Towards the continuous production of high crystallinity graphene via electrochemical exfoliation with molecular in situ encapsulation.
Large-scale production of uniform and high-quality graphene is required for practical applications of graphene. The electrochemical exfoliation method is considered as a promising approach for the practical production of graphene. However, the relatively low production rate of graphene currently hinders its usage. Here, we demonstrate, for the first time, a rapid and high-yield approach to exfoliate graphite into graphene sheets via an electrochemical method with small molecular additives; where in this approach, the use of melamine additives is able to efficiently exfoliate graphite into high-quality graphene sheets. The exfoliation yield can be increased up to 25 wt% with melamine additives compared to electrochemical exfoliation without such additives in the electrolyte. The proposed mechanism for this improvement in the yield is the melamine-induced hydrophilic force from the basal plane; this force facilitates exfoliation and provides in situ protection of the graphene flake surface against further oxidation, leading to high-yield production of graphene of larger crystallite size. The residual melamine can be easily washed away by water after collection of the graphene. The exfoliation with molecular additives exhibits higher uniformity (over 80% is graphene of less than 3 layers), lower oxidation density (C/O ratio of 26.17), and low defect level (D/G < 0.45), which are characteristics superior to those of reduced graphene oxide (rGO) or of a previously reported approach of electrochemical exfoliated graphene (EC-graphene). The continuous films obtained by the purified graphene suspension exhibit a sheet resistance of 13.5 kΩ □(-1) at ∼95% transmittance. A graphene-based nanocomposite with polyvinyl butyral (PVB) exhibits an electrical conductivity of 3.3 × 10(-3) S m(-1) for the graphene loading fraction of 0.46 vol%. Moreover, the melamine functionalized graphene sheets are readily dispersed in the aqueous solution during the exfoliation process, allowing for the production of graphene in a continuous process. The continuous process for producing graphene was demonstrated, with a yield rate of 1.5 g h(-1). The proposed method can produce high-crystallinity graphene in a fast and high-yield manner, which paves the path towards mass production of high-quality graphene for a variety of applications.


West Nile Virus in Brazil.
Background: West Nile virus (WNV) was first sequenced in Brazil in 2019, when it was isolated from a horse in the Espírito Santo state. Despite multiple studies reporting serological evidence suggestive of past circulation since 2004, WNV remains a low priority for surveillance and public health, such that much is still unknown about its genomic diversity, evolution, and transmission in the country. Methods: A combination of diagnostic assays, nanopore sequencing, phylogenetic inference, and epidemiological modeling are here used to provide a holistic overview of what is known about WNV in Brazil. Results: We report new genetic evidence of WNV circulation in southern (Minas Gerais, São Paulo) and northeastern (Piauí) states isolated from equine red blood cells. A novel, climate-informed theoretical perspective of the potential transmission of WNV across the country highlights the state of Piauí as particularly relevant for WNV epidemiology in Brazil, although it does not reject possible circulation in other states. Conclusion: Our output demonstrates the scarceness of existing data, and that although there is sufficient evidence for the circulation and persistence of the virus, much is still unknown on its local evolution, epidemiology, and activity. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics with spill-over potential to humans.


Studies of cultured lymphocytes of the owl monkey (Aotus trivirgatus) infected with Herpesvirus saimiri.
The lymphocytes of five owl monkeys (Aotus trivirgatus) infected with Herpesvirus saimiri and three control monkeys were studied. Lymphocytes were separated on Ficoll-Hypaque gradients, incubated in suspension cultures, and prepared for electron microscopic and immunofluorescent study at 24, 48, and 72 hours after the beginning of culture. Buffy coats of whole blood obtained immediately after bleeding were also prepared for study. At the time of the study, four of the five infected monkeys had died with malignant lymphoma and lymphocytic leukemia. Herpesvirus saimiri virions were demonstrated by electron microscopy and H saimiri antigens by immunofluorescence in 1-20% of the lymphocytes from infected monkey in two of five cultures at 24 hours after culture, four of five at 48 hours after culture, and all of five at 72 hours after culture. There was good agreement between the electron microscopic and the immunofluorescent data. None of the control monkey cultures and none of the buffy coat preparations contained H saimiri virions or antigens. By electron microscopy, the great majority of the virus particles were nucleocapsids within the nuclei of lymphocytes. Enveloped virions were seldom observed. There was some evidence to suggest that the higher the percentage of lymphocyte containing H saimiri, the poorer the prognosis for the monkey. Herpesvirus saimiri was isolated from all five infected monkeys by co-cultivation of lymphocytes with Vero cells. Control lymphocyte co-cultivations were negative.


Lung Function and Health Status in Individuals with Severe Alpha-1-Antitrypsin Deficiency at the Age of 42.
Severe hereditary alpha-1-antitrypsin deficiency (AATD) is a known risk factor for the early development of pulmonary emphysema and COPD, especially in smokers. By the Swedish national screening programme carried out from 1972 to 1974, a cohort of individuals with severe (PiZZ) AATD was identified and has been followed up regularly. The aim of this study was to investigate health status, quality of life and lung function in this cohort at the age of 42 years compared with an age-matched control group randomly selected from the population registry. All study participants answered a questionnaire on smoking habits, symptoms, occupation, exposure to airway irritants and quality of life using Saint George's Respiratory Questionnaire (SGRQ). They underwent complete pulmonary function tests (PFT) and forced oscillation technique (FOT) for the measurement of airway resistance and reactance. Blood samples were taken for allergies and IgG-subclasses as an indicator of increased risk of airway infections. The residual volume (RV), total lung capacity (TLC) and RV/TLC ratio were significantly higher in the PiZZ ever-smokers compared to the PiMM ever-smokers and PiZZ never-smokers (p < 0.05). The resistance in the upper, small and total airways was significantly lower in PiZZ subjects compared to PiMM subjects (p < 0.05). A greater proportion of PiZZ never-smokers had an FEV1/VC ratio <0.7 than PiMM never-smokers (p = 0.043). PiZZ subjects with occupational exposure to airway irritants showed a significantly lower FEV1, VC and higher RV/TLC ratio than PiMM individuals with exposure (p < 0.05). At the age of 42, ever-smoking PiZZ individuals have signs of COPD, and also PiZZ never-smokers have early, physiological signs of emphysema.


Inhalation Injury Does Not Influence the Amount of Blood Transfused to Major Burn Patients: A Secondary Analysis from the Transfusion Requirement in Burn Care Evaluation Study.
Patients with major burn injuries typically require numerous blood transfusions. It is not known if an inhalation injury (INHI) directly influences the need for blood transfusion. The purpose of this study was to determine whether INHI increases the amount of blood transfused to major burn patients. A secondary analysis from the Transfusion Requirement in Burn Care Evaluation (TRIBE) study was conducted. Patients with INHI were compared with patients without INHI. The number of red blood cell (RBC) transfusions per day (RBC per day) between INHI and No INHI was analyzed with a multivariable regression. Patients with INHI (n = 78) had significantly larger burns (P = .0004), larger full-thickness burns (P = .0007), greater admission APACHE score (P < .0001), higher admission multiple organ dysfunction scores (P < .0001), and were transfused more RBC per day (P = .009) than No INHI patients (n = 267). In the multivariable regression analysis, RBC per day was significantly associated with the %TBSA burn (P < .0001), age of the patient (P = .004), the need for more than 1 day of mechanical ventilation (P < .0001), the occurrence of at least one blood stream infection (BSI; P = .044), and being assigned to the liberal transfusion arm of TRIBE (P < .001) but not the presence of INHI (P = .056). The null hypothesis that INHI exerts no influence on the amount of blood transfused could not be rejected. Larger burn size, advanced patient age, mechanical ventilation, and BSIs are important determinants of the blood transfusion rate in major burn patients.


Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins.
It is now established that CD1 molecules present lipid antigens to T cells, although it is not clear how the exchange of lipids between membrane compartments and the CD1 binding groove is assisted. We report that mice deficient in prosaposin, the precursor to a family of endosomal lipid transfer proteins (LTP), exhibit specific defects in CD1d-mediated antigen presentation and lack Valpha14 NKT cells. In vitro, saposins extracted monomeric lipids from membranes and from CD1, thereby promoting the loading as well as the editing of lipids on CD1. Transient complexes between CD1, lipid, and LTP suggested a "tug-of-war" model in which lipid exchange between CD1 and LTP is on the basis of their respective affinities for lipids. LTPs constitute a previously unknown link between lipid metabolism and immunity and are likely to exert a profound influence on the repertoire of self, tumor, and microbial lipid antigens.


Clinical significance of SARS-CoV-2-specific IgG detection with a rapid antibody kit for COVID-19 patients.
The longitudinal observation of the detection of antibody responses to SARS-CoV-2 using antibody kits during the clinical course of COVID-19 is not yet fully investigated. To understand the significance of the detection of anti-SARS-CoV-2 antibodies, particularly IgG, using a rapid antibody kit, during the clinical course of COVID-19 patients with different severities. Sixty-three serum samples from 18 patients (5 asymptomatic and 13 symptomatic patients) were retrospectively examined using a commercial SARS-CoV-2 IgM/IgG antibody kit. PCR positivity of patient samples was also examined as a marker of current SARS-CoV-2 infection. IgG antibodies were detected in all cases in this study. The IgG detection rates reached 100.0% in samples collected on day 13 or later. IgG seropositivity after an initial negative status was observed in 13 patients (3/5 asymptomatic and 10/13 symptomatic cases). Interestingly, the persistence of both PCR and IgG positivity was detected in seven cases, of which three were asymptomatic. The longest overlap duration of the PCR and IgG positivity was 17 days in asymptomatic status. SARS-CoV-2-specific IgG production can be detected in all infected individuals, using a rapid antibody kit, irrespective of clinical status. However, these findings suggest that, in some infected individuals, particularly those with asymptomatic status, the presence of virus-specific IgG antibodies does not imply prompt viral clearance.


Follicle-stimulating hormone activation of glycogen phosphorylase in the Sertoli cell-enriched rat testis.
The potential role of glycogen phosphorylase in providing energy for the Sertoli cell-enriched testis has been investigated. This enzyme is detectable in testes from rats 6-54 days of age. Glycogen phosphorylase in isolated Sertoli cell-enriched testes is specifically stimulated by FSH. Maximal activation (2-fold) is obtained within 10 min after adding 0.5 micrograms FSH/ml to isolated immature testes (16 days old). There is only a 1.1-fold activation by FSH in testes from mature (34 days old) animals. The sensitivity to the gonadotropin can be restored by adding 1-methyl-3-isobutylxanthine, a phosphodiesterase inhibitor, with the FSH. Phosphorylase can be activated by effectors that mimic the actions of the two proposed mediators of FSH action, cAMP and Ca+2. Phosphorylase from testis of either age is maximally activated by an analog of cAMP, 8-bromo-cAMP. While phosphorylase is rapidly activated 1.4-fold by incubating isolated testis for 2 min with A23187, a Ca+2 ionophore, the age, time, and dose dependence of FSH activation are consistent with conversion mediated by cAMP. Phosphorylase was localized in cultured Sertoli cells by indirect immunofluorescence microscopy. Affinity-purified antiphosphorylase decorated cytoskeletal structures that resemble stress fibers, suggesting that phosphorylase may function in Sertoli cells to provide energy for cytoskeletal motility.


Nuclear Magnetic Resonance-Based Metabolomics of Human Filtered Serum: A Great White Hope in Appraisal of Chronic Stable Angina and Myocardial Infarction.
Biochemical detection of chronic stable angina (CSA) and myocardial infarction (MI) are challenging. To address the shortcomings of the conventional biochemical approach for detection of MI, we applied serum lacking proteins and lipoprotein-based metabolomics in an approach using proton nuclear magnetic resonance (1H NMR) spectroscopy for screening of coronary artery disease (CAD) and especially MI. Our aim was to discover differential biomarkers among subjects with normal coronary (NC), CSA, and MI. The study comprised serum samples from nondiabetic angiographically proven CAD [CSA (n = 88), MI (n = 90)] and NC (n = 55). 1H NMR spectroscopy was used to acquire metabolomics data. Clinical variables such as troponin I (TI), lactate dehydrogenase (LD), creatine kinase (CK, CK-MB, CK-MM), serum creatinine, and lipid profiles were also measured in all subjects. Metabolomic data and clinical measures were appraised separately using a chemometric approach and ROC analysis. The screening outcomes revealed that the pattern of methylguanidine, lactate, creatinine, threonine, aspartate, and trimethylamine (TMA), and TI, LD, CK, and serum creatinine were changed in CAD compared to NC. Statistical analysis demonstrated high precision (93.6% by NMR and 67.4% by clinical measures) to distinguish CAD from NC. Further analysis indicated that methylguanidine, arginine, and threonine, and TI, LD, and serum creatinine were significantly changed in CSA compared to MI. Statistical analysis demonstrated high accuracy (88.2% by NMR and 92.1% by clinical measures) to discriminate CSA from MI. In contrast to other laboratory methods, 1H NMR-based metabolomics of filtered sera appears to be a robust, rapid, and minimally invasive approach to probe CSA and MI.


A cross-national epidemiological study of mania.
An epidemiological study of the first admission rate for mania was carried out in London and Aarhus. The case registers in these two centres were used to conduct a retrospective study of case notes covering several years, and a screening procedure was used for the prospective collection of new cases over the course of one year. The annual incidence of mania was found to be virtually identical in both centres. The retrospective study gave a figure of 2-6 per 100,000 population in both Aarhus and London. But the London sample was found to contain 45 per cent of immigrants in contrast to the Aarhus sample in which only a negligible proportion were born outside Denmark. Male West Indians, in particular, were over-represented in the London sample.


Realising the European network of biodosimetry: RENEB-status quo.
Creating a sustainable network in biological and retrospective dosimetry that involves a large number of experienced laboratories throughout the European Union (EU) will significantly improve the accident and emergency response capabilities in case of a large-scale radiological emergency. A well-organised cooperative action involving EU laboratories will offer the best chance for fast and trustworthy dose assessments that are urgently needed in an emergency situation. To this end, the EC supports the establishment of a European network in biological dosimetry (RENEB). The RENEB project started in January 2012 involving cooperation of 23 organisations from 16 European countries. The purpose of RENEB is to increase the biodosimetry capacities in case of large-scale radiological emergency scenarios. The progress of the project since its inception is presented, comprising the consolidation process of the network with its operational platform, intercomparison exercises, training activities, proceedings in quality assurance and horizon scanning for new methods and partners. Additionally, the benefit of the network for the radiation research community as a whole is addressed.


[Ultrasonography of the rotator cuff of the shoulder].
Clinical examination for rotator cuff (RC) tear is rarely conclusive. Arthrography has been considered the standard diagnostic procedure for detection of rotator cuff tears. Ultrasonography (US) is less time-consuming and less expensive than arthrography and is, in addition, noninvasive. During recent years, many reports concerning US evaluation of RC tears have been published, but with different results about the diagnostic value of the examination. Recently, some authors have pointed out the ability of US in visualizing degenerative changes in the RC and that it is difficult to differentiate between tears and degenerative changes. By review of the English literature, we conclude that the experienced examiner with proper equipment can confidently differentiate between normal and pathological RC an that in quite a number of cases it is possible to differentiate tears from degenerative changes. In case of doubt, the examination should be supplemented by shoulder arthrography. In the hands of an experienced examiner with proper equipment US seems to be suitable as the initial imaging modality for evaluation of RC.


Bacterial endotoxin (lipopolysaccharide) binds to the surface of gold nanoparticles, interferes with biocorona formation and induces human monocyte inflammatory activation.
Nanoparticles (NPs) are easily contaminated by bacterial endotoxin (lipopolysaccharide [LPS]). The presence of LPS can be responsible for many immune/inflammatory effects attributed to NPs. In this study, we examined the effects of LPS adsorption on the NP surface on the formation of a biocorona in biological fluids and on the subsequent inflammation-inducing activity of NPs. Different gold (Au) NPs with sizes ranging from 10 to 80 nm and with different surface functionalization (sodium citrate, lipoic acid, and branched polyethyleneimine (BPEI), or polyethylene glycol (PEG)) were exposed to E. coli LPS under different conditions. The binding capacity of LPS to the surface of AuNPs was dose- and time-dependent. LPS attached to sodium citrate and lipoic acid coatings, but did not adhere to BPEI- or PEG-coated NPs. By computational simulation, the binding of LPS to AuNPs seems to follow the Langmuir absorption isotherm. The presence of LPS on AuNP surface interfered and caused a decrease in the formation of the expected biomolecular corona upon incubation in human plasma. LPS-coated AuNPs, but not the LPS-free NPs, induced significant inflammatory responses in vitro. Notably, while free LPS did also induce an anti-inflammatory response, LPS bound to NPs appeared unable to do so. In conclusion, the unintentional adsorption of LPS onto the NP surface can affect the biocorona formation and the inflammatory properties of NPs. Thus, for an accurate interpretation of NP interactions with cells, it is extremely important to be able to distinguish the intrinsic NP biological effects from those caused by biologically active contaminants such as endotoxin.


Role of dentifrices on abrasion of enamel exposed to an acidic drink.
To evaluate in vitro the abrasive potential of different dentifrices on enamel previously exposed to an acidic soft drink. 150 bovine enamel slabs measuring 6 x 3 x 2 mm were grounded flat and polished. Surface roughness was measured to obtain Ra (microm) baseline values using a profilometer. The slabs' outer surface was covered with a tape except for a 3 x 4 mm window. According to a randomized complete block design, specimens were exposed to an acidic drink or distilled water (control) for 5 minutes, and then to artificial saliva for 1 minute. Next, the experimental units were submitted to 5,000 brushing strokes using one of four dentifrices - regular (RE), baking soda (BS), tartar control (TC) or whitening (WT) - or distilled water as control (CO) (n=15). At the end of five repetitions of this erosive/abrasive cycle, the tape was removed and final readings of surface roughness were carried out. Roughness gain consisted of the subtraction of the baseline values from the post-treatment measurements. Also, the enamel wear due to erosive/abrasive challenges was profilometrically determined. ANOVA did not show significant interaction between enamel condition (eroded and sound) and dentifrice (P> 0.05) for both roughness gain and wear. No significant effect was found for enamel condition and dentifrice in the wear analysis. The exposure of enamel to the acidic drink provided higher roughness gain than did distilled water. Tukey's test evidenced that TC yielded significantly greater increase in surface roughness than did both CO and WT, whereas BS and RE induced an intermediate roughness gain.


Identifying New/Emerging Psychoactive Substances at the Time of COVID-19; A Web-Based Approach.
COVID-19-related disruptions of people and goods' circulation can affect drug markets, especially for new psychoactive substances (NPSs). Drug shortages could cause a change in available NPS, with the introduction of new, unknown, substances. The aims of the current research were to use a web crawler, NPSfinder®, to identify and categorize emerging NPS discussed on a range of drug enthusiasts/psychonauts' websites/fora at the time of the pandemic; social media for these identified NPS were screened as well. The NPSfinder® was used here to automatically scan 24/7 a list of psychonaut websites and NPS online resources. The NPSs identified in the time frame between January and August 2020 were searched in both the European Monitoring Center for Drugs and Drug Addictions (EMCDDA)/United Nations Office on Drugs and Crime (UNODC) databases and on social media (Facebook, Twitter, Instagram, Pinterest, and YouTube) as well, with a content qualitative analysis having been carried out on reddit.com. Of a total of 229 NPSs being discussed at the time of the pandemic, some 18 NPSs were identified for the first time by the NPSfinder®. These included six cathinones, six opioids, two synthetic cannabinoid receptor agonists (SCRAs), two phenylcyclohexylpiperidine (PCP)-like molecules, and two psychedelics. Of these NPSs, 10 were found to be previously unreported to either the UNODC or the EMCDDA. Of these 18 NPSs, opioids and cathinones were the most discussed on social media/reddit, with the highest number of threads associated. Current findings may support the use of both automated web crawlers and social listening approaches to identify emerging NPSs; the pandemic-related imposed restrictions may somehow influence the demand for specific NPS classes.


[Hypovolemic shock during surgery caused by a rectus sheath hematoma].
Prophylactic treatment with low molecular weight heparins (LMWH) is currently widely used to prevent thromboembolic events. However, such treatment is not free of risk. Among the possible complications described is rectus sheath hematoma. We report the case of a patient undergoing surgery for a hypophysial adenoma approached by the transsphenoidal route. He received LMWH prophylaxis for thromboembolism and showed a tendency to hypotension during surgery. The patient's condition deteriorated to hypovolemic shock accompanied by episodes of atrial fibrillation with rapid ventricular response. With the transfusion of medications, blood products and plasma volume expanders, the patient was stabilized and surgery was completed. A computed tomography scan then revealed a hematoma occupying the greater part of the left anterior rectus muscle. With conservative wait-and-see treatment the abdominal symptoms disappeared and the hematoma gradually receded until fully resolved. Spontaneous rectus sheath hematoma is a rare condition. Presentation is quite nonspecific and computed tomography is needed for reaching a firm diagnosis. When a hematoma is large, the initial clinical picture may include hypovolemic shock, which may develop during surgery if the hematoma is not diagnosed early. Intraoperative management will be much more difficult than it would have been if diagnosis and treatment had taken place before the operation.


A Literature Survey with the Focus on Magnetically Coupled Wireless Power Transfer Systems Developed for Engineering and Biomedical Applications.
Wireless power transfer (WPT) is the transmission of electrical energy to other external/internal devices without the need for wire connection. Such a system is useful to power electrical devices as a promising technology for various emerging applications. The implementation of devices integrated with WPT alters the existing technologies and enhance the theoretical concept for future works. Over the last decade, various studies have been conducted on the applications of magnetically coupled WPT systems, where a general overview over such devices would be beneficial. Hence, this paper presents a comprehensive review over various WPT systems developed for commercially existing applications. The importance of WPT systems is first reported from the engineering point of view, followed by their uses in biomedical devices.


Gastroduodenal Disorders.
Symptoms that can be attributed to the gastroduodenal region represent one of the main subgroups among functional gastrointestinal disorders. A slightly modified classification into the following 4 categories is proposed: (1) functional dyspepsia, characterized by 1 or more of the following: postprandial fullness, early satiation, epigastric pain, and epigastric burning, which are unexplained after a routine clinical evaluation; and includes 2 subcategories: postprandial distress syndrome that is characterized by meal-induced dyspeptic symptoms and epigastric pain syndrome that does not occur exclusively postprandially; the 2 subgroups can overlap; (2) belching disorders, defined as audible escapes of air from the esophagus or the stomach, are classified into 2 subcategories, depending on the origin of the refluxed gas as detected by intraluminal impedance measurement belching: gastric and supragastric belch; (3) nausea and vomiting disorders, which include 3 subcategories: chronic nausea and vomiting syndrome; cyclic vomiting syndrome; and cannabinoid hyperemesis syndrome; and (4) rumination syndrome.


Oscillating field stimulation promotes recovery after spinal cord injury in rats: Assessment using behavioral, electrophysiological and histological evaluations.
We explored whether oscillating field stimulation (OFS) could efficiently promote motor function recovery in rat model of spinal cord injury. SD rats with spinal cord injury induced by Allen method was divided into two groups, experimental group rats received active stimulator units and control group rats received sham (inoperative) stimulator units. The electric field intensity was 600μV/mm, and the polarity alternated every 15 min. The results showed that the experimental group rats had significantly better locomotor function recovery (inclined-plane testing and modified Tarlov motor grading scale) 5 weeks after the injury (P<;0.05). OFS treatment significantly decreased motor evoked potential (MEP) latency differences and amplitude differences 4 w and 8 w post injury (P<;0.05, P<;0.01). Furthermore, the number of axons was quantified by immunofluorescence staining of nerve fiber (NF), increased axon numbers were observed at 4 w and 8 w in experimental group (P<;0.05). These findings suggest OFS can promote motor function recovery in SCI rats, and this effect may be related to the improving axon regeneration in spinal cord.


Carotid intima-media thickness and ınsulin resistance changes in patients who underwent sleeve gastrectomy: A prospective study.
Our aim was to examine changes in insulin resistance, Carotid Intima-Media Thickness (CIMT), in morbid obese patients without any known associated chronic diseases who underwent sleeve gastrectomy. The subjects of this study were patients with minimum BMI of 40, who did not have any known chronic diseases. Sleeve gastrectomy was performed and perioperative control endoscopy was performed. The following values were measured before the operation and after follow-up period after the operation: Fasting blood glucose and insulin, lipid profile, BMI, liver function tests, right and left CIMT. Furthermore, the patients' insulin resistance was calculated by HOMA method, and the values of 2.7. Six-teen patients (14 women and 2 men, average age: 39.12 ± 10.63 years), who did not have a known additional chronic disease, took part in the study. There was a significant difference between baseline and follow-up values of the patients, and the mean weight loss was 20.5%. Given the statistical evaluation of baseline and follow-up values, there was a significant difference in BMI, insulin resistance rates and right and left CIMT values. Bariatric surgery may provide some additional advantages for the management of cardiovascular risks in obese patients. However, it should be kept in mind that the most important components of fight against obesity are appropriate diet and exercise programs.


Amantadine-resistant influenza A in nursing homes. Identification of a resistant virus prior to drug use.
Amantadine hydrochloride and rimantadine hydrochloride have been used for treatment and prevention of influenza A infection in nursing home residents. Outbreaks of influenza A (H3N2) virus infection occurred in three nursing homes in Yakima County, Washington, during January 1992. Amantadine was used for case treatment and prophylaxis in all three nursing homes. Ten influenza A (H3N2) viruses isolated during the outbreaks were examined for resistance to amantadine and rimantadine by means of an enzyme immunoassay and by sequencing of the viral nucleic acid that encodes the transmembrane domain of the M2 protein. Five of the outbreak strains were resistant and had the same mutation (position 31, serine to asparagine) in the M2 protein. The resistant viruses included one that had been recovered prior to any use of amantadine and another that was recovered within 48 hours of the first drug administration. To our knowledge, this is the first report of influenza A virus with RNA sequence-documented resistance to amantadine and rimantadine without exposure to either drug, and the shortest reported period between institution of amantadine therapy and isolation of a resistant influenza A virus strain. These results suggest that surveillance for amantadine- and rimantadine-resistant influenza A is needed, because use of these drugs will probably increase.


Anterolateral Knee Extra-articular Stabilizers: A Robotic Sectioning Study of the Anterolateral Ligament and Distal Iliotibial Band Kaplan Fibers.
The individual kinematic roles of the anterolateral ligament (ALL) and the distal iliotibial band Kaplan fibers in the setting of anterior cruciate ligament (ACL) deficiency require further clarification. This will improve understanding of their potential contribution to residual anterolateral rotational laxity after ACL reconstruction and may influence selection of an anterolateral extra-articular reconstruction technique, which is currently a matter of debate. Hypothesis/Purpose: To compare the role of the ALL and the Kaplan fibers in stabilizing the knee against tibial internal rotation, anterior tibial translation, and the pivot shift in ACL-deficient knees. We hypothesized that the Kaplan fibers would provide greater tibial internal rotation restraint than the ALL in ACL-deficient knees and that both structures would provide restraint against internal rotation during a simulated pivot-shift test. Controlled laboratory study. Ten paired fresh-frozen cadaveric knees (n = 20) were used to investigate the effect of sectioning the ALL and the Kaplan fibers in ACL-deficient knees with a 6 degrees of freedom robotic testing system. After ACL sectioning, sectioning was randomly performed for the ALL and the Kaplan fibers. An established robotic testing protocol was utilized to assess knee kinematics when the specimens were subjected to a 5-N·m internal rotation torque (0°-90° at 15° increments), a simulated pivot shift with 10-N·m valgus and 5-N·m internal rotation torque (15° and 30°), and an 88-N anterior tibial load (30° and 90°). Sectioning of the ACL led to significantly increased tibial internal rotation (from 0° to 90°) and anterior tibial translation (30° and 90°) as compared with the intact state. Significantly increased internal rotation occurred with further sectioning of the ALL (15°-90°) and Kaplan fibers (15°, 60°-90°). At higher flexion angles (60°-90°), sectioning the Kaplan fibers led to significantly greater internal rotation when compared with ALL sectioning. On simulated pivot-shift testing, ALL sectioning led to significantly increased internal rotation and anterior translation at 15° and 30°; sectioning of the Kaplan fibers led to significantly increased tibial internal rotation at 15° and 30° and anterior translation at 15°. No significant difference was found when anterior tibial translation was compared between the ACL/ALL- and ACL/Kaplan fiber-deficient states on simulated pivot-shift testing or isolated anterior tibial load. The ALL and Kaplan fibers restrain internal rotation in the ACL-deficient knee. Sectioning the Kaplan fibers led to greater tibial internal rotation at higher flexion angles (60°-90°) as compared with ALL sectioning. Additionally, the ALL and Kaplan fibers contribute to restraint of the pivot shift and anterior tibial translation in the ACL-deficient knee. This study reports that the ALL and distal iliotibial band Kaplan fibers restrain anterior tibial translation, internal rotation, and pivot shift in the ACL-deficient knee. Furthermore, sectioning the Kaplan fibers led to significantly greater tibial internal rotation when compared with ALL sectioning at high flexion angles. These results demonstrate increased rotational knee laxity with combined ACL and anterolateral extra-articular knee injuries and may allow surgeons to optimize the care of patients with this injury pattern.


Co-Expression of Putative Cancer Stem Cell Markers CD44 and CD133 in Prostate Carcinomas.
Cancer stem cells (CSCs) are the main players of prostate tumorigenesis thus; characterization of CSCs can pave the way for understanding the early detection, drug resistance, metastasis and relapse. The current study was conducted to evaluate the expression level and clinical significance of the potential CSC markers CD44 and CD133 in a series of prostate tissues. One hundred and forty eight prostate tissues composed of prostate cancer (PCa), high-grade prostatic intraepithelial neoplasia (HGPIN), and benign prostate hyperplasia (BPH) were immunostained for the putative CSC markers CD44 and CD133. Subsequently, the correlation between the expression of these markers and the clinicopathological variables was examined. A higher level of CD44 expression was observed in 42% of PCa, 57% of HGPIN, and 42% BPH tissues. In the case of CD133 expression PCa, HGPIN, and BPH samples demonstrated high immunoreactivity in 46%, 43%, and 42% of cells, respectively. Statistical analysis showed an inverse significant correlation between CD44 expression with Gleason score of PCa (P = 0.02), while no significant correlation was observed between CD133 expression and clinicopathological parameters. A significant reciprocal correlation was observed between the expression of two putative CSC markers CD44 and CD133 in PCa specimens while not indicating clinical significance. Further clinical investigation is required to consider these markers as targets of new therapeutic strategies for PCa.


Bavachin suppresses human placental choriocarcinoma cells by targeting electron transport chain complexes and mitochondrial dysfunction.
Phytoestrogens are naturally derived estrogen-like therapeutic compounds that have long been studied for their role as anti-cancer agents and supplements during chemotherapy. Bavachin is a therapeutic phytoestrogen used to treat cancer, inflammation, and diabetes mellitus. Though the therapeutic effects of bavachin on various diseases have been explored, its anti-cancer effects and related mechanisms in human placental choriocarcinoma remain unknown. This is the first study to identify the anti-cancer potential of bavachin on human placental choriocarcinoma cell lines JEG3 and JAR. Placental mitochondria support the elevated energy production required for placental development, through oxidative phosphorylation (OXPHOS). Based on this concept, we hypothesized that mitochondrial targeting by bavachin may contribute to anti-cancer activities in high-OXPHOS subtypes of cancer such as placental choriocarcinoma. Apoptosis and caspase activities were increased by bavachin in placental choriocarcinoma cells. Bavachin altered metabolic phenotypes by regulating electron transport chain complex and OXPHOS to suppress choriocarcinoma cell proliferation. It also led to calcium disruption and endoplasmic reticulum stress accompanied by mitochondrial membrane potential depolarization. It showed synergistic anti-cancer effects with paclitaxel on placental choriocarcinoma cells. Taken together, we suggest that bavachin has therapeutic potential against placental choriocarcinoma and may be used to counter paclitaxel-induced toxicity.


General synthesis and aggregation behaviour of a series of single-chain 1,omega-bis(phosphocholines).
The synthesis and physicochemical characterisation of a series of polymethylene-1,omega-bis(phosphocholines) with even-numbered chain lengths between 22 and 32 carbon atoms is described. Two new synthetic strategies for the preparation of long-chain 1,omega-diols as hydrocarbon building blocks are presented. The temperature-dependent self-assembly of the single-chain bolaamphiphiles was investigated by cryo transmission electron microscopy (cryo-TEM), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FTIR).


LAMP1/2 as potential diagnostic and prognostic marker for brain lower grade glioma: A review.
Brain lower grade glioma (LGG) is a common type of glioma. The current treatment methods still have some limitations, and some LGG patients will inevitably continue to deteriorate after treatment. We found the value of lysosomal associated membrane proteins (LAMPs) in the diagnosis and prognosis of LGG, which helps to enhance the clinical understanding of LGG treatment and improved prognosis. We assess the role of LAMPs in LGG, via the publicly available TCGA database. We explored expression levels of LAMPs in LGG using GEPIA2, cBioPortal, and UALCAN databases. The correction of LAMPs expression levels with immune cell infiltration in LGG patient was assessed by TIMER database. The Lysosomal associated membrane protein 1 (LAMP1)/2/4 mRNA levels were significantly higher in LGG patients than in healthy controls. Morover, high mRNA expressions of LAMP1/2/Lysosomal associated membrane protein 3 were associated with poor overall survival. We found that the immune invasion of LGG was almost significantly correlated with the expression of LAMPs. The results suggested that mRNA expressions of LAMP1 and LAMP4 were significantly associated with histological subtypes in LGG patients. lysosomal associated membrane protein 2 and LAMP5 were significantly down-regulated expression in samples of TP53 mutant in LGG compared to TP53 wild type. In addition, Lysosomal associated membrane protein 3 and LAMP4 were significantly overexpressed in samples of TP53 mutant in LGG Enrichment analysis applied to each component indicated that biological function was primarily associated with series of pathways in synapse and immunity.


The Effect of Psychosocial Factors and Patients' Perception of Tuberculosis Treatment Non-Adherence in Addis Ababa, Ethiopia.
Although there are several studies reported on factors affecting tuberculosis (TB) treatment non-adherence, there is information gap on psychosocial and patients' perceptions aspects. Therefore, this study was aimed to investigate the effect of psychosocial factors and patients' perceptions on TB treatment non-adherence in Ethiopia. A cross sectional study was conducted in Addis Ababa from May to December, 2014. Thirty one health facilities were randomly selected and 698 TB patients, who had been on treatment, were enrolled consecutively using patient registration number. Structured questionnaire was used to collect data on demographics, knowledge, psychological distress, alcohol use, tobacco smoking and six HBM domains. Treatment adherence level was the main outcome variable, and it measured using visual analog scale. Statistical Package for Social Sciences version 20 was used for data analysis. Non-adherence level within last one month prior to the study was 19.5%. After controlling for all potential confounding variables, Antiretroviral Therapy (ART) status (Adjusted Odds Ratio (AOR) = 1.79, 95% Confidence interval (CI) (1.09 -2.95)), alcohol use (AOR = 2.11, 95% CI (1.33-3.37)), economic status (AOR = 0.53, 95% CI (0.33-0.82)), perceived barriers (AOR = 1.21, 95% CI (1.10-1.47)) and psychological distress (AOR = 1.83, 95% CI (1.47-2.29)) were independently associated with TB treatment non-adherence. ART status, economic status, alcohol use, perceived barrier and psychological distress are the major areas that need to be targeted with health promotion intervention to enhance TB treatment adherence.


Mixotrophy of Platanthera minor, an orchid associated with ectomycorrhiza-forming Ceratobasidiaceae fungi.
• We investigated the fungal symbionts and carbon nutrition of a Japanese forest photosynthetic orchid, Platanthera minor, whose ecology suggests a mixotrophic syndrome, that is, a mycorrhizal association with ectomycorrhiza (ECM)-forming fungi and partial exploitation of fungal carbon. • We performed molecular identification of symbionts by PCR amplifications of the fungal ribosomal DNA on hyphal coils extracted from P. minor roots. We tested for a (13)C and (15)N enrichment characteristic of mixotrophic plants. We also tested the ectomycorrhizal abilities of orchid symbionts using a new protocol of direct inoculation of hyphal coils onto roots of Pinus densiflora seedlings. • In phylogenetic analyses, most isolated fungi were close to ECM-forming Ceratobasidiaceae clades previously detected from a few fully heterotrophic orchids or environmental ectomycorrhiza surveys. The direct inoculation of fungal coils of these fungi resulted in ectomycorrhiza formation on P. densiflora seedlings. Stable isotope analyses indicated mixotrophic nutrition of P. minor, with fungal carbon contributing from 50% to 65%. • This is the first evidence of photosynthetic orchids associated with ectomycorrhizal Ceratobasidiaceae taxa, confirming the evolution of mixotrophy in the Orchideae orchid tribe, and of ectomycorrhizal abilities in the Ceratobasidiaceae. Our new ectomycorrhiza formation technique may enhance the study of unculturable orchid mycorrhizal fungi.


Effects of acute psychological stress on placebo and nocebo responses in a clinically relevant model of visceroception.
There is evidence to suggest a role of emotions in placebo and nocebo effects, but whether acute psychological stress changes the magnitude of placebo or nocebo responses has not been tested. In a clinically relevant model of visceroception, we assessed effects of acute psychological stress on changes in urgency and pain in response to positive or negative treatment suggestions. In 120 healthy volunteers, perceived urge-to-defecate and pain in response to individually calibrated rectal distensions were measured with visual analogue scales during a BASELINE. Participants then underwent the Trier Social Stress Test (N = 60) or a simple cognitive task (control, N = 60) and were randomized to positive (placebo), negative (nocebo), or neutral treatment information regarding intravenous administration of saline. The series of distensions was repeated, and changes in visual analogue scales from BASELINE to TEST were compared between groups using analysis of covariance and planned post hoc tests. Treatment information emerged as a main factor (P <0.001), supporting treatment information effects for both urgency and pain. Effects for urgency were modulated by stress (interaction effect: P <0.05): Positive information reduced urgency (P = 0.025), while negative information increased urgency (P = 0.026) only in stressed groups. For pain, effects of stress emerged for nocebo responses, which were only evident in stressed groups (P = 0.009). This is the first experimental study supporting effects of acute psychological stress on placebo and nocebo responses in visceroception. Results call for mechanistic as well as patient studies to assess how psychological stress shapes patients' treatment expectations and thereby affects health outcomes.


Basic science for the clinician 37: Protecting against autoimmunity-tolerance: mechanisms of negative selection in the thymus.
As noted in previous articles in this series, tolerance, the ability of the immune system to differentiate self from nonself and leave the former alone, is a vital characteristic of a successful (and safe) immune system. With the detection of the molecule called aire (autoimmune regulator), the mechanism whereby autoreactive thymocytes encounter extrathymic proteins within the thymus and therefore are deleted, is now far better understood; aire was the subject of a prior article in this series. The absence of aire leads to autoimmune polyendocrinopathy, proof that aire is the center of an amazing "filtering" system. However, there are other mechanisms at work. Irregularities in expression of other proteins such as hypoxia-induced factor-1 (HIF-1) and CTLA4, have been implicated in autoimmune disease, the former in rheumatoid arthritis, the latter in autoimmune thyroid disease and lupus. Defects in intracellular factors involved in transcription of key apoptotic proteins have also been implicated in the escape of autoreactive thymocytes from the thymus, leading to autoimmune and lymphoproliferative syndromes as well. Changes in the proteins that oversee acetylation of histone lead to differential patterns of gene expression. At least 2 proteins involved in this process, HDAC and nur77, have been implicated in changes in survival of thymocytes. Yet again, there are multiple layers at work in the immune system; I have no idea how many more will be brought to light, which are phylogenetically most ancient or which will prove the most clinically relevant. For now, it is enough to bask in our new-found knowledge and know that the time from laboratory oddity, to animal model development, to therapeutic and/or diagnostic applications grows shorter each year since the molecular biologic revolution.


Inflammatory myofibroblastic tumor of renal pelvis presenting with prolonged fever and abdominal pain in children: report of 1 case and review of literature.
Inflammatory myofibroblastic tumor is a reactive proliferative lesion that occurs extremely rarely in the renal pelvis, especially during childhood. We report 1 such case that occurred in a child who presented with prolonged fever and abdominal pain. Ultrasonography and abdominal computed tomography revealed a left renal pelvic mass. She received conservative surgical treatment. The diagnosis was confirmed by pathological and immunohistochemical studies. Distinguishing inflammatory myofibroblastic tumor from other malignant renal pelvic tumors in children is essential to preventing unnecessary nephrectomy.


A lower ongoing pregnancy rate can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing IVF with GnRH antagonists.
Eliciting an endogenous LH surge by GnRH-agonist for the induction of final oocyte maturation may be more physiological compared with the administration of HCG. However, the efficacy of this intervention in patients treated for IVF with GnRH antagonists remains to be assessed. 106 patients were randomized to receive either 10 000 IU urinary HCG or 0.2 mg Triptorelin for triggering final oocyte maturation. Ovarian stimulation for IVF was performed with a fixed dose of 200 IU recombinant FSH and GnRH antagonist was started on stimulation day 6. Luteal phase was supported with micronized vaginal progesterone and oral estradiol. The study was monitored continuously for safety and stopping rules were established. No significant differences were present in the number of cumulus-oocyte complexes retrieved, in the proportion of metaphase II oocytes, in fertilization rates or in the number and quality of the embryos transferred between the two groups. However, a significantly lower probability of ongoing pregnancy in the GnRH agonist arm prompted discontinuation of the trial, according to the stopping rules established (odds ratio 0.11; 95% confidence interval 0.02-0.52). Lower probability of ongoing pregnancy can be expected when GnRH agonist is used for triggering final oocyte maturation instead of HCG in patients undergoing ovarian stimulation for IVF with GnRH antagonists.


Coronary risk factors: new perspectives.
The predisposing and precipitating causes of acute myocardial infarction (MI) are multiple; furthermore, different individuals may have different susceptibility, to a large extent genetically determined, to each of them. In spite of the complex aetiology of MI and of our limited knowledge of the causes responsible for the formation of persistent occlusive thrombosis in epicardial coronary arteries, the achievements obtained by controlling traditional risk factors are remarkable. Traditional risk factors, however, have a limited sensitivity among subjects with low/moderate levels of risk. Furthermore, in particular among subjects at medium risk, current preventive strategies are limited by the low incidence of preventable events which makes it necessary to also treat the vast majority of subjects who would not develop cardiac events even without any treatment. An improvement in preventive strategies for IHD can be achieved with the identification of: (1) new risk factors; (2) genotypes enhancing the susceptibility to specific risk factors; (3) phenotypes and genotypes making patients susceptible to specific preventive strategies; (4) genotypes protecting from risk factors. Although a word of caution is necessary as a number of recent studies on genetic markers, on new risk factors and on the interaction between genetic markers and environment have failed to withstand the rigour of population-based studies, the early findings available to date suggest that cost-effective preventive strategies based on individual susceptibility to specific predisposing and precipitating causes of MI may become a reality in the foreseeable future.


Implementation strategies for the first licensed dengue vaccine: A meeting report.
Dengue vaccination would enhance the control of dengue, one of the most frequent vector-borne viral diseases globally. CYD-TDV is the first dengue vaccine to be licensed, but global uptake has been hampered due to its use being limited to seropositive persons aged 9 years and above, and the need for a 3-dose schedule. The Partnership for Dengue Control (PDC) organized a meeting with key opinion leaders and stakeholders to deliberate on implementation strategies for the use of CYD-TDV. New data have emerged that support the shortening of the primary schedule from a 3 to 2 dose schedule, extending the age range below 9 to 6 years of age, and expanding the indication from endemic populations to also include travelers to endemic areas. Cost-effectiveness may improve with the modified 2-dose regimen and with multiple testing. Strategies to implement a dengue vaccination program have been developed, in particular school-based strategies. A range of delivery scenarios can then be considered, using various settings for each step of the intervention. However, several challenges remain, including communication about limiting the use of this vaccine to seropositive individuals only. Affordability will vary from country to country, as will government commitment and community acceptance. Well-tailored communication strategies that target key stakeholders are expected to make up a significant part of any future dengue vaccination program.


Current Strategies for the Production of Sustainable Biopolymer Composites.
Rapid global population growth has led to an exponential increase in the use of disposable materials with a short life span that accumulate in landfills. The use of non-biodegradable materials causes severe damage to the environment worldwide. Polymers derived from agricultural residues, wood, or other fiber crops are fully biodegradable, creating the potential to be part of a sustainable circular economy. Ideally, natural fibers, such as the extremely strong fibers from hemp, can be combined with matrix materials such as the core or hurd from hemp or kenaf to produce a completely renewable biomaterial. However, these materials cannot always meet all of the performance attributes required, necessitating the creation of blends of petroleum-based and renewable material-based composites. This article reviews composites made from natural and biodegradable polymers, as well as the challenges encountered in their production and use.


Thermoregulation is impaired in an environment without circadian time cues.
Squirrel monkeys synchronized to a 24-hour light-dark cycle show a prominent circadian rhythm in body temperature which is regulated against mild environmental cold exposures throughout the 24-hour day. However, cold exposures produce significant decreases in core body temperature when the circadian rhythms of the animal are free-running in the absence of environmental time cues. Effective thermoregulation appears to require the precise internal synchronization of the circadian timekeeping system.


Construct validity of medicare chemotherapy claims: the case of 5FU.
The elderly are under represented in clinical trials of cancer therapy and the elderly who are enrolled may be unrepresentative. To assess whether Medicare claims data might be used to understand the benefits and tolerance of chemotherapy in the general elderly population, the construct validity of Medicare 5FU claims for elderly colon cancer patients within the SEER-Medicare data set was determined. In this validation study of Medicare chemotherapy claims from the linked the SEER-Medicare data set, the patterns of 5FU chemotherapy claims were evaluated for an incident cohort of elderly colon cancer patients (n = 15,039) during the 13 months following their diagnosis. Patterns of Medicare National Claims History (NCH) 5FU claims were evaluated with respect to prespecified patient-level disease and demographic factors from the data set. Twenty-two percent of patients had at least one detectable 5FU claim during the observation period. Among those patients, the median dose of 5FU was 1000 mg, the median interval between 5FU claims was 7 days, and the median number of claims during this period was 24. Multivariate regression revealed expected associations between demographic and disease factors and the likelihood of having a Medicare NCH 5FU claim. With increasing cancer stage, patients' likelihood of having a 5FU claim increased. Younger patients, married patients, white patients, patients with low comorbidity, and patients living in urban and less impoverished regions were each more likely to have 5FU claims. Because their pattern is consistent with the standard of medical care and with previously described associations with disease and demographic factors, it was concluded that Medicare NCH claims for 5FU administration in the SEER-Medicare data set exhibit construct validity. Criterion validation studies with an external gold standard should be pursued to determine the sensitivity and specificity of chemotherapy codes in the Medicare NCH files.


Depression in the elderly.
Depression is a common psychiatric problem in old age. The magnitude of the problem will become greater as this segment of the population grows. Depression is often overlooked in the elderly, contributing to a greater risk of suicide in this group than in younger patients. Depression may be masked by hypochondriasis or somatization. Special problems in diagnosis include bipolar disorder, pseudodementia, pathological grief, and organic mood disorder as related to medications or physical illness. Pharmacokinetic changes with aging need to be kept in mind by physicians treating the elderly with antidepressant medications. Tricyclic antidepressants are the traditional first line pharmacologic agents. Tricyclics with a low side effect profile, such as desipramine or nortriptyline, are generally preferred. However, newer medications including serotonin reuptake inhibitors and bupropion are becoming more widely used. Other medications, including monoamine oxidase inhibitors, lithium, and stimulants, also have a place in the treatment of depression in old age. Electroconvulsive therapy is a useful treatment for patients with treatment-resistant or psychotic depression. Psychotherapy in the elderly has not been well studied, but is believed to be effective if patients are properly selected for therapy and appropriate modifications are made.


Cdc42 couples septin recruitment to the axial landmark assembly via Axl2 in budding yeast.
Cell polarization generally occurs along a single axis that is directed by a spatial cue. Cells of the budding yeast Saccharomyces cerevisiae undergo polarized growth and oriented cell division in a spatial pattern by selecting a specific bud site. Haploid a or α cells bud in the axial pattern in response to a transient landmark that includes Bud3, Bud4, Axl1 and Axl2. Septins, a family of filament-forming GTP-binding proteins, are also involved in axial budding and are recruited to an incipient bud site, but the mechanism of recruitment remains unclear. Here, we show that Axl2 interacts with Bud3 and the Cdc42 GTPase in its GTP-bound state. Axl2 also interacts with Cdc10, a septin subunit, promoting efficient recruitment of septins near the cell division site. Furthermore, a cdc42 mutant defective in the axial budding pattern at a semi-permissive temperature had a reduced interaction with Axl2 and compromised septin recruitment in the G1 phase. We thus propose that active Cdc42 brings Axl2 to the Bud3-Bud4 complex and that Axl2 then interacts with Cdc10, linking septin recruitment to the axial landmark.


Preoperative findings in non-gynecologic carcinomas metastasizing to the ovaries.
This study evaluated whether preoperative findings are useful prognostic indicators in patients with non-gynecologic carcinomas metastasizing to the ovaries. Fifty-three patients were analyzed. Primary sites of carcinoma were discovered after gynecologic surgery in 20 patients. In 10 patients, primary sites of carcinoma were discovered during gynecologic surgery. Thirty-one patients received surgery on the primary site before gynecologic surgery. The primary site could not be identified in 2 patients. The 5-year survival rate was 40.0% in patients, who underwent surgery on the primary site before gynecologic surgery. However, the 5-year survival rate was 12.2% in patients, who underwent surgery on the primary site during or after gynecologic surgery. The CEA level was significantly lower in the stomach primary group than in the intestine primary group. However, CA125 was the only marker significantly affecting survival. In comparison with primary ovarian carcinoma, the sensitivity of CEA was significantly higher for non-gynecologic ovarian carcinoma, while that of CA125 was significantly less sensitive for non-gynecologic ovarian carcinoma. In conclusion, the prognosis was better in patients, who had undergone resection of primary carcinoma before gynecologic surgery on non-gynecologic ovarian carcinoma. CEA is a useful marker to distinguish non-gynecologic from primary ovarian carcinoma, while CA125 is the only significant prognostic marker for non-gynecologic ovarian carcinoma.


Friedreich ataxia patient tissues exhibit increased 5-hydroxymethylcytosine modification and decreased CTCF binding at the FXN locus.
Friedreich ataxia (FRDA) is caused by a homozygous GAA repeat expansion mutation within intron 1 of the FXN gene, which induces epigenetic changes and FXN gene silencing. Bisulfite sequencing studies have identified 5-methylcytosine (5 mC) DNA methylation as one of the epigenetic changes that may be involved in this process. However, analysis of samples by bisulfite sequencing is a time-consuming procedure. In addition, it has recently been shown that 5-hydroxymethylcytosine (5 hmC) is also present in mammalian DNA, and bisulfite sequencing cannot distinguish between 5 hmC and 5 mC. We have developed specific MethylScreen restriction enzyme digestion and qPCR-based protocols to more rapidly quantify DNA methylation at four CpG sites in the FXN upstream GAA region. Increased DNA methylation was confirmed at all four CpG sites in both FRDA cerebellum and heart tissues. We have also analysed the DNA methylation status in FRDA cerebellum and heart tissues using an approach that enables distinction between 5 hmC and 5 mC. Our analysis reveals that the majority of DNA methylation in both FRDA and unaffected tissues actually comprises 5 hmC rather than 5 mC. We have also identified decreased occupancy of the chromatin insulator protein CTCF (CCCTC-binding factor) at the FXN 5' UTR region in the same FRDA cerebellum tissues. Increased DNA methylation at the FXN upstream GAA region, primarily 5 hmC rather than 5 mC, and decreased CTCF occupancy at the FXN 5' UTR are associated with FRDA disease-relevant human tissues. The role of such molecular mechanisms in FRDA pathogenesis has now to be determined.


Resident educational time study: a tale of three specialties.
To compare amounts of in-hospital time use by PGY1 residents during rotations in emergency medicine (EM), internal medicine (IM), and surgery. This article reports the general study methodology and focuses on the educational aspects of residency time use. A cross-sectional, observational study of the activities of EM PGY1 residents was performed while the residents were on duty during the 3 specialty rotations. The activities were recorded by an observer using a log with predetermined categories for clinical/service, educational, and personal areas. A time-blocked, convenience sample of resident shifts was observed for each service rotation. The sample was proportional to the total number of hours for which a PGY1 resident was expected to be in the hospital during a rotation on that service. No attempt was made to sample the same resident at all time periods or on all rotations. Twelve PGY1 residents were observed for a total of 166 hours on surgery, 156 hours on IM, and 120 hours on EM. These hourly amounts were representative of a typical 2-week span of service on each rotation for the residents. On average, the residents spent 57% of their time on clinical or service-oriented activities, 24% on educational activities, and 19% on personal activities. The proportions of time devoted to the 3 major areas were similar for the 3 rotations. In all 3 rotations, the largest proportion of time was spent on patient-focused education (81% to 92% of total educational time). Only 2% to 11% of educational time was devoted to self-education. Within the patient-focused education category, proportionately less resident time with faculty occurred on the surgery rotation than on the EM and IM rotations (18% vs 30% and 27%, respectively). The general breakdowns of clinical/service, educational, and personal time use by PGY1 residents are proportionately similar for the 3 service rotations. Patient-focused education is the primary mode of education for all services. In-hospital, self-education time is limited. Clinical teaching is largely by nonfaculty. The educational implications of these findings are discussed.


1997 summary: National Hospital Discharge Survey.
This report presents national estimates of the use of non-Federal short-stay hospitals in the United States during 1997. Numbers and rates of discharges, diagnoses, and procedures are shown by age and sex. Discharges are also shown by geographic region of the hospital. Average lengths of stay are presented for all discharges and for selected diagnostic categories by age and by sex. The estimates are based on medical abstract data collected through the National Hospital Discharge Survey for 1997. The survey has been conducted annually by the National Center for Health Statistics since 1965. Diagnoses and procedures presented are coded according to the International Classification of Diseases, 9th Revision, Clinical Modification, or ICD-9-CM.


[Mean molecule peptides of plasma and blood serum].
The concentration of mean molecule peptides is by far less in serum versus plasma. The concentration of mean molecule peptides in serum can go down, in endotoxicosis degrees 3-4, to normal values, whereas it can exceed 3-4-fold the normal value in plasma. The most pronounced reduction of peptides' concentration in serum was registered for the fraction with the molecular weight ranging from 800 to 3000 D.


Inhibition of doxorubicin-induced autophagy in hepatocellular carcinoma Hep3B cells by sorafenib--the role of extracellular signal-regulated kinase counteraction.
A multikinase inhibitor of the Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, sorafenib, is increasingly being used in the management of hepatocellular carcinoma, and its combination with conventional chemotherapeutics has stimulated particular interest. Although the combination of sorafenib with doxorubicin (DOX) is presently being investigated in a phase III randomized trial, little is known about the molecular mechanisms of their interaction. Because DOX causes cell death through upregulation of the MEK/ERK pathway, and sorafenib has an opposite influence on the same cascade, we hypothesized that co-treatment with these drugs may lead to an antagonistic effect. DOX treatment arrested proliferation and induced autophagic cell death in Hep3B cells, whereas apoptotic changes were not conspicuous. Sorafenib alone affected viability and caused massive mitochondrial degradation. However, when added together with DOX, sorafenib facilitated cell cycle progression, increased survival, and reduced autophagy. To evaluate the molecular mechanisms of this phenomenon, we examined the expression of ERK1/2, protein kinase B (Akt), and cyclin D1, as well as the members of Bcl-2 family. ERK1/2 activation induced by DOX was suppressed by sorafenib. Similarly, ERK targeting with the selective inhibitor U0126 impaired DOX-induced toxicity. Treatment with sorafenib, either alone or in combination with DOX, resulted in Akt activation. The role of sorafenib-induced degradation of cyclin D1 in the suppression of DOX efficiency is discussed. In conclusion, MEK/ERK counteraction, stimulation of survival via Akt and dysregulation of cyclin D1 could contribute to the escape from DOX-induced autophagy and thus promote cancer cell survival. The use of MEK/ERK inhibitors in combination with chemotherapeutics, intended to enhance anticancer efficacy, requires the consideration of possible antagonistic effects.


Evaluation of the safety and efficacy of hydroxycitric acid or Garcinia cambogia extracts in humans.
Several studies have shown that Garcinia cambogia plays an important role in the regulation of endogenous lipid biosynthesis. This effect is specially attributed to (-)-hydroxycitric acid (HCA) inhibiting the enzyme ATP-dependent citrate lyase, which catalyzes the cleavage of citrate to oxaloacetate and acetyl-CoA. Although several studies have found that the administration of G. cambogia extracts is associated with body weight and fat loss in both experimental animals and humans, we should be cautious when interpreting the results as other randomized, placebo-controlled clinical trials have not reported the same outcomes. Furthermore, most studies in humans have been conducted on small samples and mainly in the short term. None of them have shown whether these effects persist beyond 12 weeks of intervention. Therefore, there is still little evidence to support the potential effectiveness and long-term benefits of G. cambogia extracts. With regard to toxicity and safety, it is important to note that except in rare cases, studies conducted in experimental animals have not reported increased mortality or significant toxicity. Furthermore, at the doses usually administered, no differences have been reported in terms of side effects or adverse events (those studied) in humans between individuals treated with G. cambogia and controls.


Relationship between pulmonary function, functional independence, and trunk control in patients with stroke.
Stroke often leads to abnormalities in muscle tone, posture, and motor control that may compromise voluntary motor function, thus affecting the motor control required for maintaining the synergy of both peripheral and respiratory muscles. To evaluate respiratory muscle strength, pulmonary function, trunk control, and functional independence in patients with stroke and to correlate trunk control with the other variables. This was a cross-sectional study of patients diagnosed with stroke. We assessed respiratory muscle strength, trunk control as assessed by the Trunk Impairment Scale, spirometric variables, and the Functional Independence Measure. Forty-four patients were included. Pulmonary function and respiratory muscle strength were significantly lower than predicted for the study population, and the mean Trunk Impairment Scale score was 14.3 points. The following significant correlations were found between the variables: trunk control vs. maximal inspiratory pressure (r = 0.26, p < 0.05); trunk control vs. forced vital capacity (r = 0.28, p < 0.05); trunk control vs. forced expiratory volume in one second (r = 0.29, p < 0.05), and trunk control vs. the Functional Independence Measure (r = 0.77, p < 0.05). The present study showed that respiratory muscle strength, pulmonary function, functional independence, and trunk control are reduced in patients diagnosed with stroke.


Variability and gender differences in memory T cell immunity to varicella-zoster virus in healthy adults.
Latent varicella zoster virus (VZV) can reactivate and cause zoster, the prevention of which relies upon cellular immunity to VZV. To assess temporal variation of VZV cell-mediated immunity in healthy naturally immune adults, we evaluated VZV-specific responder cell frequencies (RCF) longitudinally over 1 year in each of 25 adults. VZV-specific CD4+ T cells were detected (p < 0.003) and showed minimal variability in RCF. Additional analysis of VZV T cell RCF revealed differences between genders, with only males (p < 0.005) having detectable VZV-specific memory CD4+ T cell responses by this method. Taken together, results suggest that further studies regarding immunization of younger adults and females with the modified, high-potency live attenuated VZV vaccine may be warranted.


Multifactorial Analysis of a Biomarker Pool for Alzheimer Disease Risk in a North Indian Population.
Alzheimer disease (AD) is a progressive neurodegenerative disease with a complex multifactorial etiology. Here, we aim to identify a biomarker pool comprised of genetic variants and blood biomarkers as predictor of AD risk. We performed a case-control study involving 108 cases and 159 non-demented healthy controls to examine the association of multiple biomarkers with AD risk. The APOE genotyping revealed that ε4 allele frequency was significantly high (p value = 0.0001, OR = 2.66, 95% CI 1.58-4.46) in AD as compared to controls, whereas ε2 (p = 0.0430, OR = 0.29, CI 0.07-1.10) was overrepresented in controls. In biochemical assays, significant differences in levels of total copper, free copper, zinc, copper/zinc ratio, iron, epidermal growth factor receptor (EGFR), leptin, and albumin were also observed. The AD risk score (ADRS) as a linear combination of 6 candidate markers involving age, education status, APOE ε4 allele, levels of iron, Cu/Zn ratio, and EGFR was created using stepwise linear discriminant analysis. The area under the ROC curve of the ADRS panel for predicting AD risk was significantly high (AUC = 0.84, p < 0.0001, 95% CI 0.78-0.89, sensitivity = 70.0%, specificity = 83.8%) compared to individual parameters. These findings support the multifactorial etiology of AD and demonstrate the ability of a panel involving 6 biomarkers to discriminate AD cases from non-demented healthy controls.


EFFECTS OF HYPOTENSION DUE TO HEMORRHAGE AND OF BLOOD TRANSFUSION ON RENAL FUNCTION IN DOGS.
1. Renal blood flow is decreased by hypotension due to bleeding, and glomerular filtration rate is disproportionately decreased. After a first 40 minute stage of hypotension at about 60 mm. Hg infusion of blood with consequent restoration of the general blood volume and arterial pressure usually results in a return to normal of renal blood flow and function although renal blood flow subsequently tends to decrease. The restoration of renal blood flow and function is associated with an increase of urine flow above the control level. 2. Diodrast clearance loses its value as a measure of renal plasma flow (a) during severe or prolonged hypotension, and (b) immediately after restoration of arterial pressure by infusion after a first stage of hypotension. In the former case (a) it is decreased in consequence of decreased renal extraction of diodrast from blood which itself is presumably the result of distribution of renal blood flow through nephrons whose vascular resistance is low. (b) The disparity after transfusion is due to excretion of diodrast accumulated in the kidney tubules and, presumably, in the interstitial fluid during hypotension. The presence of diodrast and inulin in the renal interstitial fluid explains the addition of these substances to renal venous blood observed in some of these experiments. The shifting equilibrium of diodrast between renal plasma and interstitial fluid may explain some of the instances of low diodrast extraction observed in these experiments during transfusion after hypotension, and may explain also the incomplete renal extraction of diodrast under normal conditions. 3. Dogs with denervated kidneys respond to blood transfusion and restoration of arterial pressure by a disproportionately slow and incomplete return towards normal of renal clearance and, presumably, of renal blood flow. On the basis of these facts it is suggested that high spinal anesthesia may interfere with recovery of renal circulation in cases of shock treated by transfusion. 4. Profound or prolonged and repeated hypotension due to bleeding decreases the ability of normal and denervated kidneys of intact and anesthetized dogs to respond to transfusion and the restoration of arterial pressure by proportionately increased clearance and plasma flow, apparently because of renal vasoconstriction due to the release of humorally circulating vasoconstrictor substances.


Cleavable Binary Dyads: Simplifying Data Extraction and Increasing Storage Density in Digital Polymers.
Digital polymers are uniform macromolecules that store monomer-based binary sequences. Molecularly stored information is usually extracted from the polymer by a tandem mass spectrometry (MS/MS) measurement, in which the coded chains are fragmented to reveal each bit (i.e. basic coded monomer unit) of the sequence. Here, we show that data-extraction can be greatly simplified by favoring the formation of MS/MS fragments containing two bits instead of one. In order to do so, digital poly(alkoxyamine phosphodiester)s, containing binary dyads in each repeat unit, were prepared by an orthogonal solid-phase approach involving successive phosphoramidite and radical-radical coupling steps. Three different sets of monomers were considered to build these polymers. In all cases, four coded building blocks-two hydroxy-nitroxides and two phosphoramidite monomers-were required to build the dyads. Among the three studied monomer sets, one combination allowed synthesis of uniform sequence-coded polymers. The resulting polymers led to clear dyad-containing fragments in MS/MS and could therefore be efficiently decoded. Additionally, an algorithm was created to detect specific dyad fragments, thus enabling automated sequencing.


Negative effects of accompanying psychiatric disturbances on functionality among adolescents with chronic migraine.
Chronic migraine is a condition with gradually increasing prevalence among adolescents which causes severe headaches resulting in functionality loss. Factors contributing to migraine becoming chronic and negatively affecting quality of life in adolescence are still unclear. Parallel with these, we aimed to examine the effect of psychiatric symptoms on headache severity and functionality loss among adolescents with chronic migraine. We evaluated features of 50 adolescents who were diagnosed with chronic migraine according to International Classification of Headache Disorders-3 for the first time in their lives by an experienced neurologist. Sociodemographic and clinical data were collected and Pediatric Migraine Disability Assessment Score, Visual Analogue Score and DSM-5 Level 1 Cross-Cutting Symptom Measure Scores (CCSM-5) were evaluated. Semi-structured psychiatric interviews were done to those who scored higher than cut-off scores on CCSM-5. Healthy control group was constituted of cases which had similar age and sex distribution to case group. Majority of the case group was female (%78). There was a positive correlation between headache severity and computerized tomography history in emergency department. All of the psychiatric symptom scores were significantly higher in case group except for psychotic symptoms; but attention problems and manic symptoms clusters did not have significant difference according to the thresholds of CCSM-5. Receiving a psychiatric diagnosis did not affect frequency, severity or duration of headaches. There were also no relationship between depression/anxiety diagnosis and severity of headache/functionality loss. Findings suggest that; more rational treatment methods with lesser functionality loss should be developed by adopting multidisciplinary and prospective approach via psychiatric screening for adolescents with chronic migraine.


Workforce, Workload, and Burnout Among Intensivists and Advanced Practice Providers: A Narrative Review.
To assess-by literature review and expert consensus-workforce, workload, and burnout considerations among intensivists and advanced practice providers. Data were synthesized from monthly expert consensus and literature review. Workforce and Workload section workgroup of the Academic Leaders in Critical Care Medicine Task Force. Multidisciplinary care teams led by intensivists are an essential component of critical care delivery. Advanced practice providers (nurse practitioners and physician assistants) are progressively being integrated into ICU practice models. The ever-increasing number of patients with complex, life-threatening diseases, concentration of ICU beds in few centralized hospitals, expansion of specialty ICU services, and desire for 24/7 availability have contributed to growing intensivist staffing concerns. Such staffing challenges may negatively impact practitioner wellness, team perception of care quality, time available for teaching, and length of stay when the patient to intensivist ratio is greater than or equal to 15. Enhanced team communication and reduction of practice variation are important factors for improved patient outcomes. A diverse workforce adds value and enrichment to the overall work environment. Formal succession planning for ICU leaders is crucial to the success of critical care organizations. Implementation of a continuous 24/7 ICU coverage care model in high-acuity, high-volume centers should be based on patient-centered outcomes. High levels of burnout syndrome are common among intensivists. Prospective analyses of interventions to decrease burnout within the ICU setting are limited. However, organizational interventions are felt to be more effective than those directed at individuals. Critical care workforce and staffing models are myriad and based on several factors including local culture and resources, ICU organization, and strategies to reduce burden on the ICU provider workforce. Prospective studies to assess and avoid the burnout syndrome among intensivists and advanced practice providers are needed.


Formal and informal help during the year after a suicide attempt: a one-year follow-up.
The aims of this study are threefold: to investigate formal and informal help with clinical and social needs that patients who attempted suicide received during the year after their attempt; to examine whether help from services was estimated to be adequate; and to look at whether patients who repeated suicide attempt(s) during follow-up differed from those who did not. The Camberwell Assessment of Need instrument measuring 22 need areas was used in semi-structured interviews with 140 patients at 1 and 12 months after a suicide attempt. Help given from services was rated as high at both 1 and 12 months in health-related areas, but lower in areas related to social needs. Informal help was initially frequent, with some exceptions. The amount of help from services did not decrease in any need area during follow-up, neither in repeaters nor in non-repeaters. There were no changes in informal help in repeaters, while in non-repeaters informal help decreased in some areas. At both 1 and 12 months, repeaters and non-repeaters mostly found help from services to be adequate. However, in the areas of information, intimate relationships, psychotic symptoms and sexual expression about half of the patients in both groups did not consider that they had received the right type of help. The generally high level of formal help in health-related areas during the first year after a suicide attempt and the high rated adequacy of help given is satisfactory. However, in certain areas lack of formal help was evident. Informal caregivers contributed significantly to the help that patients received. The use of the Camberwell Assessment of Need instrument could improve observation on needs areas and whether help is available. Perhaps this kind of evaluation could be used earlier than after 1 year in such a vulnerable group as suicide attempters.


The development and validation of the AMPREDICT model for predicting mobility outcome after dysvascular lower extremity amputation.
The objective of this study was the development of AMPREDICT-Mobility, a tool to predict the probability of independence in either basic or advanced (iBASIC or iADVANCED) mobility 1 year after dysvascular major lower extremity amputation. Two prospective cohort studies during consecutive 4-year periods (2005-2009 and 2010-2014) were conducted at seven medical centers. Multiple demographic and biopsychosocial predictors were collected in the periamputation period among individuals undergoing their first major amputation because of complications of peripheral arterial disease or diabetes. The primary outcomes were iBASIC and iADVANCED mobility, as measured by the Locomotor Capabilities Index. Combined data from both studies were used for model development and internal validation. Backwards stepwise logistic regression was used to develop the final prediction models. The discrimination and calibration of each model were assessed. Internal validity of each model was assessed with bootstrap sampling. Twelve-month follow-up was reached by 157 of 200 (79%) participants. Among these, 54 (34%) did not achieve iBASIC mobility, 103 (66%) achieved at least iBASIC mobility, and 51 (32%) also achieved iADVANCED mobility. Predictive factors associated with reduced odds of achieving iBASIC mobility were increasing age, chronic obstructive pulmonary disease, dialysis, diabetes, prior history of treatment for depression or anxiety, and very poor to fair self-rated health. Those who were white, were married, and had at least a high-school degree had a higher probability of achieving iBASIC mobility. The odds of achieving iBASIC mobility increased with increasing body mass index up to 30 kg/m2 and decreased with increasing body mass index thereafter. The prediction model of iADVANCED mobility included the same predictors with the exception of diabetes, chronic obstructive pulmonary disease, and education level. Both models showed strong discrimination with C statistics of 0.85 and 0.82, respectively. The mean difference in predicted probabilities for those who did and did not achieve iBASIC and iADVANCED mobility was 33% and 29%, respectively. Tests for calibration and observed vs predicted plots suggested good fit for both models; however, the precision of the estimates of the predicted probabilities was modest. Internal validation through bootstrapping demonstrated some overoptimism of the original model development, with the optimism-adjusted C statistic for iBASIC and iADVANCED mobility being 0.74 and 0.71, respectively, and the discrimination slope 19% and 16%, respectively. AMPREDICT-Mobility is a user-friendly prediction tool that can inform the patient undergoing a dysvascular amputation and the patient's provider about the probability of independence in either basic or advanced mobility at each major lower extremity amputation level.


A Hydrogel-Based Epirubicin Delivery System for Intravesical Chemotherapy.
This study aimed to examine the efficacy of epirubicin-loaded gelatin hydrogel (EPI-H) in the treatment of superficial urothelium carcinoma. Hydrogel was prepared by Schiff base-crosslinking of gelatin with glutaraldehyde. EPI-H exhibited high entrapment efficiency (59.87% ± 0.51%). EPI-H also increased epirubicin accumulation in AY-27 cells when compared with the effect of aqueous solutions of epirubicin (EPI-AQ); respective epirubicin-positive cell counts were 69.0% ± 7.6% and 38.3% ± 5.8%. EPI-H also exhibited greater cytotoxicity against AY-27 cells than that of EPI-AQ; IC50 values were 13.1 ± 1.1 and 7.5 ± 0.3 μg/mL, respectively. Cystometrograms showed that EPI-H reduced peak micturition, threshold pressures, and micturition duration, and that it increased bladder compliance more so than EPI-AQ. EPI-H enhanced epirubicin penetration into basal cells of urothelium in vivo, whereas EPI-AQ did so only to the umbrella cells. EPI-H inhibited tumor growth upon intravesical instillation to tumor-bearing bladder of F344 rats, inducing higher levels of caspase-3 expression than that observed with EPI-AQ treatment; the number of caspase-3 positive cells in treated urothelium carcinoma was 13.9% ± 4.0% (EPI-AQ) and 34.1% ± 1.0%, (EPI-H). EPI-H has value as an improved means to administer epirubicin in intravesical instillation treatments for bladder cancer.


A community ability scale for chronically mentally ill consumers: Part I. Reliability and validity.
The authors describe the development, reliability testing, and validation of a 17-item instrument that measures the level of functioning of chronically mentally ill persons living in the community. The Multnomah Community Ability Scale is designed to be completed by case managers. The instrument provides a measure of the consumer's severity of disability which can, in turn, be used to: (a) describe an agency's "case mix" of clients; (b) measure consumer progress; (c) assign clients to different levels of service; and (d) assist payors in determining reimbursement. The Multnomah Community Ability Scale is aimed specifically at persons with chronic mental illness, is sensitive to differences among individuals within this special population, and is quick and easy to complete. The scale's reliability and validity have been examined in detail. Inter-rater and test-retest reliability are good. Criterion variables such as length of psychiatric hospitalization and clinicians' global ratings correlated highly with scale scores. Finally, the instrument predicts subsequent state and local hospital admissions.


Hemangioblastomas share protein expression with embryonal hemangioblast progenitor cell.
Hemangioblastomas are central nervous system (CNS) tumors of unknown histogenesis, which can occur sporadically or in von Hippel-Lindau disease. Hemangioblastomas are composed of neoplastic "stromal" cells of unknown origin, accompanied by intensive reactive angiogenesis. Failure to specify the cytologic origin of the stromal cell has precluded the development of nonsurgical therapies and limits understanding of its basic biology. We report that the stromal cells express proteins (Scl, brachyury, Csf-1R, Gata-1, Flk-1, and Tie-2) that characterize embryonic progenitor cells with hemangioblastic differentiation potential and conclude that embryonic progenitors with hemangioblast potential represent a possible cytologic equivalent of the stromal cell. We also identified a new autocrine/paracrine stimulatory loop between the receptor Tie-2 and the hypoxia-inducible factor target Ang-1, which, combined with previous observations, suggests that a variety of autocrine loops may be initiated in hemangioblastomas, depending on the differentiation status of the tumor cells and the extent of HIF downstream activation. Finally, the consistent identification of Scl in the stromal cells may help explain the unique and characteristic topographical distribution of hemangioblastomas within the CNS.


Personality & Earnings Lost: The Economic Costs of Work Cut Back Days Due to Physical and Mental Health.
Personality traits have emerged as significant contributors to physical and mental health, as well as various economic outcomes including income. Few studies have explored whether personality is related to the frequency of days lost on the job due to physical or mental health issues, and the subsequent economic losses as a result. The current study bridged the health, economic, and personality variables to determine whether personality was associated with earnings lost due to work cut back days from poor physical or mental health. We found, both concurrently and over a 10 year follow up, that high neuroticism and low openness were associated with more earnings lost due to mental health, while low extraversion was associated with more earnings lost due to physical health. These findings are interpreted in light of the effects that personality may have on an individual's career and financial outcomes, and the economic effects of untreated physical and mental health problems.


Incidental retrieval of emotional contexts in post-traumatic stress disorder and depression: an fMRI study.
In the present study, we used fMRI to assess patients suffering from post-traumatic stress disorder (PTSD) or depression, and trauma-exposed controls, during an episodic memory retrieval task that included non-trauma-related emotional information. In the study phase of the task neutral pictures were presented in emotional or neutral contexts. Participants were scanned during the test phase, when they were presented with old and new neutral images in a yes/no recognition memory task. fMRI results for the contrast between old and new items revealed activation in a predominantly left-sided network of cortical regions including the left middle temporal, bilateral posterior cingulate, and left prefrontal cortices. Activity common to all three groups when correctly judging pictures encoded in emotional contexts was much more limited. Relative to the control and depressed groups the PTSD group exhibited greater sensitivity to correctly recognised stimuli in the left amygdala/ventral striatum and right occipital cortex, and more specific sensitivity to items encoded in emotional contexts in the right precuneus, left superior frontal gyrus, and bilateral insula. These results are consistent with a substantially intact neural system supporting episodic retrieval in patients suffering from PTSD. Moreover, there was little indication that PTSD is associated with a marked change in the way negatively valenced information, not of personal significance, is processed.


The Emerging Role of Biomarkers in Adaptive Modulation of Clinical Brain Stimulation.
Therapeutic brain stimulation has proven efficacious for treatment of nervous system diseases, exerting widespread influence via disease-specific neural networks. Activation or suppression of neural networks could theoretically be assessed by either clinical symptom modification (ie, tremor, rigidity, seizures) or development of specific biomarkers linked to treatment of symptomatic disease states. For example, biomarkers indicative of disease state could aid improved intraoperative localization of electrode position, optimize device efficacy or efficiency through dynamic control, and eventually serve to guide automatic adjustment of stimulation settings. Biomarkers to control either extracranial or intracranial stimulation span from continuous physiological brain activity, intermittent pathological activity, and triggered local phenomena or potentials, to wearable devices, blood flow, biochemical or cardiac signals, temperature perturbations, optical or magnetic resonance imaging changes, or optogenetic signals. The goal of this review is to update new approaches to implement control of stimulation through relevant biomarkers. Critical questions include whether adaptive systems adjusted through biomarkers can optimize efficiency and eventually efficacy, serve as inputs for stimulation adjustment, and consequently broaden our fundamental understanding of abnormal neural networks in pathologic states. Neurosurgeons are at the forefront of translating and developing biomarkers embedded within improved brain stimulation systems. Thus, criteria for developing and validating biomarkers for clinical use are important for the adaptation of device approaches into clinical practice.


Advances in the diagnosis and treatment of broncholithiasis.
In order to determine the present clinical spectrum of broncholithiasis and the impact that chest computed tomographic (CT) scans, laminograms , and fiberoptic bronchoscopy ( FOB ) have had on the diagnosis and treatment of this entity, we reviewed our experience between 1970 and 1982. Nineteen patients were identified with this diagnosis. Cough, hemoptysis, and obstructive pneumonia were the most common presentations. Lithoptysis occurred in only 3 patients. The chest radiographic findings were nonspecific, but in 8 of the 19 patients, laminograms or chest CT scans helped establish the diagnosis; FOB was performed on 18 patients and was abnormal in each case, with 8 intrabronchial calcifications identified. However, FOB has limited therapeutic indications in this disorder. Depending on the patient's clinical status and underlying lung disease, observation, bronchoscopic removal of the stone, or surgical resection may be indicated.


Individual Cognitive Stimulation Therapy for dementia (iCST): study protocol for a randomized controlled trial.
Improving the quality of care for people with dementia and their carers has become a national priority in many countries. Cognitive Stimulation Therapy (CST) groups can be beneficial in improving cognition and quality of life for people with dementia. The aim of the current study is to develop and evaluate a home-based individual Cognitive Stimulation Therapy (iCST) programme for people with dementia which can be delivered by their family carer. This multi-centre, pragmatic randomised controlled trial (RCT) will compare the effectiveness and cost-effectiveness of iCST for people with dementia with a treatment as usual control group. The intervention consists of iCST sessions delivered by a carer for 30 minutes, 3 times a week over 25 weeks.For people with dementia the primary outcome measures are cognition assessed by the ADAS-Cog, and quality of life assessed by QoL-AD. For carers, quality of life using the SF-12 is the primary outcome measure. Using a 5% significance level, comparison of 306 participants will yield 80% power to detect an effect size of 0.35 for cognition as measured by the ADAS-Cog, and quality of life as measured by the QoL-AD. Quality of life for the carer will be measured using the SF-12. The trial will include a cost-effectiveness analysis from a public sector perspective. The UK Department of Health has recently stressed that improving access to psychological therapies is a national priority, but many people with dementia are unable to access psychological interventions. The development of a home-based individual version of CST will provide an easy to use, widely available therapy package that will be evaluated for effectiveness and cost-effectiveness in a multi centre RCT.


[Preparation of an insulin-like substance from molluscs and its antiserum].
A substance with insulin-like activity was obtained from visceral organs (excluding foot, gills and mantle) of the freshwater bivalve molluscs Unio pictorum and Anodonta cygnea. Injecting this substance to guinea pigs, antiserum was also obtained. Using the obtained antiserum in immunostaining experiments, the cells which produce insulin-like substance were identified in the intestinal epithelium of the midgut in A. cygnea.