The emerging threat of schistosomiasis spread in Pakistan.
Schistosomiasis is among the thirteen neglected tropical diseases of the world. While prevalent in a number of countries, it has only rarely been reported in Pakistan. Here we report a 25 year old male who acquired the infection during travel to Malawi and presented with haematuria and dysuria. He was successfully treated with praziquantel. The possibility of schistosomiasis becoming endemic in the country is discussed. A number of risk factors are present including dams, irrigation, increased travel and geographical proximity to endemic countries. The local presence of at least one snail species of potential hosts for Schistosoma mansoni is confirmed. We see that schistosomiasis endemicity is a possible threat in Pakistan. Solutions to prevent this include reducing travel to endemic areas, prompt recognition and treatment of cases, and health education.


Requirements for pYXXM motifs in Cbl for binding to the p85 subunit of phosphatidylinositol 3-kinase and Crk, and activation of atypical protein kinase C and glucose transport during insulin action in 3T3/L1 adipocytes.
Cbl is phosphorylated by the insulin receptor and reportedly functions within the flotillin/CAP/Cbl/Crk/C3G/TC10 complex during insulin-stimulated glucose transport in 3T3/L1 adipocytes. Cbl, via pYXXM motifs at tyrosine-371 and tyrosine-731, also activates phosphatidylinositol (PI) 3-kinase, which is required to activate atypical protein kinase C (aPKC) and glucose transport during thiazolidinedione action in 3T3/L1 and human adipocytes [Miura et al. (2003) Biochemistry 42, 14335-14341]. Presently, we have examined the importance of Cbl in activating PI 3-kinase and aPKC during insulin action in 3T3/L1 adipocytes by expressing Y371F and Y731F Cbl mutants, which nullify pYXXM binding of Cbl to SH2 domains of downstream effectors. Interestingly, these mutants inhibited insulin-induced increases in (a) binding of Cbl to both Crk and the p85 subunit of PI 3-kinase, (b) activation of Cbl-dependent PI 3-kinase, (c) activation and translocation of aPKC to the plasma membrane, (d) translocation of Glut4 to the plasma membrane, (e) and glucose transport. Importantly, coexpression of wild-type Cbl reversed the inhibitory effects of Cbl mutants. In contrast to Cbl-dependent PI 3-kinase, Cbl mutants did not significantly inhibit the activation of PI 3-kinase by IRS-1, which is also required during insulin action. Our findings suggest that (a) Cbl uses pYXXM motifs to simultaneously activate PI 3-kinase and Crk/C3G/TC10 pathways and (b) Cbl, along with IRS-1, functions upstream of PI 3-kinase and aPKCs during insulin-stimulated glucose transport in 3T3/L1 adipocytes.


[Dopamine modification of the Ca-component of the action potential in the neuron soma of the mollusk L. stagnalis].
Dopamine has been found to decrease reversibly the action potential rising phase in identified L. stagnalis neurones. Using voltage-clamp and intracellular dialysis techniques it is shown that dopamine inhibits electroexcitable Ca-current, and changes in Ca-current determine those in the action potential shape. Serotonin and adrenaline influence the Ca-current in a similar way as dopamine does. Inhibition of Ca-conductance is found not to be related to possible effect of these neuromediators on intracellular level of free Ca ions or cyclic AMP.


[Peculiarities of surgical care in case of open injuries of limbs in emergency situations in peacetime].
It was done the comparative analysis of treatment results of casualties with open injuries of limbs in emergency situations in peacetime. It was determined that traditional approach of field surgery is unacceptable for this group of casualties. It is connected with limitations of evacuation and high frequency of complications. The developed modified surgical protocol permits not only to provide specialized care to casualties with soft tissue trauma and open fracture of limbs but also to reduce frequency of deep suppuration in 1.9 times. Also it allows to decrease number of dressings for one patient and period of the wound defect preparation to reconstructive plastic surgeries in 2.6 and 1.5 times respectively.


Cellular localization of glutathione S-transferases in retinas of control and lead-treated rats.
The glutathione S-transferases (GSTs) constitute a family of cytosolic isoenzymes that are involved in the detoxication of electrophilic xenobiotics. The purpose of this investigation was to determine the concentration and cellular distribution of the various classes of cytosolic GSTs in the retina of control and triethyl lead-treated rats and thereby reveal mechanisms by which the cells are protected from damage by lead and other toxicants. The regional and cellular distribution of cytosolic GSTs in rat retina of control and lead-treated animals was studied by immunohistochemistry. Enzyme activity was determined by a spectrophotometric assay. The GST subunit distribution of the entire retina of control and lead-treated animals was determined and quantified by reverse-phase high-performance liquid chromatography (HPLC). Polyclonal antibodies against mu-class Yb1 and Yb2 GSTs were primarily and strongly reactive with Müller cells and their processes. Anti-Yb1 also reacted with photoreceptor outer segments. Antibodies against two alpha-class GSTs (Ya and Yk) were strongly reactive with Müller cells and their cell processes. Antibodies against Yp and Yc GSTs were reactive with amacrine cells and their processes, and anti-Yp antibodies were reactive against retinal ganglion cells. Treatment of rats with triethyl lead caused diminished reactions of the antibodies against Yb1 and Yp GSTs and increased reactions of anti-Ya with its retinal targets, whereas the total GST activity did not change significantly. The positive reaction between the amacrine neuronal cells of retina and the anti-Yp and anti-Yc class antisera broadens the class of neurons that contains GST enzymes protective against toxicant insult. It also has been shown that Müller cells are strongly immuno-positive for Yb1 and Yb2 GST. Because these phagocytic cells are in contact with the vitreous fluid and proximate to pigmented epithelial layer of the eye, these GSTs may protect the cells from toxicants accumulated from this fluid.


Angioplasty and stenting of the extracranial carotid arteries.
To study the feasibility and safety of stent-supported angioplasty in the treatment of atherosclerotic stenoses of the extracranial carotid arteries. Carotid angioplasty was attempted in 174 arteries (163 patients: 126 males; mean age: 71 +/- 10 years, range 47 to 93). Mean lesion length was 15.1 +/- 4.1 mm, and mean percent stenosis was 83.8% +/- 7.3% (reference diameter 5.8 +/- 0.7 mm). The majority (106, 65%) were asymptomatic (51% of all patients had severe coronary disease, 32% had peripheral vascular diseases). Patients underwent independent neurological examination, computed tomography, duplex ultrasonography, and angiography preprocedurally, 24 hours after the procedure, and at 6-month follow-up intervals. Most (142, 82%) carotid arteries were treated without cerebral protection, but a protective triple coaxial catheter was used in 32 (18%) patients. Stents (primarily Palmaz and Wallstent) were deployed routinely in all cases; 18% were implanted without predilation. Immediate technical success was 173 of 174 (99.4%) (1 access failure referred electively to surgery). Eight (4.6%) neurological complications occurred in the periprocedural period: 3 transient ischemic attacks, 2 minor strokes, and 3 major strokes (1 amaurosis and 2 hemiplegias). Two major complications developed despite cerebral protection. There were no deaths or myocardial infarctions and only 3 cervical access site hematomas. Over a mean 12.7 +/- 9.2 month follow-up (range 1 to 36), no ipsilateral neurological complications have been seen. There were 4 (2.3%) restenoses (3 redilated, 1 treated medically) and 1 mild Palmaz stent compression, all found within the first 6 months. Primary and secondary patencies at 3 years are 96% and 99%, respectively. Angioplasty with routine stenting seems feasible and safe for treating certain types of carotid stenoses even in high-surgical risk patients; however, randomized trials are necessary before this treatment can be offered as an alternative to endarterectomy.


The emerging role of Klotho in clinical nephrology.
Klotho is highly expressed in the kidney and a soluble form of Klotho functions as an endocrine substance that exerts multiple actions including the modulation of renal solute transport and the protection of the kidney from a variety of insults in experimental models. At present, the Klotho database is still largely preclinical, but the anticipated forthcoming impact on clinical nephrology can be immense. This manuscript puts these potentials into perspective for the clinician. There is renal and systemic Klotho deficiency in both acute kidney injury (AKI) and chronic kidney disease (CKD). Klotho plummets very early and severely in AKI and represents a pathogenic factor that exacerbates acute kidney damage. In CKD, Klotho deficiency exerts a significant impact on progression of renal disease and extra renal complications. In AKI, soluble Klotho levels in plasma and/or urine may serve as an early biomarker for kidney parenchymal injury. Restoration by exogenous supplementation or stimulation of endogenous Klotho may prevent and/or ameliorate kidney injury and mitigate CKD development. In CKD, Klotho levels may be an indicator of early disease and predict the rate of progression, and presence and severity of soft tissue calcification. The correction of Klotho deficiency may delay progression and forestall development of extra renal complications in CKD. Rarely does one find a molecule with such broad potential applications in nephrology. Klotho can possibly emerge on the horizon as a candidate for an unprecedented sole biomarker and intervention. Nephrologists should monitor the progress of the preclinical studies and the imminently emerging human database.


Clinical utility of plasma progesterone and blood and plasma glucose concentrations in predicting parturition in Holstein cows.
An accurate, practical, and low-cost method for predicting parturition is urgently needed in the dairy industry. The objective of this study was to evaluate changes in plasma progesterone concentration ([prog]) and glucose concentration in whole blood ([gluc]b) and plasma ([gluc]p) as predictors of parturition within 6, 12, and 24 h in primiparous and multiparous Holstein cows. Blood samples were obtained daily at approximately 0900 h from 34 primiparous and 72 multiparous Holstein cows in late gestation and the time of calving recorded to the nearest hour. Plasma [prog] was measured using an ELISA, and [gluc]b and [gluc]p using a low-cost point-of-care glucose meter. The optimal cut-point for predicting parturition was determined using binomial logistic regression with general estimating equations, because the data set consisted of repeated measures for each cow. Diagnostic test performance was evaluated by comparing the area under the receiver operating characteristic curve (AUC) and calculating the sensitivity, specificity, and κ at the optimal cut-point for predicting parturition. Plasma [prog] was the most accurate predictor of parturition within 24 h (AUC = 0.96) and 12 h (AUC = 0.93), whereas [gluc]b was the most accurate predictor of parturition within 6 h (primiparous, AUC = 0.96; multiparous, AUC = 0.86). We conclude that a decrease in plasma [prog] is currently the most accurate test for predicting calving within 24 h. Measurement of [gluc]b is a promising new test for the cow-side prediction of parturition in dairy cows due to its accuracy, practicality, and low cost.


Self-Assembled Metal-Organic Complexes for Thermally Reversible Permeabilization of Cell Membranes.
Natural and synthetic membrane active molecules increase the permeability of cell membranes. This can help cells combat multidrug efflux pumps as well as improve signaling and transfection. In this work, thermoresponsive metal-organic complexes (MOCs) have been constructed to transport cell impermeable cargo across the membrane through a pore-aiding assembly. These MOCs can be reversibly controlled as they collapse when the temperature is increased and are simultaneously regenerated when the system is cooled down to room temperature. These ON/OFF molecular valves can be potentially used to overcome multidrug resistance (MDR) in cancer cells and as building blocks for artificial cells.


A legume biofortification quandary: variability and genetic control of seed coat micronutrient accumulation in common beans.
Common beans (Phaseolus vulgaris L.), like many legumes, are rich in iron, zinc, and certain other microelements that are generally found to be in low concentrations in cereals, other seed crops, and root or tubers and therefore are good candidates for biofortification. But a quandary exists in common bean biofortification: namely that the distribution of iron has been found to be variable between the principal parts of seed; namely the cotyledonary tissue, embryo axis and seed coat. The seed coat represents ten or more percent of the seed weight and must be considered specifically as it accumulates much of the anti-nutrients such as tannins that effect mineral bioavailability. Meanwhile the cotyledons accumulate starch and phosphorus in the form of phytates. The goal of this study was to evaluate a population of progeny derived from an advanced backcross of a wild bean and a cultivated Andean bean for seed coat versus cotyledonary minerals to identify variability and predict inheritance of the minerals. We used wild common beans because of their higher seed mineral concentration compared to cultivars and greater proportion of seed coat to total seed weight. Results showed the most important gene for seed coat iron was on linkage group B04 but also identified other QTL for seed coat and cotyledonary iron and zinc on other linkage groups, including B11 which has been important in studies of whole seed. The importance of these results in terms of physiology, candidate genes and plant breeding are discussed.


GODDESS: A Goal-Directed Decision Structuring System.
This paper describes an operational version of a computerized, domain-independent, decision support system which is based on a novel, goal-directed structure for representing decision problems. The structure allows the user to state relations among aspects, effects, conditions, and goals, in addition to actions and states which are the basic components of the traditional decision tree approach. The program interacts with the user in a stylized English-like dialogue, starting with the stated objectives and proceeding to unravel the more detailed means by which these objectives can be realized. At any point in time, the program focuses the user's attention on the issues which are most crucial to the problem at hand. The structure used is more compatible with the way people encode knowledge about problems and actions, and therefore promises to offer the following advantages: 1) judgments and beliefs issued by the user constitute a more valid representation of the user's experience; and 2) the user may be guided toward the discovery of action alternatives he otherwise would not have identified.


High-speed quantum random number generation by measuring phase noise of a single-mode laser.
We present a high-speed random number generation scheme based on measuring the quantum phase noise of a single-mode laser operating at a low intensity level near the lasing threshold. A delayed self-heterodyning system has been developed to measure the random phase fluctuation. By actively stabilizing the phase of the interferometer, a random number generation rate of 500 Mbit/s has been demonstrated and the generated random numbers have passed all the DIEHARD tests.


Odontometric sexual dimorphism: a sibling correlation.
Teeth form an excellent material for anthropological, genetic, odontologic and forensic investigations. The aim of this study was to establish the genetic control of sexual dimorphism in tooth size amongst siblings of Goan children in age range of 14-22 years. Twenty-two sibling pairs were selected (22 males and 22 females) to assess genetic control of sexual dimorphism in tooth size. Alginate impressions were obtained for maxillary and mandibular arches and study models were prepared. Measurements were done using Zoom Digimatic Vernier Calipers with a resolution of 0.01 mm. Correlation between mesiodistal and buccolingual tooth sizes amongst siblings was calculated using Pearson's correlation coefficient. A statistically significant association was found between Mesiodistal Widths of Permanent Maxillary Right and Left Second Molars and between Maxillary Right and Left First Premolars amongst sibling pairs. A statistically significant association was also found between Buccolingual Widths of Mandibular Right and Left First Premolars amongst sibling pairs. This statistically significant correlation found amongst siblings establishes a genetic control over sexual dimorphism in these teeth. The genetic basis of sexual dimorphism in human dentition was ascertained as a significant correlation was found between mesio-distal and bucco-lingual widths of premolars between sibling pairs.


A practical approach to using strain echocardiography to evaluate the left ventricle.
Left ventricular (LV) evaluation is the most important use of echocardiography. Speckle tracking strain echocardiography (SE) provides a quantitative regional and global LV assessment, is an independent supplement to wall motion analysis and has been validated over the past 10 years. Despite these facts, SE is not being used routinely, especially in the United States. SE can generate longitudinal, radial, and circumferential strain measurements and LV twist. Although intriguing and potentially useful, these measurements also are confusing, complicated, time consuming, and frequently displayed as difficult-to-interpret wave forms. A pragmatic approach to SE simplifies the suggested method for strain calculation to reduce the time required and enhance reproducibility. With this modification the strain calculations take only 2-4 min. The yield is >80% in all patients. Reproducibility is at least as good as ejection fraction. Longitudinal strain is the most sensitive and reproducible of the various strain measurements, so it is the only strain we record. For simplicity, systolic strain is displayed as a positive number. Lastly, we primarily use a bullseye presentation for peak systolic strain. Many clinical examples are illustrated. However, as with all tests, SE is not perfect; there are limitations and potential false positives, but a practical approach to SE eventually should help make it a part of all echocardiographic examinations.


Clinical features in coronavirus disease 2019 (COVID-19) patients with early clearance and prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
Since the outbreak of coronavirus disease 2019 (COVID-19), the pattern of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA shedding has not been well characterized. In our study, 652 patients in Wuhan Designated Hospital were recruited, and their clinical and laboratory findings were extracted and analyzed. The median duration of SARS-CoV-2 RNA detection was 23 days [interquartile range (IQR), 18 days] from symptom onset. Compared to patients with early viral RNA clearance (<23 days after illness onset), we found that patients with late viral RNA clearance (≥23 days) had a higher proportion of clinical features, as follows: symptoms, including fever, dry cough, and sputum production; comorbidities, including hypertension, chronic kidney disease, uremia, chronic liver disease, anemia, hyperlipidemia, and bilateral lung involvement; complications, such as liver injury; delayed admission to hospital; laboratory parameters at baseline, including higher eosinophils, uric acid, cholesterol, triglycerides, and lower hemoglobin; and less treatment with arbidol, chloroquine, or any antivirals. After generalized linear regression, prolonged SARS-CoV-2 RNA shedding was independently associated with younger age; delayed admission to hospital; symptoms including fever, shivering, and sputum production; comorbidities including hypertension, diabetes, cardiovascular disease, anemia, hyperlipidemia, uremia, and lung involvement; and higher alanine aminotransferase (ALT), uric acid, and cholesterol levels at baseline. In conclusion, the factors mentioned above are associated with the negative conversion of SARS-CoV-2 RNA. A deeper insight into virological dynamics will be helpful for establishing patient discharge and quarantine release criteria.


Machine Learning Assisted Classification of Aluminum Nitride Thin Film Stress via In-Situ Optical Emission Spectroscopy Data.
In this study, we submit a complex set of in-situ data collected by optical emission spectroscopy (OES) during the process of aluminum nitride (AlN) thin film. Changing the sputtering power and nitrogen(N2) flow rate, AlN film was deposited on Si substrate using a superior sputtering with a pulsed direct current (DC) method. The correlation between OES data and deposited film residual stress (tensile vs. compressive) associated with crystalline status by X-ray diffraction spectroscopy (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM) measurements were investigated and established throughout the machine learning exercise. An important answer to know is whether the stress of the processing film is compressive or tensile. To answer this question, we can access as many optical spectra data as we need, record the data to generate a library, and exploit principal component analysis (PCA) to reduce complexity from complex data. After preprocessing through PCA, we demonstrated that we could apply standard artificial neural networks (ANNs), and we could obtain a machine learning classification method to distinguish the stress types of the AlN thin films obtained by analyzing XRD results and correlating with TEM microstructures. Combining PCA with ANNs, an accurate method for in-situ stress prediction and classification was created to solve the semiconductor process problems related to film property on deposited films more efficiently. Therefore, methods for machine learning-assisted classification can be further extended and applied to other semiconductors or related research of interest in the future.


Construction of a 600-kilobase cosmid clone contig and generation of a transcriptional map surrounding the lung cancer tumor suppressor gene (TSG) locus on human chromosome 3p21.3: progress toward the isolation of a lung cancer TSG.
The critical region on human chromosome 3p21.3 harboring a putative lung cancer tumor suppressor gene (TSG) was previously defined by allelotyping and recently refined by overlapping homozygous deletions. We report the construction of a 700-kb (cosmid and one P1 phage) clone contig covering the deletion overlap and its flanks. The minimal set of 23 cosmids comprises 600 kb and is extended by one P1 phage to 700 kb to cover the distal breakpoint of the overlap. The clone contig was extensively characterized by restriction and expression mapping to produce high resolution physical and transcription maps of the cloned region. Potential transcribed fragments were detected by hybridization with PCR-amplified cDNA libraries, direct cDNA selection "zoo" blotting, cDNA screening, and identification of 24 CpG islands. Thus far, 15 new genes represented by partial or full-length cDNAs were isolated, characterized, and precisely positioned on the contig. Two previously cloned genes, namely GNAI-2 and GNAT-1, were also positioned. In addition, the telomeric breakpoint of the NCI H740 deletion and centromeric breakpoint of the overlapping GLC20 deletion were discovered and mapped to define precisely the candidate TSG region. This large cosmid clone contig and high resolution maps will prove crucial in the identification of the lung cancer TSG(s).


Loss-of-function mutations in CAST cause peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads.
Calpastatin is an endogenous specific inhibitor of calpain, a calcium-dependent cysteine protease. Here we show that loss-of-function mutations in calpastatin (CAST) are the genetic causes of an autosomal-recessive condition characterized by generalized peeling skin, leukonychia, acral punctate keratoses, cheilitis, and knuckle pads, which we propose to be given the acronym PLACK syndrome. In affected individuals with PLACK syndrome from three families of different ethnicities, we identified homozygous mutations (c.607dup, c.424A>T, and c.1750delG) in CAST, all of which were predicted to encode truncated proteins (p.Ile203Asnfs∗8, p.Lys142∗, and p.Val584Trpfs∗37). Immunohistochemistry shows that staining of calpastatin is reduced in skin from affected individuals. Transmission electron microscopy revealed widening of intercellular spaces with chromatin condensation and margination in the upper stratum spinosum in lesional skin, suggesting impaired intercellular adhesion as well as keratinocyte apoptosis. A significant increase of apoptotic keratinocytes was also observed in TUNEL assays. In vitro studies utilizing siRNA-mediated CAST knockdown revealed a role for calpastatin in keratinocyte adhesion. In summary, we describe PLACK syndrome, as a clinical entity of defective epidermal adhesion, caused by loss-of-function mutations in CAST.


Controlled trial of fasting and one-year vegetarian diet in rheumatoid arthritis.
Fasting is an effective treatment for rheumatoid arthritis, but most patients relapse on reintroduction of food. The effect of fasting followed by one year of a vegetarian diet was assessed in a randomised, single-blind controlled trial. 27 patients were allocated to a four-week stay at a health farm. After an initial 7-10 day subtotal fast, they were put on an individually adjusted gluten-free vegan diet for 3.5 months. The food was then gradually changed to a lactovegetarian diet for the remainder of the study. A control group of 26 patients stayed for four weeks at a convalescent home, but ate an ordinary diet throughout the whole study period. After four weeks at the health farm the diet group showed a significant improvement in number of tender joints, Ritchie's articular index, number of swollen joints, pain score, duration of morning stiffness, grip strength, erythrocyte sedimentation rate, C-reactive protein, white blood cell count, and a health assessment questionnaire score. In the control group, only pain score improved score. In the control group, only pain score improved significantly. The benefits in the diet group were still present after one year, and evaluation of the whole course showed significant advantages for the diet group in all measured indices. This dietary regimen seems to be a useful supplement to conventional medical treatment of rheumatoid arthritis.


Restriction map of the Escherichia coli malA region and identification of the malT product.
A series of plaque-forming lambda h80 transducing phages carrying various portions of the malA region were isolated. A 5,800-base pair HindIII-EcoRI DNA fragment from one of these phages was cloned into pBR322 and shown to contain malT, which is the positive regulator gene of the maltose regulon, and most of malP, the structural gene for maltodextrin phosphorylase. A restriction map of the HindIII-EcoRI fragment was established, and it was correlated with the genetic map of the malA region (i) by mapping deletions which had been generated in vitro on the plasmid and (ii) by locating on the restriction map a DNA insertion of known genetic position. A 600-base pair HincII-HaeII segment was shown to contain all or part of the promoters for malT and malP, which are known to be transcribed in opposite directions. Strains carrying gene malT on a plasmid synthesized a 94,000-dalton polypeptide which was not produced by identical strains carrying similar plasmids in which malT was partially deleted. Estimates of the size of the malT gene support the conclusion that the 94,000-dalton polypeptide is the malT product.


MODIS Collection 6 shortwave-derived cloud phase classification algorithm and comparisons with CALIOP.
Cloud thermodynamic phase (ice, liquid, undetermined) classification is an important first step for cloud retrievals from passive sensors such as MODIS (Moderate-Resolution Imaging Spectroradiometer). Because ice and liquid phase clouds have very different scattering and absorbing properties, an incorrect cloud phase decision can lead to substantial errors in the cloud optical and microphysical property products such as cloud optical thickness or effective particle radius. Furthermore, it is well established that ice and liquid clouds have different impacts on the Earth's energy budget and hydrological cycle, thus accurately monitoring the spatial and temporal distribution of these clouds is of continued importance. For MODIS Collection 6 (C6), the shortwave-derived cloud thermodynamic phase algorithm used by the optical and microphysical property retrievals has been completely rewritten to improve the phase discrimination skill for a variety of cloudy scenes (e.g., thin/thick clouds, over ocean/land/desert/snow/ice surface, etc). To evaluate the performance of the C6 cloud phase algorithm, extensive granule-level and global comparisons have been conducted against the heritage C5 algorithm and CALIOP. A wholesale improvement is seen for C6 compared to C5.


Cavernous sinus metastasis from oropharyngeal squamous cell carcinoma.
Metastasis to the cavernous sinus from head and neck cancer is uncommon and has been previously reported by a few authors. It is usually a late manifestation of the primary tumor and may be the first evidence of a widespread dissemination of the disease. Main clinical findings are those related with involvement of cranial nerves III to VI as they pass through the cavernous sinus. Although diagnosis may be difficult, the appearance of clinical and radiological findings of cavernous sinus involvement in a context of head and neck cancer must alert us about an intracranial metastatic infiltration. In most cases treatment is palliative with radiotherapy and/or chemotherapy. The prognosis of this entity is poor, with survival of a few months. We present the case of cavernous sinus metastasis from oropharyngeal squamous cell carcinoma and review the literature about the clinical presentation and management of this rare entity.


[Features of the structure of arteries of the lower extremities in man].
A comparative investigation has been performed on structural peculiarities of muscle arteries having various caliber in the lower extremities and in the anterior thoracic wall (section material, 40 observations). An essential predominance of the muscle tunic thickness and deterioration of blood supply has been stated in the arterial wall and in the distal parts of the lower extremities. The structural peculiarities revealed in the arteries of the extremities are connected with functional conditions of blood supply in the zone at the vertical position of the human body (orthostatic arterial hypertension).


[Surgical treatment of acute coronoid process fractures].
This study was designed to assess the results of surgical treatment for type 2-3 coronoid process fractures and to identify factors that might influence the outcome. Thirteen male patients (mean age 35 years; range 17 to 53 years) were treated with open reduction and internal fixation for displaced coronoid fractures. According to the Regan-Morrey classification, the fractures were type 2 in nine patients (69.2%), and type 3 in four patients (30.8%). Nine patients had associated injuries (elbow dislocation, radial head or olecranon fractures, and/or ligamentous injuries). The mean duration to treatment was 2.3 days (range 1 to 7 days). Functional results were assessed according to the Mayo elbow performance score (MEPS), and signs of arthritis were assessed according to the Broberg-Morrey criteria. The mean follow-up was 41.1 months (range 12 to 96 months). A functional range of motion of the elbow joint was achieved in 10 patients (76.9%). The mean elbow range of motion was 110.7 degrees (range 85 degrees to 130 degrees ) and the mean forearm rotation was 134.2 degrees (range 120 degrees to 155 degrees ). Three patients who had comminuted fractures and associated elbow injuries had decreased range of motion. None of the patients exhibited signs of instability. The mean MEPS was 86.5 (range 75 to 100). The results were excellent in four patients (30.8%; the mean MEPS 98.8) having isolated or noncomminuted coronoid fractures, and good in nine patients (69.2%) with comminuted fractures and/or associated bone or ligament injuries. Post-traumatic arthritis was detected in seven patients (53.9%) whose mean MEPS was 81.4. Patients with an excellent functional result did not develop arthritis. All the patients returned to preinjury activity levels. Coronoid fractures are the most important component of complex elbow injuries. The presence of comminuted fractures, associated bone and ligament injuries, and post-traumatic arthritis affect the outcome adversely.


Staphylococcal nuclease high-performance liquid chromatographic characterization of diaminooctane-modified DNA and its biotin and fluorescein derivatives.
DNA was subjected to bisulfite-catalyzed transamination at the N4 sites of its cytosine residues with 1,8-diaminooctane (DAO). The product, DNA-DAO, was non-specifically degraded with a cloned staphylococcal nuclease (Nase). The products from the Nase digestion were determined by high-performance liquid chromatography (HPLC) to define the extent of reaction with DAO. Mostly, nucleoside 3'-monophosphates were obtained, along with four Nase-resistant dinucleotides: TpdGp, dApdGp, TpdCp-DAO and dApdCp-DAO. The addition of spleen phosphodiesterase II gave a faster hydrolysis and left no dinucleotides. A mixture of Nase, snake venom phosphodiesterase I and alkaline phosphatase gave a fast hydrolysis as well but two dinucleotides, apparently TpdC-DAO and dApdC-DAO, persisted. Further modification of the diaminooctyl side chains with fluorescein isothiocyanate or biotin N-hydroxysuccinimide ester was similarly investigated. Interestingly, derivatization of the DAO side chain with biotin eliminates the resistance of TpdCp-DAO and dApdCp-DAO to Nase digestion. This work provides some guidelines for using Nase, alone or with other nucleases, along with HPLC, for characterizing alkyldiamine DNA products, and should be similarly useful for studying other modifications of DNA.


Pediatric Delirium Educational Tool Development With Intensive Care Unit Clinicians and Caregivers in Canada: Focus Group Study.
Pediatric intensive care unit (PICU)-associated delirium contributes to a decline in postdischarge quality of life, with worse outcomes for individuals with delayed identification. As delirium screening rates remain low within PICUs, caregivers may be able to assist with early detection, for which they need more education, as awareness of pediatric delirium among caregivers remains limited. This study aimed to develop an educational tool for caregivers to identify potential delirium symptoms during their child's PICU stay, educate them on how to best support their child if they experience delirium, and guide them to relevant family resources. Web-based focus groups were conducted at a tertiary pediatric hospital with expected end users of the tool (ie, PICU health care professionals and caregivers of children with an expected PICU length of stay of over 48 h) to identify potential educational information for inclusion in a family resource guide and to identify strategies for effective implementation. Data were analyzed thematically to generate requirements to inform prototype development. Participants then provided critical feedback on the initial prototype, which guided the final design. In all, 24 participants (18 health care professionals and 6 caregivers) attended 7 focus groups. Participants identified five informational sections for inclusion: (1) delirium definition, (2) key features of delirium (signs and symptoms), (3) postdischarge outcomes associated with delirium, (4) tips to inform family-centered care, and (5) education or supportive resources. Participants identified seven design requirements: information should (1) be presented in an order that resembles the structure of the clinical discussion around delirium; (2) increase accessibility, recall, and preparedness by providing multiple formats; (3) aim to reduce stress by implementing positive framing; (4) minimize cognitive load to ensure adequate information processing; (5) provide supplemental electronic resources via QR codes; (6) emphasize collaboration between caregivers and the health care team; and (7) use prompting questions to act as a call to action for caregivers. Key design requirements derived from end-user feedback were established and guided the development of a novel pediatric delirium education tool. Implementing this tool into regular practice has the potential to reduce distress and assist in the early recognition and treatment of delirium in the PICU domain. Future evaluation of its clinical utility is necessary.


Nanometre-thin indium tin oxide for advanced high-performance electronics.
Although indium tin oxide (ITO) is widely used in optoelectronics due to its high optical transmittance and electrical conductivity, its degenerate doping limits exploitation as a semiconduction material. In this work, we created short-channel active transistors based on an ultra-thin (down to 4 nm) ITO channel and a high-quality, lanthanum-doped hafnium oxide dielectric of equivalent oxide thickness of 0.8 nm, with performance comparative to that of existing metal oxides and emerging two-dimensional materials. Short-channel immunity, with a subthreshold slope of 66 mV per decade, off-state current <100 fA μm-1 and on/off ratio up to 5.5 × 109, was measured for a 40-nm transistor. Logic inverters working in the subthreshold regime exhibit a high gain of 178 at a low-supply voltage of 0.5 V. Moreover, radiofrequency transistors, with as-measured cut-off frequency fT and maximum oscillation frequency fmax both >10 GHz, have been demonstrated. The unique wide bandgap and low dielectric constant of ITO provide prospects for future scaling below the 5-nm regime for advanced low-power electronics.


[Survey on risky sexual behavior and sexually transmitted diseases among adolescent students from Havana City, 1996].
The observed increase of sexually transmitted diseases (STD) in Cuba aroused the interest of carrying out a study aimed at exploring risky sexual behaviours and attitudes, and histories of STD. A crosswise descriptive study was undertaken using a randomized sample taken from the universe of adolescent students in the City of Havana during 1995-96 school year. The sample was made up by 2,793 teenagers aged 11-19 years (1,370 females and 1,423 males). Previously trained experts linked to this field collected data by means of a structured interview which had been drawn up for this end. It was confirmed that more than half of adolescent students did not use condom in their sexual intercourse 57% had more than one sexual partner along the year, 40% believed it was difficult to keep only one partner whereas 35% had more than one sexual partner at the same time. Risk and protected sexual habits were noticed, with 39% for oral-genital and 21.4% for genital-anal. 22% for the interviewed adolescent said they had histories of STD.


Inhibition of dengue virus by targeting viral NS4B protein.
We report a novel inhibitor that selectively suppresses dengue virus (DENV) by targeting viral NS4B protein. The inhibitor was identified by screening a 1.8-million-compound library using a luciferase replicon of DENV serotype 2 (DENV-2). The compound specifically inhibits all four serotypes of DENV (50% effective concentration [EC(50)], 1 to 4 μM; and 50% cytotoxic concentration [CC(50)], >40 μM), but it does not inhibit closely related flaviviruses (West Nile virus and yellow fever virus) or nonflaviviruses (Western equine encephalomyelitis virus, Chikungunya virus, and vesicular stomatitis virus). A mode-of-action study suggested that the compound inhibits viral RNA synthesis. Replicons resistant to the inhibitor were selected in cell culture. Sequencing of the resistant replicons revealed two mutations (P104L and A119T) in the viral NS4B protein. Genetic analysis, using DENV-2 replicon and recombinant viruses, demonstrated that each of the two NS4B mutations alone confers partial resistance and double mutations confer additive resistance to the inhibitor in mammalian cells. In addition, we found that a replication defect caused by a lethal NS4B mutation could be partially rescued through trans complementation. The ability to complement NS4B in trans affected drug sensitivity when a single cell was coinfected with drug-sensitive and drug-resistant viruses. Mechanistically, NS4B was previously shown to interact with the viral NS3 helicase domain; one of the two NS4B mutations recovered in our resistance analysis-P104L-abolished the NS3-NS4B interaction (I. Umareddy, A. Chao, A. Sampath, F. Gu, and S. G. Vasudevan, J. Gen. Virol. 87:2605-2614, 2006). Collectively, the results suggest that the identified inhibitor targets the DENV NS4B protein, leading to a defect in viral RNA synthesis.


Prophylaxis for infective endocarditis: antibiotic sensitivity of dental plaque.
The antibiotic sensitivity pattern of bacteria isolated from bacteraemia after dental extraction was compared with that of bacteria isolated from dental plaque samples from the same patient. The results supported the current practice of using penicillin and erythromycin empirically for prophylaxis. The prediction of the most appropriate antibiotic for prophylaxis using dental plaque samples was most accurate when the minimum inhibitory concentration (MIC) of plaque isolates were used. It appears that a predictive test using dental plaque may be of some value in patients with recent or long-term antibiotic therapy.


1-L Transcription in Parkinson's Disease.
As a chronic degenerative disorder of the central nervous system that affects both motor and non-motor systems, Parkinson's disease (PD) is very complex, and explanations and models are needed to better understand how dopaminergic neurons are affected and microglia are activated. A theoretical protein-RNA recognition code that assumes that the second letter in codons is compatible with specific amino acids involved in protein-RNA recognition was used to search for compatibility of human α-synuclein (α-syn) with mRNAs in the human transcriptome (1-L transcription). The 1-L transcription revealed compatible amino acid sequences with the ATTTA ARE (class I), PAS and polyA in α-syn, supporting a protein-RNA regulatory model. In PD, inflammatory microglia reactions, cognitive decline and motor circuit disturbances are observed. The model theoretically explains why α-syn producing neurons are less protected from inflammation and why microglia are activated. Consistent with knowledge of PD, the identified genes showed how the PI3K-AKT pathway is downregulated, how reactive oxygen species (ROS) production and sensitivity are increased, how mitochondria are destabilized, why autophagy is impaired, and why neuronal depigmentation is observed. 1-L transcription of α-syn leads to genes/proteins relevant to PD. When α-syn is accepted as a small RNA recognition protein involved in the post-transcriptional regulations, some identified genes indicate that its function is an important regulatory factor associated with intracellular and extracellular transport of RNA vesicles. These vesicles are extremely important in cellular communication. In addition, the spectrum of identified genes strongly indicates that α-syn produced by neuronal cells is required for proper regulation of inflammatory and immune responses.


Risk Factors for Development of Hypocalcemia in Patients With Cancer Treated With Bone-Modifying Agents.
This retrospective analysis describes the prevalence of and risk factors associated with the development of hypocalcemia in patients with cancer receiving bone-modifying agents (BMAs) as supportive care. Patients with cancer treated with an intravenous or subcutaneous BMA, including pamidronate, zoledronic acid, or denosumab, at a tertiary care/safety net hospital in 2005 through 2015 were included in this retrospective review. We reviewed the medical records for predictive clinical and laboratory parameters and for patient outcomes. A total of 835 patients with cancer received at least one dose of a BMA during the specified time frame; 205 patients (25%) developed hypocalcemia of CTCAE grade ≥1 within 8 weeks of BMA initiation, 18 of whom (8.8%) had grade ≥3, and 3 patients died as a result. Multivariate analysis showed that patients with hematologic malignancy (odds ratio [OR], 1.956; P=.025), bone metastases (OR, 2.443; P=.017), inpatient status (OR, 2.592; P<.001), and deficient baseline vitamin D levels (OR, 2.546; P<.023) were more likely to develop hypocalcemia. Hypercalcemia before BMA administration (OR, 0.474; P=.032) was protective. Certain patient populations, including those with hematologic malignancies and/or bone metastases, warrant closer monitoring of calcium levels while receiving BMAs because of the high rate of hypocalcemia. Low pretreatment vitamin D levels are associated with the development of hypocalcemia. These data support close monitoring of calcium levels in patients with cancer receiving BMAs, in addition to adequate repletion of vitamin D before initiation of BMAs when possible.


Structural analysis of the Trichodesmium nitrogenase iron protein: implications for aerobic nitrogen fixation activity.
Trichodesmium spp. are marine filamentous nitrogen-fixing cyanobacteria which play an important role in the nitrogen budget of the open ocean. Trichodesmium is unique in that it is nonheterocystous and fixes nitrogen during the day, while evolving oxygen through photosynthesis, even though nitrogenase is sensitive to oxygen inactivation. The sequence of the gene encoding the Fe protein component of nitrogenase from the recently cultivated isolate Trichodesmium sp. IMS 101 was used to construct a 3-dimensional model of the Fe protein, by comparison to the X-ray crystallographic structure of the Fe protein of the gamma-proteobacterium Azotobacter vinelandii. The primary differences in amino acid sequences of the Fe protein from diverse organisms do not impact the critical structural features of the Fe protein. It can be concluded that aerobic nitrogen fixation in Trichodesmium spp. is not facilitated by unique structural features of Trichodesmium Fe protein.


Prolonged effect of insulin on glucose uptake by rat skeletal muscle.
The fate of insulin, as it relates to its action on skeletal-muscle glucose uptake, was studied in non-cyclically perfused rat hindlimbs. Insulin (1m-i.u./ml) with and without (125)I-labelled insulin was infused intra-arterially for 5 or 6min. Net glucose uptake and the release of (125)I-labelled insulin into the venous effluent were evaluated by arteriovenous-difference measurements for an additional 24-32min. The infusion of insulin for 5min promoted glucose uptake, an effect that persisted throughout a subsequent 25min of perfusion in the absence of insulin. The addition of insulin antibody to the perfusate in the presence of insulin blocked the action of insulin on glucose uptake, but it failed to alter insulin action if the muscle tissue had been exposed to insulin before addition of antibody. When (125)I-labelled albumin was infused for 6min, venous effluent radioactivity decayed rapidly and remained HClO(4)-insoluble and there was no significant tissue retension of radioactivity. Comparable experiments in which (125)I-labelled insulin was infused for 6min revealed that the venous effluent radioactivity decayed more slowly, a significant amount of the (125)I-labelled insulin appeared as fragments (HClO(4)-soluble) and there was a significant retention of radioactivity in the tissue. Radioactivity in muscle tissue biopsies obtained 28min after infusion of (125)I-labelled insulin was associated largely with intact insulin and a peptide of mol.wt. 2400. The total radioactivity retained in the muscle at this time was 7% of the amount infused. An insulin bolus (1i.u.) failed to increase the discharge of this tissue-associated radioactivity. These results suggest that insulin and a product of insulin metabolism persists in muscle tissue long after the arterial presence of insulin ends. This tissue residence and processing of insulin may be important components of insulin's prolonged action on glucose uptake by skeletal muscle.


In vitro Evaluation of Cytotoxic Effects of Methanolic Leaf Extracts of Annona muricata on Oral Squamous Cell Carcinoma-15 Cell Lines and its Effect On Expression of Bcl 2-associated X protein, B-cell C/Lymphoma 2 and p53 Genes.
Due to their wide spectrum of phytochemical components and lack of side effects, the use of plants for the prevention and treatment of cancer has recently attracted increased attention. One among them is Annona muricata, commonly called soursop. According to recent investigations, several types of cancer have been successfully treated using this plant's extracts. However, studies on oral squamous cell carcinoma (SCC) are very limited. In the present study, we aimed to investigate the cytotoxic potential of leaf extract of A. muricata (LEAM) against oral tongue SCC-15 cell lines, using in vitro assays. 3-(4,5-dimethylthiazol-2-yl)-2,5-dipenyltetrazolium bromide assay was performed to assess cytotoxic activity, and the apoptotic effect was determined using gene expression analyses of Bcl 2-associated X protein (Bax), B-cell C/lymphoma 2 (Bcl-2), and tumor-suppressor phosphoprotein (p53). Significant cytotoxicity (P ≤ 0.05) with a minimum inhibitory concentration value of 40 μg/ml was observed with the LEAM on SCC-15 cell lines. A highly significant decrease was observed in Bcl-2 gene expression (P < 0.05), whereas p53 and BAX genes revealed a highly significant increase (P < 0.05) when SCC-15 cell lines were treated with LEAM in the study group compared to the control. These results show that LEAM has the potential for development as a therapeutic agent for cytotoxicity, particularly on oral SCC cells, following further investigation.


Toward Efficient Team Formation for Crowdsourcing in Noncooperative Social Networks.
Crowdsourcing has become a popular service computing paradigm for requesters to integrate the ubiquitous human-intelligence services for tasks that are difficult for computers but trivial for humans. This paper focuses on crowdsourcing complex tasks by team formation in social networks (SNs) where a requester connects to a large number of workers. A good indicator of efficient team collaboration is the social connection among workers. Most previous social team formation approaches, however, either assume that the requester can maintain information of all workers and can directly communicate with them to build teams, or assume that the workers are cooperative and be willing to join the specific team built by the requester, both of which are impractical in many real situations. To this end, this paper first models each worker as a selfish entity, where the requester prefers to hire inexpensive workers that require less payment and workers prefer to join the profitable teams where they can gain high revenue. Within the noncooperative SNs, a distributed negotiation-based team formation mechanism is designed for the requester to decide which worker to hire and for the worker to decide which team to join and how much should be paid for his skill service provision. The proposed social team formation approach can always build collaborative teams by allowing team members to form a connected graph such that they can work together efficiently. Finally, we conduct a set of experiments on real dataset of workers to evaluate the effectiveness of our approach. The experimental results show that our approach can: 1) preserve considerable social welfare by comparing the benchmark centralized approaches and 2) form the profitable teams within less negotiation time by comparing the traditional distributed approaches, making our approach a more economic option for real-world applications.


Peptide fragments of laminin and fibronectin promote migration (haptotaxis and chemotaxis) of metastatic cells.
The migration of tumour cells through basement membranes and extracellular matrices is an integral component of tumour invasion and metastasis. Laminin (LMN) and fibronectin (FN) at 1-100 micrograms/ml promote the directed migration of metastatic murine melanoma cells 40-70-fold greater than controls in modified Boyden chambers. Antibodies abrogated the migration of cells in response to the respective protein. Preincubation of melanoma cells with plasma FN had no effect on subsequent migration to LMN or FN. The migration of these cells was largely related to substratum-attached molecules and increasing adhesion gradients of cells; this has been termed haptotaxis. Peptide fragments of both FN and LMN were isolated by affinity chromatography with monoclonal antibodies, heparin or other constituents. FN has two unique domains, 80-125 K and 66 K, which promote the adhesion of tumour cells, whereas only one appeared to be responsible for promoting migration. Peptides of LMN, isolated with heparin and monoclonal antibody, define a cell migration-promoting activity within the 200 K chains of LMN. Serum spreading factor and epinectin, the latter an adhesion molecule derived from squamous epithelial tumour cells, are also capable of promoting the migration of malignant cells. Thus, directed migration of metastatic tumour cells may be promoted with peptide fragments of adhesion molecules and blocked with the respective antibody.


In vivo imaging of endothelial cell adhesion molecule expression after radiosurgery in an animal model of arteriovenous malformation.
Focussed radiosurgery may provide a means of inducing molecular changes on the luminal surface of diseased endothelium to allow targeted delivery of novel therapeutic compounds. We investigated the potential of ionizing radiation to induce surface expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on endothelial cells (EC) in vitro and in vivo, to assess their suitability as vascular targets in irradiated arteriovenous malformations (AVMs). Cultured brain microvascular EC were irradiated by linear accelerator at single doses of 0, 5, 15 or 25 Gy and expression of ICAM-1 and VCAM-1 measured by qRT-PCR, Western, ELISA and immunocytochemistry. In vivo, near-infrared (NIR) fluorescence optical imaging using Xenolight 750-conjugated ICAM-1 or VCAM-1 antibodies examined luminal biodistribution over 84 days in a rat AVM model after Gamma Knife surgery at a single 15 Gy dose. ICAM-1 and VCAM-1 were minimally expressed on untreated EC in vitro. Doses of 15 and 25 Gy stimulated expression equally; 5 Gy was not different from the unirradiated. In vivo, normal vessels did not bind or retain the fluorescent probes, however binding was significant in AVM vessels. No additive increases in probe binding were found in response to radiosurgery at a dose of 15 Gy. In summary, radiation induces adhesion molecule expression in vitro but elevated baseline levels in AVM vessels precludes further induction in vivo. These molecules may be suitable targets in irradiated vessels without hemodynamic derangement, but not AVMs. These findings demonstrate the importance of using flow-modulated, pre-clinical animal models for validating candidate proteins for vascular targeting in irradiated AVMs.


First-generation antipsychotics: not gone but forgotten.
Aims and method To identify training needs of the next generation of psychiatrists and barriers in prescribing first-generation antipsychotics (FGAs). We have surveyed psychiatry trainees in East Anglia with regard to their training experience, knowledge and attitudes to the use of oral FGAs as regular medication. Results Two-thirds of trainees were aware that first- and second-generation antipsychotics (SGAs) have similar efficacy, and a similar proportion perceived the older drugs to have more or 'stronger' side-effects. Lack of training experience was noted as the second leading concern for prescribing FGAs. A quarter of trainees received no training exposure to the older drugs and two-thirds had never initiated these drugs themselves. Although nearly 90% of trainees felt confident about initiating an oral SGA as a regular medication, only about 40% felt confident with FGAs (P<0.001). Clinical implications The survey highlights worrying gaps in training. FGAs can be used effectively, minimising side-effects, by careful dose titration, avoiding antipsychotic polypharmacy, high-dose, and high-potency drugs, thus ensuring they are not lost to future generations of psychiatrists.


[The morphology of the endocrine portion of the amphibian pancreas].
It has been shown that the endocrinous part of the pancreas in amphibia is formed of A-, B- and D-cells. B-cells are always disposed around sinusoid capillaries, while A- and D-cells lie on the islet periphery and often have no contact with capillaries. In addition to islets in the pancreas there are remnants of the so-called "external" epithelium which is represented by solitary B-cells, located in the wall of small excretory ducts. In the periinsular zone there are numerous acino-islets of A-, B- and D-types among which B-cells are prevailing.


Functional connectivity dynamically evolves on multiple time-scales over a static structural connectome: Models and mechanisms.
Over the last decade, we have observed a revolution in brain structural and functional Connectomics. On one hand, we have an ever-more detailed characterization of the brain's white matter structural connectome. On the other, we have a repertoire of consistent functional networks that form and dissipate over time during rest. Despite the evident spatial similarities between structural and functional connectivity, understanding how different time-evolving functional networks spontaneously emerge from a single structural network requires analyzing the problem from the perspective of complex network dynamics and dynamical system's theory. In that direction, bottom-up computational models are useful tools to test theoretical scenarios and depict the mechanisms at the genesis of resting-state activity. Here, we provide an overview of the different mechanistic scenarios proposed over the last decade via computational models. Importantly, we highlight the need of incorporating additional model constraints considering the properties observed at finer temporal scales with MEG and the dynamical properties of FC in order to refresh the list of candidate scenarios.


Altered metabolism and superoxide generation in neural tissue of rat embryos exposed to high glucose.
Oxygen uptake and glucose utilization of embryonic and fetal neural tissue of normal and diabetic rat pregnancy were studied. Exposure to 50 mM glucose inhibited oxygen uptake of embryonic neural tissue of normal rats by 28% at gestational day 9 (P < 0.001) and 20% at days 10-12 and 15 (P < 0.001) and stimulated glucose utilization by 132% at day 9 (P < 0.001), 50% at days 10 and 11 (P < 0.01), 168% at day 12 (P < 0.001), and 338% at day 15 (P < 0.001), indicating a Crabtree effect. The glucose-altered metabolism led to production of superoxide by the tissue, which was 1.8 to 2.4 nmol.h-1.microgram DNA-1 at days 9-12 and 1.2 nmol.h-1.microgram DNA-1 at day 15. The embryonic neural tissue of diabetic rats showed a diminished metabolic sensitivity to high glucose exposure, suggesting an impaired mitochondrial function. Consequently, the glucose-induced superoxide production was not detected in the tissue of embryos of diabetic rats. The data suggest that high concentration of glucose alters embryonic and fetal metabolism and causes generation of superoxide. Prolonged duration of the glucose-induced metabolic changes may impair cellular function and lead to embryonic dysmorphogenesis.


Cylinder Axis Agreement: Unexpected Scenarios.
The purpose of this retrospective study was to evaluate cylinder axis agreement between manifest refraction (MR), cycloplegic refraction (CR), Allegro Oculyzer ІІ and Allegro Topolyzer-Vario. We included 82 patients (32 males and 50 females, 28.1 ± 8.7 years old), with 156 eyes scheduled for wavefront optimized laser refractive surgery, photorefractive keratectomy (PRK) in 50 eyes and laser-assisted in situ keratomileusis (LASIK) in 106 eyes, for correction of simple, myopic, hyperopic or mixed astigmatism. Cylinder axis was determined under manifest and cycloplegic refractions and using Allegro Occulyzer ІІ and Allegro Topolyzer-Vario platforms. Cylinder axis agreement was assessed by intraclass correlation coefficient, Pearson correlation coefficient and by the method described by Bland and Altman. Intraclass correlation coefficient and Pearson correlation coefficient showed statistically significant cylinder axis agreement between manifest refraction, cycloplegic refraction, Allegro Oculyzer ІІ and Allegro Topolyzer-Vario (p <0.001). Despite statistically significant cylinder axis agreement between the four measuring tools, 4 of 156 eyes (2.5%) showed unexpected discrepancy between Allegro Oculyzer ІІ and Allegro Topolyzer-Vario cylinder axis. Although cylinder axis shows statistically significant agreement between manifest refraction, cycloplegic refraction, Allegro Oculyzer ІІ and Allegro Topolyzer-Vario, unexpected discrepancies occur.


Analyzing data with clumping at zero. An example demonstration.
This article demonstrates the use of two approaches to analyzing the relationship of multiple covariates to an outcome which has a high proportion of zero values. One approach is to categorize the continuous outcome (including the zero category) and then fit a proportional odds model. Another approach is to use logistic regression to model the probability of a zero response and ordinary least squares linear regression to model the non-zero continuous responses. The use of these two approaches was demonstrated using outcomes data on hours of care received from the Springfield Elder Project. A crude linear model including both zero and non-zero values was also used for comparison. We conclude that the choice of approaches for analysis depends on the data. If the proportional odds assumption is valid, then it appears to be the method of choice; otherwise, the combination of logistic regression and a linear model is preferable.


mRNA-based Vaccines Targeting the T-cell Epitope-rich Domain of Epstein Barr Virus Latent Proteins Elicit Robust Anti-Tumor Immunity in Mice.
Epstein-Barr virus (EBV) is associated with various malignancies and infects >90% of the global population. EBV latent proteins are expressed in numerous EBV-associated cancers and contribute to carcinogenesis, making them critical therapeutic targets for these cancers. Thus, this study aims to develop mRNA-based therapeutic vaccines that express the T-cell-epitope-rich domain of truncated latent proteins of EBV, including truncatedlatent membrane protein 2A (Trunc-LMP2A), truncated EBV nuclear antigen 1 (Trunc-EBNA1), and Trunc-EBNA3A. The vaccines effectively activate both cellular and humoral immunity in mice and show promising results in suppressing tumor progression and improving survival time in tumor-bearing mice. Furthermore, it is observed that the truncated forms of the antigens, Trunc-LMP2A, Trunc-EBNA1, and Trunc-EBNA3A, are more effective than full-length antigens in activating antigen-specific immune responses. In summary, the findings demonstrate the effectiveness of mRNA-based therapeutic vaccines targeting the T-cell-epitope-rich domain of EBV latent proteins and providing new treatment options for EBV-associated cancers.


A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism.
Disruption of the circadian clock exacerbates metabolic diseases, including obesity and diabetes. We show that histone deacetylase 3 (HDAC3) recruitment to the genome displays a circadian rhythm in mouse liver. Histone acetylation is inversely related to HDAC3 binding, and this rhythm is lost when HDAC3 is absent. Although amounts of HDAC3 are constant, its genomic recruitment in liver corresponds to the expression pattern of the circadian nuclear receptor Rev-erbα. Rev-erbα colocalizes with HDAC3 near genes regulating lipid metabolism, and deletion of HDAC3 or Rev-erbα in mouse liver causes hepatic steatosis. Thus, genomic recruitment of HDAC3 by Rev-erbα directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis.


Three-dimensional virtual planning of corrective osteotomies of distal radius malunions: a systematic review and meta-analysis.
The purpose of this study was to summarize and evaluate results of three-dimensional (3D-) planned corrective osteotomies of malunited distal radius fractures. 3D-planning techniques provide the possibility to address 3D-deformity that conventional planning methods might not address. We systematically searched PubMed, EMBASE and the Cochrane library for studies that performed a 3D-planned corrective osteotomy on patients with a malunited distal radius fracture. Fifteen studies with a total of 68 patients were included in the analysis. In 96% of cases, the preoperatively present palmar tilt, radial inclination and ulnar variance showed statistically significant improvement postoperatively with restoration to within 5° or 2 mm of their normal values. Mean flexion-extension, pro-supination and grip strength showed statistically significant improvement (p < 0.05). Complications were reported in 11 out of 68 patients (16%). With the current advances in 3D printing technology, 3D-planned corrective osteotomies seem a promising technique in the treatment of complex distal radius malunions. Level of evidence IV Systematic review of case series, Level IV.


Managing CNS disease in adults with acute lymphoblastic leukemia.
The central nervous system (CNS) is an important site of involvement by acute lymphoblastic leukemia (ALL) in adults. The prevalence is sufficiently high that prophylactic treatment is routinely given to this sanctuary site in order to eradicate occult disease that might otherwise lead to a relapse. A lumbar puncture should be routinely performed in all newly diagnosed patients with ALL. The risks of CNS leukemia vary by phenotype and genotype. Preventive treatment of the CNS during post-remission therapy has become an integral part of all current ALL treatment protocols. Most treatment regimens combine multiple doses of intrathecal chemotherapy with high-dose systemic methotrexate and/or cytarabine. Cranial irradiation is less commonly used for prophylaxis but is still the most effective treatment for overt CNS leukemia. Recurrences within the CNS usually coincide with or predict soon afterwards for systemic relapse in the marrow and blood.


Amplification of chirality through self-replication of micellar aggregates in water.
We describe a system in which the self-replication of micellar aggregates results in a spontaneous amplification of chirality in the reaction products. In this system, amphiphiles are synthesized from two "clickable" fragments: a water-soluble "head" and a hydrophobic "tail". Under biphasic conditions, the reaction is autocatalytic, as aggregates facilitate the transfer of hydrophobic molecules to the aqueous phase. When chiral, partially enantioenriched surfactant heads are used, a strong nonlinear induction of chirality in the reaction products is observed. Preseeding the reaction mixture with an amphiphile of one chirality results in the amplification of this product and therefore information transfer between generations of self-replicating aggregates. Because our amphiphiles are capable of catalysis, information transfer, and self-assembly into bounded structures, they present a plausible model for prenucleic acid "lipid world" entities.


Adaptive mutation and slow-growing revertants of an Escherichia coli lacZ amber mutant.
We have studied revertants, selected on lactose minimal agar medium, of the Escherichia coli lacZam strain that was first used by Cairns and his colleagues to demonstrate the phenomenon of "adaptive mutation." We have found, by performing appropriate reconstruction studies, that most of the late-arising Lac+ revertants of this lac amber strain (appearing as colonies in 3-5 days) are slow-growing ochre suppressor mutants that probably existed in the culture prior to plating and cannot, therefore, be classified as "adaptive." The appearance of a small number of fast-growing, late-arising Lac+ revertants may result from residual cell growth and turnover or from phenomena related to the fact that the lacZam mutation in strain SM195 is carried on an F' plasmid. Thus, the appearance of late-arising revertants in this lacZam system does not provide convincing evidence that selective conditions specifically increase the rate of occurrence of favorable mutations.


The use of the electrocardiogram to identify epicardial coronary and tissue reperfusion in acute myocardial infarction.
The standard 12-lead electrocardiogram (ECG) gives us crucial information concerning myocardial perfusion and the success of reperfusion therapy for ST elevation acute myocardial infarction. Continuous monitoring has advantages over repeated snapshot recordings. There are four electrocardiographic markers for prediction of the perfusion status of the ischemic myocardium: (1) ST-segment measurements, (2) T-wave configuration, (3) QRS changes, and (4) reperfusion arrhythmias. Complete and stable (> or = 70%) resolution of ST-segment elevation is associated with better outcome and preservation of left ventricular function than partial (30 to 70%) or no (<30%) ST-segment resolution. Early inversion of the T waves after initiation of reperfusion therapy is another marker of myocardial reperfusion and a good prognostic sign. Using standard 12-lead ECG, dynamic changes in Q-wave number, amplitude, and width; R-wave amplitude; and S-wave appearance are detected during reperfusion therapy. However, the significance of these changes has not been clarified. Reperfusion arrhythmias, especially bradycardia and accelerated idioventricular rhythm, are detected occasionally during reperfusion therapy, but the value of reperfusion arrhythmias as a marker of coronary artery patency is still debatable. Dynamic changes in the QRS complexes, ST segments and T waves occur during reperfusion therapy and the days after. Whereas changes in ST-segment amplitude have been extensively studied, the significance of QRS-complex and T-wave changes is less clear, and especially whether changes in the QRS complex and T wave may be complementary and additive to ST-segment monitoring. It has remained unclear whether electrocardiographic signs of reperfusion and reischemia should be used for therapeutic decision making in the clinical setting.


Comparison of the efficacy and safety of 2% lidocaine HCl with different epinephrine concentration for local anesthesia in participants undergoing surgical extraction of impacted mandibular third molars: A multicenter, randomized, double-blind, crossover, phase IV trial.
The most commonly impacted tooth is the third molar. An impacted third molar can ultimately cause acute pain, infection, tumors, cysts, caries, periodontal disease, and loss of adjacent teeth. Local anesthesia is employed for removing the third molar. This study aimed to evaluate the efficacy and safety of 2% lidocaine with 1:80,000 or 1:200,000 epinephrine for surgical extraction of bilateral impacted mandibular third molars. Sixty-five healthy participants underwent surgical extraction of bilateral impacted mandibular third molars in 2 separate visits while under local anesthesia with 2% lidocaine with different epinephrine concentration (1:80,000 or 1:200,000) in a double-blind, randomized, crossover trial. Visual analog scale pain scores obtained immediately after surgical extraction were primarily evaluated for the 2 groups receiving different epinephrine concentrations. Visual analog scale pain scores were obtained 2, 4, and 6 hours after administering an anesthetic. Onset and duration of analgesia, onset of pain, intraoperative bleeding, operator's and participant's overall satisfaction, drug dosage, and hemodynamic parameters were evaluated for the 2 groups. There were no statistically significant differences between the 2 groups in any measurements except hemodynamic factors (P >.05). Changes in systolic blood pressure and heart rate following anesthetic administration were significantly greater in the group receiving 1:80,000 epinephrine than in that receiving 1:200,000 epinephrine (P ≤.01). The difference in epinephrine concentration between 1:80,000 and 1:200,000 in 2% lidocaine liquid does not affect the medical efficacy of the anesthetic. Furthermore, 2% lidocaine with 1:200,000 epinephrine has better safety with regard to hemodynamic parameters than 2% lidocaine with 1:80,000 epinephrine. Therefore, we suggest using 2% lidocaine with 1:200,000 epinephrine rather than 2% lidocaine with 1:80,000 epinephrine for surgical extraction of impacted mandibular third molars in hemodynamically unstable patients.


Advances in imaging in the postoperative patient with a rising prostate-specific antigen level.
Imaging prostate cancer continues to represent a clinical challenge for both primary and recurrent disease. In the evaluation of the persistent/recurrent/metastatic prostate cancer, knowledge of cancer location (local v distant), size, and extent are essential in order to design a treatment, tailored to each patient's needs. There are evidence-based guidelines for the use of imaging in assessing the presence of distant spread of prostate cancer. Radionuclide bone scans and computed tomography (CT), magnetic resonance imaging (MRI), and/or positron emission tomography (PET) supplement clinical and biochemical evaluations (prostate-specific antigen [PSA]) for suspected metastatic disease to bones and lymph nodes. There is no consensus about the use of imaging in the evaluation of local tumor recurrence. The use of ultrasound has been limited to biopsy guidance of the prostatic bed, or percutaneous biopsy of enlarged lymph nodes detected on CT or MRI. The use of MRI is evolving. Recent studies indicate that the use of MRI provides valuable information in the evaluation of local tumor recurrence, and nodal and bony metastases. In a patient post-radiation therapy, the method of combining MRI anatomic information with MR spectroscopic metabolic information is evolving. Another modality offering information about anatomy and metabolism of the local disease is PET/CT. The value of PET/CT at present is controversial, but new studies exploring the role of PET/CT in aggressive prostate cancer are promising.


[Morphofunctional features of 10-12-day-old rabbit lymphoid tissue].
Histological, cytological, enzymatic (acid and alkaline phosphatase, SDG and alpha-GPhDG), immunomorphological (RNA, DNA, amount of T- and B-lymphocytes) peculiarities in structure of the lymphatic system organs have been studied in 10-12-day-old rabbits. It has been stated that T-lymphocytes predominant (in total amount) among the lymphoid cells in the organs; there is an essential amount of inactive cells. Besides, the activity of the hydrolytic enzymes is greater than that of the mitochondrial ones. Lymphatic follicles and T-zones in the organs are poorly developed, light centers, as a rule, are not formed, diffuse lymphoid tissue predominates.


Investigation of efflorescence of inorganic aerosols using fluorescence spectroscopy.
The phase transition is one of the most fundamental phenomena affecting the physical and chemical properties of atmospheric aerosols. Efflorescence, in particular, is not well understood, partly because the molecular interactions between the solute and water molecules of saturated or supersaturated solution droplets have not been well characterized. Recently, we developed a technique that combines the use of an electrodynamic balance and a fluorescence dye, 8-hydroxyl-1,3,6-pyrenetrisulfonate (pyranine), to study the distributions of solvated and free water in aqueous droplets (Choi, M. Y.; Chan, C. K.; Zhang, Y. H. J. Phys. Chem. A 2004, 108, 1133). We found that the equality of the amounts of solvated and free water is a necessary but not sufficient condition for efflorescence. For efflorescing compounds such as Na2SO4, (NH4)2SO4, and a mixture of NaCl and Na2SO4, the amount of free water decreases, while that of solvated water is roughly constant in bulk measurements and decreases less dramatically than that of free water in single-particle measurements as the relative humidity (RH) decreases. Efflorescence of the supersaturated droplets of these solutions occurs when the amounts of free and solvated water are equal, which is consistent with our previous observation for NaCl. For nonefflorescing compounds in single-particle levitation experiments such as MgSO4 and Mg(NO3)2, the amounts of free and solvated water are equal at a water-to-solute molar ratio of about 6, at which spectral changes due to the formation of contact ion pairs between magnesium and the anions occur as shown by Raman spectroscopy. Fluorescence imaging shows that the droplets of diluted Mg(NO3)2 (at 80% RH) and MgSO4 are homogeneous but those of NaCl, Na2SO4, (NH4)2SO4, and supersaturated Mg(NO3)2 (at 10% RH) are heterogeneous in terms of the solvated-to-free water distribution. The solvated-to-free water ratios in NaCl, Na2SO4, and (NH4)2SO4 droplets are higher in the outer regions by about half a radius deep than at the center of the droplets.


Milk production and intake of lactating cows fed raw or extruded peas.
Primiparous (n = 9) and multiparous (n = 18) Holstein cows averaging 584 +/- 15 kg of body weight (mean +/- SE) were allotted at 2 wk postpartum to nine groups (3 primiparous and 6 multiparous) of 3 cows each to determine the effects of pea extrusion on ruminal degradability and milk production. Cows were fed a total mixed diet based on timothy silage and concentrate for ad libitum intake. The experiment was carried out between wk 4 and 15 of lactation. Cows within each group were assigned randomly to isonitrogenous and isoenergetic concentrates based on corn plus soybean meal, raw peas, or extruded peas. Extrusion of peas increased the ruminal degradability of starch but had no effect on the ruminal degradability of crude protein. Cows fed extruded peas had higher dry matter intakes and plasma urea N concentrations than did those fed soybean meal; no differences were detected between cows fed extruded and raw peas. Production of 4% fat-corrected milk and milk composition generally were similar for cows fed the various diets. Digestibilities of dry matter and N were higher for cows fed extruded peas than for cows fed soybean meal or raw peas. These data suggest that peas can substitute for soybean meal as the protein source in diets of early lactation cows without adverse effects on production and that, in this study, the extrusion of peas had no beneficial effect on milk production.


Molecular characterization of vancomycin-resistant enterococcus faecium isolates from mainland China.
Little is known about vancomycin-resistant enterococci in China. Thirteen pulsed-field gel electrophoresis-confirmed heterogeneous VanA-type vancomycin-resistant Enterococcus faecium (VRE) isolates were obtained from five Chinese hospitals from 2001 to 2005. The isolates were typed by multilocus sequence typing into nine different sequence types (STs), including five new STs (ST18, ST25, ST78, ST203, ST320, ST321, ST322, ST323, and ST335). Vancomycin resistance in each isolate was encoded on conjugative plasmids; two of the plasmids, pZB18 (67 kbp) and pZB22 (200 kbp), were highly conjugative and were able to transfer at high frequencies of around 10(-4) and 10(-7) per donor cell in broth mating, respectively. None of the plasmids identified in these isolates carried traA, which is usually conserved in the pMG1-like highly conjugative plasmid for E. faecium, implying that pZB18 and pZB22 were novel types of a highly conjugative plasmid in enterococci. Thirteen Tn1546-like elements encoding VanA-type VRE on the conjugative plasmids were classified into six types (types I to VI), and most of them contained both IS1216V and IS1542 insertions. The isolates carrying the type II element were predominant. The six type elements were different from that of a VanA-type Enterococcus faecalis strain isolated from Chinese chicken meat. The results suggested that the disseminations of VRE in these areas were by Tn1546-like elements being acquired by the conjugative plasmids and transferred among E. faecium strains.


Amplification and specific expression of T-bet gene in nasal NK/T-cell lymphoma.
To define the specific genetic alterations in nasal natural killer/T-cell lymphoma (N-NK/T-L), the assay of restriction landmark genomic scanning (RLGS), a genome-wide method, was used to investigate a pair of genomic DNA from N-NK/T-L cells and peripheral blood leukocytes of the same patient. The intensified spots in displayed N-NK/T-L gel of RLGS were subjected to bioinformatic analysis by virtual genome scan (VGS) and one of candidate spots proved to be T-bet gene (T-box expressed in T-cell). The pair of samples was consequently analysed by Southern hybridization, revealing genomic amplification of T-bet but not different status of DNA methylation. The amplification of T-bet was also discovered in other cases of N-NK/T-L by dot blotting. The expression of T-bet was investigated by in situ hybridization (ISH) and immunohistochemistry (IHC). The results showed that T-bet predominantly expressed in N-NK/T-L (ISH: 90.0%, 18/20; IHC: 80%, 16/20), while few cases of B-cell lymphoma (ISH: 11.8%, 2/17; IHC: 17.6%, 3/17) or T-cell lymphoma (ISH: 33.3%, 2/6; IHC: 16.7%, 1/6) were positive. The difference of T-bet expression in either ISH or IHC between N-NK/T-L and B-cell lymphoma or T-cell lymphoma was statistically significant (P < 0.05). Moreover, the expression of T-bet was not detected in normal spleen tissue and chronic inflammatory nasal mucosa. The results suggested that the amplification of T-bet gene or resulting its over-expression of T-bet gene might be involved in the development of N-NK/T-L and thus it should be worth confirming whether the over-expression of T-bet be helpful to the diagnosis of N-NK/T-L in further study.


Long-term Outcomes of Hypofractionated Stereotactic Radiotherapy for the Treatment of Perioptic Nonfunctioning Pituitary Adenomas.
The efficacy of stereotactic radiotherapy (SRT) has been well established for postoperative residual and recurrent nonfunctioning pituitary adenomas (NFPAs). However, the risk of visual impairment due to SRT for lesions adjacent to the optic pathways remains a topic of debate. Herein, we evaluated the long-term clinical outcomes of hypofractionated stereotactic radiotherapy (HFSRT) for perioptic NFPAs. From December 2002 to November 2015, 32 patients (18 males and 14 females; median age 63 years; range, 36-83 years) with residual or recurrent NFPAs abutting or displacing the optic nerve and/or chiasm (ONC) were treated with HFSRT. The median marginal dose was 31.3 Gy (range, 17.2-39.6) in 8 fractions (range, 6-15). Magnetic resonance imaging (MRI) and visual and hormonal examinations were performed before and after HFSRT. The median follow-up period was 99.5 months (range, 9-191). According to MRI findings at the last follow-up, the tumor size had decreased in 28 (88%) of 32 patients, was unchanged in 3 (9%), and had increased in 1 (3%). The successful tumor size control rate was 97%. Visual functions remained unchanged in 19 (60%) out of 32 patients, improved in 11 (34%), and deteriorated in 2 (6%). Two patients had deteriorated visual functions; no complications occurred because of the HFSRT. One patient developed hypopituitarism that required hormone replacement therapy. The result of this long-term follow-up study suggests that HFSRT is safe and effective for the treatment of NFPAs occurring adjacent to the ONC.


Post-cataract Surgery Fungal Endophthalmitis: Management Outcomes and Prognostic Factors.
Purpose: To describe the clinical and microbiological features, management outcomes, and prognostic factors of visual improvement in post-cataract surgery fungal endophthalmitis.Methods: We evaluated 17 patients with culture-confirmed fungal endophthalmitis following cataract surgery. Data were collected regarding intravitreal antibiotics and antifungals, pars plana vitrectomy (PPV), intraocular lens (IOL) explantation, and scleral-fixated IOL (SFIOL) implantation. Clinical outcomes were recorded in terms of visual acuity and management strategies.Results: PPV was performed as a primary procedure at first presentation in three eyes. Fourteen eyes (82.3%) received intravitreal voriconazole. IOL explantation was performed in four eyes, followed by an SFIOL implantation in three eyes. Six eyes additionally presented with keratitis. At the final follow-up, cases having visual acuity ≥6/60 doubled from 17.6% to 35.3%. Eyes receiving antifungals had a trend toward worse visual outcome.Conclusions: Corneal involvement in addition to endophthalmitis and the presence of Aspergillus terreus were found to be poor prognostic markers.


Single dose oral codeine, as a single agent, for acute postoperative pain in adults.
Codeine is an opioid metabolised to active analgesic compounds, including morphine. It is widely available by prescription, and combination drugs including low doses of codeine are commonly available without prescription. To assess the efficacy, the time to onset of analgesia, the time to use of rescue medication and any associated adverse events of single dose oral codeine in acute postoperative pain. We searched CENTRAL, MEDLINE, EMBASE and PubMed to November 2009. Single oral dose, randomised, double-blind, placebo-controlled trials of codeine for relief of established moderate to severe postoperative pain in adults. Studies were assessed for methodological quality and data independently extracted by two review authors. Summed total pain relief (TOTPAR) or pain intensity difference (SPID) over 4 to 6 hours were used to calculate the number of participants achieving at least 50% pain relief, which were used to calculate, with 95% confidence intervals, the relative benefit compared to placebo, and the number needed to treat (NNT) for one participant to experience at least 50% pain relief over 4 to 6 hours. Numbers using rescue medication over specified time periods, and time to use of rescue medication, were sought as additional measures of efficacy. Data on adverse events and withdrawals were collected. Thirty-five studies were included (1223 participants received codeine 60 mg, 27 codeine 90 mg, and 1252 placebo). Combining all types of surgery (33 studies, 2411 participants), codeine 60 mg had an NNT of at least 50% pain relief over 4 to 6 hours of 12 (8.4 to 18) compared with placebo. At least 50% pain relief was achieved by 26% on codeine 60 mg and 17% on placebo.Following dental surgery the NNT was 21 (12 to 96) (15 studies, 1146 participants), and following other types of surgery the NNT was 6.8 (4.6 to 13) (18 studies, 1265 participants). The NNT to prevent use of rescue medication within 4 to 6 hours was 11 (6.3 to 50) (11 studies, 765 participants, mostly non-dental); the mean time to its use was 2.7 hours with codeine and 2.0 hours with placebo. More participants experienced adverse events with codeine 60 mg than placebo; the difference was not significant and none were serious. Two adverse event withdrawals occurred with placebo. Single dose codeine 60 mg provides good analgesia to few individuals, and does not compare favourably with commonly used alternatives such as paracetamol, NSAIDs and their combinations with codeine, especially after dental surgery; the large difference between dental and other surgery was unexpected. Higher doses were not evaluated.


Tear osmolality and ferning patterns in postmenopausal women.
To compare tear osmolality and ferning patterns in postmenopausal women (PMW) with and without dry eye symptoms. Thirty-seven healthy PMW (>50 years of age), not on hormone replacement therapy, were categorized as being symptomatic or asymptomatic of dry eye based on their responses to an Allergan "Single-Item Score Dry Eye Questionnaire" (SIDEQ). They subsequently completed the Allergan "Ocular Surface Disease Index" (OSDI) questionnaire. Tear samples were collected from participants to evaluate osmolality and ferning patterns. A novel freezing point depression osmometer (Advanced Instruments Inc., Model 3100 Tear Osmometer), was used to measure the osmolality of the tear film. The tear ferning test was performed and evaluated for the quality of ferning based on the Rolando grading system. SIDEQ responses revealed 21 symptomatic and 16 asymptomatic participants. The OSDI total score was 6.5 +/- 5.9 for the non-dry-eyed (NDE) group and 25.7 +/- 12.4 for the dry-eyed (DE) group. The subscores for the DE group were significantly greater than the NDE group (p < 0.001). Osmolality values in DE individuals were significantly different from NDE (328.1 +/- 20.8 vs. 315.1 +/- 11.3 mOsm/kg; p = 0.02). Fifty percent of the DE participants showed type II ferning patterns and 29% of the DE participants showed type III ferning patterns, whereas the NDE participants showed either type I (44%) or II (66%) ferning patterns. There was a significant difference between the DE and NDE participants for the ferning patterns (p = 0.019). There was no significant correlation between tear osmolality and tear ferning (DE: r = 0.12; p > 0.05, NDE: r = -0.17; p > 0.05). Osmolality in mild and moderately DE PMW is higher than in NDE PMW and tear ferning is a rapid, simple, noninvasive laboratory procedure that indicates altered tear quality in PMW with symptoms of dry eye.


Tuberculosis of the axis in a patient with systemic sarcoidosis: technique of posterior open biopsy of the dens: case report.
This case report illustrates the importance of obtaining tissue from a destructive lesion of the dens in a patient with systemic sarcoidosis. Although sarcoidosis can involve the axial skeleton, tissue obtained at the time of C1-C2 fusion demonstrated unsuspected pathological features, which dramatically altered the subsequent medical treatment. The technique of open posterior biopsy of the dens is illustrated, and the advantages of the approach are discussed. A 40-year-old woman with systemic sarcoidosis developed neck pain and atlantoaxial instability. Imaging revealed multiple thoracic and cervical vertebral abnormalities, including a destructive enhancing lesion involving the base of the dens. At the time of posterior C1-C2 fusion, we elected to perform an open biopsy of the base of the dens. A 16-gauge biopsy needle was introduced along the medial portion of the left C2 pars, aiming medially toward the base of the odontoid process. This procedure was performed under direct observation, with fluoroscopic guidance. The biopsy specimen contained caseating granulomas, and cultures were positive for Mycobacterium tuberculosis. The unusual presentation, the technique, and the importance of obtaining tissue to confirm the diagnosis of tuberculous involvement of the dens are emphasized. The relationship between sarcoidosis and tuberculosis reported in the literature is reviewed. In the current case, cell wall-positive tuberculous bacteria were cultured, confirming the presence of two separate diseases in the same patient.


["Loss of perspective is my disease" -- subjective feelings of long-term unemployed].
Nowadays job loss implies the risk of long-term unemployment particularly in former East Germany. Many physical, psychological and social problems are associated with unemployment. However, health of long-term unemployed may not decrease continually, but may be subject to fluctuations according to different phases of unemployment and short-term work. This expectation was examined by structured interviews with long-term unemployed (10 men and women) working in temporary job-creating-schemes (ABM). We asked for determinants of health and subjectively perceived associations between health and employment as well as for conditions of life and work. The employees were on average 55 years old and more than 7 years without work before joining the ABM. Psychosocial complaints such as depression, sleep disorders or nervousness appeared after approximately three months of unemployment. Subjective health improved during job-creating-schemes, depending on specific work conditions, but deteriorate at its end again. Most of the ABM-employees don't have any perspective of future employment. The well-known association between unemployment and health was confirmed. Furthermore, the study gave new insights into psychological strains of long-term unemployed and subjective work loads during ABM. Future prospects were proved to be an important determinant of health ('lack of perspective is my illness'). From this measures of health promotion for long-term unemployed within ABM companies and other institutions can be derived.


Brain derived neurotrophic factor and cognitive status: the delicate balance among people living with HIV, with and without alcohol abuse.
The advent of combination antiretroviral therapy(cART) has lead to a significant reduction in morbidity and mortality among people living with HIV(PLWH). However, HIV-associated neurocognitive disorders (HAND) still remain a significant problem. One possible mechanism for the persistence of these disorders is through the effect of HIV on brain-derived neurotrophic factor (BDNF). BDNF is influenced by various factors including hazardous alcohol use (HAU), which is prevalent among PLWH. This study attempts to elucidate the relationships between HAU, BDNF and HAND. Cross-sectional analyses were conducted on a sample of 199 hazardous alcohol users and 198 non-HAU living with HIV. Members of each group were matched according to sociodemographic characteristics and CD4 count. Research procedures included validated questionnaires, neuropsychological assessments and a blood sample to obtain BDNF and immune measurements. Hazardous alcohol users showed either significantly lower or significantly higher BDNF levels compared to the Non-hazardous (OR=1,4; 95% CI: 1-2.1, p = 0.003). Therefore, for additional analyses, subjects were categorized based on BDNF values in: Group 1 < 4000, Group 2: 4001-7,999 (reference group), and Group 3 for those >8,000 pg/mL. Groups 1 and 3 performed significantly worse than those in Group 2 in the domains of processing speed, auditory-verbal and visuospatial learning and memory. Multivariate analyses confirmed that HAU and BDNF are significant contributors of HAND. Our findings offer novel insights into the relationships between BDNF, and alcohol use among PLWH. Our results also lend support to expanding clinical movement to use BDNF as an intervention target for PLWH, in those with evidence of deficiencies, and highlight the importance of including HAUat the inception of clinical trials.


BAFF augments certain Th1-associated inflammatory responses.
B cell-activating factor belonging to the TNF family (BAFF; BLyS) is a critical regulator of B cell maturation and survival, and its overexpression in BAFF transgenic (Tg) mice results in the development of autoimmune disorders. BAFF also affects T cell function through binding to one of the BAFF receptors, BAFF-R. Using BAFF Tg mice, we examined a typical Th1-mediated response, the cutaneous delayed-type hypersensitivity reaction, and found a much greater degree of paw swelling and inflammation than in control mice. Importantly, delayed-type hypersensitivity scores correlated directly with BAFF levels in serum. Conversely, in a Th2-mediated model of allergic airway inflammation, BAFF Tg mice were largely protected and showed markedly reduced Ag-specific T cell proliferation and eosinophil infiltration associated with the airways. Thus, local and/or systemically distributed BAFF affects Th1 and Th2 responses and impacts on the course of some T cell-mediated inflammatory reactions. Our results are consistent with the idea that BAFF augments T cell as well as B cell responses, particularly Th1-type responses. Results in BAFF Tg mice may reflect the situation in certain autoimmune patients or virally infected individuals, because BAFF levels in blood are comparable.


Gene doping.
Together with the rapidly increasing knowledge on genetic therapies as a promising new branch of regular medicine, the issue has arisen whether these techniques might be abused in the field of sports. Previous experiences have shown that drugs that are still in the experimental phases of research may find their way into the athletic world. Both the World Anti-Doping Agency (WADA) and the International Olympic Committee (IOC) have expressed concerns about this possibility. As a result, the method of gene doping has been included in the list of prohibited classes of substances and prohibited methods. This review addresses the possible ways in which knowledge gained in the field of genetic therapies may be misused in elite sports. Many genes are readily available which may potentially have an effect on athletic performance. The sporting world will eventually be faced with the phenomena of gene doping to improve athletic performance. A combination of developing detection methods based on gene arrays or proteomics and a clear education program on the associated risks seems to be the most promising preventive method to counteract the possible application of gene doping.