Surgical management of piriform sinus fistula.
Four cases of acute cervical abscess resulting from infection through the left piriform sinus fistula are described. The fistula seems to be related to the cause of infection in many of previously reported cases of acute suppurative thyroiditis or "recurrent lateral cervical fistula." Complete removal of the fistula is essential to a permanent cure, and the guide of a Fogarty catheter through the fistula is useful at operation for patients with repeated infection.


Acquired immune deficiency syndrome.
Acquired immune deficiency syndrome, or AIDS, is an unexplained severe disturbance of the cell-mediated immune system that renders victims susceptible to a group of otherwise-rare diseases and infections, chiefly Kaposi's sarcoma and Pneumocystis carinii pneumonia. AIDS has been the object of intensive research since mid-1981 when the syndrome was first described by the Centers for Disease Control (CDC). The victims fall into four main group: homosexually-active males, IV drug users, Haitians, and hemophiliacs. The CDC has noted a doubling of AIDS cases every six months, with the current count--as of June 27, 1983--being 1,676, and the overall mortality rate 39%. The outbreak is most severe in New York City, with the remainder concentrated primarily in other major American cities. Cases have also been reported in 38 states, Washington, D.C., and Puerto Rico. At present there are no specific diagnostic tests (diagnosis is primarily clinical), and there is still no specific treatment.


Equivalent circuit for birdcage resonators.
We present an equivalent circuit analysis for both low pass and high pass birdcage resonators loaded with lossy samples. In a generalization of the method of Hoult and Lauterbur (J. Magn. Reson. 34, 425 (1979)), we also derive circuit component values by application of the laws of electrodynamics. Measured resonance spectra, quality factors, and feed point impedances in a test resonator are shown to be in agreement with those predicted by the proposed model.


Ab initio potential energy surface and bound states for the Kr-OCS complex.
The first ab initio potential energy surface of the Kr-OCS complex is developed using the coupled-cluster singles and doubles with noniterative inclusion of connected triples [CCSD(T)]. The mixed basis sets, aug-cc-pVTZ for the O, C, and S atom, and aug-cc-pVQZ-PP for the Kr atom, with an additional (3s3p2d1f) set of midbond functions are used. A potential model is represented by an analytical function whose parameters are fitted numerically to the single point energies computed at 228 configurations. The potential has a T-shaped global minimum and a local linear minimum. The global minimum occurs at R = 7.146 a(0), θ = 105.0° with energy of -270.73 cm(-1). Bound state energies up to J = 9 are calculated for three isotopomers (82)Kr-OCS, (84)Kr-OCS, and (86)Kr-OCS. Analysis of the vibrational wavefunctions and energies suggests the complex can exist in two isomeric forms: T-shaped and quasi-linear. The calculated transition frequencies and spectroscopic constants of the three isotopomers are in good agreement with the experimental values.


Combination of Weight-Bearing Training and Anti-MSTN Polyclonal Antibody Improve Bone Quality In Rats.
Weight-bearing exercise is beneficial to bone health. Myostatin (MSTN) deficiency has a positive effect on bone formation. We wondered if a combination of weight-bearing training and polyclonal antibody for MSTN (MsAb) would augment bone formation to a greater degree than single treatment. In this study, rats were randomly assigned to four groups: Control, weight-bearing training (WT), MsAb, and WT+MsAb. The trained rats ran at 15 m/min bearing with 35% of their body weight, 40 min/day (2 min of running followed by 2 min of rest), 6 days/week, for 8 weeks. The rats with MsAb were injected once a week with MsAb for 8 weeks. MicroCT analysis showed that compared with the MsAb group, WT+MsAb significantly enhanced cortical bone mineral density (BMD) (p < .01), bone volume over total volume (BV/TV) (p < .01), trabecular thickness (p < .05), and reduced trabecular separation (Tb.Sp) (p < .01). Compared with the WT group, WT+MsAb significantly increased trabecular BMD (p < .05), BV/TV (p < .05), and decreased Tb.Sp (p < .05). Three-point bending test demonstrated that MsAb failed to improve bone biomechanical properties (p > .05), weight-bearing training significantly increased energy absorption (p < .05) and elastic modulus (p < .05). However, when they combined, biomechanical properties including maximum load (p < .05), stiffness (p < .05), elastic modulus (p < .01) and energy absorption (p < .01) were all significantly enhanced. In conclusion, the combination of weight-bearing training and MsAb have a greater positive effect on bone than treatment with either MsAb or weight-bearing training alone, suggesting that resistance training in combination with MSTN antagonists could be an effective approach for improving bone health and reducing osteoporosis risk.


Single organelle function and organization as estimated from Arabidopsis mitochondrial proteomics.
Mitochondria host vital cellular functions, including oxidative phosphorylation and co-factor biosynthesis, which are reflected in their proteome. At the cellular level plant mitochondria are organized into hundreds of discrete functional entities, which undergo dynamic fission and fusion. It is the individual organelle that operates in the living cell, yet biochemical and physiological assessments have exclusively focused on the characteristics of large populations of mitochondria. Here, we explore the protein composition of an individual average plant mitochondrion to deduce principles of functional and structural organisation. We perform proteomics on purified mitochondria from cultured heterotrophic Arabidopsis cells with intensity-based absolute quantification and scale the dataset to the single organelle based on criteria that are justified by experimental evidence and theoretical considerations. We estimate that a total of 1.4 million protein molecules make up a single Arabidopsis mitochondrion on average. Copy numbers of the individual proteins span five orders of magnitude, ranging from >40 000 for Voltage-Dependent Anion Channel 1 to sub-stoichiometric copy numbers, i.e. less than a single copy per single mitochondrion, for several pentatricopeptide repeat proteins that modify mitochondrial transcripts. For our analysis, we consider the physical and chemical constraints of the single organelle and discuss prominent features of mitochondrial architecture, protein biogenesis, oxidative phosphorylation, metabolism, antioxidant defence, genome maintenance, gene expression, and dynamics. While assessing the limitations of our considerations, we exemplify how our understanding of biochemical function and structural organization of plant mitochondria can be connected in order to obtain global and specific insights into how organelles work.


Characterization of redox and salinity-tolerant alkaline protease from Bacillus halotolerans strain DS5.
Bacillus halotolerans DS5 was isolated and identified as a halophilic microbe according to 16S rRNA analysis and the physical and chemical indices of the strain. A new alkaline protease (designated as prot DS5) from Bacillus halotolerans DS5 was produced, purified, and characterized. After 12 h incubation in the medium with 1% dextrin, 0.5% NaCl, 2% soluble starch, and 1% yeast extract (pH 7.0), it could reach the maximum enzyme activity (279.74 U/ml). The prot DS5 was stable in the pH range of 6.0-12.0 and the temperature range of 40-60°C, with maximal hydrolytic activities at pH 9 and at 50°C. In the presence of Ca2+, Mn2+, Ba2+, Mg2+, and Fe3+, protease activity was enhanced. The prot DS5 was maintained highly stable in NaCl (up to 2.5 mol/L), reducing and oxidizing agents. The prot DS5 also exhibited compatibility in other detergent ingredients, such as non-ionic and anionic surfactants. These properties of prot DS5 make this enzyme suitable for various industrial applications (e.g., detergents and leather).


[Morphology and distribution of Thysanophora crinita (Stylommatophora: Thysanophoridae) in Nicaragua].
A morphological characterization of Thysanophora crinita (Fulton, 1916-1917), including a redescription of the shell and the first description of the genital system, the radula and the jaw, are made based on 58 living individuals and 1378 empty shells; the sample considered for biometry was of 81 specimens. Means and ranges were 3.51 mm (2.6-4.9) diameter and 2 mm (1.5-2.5) height. This species exhibits a discoidal-depressed shell, with an opaque hairy periostracum as its most remarkable feature. The genital system is typical of the genus, with a well developed penis and a pear-shaped bursa copulatrix. Jaw: 16 to 18 narrow plates and radula with 72 transversal rows, formula: (C/3 + 5L/2 + 6M/2) x 2. The Nicaraguan populations of T. crinita are very similar to T. crinita from Cartagena and T.c. arubana, and show dimensions intermediate between both. This species was previously known from Carthagena, Colombia and is reported from Nicaragua for the first time. A distribution map is included.


Study on cardioactive effects of brazilein.
Brazilein (6a,7-dihydro-3,6a,10-trihydroxy-benz[b]indeno[1,2-d]pyran-9(6H)-one) is a compound obtained in a large amount from Caesalpinia sappan ethanol extracts with a high purity of about 98%. In isolated cardiac tissues, we found that brazilein exhibited a positive inotropic action in a concentration-dependent manner with little effect on heart rate and coronary perfusion. To study its possible mode of action, isolated rat hearts were treated with propranolol. This treatment did not alter the cardiotonic effect of brazilein, suggesting that this effect does not involve stimulation of beta-adrenoceptors. On the other hand, an analysis of the interaction between Na(+),K(+)-ATPase and brazilein was carried out. Albino guinea pig erythrocytes (mainly alpha1-Na(+),K(+)-ATPase isoforms) enriched with Na(+),K(+)-ATPase isoforms were utilized to compare the inhibition promoted by brazilein with that of classical inhibitors such as the cardiac glycoside deslanoside. Analysis of inhibition curves revealed that unlike deslanoside, brazilein had a relatively low affinity for erythrocyte isoforms and failed to completely inhibit the Na(+),K(+)-ATPase activity. The extent of the maximum inhibition rate was about 50%. The inhibitory effect of brazilein was not antagonized by 10 mmol/l K(+), as observed with deslanoside. Electrocardiogram research in vivo showed that brazilein did not induce the ventricular arrhythmias observed with deslanoside, suggesting that brazilein might have a less adverse effect and higher therapeutic index than cardiac glycosides. In light of all the above-mentioned observations, it can be concluded that brazilein, a molecule with a non-steroidal skeleton, produced its positive inotropic effect through inhibiting Na(+),K(+)-ATPase and could thus serve as a structural paradigm to develop new inotropic drugs.


Concurrent validity of the Wechsler abbreviated scale of intelligence and the Kaufman brief intelligence test among psychiatric inpatients.
This study examined the convergent and discriminant validity of the Wechsler Abbreviated Scale of Intelligence and the Kaufman Brief Intelligence Test for 85 psychiatric inpatients. The correlation between the WASI Full Scale and K-BIT Composite IQ scores was significant (r = .89, p < .001). Multitrait-multimethod analysis of the subtest scores showed that the K-BIT had higher internal consistency for its two subtests but, therefore, less differentiation of cognitive functioning than the brief Wechsler scale, as would be expected due to the larger number and diversity of the latter subtests. Correlations among the Wechsler scale subtests were lower than among those for the K-BIT, so the former may tap different cognitive functions and yield more clinically useful information than the latter. This brief Wechsler scale appears to be a valid screening measure of verbal, performance. and general intellectual ability for use with an inpatient psychiatric population when considerations of the setting or patient preclude administration of a longer measure of intellectual ability.


Is radical prostatectomy the "gold standard" for localized prostate cancer?
The purpose of this article is to review the pertinent literature and compare the outcomes after radical prostatectomy (RP) and radiotherapy (RT). The probability of cure is similar after either RP or RT. The likelihood of significant treatment complications is probably higher after RP compared with RT. Preservation of erectile function is at least as good or better with RT compared with RP. Urinary continence is more likely to be preserved after RT compared with RP. Each treatment results in distinct patterns of adverse changes in quality of life that are worsened by factors including obesity, large prostate size, high prostate-specific antigen (PSA), and older age.


Brain activations associated with fearful experience show common and distinct patterns between younger and older adults in the hippocampus and the amygdala.
Revisiting threat-related scenes elicits fear and activates a brain network related to cognitive-affective processing. Prior experience may contribute to the present fearful experience. We aimed to investigate (a) patterns of brain activation associated with individual differences in past fearful experiences (pFear) and the present fear elicited by watching videos (eFear) and (b) age-related differences in the activation patterns. Forty healthy adults, including 20 younger adults (YA) and 20 older adults (OA), underwent functional magnetic resonance imaging while watching videos containing high- and low-threat scenes of medical treatment. Both age subgroups showed positive correlations between pFear and bilateral hippocampal activation. Only YA showed threat-related activation in the bilateral anterior insula and activation positively correlated with pFear in the bilateral S1 and the amygdala. The evidence suggests that the hippocampus, amygdala and S1 may play key roles in bridging past fearful experiences and the present fear elicited by revisiting visual scenes and that the interaction between memory and emotional processing may be age dependent.


Electromechanical-assisted training for walking after stroke.
Electromechanical and robotic-assisted gait training devices are used in rehabilitation and might help to improve walking after stroke. This is an update of a Cochrane Review first published in 2007. To investigate the effects of automated electromechanical and robotic-assisted gait training devices for improving walking after stroke. We searched the Cochrane Stroke Group Trials Register (last searched April 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 2), MEDLINE (1966 to November 2012), EMBASE (1980 to November 2012), CINAHL (1982 to November 2012), AMED (1985 to November 2012), SPORTDiscus (1949 to September 2012), the Physiotherapy Evidence Database (PEDro, searched November 2012) and the engineering databases COMPENDEX (1972 to November 2012) and INSPEC (1969 to November 2012). We handsearched relevant conference proceedings, searched trials and research registers, checked reference lists and contacted authors in an effort to identify further published, unpublished and ongoing trials. We included all randomised and randomised cross-over trials consisting of people over 18 years old diagnosed with stroke of any severity, at any stage, or in any setting, evaluating electromechanical and robotic-assisted gait training versus normal care. Two review authors independently selected trials for inclusion, assessed methodological quality and extracted the data. The primary outcome was the proportion of participants walking independently at follow-up. In this update of our review, we included 23 trials involving 999 participants. Electromechanical-assisted gait training in combination with physiotherapy increased the odds of participants becoming independent in walking (odds ratio (OR) (random effects) 2.39, 95% confidence interval (CI) 1.67 to 3.43; P < 0.00001; I² = 0%) but did not significantly increase walking velocity (mean difference (MD) = 0.04 metres/s, 95% CI -0.03 to 0.11; P = 0.26; I² = 73%) or walking capacity (MD = 3 metres walked in six minutes, 95% CI -29 to 35; P = 0.86; I² = 70%). The results must be interpreted with caution because (1) some trials investigated people who were independent in walking at the start of the study, (2) we found variations between the trials with respect to devices used and duration and frequency of treatment, and (3) some trials included devices with functional electrical stimulation. Our planned subgroup analysis suggests that people in the acute phase may benefit but people in the chronic phase may not benefit from electromechanical-assisted gait training. Post hoc analysis showed that people who are non-ambulatory at intervention onset may benefit but ambulatory people may not benefit from this type of training. Post hoc analysis showed no differences between the types of devices used in studies regarding ability to walk, but significant differences were found between devices in terms of walking velocity. People who receive electromechanical-assisted gait training in combination with physiotherapy after stroke are more likely to achieve independent walking than people who receive gait training without these devices. Specifically, people in the first three months after stroke and those who are not able to walk seem to benefit most from this type of intervention. The role of the type of device is still not clear. Further research should consist of a large definitive, pragmatic, phase III trial undertaken to address specific questions such as the following: What frequency or duration of electromechanical-assisted gait training might be most effective? How long does the benefit last?


[Effect of thrombolytic agents on platelets and blood coagulation system].
The effect of tissue-type plasminogen activator (tPA) on platelet aggregation and blood coagulation was investigated. Collagen-induced platelet aggregation in washed platelet suspension was significantly inhibited by the addition of tPA, but the effect was limited when platelet rich plasma was used instead of washed platelets because of the presence of alpha 2-antiplasmin in plasma. The diluted prothrombin time was significantly shortened by the addition of tPA to normal plasma, and although the levels of molecular markers of thrombin formation were increased compared to that of normal controls, the increase was diminished when factor VII-deficient plasma was used, suggesting that tPA enhances factor VII. The activated factor VII concentration was significantly increased by the addition of plasmin to factor VII solution. These findings suggest that tPA enhances the coagulation system by factor VII activation through the generation of plasmin in normal plasma. This enhancing effect of tPA on coagulation system may be partly related to vascular reocclusion after thrombolytic therapy.


Regulated endosomal trafficking of Diacylglycerol lipase alpha (DAGLα) generates distinct cellular pools; implications for endocannabinoid signaling.
Diacylglycerol lipase alpha (DAGLα) generates the endocannabinoid (eCB) 2-arachidonylglycerol (2-AG) that regulates the proliferation and differentiation of neural stem cells and serves as a retrograde signaling lipid at synapses. Nothing is known about the dynamics of DAGLα expression in cells and this is important as it will govern where 2-AG can be made and released. We have developed a new construct to label DAGLα at the surface of live cells and follow its trafficking. In hippocampal neurons a cell surface pool of DAGLα co-localizes with Homer, a postsynaptic density marker. This surface pool of DAGLα is dynamic, undergoing endocytosis and recycling back to the postsynaptic membrane. A similar cycling is seen in COS-7 cells with the internalized DAGLα initially transported to EEA1 and Rab5-positive early endosomes via a clathrin-independent pathway before being transported back to the cell surface. The internalized DAGLα is present on reticular structures that co-localize with microtubules. Importantly, DAGLα cycling is a regulated process as inhibiting PKC results in a significant reduction in endocytosis. This is the first description of DAGLα cycling between the cell surface and an intracellular endosomal compartment in a manner that can regulate the level of the enzyme at the cell surface.


A novel experimental approach for the selective isolation and characterization of human RNase MRP.
RNase MRP is a ribonucleoprotein complex involved in the endoribonucleolytic cleavage of different RNAs. Mutations in the RNA component of the RNP are the cause of cartilage hair hypoplasia. Patients with cartilage hair hypoplasia are characterized by skeletal dysplasia. Biochemical purification of RNase MRP is desired to be able to study its biochemical function, composition and activity in both healthy and disease situations. Due to the high similarity with RNase P, a method to specifically isolate the RNase MRP complex is currently lacking. By fusing a streptavidin-binding RNA aptamer, the S1m-aptamer, to the RNase MRP RNA we have been able to compare the relative expression levels of wildtype and mutant MRP RNAs. Moreover, we were able to isolate active RNase MRP complexes. We observed that mutant MRP RNAs are expressed at lower levels and have lower catalytic activity compared to the wildtype RNA. The observation that a single nucleotide substitution at position 40 in the P3 domain but not in other domains of RNase MRP RNA severely reduced the binding of the Rpp25 protein subunit confirmed that the P3 region harbours the main binding site for this protein. Altogether, this study shows that the RNA aptamer tagging approach can be used to identify RNase MRP substrates, but also to study the effect of mutations on MRP RNA expression levels and RNase MRP composition and endoribonuclease activity.


[Site-specific recombinases in genetic engineering: modern in vivo technologies].
Current advances in the field of site-specific recombinases (SSR) and their application for pro- and eukaryotic genomics are reviewed. Functions of SSR and main types of the genetic rearrangements they catalyze are outlined. Examples described in the review show the potential of SSR for studies of a diverse array of fundamental and applied problems, which are not easily solved (or not solved at all) with the help of other experimental approaches. Use of SSR for wider set of biological systems, generation of recombinases with a strict temporal and spatial control of their activity and search for SSR displaying new substrate specificity are major directions of development of SSR-based technology.


NYHA Functional Classification and Outcomes After Transcatheter Mitral Valve Repair in Heart Failure: The COAPT Trial.
The aim of this study was to evaluate the outcomes of MitraClip implantation versus guideline-directed medical therapy (GDMT) in patients with secondary mitral regurgitation (SMR) according to baseline functional status as assessed by the widely used New York Heart Association (NYHA) functional classification. Patients with heart failure (HF) and impaired functional status at baseline have poor prognosis. Whether the effects of transcatheter repair of secondary SMR in patients with HF are influenced by baseline functional status is unknown. In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, patients with HF with moderate to severe or severe SMR who remained symptomatic despite maximally tolerated GDMT were randomized to MitraClip implantation versus GDMT alone. Outcomes were evaluated according to baseline functional status as assessed using the NYHA functional classification. The primary endpoint of interest was the rate of death or HF-related hospitalization (HFH) at 2 years in time-to-first-event analyses. Among 613 randomized patients, 240 were in NYHA functional class II (39.2%), 322 were in NYHA functional class III (52.5%), and 51 were in ambulatory NYHA functional class IV (8.3%). Rates of death or HFH were progressively higher with increasing NYHA functional class. Compared with GDMT alone, MitraClip implantation resulted in lower 2-year rates of death or HFH consistently in patients in NYHA functional class II (39.7% vs. 63.7%; hazard ratio [HR]: 0.54; 95% confidence interval [CI]: 0.37 to 0.77), NYHA functional class III (46.6% vs. 65.5%; HR: 0.60; 95% CI: 0.45 to 0.82), and NYHA functional class IV (66.7% vs. 85.2%; HR: 0.55; 95% CI: 0.28 to 1.10; pinteraction = 0.86). Greater improvements in quality of life at 2 years were observed in patients treated with the MitraClip compared with GDMT irrespective of baseline functional status. The NYHA functional classification provides prognostic utility in patients with HF and moderate to severe or severe SMR. In the COAPT trial, the benefits of MitraClip implantation were consistent in patients with better or worse functional status as assessed by NYHA functional class. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] [COAPT]; NCT01626079).


Tenofovir: what have over 1 million years of patient experience taught us?
Several groundbreaking trials and over 1 million years of patient experience have established tenofovir as an important component of HIV treatment. Tenofovir has demonstrated potent antiviral efficacy, with a low risk of developing resistance when used as part of an effective combination regimen. It is generally well tolerated, with a low risk of lipoatrophy and a favourable effect on lipid profile compared with older nucleoside analogue agents such as stavudine or zidovudine. Clinical data suggest that switching from thymidine analogues to a tenofovir-containing regimen can benefit patients with lipid abnormalities or lipoatrophy. This article reviews the development of tenofovir, including pivotal studies that have influenced HIV clinical practice.


[An uncommon cause of gynecomastia: testicular Leydig cell tumor. Hormonal profile before and after orchiectomy].
Leydig cell tumors (LTC) are uncommon neoplasms arising from gonadal stroma that account for 1-3% of all testicular tumors. We report a case of LCT in a 36 years old man who had been suffering from painful bilateral gynecomastia for one year. Endocrine function tests showed decreased gonadotropin concentrations, and reduction of testosterone/estradiol ratio. Ultrasonography revealed a 10-12 mm hypoechoic area in the right testis, not evident on physical examination. Right orchiectomy was performed and histological examination confirmed the supposed existence of a LCT. After surgery, the gynecomastia has completely disappeared and hormonal alterations returned to normal.


[A case of fibrous pseudotumor arising from the paratesticular area].
Intrascrotal fibrous pseudotumor is rarely observed, and only 40 cases have been reported in Japan. A 65-year-old male patient visited this hospital due to a painless right scrotal mass. Computed tomography demonstrated a solid mass with a cystic component ; however, the exact location of the mass in relation to other scrotal contents was not determined. Intraoperative findings revealed a solid mass, 2 cm in diameter, in the tunica vaginalis. The mass could not be dissected from the epididymis ; therefore, high orchiectomy was indicated. A histopathological diagnosis of fibrous pseudotumor was made. The patient's postoperative course was uneventful, and no recurrence has been found. It is difficult to make a diagnosis of paratesticuler tumor based on preoperative radiological results and even macroscopic observation during surgery. We strongly recommend that it is necessary to undergo high orchiectomy for a fibrous pseudotumor in which dissection from the peripheral tissue is very difficult since it may involve various types which may lead to a diagnosis of malignancy.


Feasibility of linking external valuation sources to bedside-caregiver activities in interdisciplinary patient care standards.
Establishing accurate and standardized values for bedside-care activities is crucial to the development of resource utilization prediction and management systems. We describe our experience of associating a representative sample of activities extracted from interdisciplinary patient care standards developed at Intermountain Healthcare with an external database of time & motion valued actions. The association exercise revealed important considerations for the development of a standard methodology for linking activities to future national or international standardized value units.


Clinical pearls for the monitoring and treatment of antipsychotic induced metabolic syndrome.
Antipsychotic medications increase the risk of metabolic syndrome, which then increases the risk of atherosclerotic cardiovascular disease and premature death. Routinely monitoring for signs of metabolic syndrome in patients taking antipsychotics allows for early detection and intervention. Psychiatric pharmacists can improve patient care through metabolic syndrome monitoring and recommendation of appropriate interventions. Monitoring for the metabolic adverse effects of antipsychotics, management of weight gain, and management of lipids and blood pressure are explored through 2 patient cases.


Adhesive capsulitis: a case study.
Adhesive capsulitis (AC), also known as frozen shoulder, is a common and painful musculoskeletal disorder. The shoulder is a complex joint comprising 3 bones and multiple muscle groups, ligaments, and tendons. Accompanying the inflammation of the joint is stiffness that greatly restricts the patient's motion and strength. AC is a treatable condition requiring months of daily physical therapy. The reports that 1 in 7 Americans has a musculoskeletal impairment including shoulder problems that accounted for 14 million visits to physicians' offices in 2003. It is imperative that practitioners accurately assess and diagnose the patient with shoulder pain to facilitate an appropriate plan of care. This paper will discuss the case of a patient with AC including differential diagnoses, pathophysiology, and treatment options.


Video image analysis as a potential grading system for Uruguayan beef carcasses.
A study was conducted in 2 phases to evaluate the effectiveness of 1) the VIAscan Beef Carcass System (BCSys; hot carcass system) and the CVS BeefCam (chilled carcass system), used independently or in combination, to predict Uruguayan beef carcass fabrication yields; and 2) the CVS BeefCam to segregate Uruguayan beef carcasses into groups that differ in the Warner-Bratzler shear force (WBSF) values of their LM steaks. The results from the meat yield phase of the present study indicated that the prediction of saleable meat yield percentages from Uruguayan beef carcasses by use of the BCSys or CVS BeefCam is similar to, or slightly better than, the use of USDA yield grade calculated to the nearest 0.1 and was much more effective than prediction based on Uruguay National Institute of Meat (INAC) grades. A further improvement in fabrication yield prediction could be obtained by use of a dual-component video image analysis (VIA) system. Whichever method of VIA prediction of fabrication yield is used, a single predicted value of fabrication yield for every carcass removes an impediment to the implementation of a value-based pricing system. Additionally, a VIA method of predicting carcass yield has the advantage over the current INAC classification system in that estimates would be produced by an instrument rather than by packing plant personnel, which would appeal to cattle producers. Results from the tenderness phase of the study indicated that the CVS BeefCam output variable for marbling was not (P > 0.05) able to segregate steer and heifer carcasses into groups that differed in WBSF values. In addition, the results of segregating steer and heifer carcasses according to muscle color output variables indicate that muscle maturity and skeletal maturity were useful for segregating carcasses according to differences in WBSF values of their steaks (P > 0.05). Use of VIA to predict beef carcass fabrication yields could improve accuracy and reduce subjectivity in comparison with use of current INAC grades. Use of VIA to sort carcasses according to muscle color would allow for the marketing of more consistent beef products with respect to tenderness. This would help facilitate the initiation of a value-based marketing system for the Uruguayan beef industry.


Neuropathology and therapeutic intervention in spinal and bulbar muscular atrophy.
Spinal and bulbar muscular atrophy (SBMA) is a hereditary motor neuron disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The histopathological finding in SBMA is loss of lower motor neurons in the anterior horn of the spinal cord as well as in the brainstem motor nuclei. Animal studies have revealed that the pathogenesis of SBMA depends on the level of serum testosterone, and that androgen deprivation mitigates neurodegeneration through inhibition of nuclear accumulation of the pathogenic AR. Heat shock proteins, ubiquitin-proteasome system and transcriptional regulation are also potential targets of therapy development for SBMA.


Maternal depressive symptoms during pregnancy, and newborn irritability.
Maternal depression is associated with a wide range of adverse outcomes for children, including poor mother-infant interactions at 3 months post-partum. The aim of this study is to determine whether maternal depressive symptoms during pregnancy are associated with neonatal neurobehavioral functioning, as measured by the Neurologic and Adaptive Capacity Scale. The study population consists of 1,123 mothers and their term infants who were participants in a larger study of maternal health and infant outcomes. Women were administered the Center for Epidemiologic Studies-Depression (CES-D) questionnaire for depressive symptoms during their pregnancy. Their infants were subsequently assessed by a pediatrician blind to their CES-D scores. The CES-D score was associated with unconsolability and excessive crying (p less than 0.01). The higher the mother's CES-D score, the more likely it was that the infant would be unconsolable or cry excessively. Mothers with CES-D scores at the 90th percentile were 2.6 times more likely to have unconsolable newborns, compared with women with CES-D scores at the 10th percentile (95% C.I. = 1.54, 4.23). When potentially confounding variables, such as cigarette smoking, alcohol, marijuana, and cocaine use, poor weight gain, income, birth weight, and other drug use, were controlled, the relationship between CES-D score and newborn unconsolability and excessive crying remain unchanged. The results of this study suggest that the relationship between early childhood problems and maternal depressive symptoms may be part of a sequence that starts with depressive symptoms during pregnancy.


Detection of Campylobacter jejuni in rectal swab samples from Rousettus amplexicaudatus in the Philippines.
Bats are the second diversity species of mammals and widely distributed in the world. They are thought to be reservoir and vectors of zoonotic pathogens. However, there is scarce report of the evidence of pathogenic bacteria kept in bats. The precise knowledge of the pathogenic bacteria in bat microbiota is important for zoonosis control. Thus, metagenomic analysis targeting the V3-V4 region of the 16S rRNA of the rectal microbiota in Rousettus amplexicaudatus was performed using high throughput sequencing. The results revealed that 103 genera of bacteria including Camplyobacter were detected. Campylobacter was second predominant genus, and Campylobacter coli and Campylobacter jejuni were identified in microbiome of R. amplexicaudatus. Campylobacteriosis is one of the serious bacterial diarrhea in human, and the most often implicated species as the causative agent of campylobacteriosis is C. jejuni. Therefore, we investigated the prevalence of C. jejuni in 91 wild bats with PCR. As a result of PCR assay targeted on 16S-23S intergenic spacer, partial genome of C. jejuni was detected only in five R. amplexicaudatus. This is the first report that C. jejuni was detected in bat rectal swab samples. C. jejuni is the most common cause of campylobacteriosis in humans, transmitted through water and contact with livestock animals. This result indicated that R. amplexicaudatus may be a carrier of C. jejuni.


High association between accessory soleus muscle and Achilles tendonopathy.
This study investigated the association between accessory soleus muscle and abnormalities of the Achilles tendon. The authors reviewed 15 consecutive cases with a diagnosis of accessory soleus muscle from a computerized database of ankle magnetic resonance (MR) examinations reported between January 1998 and January 2007. On review, two cases were eliminated because of an incorrect initial diagnosis: One patient had a low lying soleus attachment to the Achilles tendon, while the other had a prominent flexor hallucis longus tendon partially obliterating Kager's fat. The remaining 13 cases with accessory soleus muscles were evaluated for Achilles tendon abnormalities. There were 13 cases of accessory soleus muscles in 11 patients; two patients had bilateral accessory soleus muscles (the only study patients with bilateral MR examinations in our sample). There were five male and six female patients ranging from 15 to 81 years of age (mean 48). There were nine cases (69.2%) in which Achilles tendonopathy was associated with accessory soleus muscle, including tendonopathy of each Achilles tendon in the two patients with bilateral accessory muscles. In our small patient population, there was a high association between accessory soleus muscle and Achilles tendonopathy.


Two-period contra-directional grating assisted coupler.
We present the design, analysis, and experimental characterization of a novel integrated add-drop filter capable of filtering simultaneously two independent channels that is based on a contra-directional grating assisted coupler with two different periods. The device performance is explained using Fourier analysis and confirmed with numerical simulations using the eigenmode expansion method. The devices were fabricated using electron-beam lithography on a silicon-on-insulator wafer with a 220 nm thick device layer. The Fourier analysis, simulations and experimental results are in agreement and show that the drop port response of the two-period configuration is the superposition of the drop port responses of two single-period gratings. Therefore, the output channels at drop port can be designed independently and can have different bandwidths.


A broadly conserved pathway generates 3'UTR-directed primary piRNAs.
Piwi-interacting RNAs (piRNAs) are approximately 24-30 nucleotide regulatory RNAs that are abundant in animal gonads and early embryos. The best-characterized piRNAs mediate a conserved pathway that restricts transposable elements, and these frequently engage a "ping-pong" amplification loop. Certain stages of mammalian testis also accumulate abundant piRNAs of unknown function, which derive from noncoding RNAs that are depleted in transposable element content and do not engage in ping-pong. We report that the 3' untranslated regions (3'UTRs) of an extensive set of messenger RNAs (mRNAs) are processed into piRNAs in Drosophila ovaries, murine testes, and Xenopus eggs. Analysis of different mutants and Piwi-class immunoprecipitates indicates that their biogenesis depends on primary piRNA components, but not most ping-pong components. Several observations suggest that mRNAs are actively selected for piRNA production for regulatory purposes. First, genic piRNAs do not accumulate in proportion to the level of their host transcripts, and many highly expressed transcripts lack piRNAs. Second, piRNA-producing mRNAs in Drosophila and mouse are enriched for specific gene ontology categories distinct from those of simply abundant transcripts. Third, the protein output of traffic jam, whose 3'UTR generates abundant piRNAs, is increased in piwi mutant follicle clones. We reveal a conserved primary piRNA pathway that selects and metabolizes the 3'UTRs of a broad set of cellular transcripts, probably for regulatory purposes. These findings strongly increase the breadth of Argonaute-mediated small RNA systems in metazoans.


Hypervariable-control-region sequences reveal global population structuring in a long-distance migrant shorebird, the Dunlin (Calidris alpina).
Hypervariable segments of the control region of mtDNA as well as part of the cytochrome b gene of Dunlins were amplified with PCR and sequenced directly. The 910 base pairs (bp) obtained for each of 73 individuals complete another of the few sequencing studies that examine the global range of a vertebrate species. A total of 35 types of mtDNA were detected, 33 of which were defined by the hypervariable-control-region segments. Thirty of the latter were specific to populations of different geographic origin in the circumpolar breeding range of the species. The remaining three types indicate dispersal between populations in southern Norway and Siberia, but female-mediated flow of mtDNA apparently is too low to overcome the effects of high mutation rates of the control-region sequences, as well as population subdivision associated with historical range disjunctions. A genealogical tree relating the types grouped them into five populations: Alaska, West Coast of North America, Gulf of Mexico, western Europe, and the Taymyr Peninsula. The Dunlin is thus highly structured geographically, with measures of mutational divergence approaching 1.0 for fixation of alternative types in different populations. High diversity of types within populations as well as moderate long-term effective population sizes argue against severe population bottlenecks in promoting this differentiation. Instead, population fragmentation in Pleistocene refuges is the most plausible mechanism of mtDNA differentiation but at a much earlier time scale than suggested previously with morphometric data.


Characterization of proteins in rat and human intestinal surfactant-like particles.
Phospholipid-rich particles isolated from the apical surface of rat enterocytes have surfactant-like properties and are enriched for intestinal alkaline phosphatase. Purified intact rat particles were used to produce antibodies in rabbits. Antiserum against the rat particle identified major proteins of 48, 68, 98, and 118 kDa on Western blots of isolated rat surfactant-like particle and did not detect any protein in rat intestinal basolateral membranes, rat brush border membranes, or human particles, but did detect a single 180-kDa protein in a preparation of rat milk fat globules, and two proteins (66 and 103 kDa) in rat pulmonary surfactant. The proteins detected on Western blot corresponded with the major proteins identified by Coomassie blue staining. Similar particles were isolated from the apical surface of human intestine and had an enzyme composition, buoyant density, and lipid content similar to those of the rat particles. Antiserum raised against the human jejunal particle detected proteins in the human particle by Western blot that were similar in size with the rat particle proteins (33, 52, 75, 82, and 118 kDa), but did not cross-react with human brush border or rat particle proteins. These studies demonstrate that the surfactant-like particles are present in human as well as rat intestinal tissue, demonstrate similar enzyme and protein content, and confirm their unique identity, distinct from apical brush border or basolateral membranes.


Comparison of detection methods for Escherichia coli O157 in beef livers and carcasses.
Beef organ meat, such as liver, and beef are major food sources contaminated with Escherichia coli O157. This study investigated the detection method of E. coli O157 in beef liver and carcass. In an experiment with beef liver inoculated with E. coli O157, the direct plating method, plating after the immunomagnetic separation (IMS) method, and Shiga toxin (Stx)-producing E. coli detection and E. coli O157 detection loop-mediated isothermal amplification (LAMP) assays were compared for the detection of Stx-producing E. coli O157. Fifty percent and 45% of samples were positive by Stx-producing E. coli detection LAMP assay and E. coli O157 detection LAMP assay, respectively. Thirty-five percent and 10% of samples were positive by the IMS method and direct plating method, respectively. In an examination of beef swab samples, contamination frequencies with E. coli O157 were analyzed by LAMP assays and the IMS method. E. coli O157 was detected in 12 of 230 samples (5.2%). There was no sample positive for E. coli O157 isolation but negative for LAMP assays for Stx gene and O157 antigen gene. Four samples (1.7%) were positive by both LAMP assays but negative by the IMS method. The result that there was no sample positive for the O157 antigen gene, but not the Stx gene, indicated that the IMS method failed to detect E. coli O157. Twenty-nine samples (12.6%) were positive for the Stx gene but not the O157 antigen gene. The results indicated that screening of Stx gene and O157 antigen gene by LAMP assays is effective in saving time and effort to isolate E. coli O157 by the IMS method because the LAMP assay is more sensitive. This suggested that samples positive for Stx gene and O157 antigen gene should be examined by the IMS method to isolate E. coli O157.


Pharmacologic treatment of neonatal sepsis: antimicrobial agents and immunotherapy.
Antimicrobial agents and immunotherapies in the management of neonatal sepsis are discussed. The rationale for the selection of the most commonly used antibacterial drugs, their mechanisms of actions, and indications for use are described. Immunotherapies, both those in clinical use and those under investigation, are discussed. Antibacterial drugs remain the standard of care, but immunotherapy offers the potential for improving outcomes for neonates, especially those who are premature.


3D Printing of Oil Paintings Based on Material Jetting and Its Reduction of Staircase Effect.
Material jetting is a high-precision and fast 3D printing technique for color 3D objects reproduction, but it also suffers from color accuracy and jagged issues. The UV inks jetting processes based on the polymer jetting principle have been studied from printing materials regarding the parameters in the default layer order, which is prone to staircase effects. In this work, utilizing the Mimaki UV inks jetting system with a variable layer thickness, a new framework to print a photogrammetry-based oil painting 3D model has been proposed with the tunable coloring layer sequence to improve the jagged challenge between adjacent layers. Based on contour tracking, a height-rendering image of the oil painting model is generated, which is further segmented and pasted to the corresponding slicing layers to control the overall printing sequence of coloring layers and white layers. The final results show that photogrammetric models of oil paintings can be printed vividly by UV-curable color polymers, and that the proposed reverse-sequence printing method can significantly improve the staircase effect based on visual assessment and color difference. Finally, the case of polymer-based oil painting 3D printing provides new insights for optimizing color 3D printing processes based on other substrates and print accuracy to improve the corresponding staircase effect.


The small-subunit polypeptide of methylamine dehydrogenase from Methylobacterium extorquens AM1 has an unusual leader sequence.
The nucleotide sequence for the N-terminal region of the small subunit of methylamine dehydrogenase from Methylobacterium extorquens AM1 has revealed a leader sequence that is unusual in both its length and composition. Gene fusions to lacZ and phoA show that this leader sequence does not function in Escherichia coli but does function in M. extorquens AM1.


Targeting of large liposomes with lectins increases their binding to plant protoplasts.
Soybean agglutinin, peanut agglutinin, and concanavalin A were covalently bound by condensation reaction to gangliosides and ceramides incorporated within the bilayer of multilamellar and unilamellar liposomes. These modified liposomes had a much higher affinity for carrot and tobacco protoplasts except when concanavalin A was used.In addition, soybean agglutinin and concanavalin A were attached by ligand-specific binding to liposomes containing cholesterol molecules derivatized with each lectin-specific sugar. This procedure allowed efficient crosslinking of liposomes to protoplasts. The same effect was achieved with soybean agglutinin and peanut agglutinin when derivatized cholesterol was replaced by gangliosides. The implications of these findings for the liposome-mediated nucleic acid transfer into protoplasts are discussed.


Targeting sigma-1 receptor with fluvoxamine ameliorates pressure-overload-induced hypertrophy and dysfunctions.
We here investigated the effect of sigma-1 receptor (Sig-1R) stimulation with fluvoxamine on myocardial hypertrophy, cardiac functional recovery and defined mechanisms underlying its cardioprotective action. Wistar rats subjected to bilateral ovariectomy (OVX) were treated with abdominal aortic banding between the right and left renal arteries. To confirm the cardioprotective role of Sig-1R stimulation, we treated the rats with Sig-1R agonist (fluvoxamine, 0.5 and 1 mg/kg) orally once a day for 4 weeks after the onset of aortic banding. Interestingly, the expression of Sig-1R in the left ventricle (LV) decreased significantly 4 weeks after pressure overload (PO)-induced hypertrophy in OVX rats. The fluvoxamine administration significantly attenuated PO-induced myocardial hypertrophy with concomitant increase in the expression of Sig-1R in LV. Fluvoxamine also attenuated hypertrophy-induced impaired LV functions. The cardioprotective effect of fluvoxamine was nullified by treatment with Sig-1R antagonist (NE-100; 1 mg/kg). Fluvoxamine treatment significantly restored PO-induced impaired eNOS and Akt activity in the LV. We here found, for the first time, the potential role of Sig-1R expression in the heart in attenuating PO-induced hypertrophy in OVX rats. Fluvoxamine treatment protects PO-induced cardiac injury via upregulation of Sig-1R and stimulation of Sig-1R-mediated Akt-eNOS signaling in ovariectomized rats.


Psychosocial risk factors of erectile dysfunction among heterosexual men living with HIV.
ABSTRACTThe risk of erectile dysfunction (ED) is significantly higher in men living with HIV (MLWH). Despite the adverse effects of ED on quality of life for MLWH, there is a lack of research on the psychosocial factors that may influence ED, especially among heterosexual MLWH. According to a recent systematic review, findings on the psychosocial risk factors of ED in past studies have been largely conflicting or inconclusive. To bridge this gap, we analyzed psychosocial and other correlates of ED among a sample of 317 primarily Black and Latino heterosexual adult MLWH in New York City. Data collection involved quantitative surveys administered using a combination of computer-assisted personal interview and audio computer-assisted self-interview techniques. After adjusting for age and general health, the relative risk of ED among heterosexual men living with HIV was associated with higher HIV-related stigma, anxiety, depression, and negative HIV-coping; greater social support was associated with a lower risk of ED. In addition, the data were consistent with the potential effects of childhood emotional, physical, and sexual abuse and structural discrimination on the risk of ED. Overall, our research findings help provide a better understanding of the psychosocial factors associated with ED among heterosexual MLWH.


Unraveling the mechanism of a reversible photoactivated molecular proton crane.
We study the structural dynamics of the photoactivated molecular proton crane 7-hydroxy-8-(morpholinomethyl)quinoline using femtosecond UV-pump IR-probe spectroscopy. Upon electronic excitation, a proton is transferred from the hydroxy to the amine group located on the rotatable morpholino side group. This morpholino group subsequently delivers the proton to the aromatic quinoline nitrogen by rotation around the C-C bond. Time-resolved vibrational spectroscopy allows us to study this process in unprecedented detail. We find that the transport of the proton involves multiple time scales. Upon photoexcitation, the OH proton is transferred within <300 fs to the morpholino side group. After this, the intramolecular hydrogen bond that locks the crane arm breaks with a time constant of 36 ± 1 ps. Subsequently, the protonated crane arm rotates with a time constant of 334 ± 12 ps to deliver the proton at the quinoline moiety. After the proton crane has returned to its electronic ground state with a time constant 700 ± 22 ps, the proton is transferred back from the quinoline nitrogen to the negatively charged O atom. The time constant of the back rotation is 39.8 ± 0.2 ns, about 200 times slower than the forward proton transfer.


Both adenosine A1- and A2-receptors are required to stimulate microglial proliferation.
The neuromodulator adenosine is one of the major endogenous inhibitors of overactive excitatory neurotransmission. Adenosine receptors have been identified on neuronal but also on glial surfaces, indicating a role of glial cells in mediation of adenosine effects. Microglia, the immunocompetent cells of the brain, typically respond with proliferation, migration and production of inflammatory substances to viral or bacterial stimuli or to cell damage and degeneration. Since adenosine is released in large amounts in conditions of, for example, hypoxic or ischemic stress, it might be involved in the activation process of microglia. Proliferation of microglia was determined by incorporation of [3H]thymidine into microglial DNA after stimulation with adenosine A1- and A2-receptor agonists. N6-Cyclopentyl adenosine (CPA) and CGS-21680, a specific adenosine A2-receptor agonist had no effect on microglial proliferation. However, combinations of CPA and CGS-21680 as well as the mixed agonist, N6-ethyl-carboxamido adenosine (NECA) increased incorporation of radiolabel above controls. The effect of NECA was inhibited by the adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). From these results, it is concluded that proliferation of microglia can be increased only by simultaneous stimulation of both adenosine A1- and A2-receptors. Targeted interference with the activation of A1-adenosine receptors by specific drugs appears to be sufficient to reduce microglial activation. The findings may have implications for the treatment of neurodegenerative diseases in which microglial activation is supposed to play a causative role.


Perfluoroalkyl substance concentrations in a terrestrial raptor: relationships to environmental conditions and individual traits.
Accumulation of persistent organic pollutants (POPs) in wildlife may be influenced by the physical and biotic environment, and concentrations vary greatly among areas, seasons, and individuals. Different hypotheses about sources of variation in perfluoroalkyl substance (PFAS) concentrations were examined in eggs (n = 107) of tawny owls (Strix aluco) collected over a 24-yr period (1986-2009) in Norway. Predictor variables included the North Atlantic Oscillation (NAO), temperature, snow, food availability (vole abundance), and individual traits such as age, body condition, and clutch size. Concentrations of both perfluoro-octane sulfonate (PFOS) and perfluoroalkyl carboxylates (PFCAs) varied several fold in the population, both inter- and intra-annually. Moreover, individuals laid eggs with several times higher or lower PFAS concentrations within few years (1 yr-5 yr). After controlling for temporal trends (i.e., declining PFOS and increasing PFCA concentrations), both PFOS and PFCAs were positively associated to the winter NAO in the previous year (NAOy - 1 ), suggesting that atmospheric transport may be affecting the input of PFASs to the local ecosystem. Perfluoro-octane sulfonate was negatively related to temperature, but the pattern was complex as there was an interaction between temperature and the feeding conditions. The PFOS accumulation was highest in years with high vole abundance and low to medium temperatures. For PFCAs, there was an interaction between NAOy - 1 and feeding conditions, suggesting that strong air transport toward Norway and high consumption of voles led to a moderate increase in PFCA accumulation. The individual traits, however, had very little impact on the concentrations of PFASs in the eggs. The present study thus suggests that annual variation in environmental conditions influences the concentrations of PFASs in a terrestrial raptor such as the tawny owl.


Study on cutoff value setting for differential diagnosis between Graves' disease and painless thyroiditis using the TRAb (Elecsys TRAb) measurement via the fully automated electrochemiluminescence immunoassay system.
The purposes of this study are to set the Elecsys TRAb cutoff value by which GD and PT can be accurately diagnosed simply; and to investigate the usefulness of the vascularity index (VI) obtained from power Doppler sonography (PDS). Using 109 normal controls, 186 GD patients, and 109 PT patients who were diagnosed through Tc-99m uptake, we set the cutoff value by conducting ROC analysis on the Elecsys TRAb values. The cutoff value as a result of the ROC analysis on the Elecsys TRAb values of the normal controls and GD patients was 0.8 IU/L with 100% of sensitivity and specificity. Because all 89 cases (81.6% of the entire PT cases) with Elecsys TRAb =<0.8 IU/L are PT, the cutoff =<0.8IU/L can thus be diagnosed as PT. In contrast, because all 166 cases (88.7% of the entire GD) with Elecsys TRAb >=3.0 IU/L except for one case of PT are GD, the cutoff >=3.0 IU/L can be diagnosed as GD. So Elecsys TRAb between 0.8-3.0 IU/L was dubbed gray zone (GZ). Finally, the cutoff value of 1.5 IU/L from the ROC on the PT and GD cases was chosen as the cutoff with 96.2% of sensitivity and 94.6 of specificity. All PDS VI >=80% were GD including 4 of 6 cases with GZ and all PDS VI <50% plus Elecsys TRAb-negative cases were PT including 4 of 5 cases with GZ. In conclusion, Elecsys TRAb cutoff and VI value for differential diagnosis between GD and PT has been set successfully.


[A method of fractionating bone marrow cells in a density gradient using a mixture of Ficoll and Verografin].
The authors suggest a method for hemopoietic tissue cell fractionation into populations enriched for various hemopoietic elements. Centrifugation in a three-layer density gradient of mixtures of ficoll and verografin (d1 = 1.03 g/cm3, d2 = 1.09 g/cm3, d3 = 1.1 g/cm3) resulted in three fractions. The first contained lymphoid cells, the second erythroid cells (89.1 +/- 7.3%), and the third consisted of white blood cells (78.5 +/- 6.3%).


Amyloid and tau cerebrospinal fluid biomarkers in HIV infection.
Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPalpha and sAPPbeta), amyloid beta fragment 1-42 (Abeta1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. CSF sAPPalpha and sAPPbeta concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Abeta1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. Parallel reductions of CSF sAPPalpha and sAPPbeta in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.


Elimination of matrix and spectral interferences in the measurement of lead and cadmium in urine and blood by electrothermal atomic absorption spectrometry with deuterium background correction.
Direct measurement of lead and cadmium in blood and urine by electrothermal atomic absorption spectrometry with deuterium background correction (D2-AAS) is prone to severe matrix and spectral interferences. We overcame these effects by coating the L'vov platform with ammonium molybdate, reducing the atomization time, introducing a post-atomization cooling step, carefully selecting ashing and atomization temperatures, and using an appropriate procedure for matrix modification. To determine Pb and Cd in blood and urine, we used matrix-matched calibration curves. With the proposed procedure for sample preparation, both Pb and Cd in whole blood can be determined in the same diluted sample. Results obtained by D2-AAS correlate closely with those by Zeeman-corrected AAS. Detection limits (mean blank + 3 SDblank) for Pb in urine and blood were 4 micrograms/L. For cadmium, the detection limits were 0.4 and 0.1 micrograms/L for urine and blood analysis, respectively. Between-run CVs were less than 5.0%.


Interpretation of biological experiments changes with evolution of the Gene Ontology and its annotations.
Gene Ontology (GO) enrichment analysis is ubiquitously used for interpreting high throughput molecular data and generating hypotheses about underlying biological phenomena of experiments. However, the two building blocks of this analysis - the ontology and the annotations - evolve rapidly. We used gene signatures derived from 104 disease analyses to systematically evaluate how enrichment analysis results were affected by evolution of the GO over a decade. We found low consistency between enrichment analyses results obtained with early and more recent GO versions. Furthermore, there continues to be a strong annotation bias in the GO annotations where 58% of the annotations are for 16% of the human genes. Our analysis suggests that GO evolution may have affected the interpretation and possibly reproducibility of experiments over time. Hence, researchers must exercise caution when interpreting GO enrichment analyses and should reexamine previous analyses with the most recent GO version.


Lichen planopilaris in men: a retrospective clinicopathologic study of 19 patients.
Lichen planopilaris (LPP) is a scarring alopecia rarely described in men. To investigate the clinical and histopathologic features of LPP in men. We performed a retrospective cohort study of male patients with LPP seen at Mayo Clinic between 1992 and 2016. Nineteen men with biopsy-confirmed LPP were included. The disease most commonly presented with diffuse (42.1%) or vertex scalp (42.1%) involvement. None of the patients had eyebrow or body hair involvement. Perifollicular erythema (94.7%) and pruritus (57.9%) were the most frequent clinical findings. Androgenetic alopecia (AGA) co-occurred in 26.3% of patients. Mucosal lichen planus was found in four patients (21.1%). Thyroid disease occurred in three patients (15.8%). Disease improvement (47.3%) occurred with combination topical and systemic therapy, topical clobetasol monotherapy, and minocycline monotherapy. LPP in men has similar clinical and histologic presentations as reported in women. Nonscalp hair loss appears less likely in men with classic LPP than reported in men with frontal fibrosing alopecia, while mucosal lichen planus and thyroid disease appear to be more common in classic LPP. Men with AGA can present with new-onset concomitant LPP. Limitations included small study size, variable follow-up, and lack of standardized clinical assessment due the study's retrospective nature.


Implementing research in nurse-led care.
In response to research showing that people waiting for cardiac surgery had a high prevalence of uncorrected coronary heart disease risk factors, a nurse-led shared care scheme was developed. A randomised controlled trial of the service demonstrated significant improvements in risk factors among the intervention group. The study is used as an example of how research findings have been used to identify an area for practice development.


[@HOME is a new Eu-Project in Tele Home care].
@Home is a robust platform for real-time remote monitoring of patients at their home by doctors at the hospital. Health monitoring sensors, which have the capability to measure quick and easy vital parameters such as blood pressure, pulse rate, temperature, oxygen saturation (SpO2), as well as ECG 12 leads are used. Additionally, an advantage of the platform is that all the sensors are wearable and the patient is able to walk around indoors or outdoors. Moreover, the sensors are able to convey the recorded data over Bluetooth, a short-range wireless communication, to any Bluetooth enabled device such as Desktop computer or a Pocket PC.


Corticosteroid therapy exacerbates the reduction of melatonin in multiple sclerosis.
Corticosteroid therapy is employed in multiple sclerosis (MS), a neurological abnormality characterized by an inflammatory process. Melatonin, a potent sleep-promoting and circadian phase regulatory hormone, is produced mainly in the pineal gland whose inhibition leads to sleep disturbances. In this study, methylprednisolone (MP) corticosteroid treatment was used in an acute experimental autoimmune encephalomyelitis (EAE) rat model (intraperitoneal, 30 mg/kg) and in MS patients (intravenous, 1000 mg/day), followed by assessing melatonin serum levels. Results showed that mean clinical scores were significantly improved in MP- versus PBS-treated EAE rats (1.5 vs 4.1, respectively). In addition, MP was found to induce a significant decrease in serum IFN-γ, whereas IL-4 levels were significantly increased, in comparison to PBS-treated EAE rats. The ratio of IFN-γ/IL-4, which acts as an indicator of Th-1/Th-2, was significantly lower in MP treated, compared to PBS treated EAE rats or controls. Moreover, serum levels of melatonin showed a significant decrease in the MP group, compared to normal rats. Moreover, MP therapy for 1 or 2 days resulted in a significant reduction of melatonin serum levels in MS patients. Since corticosteroids cause a reduction in melatonin serum levels, an important hormone in sleep regulation, their prescription to MS patients should be carefully considered. Corticosteroids could be a cause of insomnia and sleep disturbance in patients receiving this type of medication.


Stiffening of the Extrapulmonary Arteries From Rats in Chronic Hypoxic Pulmonary Hypertension.
Changes in the compliance properties of large blood vessels are critical determinants of ventricular afterload and ultimately dysfunction. Little is known of the mechanical properties of large vessels exhibiting pulmonary hypertension, particularly the trunk and right main artery. We initiated a study to investigate the influence of chronic hypoxic pulmonary hypertension on the mechanical properties of the extrapulmonary arteries of rats. One group of animals was housed at the equivalent of 5000 m elevation for three weeks and the other held at ambient conditions of ~1600 m. The two groups were matched in age and gender. The animals exposed to hypobaric hypoxia exhibited signs of pulmonary hypertension, as evidenced by an increase in the RV/(LV+S) heart weight ratio. The extrapulmonary arteries of the hypoxic animals were also thicker than those of the control population. Histological examination revealed increased thickness of the media and additional deposits of collagen in the adventitia. The mechanical properties of the trunk, and the right and left main pulmonary arteries were assessed; at a representative pressure (7 kPa), the two populations exhibited different quantities of stretch for each section. At higher pressures we noted less deformation among the arteries from hypoxic animals as compared with controls. A four-parameter constitutive model was employed to fit and analyze the data. We conclude that chronic hypoxic pulmonary hypertension is associated with a stiffening of all the extrapulmonary arteries.


Hypoxia-induced phosphorylation of Chk2 in an ataxia telangiectasia mutated-dependent manner.
Chk2 is a serine/threonine kinase that signals to cell cycle arrest, DNA repair, and apoptotic pathways following DNA damage. It is activated by phosphorylation in response to ionizing radiation, UV light, stalled replication forks, and other types of DNA damage. Hypoxia is a common feature of solid tumors and has been shown to affect the regulation of many genes, including several DNA repair factors. We show here that Chk2 is phosphorylated on Thr68 and thereby activated in cells in response to hypoxia, and that this phosphorylation is dependent on the damage response kinase ataxia telangiectasia mutated (ATM) but not on the related kinase ATM and Rad3-related. Moreover, phosphorylation of Chk2 under hypoxia was attenuated in cells deficient in the repair factors MLH1 or NBS1. Finally, Chk2 serves to protect cells from apoptosis under hypoxic growth conditions. These results identify hypoxia as a new stimulus for Chk2 activation in an ATM-, MLH1-, and NBS1-dependent manner, and they suggest a novel pathway by which tumor hypoxia may influence cell survival and DNA repair.


The Effect of Molecular Weight on the Antibacterial Activity of N,N,N-Trimethyl Chitosan (TMC).
N,N,N-trimethyl chitosan (TMC) with 93% degree of trimethylation was synthesized. TMC and the chitosan starting material were subjected to acidic hydrolysis to produce 49 different samples with a reduced average molecular weight (Mw) ranging from 2 to 144 kDa. This was done to allow the investigation of the relationship between antibacterial activity and Mw over a wide Mw range. NMR investigation showed that hydrolysis did not affect the degree of trimethylation (DSTRI) or the structure of the polymer backbone. The activity of TMC against Staphylococcus aureus (S. aureus) increased sharply with Mw until a certain Mw value (critical Mw for high activity, CMW) was reached. After the CMW, the activity was not affected by a further increase in the Mw. A similar pattern of activity was observed for chitosan. The CMW was determined to be 20 kDa for TMC and 50 kDa for chitosan.


Quebec dental manpower and demand for dental care from 1985-1988.
The rapid growth in the number of practising dentists is a major concern of the dental profession in industrialized countries. Three surveys conducted in Quebec in 1971 (N = 1552), 1985 (N = 840) and 1988 (N = 1059) examined the growth in dental manpower and demand for dental care between 1985 and 1988 and made a comparison with the 1971-1985 period. On average, the yearly increase in the number of active dentists was 4.2 per cent between 1971 and 1985 whereas the yearly increase between 1985 and 1988 was only 2.5 per cent. The percentage of the population using dental services annually was 47 per cent in 1988, compared to 51 per cent in 1985. An age-specific comparison with the United States showed that the proportion of Quebec adults visiting the dentist within the last 12 months varied between 30 per cent and 63 per cent and that of the U.S. between 41 per cent and 61 per cent. Thus, as the number of active dentists continues to grow, albeit at a slower rate, the demand for dental care appears to have reached a plateau and has attained the American level for adults under 50 years of age.


The role of genomics in the discovery of novel targets for antibiotic therapy.
The emergence of antibiotic resistance and multi-drug resistance in bacterial pathogens underscores the need for the development of novel classes of antibiotics. The availability of complete genome sequence data from many important human pathogens provides a wealth of fundamental information. This allows us to define each gene and thus to better understand molecular pathogenesis. New techniques have enabled the identification and characterization of genes that are critical for bacterial growth and survival during infection. The combination of genome sequence data and new technologies make it possible to systematically explore the function of each open reading frame in a genome and identify any potential molecular targets for drug discovery. With particular emphasis on antibacterial therapy, this review discusses genome-based technologies and their important applications to anti-infective drug discovery.


Coralmycin Derivatives with Potent Anti-Gram Negative Activity Produced by the Myxobacteria Corallococcus coralloides M23.
Seven new coralmycin derivatives, coralmycins C (1), D (2), E (3), F (4), G (5), H (6), and I (7), along with three known compounds, cystobactamids 891-2 (8), 905-2 (9), and 507 (10), were isolated from a large-scale culture of the myxobacteria Corallococcus coralloides M23. The structures of these compounds, including their relative stereochemistries, were elucidated by interpretation of their spectroscopic and CD data. The structure-activity relationships of their antibacterial and DNA gyrase inhibitory activities indicated that the para-nitrobenzoic acid unit is critical for the inhibition of DNA gyrase and bacterial growth, while the nitro moiety of the para-nitrobenzoic acid unit and the isopropyl chain at C-4 could be important for permeability into certain Gram-negative bacteria, including Pseudomonas aeruginosa and Klebsiella pneumoniae, and the β-methoxyasparagine moiety could affect cellular uptake into all tested bacteria. These results could facilitate the chemical optimization of coralmycins for the treatment of multidrug-resistant Gram-negative bacteria.


Status of oocytes and embryos of X-autosome translocation carrier sows.
The impact of an X-autosome translocation t(Xp+; 14q-), on ovulation, fertilization and embryo survival in carrier sows, was examined and compared with these parameters of normal sows. Corpora lutea counts during week-2 and week-4 of gestation were similar in normal and carrier sows (14.4 +/- 1.36 and 15.5 +/- 2.18) although embryo recovery (11.0 +/- 1.87 and 6.0 +/- 1.47) was lower than that from normal sows (12.8 +/- 1.46 and 11.5 +/- 0.87), at these stages. Among the embryos karyotyped from the week-2 embryos of carrier sows, 42% were normal, 26.4% were carriers and 31.6% were of unbalanced chromosome make-up, and of the week-4 embryos of carriers, 33.3% were normal, 57.1% were carriers and 9.1% were chromosomally unbalanced females. The preponderance of females among the unbalanced embryos recovered at week-2 of gestation (11_ and 1_) and the total absence of males among those recovered at week-4, suggest that oocytes with unbalanced chromosome constitution are eliminated before week-2 of gestation if they are fertilized by Y bearing sperm, and that the unbalanced oocytes fertilized by X bearing sperm survive up to the peri-attachment stage even though all chromosomally unbalanced embryos are eliminated before term regardless of their sex.


Leaf Size Development Differences and Comparative Trancriptome Analyses of Two Poplar Genotypes.
The plant leaf, the main organ of photosynthesis, is an important regulator of growth. To explore the difference between leaf size of Populusdeltoides 'Danhong' (Pd) and Populus simonii 'Tongliao1' (Ps), we investigated the leaf length, leaf width, leaf thickness, leaf area, leaf mass per area (LMA), and cell size of leaves from two genotypes and profiled the transcriptome-wide gene expression patterns through RNA sequencing. Our results show that the leaf area of Pd was significantly larger than that of Ps, but the epidermal cell area was significantly smaller than that of Ps. The difference of leaf size was caused by cell numbers. Transcriptome analysis also revealed that genes related to chromosome replication and DNA repair were highly expressed in Pd, while genes such as the EXPANSIN (EXPA) family which promoted cell expansion were highly expressed in Ps. Further, we revealed that the growth-regulating factors (GRFs) played a key role in the difference of leaf size between two genotypes through regulation of cell proliferation. These data provide a valuable resource for understanding the leaf development of the Populus genus.


[Non-invasive methods of control of the intestinal motility in surgical practice].
Selective spectral peripheric electrogastroenterography (SSPEGEG), the noninvasive method of the gut functional state estimation, is based on registration of biopotentials from the body surface, generated by stomach and intestine, using apparatus-program unit on the PC IBM base. The possibilities and advantages of this method in comparison with others (roentgenological, radiological, radionuclide, balloonographic and tensiographic) were considered. The principles of the SSPEGEG application for clinical monitoring conduction are adduced.


Induction of deoxyribonucleic Acid synthesis in potato tuber slices: role of protein synthesis.
Timing of protein synthesis which is a prerequisite to DNA synthesis induced in potato tuber tissue (Solanum tuberosum L.) by cut injury has been studied using cycloheximide. The induction of DNA synthesis which was measured by incorporation of (3)H-thymidine was completely inhibited when the inhibitor was applied to the tuber discs immediately after slicing. When the application of cycloheximide was delayed for 6 hours or more after slicing, DNA synthesis was observed but its rate was reduced to 20% of control. The inhibitory effect of cycloheximide, however, rapidly decreased when the inhibitor was applied at 6 or less hours immediately prior to determination of DNA synthesis. The effect of cycloheximide on the incorporation of (14)C-leucine suggests that the change in the effect of cycloheximide on the induction of DNA synthesis is not due to incomplete inhibition of protein synthesis. Cycloheximide did not have significant effects on either uptake or phosphorylation of (3)H-thymidine in the discs. Inhibition of both protein and DNA synthesis by cycloheximide was reversed by washing and further incubation of the discs. Almost no qualitative difference was detected by buoyant density analysis between DNA formed under inhibition of protein synthesis of the later stage and DNA synthesized under normal conditions. These results suggest that DNA synthesis induced in potato tuber tissue by cut injury requires continuous synthesis of new protein molecules in a characteristically programmed sequence.


How Are Patients Reviewing Spine Surgeons Online? A Sentiment Analysis of Physician Review Website Written Comments.
A Sentiment Analysis of online reviews of spine surgeons. Physician review websites have significant impact on a patient's provider selection. Written reviews are subjective, but sentiment analysis through machine learning can quantitatively analyze these reviews. This study analyzes online written reviews of spine surgeons and reports biases associated with demographic factors and trends in words utilized. Online written and star-reviews of spine surgeons were obtained from healthgrades.com. A sentiment analysis package was used to analyze the written reviews. The relationship of demographic variables to these scores was analyzed with t-tests and word and bigram frequency analyses were performed. Additionally, a multiple regression analysis was performed on key terms. 8357 reviews of 480 surgeons were analyzed. There was a significant difference between the means of sentiment analysis scores and star scores for both gender and age. Younger, male surgeons were rated more highly on average (P < .01). Word frequency analysis indicated that behavioral factors and pain were the main contributing factors to both the best and worst reviewed surgeons. Additionally, several clinically relevant words, when included in a review, affected the odds of a positive review. The best reviews laud surgeons for their ability to manage pain and for exhibiting positive bedside manner. However, the worst reviews primarily focus on pain and its management, as exhibited by the frequency and multivariate analysis. Pain is a clear contributing factor to reviews, thus emphasizing the importance of establishing proper pain expectations prior to any intervention.


Valorization of Cladophora glomerata Biomass and Obtained Bioproducts into Biostimulants of Plant Growth and as Sorbents (Biosorbents) of Metal Ions.
The aim of this study was to propose a complete approach for macroalgae biomass valorization into products useful for sustainable agriculture and environmental protection. In the first stage, the effects of macroalgal extracts and ZnO NPs (zinc oxide nanoparticles) on the germination and growth of radish were examined. Macroalgal extract was produced from freshwater macroalga, i.e., Cladophora glomerata by ultrasound assisted extraction (UAE). The extract was used to biosynthesize zinc oxide nanoparticles. In germination tests, extracts and solutions of ZnO NPs were applied on paper substrate before sowing. In the second stage, sorption properties of macroalga, post-extraction residue, and ZnO NPs to absorb Cr(III) ions were examined. In the germination tests, the highest values of hypocotyl length (the edible part of radish), i.e., 3.3 and 2.6 cm were obtained for 60 and 80% extract (among the tested concentrations 20, 40, 60, 80, and 100%) and 10 and 50 mg/L NPs, respectively. The highest sorption capacity of Cr(III) ions (344.8 mg/g) was obtained by both macroalga and post-extraction residue at a pH of 5 and initial Cr(III) ions concentration of 200 mg/L. This study proves that macroalgae and products based on them can be applied in both sustainable agriculture and wastewater treatment.


VEGF inhibitors for the treatment of neovascular age-related macular degeneration.
Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world for those patients aged 50 years or older. Neovascular AMD, a subtype characterized by the growth of new, pathologic blood vessels, results in most of the cases of severe and rapid vision loss associated with AMD. A critical activator of angiogenesis in neovascular AMD is VEGF. Several therapies have been and are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, VEGF receptor decoy VEGF Trap, small interfering RNA-based therapies bevasiranib and AGN211745, sirolimus, and tyrosine kinase inhibitors including vatalanib, pazopanib, TG100801, TG101095, AG013958 and AL39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still investigational in nature offer the potential for further advances.


Insulin resistance and promotion of aberrant crypt foci in the colons of rats on a high-fat diet.
McKeown-Eyssen and Giovannucci recently proposed that the etiology of insulin resistance (IR) and colorectal cancer (CRC) are related. They suggested that diets high in fat and energy and low in complex carbohydrates and a sedentary life-style lead to IR and that the associated hyperinsulinemia, hypertriglyceridemia, and glycemia lead to increased CRC risk through the growth-promoting effect of insulin or the increased availability of energy. We reasoned that if diet affects colon carcinogenesis through its effect on IR, evidence of colon cancer promotion would be preceded by evidence of IR. To test this expectation, we compared the effects of a high-fat (HF, 59% energy) diet and a low-fat (LF, 11% energy) diet on indirect measures of IR and promotion in azoxymethane-initiated F344 rats. Promotion was assessed as growth of aberrant crypt foci (ACF) at 100 days after initiation. The HF diet increased ACF size 1.4 times (95% confidence interval = 1.30-1.58) that of the LF diet. The HF diet also led to impaired oral glucose tolerance tests measured at 4, 32, 60, and 88 days and characterized by an average increased glucose concentration of 0.78 +/- 0.17 mmol/l (p < 0.001). It also resulted in an impaired intravenous glucose tolerance test and elevated levels of serum insulin after a glucose gavage. We concluded that with this model a high-fat diet leads to evidence of IR before it is possible to demonstrate CRC promotion, thus providing support, necessary but not sufficient, for the causal hypothesis linking IR and CRC. Possible mechanisms linking diet, IR, and promotion are considered.


The G20210A mutation does not affect the stability of prothrombin mRNA in vivo.
The activated form of prothrombin plays pivotal roles in the regulation of crucial coagulation, fibrinolytic, and cellular processes. Among several congenital genetic defects affecting the prothrombin gene, a G-->A mutation at position 20210--the accepted polyadenylation site--has been linked to hyperprothrombinemia and a corresponding increase in venous and arterial thrombotic risk. The current study substantiates the hypothesis that the 20210A mutation effects posttranscriptional dysregulation of the prothrombin messenger RNA (mRNA). Moreover, data from experiments carried out in fresh liver tissue indicate that the 20210A mutation does not affect prothrombin mRNA stability but, rather, effects a change in the location of the 3'-cleavage/polyadenylation reaction. Based upon this evidence, we propose an alternate model for the dysregulated expression of the prothrombin 20210A gene that does not require a change in the stability of its mRNA.


Scanning electron microscopy of intact colonies of microorganisms.
Colonies of S. mutans OMZ61, Streptococcus sp. D182, Staphylococcus aureus Oxford NCTC 6571, and Candida albicans type A, MRL 3153 were grown on various media. Cubes of agar bearing two to three colonies were excised and processed for scanning electron microscopy. The characteristic shape of the colonies was seen when examined at low magnifications. At a magnification of 2,000 diameters, the arrangement of individual organisms within the colonies was observed. Plano-convex colonies consisted of uniformly distributed organisms, whereas S. mutans colonies presented a more complex arrangement possibly associated with the production of extracellular polysaccharides. Certain colonies were totally or partially covered by an adherent film through which the outline of the organisms could be distinguished.


Handgrip contribution to lactate production and leg power during high-intensity exercise.
The purpose of this study was to examine the upper-body contribution via handgrip to power profiles and blood lactate concentrations during high-intensity cycle ergometry. Nine trained male subjects each completed a 20-s high-intensity cycle ergometer test twice, in a random manner, using two protocols, with a handgrip (WG), and without handgrip (WOHG). Capillary (earlobe) blood samples were obtained pre- and post-exercise. Blood samples were corrected for plasma volume changes and analyzed to determine blood lactate concentrations. In the WG protocol, mean (+/-SEM) blood lactate concentrations sampled over the three conditions were 0.98 +/- 0.33 mmol.L-1, 5.68 +/- 0.46 mmol.L-1, and 9.14 +/- 0.38 mmol.L-1, respectively. During the WOHG protocol, blood lactate values recorded were 0.99 +/- 0.26 mmol.L-1, 5.58 +/- 0.58 mmol.L-1, and 7.62 +/- 0.65 mmol.L-1, respectively. Differences were found (P < 0.05) from rest to 4 min after exercise for both groups. Differences in concentrations were also observed between groups at the 4-min postexercise blood-sampling stage. Peak power output values recorded using the WG protocol were also greater (1461 +/- 94 W vs 1136 +/- 88 W; P < 0.05). No differences were recorded for mean power output (MPO), fatigue index (FI), or work done (WD). Results indicate significant differences in power output and blood lactate concentrations between protocols. These findings suggest that the performance of traditional style leg-cycle ergometry requires a muscular contribution from the whole body. As such, researchers should consider this, both in terms of the allocation of ergometer loads, and in the analysis of blood-borne metabolites.


Formulation and antitumor efficacy of liposomal-caprylated-TNF-SAM2.
The tumor necrosis factor (TNF) mutant TNF-SAM2 has previously been shown to have a therapeutic profile superior to parental TNF. To initially evaluate the characteristics of liposomal formulations of TNF-SAM2, it was modified with the N-hydroxysuccinimide ester of caprylic acid to increase its hydrophobic binding to multilamellar and small unilamellar vesicles (MLVs and SUVs). Native PAGE and fluorescamine analysis of acetylated parental TNF and TNF-SAM2 indicated that these proteins both displayed trimeric structures based on crosslinking/SDS-PAGE analysis and behaved similarly with respect to reactivity of their amino functions. Limited N-terminal sequencing analysis of partially acetylated (approx 3 acetyl groups per trimer) TNF-SAM2 indicated that the N-terminal Val was not modified; this was also concluded based on HPLC/mass spectrometric (LC-MS) analysis of Glu C digests. LC-MS analysis of tryptic digests of the acetylated TNF-SAM2 indicated that Lys-98 was unreactive. Molecular ions corresponding to acetylated Lys-containing peptides for all five other Lys residues could be detected; none appeared hyperreactive, but Lys-11 appeared hyporeactive. MLVs composed of DMPC/DMPG (7:3) and SUVs composed of DPPC/DSPC (1:1) displayed high capacity for binding to caprylated TNF-SAM2. These formulations of caprylated TNF-SAM2 displayed tumor necrotizing and growth-inhibitory activity in a syngeneic tumor model, and may be candidates for clinical development.


Electrochromism in Electropolymerized Films of Pyrene-Triphenylamine Derivatives.
Two star-shaped multi-triphenylamine derivatives 1 and 2 were prepared, where 2 has an additional phenyl unit between a pyrene core and surrounding triphenylamine units. The oxidative electropolymerization of 1 and 2 occurred smoothly to give thin films of polymers P1 and P2. The electrochemistry and spectroelectrochemistry of P1 and P2 were examined, showing two-step absorption spectral changes in the near-infrared region. The electrochromic properties, including contrast ratio, response time, and cyclic stability of P1 and P2 were investigated and compared. Thin film of P2 displays slightly better electrochromic performance than P1, with a contrast ratio of 45% at 1475 nm being achieved.


Effects of oral androstenedione administration on serum testosterone and estradiol levels in postmenopausal women.
Androstenedione is a steroid hormone and an intermediate in the synthetic pathway of both testosterone and estradiol in men and women. It is available without prescription and taken with the expectation that it may have beneficial effects on strength, general well-being, libido, and quality of life. Although studies have shown that oral androstenedione increases serum testosterone and estradiol levels in men, the hormonal effects of androstenedione in postmenopausal women are unknown. We randomly assigned 30 healthy postmenopausal women to receive 0, 50, or 100 mg androstenedione as a single oral dose. After androstenedione administration, we made hourly measurements of serum androstenedione, estrone, estradiol, and testosterone concentrations during 12 h of frequent blood sampling. The mean change (+/-SD) in serum androstenedione area under the curve (AUC) was greater in both the 50-mg (79 +/- 39%) and 100-mg dose groups (242 +/- 184%) than in the control group (-29 +/- 28%) (P < 0.0001 for controls vs. 50-mg group and controls vs. 100-mg group). The mean change in serum androstenedione AUC was also greater in the 100-mg than 50-mg dose group (P = 0.0026). The mean change in serum estrone AUC was greater in both the 50-mg (108 +/- 72%) and 100-mg dose groups (116 +/- 119%) than in the control group (-5 +/- 19%), although the control vs. 100-mg group comparison did not quite meet statistical significance (P < 0.0001 for controls vs. 50-mg group, P = 0.0631 controls vs. 100-mg group). The mean change in serum estradiol AUC remained stable after supplementation in all groups without any between-group differences observed (-11 +/- 17%, 2.8 +/- 34%, -11 +/- 27%, for the control, 50-mg, and 100-mg groups, respectively). The mean change in serum testosterone AUC was greater in both the 50-mg (185 +/- 146%) and 100-mg dose groups (457 +/- 601%) than in the control group (-27 +/- 13%) (P < 0.0001 for controls vs. 50-mg group and for controls vs. 100-mg group). The mean change in testosterone AUC was also greater in the 100-mg dose group than 50-mg dose group (P = 0.0257). There was considerable individual variability in the changes of serum androstenedione, estrone, and testosterone levels in the treated groups with peak serum testosterone levels exceeding the upper limit of normal in 4 of 10 women in the 50-mg dose group and 6 of 10 in the 100-mg dose group. We concluded that the acute administration of both 50-mg and 100-mg of androstenedione increases serum testosterone and estrone levels, but not estradiol levels, in postmenopausal women. If these hormonal effects are sustained during long-term administration, regular use of this supplement by postmenopausal women could thus cause both beneficial and adverse effects.


Modulation of benzo[a]pyrene diolepoxide-DNA adduct levels in human white blood cells by CYP1A1, GSTM1 and GSTT1 polymorphism.
The modulation of benzo[a]pyrene diolepoxide (BPDE)-DNA adduct levels by polymorphisms in the CYP1A1, GSTM1 and GSTT1 genes was assessed in leukocytes of Caucasian males. Eighty-nine coke oven workers (35 smokers, 36 ex-smokers and 18 non-smokers) were recruited from job categories with different exposure levels to polycyclic aromatic hydrocarbons (PAH), together with 44 power plant workers (all smokers) not exposed to PAH. BPDE-DNA adducts were detected in 69 of 133 (52%) DNA samples with a 100-fold variation (range 0.2-44 adducts/10(8) nt) and a median of 1.6 adducts/10(8) nt. All samples with the GSTM1 active genotype (n = 59) and five out of 74 samples with GSTM1*0/*0 (7%) showed non-detectable adducts (<0.2 adducts/10(8) nt) and 69 of 74 subjects with GSTM1*0/*0 (93%) had detectable adducts (>0.2 adducts/10(8) nt). The difference in adduct level between the GSTM1*0/*0 and GSTM1 active genotypes was highly significant (P < 0.0001). No significant difference in adduct level between the GSTT1*0/*0 and GSTT1 active genotypes was seen. All heterozygotes (CYP1A1*1/*2) from subjects of GSTM1 active type did not have detectable adducts. Among the GSTM1-deficient individuals (n = 69), 42 with the CYP1A1*1/*1 genotype showed a lower adduct level (median 1.3, range 0.2-4.1 adducts/10(8) nt) compared with 26 individuals with heterozygous mutated CYP1A1*1/*2 genotypes (median 2.5, range 0.4-6.1 adducts/10(8) nt, P < 0.015). One individual with low PAH exposure and the rare combination CYP1A1*2A/*2A-GSTM1*0/*0 showed an extremely high level of 44 adducts/10(8) nt. Significant differences in detectable adduct levels were found between the CYP1A1*1/*1 and CYP1A1*1/*2 genotypes in the exposed group low + medium (P = 0.01) and for all adduct levels, detectable and non-detectable (set at a fixed value), in highly exposed individuals and in ex-smokers (P = 0.03), whereas no such differences were observed in the control group. Mutated CYP1A1*1/*2 increased the adduct level in non-smokers from the exposed group (1.4 versus 2.2 adducts/10(8) nt), but had no effect on the smokers from the exposed group (2.3 versus 2.8 adducts/10(8) nt). When all variables were dichotomized, statistical evaluation showed that CYP1A1 status (P = 0.015), PAH exposure (P = 0.003) and smoking (P = 0.006) had significant effects on adduct levels which increased in the order: CYP1A1*1/*1 < CYP1A1(*1/*2 or *2A/*2A); environmental exposure < occupational exposure; non-smokers < smokers, whereby adducts increased with cigarette dose and the duration of smoking. Higher levels of BPDE-DNA adducts in individuals with the combined CYP1A1(1/*2 or *2A/*2A)-GSTM1*0/*0 genotype suggest that these genotype combinations are at increased risk for contracting lung cancer when exposed to PAH.