The development of a short measure of physical function for hip OA HOOS-Physical Function Shortform (HOOS-PS): an OARSI/OMERACT initiative.
To derive a cross-culturally valid, short measure of physical function using function subscales (daily living and sports and recreation) of the Hip disability and Osteoarthritis Outcome Score (HOOS). Rasch analysis was conducted on data from individuals from multiple countries who had hip osteoarthritis (OA). Fit of the data to the Rasch model was evaluated by model chi(2) and item fit statistics (chi(2), size of residual, and F-test). Differential item functioning was evaluated by gender, age and country. Unidimensionality was evaluated by factor analysis of residuals. Individual data sets were analyzed and data pooled and re-analyzed for fit to the model. Regression modeling was conducted to derive a nomogram converting raw summed scores to Rasch derived interval scores. Seven data sets were included (n=2991), ages 19-96 years, male/female ratio was 1:1.23. The final model included five HOOS items. From the easiest to most difficult, the items (logit) were as follows: sitting (1.832), descending stairs (0.729), getting in/out of bath or shower (0.255), twisting/pivoting on loaded leg (-0.221) and running (-2.595). The separation index was 0.80. The daily activity and sports and recreational items of the HOOS were reduced to five items achieving a feasible, short measure of physical function with interval level properties. This tool has potential for use as the function component of an OA severity scoring system. Further testing of this measure is warranted.


Exploring Individual and Contextual Factors Associated With Sexual Risk and Substance Use Among Underserved GBQMSM and Transgender and Nonbinary Persons in South Central Appalachia.
Gay, bisexual, queer, and other men who have sex with men (GBQMSM) and transgender and nonbinary persons are at elevated risk for HIV, sexually transmitted infections (STIs), and hepatitis C (HCV); in Appalachia, these communities experience more disease burden. However, little is known about the factors influencing risk. Sixteen semistructured in-depth interviews were conducted examining factors influencing prevention and care. Data were analyzed using constant comparison methodology. Fifteen themes emerged within four domains: social environment (e.g., microaggressions across gender, sexual orientation, and racial identities), substance use (e.g., high prevalence, use as coping mechanism), sexual health (e.g., misinformation and denial of risk for HIV and STIs), and access to health care (e.g., cost and transportation barriers, lack of local respectful care). Findings highlighted salient barriers and assets influencing prevention and care and suggest that multilevel interventions are needed to improve access to and use of HIV, STI, and HCV prevention and care services.


Post-saline infusion test aldosterone levels indicate severity and outcome in primary aldosteronism.
The saline infusion test (SIT) is widely used as a confirmatory test for primary aldosteronism (PA). SIT results are judged as follows: post-test aldosterone levels <50 ng/l exclude PA, whereas levels >50 ng/l confirm PA. We hypothesized that post-SIT aldosterone concentrations indicate the severity of PA and might predict outcome. The study includes 256 PA patients of the German Conn's Registry who prospectively underwent SIT. The data of 126 patients with complete follow-up of 1.2±0.3 years after diagnosis were analyzed. The patients were divided into two groups with post-SIT aldosterone levels of 50-100 ng/l (group 1; n=38) and of >100 ng/l (group 2; n=88). Patients in group 2 had a significantly shorter duration of hypertension (7.5 vs 11.7 years (median), P=0.014), higher systolic blood pressure (BP; 151±16 vs 143±17 mmHg, P=0.036), lower serum potassium (3.3±0.6 vs 3.5±0.4 mmol/l, P=0.006), higher 24-h urine protein excretion (7.4 vs 5.4 mg/dl (median), P=0.012), and were more often female (P=0.038). They showed more often unilateral disease (P<0.005) with larger tumors (14±10 vs 7±10 mm, P=0.021), underwent more often adrenalectomy (75% vs 37%, P<0.005), required a lower number of antihypertensive drugs after adrenalectomy (1.2±1.2 vs 2.5±1.4, P=0.001), had a faster normalization of urinary protein excretion (with medical treatment P=0.049; with Adx P<0.005) at follow-up, and more frequently underlying well-characterized mutation (P=0.047). PA patients with post-SIT aldosterone levels of >100 ng/l have a more rapid development of PA caused more frequently by unilateral disease with larger aldosterone-producing adenomas. However, this group of patients may have a significantly better outcome following specific treatment.


The diagnostic value of electron microscopy in human immunodeficiency virus-positive patients with gastrointestinal disease.
Our aim was to determine the diagnostic value of electron microscopy in evaluating the etiology of gastrointestinal disease in patients infected with the human immunodeficiency virus (HIV). A retrospective review of electron microscopic and light microscopic results of all HIV-positive patients with gastrointestinal and liver diseases was made during a 3-year period from June 1995 to June 1998. A total of 145 HIV-positive patients had their electron microscopy specimens reviewed. Of these, 136 were investigated for diarrhea, and the other 9 for increased liver enzymes. Twenty-seven of the 145 (18.6%) HIV-positive patients had a pathogen identified by electron microscopy, compared with only 13 of 145 (9%) identified by light microscopy (P < 0.005). The sensitivity of light microscopy for detecting opportunistic pathogens was 68%. Twenty-one of the 27 (77.8%) patients diagnosed by electron microscopy had microsporidiosis, and the most commonly diagnosed species was Enterocytozoon bieneusi. Light microscopy failed to identify 12 cases of microsporidiosis and 2 cases of leishmaniasis. Electron microscopy contributes substantially to the identification of pathogens in HIV-positive patients. Light microscopy failed to identify one of every two pathogens diagnosed by electron microscopy.


Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel.
A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups. To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development. Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded. Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be achievement of complete clearance, owing to previously established clinical benefits for patients. Cutaneous and ocular features are defined. Treatments have been reassessed in line with recent evidence and the prior treatment algorithm updated. Combination therapy is recommended to benefit patients with multiple features. Ongoing monitoring and dialogue should take place between physician and patients, covering defined factors to maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case studies have been developed from consensus statements. The current survey updates previous recommendations as a basis for local guideline development and provides clinical tools to facilitate a phenotype approach in practice and improve rosacea patient management. What's already known about this topic? A transition to a phenotype approach in rosacea is underway and is being recommended by multiple working groups. New research has become available since the previous ROSCO consensus, necessitating an update and extension of recommendations. What does this study add? We offer updated global recommendations for clinical practice that account for recent research, to continue supporting the transition to a phenotype approach in rosacea. We present prototype clinical tools to facilitate use of the phenotype approach in practice and improve management of patients with rosacea.


EEG-based Objective Quality Assessment of Interrupted Speech.
As an important dimension of speech degradation, interruption destroys the acoustic waveform information of a speech signal and seriously affects the quality rating in speech perception. Existing studies assessing the quality of interrupted speech mainly focus on subjective methods. This work used event-related potentials (ERPs) to objectively investigate the effects of two interruption factors (i.e., interruption duty cycle and interruption rate) on the perceived quality of the periodically interrupted speech. An oddball-paradigm based ERP experiment was designed, and the periodically interrupted stimuli were presented to participants in the ERP experiment. Meanwhile, participants were instructed to provide their subjective quality ratings of interrupted speech under the same interruption conditions. The experimental results showed that the degree of both interruption duty cycle and interruption rate affected the peak latency of mismatch negativity (MMN) of the collected ERP response, with a smaller MMN peak latency under conditions with a smaller interruption duty cycle or a larger interruption rate. These findings are largely consistent with the subjective quality rating results, suggesting that the peak latency of MMN response can be potentially used as an objective quality indicator of the periodically interrupted speech.


SG-WAS: A New Wireless Autonomous Night Sky Brightness Sensor.
The main features of SG-WAS (SkyGlow Wireless Autonomous Sensor), a low-cost device for measuring Night Sky Brightness (NSB), are presented. SG-WAS is based on the TSL237 sensor -like the Unihedron Sky Quality Meter (SQM) or the STARS4ALL Telescope Encoder and Sky Sensor (TESS)-, with wireless communication (LoRa, WiFi, or LTE-M) and solar-powered rechargeable batteries. Field tests have been performed on its autonomy, proving that it can go up to 20 days without direct solar irradiance and remain hibernating after that for at least 4 months, returning to operation once re-illuminated. A new approach to the acquisition of average NSB measurements and their instrumental uncertainty (of the order of thousandths of a magnitude) is presented. In addition, the results of a new Sky Integrating Sphere (SIS) method have shown the possibility of performing mass device calibration with uncertainties below 0.02 mag/arcsec2. SG-WAS is the first fully autonomous and wireless low-cost NSB sensor to be used as an independent or networked device in remote locations without any additional infrastructure.


Primaquine-chloroquine prophylaxis against malaria in Southeast-Asian refugees entering South Australia.
In 1980, the incidence of malaria among Southeast-Asian refugees arriving in South Australia rose substantially to 22.0 cases/1000 arrivals. All these cases were caused by Plasmodium vivax, and the majority occurred in the small proportion of refugees who had arrived by way of Indonesian camps of asylum (59.2 cases/1000 arrivals). The commencement of an eight-week prophylactic regimen with primaquine (22.5 mg/week) and chloroquine (300 mg/week; 600 mg first dose) by 1388 refugees proved significantly effective in reducing the incidence of malaria among this population. The regimen was administered without the assessment of glucose-6-phosphate dehydrogenase levels, and a transient haemoglobinuria occurred in only one refugee. Other side-effects were minimal when the administration of drugs was delayed until several days after the arrival of the refugee in Australia.


Individualizing the dialysate in the hemodialysis patient.
In most outpatient centers the dialysate is prepared centrally such that the composition of the dialysate is the same for all patients. When delivered in this manner most patients tolerate the procedure well. However, there are patients who tolerate the procedure poorly, which has prompted a great deal of research focused on individualizing the composition of the dialysate in order to improve patient tolerability. Prescribing a patient-specific dialysate will become increasingly important as the age of and number of comorbid conditions increase in the dialysis population. Patients with end-stage renal disease (ESRD) depend on dialysis to maintain fluid and electrolyte balance. Hemodialysis allows for solutes to diffuse between blood and dialysate such that, over the course of the procedure, plasma composition is restored toward normal values. The makeup of the dialysate is of paramount importance in accomplishing this goal. In most out-patient settings patients receive hemodialysis using dialysate prepared in bulk and delivered via a central delivery system so that the composition of the dialysate is the same for all patients. While most patients tolerate the procedure when administered in this fashion, many patients suffer from hemodynamic instability or symptoms of dialysis disequilibrium. One strategy to improve the clinical tolerance to dialysis is to adjust the dialysate composition according to the individual characteristics of the patient. This article reviews recent developments on how the dialysate can be manipulated in order to improve patient tolerance. Individualizing the dialysate composition is likely to gain increasing importance given the advancing age and increasing number of comorbid conditions found in ESRD patients.


Gemcitabine-based adjuvant chemotherapy for patients with advanced gallbladder cancer.
We investigated effects of gemcitabine-based adjuvant chemotherapy (GEM) on prognosis of patients with gallbladder cancer. We retrospectively analyzed outcomes of 36 patients who underwent radical resection for gallbladder cancer from 2001 through to 2012, using χ(2) for prognostic factors and Kaplan-Meier estimator and log-rank tests for survival data. The GEM group had higher rates of lymph node positivity and distant metastasis, higher UICC stage and fewer R0 resections; their 5-year survival rate (60%) did not significantly differ from that of the controls (70.0%), nor was GEM a significant prognostic factor in univariate analysis. However, among patients who underwent R1 and R2 resections, GEM significantly improved prognosis in both univariate and multivariate analyses. Median survival of the R1/2 GEM group (66.4 months) was significantly better than that of controls (5.4 months) (p=0.002). GEM improved prognosis of patients with gallbladder cancer after R1/R2 resections.


Antepartum external cephalic version under tocolysis.
Reported are 172 patients considered for external cephalic version at gestational age greater than 37 weeks. Their outcome was compared with 40 similar patients in whom external version was not attempted. One hundred fifty-eight patients had attempted version, and success was achieved in 122 (77%). Intrapartum vertex presentation occurred in 12% of the control population and in 77% of the version patients. Cesarean section was performed in 80% of the control patients and in 32% of the version patients. There were no maternal or fetal complications directly attributable to external cephalic version. Antepartum external cephalic version under tocolysis is associated with a high success rate, an acceptably low rate of complications, and a decreased incidence of cesarean section for breech presentation at term.


Anthocyanins and Their Metabolites as Therapeutic Agents for Neurodegenerative Disease.
Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), are characterized by the death of neurons within specific regions of the brain or spinal cord. While the etiology of many neurodegenerative diseases remains elusive, several factors are thought to contribute to the neurodegenerative process, such as oxidative and nitrosative stress, excitotoxicity, endoplasmic reticulum stress, protein aggregation, and neuroinflammation. These processes culminate in the death of vulnerable neuronal populations, which manifests symptomatically as cognitive and/or motor impairments. Until recently, most treatments for these disorders have targeted single aspects of disease pathology; however, this strategy has proved largely ineffective, and focus has now turned towards therapeutics which target multiple aspects underlying neurodegeneration. Anthocyanins are unique flavonoid compounds that have been shown to modulate several of the factors contributing to neuronal death, and interest in their use as therapeutics for neurodegeneration has grown in recent years. Additionally, due to observations that the bioavailability of anthocyanins is low relative to that of their metabolites, it has been proposed that anthocyanin metabolites may play a significant part in mediating the beneficial effects of an anthocyanin-rich diet. Thus, in this review, we will explore the evidence evaluating the neuroprotective and therapeutic potential of anthocyanins and their common metabolites for treating neurodegenerative diseases.


Unit dose calendar packaging and elderly patient compliance.
A controlled trial of the effect of a unit dose system of tablet/capsule calendar packaging (Webster-Pak) on the rate of successful self medication both in hospital and after discharge to the community has been completed in a geriatric assessment and rehabilitation unit. Eighty-four elderly patients, 45 using calendar packs (study), and 39 using conventional bottles or packs (control), were followed for three months after discharge. There was a significant improvement in patient compliance in the study group over controls on discharge (86.7% vs 66.7%), 10 days (68.8% vs 41.0%), one month (64.4% vs 38.5%) and three months (48.9% vs 23.1%) after discharge. Unit dose packaging is a cost effective method of improving the delivery of medicine in elderly patients, and should be available as part of the health budget.


Physiotherapy for cystic fibrosis in Australia and New Zealand: A clinical practice guideline.
Physiotherapy management is a key element of care for people with cystic fibrosis (CF) throughout the lifespan. Although considerable evidence exists to support physiotherapy management of CF, there is documented variation in practice. The aim of this guideline is to optimize the physiotherapy management of people with CF in Australia and New Zealand. A systematic review of the literature in key areas of physiotherapy practice for CF was undertaken. Recommendations were formulated based on National Health and Medical Research Council (Australia) guidelines and considered the quality, quantity and level of the evidence; the consistency of the body of evidence; the likely clinical impact; and applicability to physiotherapy practice in Australia and New Zealand. A total of 30 recommendations were made for airway clearance therapy, inhalation therapy, exercise assessment and training, musculoskeletal management, management of urinary incontinence, managing the newly diagnosed patient with CF, delivery of non-invasive ventilation, and physiotherapy management before and after lung transplantation. These recommendations can be used to underpin the provision of evidence-based physiotherapy care to people with CF in Australia and New Zealand.


Plasma and tissue digoxin concentrations in patients undergoing cardiopulmonary bypass.
Plasma myocardial, and skeletal muscle digoxin concentrations were measured in 32 patients undergoing cardiopulmonary bypass who were on long-term treatment with digoxin. The patients were divided into 4 groups according to the daily digoxin dose and the interval between discontinuation of the drug and operation. Before bypass, the mean digoxin concentrations were 1.58 nmol/l (1.24 ng/ml) in plasma 65.2 nmol/kg (50.9 ng/g) in the atria, 121.4 nmol/kg (94.98 ng/g) in 11 papillary muscles, and 16.6 nmol/kg (13.0 ng/g) in skeletal muscle. Mean atrial digoxin concentrations were significantly lower tham mean papillary muscle concentrations in 11 patients. Ratios of plasma of myocardial or skeletal muscle digoxin concentrations were very variable. Generally digoxin concentrations were higher in patients on the larger digoxin dose and with the shorter discontinuation time before surgery. These differences attained significance only with plasma digoxin concentrations. There was a slight fall in plasma digoxin concentration during cardiopulmonary bypass but no significant differences were observed between plasma, atrial, or skeletal muscle digoxin concentrations before and at the end of bypass. No clear relation was seen between plasma or atrial digoxin concentrations and postoperative cardiotoxicity. Stopping digoxin 48 hours before operation appeared to account for pre- or post-bypass plasma digoxin concentrations of less than 1.0 nmol/l (0.8 ng/ml) in most of the instances encountered, whereas the 3 patients who developed pulsus bigeminus postoperatively had received 0.5 mg digoxin only 24 hours before operation.


Plastic scintillation dosimetry: comparison of three solutions for the Cerenkov challenge.
In scintillation dosimetry, a Cerenkov background signal is generated when a conventional fibre optic is exposed to radiation produced by a megavoltage linear accelerator. Three methods of measuring dose in the presence of Cerenkov background are compared. In the first method, a second background fibre is used to estimate the Cerenkov signal in the signal fibre. In the second method, a colour camera is used to measure the combined scintillation and Cerenkov light in two wavelength ranges and a mathematical process is used to extract the scintillation signal. In the third method, a hollow air core light guide is used to carry the scintillation signal through the primary radiation field. In this paper, the strengths and weaknesses of each dosimetry system are identified and recommendations for the optimum method for common clinical dosimetry situations are made.


Electronic studies on oligothienylenevinylenes: understanding the nature of their ground and excited electronic states.
The electronic and molecular structures of a family of oligothienylenevinylenes for organic solar cells are studied by means of UV/Vis, fluorescence and Raman spectroscopy, aided by quantum chemical calculations. By using different anchoring groups, the alteration of the electronic properties upon inserting electron-withdrawing groups into different positions on the oligothienylenevinylene backbone is determined. In addition, a thorough study of the photophysical properties is carried out to understand their potential use in optoelectronic devices. The charge defect of one of these systems is analysed to elucidate the possible charge carriers photogenerated during device operation.


[Etiology of trauma and diagnosis in road traffic injuries].
Recognition of injuries on victims of vehicular fatalities should be performed with the help of means of precise instrumental diagnosis on the basis of information about the etiology of the injury which should be contained in the medical documents.


Dissection of the structure-forming activity from the structure-guiding activity of silicatein: a biomimetic molecular approach to print optical fibers.
Silicateins, a group of proteins forming the proteinaceous axial filaments of the inorganic biosilica spicules of the siliceous sponges, are unique in their dual function to exhibit both structure-guiding (providing the structural platform for the biosilica product) and structure-forming activities (enzymatic function: biosilica synthesis from ortho-silicate). The primary translation product of the silicatein gene comprises a signal peptide, a pro-peptide and, separated by an autocatalytic cleavage site glutamine/aspartic acid [Q/D], the sequence of the mature silicatein protein. In order to dissect the biocatalytic, structure-forming activity of silicatein from its structure-guiding function, two mutated genes were constructed based on the silicatein-α gene of the demosponge Suberites domuncula. (i) A gene encoding for a non-processed silicatein that was mutated, by replacing Q/D [Gln (Q)/Asp (D)] by Q/Q, at the cleavage site within the primary translation product between the pro-peptide and the mature enzyme of wild type silicatein. (ii) A gene encoding for a mature enzymatically-active silicatein in which the S-stretch was replaced by a Q-stretch. The enzymatic activity of the mutated protein was significantly enhanced in the presence of the sponge-specific silicatein-interacting protein, silintaphin-1. The two recombinant proteins were applied for micro-contact printing. Using this technique, parallel layers (diameter 10 μm) of the enzymatically inactive, non-processed silicatein were printed onto a gold surface and used as a structure-guiding template for coating with the soluble enzymatically active silicatein. The experiments revealed that after enzymatic reaction with an ortho-silicate substrate a biosilica mantle is formed that can act as a light waveguide.


Disposition of marbofloxacin in vulture (Gyps fulvus) after intravenous administration of a single dose.
The pharmacokinetics properties of marbofloxacin were studied in adult Eurassian Griffon vulture after single-dose intravenous (IV) administration of 2mg/kg. Drug concentration in plasma was determined by high-performance liquid chromatography and the data obtained were subjected to compartmental and non-compartmental kinetic analysis. Marbofloxacin presented a volume of distribution at steady-state (Vdss) of 1.51±0.22L and total plasma clearance (Cl) of 0.109±0.023L/hkg. The permanence of this drug was long in vultures (T(1/2)(λ)=12.51±2.52h; MRT(∞)=13.54±2.29h). The optimal dose of marbofloxacin estimated is 2.73mg/kg per day for the treatment of infections in vultures with MIC(90)=0.2μg/mL.


Tobacco industry's 'behind the scenes' tactics in Singapore.
Tobacco companies have maintained a profitable business in Singapore, despite its strong anti-tobacco climate and commitment to protect public health policymaking from tobacco industry interference in line with Framework Convention on Tobacco Control Article 5.3. This study describes how tobacco companies influence policymaking in a highly regulated environment such as Singapore's, where there is a strong government commitment to Article 5.3. Analysis of internal tobacco industry documents detailing the industry's lobbying activities in Singapore, retrieved via snowball searches in the Truth Tobacco Industry Documents Library. Subsequently, we conducted one-on-one interviews with key informants from sectors mentioned in the documents (academia, arts, government, public health, media, trade, education) to fill gaps in information and provide context to events described in the documents. In the 1980s and 1990s, tobacco companies observed that, to influence policy within Singapore's 'hostile' environment, they needed to use 'behind the scenes' tactics, targeting influential individuals at social functions or industry-sponsored events. Tobacco companies used arts and education sponsorships primarily for political purposes, to gain visibility with policymakers. Tobacco companies cultivated relationships with academic researchers and the media to avoid smoke-free legislation in the 1990s and, in the 2010s, appear to have used similar tactics to challenge Singapore's e-cigarette ban. Countries with a strong commitment to Article 5.3 should consider the tobacco industry's potential interference in policymaking beyond relationships in the government sector, particularly in academia, arts, education and the media, and the more subtle or indirect manners in which these relationships are built.


Design and development of nanovehicle-based delivery systems for preventive or therapeutic supplementation with flavonoids.
To date more than 4000 compounds are recognized to belong to the class of flavonoids. These natural phenolic drugs are poorly soluble in water and are rapidly degraded and metabolized in the human body, but nevertheless are very promising for their potential contribution to the prevention and therapy of major chronic diseases, including cardiovascular and neurodegenerative diseases and cancer. In recent years a number of flavanols (e.g. catechins), flavonols (e.g. quercetin, myricetin) and isoflavones (e.g. genistein, daidzein) have been confirmed to possess strong antioxidant, anti-inflammatory, anti-proliferative and anti-aging activities. Incorporation into lipidic or polymer-based nanoparticles appears to markedly help the oral delivery of flavonoids, as these particles can protect the drug from degradation in the gastrointestinal tract and, by virtue of their unique absorption mechanism through the lymphatic system, also from first-pass metabolism in the liver. In addition, both oral and parenteral administration of flavonoids exploits a pharmacologic delivery route that guarantees sustained release of the active principle at the desired site of action. A comprehensive review of studies currently available on the in vitro and in vivo experimental administration of flavonoids by means of nanovectors may be of use as a foundation for the development of advanced delivery systems for these powerful compounds, in view of their adoption in primary and secondary disease prevention.


Scalable synthesis of nanoporous atomically thin graphene membranes for dialysis and molecular separations via facile isopropanol-assisted hot lamination.
Scalable graphene synthesis and facile large-area membrane fabrication are imperative to advance nanoporous atomically thin membranes (NATMs) for molecular separations. Although chemical vapor deposition (CVD) allows for roll-to-roll high-quality monolayer graphene synthesis, facile transfer with atomically clean interfaces to porous supports for large-area NATM fabrication remains extremely challenging. Sacrificial polymer scaffolds commonly used for graphene transfer typically leave polymer residues detrimental to membrane performance and transfers without polymer scaffolds suffer from low yield resulting in high non-selective leakage through NATMs. Here, we systematically study the factors influencing graphene NATM fabrication and report on a novel roll-to-roll manufacturing compatible isopropanol-assisted hot lamination (IHL) process that enables scalable, facile and clean transfer of CVD graphene on to polycarbonate track etched (PCTE) supports with coverage ≥99.2%, while preserving support integrity/porosity. We demonstrate fully functional centimeter-scale graphene NATMs that show record high permeances (∼2-3 orders of magnitude higher) and better selectivity than commercially available state-of-the-art polymeric dialysis membranes, specifically in the 0-1000 Da range. Our work highlights a scalable approach to fabricate graphene NATMs for practical applications and is fully compatible with roll-to-roll manufacturing processes.


Long-distance transmission patterns modelled from SNP barcodes of Plasmodium falciparum infections in The Gambia.
Malaria has declined significantly in The Gambia and determining transmission dynamics of Plasmodium falciparum can help targeting control interventions towards elimination. This can be inferred from genetic similarity between parasite isolates from different sites and timepoints. Here, we imposed a P. falciparum life cycle time on a genetic distance likelihood model to determine transmission paths from a 54 SNP barcode of 355 isolates. Samples were collected monthly during the 2013 malaria season from six pairs of villages spanning 300 km from western to eastern Gambia. There was spatial and temporal hierarchy in pairwise genetic relatedness, with the most similar barcodes from isolates within the same households and village. Constrained by travel data, the model detected 60 directional transmission events, with 27% paths linking persons from different regions. We identified 13 infected individuals (4.2% of those genotyped) responsible for 2 to 8 subsequent infections within their communities. These super-infectors were mostly from high transmission villages. When considering paths between isolates from the most distant regions (west vs east) and travel history, there were 3 transmission paths from eastern to western Gambia, all at the peak (October) of the malaria transmission season. No paths with known travel originated from the extreme west to east. Although more than half of all paths were within-village, parasite flow from east to west may contribute to maintain transmission in western Gambia, where malaria transmission is already low. Therefore, interrupting malaria transmission in western Gambia would require targeting eastern Gambia, where malaria prevalence is substantially higher, with intensified malaria interventions.


Health characteristics of older Australian dietary supplement users compared to non-supplement users.
The aim of this study was to measure the prevalence of dietary and health supplement use among Australians aged 65 years and over, and to contrast the health differences between supplement users and non-supplement users. Data was obtained from 1,263 randomly selected older Australians, who provided general demographic data, in addition to information related to their health, symptoms experienced and uses of medication, including dietary supplements. Supplement use was reported by 43% of the sample (52% of females and 35% of males). This investigation has revealed distinct differences in the health profile of older supplement users compared to non-users. Although there was no difference in the number of visits to medical doctors or self-rated health status between supplement users and non-supplement users, supplement users were more likely to report arthritis and osteoporosis, and experience more symptoms and consume more medication than non-supplement users. In contrast, there was a reduced likelihood of taking a supplement for those with hypertension and by those using blood pressure medication and heart tablets. These results suggest that older dietary supplement users may benefit from education and professional advice to assist them make appropriate and informed choices, particularly if they expect these preparations to attenuate their health concerns.


Compact Quad Band MIMO Antenna Design with Enhanced Gain for Wireless Communications.
In this paper, a novel microstrip line-fed meander-line-based four-elements quad band Multiple Input and Multiple Output (MIMO) antenna is proposed with a gain enhancement technique. The proposed structure resonates at four bands simultaneously, that is, 1.23, 2.45, 3.5 and 4.9 GHz, which resemble GPS L2, Wi-Fi, Wi-MAX and WLAN wireless application bands, respectively. The unit element is extended to four elements MIMO antenna structure exhibiting isolation of more than 22 dB between the adjacent elements without disturbing the resonant frequencies. In order to enhance the gain, two orthogonal microstrip lines are incorporated between the antenna elements which result in significant gain improvement over all the four resonances. Furthermore, the diversity performance of the MIMO structure is analyzed. The Envelope Co-Relation Coefficient (ECC), Diversity Gain (DG), Channel Capacity Loss (CCL), Mean Effective Gain (MEG) and Multiplexing Efficiency are obtained as 0.003, 10 dB, 0.0025 bps/Hz, -3 dB (almost) and 0.64 (min.), respectively, which are competent and compatible with practical wireless applications. The Total Active Reflection Coefficient (TARC) resembles the characteristic of the individual antenna elements. The layout area of the overall MIMO antenna is 0.33 λ × 0.29 λ, where λ is the free-space wavelength corresponding to the lowest resonance. The advantage of the proposed structure has been assessed by comparing it with previously reported MIMO structures based on number of antenna elements, isolation, gain, CCL and compactness. A prototype of the proposed MIMO structure is fabricated, and the measured results are found to be aligned with the simulated results.


Maximal lipid oxidation in patients with type 2 diabetes is normal and shows an adequate increase in response to aerobic training.
Insulin resistance in subjects with type 2 diabetes (T2D) and obesity is associated with an imbalance between the availability and the oxidation of lipids. We hypothesized that maximal whole-body lipid oxidation during exercise (FATmax) is reduced and that training-induced metabolic adaptation is attenuated in T2D. Obese T2D (n = 12) and control (n = 11) subjects matched for age, sex, physical activity and body mass index completed 10 weeks of aerobic training. Subjects were investigated before and after training with maximal and submaximal exercise tests and euglycaemic-hyperinsulinaemic clamps combined with muscle biopsies. Training increased maximal oxygen consumption (VO(2max)) and muscle citrate synthase activity and decreased blood lactate concentrations during submaximal exercise in both groups (all p < 0.01). FATmax increased markedly (40-50%) in both T2D and control subjects after training (all p < 0.001). There were no significant differences in these variables and lactate threshold (%VO(2max)) between groups before or after training. Insulin-stimulated glucose disappearance rate (Rd) was lower in T2D vs. control subjects both before and after training. Rd increased in response to training in both groups (all p < 0.01). There was no correlation between Rd and measures of oxidative capacity or lipid oxidation during exercise or the training-induced changes in these parameters. FATmax was not reduced in T2D, and muscle oxidative capacity increased adequately in response to aerobic training in obese subjects with and without T2D. These metabolic adaptations to training seem to be unrelated to changes in insulin sensitivity and indicate that an impaired capacity for lipid oxidation is not a major cause of insulin resistance in T2D.


Does patient-reported perception of pain differ based on surgical approach in total hip arthroplasty?
Whether patient-reported pain differs among surgical approaches in total hip arthroplasty (THA) remains unclear. This study's purposes were to determine differences in pain based on surgical approach (direct anterior (DA) vs posterolateral (PL)) and PL approach incision length. This was a retrospective investigation from two centres and seven surgeons (three DA, three PL, one both) of primary THAs. PL patients were categorized for incision length (6 cm to 8 cm, 8 cm to 12 cm, 12 cm to 15 cm). All patients had cementless femoral and acetabular fixation, at least one year's follow-up, and well-fixed components. Patients completed a pain-drawing questionnaire identifying the location and intensity of pain on an anatomical diagram. Power analysis indicated 800 patients in each cohort for adequate power to detect a 4% difference in pain (alpha = 0.05, beta = 0.80). A total of 1848 patients (982 DA, 866 PL) were included. PL patients were younger (59.4 years, sd 12.9 vs 62.7 years, sd 9.7; p < 0.001) and had shorter follow-up (3.3 years, sd 1.3 vs 3.7 years, sd 1.3; p < 0.001). DA patients reported decreased moderate to severe trochanteric (14% vs 21%; p < 0.001) and groin pain (19% vs 24%; p = 0.004) than PL patients. There were no differences in anterior, lateral, or posterior thigh, back, or buttock pain between cohorts (p = 0.05 to 0.7). PL approach incision length did not impact the incidence or severity of pain (p = 0.3 to 0.7). A significant proportion of patients perceive persistent pain following THA regardless of approach. DA patients reported less trochanteric and groin pain versus PL patients. PL incision length did not influence the incidence or severity of patient-reported pain. Cite this article: Bone Joint J 2019;101-B(6 Supple B):31-36.


A simple procedure for the isolation of protein disulphide-isomerase.
A two-step procedure is described for the purification of protein disulphide-isomerase (PDI). This procedure is based on the previous finding that the beta-subunit of the prolyl 4-hydroxylase tetramer (alpha 2 beta 2) is identical with PDI [Koivu, Myllylä, Helaakoski, Pihlajaniemi, Tasanen & Kivirikko (1987) J. Biol. Chem. 262, 6447-6449; Pihlajaniemi, Helaakoski, Tasanen, Myllylä, Huhtala, Koivu & Kivirikko (1987) EMBO J. 6, 643-649]. The procedure involves purification of the prolyl 4-hydroxylase tetramer by a simple affinity chromatography and subsequent isolation of the beta-subunit from the dissociated tetramer by ion-exchange chromatography.


The Transaxillary Approach via Prosthetic Conduit for Transcatheter Aortic Valve Replacement With the New-Generation Balloon-Expandable Valves in Patients With Severe Peripheral Artery Disease.
Background: The left subclavian artery (LSA) is an infrequently used alternative access route for patients with severe peripheral artery disease (PAD) in patients who underwent transcatheter aortic valve replacement (TAVR). We report a new endovascular approach for TAVR combining an axillary prosthetic conduit-based access technique with new-generation balloon-expandable TAVR prostheses. Methods and Results: Between January 2020 and December 2020, 251 patients underwent TAVR at the West German Heart and Vascular Center. Of these, 10 patients (3.9%) were deemed to be treated optimally by direct surgical exposure of the left or right axillary artery via a surgically adapted prosthetic conduit. All procedures were performed under general anesthesia. One procedural stroke occurred due to severe calcification of the aortic arch. No specific complications of the subclavian access site (vessel rupture, vertebral, or internal mammary ischemia) were reported. Two minor bleedings from the access site could be treated conservatively. No surgical revision was necessary. Conclusion: The axillary prosthetic conduit-based access technique using new-generation balloon-expandable valves allows safe and successful TAVR in a subgroup of patients with a high risk of procedural complications due to severe peripheral vascular disease. Considering the increasing number of patients referred for TAVR, this approach could represent an alternative for patients with limited access sites.


Inappropriate leptin secretion in thalassemia: a potential cofactor of pubertal timing derangement.
The objective of the present study was to gain a better understanding of the role played by scarce leptin production in the deranged sexual development observed in patients with thalassemia. We studied 101 patients at different stages of puberty. Patients of both sexes were divided into three groups according to Tanner stages: T1-2 (20 males and 12 females), T3-4 (9 males and 4 females) and T5 (48 males and 8 females). Serum levels of leptin, ferritin, testosterone and estradiol were assessed. Leptin levels were adjusted for body mass index (BMI) using reference ranges stratified on the basis of gender and pubertal development. Deviations from the mean reference values were evaluated by calculating the standard deviation scores. Mean leptin standard deviation scores were significantly lower than expected in pubertal stage T1-2 and T3-4 in males and T3-4 and T5 in females. The peak leptin level was delayed in boys (13 years). In girls, parallelism between leptin and BMI was present until age 7-10 years; thereafter, although BMI constantly increased, leptin levels fell dramatically. Mean ferritin levels were significantly higher in pubertal stage T1-2 among males and in T5 among females. These findings show that in thalassemia adipose tissue is unable to assure adequate leptin production just when the highest leptin secretion is required and suggest that this inappropriate leptin secretion may be a cofactor of the derangement in pubertal timing observed in patients with thalassemia.


[Modern ideas on the treatment of dislocations and fracture-dislocations in the elbow joint].
The authors describe the causes and surgical methods of treatment of fresh and long-standing dislocations and fracture-dislocations in the elbow joint. The indications to using different operative methods and technical-surgical interventions are described in details as well as long-term results of treatment by the literature data. The current methods and the authors' methods of prophylactics and treatment of postoperative complications are analyzed. The methods of rehabilitation of such patients are also described.


Cosegregation of cell wall and DNA in Bacillus subtilis.
Cosegregation of cell wall and DNA of a lysis-negative mutant of Bacillus subtilis was examined by continuously labeling (i) cell wall, (ii) DNA, and (iii) both cell wall and DNA. After four to five generations of chase in liquid media it was found by light microscope autoradiography that the numbers of wall segregation units per cell are 29 and 9 in rich and minimal medium, respectively. Under the same conditions the numbers of segregation units of DNA were almost 50% lower: 15 and 5, respectively. Simultaneous labeling of cell wall and DNA (iii) provided figures almost identical to those obtained for cell wall alone, (i), implying cosegregation of the two components. Statistical analysis ruled out their random distribution into daughter cells. Measurements of the positions of grain clusters at the end of the chase period along chains of cells, each derived from a single cell at the beginning of chase, show that cell wall units are localized according to a symmetrical pattern, whereas those of DNA are distributed in an asymmetrical but highly regular way. It appears that of two cell wall units of the same age one only has a strand of DNA attached to it. We present a simple diagrammatic model of cell wall organization and DNA-cell wall association which is compatible with our observations. Finally, we discuss previous experiments pertinent to cosegregation of cell wall and DNA obtained with cells grown on solid media as well as with germinating spores; an explanation for the independent segregation of cell wall and DNA observed in the latter case is advanced.


Uptake and release of calcium by canine gastric corpus smooth muscle plasma membrane enriched fraction.
Calcium movements across plasma membrane enriched vesicles isolated from canine gastric corpus smooth muscle were investigated. The ATP-dependent Ca2+ uptake increased with time up to 10 min. The uptake for the initial 2-min period was approximately linear with time. The apparent initial velocity of the ATP-dependent Ca2+ uptake increased monotonically with free Ca2+ concentration from 0.1 to 2 microM, and further increases in free Ca2+ concentration did not increase the Ca2+ uptake. The free Ca2+ dependence curve could be described with a Hill coefficient of approximately 1.0 and Km of 0.85 +/- 0.01 microM for free Ca2+ concentration. Passive Ca2+ uptake (reaction time = 1 h) also increased with increasing free Ca2+ concentrations from 0.02 to 4.0 mM. Dilution of loaded vesicles in isotonic media containing EGTA led to initial rapid loss (less than 1 min) followed by a slower release which showed simple exponential decay. The t 1/2 values of the slower Ca2+ loss from these vesicles were 16.1 +/- 0.9 min (actively loaded n = 5) and 18.4 +/- 0.9 min (passively loaded n = 3), respectively. Dilution in isotonic medium containing both EGTA and A23187 released all the sequestered Ca2+ from these loaded vesicles.


Update on inflammation in chronic kidney disease.
Despite recent advances in chronic kidney disease (CKD) and end-stage renal disease (ESRD) management, morbidity and mortality in this population remain exceptionally high. Persistent, low-grade inflammation has been recognized as an important component of CKD, playing a unique role in its pathophysiology and being accountable in part for cardiovascular and all-cause mortality, as well as contributing to the development of protein-energy wasting. The variety of factors contribute to chronic inflammatory status in CKD, including increased production and decreased clearance of pro-inflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, including those related to dialysis access, altered metabolism of adipose tissue, and intestinal dysbiosis. Inflammation directly correlates with the glomerular filtration rate (GFR) in CKD and culminates in dialysis patients, where extracorporeal factors, such as impurities in dialysis water, microbiological quality of the dialysate, and bioincompatible factors in the dialysis circuit play an additional role. Genetic and epigenetic influences contributing to inflammatory activation in CKD are currently being intensively investigated. A number of interventions have been proposed to target inflammation in CKD, including lifestyle modifications, pharmacological agents, and optimization of dialysis. Importantly, some of these therapies have been recently tested in randomized controlled trials. Chronic inflammation should be regarded as a common comorbid condition in CKD and especially in dialysis patients. A number of interventions have been proven to be safe and effective in well-designed clinical studies. This includes such inexpensive approaches as modification of physical activity and dietary supplementation. Further investigations are needed to evaluate the effects of these interventions on hard outcomes, as well as to better understand the role of inflammation in selected CKD populations (e.g., in children).


Effect of ethanol on activity of the plasma-membrane ATPase in, and accumulation of glycine by, Saccharomyces cerevisiae.
The pH optimum of the ATPase activity in plasma membranes from Saccharomyces cerevisiae NCYC 431 from 8 h cultures was around 6.5 and that in membranes from organisms from 16 h cultures near 6.0. The Km[ATP] of the enzyme was virtually unaffected by the age of the culture from which organisms were harvested, although the Vmax of the enzyme in membranes from organisms from 8 h cultures was higher than that for organisms from 16 h cultures. Ethanol non-competitively inhibited ATPase activity in membranes, although the inhibition constant for the enzyme from organisms from 8 h cultures was lower than that from organisms from 16 h cultures. Glycine accumulation by the general amino acid permease was non-competitively inhibited by ethanol. Inhibition constants were virtually the same for glycine uptake by deenergized organisms from 8 h and 16 h cultures, but under energized conditions the value was greater for organisms from 16 h rather than 8 h cultures. The data indicate that inhibition of plasma-membrane ATPase activity by ethanol could account, at least in part, for inhibition of glycine accumulation by ethanol.


Image-Based Tools and Analysis for Human RVOT/RV Structures.
The right-ventricular (RV) outflow tract (RVOT) and the transition to the RV free wall are recognized sources of arrhythmia in human hearts. However, we do not fully understand myocardial tissue structures in this region. Human heart tissue was processed for optical clarity, labelled with wheat-germ agglutin (WGA) and anti-Cx43, and imaged on a custom-built line scanning confocal microscope. The 3D images were analyzed for myocyte gross structures and cell morphology. There were regions of high organization as well as rapid changes to more heterogeneous regions. Preliminary cell segmentations were used to estimate cell morphology. Observed RVOT/RV structure is consistent with known arrhythmic substrates.Clinical Relevance- New views of human tissue structure enable clearer clinical understanding of arrhythmogenic activation pathways and targets for invasive treatment such as RF ablation.


Resveratrol glucosylation by GTF-SI from Streptococcus mutans: computational insights into a GH70 family enzyme.
Resveratrol, a polyphenolic compound known for its health benefits but limited by poor water solubility and low bioavailability, represents a valuable substrate for glucosylation by carbohydrate-active enzymes such as glucosyltransferase-SI (GTF-SI). Using quantum mechanics/molecular mechanics (QM/MM) calculations and molecular dynamics simulations, this study reveals the atomic scale dynamics of resveratrol glucosylation by wild-type GTF-SI. This enzyme exhibited an energy barrier of 8.8 kcal mol-1 and an exothermic process, both consistent with experimental data of similar enzymes. We report a concerted and synchronous reaction mechanism for the catalytic step, characterized by an oxocarbenium ion-like transition state, and elucidate a conformational itinerary of the glucosyl moiety (4H3/E3) → [E3]‡ → 4C1, which aligns with the consistent patterns observed across enzymes of the GH13 and GH70 families. A key interaction was observed between Asp477 and the OH group on carbon 6 of the glucosyl moiety, together with a 2.0 kcal mol-1 transition state stabilization by three water molecules within the active site. Comparative insights with the previously studied Q345F SP enzyme system shed light on the unique and common features that govern transglucosylation reactions. Importantly, the calculated activation barriers strongly support the capability of GTF-SI to facilitate resveratrol glucosylation. This study advances our understanding of the transglucosylation reaction and opens up new ways for the glycodiversification of organic compounds such as polyphenols, thus expanding their potential applications in the food, cosmetic, and pharmaceutical industries.


Proteolytic degradation of the nuclear isoform of uracil-DNA glycosylase occurs during the S phase of the cell cycle.
Uracil-DNA glycosylases are enzymes that remove uracil from DNA and initiate base-excision repair. These enzymes play a key role in maintaining genomic integrity by reducing the mutagenic events caused by G:C to A:T transition mutations. The recent finding that a family of RNA editing enzymes (APOBECs) can deaminate cytosine in DNA has raised the interest in these base-excision repair enzymes. This research focuses on the regulation of the nuclear isoform of uracil-DNA glycosylase, a 36000 Da protein that contains a unique 44 amino acid N-terminus. In synchronized HeLa cells, UDG1A protein levels decrease to barely detectable levels during the S phase of the cell cycle. Immunoblot analysis of immunoprecipitated or affinity-isolated UDG1A reveals ubiquitin-conjugated UDG1A when proteolysis is inhibited using N-acetyl-leu-leu-norleu-al or MG132, inhibitors of proteosomal dependent protein degradation. Transient transfection experiments, with histidine-tagged ubiquitin, were used to confirm that endogenous UDG1A is ubiquitinated in vivo. Addition of the nuclear export inhibitor, leptomycin B, prevents ubiquitination and degradation of UDG1A. This indicates that translocation from the nucleus may be a step in UDG1A turnover. Finally, UDG1A protein degradation is prevented when cells are incubated with the cyclin-dependent kinase inhibitor, roscovitine. These results suggest that protein phosphorylation and/or nuclear export participate in the post-translational regulation of UDG1A protein levels.


The pamamycins: developmental autoregulators and antibiotics from Streptomyces alboniger. A review and update.
A brief review and update of current studies on the pamamycins is presented. The pamamycins are a group of macrolides isolated from Streptomyces alboniger which function as autoregulators in streptomycetes. At low concentrations, they stimulate the formation of aerial mycelium and, at higher concentrations, they inhibit the growth of these organisms. In addition, the pamamycins have potent antibiotic activity against gram-positive bacteria, fungi and mycobacteria. The possible mode of action of these compounds is discussed, together with their possible value against multiple antibiotic-resistant M. tuberculosis.


Return to flying after head injuries: a review.
The pathology of head injury is discussed in relation to severity and to the chance of recovery. Return to flying status, then, depends mainly on the hazard of subsequent post-traumatic epilepsy (PTEP). Assessment of the threat of PTEP is based on the incidence of onset of PTEP within 1 year (75%) and 2 years (85%) of head injury in those who will develop the complication. Clear risk markers which increase the chances of later PTEP include past history of febrile convulsions, family history of epilepsy, "early" PTEP, intracranial haematoma, and depressed skull fracture. The persisting risk in depressed skull fracture is itself adversely affected by early epilepsy, dural laceration, focal neurological signs, and post-traumatic amnesia longer than 24 h. Permanent prohibition on grounds of initial severity can rarely be warranted. A cautious open-minded assessment of each individual by AMEs with specialist referral where indicated is recommended.


NICOTINIC ACID ANALOGS: EFFECTS ON RESPONSE OF CHICK EMBRYOS AND HENS TO ORGANOPHOSPHATE TOXICANTS.
Embryonic abnormalities are known to be induced in chick embryos when they are injected with certain organophosphate insecticides prior to incubation. The marked teratogenic effects of Bidrin [3-(dimethoxyphosphinyloxy) N, N-dimethyl-cis-crotonamide] can be alleviated by many analogs of nicotinamide and nicotinamide adenine dinucleotide. Successive hydroxylation and N-dealkylation of Bidrin in the egg are not greatly altered by injection of nicotinamide. The delayed neurotoxicity in adult hens after administering tri-o-cresyl phosphate is also partially relieved by administering certain nicotinamide analogs.


Prevalence of Kaposi's sarcoma-associated herpesvirus among intravenous drug users: a systematic review and meta-analysis.
Intravenous drug users (IDUs) have been demonstrated to be highly vulnerable to HIV/AIDS. Nevertheless, the prevalence of Kaposi's sarcoma associated herpesvirus (KSHV), an important co-infected agent with HIV, among this population remained obscure. We conducted a systematic review on the epidemiological features of KSHV among IDUs worldwide. Eligible studies were retrieved from 6 electronic databases (PubMed, EMBASE, Web of Science, CBM, CNKI and Wanfang). We calculated the pooled prevalence and 95% confidence interval (CI) overall and among subgroups using either random-effects model or fixed-effects model depending on between-study heterogeneity. The potential publication bias was assessed by the Egger's test. A meta-regression analysis was performed to explore the sources of heterogeneity. Finally, twenty-two studies with a total sample of 7881 IDUs were included in the analysis. The pooled prevalence of KSHV was 14.71% (95% CI 11.12%-19.46%) among IDUs. Specifically, KSHV prevalence was 10.86% (95% CI 6.95%-16.96%) in HIV-negative IDUs, and 13.56% (95% CI 10.57%-17.38%) in HIV-positive IDUs. Moreover, prevalence among IDUs from the three continents involved in the current study was similar: 16.10% (95%CI 7.73%-33.54%) in Asia; 14.22% (95%CI 8.96%-22.57%) in Europe and 14.06% (95%CI 11.38%-17.37%) in America. Globally, IDUs are at higher risk of the KSHV infection when compared with the general population, regardless of geographical region or HIV-infection status.


[Immunoenzyme method for demonstrating the antigen and antibodies to the human immunodeficiency virus and its use for the serological examination of different population groups].
An enzyme immune diagnosticum for the detection of the antigen and antibody to human immunodeficiency virus (HIV) has been developed at D. I. Ivanovskiĭ Institute of Virology of the USSR AMS. The method is based on the principle of competitive analysis using an antiviral conjugate which allows the sera to be tested without preliminary dilution and ensures a high sensitivity of the diagnosticum. The survey for HIV antibody covered 5743 subjects, among them 4898 Soviet citizens predominantly belonging to high risk groups of contracting AIDS infection, and 845 foreigners. No antibody to HIV has been detected in any of the Soviet citizens. Among the foreigners, antibody to HIV were detected in 6 subjects, all of them arriving from different African countries.


The added benefits and efficacy of atherectomy in the lower limb.
Atherectomy has been used as an adjunct therapy for balloon angioplasty and/or stent placement in the superficial femoral artery for many years, but has never gained global popularity in the treatment of peripheral arterial disease, most probably related to the conflicting results as published in the literature. Novel techniques that have been developed over the past years are yielding promising results in the infrainguinal region. This paper will describe the added benefits of atherectomy as compared to plain old balloon angioplasty and bail-out bare-metal stenting, both in the treatment of primary lesions of the superficial femoral artery as well as in cases of in-stent restenosis.


Prognosis of sporadic resected small (≤2 cm) nonfunctional pancreatic neuroendocrine tumors - a multi-institutional study.
Malignant potential of small (≤20 mm) nonfunctional pancreatic neuroendocrine tumors (sNF-PNET) is difficult to predict and management remain controversial. The aim of this study was to assess the prognosis of sporadic nonmetastatic sNF-PNETs. Patients were identified from databases of 16 centers. Outcomes and risk factors for recurrence were identified by uni- and multivariate analyses. sNF-PNET was resected in 210 patients, and 66% (n = 138) were asymptomatic. Median age was 60 years, median tumor size was 15 mm, parenchyma-sparing surgery was performed in 42%. Postoperative mortality was 0.5% (n = 1), severe morbidity rate was 14.3% (n = 30), and 14 of 132 patients (10.6%) with harvested lymph nodes had metastatic lymph nodes. Tumor size, presence of biliary or pancreatic duct dilatation, and WHO grade 2-3 were independently associated with recurrence. Patients with tumors sized ≤10 mm were disease free at last follow-up. The 1-, 3- and 5-year disease-free survival rates for patients with tumors sized 11-20 mm on preoperative imaging were 95.1%, 91.0%, and 87.3%, respectively. In sNF-PNETs, the presence of biliary or pancreatic duct dilatation or WHO grade 2-3 advocate for surgical treatment. In the remaining patients, a wait-and-see policy might be considered.


Transplantation of human umbilical cord blood cells for the repair of myocardial infarction.
Cell therapy for myocardial disease is a rapidly evolving medical field. A vast and growing body of evidence indicates that cell-based strategies have promising therapeutic potential. Recent clinical and pre-clinical studies demonstrate a varying degree of improvement in cardiac function using different sources of adult stem cell types such as bone marrow-derived progenitor cells and skeletal myoblasts. However, the currently available regimens for cell transplantation into the infarcted myocardium have limitations from practical points of view, in particular the logistics in harvesting donor cells. Accordingly, there is an urgent need for a new source of adult stem cells. Human umbilical cord blood (HUCB) is a good candidate and appears to have several key advantages. HUCB is a viable and practical source of progenitor cells. Compared to bone marrow, HUCB contains a higher number of immature stem/progenitor cells. The aim of our review is to provide an update on the preclinical experiments with emphasis on the possible mechanisms underlying the therapeutic benefits of HUCB cell transplantation for myocardial infarction.


Caregiver outcomes of a dementia care program.
The University of California, Los Angeles Alzheimer's and Dementia Care (ADC) program enrolls persons living with dementia (PLWD) and their family caregivers as dyads to work with nurse practitioner dementia care specialists to provide coordinated dementia care. At one year, despite disease progression, overall the PLWDs' behavioral and depressive symptoms improved. In addition, at one-year, overall caregiver depression, strain, and distress related to behavioral symptoms also improved. However, not all dyads enrolled in the ADC program showed improvement in these outcomes. We conducted a mixed qualitative-quantitative study to explore why some participants did not benefit and what could be changed in this and other similar dementia management programs to increase the percentage who benefit. Semi-structured interviews (N=12) or surveys (N=41) were completed with 53 caregivers by telephone, mail and online. Seven areas for potential program improvement were identified from the first 12 interviews. These included: recommendations that did not match caregivers' perceived care needs, barriers to accessing care and utilizing resources, differing care needs based on stage of dementia, needing services not offered by the ADC, needing more education or support, behavioral recommendations that the caregiver felt did not work, and poor rapport of the dementia expert with caregivers. Despite having been identified as having had no clinical benefit from participating in the program, most caregivers (85%) reported that the program was very beneficial or extremely beneficial. Respondents identified the close, longitudinal relationship and access to a dementia care expert as particularly beneficial. This dichotomy highlights that perceived benefit for most of the interviewed caregivers was not captured with the formal instruments used by the program.


A Comprehensive Literature Review on the Clinical Presentation, and Management of the Pandemic Coronavirus Disease 2019 (COVID-19).
Coronavirus disease 2019 (COVID-19) is a declared global pandemic. There are multiple parameters of the clinical course and management of the COVID-19 that need optimization. A hindrance to this development is the vast amount of misinformation present due to scarcely sourced manuscript preprints and social media. This literature review aims to presents accredited and the most current studies pertaining to the basic sciences of SARS-CoV-2, clinical presentation and disease course of COVID-19, public health interventions, and current epidemiological developments. The review on basic sciences aims to clarify the jargon in virology, describe the virion structure of SARS-CoV-2 and present pertinent details relevant to clinical practice. Another component discussed is the brief history on the series of experiments used to explore the origins and evolution of the phylogeny of the viral genome of SARS-CoV-2. Additionally, the clinical and epidemiological differences between COVID-19 and other infections causing outbreaks (SARS, MERS, H1N1) are elucidated. Emphasis is placed on evidence-based medicine to evaluate the frequency of presentation of various symptoms to create a stratification system of the most important epidemiological risk factors for COVID-19. These can be used to triage and expedite risk assessment. Furthermore, the limitations and statistical strength of the diagnostic tools currently in clinical practice are evaluated. Criteria on rapid screening, discharge from hospital and discontinuation of self-quarantine are clarified. Epidemiological factors influencing the rapid rate of spread of the SARS-CoV-2 virus are described. Accurate information pertinent to improving prevention strategies is also discussed. The penultimate portion of the review aims to explain the involvement of micronutrients such as vitamin C and vitamin D in COVID19 treatment and prophylaxis. Furthermore, the biochemistry of the major candidates for novel therapies is briefly reviewed and a summary of their current status in the clinical trials is presented. Lastly, the current scientific data and status of governing bodies such as the Center of Disease Control (CDC) and the WHO on the usage of controversial therapies such as angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs) (Ibuprofen), and corticosteroids usage in COVID-19 are discussed. The composite collection of accredited studies on each of these subtopics of COVID-19 within this review will enable clarification and focus on the current status and direction in the planning of the management of this global pandemic.


Rediscovering Potential Molecular Targets for Glioma Therapy Through the Analysis of the Cell of Origin, Microenvironment and Metabolism.
Gliomas are the most common type of malignant brain tumors. Despite significant medical advances, gliomas remain incurable and are associated with high mortality. Although numerous biomarkers of diagnostic value have been identified and significant progress in the prognosis of the outcome has been made, the treatment has not been parallelly improved during the last three decades. This review summarizes and discusses three aspects of recent discoveries related to glioma, with the objective to highlight the advantages of glioma-specific drugs targeting the cell of origin, microenvironment, and metabolism. Given the heterogeneous nature of gliomas, various cell populations have been implicated as likely sources of the tumor. Depending on the mutation(s) acquired by the cells, it is believed that neural stem/progenitor cells, oligodendrocyte progenitor cells, mature neurons, and glial cells can initiate cell transformation into a malignant phenotype. The level of tumorigenicity appears to be inversely correlated with the maturation of a given cell population. The microenvironment of gliomas includes non-cancer cells such as immune cells, fibroblasts, and cells of blood vessels, as well as secreted molecules and the extracellular matrix, and all these components play a vital role during tumor initiation and progression. We will discuss in detail how the tumor microenvironment can stimulate and drive the transformation of non-tumor cell populations into tumor-supporting cells or glioma cells. Metabolic reprogramming is a key feature of gliomas and is thought to reflect the adaptation to the increased nutritional requirements of tumor cell proliferation, growth, and survival. Mutations in the IDH gene can shape metabolic reprogramming and may generate some vulnerabilities in glioma cells, such as abnormal lipid metabolism and sensitivity to endoplasmic reticulum stress (ERS). We will analyze the prominent metabolic features of malignant gliomas and the key pathways regulating glioma metabolism. This review is intended to provide a conceptual background for the development of glioma therapies based on the properties of tumor cell populations, microenvironment, and metabolism.


Signet ring cell lobular carcinoma of the breast presenting in a cervicovaginal smear. A case report.
The presence of extragenital malignant cells in cervicovaginal smears is a rare and usually late event in a patient with a long history of cancer. This, to the best of our knowledge, is the first case of breast cancer initially diagnosed on a Pap smear. A 50-year-old woman presented with abdominal distension and weight gain. A Pap smear showed numerous signet ring cells and was diagnosed as signet ring cell adenocarcinoma, most likely metastatic from the breast or stomach. Subsequent evaluation revealed bilateral adnexal masses and inguinal lymphadenopathy, leading to hysterectomy and bilateral salpingo-oophorectomy. The ovaries, corpus and cervix were involved by signet ring cell carcinoma. The metastatic tumor proved to be positive for CK7, CEA, estrogen receptor and progesterone receptors and negative for CK20. Despite the absence of a discrete palpable breast mass, a mammogram was recommended based on these results, and an ensuing breast biopsy showed the presence of an infiltrating lobular carcinoma. Lobular carcinoma of the breast may present in a cervicovaginal smear. Correct interpretation of signet ring cells as metastatic, most likely from the breast or stomach, is helpful in guiding management.


Radiation dose and image quality of CT fluoroscopy with partial exposure mode.
The present study aimed to evaluate the scan technique of computed tomography (CT)-guided puncture procedures using partial exposure mode (PEM) on the radiation dose of the operator's hand and image quality. Radiation dose was evaluated using three types of scanning methods: one-shot scan (OS), OS with a bismuth shield added (OSBismuth), and a half-scan (i.e., PEM) capable of an adjustable exposure angle. Dose evaluation was performed using a torso phantom, while a circular phantom simulating the liver parenchyma and lesions was used for image quality evaluation. For each scanning method, four measurements were made to determine the radiation dose to the operator's hand and the dose distribution on the surface of the patient's torso; the output-dose profile was determined from five measurements. Image quality was evaluated in terms of contrast and contrast-to-noise ratio (CNR). Analysis of variance (ANOVA) or Friedman test were used for comparison between groups as appropriate. The post hoc tests were Tukey's honestly difference (HSD) test for parametric data or Wilcoxon signed rank test with Bonferroni correction for nonparametric data. The PEM yielded a radiation dose to the operator's hand that was 84% (0.35 vs. 2.33 mGy) lower than that of the OS. The dose to the patient's torso was reduced by 35% and 68% for the OSBismuth and PEM, respectively, relative to that of the OS. Compared with the CNR of the other two scanning methods (OS, 2.9±0.1; OSBismuth, 2.9±0.1), the PEM increased the standard deviation and decreased the CNR (2.1±0.04, Tukey's HSD, P < 0.001 for all). Images acquired with PEM showed visibility equivalent to that of other scanning methods when window conditions were adjusted. This study demonstrated that CT-guided puncture procedure using PEM effectively reduces the operator's exposure to radiation while minimizing image quality deterioration.


Isolation, structural characterization, and bioactivities of neutral polysaccharides from Zizania latifolia.
The swollen culm (also known as Jiaobai) of Zizania latifolia is formed by the smut Ustilago esculenta invades the Z. latifolia. The new tissue formed due to the symbiotic relationship has entices the attention of researchers to study its polysaccharide structure along with biological evaluation. Five fractions of polysaccharides were obtained owing to hot water extraction, alcoholic precipitation, and chromatographic purification. Bioactivity assays showed that ZLPs have good antioxidant, hypoglycemic activities and protective activity against oxidative damage. The ZLP-1 and ZLP-2 were determined to be neutral polysaccharides with high purity, exhibiting propitious bioactivity, consequently they were subjected to indispensable structural characterization. These results showed that ZLP-1 has molecular weight (Mw) of 103 kDa and glucose (Glc) (76.68 %) as the primary monosaccharide; the ZLP-2 has Mw of 122 kDa and galactose (Gal) (41.04 %) and arabinose (Ara) (27.12 %). Structural elucidation by methylation and nuclear magnetic resonance (NMR) analysis suggested ZLP-1 is a glucan, with →3)-β-Glcp-(1→3)-β-Glcp-(1→4)-β-Glcp-(1→4)-β-Glcp-(1→3,6)-β-Galp-(1→3)-β-Glcp-(1→ as the mainchain and the terminal Araf and Glcp; the ZLP-2 is a Galactoxylan, with →3,4)-β-xylp-(1→3)-β-Galp-(1→3,6)-β-Galp-(1→3,6)-β-Galp-(1→ as the mainchain and the terminal Araf and Glcp. The structural arrangements provide a chemical basis for understanding the nutritional and pharmacological activities of polysaccharides from Zizania latifolia.


Rhythm of Life Aid (ROLA): an integrated sensor system for supporting medical staff during cardiopulmonary resuscitation (CPR) of newborn infants.
During the stress of cardiopulmonary resuscitation (CPR), it is difficult to maintain the right rhythm and correct ratio of insufflations to chest compressions and to exert the compressions at a constant pressure. In this paper, we propose and demonstrate an integrated sensor system-the "Rhythm of Life Aid" (ROLA) to support medical staff during CPR of newborn infants. The design concept is based on interactive audio and visual feedback with consideration of functionalities and user friendliness. A prototype ROLA device is built, consisting of a transparent foil integrated with pressure sensor and electroluminescent foil actuators for indication of the exerted chest compression pressure, as well as an audio box to generate distinctive sounds as audio guidance for insufflations and compressions. To evaluate the performance of the ROLA device, a sensory mannequin and a dedicated software interface are implemented to give immediate feedback and record data for further processing. Tests of the ROLA prototype on the sensory mannequin by ten pairs of a doctor and a nurse at Máxima Medical Centre in Veldhoven, The Netherlands show that the use of ROLA device achieves a more constant rhythm and pressure of chest compressions during CPR of newborn infants.


An overlapping reading frame in the PRNP gene encodes a novel polypeptide distinct from the prion protein.
The prion protein gene PRNP directs the synthesis of one of the most intensively studied mammalian proteins, the prion protein (PrP). Yet the physiological function of PrP has remained elusive and has created controversies in the literature. We found a downstream alternative translation initiation AUG codon surrounded by an optimal Kozak sequence in the +3 reading frame of PRNP. The corresponding alternative open reading frame encodes a polypeptide termed alternative prion protein (AltPrP) with a completely different amino acid sequence from PrP. We introduced a hemagglutinin (HA) tag in frame with AltPrP in PrP cDNAs from different species to test the expression of this novel polypeptide using anti-HA antibodies. AltPrP is constitutively coexpressed with human, bovine, sheep, and deer PrP. AltPrP is localized at the mitochondria and is up-regulated by endoplasmic reticulum stress and proteasomal inhibition. Generation of anti-AltPrP antibodies allowed us to test for endogenous expression of AltPrP in wild-type human cells expressing PrP. By transfecting cells with siRNA against PrP mRNA, we repressed expression of both PrP and AltPrP, confirming endogenous expression of AltPrP from PRNP. AltPrP was also detected in human brain homogenate, primary neurons, and peripheral blood mononuclear cells. These results demonstrate an unexpected function for PRNP, which, in addition to plasma membrane-anchored PrP, also encodes a second polypeptide termed AltPrP.


[Dislocation of total hip endoprosthesis with special reference to various techniques].
1238 primary total hip replacements for arthritis were performed in our hospital from 1980 until 1988. 26 dislocations (2.1%) were registered during this period. No differences became obvious regarding age, sex, type of prosthesis and different concepts of postoperative treatment. After the posterior approach dislocations occurred in 18 (3.1%) of the cases, 8 dislocations (1.2%) were found after the transgluteal approach. The dislocation rate was significantly higher for the posterior approach. Derotation braces were not able to decrease the risk of redislocation. Most of the dislocations happened during the first postoperative week. The most frequent occasions were rotation of the operated leg while lying in bed and deep sitting positions. Performing the posterior approach for primary total hip arthroplasty the surgeon has to realize the higher dislocation rate.


Activation domain-specific and general transcription stimulation by native histone acetyltransferase complexes.
Recent progress in identifying the catalytic subunits of histone acetyltransferase (HAT) complexes has implicated histone acetylation in the regulation of transcription. Here, we have analyzed the function of two native yeast HAT complexes, SAGA (Spt-Ada-Gcn5 Acetyltransferase) and NuA4 (nucleosome acetyltransferase of H4), in activating transcription from preassembled nucleosomal array templates in vitro. Each complex was tested for the ability to enhance transcription driven by GAL4 derivatives containing either acidic, glutamine-rich, or proline-rich activation domains. On nucleosomal array templates, the SAGA complex selectively stimulates transcription driven by the VP16 acidic activation domain in an acetyl coenzyme A-dependent manner. In contrast, the NuA4 complex facilitates transcription mediated by any of the activation domains tested if allowed to preacetylate the nucleosomal template, indicating a general stimulatory effect of histone H4 acetylation. However, when the extent of acetylation by NuA4 is limited, the complex also preferentially stimulates VP16-driven transcription. SAGA and NuA4 interact directly with the VP16 activation domain but not with a glutamine-rich or proline-rich activation domain. These data suggest that recruitment of the SAGA and NuA4 HAT complexes by the VP16 activation domain contributes to HAT-dependent activation. In addition, extensive H4/H2B acetylation by NuA4 leads to a general activation of transcription, which is independent of activator-NuA4 interactions.


Exogenous nucleosides are required for the morphogenesis of the human filarial parasite Brugia malayi.
The nematode parasites Wuchereria bancrofti, Brugia malayi, and B. timori cause a human disease known as lymphatic filariasis, which afflicts approximately 120 million people worldwide. The parasites enter the human host from the mosquito as L3 or infective larvae and subsequently differentiate through 2 molts. In this communication, I report that B. malayi and B. pahangi depend on an exogenous source of at least 1 purine and 1 pyrimidine nucleoside to complete the L3 to L4 molt. The requirement for exogenous nucleosides opens the door for possible chemotherapeutic intervention.


Non-testosterone management of male hypogonadism: an examination of the existing literature.
Testosterone deficiency is defined as a total testosterone level <300 ng/dL confirmed on two early morning lab draws. Testosterone therapy has historically been offered to men with symptomatic testosterone deficiency in the form of injections, gels, or pellets. However, these treatments are invasive or have undesirable effects including the risk of drug transference. Additionally, testosterone therapy has been associated with increases in hematocrit and controversy remains regarding the risk of cardiovascular and thromboembolic events while on testosterone therapy. As such, much interest has recently been focused on alternative treatment options for testosterone deficiency in the form of orally-administered medications with more favorable side effect profiles. Lifestyle modifications and varicocelectomy have been shown to raise endogenous testosterone production. Similarly, SERMs and aromatase inhibitors (AIs) have been shown to raise testosterone levels safely and effectively. Human chorionic gonadotropin (hCG) remains the only FDA-approved non-testosterone treatment option for testosterone deficiency in men. However, this medication is expensive and requires patient-administered injections. Over the counter herbal supplements and designer steroids remain available though they are poorly studied and are associated with the potential for abuse as well as increased hepatic and cardiovascular risks. This review aims to discuss the existing treatment alternatives to traditional testosterone therapy, including efficacy, safety, and side effects of these options. The authors suggest that the SERM clomiphene citrate (CC) holds the greatest promise as a non-testosterone treatment option for testosterone deficiency.


Crystallization and preliminary X-ray diffraction analysis of human IL-22 bound to its soluble decoy receptor IL-22BP.
Interleukin-22 (IL-22) is a pleiotropic cytokine that is involved in inflammatory responses. Human IL-22 was incubated with its soluble decoy receptor IL-22BP (IL-22 binding protein) and the IL-22-IL-22BP complex was crystallized in hanging drops using the vapour-diffusion method. Suitable crystals were obtained from polyethylene glycol solutions and diffraction data were collected to 2.75 A resolution. The crystal belonged to the tetragonal space group P4(1), with unit-cell parameters a = b = 67.9, c = 172.5 A, and contained two IL-22-IL-22BP complexes per asymmetric unit.


[Percutaneous effects of iodine inhibit the development of experimental silicosis].
Experiments on white rats proved that the silicotic pulmonary changes slowed with the tails periodically immersed into iodine solution. Those pulmonary changes were due to inhalation of quartzite dust and especially due to intratracheal administration of standardized quartz dust DQ12. Influenced by inhalation of dust containing quartz, the rats demonstrated characteristic alterations in cytologic features of bronchial and alveolar lavage water. The "iodine baths" also declined those alterations, that may prove higher resistance of pulmonary macrophages to cytotoxic effects of quartz. This hypothesis finds a support in experiments with culture of rat peritoneal macrophages. If incubated in a medium with low iodine concentrations and subsequently washed off, the macrophages demonstrate lower incidence of cytotoxic effects due to the next incubation with particles of DQ12. The macrophage's higher resistance against cytotoxic agents is believed to result directly in antisilicotic effect of iodine, so "iodine baths" could be recommended for pathogenetic therapy and medical prophylaxis of silicosis.


Ultrasound-induced microbubble coalescence.
We studied the interaction of ultrasound contrast agent bubbles coated with a layer of lipids, driven by 0.5 MHz ultrasound. High-speed photography on the submicrosecond timescale reveals that some bubbles bounce off each other, while others show very fast coalescence during bubble expansion. This fast coalescence cannot be explained by dissipation-limited film drainage rates. We conclude that the lipid shell ruptures upon expansion, exposing clean free bubble interfaces that support plug flow profiles in the film and inertia-limited drainage whose time scales match those of the observed coalescence.


Impact of switching from different treatment regimens to a fixed-dose combination pill (polypill) in patients with cardiovascular disease or similarly high risk.
Aims Cardiovascular fixed-dose combination pills, or polypills, may help address the widespread lack of access and adherence to proven medicines. Initiation of polypill-based care typically entails switching from current separately taken medications. Given the heterogeneity in usual care, there is interest in the impact of polypill treatment across different patterns of prior medication regimen. Methods A total of 2004 participants with established cardiovascular disease or estimated 5-year cardiovascular risk of over 15% were randomised to polypill-based treatment (aspirin 75 mg, simvastatin 40 mg, lisinopril 10 mg and either atenolol 50 mg or hydrochlorothiazide 12.5 mg) or usual care. Baseline medications were classified by potency relative to polypill components. Estimated cardiovascular risk reduction was calculated by combining risk factor changes with results seen in meta-analyses of previous randomised trials. Results For cholesterol reduction conferred by polypills, there was a dose response across baseline statin groups, with mean low-density lipoprotein (LDL)-cholesterol differences of 0.37, 0.22, 0.14 and 0.07 mmol/L among patients taking no statin, less potent, equipotent and more potent statin at baseline, respectively. Similarly there were differences in mean systolic BP of 5.4, 6.2, 3.3 and 1.8 mmHg among patients taking 0, 1, 2 or 3 BP-lowering agents. Among patients taking more potent statins at baseline, there was no significant difference in LDL-cholesterol but there were benefits for BP and aspirin adherence. Similar results were seen among patients taking 3 BP-lowering agents at baseline. Switching to a polypill-based strategy resulted in estimated cardiovascular relative risk reductions across a wide range of usual care patterns of antiplatelet, statin and BP-lowering therapy prescribing. Conclusion Adherence benefits from switching to a polypill resulted in risk factor changes that were at least as good as usual care across a wide variety of treatment patterns, including equally potent or more potent regimens. The benefits of switching to polypill-based care were greatest among those stepped up from partial treatment or less potent treatment.


Wick catheter in evaluating and treating compartment syndromes.
We prospectively analyzed 45 patients with suspected compartment syndromes involving 55 extremities to determine the role of the wick catheter in their management. The wick catheter technic allows the continuous monitoring of interstitial pressure and provides an objective assessment of compartment pressure. Indications for catheter use, technics for catheter preparation and insertion, and guidelines for the timing of fasciotomy are presented. Clinical evaluation of every extremity injury must be tempered by suspicion and vigilance to detect compartment syndromes early enough to prevent ischemic contracture. Providing reliable and accurate pressure determinations without significant morbidity, the wick allows continuous monitoring of interstitial compartmental pressure and objective indications for fasciotomy.


A Feasibility and Acceptability Trial of Social Cognitive Therapy in Early Psychosis Delivered Through a Virtual World: The VEEP Study.
Addressing specific social cognitive difficulties is an important target in early psychosis and may help address poor functional outcomes. However, structured interventions using standard therapy settings including groups suffer from difficulties in recruitment and retention. To address these issues, we aimed to modify an existing group social cognitive intervention entitled 'Social Cognition and Interaction Training' (SCIT) to be delivered through a virtual world environment (Second Life ©). A single arm nonrandomized proof-of-concept trial of SCIT-VR was conducted. Five groups of three to five individuals per group were recruited over 6 months. Eight sessions of SCIT-VR therapy were delivered through the virtual world platform Second Life© over a 5-week intervention window. Feasibility was examined using recruitment rates and retention. Acceptability was examined using qualitative methods. Secondary outcomes including social cognitive indices, functioning, and anxiety were measured pre- and postintervention. The SCIT-VR therapy delivered was feasible (36% consent rate and 73.3% intervention completion rate), acceptable (high overall postsession satisfaction scores) and safe (no serious adverse events), and had high levels of participant satisfaction. Users found the environment immersive. Prepost changes were found in emotion recognition scores and levels of anxiety. There were no signs of clinical deterioration on any of the secondary measures. This proof-of-concept pilot trial suggested that delivering SCIT-VR through a virtual world is feasible and acceptable. There were some changes in prepost outcome measures that suggest the intervention has face validity. There is sufficient evidence to support a larger powered randomized controlled trial. ISRCTN, identifier 41443166.


Application of local heat induces capillary recruitment in the Pallid bat wing.
Skin blood flow increases in response to local heat due to sensorineural and nitric oxide (NO)-mediated dilation. It has been previously demonstrated that arteriolar dilation is inhibited with NO synthase (NOS) blockade. Flow, nonetheless, increases with local heat. This implies that the previously unexamined nonarteriolar responses play a significant role in modulating flow. We thus hypothesized that local heating induces capillary recruitment. We heated a portion (3 cm2) of the Pallid bat wing from 25 degrees C to 37 degrees C for 20 min, and measured changes in terminal feed arteriole (approximately 25 microm) diameter and blood velocity to calculate blood flow (n = 8). Arteriolar dilation was reduced with NOS and sensorineural blockade using a 1% (wt/vol) NG-nitro-L-arginine methyl ester (L-NAME) and 2% (wt/vol) lidocaine solution (n = 8). We also measured changes in the number of perfused capillaries, and the time precapillary sphincters were open with (n = 8) and without (n = 8) NOS plus sensorineural blockade. With heat, the total number of perfused capillaries increased 92.7 +/- 17.9% (P = 0.011), and a similar increase occurred despite NOS plus sensorineural blockade 114.4 +/- 30.0% (P = 0.014). Blockade eliminated arteriolar dilation (-4.5 +/- 2.1%). With heat, the percent time precapillary sphincters remained open increased 32.3 +/- 6.0% (P = 0.0006), and this increase occurred despite NOS plus sensorineural blockade (34.1 +/- 5.8%, P = 0.0004). With heat, arteriolar blood flow increased (187.2 +/- 28.5%, P = 0.00003), which was significantly attenuated with NOS plus sensorineural blockade (88.6 +/- 37.2%, P = 0.04). Thus, capillary recruitment is a fundamental microvascular response to local heat, independent of arteriolar dilation and the well-documented sensorineural and NOS mechanisms mediating the response to local heat.


A FQHPSFI peptide selectively binds to LPS-activated alveolar macrophages and inhibits LPS-induced MIP-2 production.
The goal of this study was to identify peptides selectively binding to lipopolysaccharide (LPS)-activated alveolar macrophages (AMs) and to characterize their effects on the production of LPS-induced cytokines. A phage display library was sequentially screened by binding phages to unmanipulated AMs and then to LPS-activated AMs. Individual phage clones were identified by cell-based ELISA. Positive phage clones were characterized by DNA sequencing and bioinformatics analysis. Binding specificity of the selected phage to LPS-activated AMs was tested using immunofluorescent staining. The selected candidate peptide was chemically synthesized to determine whether it could modulate LPS-induced cytokine production in AMs. Twenty-two out of 40 phage clones selected randomly after four rounds of biopanning bound selectively to LPS-activated AMs, and 12 of them displayed novel peptides. A phage clone displaying FQHPSFI peptide bound effectively to LPS-activated AMs, but not to other cells tested. Furthermore, the synthetic FQHPSFI peptide, but not seven point mutants tested, competitively inhibited the binding of the phage clone to LPS-activated AMs. Importantly, the FQHPSFI peptide significantly inhibited LPS-stimulated microphage inflammatory protein 2 (MIP-2) production in vitro. Our data demonstrate that phage display technology is a powerful tool for the identification of bioactive peptides. The identified FQHPSFI peptide may be used for the modulation of LPS-stimulated MIP-2 production in AMs.


SPARC mediates early extracellular matrix remodeling following myocardial infarction.
Secreted protein, acidic, and rich in cysteine (SPARC) is a matricellular protein that functions in the extracellular processing of newly synthesized collagen. Collagen deposition to form a scar is a key event following a myocardial infarction (MI). Because the roles of SPARC in the early post-MI setting have not been defined, we examined age-matched wild-type (WT; n=22) and SPARC-deficient (null; n=25) mice at day 3 post-MI. Day 0 WT (n=28) and null (n=20) mice served as controls. Infarct size was 52 ± 2% for WT and 47 ± 2% for SPARC null (P=NS), indicating that the MI injury was comparable in the two groups. By echocardiography, WT mice increased end-diastolic volumes from 45 ± 2 to 83 ± 5 μl (P < 0.05). SPARC null mice also increased end-diastolic volumes but to a lesser extent than WT (39 ± 3 to 63 ± 5 μl; P < 0.05 vs. day 0 controls and vs. WT day 3 MI). Ejection fraction fell post-MI in WT mice from 57 ± 2 to 19 ± 1%. The decrease in ejection fraction was attenuated in the absence of SPARC (65 ± 2 to 28 ± 2%). Fibroblasts isolated from SPARC null left ventricle (LV) showed differences in the expression of 22 genes encoding extracellular matrix and adhesion molecule genes, including fibronectin, connective tissue growth factor (CTGF; CCN2), matrix metalloproteinase-3 (MMP-3), and tissue inhibitor of metalloproteinase-2 (TIMP-2). The change in fibroblast gene expression levels was mirrored in tissue protein extracts for fibronectin, CTGF, and MMP-3 but not TIMP-2. Combined, the results of this study indicate that SPARC deletion preserves LV function at day 3 post-MI but may be detrimental for the long-term response due to impaired fibroblast activation.


A systematic review of genetic polymorphisms and breast cancer risk.
Studies investigating the relationship between common genetic variants and cancer risk are being reported with rapidly increasing frequency. We have identified 46 published case-control studies that have examined the effect of common alleles of 18 different genes on breast cancer risk. Of these, 12 report statistically significant associations, none of which were reported by more than one study. However, many of the studies were small: 10 of the 46 had 80% power or greater to detect a rare allele homozygote relative risk <2.5. We therefore combined the results of individual studies to obtain more precise estimates of risk. Statistically significant differences in genotype frequencies were found in three case-control comparisons of unselected cases. These were for CYP19 (TTTA)n polymorphism [(TTTA)10 carrier odds ratio (OR) = 2.33; P = 0.002], the GSTP1 Ile105Val polymorphism (Val carrier OR = 1.60; P = 0.02), and the TP53 Arg72Pro polymorphism (Pro carrier OR = 1.27; P = 0.03). In addition, the GSTM1 gene deletion was found to be significantly associated with postmenopausal breast cancer (null homozygote OR = 1.33; P = 0.04). There was also some evidence that homozygotes for the PR PROGINS allele are protected against breast cancer, although this result was of borderline statistical significance. For polymorphisms in BRCA1, COMT, CYP17, CYP1A1, NAT1, and NAT2, the best estimate of risk either from the individual studies or the meta-analyses was sufficiently precise to exclude a relative risk of 1.5 or greater. For the polymorphisms in EDH17B2, ER, CYP2D6, CYP2E1, GSTT1, HSP70, and TNFalpha, the risk estimates, although nonsignificant, were insufficiently precise to exclude a moderate risk (>1.5). Precise estimation of the risks associated with these and other as yet untested genes, as well as investigation of more complex risks arising from gene-gene and gene-environment interactions, will require much larger studies.