Surface enhanced Raman scattering traceable and glutathione responsive nanocarrier for the intracellular drug delivery.
A surface enhanced Raman scattering (SERS) traceable nanocarrier is presented through a simple strategy for the intracellular redox environment triggered drug delivery. Basically, the nanocarrier has a core-shell structure, with the Raman molecule tagged Au@Ag nanorods as the SERS active core and mesoporous silica (MS) as the drug containing shell. In the presented system, the locations of nanocarriers can be tracked by SERS signals while those of drugs can be monitored through their fluorescence, allowing the simultaneous investigation of the intracellular distribution of both the nanocarriers and the drugs. To endow the nanocarrier with the glutathione (GSH) responsive behavior, disulfide, which can be cleaved by GSH, is used to directly attach drug molecules to the MS. Compared with other disulfide based drug delivery strategies, this is a quite simple and efficient method. The experimental results confirmed that the drug release can be triggered by the stimuli. Moreover, after the cellular uptake of the nanocarriers, a gradual drug release from the nanocarriers was observed by monitoring both the fluorescence of the drug molecules and the SERS signals of the nanocarriers. Considering its stimuli-responsive properties, this kind of nanocarrier would have great potential in improving the efficacy of cancer chemotherapy by avoiding premature drug leakage. More importantly, this SERS based tracking method of the nanocarrier would be more powerful than that based only on the fluorescence of the drug in the studies of drug release dynamic processes.


Immune factors in breast milk and the development of atopic disease.
Breast-feeding provides protection against infections and contains numerous factors that modulate and promote the development of the infant immune system. These factors include secretory IgA, antimicrobial proteins like CD14, cytokines, and fatty acids. Studies examining the role of breast-feeding in the development of allergic disease in infants demonstrate potentially protective as well as neutral or nonprotective effects, likely due to the heterogeneity in their study design. In this overview, we explore the potential role of immune factors in the breast milk, as well as selected probiotics, in the development of allergy.


A Bottom Up Perspective to Understanding the Dynamics of Team Roles in Mission Critical Teams.
There is a long history, dating back to the 50 s, which examines the manner in which team roles contribute to effective team performance. However, much of this work has been built on ad hoc teams working together for short periods of time under conditions of minimal stress. Additionally, research has been conducted with little attention paid to the importance of temporal factors, despite repeated calls for the importance of considering time in team research (e.g., Mohammed et al., 2009). To begin to understand team roles and how temporal aspects may impact the types of team roles employed when teams are working in extreme mission critical environments, the current manuscript uses a data-driven, bottom-up approach. Specifically, we employ the use of retrospective historical data as our input and a historiometric approach (Simonton, 2003). Source documents consist primarily of autobiographies, memoires, biographies, and first-hand accounts of crew interaction during spaceflight. Critical incidents regarding team interaction were extracted from these source documents and independently coded for team roles by two trained raters. Results of the study speak to the importance of task and social roles within teams that are predominantly intact and operating in extreme environments where mistakes can be life threatening. Evidence for the following task (i.e., coordinator, boundary spanner, team leader, evaluator, critic, information provider, team player, and innovator) and social roles (i.e., team builder, nurturer, harmonizer, entertainer, jokester, and the negative roles of attention seeker and negativist) were found. While it is often task roles that receive the greatest attention, results point to the importance of not neglecting the socioemotional health of the team (and the corresponding roles). Results also indicated that while some roles were consistently enacted independent of temporal considerations (e.g., mission length), the degree to which others were enacted varied across missions of differing lengths. Additionally, based on the current sample we see the following trends: (1) increased enactment of the team builder role as mission duration increases, (2) prominence of the entertainer role, and (3) increased emphasis on the visionary/problem solver role on missions over 2 years.


Memory complaints in nondemented men predict future pathologic diagnosis of Alzheimer disease.
The validity of memory complaints as a predictor of Alzheimer disease (AD) was assessed in 237 Japanese-American men autopsied at ages 74 to 97 years. These men were free of dementia at the time memory complaints were assessed 1 to 11 years earlier. Memory complaints were found to predict the neuropathologic diagnosis of AD after adjusting for age, time to death, education, depression, and cognitive functioning.


The Role of Lingual Bone Grafting in the Treatment of Displaced Edentulous Mandibular Fracture with Severe Atrophy.
Treatment of edentulous atrophic mandible with severe atrophy is a challenge based on local conditions and systemic diseases confronted by the age group affected. If bone grafting is indicated, it is often used in lateral or inferior aspects of the mandible. A 70-year-old male with a unilateral fracture of the atrophied left mandibular body was managed by lingual bone grafting and inferior border miniplate fixation to prevent two common problems after fracture healing; the need for plate removal before denture fabrication and facial asymmetry in the unilateral body fracture. If bone grafting is indicated in the management of displaced edentulous mandibular fracture with severe atrophy, a combination of plating at the inferior border of the mandible and lingual corticocancellous bone grafting should be considered in treatment planning.


Early esophageal adenocarcinoma detection using deep learning methods.
This study aims to adapt and evaluate the performance of different state-of-the-art deep learning object detection methods to automatically identify esophageal adenocarcinoma (EAC) regions from high-definition white light endoscopy (HD-WLE) images. Several state-of-the-art object detection methods using Convolutional Neural Networks (CNNs) were adapted to automatically detect abnormal regions in the esophagus HD-WLE images, utilizing VGG'16 as the backbone architecture for feature extraction. Those methods are Regional-based Convolutional Neural Network (R-CNN), Fast R-CNN, Faster R-CNN and Single-Shot Multibox Detector (SSD). For the evaluation of the different methods, 100 images from 39 patients that have been manually annotated by five experienced clinicians as ground truth have been tested. Experimental results illustrate that the SSD and Faster R-CNN networks show promising results, and the SSD outperforms other methods achieving a sensitivity of 0.96, specificity of 0.92 and F-measure of 0.94. Additionally, the Average Recall Rate of the Faster R-CNN in locating the EAC region accurately is 0.83. In this paper, recent deep learning object detection methods are adapted to detect esophageal abnormalities automatically. The evaluation of the methods proved its ability to locate abnormal regions in the esophagus from endoscopic images. The automatic detection is a crucial step that may help early detection and treatment of EAC and also can improve automatic tumor segmentation to monitor its growth and treatment outcome.


Axillary acne agminata (lupus miliaris disseminatus faciei with axillary involvement).
Acne agminata (AA) and lupus miliaris disseminatus faciei (LMDF) have been used to describe very similar clinical conditions and it is now generally accepted that they are synonymous. The cause of these disorders has not been determined. Clinically the disease presents with often agminated redbrown to yellow papules which occasionally become pustular. Microscopically, superficial granulomatous inflammation with perifollicular caseating granulomas is the hallmark. Axillary involvement with LMDF has rarely been reported; in this area AA has been the preferred term. When only the axillae are affected, it may be difficult to distinguish acne agminata from other granulomatous diseases, especially from granulomas caused by antiperspirants containing aluminumzirconium complexes. We describe a 36-year-old woman with axillary acne agminata.


Pig alpha1, 3galactosyltransferase: a major target for genetic manipulation in xenotransplantation.
Terminal carbohydrate residues of glycolipids and glycoproteins display polymorphism among as well as within various species. With the exception of Old World monkeys, great apes and man, the Gala1,3Gal structure is widely expressed in all mammals examined so far. The lack of expression of the glycosyltransferase responsible for the synthesis of Gala1,3Gal leads to the production of high titers of natural antibodies (NAb) against the Gala1,3Gal of other species. The inactivation of this gene occurred during early evolution of primates. Neutralization of viruses (e.g. retroviruses) carrying the epitope, by the pre-formed human NAb, indicates one possible evolutionary reason for the polymorphism of terminal carbohydrates among as well as within species. It has been shown that this epitope constitutes the major target, on pig endothelial cells (EC), for the pre-formed human NAb resulting in a hyperacute rejection (HAR) response. This currently makes transplantation of e.g. pig organs to humans impossible. Efforts are currently underway to prevent or to eradicate the expression of this epitope in transgenic pigs. Such pigs are likely to display a greatly increased resistance to the HAR.


Predictive Value of Baseline Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) Assessments for Identifying Risk of Prospective Reports of Suicidal Behavior During Research Participation.
Examine the ability of baseline electronic Columbia-Suicide Severity Rating Scale lifetime suicidal ideation and behavior categories to predict prospective reports of suicidal behavior in psychiatric and non-psychiatric research participants. Meta-analysis of 74,406 eC-SSRS assessments completed between September 2009 and December 2012. Thirty-three clinical research studies that used the electronic Columbia-Suicide Severity Rating Scale to assess suicidal ideation and behavior at baseline and prospectively during follow-up visits. Records from 6,760 patients with psychiatric disorders (opioid dependence, generalized anxiety, major depressive, and posttraumatic stress disorders) and 2,077 nonpsychiatric disorder patients (chronic obstructive pulmonary disease, epilepsy, fibromyalgia, human immunodeficiency virus, insomnia, multiple sclerosis, osteoarthritis, pain/back pain, Parkinson's disease, restless leg syndrome) were analyzed. Electronic Columbia-Suicide Severity Rating Scale assessment of lifetime suicidal ideation (5 severity levels) and suicidal behavior (4 types) at baseline and prospectively reported suicidal behavior during study participation. Increasingly more severe lifetime suicidal ideation at baseline was associated with a progressively greater likelihood of prospectively reported suicidal behavior during study participation. Intent to act on suicidal ideation was most predictive of reports of suicidal behavior. Reports of lifetime suicidal behaviors at baseline also predicted subsequent suicidal behavior, and multiple lifetime behaviors monotonically increased prospective risk of suicidal behavior. Baseline suicidal ideation and behavior predicted future suicidal behavior in both psychiatric and non-psychiatric trials. Lifetime reports of suicidal ideation and/or behavior at baseline significantly increased risk of prospectively reporting suicidal behavior during research trial participation in both psychiatric and nonpsychiatric patients. Lifetime prevalence of suicidal ideation and behavior is higher among psychiatric patients, but also presents a safety concern among nonpsychiatric patients when reported.


Prediction of mortality 1 year after hospital admission.
Hospital admission, especially for the elderly, can be a seminal event as many patients die within a year. This study reports the prediction of death within a year of admission to hospital of the Simple Clinical Score (SCS) and ECG dispersion mapping (ECG-DM). ECG-DM is a novel technique that analyzes low-amplitude ECG oscillations and reports them as the myocardial micro-alternation index (MMI). a convenient sample of 430 acutely ill medical patients (mean age 67.9 ± 16.6 years) was followed up for 1 year after their last admission to hospital. Seventy-four (16.3%) patients died within a year-all but seven had a SCS ≥5 and 40% of those with an MMI ≥50% died. Only six of variables were found by logistic regression to be independent predictors of mortality (i.e. age, MMI, SCS, a discharge diagnosis of cancer, hemoglobin <11 gm% and prior illness that required the patient to spend >50% of daytime in bed). The SCS and MMI plus age were comparable predictors of 1-year mortality: SCS ≥12 predicted 1-year mortality with the highest odds (16.1, chi square 79.09, p < 0.0001) and a score of age plus MMI >104 had an odds ratio of 9.4 (chi square 73.50, p < 0.0001), identified 69% of deaths, and 43% of the 119 patients who exceeded this score were dead within a year. SCS and ECG-DM plus age are clinically useful for long-term prognostication. ECG-DM is inexpensive, only takes a few seconds to perform and requires no skill to interpret.


Porcine reproductive and respiratory syndrome type 1 viruses induce hypoplasia of erythroid cells and myeloid cell hyperplasia in the bone marrow of experimentally infected piglets independently of the viral load and virulence.
Porcine reproductive and respiratory syndrome viruses (PRRSV) present a wide phenotypic and genetic diversity. Experimental infections have demonstrated viral replication, including highly pathogenic strains (HP-PRRSV), in primary lymphoid organs such as the thymus. However, studies of the bone marrow are scarce but necessary to help elucidate the immunobiology of PRRSV strains of differing virulence. In this study, whereas viral RNA was detected within the bone marrow of animals experimentally infected with both low virulent Lelystad (LV) and 215-06 PRRSV-1 strains and with the highly virulent SU1-bel strain, PRRSV positive cells were only occasionally detected in one SU1-bel infected animal. PRRSV RNA levels were associated to circulating virus with the highest levels detected in LV-infected pigs. At 3 dpi, a decrease in the proportion of haematopoietic tissue and number of erythroid cells in all infected groups was associated with an increase in TUNEL or cleaved caspase 3 labelling and higher counts of myeloid cells compared to control. The expression of IL-1α and IL-6 was elevated at the beginning of the infection in all infected animals. The expression of TNF-α was increased at the end of the study in all infected groups with respect to control. Different PRRSV-1 strains induced, presummably by indirect mechanisms and independently of viral load and strain virulence, moderate and sustained hypoplasia of erythroid cells and myeloid cell hyperplasia at early stages of infection. These changes were paralleled by a peak in the local expression of IL-1α, IL-6 and TNF-α in all infected groups.


Manual Acupuncture or Combination of Rehabilitation Therapy to Treat Poststroke Dysphagia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Backgroundand Objective. Poststroke dysphagia is one of the most common stroke complications with high morbidity and long course, while acupuncture treatment is easily accepted by patients due to its reliability, feasibility, simple operation, low price, and quick effect. Our objective was to evaluate the efficacy of manual acupuncture in poststroke dysphagia patients. Methods. Databases including Medline, Web of Science, PubMed, Cochrane Library databases, EMBASE, CNKI (China National Knowledge Infrastructure), WanFang (WanFang Database), and VIP (Chongqing VIP) were searched from inception until Aug 19, 2022. Data were analyzed using Revman 5.3, Stata 14.0, and TSA 0.9.5.10 Beta software. Evidence quality evaluation was performed by using GRADE profiler 3.6. Results. A total of 33 randomized control trials (RCTs) enrolled 2680 patients. Meta-analysis results revealed that compared to rehabilitation, acupuncture decreased water swallow test (WST) and standard swallowing assessment (SSA) scores. Meanwhile, in contrast to rehabilitation alone, integration of acupuncture with rehabilitation effectively decreased WST and SSA scores; improved swallowing scores of videofluoroscopic swallowing study (VFSS), swallowing scores of Fujishima Ichiro, Barthel index (BI), and swallowing quality of life questionnaire (SWAL-QOL); reduced the aspiration rates as well as aspiration pneumonia; and shortened the duration of empty swallowing and the duration of 5 mL water swallowing. Pooled analysis did not reveal any significant differences in dysphagia outcome severity scores (DOSS) (p=0.15 > 0.05p) between the acupuncture group combined with rehabilitation group and the rehabilitation group alone. After the risk-of-bias assessment, these studies were not of low quality, except in terms of allocation concealment and blindness. Evidence quality evaluation showed that allocation concealment and blindness led to a downgrade and primary outcomes' evaluation of acupuncture combined with rehabilitation were ranked as moderate-quality evidence while acupuncture alone was ranked as low-quality. Conclusion. This meta-analysis provided positive pieces of evidences that acupuncture and acupuncture combined with rehabilitation were better than using rehabilitation alone in the treatment of poststroke dysphagia.


A syndromic form of X-linked mental retardation: the Coffin-Lowry syndrome.
Coffin-Lowry syndrome (CLS, OMIM 303600) is an X-linked inherited disorder characterised in male patients by growth and psychomotor retardation, hypotonia and progressive skeletal changes. Typically, male patients are of short stature and exhibit a characteristic coarse face with a prominent forehead, orbital hypertelorism, downslanting palpebral fissures, thick lips, a thick nasal septum with anteverted nares, and irregular or missing teeth. Their large and soft hands with lax skin and tapering fingers, are usually a strong diagnostic feature. Some patients present with additional complications including, sensorineural deafness, seizures, drop episodes and cardiac disease. There is some variability in the mental development of affected males, but most of the males who receive appropriate care appear to be moderately affected. A majority of carrier females have only minimal findings (mild facial coarsening, tapering fingers and obesity). Early diagnosis of CLS is essential for proper management, including survey of some specific complications already mentioned, and for genetic counselling. Establishing the diagnosis in very young children is often much more difficult than in older patients since physical characteristics are milder and not specific. Loss of function mutations in the gene encoding the growth-factor induced protein kinase ribosomal S6 kinase are responsible for CLS. A mutation has been detected in about 50% of patients with clinical features suggestive of CLS, and over 80 different mutations have so far been identified. They are distributed throughout the gene, the vast majority being unique to single families and a high proportion appear to be de novo events. Some missense mutations are associated with milder phenotypes. In one family, a missense mutation was associated solely with mild mental retardation and no other clinical feature. Coffin-Lowry syndrome is a well characterised entity and a detailed clinical examination usually allows diagnosis. However, recognising it in very young children is often difficult since physical characteristics are mild and not specific. In addition, most cases are sporadic. Screening for ribosomal S6 kinase mutations is essential in most cases to confirm the diagnosis as well as for genetic counselling.


Antioxidant and anti-inflammatory medicinal plants have potential role in the treatment of cardiovascular disease: a review.
Cardiovascular disease is a compound name for clusters of disorders afflicting the heart and blood vessels; it is assuming an increasing role as a major cause of morbidity and mortality. Unhealthy practices such as smoking, high intake of saturated fat and cholesterol, diabetes and physical inactivity are predisposing factors. The risk factors cause alteration in vascular integrity, compromised membrane integrity, increase free radical generation and reduced endogenous antioxidant system resulting in oxidative stress. Substance with ability to maintain vascular integrity, prevent, or reduce radical formation are able to treat cardiovascular disease. Conventional drugs in use to this effect are with side effect and as alternative, medicinal plants are increasingly gaining acceptance from the public and medical professionals. Reports have shown that bioactive compounds in plants with antioxidant, anti-inflammatory, ability to protect vascular endothelium, prevent lipid oxidation, and augment endogenous antioxidant system are cardioprotective. Phenolics and flavonoids in medicinal plants have been widely reported to play these major roles. This study reviewed the role of bioactive compounds in medicinal plants using a wide range database search.


[Anesthesia and cardiac pacing].
Nowadays, anaesthetists often have to deal with pacemaker patients. All the problems encountered in the anaesthetic management of such patients are discussed in this paper: the pacemaker, specific risks linked to the pacemaker, monitoring of such patients, and temporary pacing. The preoperative assessment of pacemaker function is an absolute necessity. The technical characteristics of the pacemaker can be found in the patient's booklet. The clinical history should reveal a possible malfunction (syncopes). The underlying cardiac disease should be known, as it will have repercussions on the anaesthetic and surgical risks. An electrocardiogram and measurement of blood electrolytes must be carried out. There are three major risks linked to the pacemaker during surgery: 1) the loss of pacing by threshold (drugs, dyskaliemia); threshold (drugs, dyskalemia); 2) ventricular fibrillation (the intracardiac electrode conducting the electrocautery currents); 3) reprogramming or damaging of the pacemaker by electrocautery, cardioversion or nuclear magnetic resonance. The only mandatory monitoring of these patients is the electrocardioscope. Other monitoring techniques will be dictated by the underlying cardiac disease or the surgery planned. Temporary pacing is indicated in the same conditions as permanent pacing. However the intracardiac electrode can be displaced by moving the patient; the efficacy of pacing must therefore be continuously checked. During cardiac surgery, with cardiopulmonary bypass, conduction disturbances can occur. Temporary pacing electrodes should therefore be sewn onto the ventricular epicardium for the duration of the surgery; atrial electrodes should be added if sinus troubles can be expected. Oesophageal pacing is possible in the operating theatre because it is easily and rapidly set up: a bipolar oesophageal electrode linked to an external pacer can speed up the heart (atrial dysfunction) or slow down a tachycardia. An oesophageal electrocardiogram can also be carried out with this electrode. Swan-Ganz catheters can be also used for temporary pacing: either with two pairs of electrodes, atrial and ventricular respectively--this system being useful in a patient who does not move--or with a newer system where a single small electrode is introduced into the right ventricle by a special lumen in the Swan-Ganz catheter. Although external pacing was historically the first technique to be developed, it was abandoned because of the muscle pains it gave. Recently, a new technique of external pacing, with large electrodes and longer stimuli, has been developed for use in emergency situations.(ABSTRACT TRUNCATED AT 400 WORDS)


Cytokine biomarkers to predict antitumor responses to nivolumab suggested in a phase 2 study for advanced melanoma.
Promising antitumor activities of nivolumab, a fully humanized IgG4 inhibitor antibody against the programmed death-1 protein, were suggested in previous phase 1 studies. The present phase 2, single-arm study (JAPIC-CTI #111681) evaluated the antitumor activities of nivolumab and explored its predictive correlates in advanced melanoma patients at 11 sites in Japan. Intravenous nivolumab 2 mg/kg was given repeatedly at 3-week intervals to 35 of 37 patients enrolled from December 2011 to May 2012 until they experienced unacceptable toxicity, disease progression, or complete response. Primary endpoint was objective response rate. Serum levels of immune modulators were assessed at multiple time points. As of 21 October 2014, median response duration, median progression-free survival, and median overall survival were 463 days, 169 days, and 18.0 months, respectively. The overall response rate and 1- and 2-year survival rates were 28.6%, 54.3%, and 42.9%, respectively. Thirteen patients remained alive at the end of the observation period and no deaths were drug related. Grade 3-4 drug-related adverse events were observed in 31.4% of patients. Pretreatment serum interferon-γ, and interleukin-6 and -10 levels were significantly higher in the patients with objective tumor responses than in those with tumor progression. In conclusion, giving repeated i.v. nivolumab had potent and durable antitumor effects and a manageable safety profile in advanced melanoma patients, strongly suggesting the usefulness of nivolumab for advanced melanoma and the usefulness of pretreatment serum cytokine profiles as correlates for predicting treatment efficacy.


Surgery for expansion of spinal tuberculoma during antituberculous chemotherapy: a case report.
We report a case of intramedullary spinal tuberculoma in a girl aged 2 years and 6 months. At the age of 18 months, the patient was hospitalized for 2 months with tuberculous meningitis. Tuberculomas then appeared in the thoracic spinal cord, and the patient developed paraparesis despite continuation of chemotherapy. Spinal magnetic resonance imaging demonstrated multiple ring-enhanced lesions in the cord on the T1-weighted image; on the T2-weighted image, the lesions had a bright core surrounded by a hypointense rim. Laminectomy and partial excision were performed, and the paraparesis improved. In addition to antituberculous chemotherapy and dexamethasone, surgical decompression was needed to treat the expansion of the spinal tuberculoma.


Effect of patient positioning on the evaluation of myocardial perfusion SPECT.
ECG-gated SPECT myocardial perfusion imaging is usually acquired in supine position. However, some patients are not comfortable in this position for a variety of personal or medical reasons. Our aim was to investigate the effect of patient positioning on quantitative SPECT imaging results using normal supine database. 55 patients (mean age 58.5 ± 8.3 years) were enrolled in this prospective study. Each patient had a pair of ECG-gated stress SPECT myocardial perfusion images acquired on two gamma cameras: one in supine position and the other in upright sitting position. Left ventricular (LV) ejection fraction (EF), end-diastolic (ED), and end-systolic (ES) left ventricular volumes (V), LV mass, summed stress perfusion defect score (SSS), and total severity score (TSS) were calculated automatically relative to a supine normal reference database. There were no significant differences in LVEF using the two cameras (0.65 ± 0.08 vs. 0.66 ± 0.10; P > 0.1). However, EDV, ESV, and LV mass were significantly smaller in sitting position than in supine position (89 vs. 80 ml; 33 vs. 29 ml and 115 vs. 109 ml, respectively, all P < 0.0001). On the other hand, SSS and TSS were significantly higher in sitting position than in supine position (5.16 vs. 8.73 and 166.82 vs. 288.27, both P < 0.0001). Overall, more studies in sitting position were interpreted as abnormal than in supine position (P < 0.05). Patient positioning has a significant impact on quantitative gated SPECT imaging results. Using a supine normal reference database, SSS and TSS were larger in sitting position than in supine position. Thus, for imaging in sitting position, separate normal limits are required.


Telomerase inhibitors for the treatment of brain tumors and the potential of intranasal delivery.
A fundamental limitation in the treatment of brain tumors is that < 1% of most therapeutic agents administered systemically are able to cross the blood-brain barrier (BBB). The development of new strategies that circumvent the BBB should increase the likelihood of tumor response to selected therapeutic agents. Intranasal delivery (IND) is a practical, noninvasive method of bypassing the BBB to deliver therapeutic agents to the brain. This technique has demonstrated promising results in the treatment of neurological disorders. Telomerase is a reverse transcriptase that is expressed in the vast majority of malignant gliomas, although not in the healthy brain. Telomerase inhibition can therefore be used as a therapeutic strategy for selectively targeting malignant gliomas. The first successful IND of a telomerase inhibitor as a therapy for brain tumors was GRN-163, an oligonucleotide N3'-->5' thiophosphoramidate telomerase inhibitor, which was successfully administered into intracerebral tumors in rats with no apparent toxicity. GRN-163 exhibited favorable tumor uptake and inhibited tumor growth, leading to prolonged lifespan in treated animals. The IND of telomerase inhibitors represents a new therapeutic approach that appears to selectively kill tumor cells, without inducing toxic effects in the surrounding healthy brain tissue.


The gender perspective in climate change and global health.
Population health is a primary goal of sustainable development. United Nations international conferences like the Beijing Platform for Action have highlighted the key role of women in ensuring sustainable development. In the context of climate change, women are affected the most while they display knowledge and skills to orient themselves toward climate adaptation activities within their societies. To investigate how the gender perspective is addressed as an issue in research and policy-making concerning climate change and global health. A broad literature search was undertaken using the databases Pubmed and Web of Science to explore the terms 'climate change,' 'health,' 'gender,' and 'policy.' Climate change and health-related policy documents of the World Health Organization (WHO) and National Communications and National Adaptation Programs of Action reports submitted to the United Nations Framework Convention on Climate Change of selected countries were studied. Assessment guidelines to review these reports were developed from this study's viewpoint. The database search results showed almost no articles when the four terms were searched together. The WHO documents lacked a gender perspective in their approach and future recommendations on climate policies. The reviewed UN reports were also neutral to gender perspective except one of the studied documents. Despite recognizing the differential effects of climate change on health of women and men as a consequence of complex social contexts and adaptive capacities, the study finds gender to be an underrepresented or non-existing variable both in research and studied policy documents in the field of climate change and health.


Thoughts about biofilm in dialysis water systems.
What is a biofilm? Basically, a biofilm is formed when a structure or a surface has a growth on it. The growth consists of a community of micro-organisms, which is active. Growth means that there are metabolic processes taking place. The amount of organisms can be low, and at the beginning there is always just a few, in principle, just one. The surface area covered can also be very small. This will change over time due to the nutritional situation. In this paper the phenomena of surface growth (biofilm) will be reviewed and commented on.


Tumor-derived exosomes promote carcinogenesis of murine oral squamous cell carcinoma.
Circulating tumor-derived exosomes (TEX) interact with a variety of cells in cancer-bearing hosts, leading to cellular reprogramming which promotes disease progression. To study TEX effects on the development of solid tumors, immunosuppressive exosomes carrying PD-L1 and FasL were isolated from supernatants of murine or human HNSCC cell lines. TEX were delivered (IV) to immunocompetent C57BL/6 mice bearing premalignant oral/esophageal lesions induced by the carcinogen, 4-nitroquinoline 1-oxide (4NQO). Progression of the premalignant oropharyngeal lesions to malignant tumors was monitored. A single TEX injection increased the number of developing tumors (6.2 versus 3.2 in control mice injected with phosphate-buffered saline; P < 0.0002) and overall tumor burden per mouse (P < 0.037). The numbers of CD4+ and CD8+ T lymphocytes infiltrating the developing tumors were coordinately reduced (P < 0.01) in mice injected with SCCVII-derived TEX relative to controls. Notably, TEX isolated from mouse or human tumors had similar effects on tumor development and immune cells. A single IV injection of TEX was sufficient to condition mice harboring premalignant OSCC lesions for accelerated tumor progression in concert with reduced immune cell migration to the tumor.


High central venous oxygen saturation is associated with mitochondrial dysfunction in septic shock: A prospective observational study.
To test the hypothesis that an impaired mitochondrial function is associated with altered central venous oxygen saturation (ScvO2 ), venous-to-arterial carbon dioxide tension difference (delta PCO2 ) or serum lactate in sepsis patients. This prospective cohort study was conducted in a single tertiary emergency department between April 2017 and March 2019. Patients with suspected sepsis were included in the study. Serum lactate was obtained in sepsis, ScvO2 and delta PCO2 were evaluated in septic shock patients. Mitochondrial function was determined from the peripheral blood mononuclear cells. Forty-six patients with suspected sepsis were included. Of these, twenty patients were septic shock. Mitochondrial oxidative stress levels were increased in the high ScvO2 group (ScvO2 > 80%, n = 6), compared with the normal (70%-80%, n = 9) and low ScvO2 (<70%, n = 5) groups. A strong linear relationship was observed between the mitochondrial oxidative stress and ScvO2 (r = .75; P = .01). However, mitochondrial respiration was increased in the low ScvO2 group. In addition, mitochondrial complex II protein levels were significantly decreased in the high ScvO2 group (P < .05). Additionally, there was no correlation between serum lactate, delta PCO2 , and mitochondria oxidative stress or mitochondria function. ScvO2 can be potentially useful for developing new therapeutics to reduce mitochondrial dysfunction in septic shock patient.


Design and implementation of dynamic logic gates and R-S flip-flop using quasiperiodically driven Murali-Lakshmanan-Chua circuit.
We report the propagation of a square wave signal in a quasi-periodically driven Murali-Lakshmanan-Chua (QPDMLC) circuit system. It is observed that signal propagation is possible only above a certain threshold strength of the square wave or digital signal and all the values above the threshold amplitude are termed as "region of signal propagation." Then, we extend this region of signal propagation to perform various logical operations like AND/NAND/OR/NOR and hence it is also designated as the "region of logical operation." Based on this region, we propose implementing the dynamic logic gates, namely, AND/NAND/OR/NOR, which can be decided by the asymmetrical input square waves without altering the system parameters. Further, we show that a single QPDMLC system will produce simultaneously two outputs which are complementary to each other. As a result, a single QPDMLC system yields either AND as well as NAND or OR as well as NOR gates simultaneously. Then, we combine the corresponding two QPDMLC systems in a cross-coupled way and report that its dynamics mimics that of fundamental R-S flip-flop circuit. All these phenomena have been explained with analytical solutions of the circuit equations characterizing the system and finally, the results are compared with the corresponding numerical and experimental analysis.


Microbiological and Chemical Characteristics of Wet Coffee Fermentation Inoculated With Hansinaspora uvarum and Pichia kudriavzevii and Their Impact on Coffee Sensory Quality.
Hansinaspora uvarum and Pichia kudriavzevii were used as starter cultures to conduct inoculated wet fermentations of coffee beans, and their growth, metabolic activities and impact on the flavor, aroma and overall sensory quality of coffee were compared with spontaneous fermentation (control). H. uvarum and P. kudriavzevii dominated the fermentations, growing to maximum populations of about 10.0 log CFU/ml compared with 8.0 log CFU/ml in the spontaneous fermentation. The dominance of the inoculated yeasts led to faster and more complete utilization of sugars in the mucilage, with resultant production of 2-3 fold higher concentrations of metabolites such as glycerol, alcohols, aldehydes, esters, and organic acids in the fermented green beans. Cup tests showed coffee produced from the inoculated fermentations, especially with P. kudriavzevii, received higher scores for flavor, aroma and acidity than the control. The findings of this study confirmed the crucial role of yeasts in the wet fermentation of coffee beans and their contribution to high quality coffee, and demonstrated the potential H. uvarum and P. kudriavzevii as starter cultures in the process.


Photonic Cellulose Films with Vivid Structural Colors: Fabrication and Selectively Chemical Response.
Recent advances in structural-color cellulose nanocrystal (CNC) materials have been made toward chemical sensing applications; however, such materials lack sufficient color chroma for naked-eye observation, and their selective recognition to given chemicals as well as the corresponding mechanism has rarely been reported. Here, a dopamine-infiltration and post-polymerization approach is proposed to construct vivid structural-color composite films. The chiral nematic structure of CNC enables the structural coloration, while the strong light absorption of the polymeric co-phase, polydopamine (PDA) enhances the color chroma and visibility. By controlling the PDA amount, the composite films can detect organic solvents quantitatively and selectively via visible color changes. From the viewpoint of the compatibility and similitude principle, notably, a critical solubility parameter distance (R0) between PDA and "active" solvents is defined with a three-dimensional Hansen solubility sphere; this well constructs a rule for the sensing selectivity of the chemochromic composite films. The findings pave the foundation for the design of colorimetric sensors with specifically testing objects.


Simultaneous analysis of steviol and steviol glycosides by liquid chromatography with ultraviolet detection on a mixed-mode column: application to Stevia plant material and Stevia-containing dietary supplements.
Simultaneous separation of steviol and steviol glycosides is challenging because of differences in their polarity and chemical structure. In this study, simultaneous analysis of steviol and steviol glycosides was achieved by LC with UV detection using a mixed-mode RP weak anion exchange chromatography column. Steviol and seven steviol glycosides were analyzed on an Acclaim Mixed-Mode Wax-1 (Dionex) column with a linear gradient of deionized water adjusted to pH 3.00 with phosphoric acid and acetonitrile. The extraction was performed by sonicating dry plant material at 40 degreesC in acetonitrile-water (30 + 70, v/v). LOQ values (mg/g dry weight of plant material) were rebaudioside B, 0.50; steviol, 0.70, dulcoside A, 1.0; steviolbioside, 1.2; stevioside and rebaudioside C, 2.0; rebaudioside D, 3.3; and rebaudioside A, 5.0. The method demonstrated suitable performance for all analytes tested with respect to accuracy (mean recoveries 95-99%), intraday and interday precision for retention times (0.070-0.28% and 0.33-1.0% RSD, respectively), and linearity. The method was used to authenticate steviol glycosides in several samples of Stevia plant material as well as to quantitate steviol glycosides in dietary supplements containing Stevia.


Porphyromonas gingivalis RagB is a proinflammatory signal transducer and activator of transcription 4 agonist.
Periodontal diseases are semi-ubiquitous and caused by chronic, plaque-induced inflammation. The 55-kDa immunodominant RagB outer membrane protein of Porphyromonas gingivalis, a keystone periodontal pathogen, has been proposed to facilitate nutrient transport. However, potential interactions between RagB and the innate response have not been examined. We determined that RagB exposure led to the differential and dose-related expression of multiple genes encoding proinflammatory mediators [interleukin-1α (IL-1α), IL-1β, IL-6, IL-8 and CCL2; all P < 0.05] in primary human monocytes and to the secretion of tumor necrosis factor and IL-8, but not interferon-γ or IL-12. RagB was shown to be a Toll-like receptor 2 (TLR2) and TLR4 agonist that activated signal transducer and activator of transcription 4 and nuclear factor-κB signaling, as determined by a combination of blocking antibodies, pharmaceutical inhibitors and gene silencing. In keeping, a ΔragB mutant similarly exhibited reduced inflammatory capacity, which was rescued by ragB complementation. These results suggest that RagB elicits a major pro-inflammatory response in primary human monocytes and, therefore, could play an important role in the etiology of periodontitis and systemic sequelae.


Lipids and lipoproteins among Ethiopian immigrants: comparison of operations Solomon and Moses.
Lipid and lipoprotein levels and body mass index were compared between two immigrations of Ethiopian Jews to Israel. Those who came in Operation Moses in 1984-85 were survivors of a long trek across hundreds of kilometers and severe food deprivation. Those who immigrated in Operation Solomon in 1991 were bussed from their villages to Addis Ababa where public health care and food were provided and a few months later they were airlifted to Israel. Total cholesterol among the Operation Solomon immigrants was higher than those obtained in Operation Moses in the different age-groups studied, in both sexes. High density lipoprotein-cholesterol was significantly higher and triglycerides lower in Operation Solomon compared with those of Operation Moses. Body mass indices of the Ethiopians in both immigrations were significantly lower than in the Israeli-born population but those who arrived in 1991 were heavier than those in the 1984-85 Operation Moses. The data on the Ethiopian Jews who arrived in Operation Solomon were not affected by the environmental hardships experienced by those who arrived in the 1984-85 Operation Moses. Therefore their exposure to a Western life-style, such as smoking, contraceptive use, change in diet and its effect on arteriosclerosis, diabetes mellitus and coronary heart disease will be of great interest.


[Safety and efficacy of transcatheter aortic valve replacement through transcarotid approach for patients with severe aortic valve stenosis].
Objective: To investigate the safety and efficacy of transcatheter aortic valve replacement(TAVR) through transcarotid approach for patients with severe aortic valve stenosis. Methods: The clinical data of 9 symptomatic severe aortic valve stenosis patients who had high or prohibitive risk for surgery and not suitable for TAVR through femoral artery access,and thus received TAVR through transcarotid approach in our hospital from November 2015 to February 2017 were retrospectively analyzed.The patients were followed up to observe the safety and efficacy of the procedure. Results: There were 4 male and 5 female patients in this cohort, and age was (75.7±8.7) years old. The Society of Thoracic Surgery (STS) scores were (7.9±1.6)%. All patients were treated by left carotid artery approach. One patient experienced valve dislodgement during the procedure and received surgery, and TAVR procedure was successful in the rest 8 patients. Two patients were implanted with permanent pacemaker because of third degree atrioventricular block during the procedure.One patient had cardiac arrest during the procedure and recovered after external chest compression.One patient developed severe carotid stenosis,and there was no clinical manifestation of nerve function deficit after the procedure. All patients were followed up at (30±3) days after the procedure, and there were no adverse events. The modified Rankin scale score was 0. Echocardiography examination showed that the tranvalvular mean gradient was reduced from (63.0±19.2)mmHg(1 mmHg=0.133 kPa) on baseline to (18.1±4.9)mmHg(P<0.001), 4 cases had mild paravalvular leakage, and there was no moderate or severe paravalvular leakage.The NYHA classes was significantly improved at 30 days when compared with before the procedure(2 cases class Ⅱ, 4 cases class Ⅲ,3 cases class Ⅳ before the procedure,and 5 cases classⅠ, 4 cases class Ⅱ after the procedure, P=0.006) , and left ventricular ejection fraction increased from (55.9±13.1)% to (60.4±10.0)% (P=0.030). Conclusion: Our initial experience indicates that transcarotid TAVR is safe and effective for patients with severe aortic valve stenosis.


C-D Vibration at C2 Position of Imidazolium Cation as a Probe of the Ionic Liquid Microenvironment.
Unlike molecular solvents, imidazolium-based ionic liquids are entirely made of ions with spatial heterogeneity. There is a need for spectroscopic probes that can assess the microenvironment near the cations of these complex liquids. In this manuscript, we describe simple chemical procedures to label the C2 position of imidazolium cation with a C-D vibrational probe and show, through linear and nonlinear vibrational spectroscopies, that this C-D stretching mode can be a useful analytical tool to assess both the solvent microenvironment and solute-solvent interactions in imidazolium-based ionic liquids from the cation point of view. It is expected that this C-D vibration probe on the cation will lead to the development of innovative experimental strategies that can provide a better understanding of such ionic liquids.


Deriving Normative Data on 24-Hour Ambulatory Blood Pressure Monitoring for South Asian Children (ASHA): A Clinical Research Protocol.
The global prevalence of hypertension in children and adolescents has increased over the past 2 decades and is the strongest predictor of adult hypertension. South Asians have an increased prevalence of metabolic syndrome associated risk factors including abdominal obesity, diabetes, and hypertension. All these factors contribute to their increased cardiovascular disease burden. Accurate and early identification of hypertension in South Asian children is a necessary aspect of cardiovascular disease prevention. Ambulatory blood pressure monitoring (ABPM) is considered the gold-standard for pediatric blood pressure (BP) measurement. However, its utilization is limited due to the lack of validated normative reference data in diverse, multiethnic pediatric populations. The primary objective is to establish normative height-sex and age-sex-specific reference values for 24-h ABPM measurements among South Asian children and adolescents (aged 5-17 years) in Ontario and British Columbia, Canada. Secondary objectives are to evaluate differences in ABPM measurements by body mass index classification, to compare our normative data against pre-existing data from German and Hong Kong cohorts, and to evaluate relationships between habitual movement behaviors, diet quality, and ABPM measurements. Cross-sectional study, quasi-representative sample. Participants will be recruited from schools, community centers, and places of worship in Southern Ontario (Greater Toronto and Hamilton area, including the Peel Region) and Greater Vancouver, British Columbia. We aim to recruit 2113 nonoverweight children (aged 5-17 years) for the primary objective. We aim to recruit an additional 633 overweight or obese children to address the secondary objectives. Ambulatory BP monitoring measurements will be obtained using Spacelabs 90217 ABPM devices, which are validated for pediatric use. The ActiGraph GT3X-BT accelerometer, which has also been validated for pediatric use, will be used to obtain movement behavior data. Following recruitment, eligible children will be fitted with 24-h ABPM and physical activity monitors. Body anthropometrics and questionnaire data regarding medical and family history, medications, diet, physical activity, and substance use will be collected. Ambulatory BP monitoring data will be used to develop height-sex- and age-sex-specific normative reference values for South Asian children. Secondary objectives include evaluating differences in ABPM measures between normal weight, overweight and obese children; and comparing our South Asian ABPM data to existing German and Hong Kong data. We will also use compositional data analysis to evaluate associations between a child's habitual movement behaviors and ABPM measures. Bloodwork will not be performed to facilitate recruitment. A non-South Asian comparator cohort will not be included due to feasibility concerns. Using a convenience sampling approach introduces the potential for selection bias. Ambulatory BP monitoring is a valuable tool for the identification and follow-up of pediatric hypertension and overcomes many of the limitations of office-based BP measurement. The development of normative ABPM data specific to South Asian children will increase the accuracy of BP measurement and hypertension identification in this at-risk population, providing an additional strategy for primary prevention of cardiovascular disease.


The spectrum of positive scan patterns in parathyroid scintigraphy.
Parathyroid scintigraphy provides the clinician treating primary hyperparathyroidism with valuable information regarding the presence and location of parathyroid adenomas. In dual-phase imaging of the parathyroid glands, a widely employed technique that exploits the radiotracer washout characteristics of parathyroid adenomas, images are typically obtained at 20 minutes after administration of the radiotracer (Tc-99m sestamibi or Tc-99m tetrofosmin) and again at 2 hours after injection. Additional imaging of the thyroid is frequently performed to localize thyroid tissue, using Tc-99m pertechnetate or iodine-123.A positive examination can display one of several different patterns; a focus of increased radiotracer activity representing a parathyroid adenoma may be detected on the initial images, on the delayed images, or both. On the thyroid scan, the parathyroid adenoma (if it is discernible) may appear as a cold defect or a persistently hot focus. In our retrospective review of 148 consecutive patients over a 2-year period, 74 examinations were positive and had pathologic confirmation. These examinations were divided into 4 patterns: I (hot focus seen on initial and delayed images, and not on thyroid scan), II (hot focus seen only in initial images), III (hot focus seen only on delayed images), and IV (hot focus seen on initial, delayed and thyroid scan images). Results were as follows: pattern I, 88% (65/74); pattern II, 7% (5/74); pattern III, 3% (2/74); and pattern IV, 3% (2/74). Parathyroid adenomas produce several different patterns on dual-phase scintigraphy. To interpret the examination correctly, it is important for the radiologist to be aware of these patterns of positivity.


Analysis of a genetic hitchhiking model, and its application to DNA polymorphism data from Drosophila melanogaster.
Begun and Aquadro have demonstrated that levels of nucleotide variation correlate with recombination rate among 20 gene regions from across the genome of Drosophila melanogaster. It has been suggested that this correlation results from genetic hitchhiking associated with the fixation of strongly selected mutants. The hitchhiking process can be described as a series of two-step events. The first step consists of a strongly selected substitution wiping out linked variation in a population; this is followed by a recovery period in which polymorphism can build up via neutral mutations and random genetic drift. Genetic hitchhiking has previously been modeled as a steady-state process driven by recurring selected substitutions. We show here that the characteristic parameter of this steady-state model is alpha v, the product of selection intensity (alpha = 2Ns) and the frequency of beneficial mutations v (where N is population size and s is the selective advantage of the favored allele). We also demonstrate that the steady-state model describes the hitchhiking process adequately, unless the recombination rate is very low. To estimate alpha v, we use the data of DNA sequence variation from 17 D. melanogaster loci from regions of intermediate to high recombination rates. We find that alpha v is likely to be > 1.3 x 10(-8). Additional data are needed to estimate this parameter more precisely. The estimation of alpha v is important, as this parameter determines the shape of the frequency distribution of strongly selected substitutions.


Live attenuated seasonal and pandemic influenza vaccine in school-age children: a randomized controlled trial.
The novel influenza A(H1N1pdm09) virus emerged in North America in early 2009 and rapidly spread worldwide. In this study we report the efficacy of the live attenuated monovalent H1N1pdm09 vaccine and 2009-10 seasonal influenza vaccine in a randomized double-blind placebo-controlled trial. We enrolled 703 children aged 7-11. Each child was randomly allocated in the ratio 3:2 to receive one dose of live attenuated monovalent H1N1pdm09 vaccine or saline placebo between November 2009 and January 2010, followed after 3-10 weeks by independent random allocation to one dose of live attenuated trivalent 2009-10 seasonal influenza vaccine or saline placebo in the same ratio. Children were followed up through September 2010 with biweekly telephone calls and symptom diaries. Seasonal and pandemic influenza infections were confirmed by virologic testing of nose and throat swabs collected during acute respiratory illnesses. Overall, 30 children had confirmed influenza including 3 (0.43%) H1N1pdm09, 10 (1.4%) seasonal A(H3N2), and 17 (2.4%) influenza B. There were no significant differences in incidence rates of H1N1pdm09 or A(H3N2) between the four study arms, but receipt of the seasonal influenza vaccine was associated with a significant reduction in risk of influenza B (p<0.01). Vaccine efficacy against confirmed H1N1pdm09 infection associated with receipt of the monovalent H1N1pdm09 vaccine was 65% (95% confidence interval, CI: -281%, 97%). Vaccine efficacies against confirmed seasonal influenza A(H3N2) and B infection associated with receipt of the seasonal influenza vaccine were 31% (95% CI: -138%, 80%) and 96% (95% CI: 67%, 99%) respectively. Vaccine efficacy was consistent with other studies of the monovalent H1N1pdm09 vaccine and seasonal influenza vaccines. Our study was underpowered to provide precise estimates of vaccine efficacy due to low incidence of influenza A viruses during the study period.


Cognitive practice effects delay diagnosis of MCI: Implications for clinical trials.
Practice effects (PEs) on cognitive tests obscure decline, thereby delaying detection of mild cognitive impairment (MCI). Importantly, PEs may be present even when there are performance declines, if scores would have been even lower without prior test exposure. We assessed how accounting for PEs using a replacement-participants method impacts incident MCI diagnosis. Of 889 baseline cognitively normal (CN) Alzheimer's Disease Neuroimaging Initiative (ADNI) participants, 722 returned 1 year later (mean age = 74.9 ± 6.8 at baseline). The scores of test-naïve demographically matched "replacement" participants who took tests for the first time were compared to returnee scores at follow-up. PEs-calculated as the difference between returnee follow-up scores and replacement participants scores-were subtracted from follow-up scores of returnees. PE-adjusted cognitive scores were then used to determine if individuals were below the impairment threshold for MCI. Cerebrospinal fluid amyloid beta, phosphorylated tau, and total tau were used for criterion validation. In addition, based on screening and recruitment numbers from a clinical trial of amyloid-positive individuals, we estimated the effect of earlier detection of MCI by accounting for cognitive PEs on a hypothetical clinical trial in which the key outcome was progression to MCI. In the ADNI sample, PE-adjusted scores increased MCI incidence by 19% (P < .001), increased proportion of amyloid-positive MCI cases (+12%), and reduced proportion of amyloid-positive CNs (-5%; P's < .04). Additional calculations showed that the earlier detection and increased MCI incidence would also substantially reduce necessary sample size and study duration for a clinical trial of progression to MCI. Cost savings were estimated at ≈$5.41 million. Detecting MCI as early as possible is of obvious importance. Accounting for cognitive PEs with the replacement-participants method leads to earlier detection of MCI, improved diagnostic accuracy, and can lead to multi-million-dollar cost reductions for clinical trials.


The cerebellum regulates fear extinction through thalamo-prefrontal cortex interactions in male mice.
Fear extinction is a form of inhibitory learning that suppresses the expression of aversive memories and plays a key role in the recovery of anxiety and trauma-related disorders. Here, using male mice, we identify a cerebello-thalamo-cortical pathway regulating fear extinction. The cerebellar fastigial nucleus (FN) projects to the lateral subregion of the mediodorsal thalamic nucleus (MD), which is reciprocally connected with the dorsomedial prefrontal cortex (dmPFC). The inhibition of FN inputs to MD in male mice impairs fear extinction in animals with high fear responses and increases the bursting of MD neurons, a firing pattern known to prevent extinction learning. Indeed, this MD bursting is followed by high levels of the dmPFC 4 Hz oscillations causally associated with fear responses during fear extinction, and the inhibition of FN-MD neurons increases the coherence of MD bursts and oscillations with dmPFC 4 Hz oscillations. Overall, these findings reveal a regulation of fear-related thalamo-cortical dynamics by the cerebellum and its contribution to fear extinction.


Shin'iseihaito (Xinyiqingfeitang) Suppresses the Biofilm Formation of Streptococcus pneumoniae In Vitro.
Streptococcus pneumoniae (S. pneumoniae) is the important pathogen that causes otolaryngeal diseases such as sinusitis. S. pneumoniae frequently forms the biofilm to prevent severe circumstances such as antimicrobial agents. Shin'iseihaito (xinyiqingfeitang) is a formula of Japanese traditional Kampo medicine that has 9 crude drugs and provides the medicinal usage for sinusitis. The objective of the present study is to reveal the mechanism of antibiofilm activity by Shin'iseihaito extract (SSHT). SSHT significantly inhibited the formation of biofilm from S. pneumoniae ATCC 49619 in dose- and time-dependent manners. SSHT also significantly suppressed the biofilm formation by other five different cps types of S. pneumoniae clinical isolates. We found that the extracts of 8 out of 9 components in Shin'iseihaito had the inhibitory effects of biofilm formation, and the extract of the root of Scutellaria baicalensis had the strongest effect among the ingredients of Shin'iseihaito. We found that the capsule of SSHT-treated S. pneumoniae was significantly thinner than that of the untreated group and that SSHT reduced the hydrophobicity of bacterial cell surface. Our results suggest that Shin'iseihaito may be a useful agent for the treatment of S. pneumoniae-induced sinusitis because of the inhibition of biofilm formation of S. pneumoniae.


[Age-related and regional changes in angiotensin-converting and kinin-degrading activity in the brain of aggressive rats].
Aggressive behaviour (muricidal) induced in rats by local electrolyte lesions of septal brain area was accompanied by changes in angiotensin-converting enzyme (ACE) and total kinin-destroying activity (KDA) in different brain regions. In 2-month-old rats (30 days after septal operation) a decrease in ACE activity was observed in hypothalamus and striatum, while in the cerebellum the activity was increased. KDA in this group of aggressive rats was markedly increased in the pituitary body, hypothalamus and striatum. Half a year after septal lesion in spite of aggressive behaviour retention, ACE activity and KDA did not differ from their activity in nonmuricidal rats of the same age. These data show a distinct role of the peptides studied in the formation and maintenance of muricidal behaviour in rats of different age.


Alternative Splicing in Next Generation Sequencing Data of Saccharomyces cerevisiae.
mRNA splicing is required in about 4% of protein coding genes in Saccharomyces cerevisiae. The gene structure of those genes is simple, generally comprising two exons and one intron. In order to characterize the impact of alternative splicing on the S. cerevisiae transcriptome, we perform a systematic analysis of mRNA sequencing data. We find evidence of a pervasive use of alternative splice sites and detect several novel introns both within and outside protein coding regions. We also find a predominance of alternative splicing on the 3' side of introns, a finding which is consistent with existing knowledge on conservation of exon-intron boundaries in S. cerevisiae. Some of the alternatively spliced transcripts allow for a translation into different protein products.


The relationship between physical inactivity and mental wellbeing: Findings from a gamification-based community-wide physical activity intervention.
Mental ill health accounts for 13 per cent of total global disease burden with predictions that depression alone will be the leading cause of disease burden globally by 2030. Poor mental health is consistently associated with deprivation, low income, unemployment, poor education, poorer physical health and increased health-risk behaviour. A plethora of research has examined the relationship between physical activity and mental wellbeing; however, the influence of community-wide gamification-based physical activity interventions on mental wellbeing, to the authors' knowledge, is yet to be explored. In view of this paucity of attention, the current study examined the relationship between physical activity and mental wellbeing pre/post a community-wide, gamification-based intervention. The findings revealed that increases in mental wellbeing were significantly greater for the least active prior to the intervention, and a strong, positive correlation between increase in physical activity and increase in mental wellbeing was observed.


Effects of degrees of reaming on healing of segmental fractures in rats.
To assess the effects of graded intramedullary reaming and nailing on the healing pattern of segmental diaphyseal fractures using male Wistar rats. In male Wistar rats we produced two standardized, partial osteotomies with an eight-millimeter intermediary fragment in the femoral diaphysis. The osteotomies were subsequently manually broken. In Group A, intramedullary reaming was performed to 1.6 millimeters, and the fracture was stabilized with a 1.6-millimeter steel pin. In Group B, the femoral canal was reamed to 2.0 millimeters, and a hollow steel tube of 2.0 millimeters was installed. The rats were allowed free movement. After four, eight, and twelve weeks, eight rats in each group were sacrificed and callus formation, biomechanical properties, and bone blood flow were evaluated. The callus area was relatively constant with time in Group B, whereas a reduction was observed in Group A at twelve weeks. The biomechanical properties increased throughout the experimental period in both groups, and no significant differences between the groups were detected in bending moment, bending rigidity, or fracture energy. Total bone blood flow was substantially increased at four weeks in both groups and decreased throughout the experimental period. In addition, blood flow of the segmental fractured area was substantially increased after four weeks and decreased gradually thereafter. The increases in blood flow tended to be largest in the moderately reamed group. This study indicates that the degree of reaming does not significantly affect the healing pattern measured as restoration of mechanical characteristics.


Case series: two cases of an atypical presentation of oral granular cell tumour.
This paper describes two cases of oral granular cell tumours with an atypical clinical presentation; both are in females aged between 45 and 63 years of age. Granular cell tumours are unusual soft tissue neoplasm of neural or Schwann cell origin. Oral GCTs usually present clinically as pink or yellow small sessile lesions. GCTs are usually benign in nature; however they can present in a malignant form in fewer than 2% of cases. In benign cases treatment is surgical and usually curative with extremely low recurrence rates.


Uncovered Microbial Diversity in Antarctic Cryptoendolithic Communities Sampling three Representative Locations of the Victoria Land.
The endolithic niche represents an ultimate refuge to microorganisms in the Mars-like environment of the Antarctic desert. In an era of rapid global change and desertification, the interest in these border ecosystems is increasing due to speculation on how they maintain balance and functionality at the dry limits of life. To assure a reliable estimation of microbial diversity, proper sampling must be planned in order to avoid the necessity of re-sampling as reaching these remote locations is risky and requires tremendous logistical and economical efforts. In this study, we seek to determine the minimum number of samples for uncovering comprehensive bacterial and fungal diversity, comparing communities in strict vicinity to each other. We selected three different locations of the Victoria Land (Continental Antarctica) at different altitudes and showing sandstone outcrops of a diverse nature and origin-Battleship promontory (834 m above sea level (a.s.l.), Southern VL), Trio Nunatak (1,470 m a.s.l., Northern VL) and Mt New Zealand (3,100 m a.s.l., Northern VL). Overall, we found that a wider sampling would be required to capture the whole amplitude of microbial diversity, particularly in Northern VL. We concluded that the inhomogeneity of the rock matrix and the stronger environmental pressure at higher altitudes may force the communities to a higher local diversification.


Vaginal reconstruction with a double-sided biomembrane-a preclinical experimental study on large animals.
Tissue engineering techniques bring the promise of vaginal reconstruction with low invasiveness and fewer complications. However, existing biomaterial scaffolds remain limited in efficient vaginal recovery, focusing only on regenerating an epithelial layer, but muscle layers are missing or abnormal. The lack of a multi-tissue hierarchical structure in the reconstructed vagina leads to shrinking, stenosis, and fibrosis. Here, an acellular matrix named a double-sided biomembrane (DBM) is demonstrated for vaginal recovery. The regeneration of epithelial and muscle layers is achieved simultaneously since the smooth side of the DBM is helpful for guiding epithelial cell growth, while its loose and porous side guides muscle cell growth. In addition, the DBM demonstrates excellent mechanical properties similar to vaginal tissue, and hydrophilicity. Therefore, neovaginas were observed in the fourth and twelfth weeks after DBMs were transplanted to repair full-thickness vaginal defects (4 cm) that we established in large animals. The DBMs can effectively promote rapid epithelialization, the formation of large muscle bundles, higher rates of angiogenesis, and the restoration of physiological function in a neovagina. That is, the injured vagina achieves nearly complete recovery in anatomy and function, similar to a normal vagina. These preclinical results indicate that the DBM has prospects for vaginal injury repair.


[Formation of spheriods by cultured human diploid cells].
When human lung diploid fibroblasts are grown in micro-wells in presence of the organic buffer HEPES in an atmosphere of 5% of CO2, the cells migrate and form spheroids. Histologic examination reveals the presence of fibroblastic and epithelioid cells in these spheroids. Signs of degeneration are seen in both cell types under the electron microscope. Following dissociation of the spheroids and their subculture in absence of HEPES, the cells reverse to their original fibroblast-like morphology and grow in monolayer.


Structure and function of an antifreeze polypeptide from ocean pout, Macrozoarces americanus: role of glutamic acid residues in protein stability and antifreeze activity by site-directed mutagenesis.
The successful expression and purification of the recombinant ocean pout antifreeze polypeptide (rAFP) in Escherichia coli have enabled the study of its structure-function relationship by site-directed mutagenesis. The role of carboxyl groups at Glu23 and Glu36 of the rAFP was probed by replacing these residues with either glutamine or alanine residues as both single and double mutants. The AFP mutants were expressed, purified and characterized in terms of primary and secondary structures, thermal stability and antifreeze activities. The properties of these mutants were compared with those of the rAFP. Three distinct functions are identified for the carboxyl groups: (i) the negative charges at positions 23 and 36 are involved in the thermal stability of the polypeptide; (ii) the negative charges at positions 23 and 36 contribute to the thermal hysteretic activities of the polypeptide; and (iii) the negative charge at position 23 and hydrogen-bonding ability at position 36 contribute to the ice-binding activity of the polypeptide.


Methyl Acetate Synthesis by Esterification on the Modified Ferrierite: Correlation of Acid Sites Measured by Pyridine IR and NH3-TPD for Steady-State Activity.
The amounts of Brønsted acid sites on K, P, and Zr-modified microporous Ferrierite zeolite were investigated through pyridine FT-IR and NH3-TPD analyses. P-modified Ferrierite showed a superior catalytic activity for methyl acetate synthesis by esterification of methanol and acetic acid. The catalytic activity at steady-state with the acidic properties of as-prepared catalysts was well correlated with the results of pyridine FT-IR (intensity ratio of Brønsted acid sites to total acid sites) compared with that of NH3-TPD. The results can suggest the proper and simple method to estimate the esterification activity at steady-state using the measured acid sites on the as-prepared zeolites.


The Lymphatic Headmaster of the Mast Cell-Related Splanchnic Inflammation in Portal Hypertension.
Portal hypertension is a common complication of liver disease, either acute or chronic. Consequently, in chronic liver disease, such as the hypertensive mesenteric venous pathology, the coexisting inflammatory response is classically characterized by the splanchnic blood circulation. However, a vascular lymphatic pathology is produced simultaneously with the splanchnic arterio-venous impairments. The pathological increase of the mesenteric venous pressure, by mechanotransduction of the venous endothelium hyperpressure, causes an inflammatory response involving the subendothelial mast cells and the lymphatic endothelium of the intestinal villi lacteal. In portal hypertension, the intestinal lymphatic inflammatory response through the development of mesenteric-systemic lymphatic collateral vessels favors the systemic diffusion of substances with a molecular pattern associated with damage and pathogens of intestinal origin. When the chronic hepatic insufficiency worsens the portal hypertensive inflammatory response, the splanchnic lymphatic system transports the hyperplasied intestinal mast cells to the mesenteric lymphatic complex. Then, an acquired immune response regulating a new hepato-intestinal metabolic scenario is activated. Therefore, reduction of the hepatic metabolism would reduce its key centralized functions, such as the metabolic, detoxifying and antioxidant functions which would try to be substituted by their peroxisome activity, among other functions of the mast cells.


FOXO1-mediated epigenetic modifications are involved in the insulin-mediated repression of hepatocyte aquaporin 9 expression.
Aquaporin (AQP) 9 transports glycerol and water, and belongs to the aquaglyceroporin subfamily. Insulin acts as a negative regulator of AQP9, and FOXO1 has the ability to mediate the regulatory effects of insulin on target gene expression. The aim of the present study was to determine whether insulin‑induced repression of AQP9 involved an epigenetic mechanism. HepG2 human hepatocyte cells were treated with 500 µM insulin for different durations. AQP9 mRNA expression levels were determined by quantitative polymerase chain reaction (qPCR), and histone H3 acetylation, phosphorylation and methylation at the insulin responsive element (IRE) of the AQP9 promoter was assessed using chromatin immunoprecipitation coupled with qPCR. The effects of lentiviral FOXO1 overexpression on AQP9 expression levels and H3 modifications at the AQP9 promoter were also determined. The insulin treatment resulted in a significant and time‑dependent reduction in AQP9 mRNA expression levels in HepG2 cells, as compared with untreated cells (P<0.05). In the insulin‑treated cells, the levels of H3 acetylation and phosphorylation were significantly reduced (P<0.05), but the level of H3 methylation was increased. Enforced expression of FOXO1 increased AQP9 mRNA and protein expression levels in HepG2 cells. Furthermore, FOXO1 overexpression promoted H3 acetylation and phosphorylation, and reduced H3 methylation at the IRE locus of the AQP9 promoter. These data provide, to the best of our knowledge, the first evidence that insulin‑induced transcriptional suppression of AQP9 expression in hepatocytes involves FOXO1‑mediated H3 modifications at the IRE locus in the promoter.


Vocational rehabilitation for veterans with felony histories and mental illness: 12-month outcomes.
Lack of employment is an important barrier to successful reintegration encountered by those released from prison with mental illnesses and/or substance use disorders. This study compares 3 different vocational reintegration modalities for a veteran population: (a) basic services; (b) self-study using the About Face Vocational Manual; and (c) the About Face Vocational Program, a standardized group program focused on the About Face Vocational Manual. One-hundred eleven veterans with a history of at least one felony conviction and a mental illness and/or substance use disorder were recruited from a large urban Veterans Affairs (VA) medical center. Veterans were assigned to 1 of the 3 conditions and followed for 12 months. At the end of the 1-year follow-up period, veterans in the group condition had superior competitive and stable employment rates, as well as faster times to employment compared with both the basic and self-study conditions. The self-study condition was generally indistinguishable from the basic services condition. Overall, new employment during the last 6 months of the follow-up period was relatively low. The findings support the use of standardized group vocational reintegration programs such as the About Face Vocational Program. Limitations and implications are discussed. (PsycINFO Database Record


Immediate effects of a single session of robot-assisted gait training using Hybrid Assistive Limb (HAL) for cerebral palsy.
[Purpose] Robot-assisted gait training (RAGT) using Hybrid Assistive Limb (HAL, CYBERDYNE) was previously reported beneficial for stroke and spinal cord injury patients. Here, we investigate the immediate effect of a single session of RAGT using HAL on gait function for cerebral palsy (CP) patients. [Subjects and Methods] Twelve patients (average age: 16.2 ± 7.3 years) with CP received a single session of RAGT using HAL. Gait speed, step length, cadence, single-leg support per gait cycle, hip and knee joint angle in stance, and swing phase per gait cycle were assessed before, during, and immediately after HAL intervention. [Results] Compared to baseline values, single-leg support per gait cycle (64.5 ± 15.8% to 69.3 ± 12.1%), hip extension angle in mid-stance (149.2 ± 19.0° to 155.5 ± 20.1°), and knee extension angle in mid-stance (137.6 ± 20.2° to 143.1 ± 19.5°) were significantly increased immediately after intervention. Further, the knee flexion angle in mid-swing was significantly decreased immediately after treatment (112.0 ± 15.5° to 105.2 ± 17.1°). Hip flexion angle in mid-swing also decreased following intervention (137.2 ± 14.6° to 129.7 ± 16.6°), but not significantly. Conversely, gait speed, step length, and cadence were unchanged after intervention. [Conclusion] A single-time RAGT with HAL improved single-leg support per gait cycle and hip and knee joint angle during gait, therapeutically improving gait function in CP patients.


Concurrent use of a lumboperitoneal shunt with programmable valve and ventricular access device in the treatment of pseudotumor cerebri: review of 40 cases.
The authors evaluated the efficacy of treating patients with pseudotumor cerebri (PTC) and headaches due to increased intracranial pressure (ICP) by using a lumboperitoneal (LP) shunt with a programmable valve and ventricular access device (VAD). Forty patients in whom PTC was diagnosed were treated using LP shunts with programmable valves and wand-guided placement of a VAD. All patients had papilledema and high opening pressure during spinal tap. The mean follow-up was 18 months (range 3-72 months). When patients complained of headaches that suggested shunt malfunction, the ventricular reservoir was tapped at bedside to assess ICP. The programmable valve was adjusted based on the patient's headache and ICP. The VAD was tapped in 21 patients, and the LP valve was redialed in 14. Shunt malfunction was diagnosed accurately. The 10 patients undergoing revision were all found to have shunt obstruction except 1 whose valve was replaced because it could not be reprogrammed. No patient treated with a shunt developed a Chiari malformation. The VAD was exposed in 4 patients with infection or wound breakdown. The LP shunt was revised in 2 patients who developed a pseudomeningocele. In 1 patient, a small bowel obstruction responded to conservative management. Seven patients had headaches despite documented normal ICP. That is, the headaches were unrelated to shunt function, and these patients were referred to a pain management clinic. Lumboperitoneal shunts with programmable valves effectively controlled the outflow of lumbar cerebrospinal fluid to ameliorate the symptoms of PTC. The VAD permitted assessment of ICP and thus, indirectly, LP shunt function, and benefits outweighed risks. The programmable valve permitted cerebrospinal fluid flow to be adjusted based on patients' clinical status and ICP to be measured by the VAD.


Causal attributions and health behavior choices among stroke and transient ischemic attack survivors.
To reduce the risk of a recurring event in patients who have suffered an initial stroke or transient ischemic attack (TIA), nurses are challenged with implementing and promoting changes in lifestyle and adherence to treatment regimens. Assessing patients' beliefs about the cause of the stroke or TIA is important to understanding their subsequent health behaviors. This study describes the causal attributions and health behavior choices of 9 participants following a stroke or TIA. Attributions were categorized as internal or external and cross-tabulated by controllability. The attributions were compared with health behavior choices. All participants attempted to make causal attributions, both internal (e.g., anxiety, hypertension, lifestyle) and external (e.g., stress, fate). Those making external attributions demonstrated poorer health behavior choices than those making internal attributions; controllability had no influence on behavior. Patients diagnosed more than 6 months before the study tended to make more external attributions. The results can help nurses understand the beliefs that drive the health behavior choices made by stroke and TIA survivors and guide them in tailoring prevention strategies and engaging patients in preventive activities.


Video-assisted thoracoscopic surgery using single-lumen endotracheal tube anesthesia.
Most general thoracic surgeons use double-lumen endotracheal tube (DLET) anesthesia for all video-assisted thoracoscopic surgery (VATS). We evaluated a single-lumen endotracheal tube (SLET) for VATS for drainage of pleural effusions and pleural biopsies. A consecutive series of patients with recurrent pleural effusions underwent VATS using an SLET and only one incision. Operations were accomplished via one 2-cm incision using a 5-mm rigid thoracoscope and mediastinoscopic biopsy forceps for directed pleural biopsies. A working area was accomplished with low tidal volumes. There were 376 patients (191 women). The indications for VATS were a nondiagnosed or benign pleural effusion in 294 patients, and a malignant effusion in 82 patients. Two hundred eight patients underwent biopsy of the parietal pleura, and mean operative time was 17 min. Adequate visibility was obtained in all. When compared to preoperative cytology, VATS was more sensitive (45% compared to 99%, p < 0.001), had a higher negative predictive value (56% compared to 99%, p < 0.001), and was more accurate (67% compared to 99%, p < 0.001). Forty-seven percent of patients with a history of cancer had false-negative preoperative cytology results. Complications occurred in seven patients (2%), and there were three operative deaths (none related to the operative procedure). VATS using SLET and only one incision is possible, and it affords excellent visualization of the pleural space, allowing pleural biopsies and talc insufflation. It avoids the risk, time, and cost of a DLET. It is significantly more sensitive and accurate than preoperative cytology, and it should be considered as the diagnostic and therapeutic procedure of choice in patients with recurrent pleural effusions.


Protein kinase structure and function analysis with chemical tools.
Protein kinases are the largest enzyme superfamily involved in cell signal transduction and represent therapeutic targets for a range of diseases. There have been intensive efforts from many labs to understand their catalytic mechanisms, discover inhibitors and discern their cellular functions. In this review, we will describe two approaches developed to analyze protein kinases: bisubstrate analog inhibition and phosphonate analog utilization. Both of these methods have been used in combination with the protein semisynthesis method expressed protein ligation to advance our understanding of kinase-substrate interactions and functional elucidation of phosphorylation. Previous work on the nature of the protein kinase mechanism suggests it follows a dissociative transition state. A bisubstrate analog was designed against the insulin receptor kinase to mimic the geometry of a dissociative transition state reaction coordinate distance. This bisubstrate compound proved to be a potent inhibitor against the insulin receptor kinase and occupied both peptide and nucleotide binding sites. Bisubstrate compounds with altered hydrogen bonding potential as well as varying spacers between the adenine and the peptide demonstrate the importance of the original design features. We have also shown that related bisubstrate analogs can be used to potently block serine/threonine kinases including protein kinase A. Since many protein kinases recognize folded protein substrates for efficient phosphorylation, it was advantageous to incorporate the peptide-ATP conjugates into protein structures. Using expressed protein ligation, a Src-ATP conjugate was produced and shown to be a high affinity ligand for the Csk tyrosine kinase. Nonhydrolyzable mimics of phosphoSer/phosphoTyr can be useful in examining the functionality of phosphorylation events. Using expressed protein ligation, we have employed phosphonomethylene phenylalanine and phosphonomethylene alanine to probe the phosphorylation of Tyr and Ser, respectively. These tools have permitted an analysis of the SH2-phosphatases (SHP1 and SHP2), revealing a novel intramolecular stimulation of catalytic activity mediated by the corresponding phosphorylation events. They have also been used to characterize the cellular regulation of the melatonin rhythm enzyme by phosphorylation.


Important anatomical landmarks in the lateral nasal wall.
The study aimed to investigate the anatomy of the lateral nasal wall to provide a set of measurements among some important anatomical landmarks and to reveal the relationship between them. Fifty half heads were dissected to determine the distances between important landmarks in the lateral nasal wall for endoscopic sinus surgery. Landmarks were measured with an electronic caliper. This study was carried out between December 2002 and February 2003 at the Anatomy Research Laboratory, Faculty of Medicine, Akdeniz University, Antalya, Turkey. Results were provided as mean +/- standard deviation. In our study, some of the critical distances as in the lateral nasal wall were measured and results showed consistency to the data found in the literature. Our results are useful to achieve safe endoscopic sinus surgery.


Relationship as an inherent component in healthy women's fatigue.
The notion of fatigue has remained ambiguous despite more than 100 years of study. Fatigue is recognized as subjective in nature, and it is studied and clinically managed as primarily intrapersonal in scope, with treatment approaches often based in an established, if unfounded, hierarchy of assumptions. When a physiologic cause for fatigue is not identifiable, fatigue complaints often are considered illegitimate. This article builds on data from the literature and from the author's previous work in women's fatigue and relatedness to suggest that interpersonal relationships may serve to exacerbate healthy women's fatigue experiences. The importance of relationship to women's life experience and the inherently relational character of women's fatigue are discussed. The author proposes the importance of including interpersonal experiences as a component of the definition of fatigue for healthy women.


Which pathologic staining method can visualize the hyperacute infarction lesion identified by diffusion MRI?: A comparative experimental study.
The study aimed to establish a staining method that could delineate the macroscopic lesion boundary of a hyperacute infarction depicted by diffusion-weighted MRI (DWI) and to validate the infarction boundary by comparing different staining methods. Thirteen rats with 1 -h middle cerebral artery (MCA) infarction were included. Five different staining methods (Hematoxylin and eosin (H&E), Nissl, 2,3,5-triphenyltetrazolium hydrochloride (TTC), microtubule associated protein 2 (MAP2), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) stains) were used to identify whether the hyperacute infarction could be histopathologically identified. Dice indices were compared to evaluate similarities in the lesion area ascertained by DWI and the staining methods. Through macroscopic lesion delineation, each region was subdivided into abnormal regions in all three stains (ROIA), abnormal in two stains (ROIB), and abnormal in only one (ROIC). Microscopic cellular changes were evaluated and graded according to each region. Mean Dice indices of the H&E stain were significantly higher than those of the Nissl- and MAP2-stained specimens (0.83 ± 0.052, 0.58 ± 0.107, and 0.56 ± 0.059, respectively; p = 0.000). Grading scores for ROIs in the DWI abnormal lesions varied by region: ROIA exhibited the most severe damage [median (IQR), 3 (1)], followed respectively by ROIB [median (IQR), 2 (0)] and ROIC [median (IQR), 1 (0)] COMPARISON WITH EXISTING METHODS: H&E stain best reflects 1 h hyperacute DWI abnormal lesions. H&E stain allowed for the macroscopic delineation of the 1 h DWI-abnormal lesions, while MAP2 and Nissl stains could only partially depict lesions.


Progressive decline in renal function induces a gradual decrease in total hemoglobin and exercise capacity.
We examined 58 patients (38 men, 20 women; mean age: 45 +/- 12 years; body mass index: 24 +/- 4 kg/m2) with a glomerular filtration rate (GFR) ranging from 3 to 32 ml/min, in order to determine the effects of a progressive decline in renal function on total hemoglobin (THb) and exercise capacity. The THb ranged from 185 to 759 g and the hemoglobin concentration ranged from 66 to 151 g/l. Maximal exercise capacity ranged from 50 to 260 W (40-143% of the expected norm). Nearly all the patients interrupted their exercise tests due to general fatigue, leg tiredness or a combination of these factors. There was a significant partial correlation between THb and GFR after sex and age had been accounted for (r = 0.39; p < 0.005). Maximal exercise capacity and THb showed a significant partial correlation after sex, age and GFR had been accounted for (r = 0.27; p < 0.05). Maximal exercise capacity showed a significant partial correlation with GFR after sex, age and THb had been accounted for (r = 0.30; P < 0.05). In conclusion, there is a gradual decline in THb and maximal exercise capacity as uremia progresses. Anemia appears to be a contributory cause responsible for the decrease in maximal exercise capacity along with other factors pertinent to uremia per se.


Conformation of the human immunoglobulin G2 hinge imparts superagonistic properties to immunostimulatory anticancer antibodies.
Monoclonal antibody (mAb) drugs that stimulate antitumor immunity are transforming cancer treatment but require optimization for maximum clinical impact. Here, we show that, unlike other immunoglobulin isotypes, human IgG2 (h2) imparts FcγR-independent agonistic activity to immune-stimulatory mAbs such as anti-CD40, -4-1BB, and -CD28. Activity is provided by a subfraction of h2, h2B, that is structurally constrained due its unique arrangement of hinge region disulfide bonds. Agonistic activity can be transferred from h2 to h1 by swapping their hinge and CH1 domains, and substitution of key hinge and CH1 cysteines generates homogenous h2 variants with distinct agonistic properties. This provides the exciting opportunity to engineer clinical reagents with defined therapeutic activity regardless of FcγR expression levels in the local microenvironment.


Assessment of the Eutrophication-Related Environmental Parameters in Two Mediterranean Lakes by Integrating Statistical Techniques and Self-Organizing Maps.
During the last decades, Mediterranean freshwater ecosystems, especially lakes, have been under severe pressure due to increasing eutrophication and water quality deterioration. In this article, we compared the effectiveness of different data analysis methods by assessing the contribution of environmental parameters to eutrophication processes. For this purpose, principal components analysis (PCA), cluster analysis, and a self-organizing map (SOM) were applied, using water quality data from two transboundary lakes of North Greece. SOM is considered as an advanced and powerful data analysis tool because of its ability to represent complex and nonlinear relationships among multivariate data sets. The results of PCA and cluster analysis agreed with the SOM results, although the latter provided more information because of the visualization abilities regarding the parameters' relationships. Besides nutrients that were found to be a key factor for controlling chlorophyll-a (Chl-a), water temperature was related positively with algal production, while the Secchi disk depth parameter was found to be highly important and negatively related toeutrophic conditions. In general, the SOM results were more specific and allowed direct associations between the water quality variables. Our work showed that SOMs can be used effectively in limnological studies to produce robust and interpretable results, aiding scientists and managers to cope with environmental problems such as eutrophication.


"… he always slaps me on my ears": the health consequences of intimate partner violence among a group of patrilineal women in Ghana.
Intimate partner violence has implications for women's health globally. Patrilineal women have been shown to have increased risk of experiencing intimate partner violence, yet, the health consequences of intimate partner violence in patrilineal women have not been thoroughly explored or documented. This study used qualitative in-depth interviews to explore the health effects of intimate partner violence among 15 ever-partnered Ghanaian patrilineal women. Participants attributed violence to several factors including gendered domestic relations, cultural and marital rites and alcohol use, among other factors. Abused women reported health problems such as feelings of worthlessness, sleeplessness, suicidal ideation, eye injuries, bodily weakness, hypertension, genital sores and the premature termination of pregnancy. Policy makers should pay particular attention to intimate partner violence-related health consequences in designing health interventions for abused women.


Bone densitometry: relevance to health care.
Since low bone density is a risk for fracture, the relevance of bone densitometry as a basis for health care assessment needs to be elucidated. Most patients with fractures are in the lower two quartiles of bone density. Bone densitometry can be used to provide a quantitative estimate of fracture risk and a measurable response to aging, disease or medical treatment in the individual. Some difficulties concerning the efficacy of screening the whole population are discussed, for instance in terms of the success of treatment. Screening to prevent fractures should be advocated in women considering HRT. Research into defining bone quality is needed, as are further studies on the pathogensis of low bone density and on the contributions of low peak bone density and rates of loss to bone density in adults.


Exposure to extremely low-frequency magnetic field affects biofilm formation by cystic fibrosis pathogens.
To evaluate the in vitro effects of extremely low-frequency magnetic field (ELF-MF) on growth and biofilm formation by Staphylococcus aureus, Pseudomonas aeruginosa, Burkholderia cepacia and Stenotrophomonas maltophilia strains from cystic fibrosis patients. The motion of selected ions (Fe, Ca, Cu, Zn, Mg, K, Na) was stimulated by the ion resonance effect, then influence on growth and biofilm formation/viability was assessed by spectrophotometry or viability count. Generally, exposure to ELF-MF significantly increased bacterial growth and affected both biofilm formation and viability, although with differences with regard to ions and species considered. Exposure to ELF-MF represents a possible new approach for treatment of biofilm-associated cystic fibrosis lung infections.


Synthesis and pharmacological examination of 1-(3-methoxy-4-methylphenyl)-2-aminopropane and 5-methoxy-6-methyl-2-aminoindan: similarities to 3,4-(methylenedioxy)methamphetamine (MDMA).
The racemate and the enantiomers of 1-(3-methoxy-4-methyphenyl)-2- aminopropane (6) and racemic 5-methoxy-6-methyl-2-aminoindan (11) were tested for stimulus generalization in the two-lever drug-discrimination paradigm. Both 6 and 11 were found to substitute with high potency in 3,4-(methylenedioxy)methamphetamine (1) and (S)-1-(1,3-benzodioxol-5-yl)-2-(methylamino)butane (2) trained rats. In the latter assay, both enantiomers of 6 had identical potencies, but their dose-response curves were not parallel. Racemic 6, but not 11, partially substituted for LSD. Racemic 6 and 11 did not substitute in (S)-amphetamine-trained rats. All of the test compounds were potent inhibitors of [3H]-5-HT uptake into synaptosomes in vitro, with the S enantiomer of 6 being most active. Rat brain monoamine levels were unaltered 1 week following a single high dose (10 or 20 mg/kg, sc) of 6 or 11, or two weeks following a subacute dosing regimen (20 mg/kg, sc, twice a day for 4 days). In addition, radioligand-binding parameters in rat brain homogenate with the 5-HT uptake inhibitor [3H]paroxetine were unchanged after subacute dosing with either racemic 6 or 11. The results indicate that compounds 6 and 11 have animal behavioral pharmacology similar to the methylenedioxy compounds 1 and 2, but that they do not induce the serotonin neurotoxicity that has been observed for the latter two drugs.