies. Among the 52 controls, the HTLV-I rate was 13.4% (n = 7). There was no difference between cases and controls (Fisher's exact test, p = 0.16). Among the 26 NHL, 4 cases fitted the criteria of ATLL and were HTLV-I-positive; 3 others who were positive for HTLV-I were a woman with lymphoblastic gastric NHL and 2 old men with an unclassified lymphoma. From the results of this limited series it is not possible to state that there is an association between NHL and HTLV-I infection. Nevertheless, cases of ATLL related to HTLV-I are reported from this area. Based on the HTLV-I seroprevalence rates reported in Gabon, the estimated incidence rate of ATL among seropositive people in Gabon appears much lower than in Japan. Different explanations can be proposed, but under-diagnosis of ATLL is probably one of the main factors.


Cognitive deficits in psychiatric disorders: Current status.
Cognition denotes a relatively high level of processing of specific information including thinking, memory, perception, motivation, skilled movements and language. Cognitive psychology has become an important discipline in the research of a number of psychiatric disorders, ranging from severe psychotic illness such as schizophrenia to relatively benign, yet significantly disabling, non-psychotic illnesses such as somatoform disorder. Research in the area of neurocognition has started unlocking various secrets of psychiatric disorders, such as revealing the biological underpinnings, explaining the underlying psychopathology and issues related to course, outcome and treatment strategies. Such research has also attempted to uproot a number of previously held concepts, such as Kraepelin's dichotomy. Although the range of cognitive problems can be diverse, there are several cognitive domains, including executive function, attention and information processing, and working memory, which appear more frequently at risk. A broad range of impairment across and within the psychiatric disorders are highlighted in this oration. The oration summarizes the studies investigating cognitive processing in different psychiatric disorders. I will also discuss the findings of my own research on neurocognitive deficits in mood disorders, schizophrenia, obsessive-compulsive disorder, somatoform disorder, including studies on 'high-risk' individuals. Tracing the evaluation of neurocognitive science may provide new insights into the pathophysiology and treatment of psychiatric disorders.


The Right Temporoparietal Junction Supports Speech Tracking During Selective Listening: Evidence from Concurrent EEG-fMRI.
Listening selectively to one out of several competing speakers in a "cocktail party" situation is a highly demanding task. It relies on a widespread cortical network, including auditory sensory, but also frontal and parietal brain regions involved in controlling auditory attention. Previous work has shown that, during selective listening, ongoing neural activity in auditory sensory areas is dominated by the attended speech stream, whereas competing input is suppressed. The relationship between these attentional modulations in the sensory tracking of the attended speech stream and frontoparietal activity during selective listening is, however, not understood. We studied this question in young, healthy human participants (both sexes) using concurrent EEG-fMRI and a sustained selective listening task, in which one out of two competing speech streams had to be attended selectively. An EEG-based speech envelope reconstruction method was applied to assess the strength of the cortical tracking of the to-be-attended and the to-be-ignored stream during selective listening. Our results show that individual speech envelope reconstruction accuracies obtained for the to-be-attended speech stream were positively correlated with the amplitude of sustained BOLD responses in the right temporoparietal junction, a core region of the ventral attention network. This brain region further showed task-related functional connectivity to secondary auditory cortex and regions of the frontoparietal attention network, including the intraparietal sulcus and the inferior frontal gyrus. This suggests that the right temporoparietal junction is involved in controlling attention during selective listening, allowing for a better cortical tracking of the attended speech stream.SIGNIFICANCE STATEMENT Listening selectively to one out of several simultaneously talking speakers in a "cocktail party" situation is a highly demanding task. It activates a widespread network of auditory sensory and hierarchically higher frontoparietal brain regions. However, how these different processing levels interact during selective listening is not understood. Here, we investigated this question using fMRI and concurrently acquired scalp EEG. We found that activation levels in the right temporoparietal junction correlate with the sensory representation of a selectively attended speech stream. In addition, this region showed significant functional connectivity to both auditory sensory and other frontoparietal brain areas during selective listening. This suggests that the right temporoparietal junction contributes to controlling selective auditory attention in "cocktail party" situations.


Systematic Molecular Design of Ketone Derivatives of Aromatic Molecules for Lithium-Ion Batteries: First-Principles DFT Modeling.
The thermodynamic and electrochemical redox properties for a set of ketone derivatives of phenalenyl and anthracene have been investigated to assess their potential application for positive electrode materials in rechargeable lithium-ion batteries. Using first-principles DFT, it was found that 1) the thermodynamic stabilities of ketone derivatives are strongly dependent on the distribution of the carbonyl groups and 2) the redox potential is increased when increasing the number of the incorporated carbonyl groups. The highest values are 3.93 V versus Li/Li+ for the phenalenyl derivatives and 3.82 V versus Li/Li+ for the anthracene derivatives. It is further highlighted that the redox potential of an organic molecule is also strongly correlated with its spin state in the thermodynamically stable form.


[Clinical study of syndrome differentiation standards for chronic skin ulcer of lower limbs].
To establish evidence and standards for syndrome differentiation of patients with chronic skin ulcer of lower limbs, which can be used to supervise and further improve the clinical treatment. The evidence and standards would also lay a foundation for the integrative evaluation system of clinical effects. This is a prospective study of clinical case collection and analysis. The syndrome factors of chronic skin ulcer of lower limbs were collected from clinical cases, and then the essential factors of syndromes were chosen to make cluster analysis and principal component analysis. After syndrome classification, specialist consultation was performed. Forecasting syndrome models were established on the basis of the statistical analysis and the specialist consultation. The syndrome factors in 338 cases of chronic skin ulcer of lower limbs were clustered into four syndrome categories including deficiency of both qi and blood, spleen deficiency with dampness encumbrance, qi deficiency with blood stasis and blood stagnation with dampness-heat. The deficiency of both qi and blood, and qi deficiency with blood stasis were merged into qi deficiency with blood stasis by expert revision. The primary and secondary symptoms were identified by principal component analysis and average ranking determined by experts. The qi deficiency with blood stasis, spleen deficiency with dampness encumbrance, and blood stagnation with dampness-heat could reflect the clinical syndrome characteristics in patients with chronic skin ulcer of lower limbs. Chronic skin ulcer of lower limbs can be differentiated in three syndrome types, and differentiation of local symptoms of the ulcer is very important in syndrome differentiation of chronic skin ulcer of lower limbs.


Functional analysis of promoter sequences of cephalosporin C biosynthesis genes from Acremonium chrysogenum: specific DNA-protein interactions and characterization of the transcription factor PACC.
An analysis of the pcbC promoter from the cephalosporin C-producing filamentous fungus Acremonium chrysogenum was performed using fungal transformants carrying reporter gene fusions. By investigating sequential deletion derivatives of the pcbC promoter region, a DNA fragment was identified, which is responsible for transcriptional activation of the pcbC gene. Sequence analysis of this fragment revealed a consensus binding site for the fungal transcription factor PACC. Gel-retardation experiments with crude extracts of A. chrysogenum confirmed the specific binding of a protein to the PACC binding site. The subsequent cloning of the pacC homolog from A. chrysogenum allowed the identification of an ORF of 621 amino acids encoded by four exons. The polypeptide shows about 35% sequence identity to other fungal PACC proteins. A PACC protein fragment synthesized in E. coli was used for in vitro binding assays, and specific binding of the zinc-finger transcription factor to its consensus binding sites in the promoter regions of four cephalosporin C biosynthesis genes could be demonstrated. The bi-directional promoters of the genes pcbAB-pcbC and cefEF-cefG contain two PACC binding sites each. The data obtained strongly suggest that, in A. chrysogenum, the zinc-finger transcription factor PACC is involved in the transcriptional regulation of the genes involved in cephalosporin C biosynthesis.


Honeycomb and necklace signs in liver abscesses secondary to melioidosis.
Melioidosis is endemic in Southeast Asia and tropical Australia with varying clinical features from benign skin lesions to fatal septicaemia. Imaging plays an important role in evaluation of the melioid liver abscesses. A 45-year-old man with underlying diabetes presented with fever and lethargy for 2 weeks and abdominal pain for 2 days. His liver was enlarged on examination. Blood investigations revealed mild leucocytosis and raised liver enzymes. Ultrasound showed multiple multiloculated hypoechoic lesions throughout the liver and spleen. CT of abdomen confirmed that some liver lesions were made up of asymmetric locules of varying sizes (honeycomb sign), while others had hypodense centre with small symmetric peripheral locules in radial fashion (necklace sign). Blood culture was positive for Burkholderia pseudomallei He was subsequently treated with ceftazidime for a month followed by oral trimethoprim-sulfamethoxazole for 3 months. Follow-up CT of abdomen a month after diagnosis and treatment showed resolving hepatic and splenic lesions.


Treatment of keloid and hypertrophic scars by iontophoretic transdermal delivery of tranilast.
The feasibility of iontophoretic transdermal delivery of tranilast (N-(3,4-dimethoxycinnamoyl) anthranilic acid) for the treatment of keloid and hypertrophic scars was evaluated in hairless rats and humans. A drug electrode containing tranilast 1.5 ml (8 mg/ml in ethanol/water (8/2, v/v) mixture) was placed on the dorsal skin surface of anaesthetised rats or the affected parts of patients, and connected to the negative pole; an electric current (0.5-4 mA for rats, 2 mA for people) was pulsed through at one minute intervals. Tranilast was effectively delivered transdermally iontophoretically into the restricted skin tissues of hairless rats and the affected parts of four patients with hypertrophic scars with no skin damage. In four other patients tranilast given iontophoretically for a period of 30 minutes a week reduced the patients' complaints of pain and itching after only one or two treatments although there were some variations among patients. These results indicate that the transdermal iontophoretic delivery of tranilast is a useful treatment for keloid and hypertrophic scars, particularly for relieving pain and itching, and is more beneficial than tranilast given orally.


Decreasing the incidence of recurrence of first time anterior shoulder dislocations with rehabilitation.
Studies of adolescent and young adult males sustaining primary anterior shoulder dislocations reveal the likelihood of recurrence to be virtually always above 50% and as high as 79% to 94%. Common among these investigations is the lack of a specific, rigidly adhered to rehabilitation program. During a 3 1/2 year period, 20 midshipmen at the United States Naval Academy sustained primary anterior shoulder dislocations. All participated in an identical treatment regimen which included a restrengthening program emphasizing the muscles of internal rotation and adduction, plus rigid restrictions of activities until the goals of their rehabilitation program were satisfied. Exercises progressed from isometrics through isotonics and isokinetics. Goals included return to full active, unrestricted duty and athletic participation which included participation in the sport that resulted in the original dislocation. Patients were followed for an average of 35.8 months (with a range of 17 to 45 months). During the period of study there were five recurrences (25%). A success rate of 75% would suggest that adherence to a specific, aggressive postdislocation rehabilitation program, plus rigid restrictions of activities until the goals of the program are satisfied, can substantially improve the likelihood of a full return to activity without recurrent shoulder dislocation.