Relationship of aminotransferases to liver histological status in chronic hepatitis C.
Serum aminotransferase levels characteristically fluctuate in chronic hepatitis C, but their relationship to grade (i.e., inflammatory activity) and stage (i.e., degree of fibrosis) of liver disease is uncertain. We therefore correlated aminotransferase levels and liver biopsy findings in 90 patients with serologically confirmed chronic hepatitis C. Mode of transmission; disease duration; symptoms and signs of liver disease; alcohol intake; autoantibody, HIV, and hepatitis B virus status; and liver biochemistries were obtained from records. Liver biopsies were 1) given a morphological diagnosis, 2) evaluated for features of chronic hepatitis C, and 3) scored with a histological activity index. Individual aminotransferase levels were not related to clinical or laboratory variables, nor were they reliably predictive of morphological diagnosis. No histological characteristics were associated with a particular range of aminotransferase values, except aminotransferases > 350 U/L, which were associated with piecemeal necrosis. Although mean values of aminotransferases were significantly lower among patients with chronic persistent hepatitis (CPH) (i.e., with minimal activity) compared with chronic active hepatitis (CAH) (mild to moderate activity) (ALT 110 U/L +/- 71 SD vs 256 +/- 211; AST 57 U/L +/- 34 vs 123 +/- 88) and in the absence of piecemeal necrosis compared with in its presence (ALT 133 +/- 84 vs 207 +/- 149; AST 73 +/- 47 vs 120 +/- 83), overlap of values was considerable between different histological groups. Aminotransferases do not predict liver histological status in chronic hepatitis C, although > or = 10-fold elevations suggest that piecemeal necrosis is present.


Global estimation of exposure to fine particulate matter (PM2.5) from household air pollution.
Exposure to household air pollution (HAP) from cooking with dirty fuels is a leading health risk factor within Asia, Africa and Central/South America. The concentration of particulate matter of diameter ≤ 2.5 μm (PM2.5) is an important metric to evaluate HAP risk, however epidemiological studies have demonstrated significant variation in HAP-PM2.5 concentrations at household, community and country levels. To quantify the global risk due to HAP exposure, novel estimation methods are needed, as financial and resource constraints render it difficult to monitor exposures in all relevant areas. A Bayesian, hierarchical HAP-PM2.5 global exposure model was developed using kitchen and female HAP-PM2.5 exposure data available in peer-reviewed studies from an updated World Health Organization Global HAP database. Cooking environment characteristics were selected using leave-one-out cross validation to predict quantitative HAP-PM2.5 measurements from 44 studies. Twenty-four hour HAP-PM2.5 kitchen concentrations and male, female and child exposures were estimated for 106 countries in Asia, Africa and Latin America. A model incorporating fuel/stove type (traditional wood, improved biomass, coal, dung and gas/electric), urban/rural location, wet/dry season and socio-demographic index resulted in a Bayesian R2 of 0.57. Relative to rural kitchens using gas or electricity, the mean global 24-hour HAP-PM2.5 concentrations were 290 μg/m3 higher (range of regional averages: 110, 880) for traditional stoves, 150 μg/m3 higher (range of regional averages: 50, 290) for improved biomass stoves, 850 μg/m3 higher (range of regional averages: 310, 2600) for animal dung stoves, and 220 μg/m3 higher (range of regional averages: 80, 650) for coal stoves. The modeled global average female/kitchen exposure ratio was 0.40. Average modeled female exposures from cooking with traditional wood stoves were 160 μg/m3 in rural households and 170 μg/m3 in urban households. Average male and child rural area exposures from traditional wood stoves were 120 μg/m3 and 140 μg/m3, respectively; average urban area exposures were identical to average rural exposures among both sub-groups. A Bayesian modeling approach was used to generate unique HAP-PM2.5 kitchen concentrations and personal exposure estimates for all countries, including those with little to no available quantitative HAP-PM2.5 exposure data. The global exposure model incorporating type of fuel-stove combinations can add specificity and reduce exposure misclassification to enable an improved global HAP risk assessment.


Emotion recognition: the role of featural and configural face information.
Several studies investigated the role of featural and configural information when processing facial identity. A lot less is known about their contribution to emotion recognition. In this study, we addressed this issue by inducing either a featural or a configural processing strategy (Experiment 1) and by investigating the attentional strategies in response to emotional expressions (Experiment 2). In Experiment 1, participants identified emotional expressions in faces that were presented in three different versions (intact, blurred, and scrambled) and in two orientations (upright and inverted). Blurred faces contain mainly configural information, and scrambled faces contain mainly featural information. Inversion is known to selectively hinder configural processing. Analyses of the discriminability measure (A') and response times (RTs) revealed that configural processing plays a more prominent role in expression recognition than featural processing, but their relative contribution varies depending on the emotion. In Experiment 2, we qualified these differences between emotions by investigating the relative importance of specific features by means of eye movements. Participants had to match intact expressions with the emotional cues that preceded the stimulus. The analysis of eye movements confirmed that the recognition of different emotions rely on different types of information. While the mouth is important for the detection of happiness and fear, the eyes are more relevant for anger, fear, and sadness.


Apocynin regulates cytokine production of CD8(+) T cells.
Apocynin is known to suppress the production of reactive oxygen species (ROS) by inhibiting NADPH oxidases, specifically phagocytic NADPH oxidase (PHOX or NOX2). Given the pro-inflammatory effects of ROS, apocynin has been studied extensively for its use as a therapeutic agent in various disease models. While the effects of apocynin on neutrophils and monocytes have been investigated, it remains to be elucidated whether apocynin modulates the effector function of T cells. In the present study, we examined the effect of apocynin on CD8(+) T cells and further investigated its mechanism of action. We found that apocynin directly inhibited the production of pro-inflammatory cytokines such as TNF-α, IFN-γ, and IL-2 in anti-CD3/anti-CD28-stimulated CD8(+) T cells. The action of apocynin was upstream of the protein kinase C and calcium signaling in the T cell receptor signaling pathway because apocynin did not inhibit cytokine production in phorbol 12-myristate 13-acetate/ionomycin-stimulated CD8(+) T cells. Electrophoretic mobility shift assays revealed that apocynin attenuated anti-CD3/anti-CD28-induced NF-κB activation in CD8(+) T cells. In the experiments with NOX2-deficient mice, we demonstrated that apocynin inhibited TNF-α production of CD8(+) T cells in a NOX2-independent manner. Taken together, we demonstrated that apocynin, a well-known NOX2 inhibitor, suppressed the cytokine production of CD8(+) T cells. We also showed the NOX2-independent action of apocynin in the inhibition of TNF-α production in CD8(+) T cells.


Different patterns of change in bone turnover markers during treatment with bone-modifying agents for breast cancer patients with bone metastases.
Bone-modifying agents are effective for treatment of breast cancer patients with bone metastases. Since their action is mediated through suppression of the osteoclast function, their efficacy can be determined by monitoring bone turnover markers. However, the clinical significance of these markers is yet to be compared. For this study, 52 breast cancer patients with bone metastases treated with zoledronic acid (n = 36) or denosumab (n = 22) were enrolled (6 patients were treated sequentially with both agents). Serum tartrate-resistant acid phosphatase-5b (TRACP-5b), pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (1CTP), N-terminal cross-linking telopeptides of type I collagen (NTX) and bone-specific alkaline phosphatase (BAP) were measured at pretreatment and 1, 3 and 6 months after treatment. Serum TRACP-5b (p < 0.0001), NTX (p = 0.0007) and BAP (p = 0.0032) decreased significantly after treatment. The baseline median value of TRACP-5b (457.5 mU/dL, range 173-1630 mU/dL) decreased to 137 mU/dL (91-795 mU/dL) 1 month after treatment. Reduction in serum NTX and BAP was greatest after 3 and 6 months, respectively. TRACP-5b, NTX and BAP were above normal levels at baseline in 62.5, 25 and 35.3 % of patients, respectively, and nearly 80 % of these patients attained normal levels during the treatment. Although bone-modifying agents reduced the baseline levels of TRACP-5b, NTX and BAP significantly, the reduction patterns differed. TRACP-5b appears to affect levels most quickly and sensitively, possibly due to its direct link to the number and activity of osteoclasts. These findings suggest that the efficacy of TRACP-5b is clinically significant when considering which bone-modifying agents to use for breast cancer patients with bone metastases.


Effects of glucosamine supplements on painful temporomandibular joint osteoarthritis: A systematic review.
The purpose of this study was to systematically review the literature for studies that assessed the effects of glucosamine supplements (GS) on pain and maximum mouth opening (MMO) restriction compared to other therapies, placebo or no intervention on painful temporomandibular joint osteoarthritis (TMJ OA). Randomised controlled trials were selected in a two-phase process. Seven electronic databases, in addition to three grey literature databases, were searched. Risk of bias was assessed using the Cochrane Collaboration's tool for assessing risk of bias in randomised trials. Twelve potentially eligible studies were identified, from which three were finally included. Furthermore, two were categorised at low risk and one at high risk of bias. Intervention groups were treated with glucosamine-sulphate, while controls were treated with placebo or ibuprofen. In two studies, GS were equally effective regarding pain reduction and mouth opening improvement compared to ibuprofen taken two or three times a day over 12 weeks; however, one study did not find significant differences in follow-up evaluations concerning these clinical variables in both glucosamine and placebo groups administered over six weeks. There is very low evidence regarding GS therapeutic effects on TMJ OA. Considering a follow-up of 12 weeks, GS were as effective as ibuprofen taken two or three times a day. However, over six weeks of medication intake, GS were not superior to placebo. Still, included studies presented major drawbacks, and therefore, conclusions must be interpreted with caution.


Genome-wide analysis of the plant-specific VQ motif-containing proteins in tomato (Solanum lycopersicum) and characterization of SlVQ6 in thermotolerance.
The VQ motif-containing (VQ) proteins are plant-specific proteins with a conserved "FxxhVQxhTG" amino acid sequence, which regulate plant growth and development. Little is known, however, about the function of VQ proteins in tomato (Solanum lycopersicum). Here, a total of 26 SlVQ proteins were confirmed and characterized using a comprehensive genome-wide analysis. The SlVQ proteins all contain the conserved motif with seven variations, which are classified into eight groups (I, II, IV-VI, VIII-X). Most of them were predicted to be localized in the nucleus. Besides, a network including SlVQ proteins interaction with WRKY transcription factors (SlWRKYs) and mitogen-activated protein kinases (SlMPKs) is proposed. In addition, among the SlVQ genes, SlVQ6 was expressed in the range of organs and tissues with the highest levels and could response to different stresses. Ectopically overexpression of SlVQ6 in Arabidopsis plants decreased high temperature tolerance. RNA sequencing analysis revealed that several stress-related genes, such as HSP70-4, RD20, GolS1 and AT4g36010 were down-regulated in SlVQ6 overexpressing plants compared to these in wild-type under normal growth conditions. This study provides critical information about SlVQ genes and their encoded proteins, as well as further research on SlVQ functions in tomato growth and development.


Is a nonstented duct-to-mucosa anastomosis using the modified Kakita method a safe procedure?
After standardization of the perioperative management of pancreaticoduodenectomy, we retrospectively compared results in nonstented pancreaticojejunostomy with external-stented pancreaticojejunostomy. The study population included 129 consecutive patients who underwent pancreaticoduodenectomy between 2004 and 2008. The postoperative mortality and morbidity were compared between 51 patients with restrictive use of external stenting (group A) and 78 patients without external stenting (group B). The patient with a pancreatic duct of less than 3 mm in diameter was 31% in group A and 46% in group B. There were no differences in postoperative morbidity and mortality between the 2 groups. Although the frequency of overall postoperative pancreatic fistula development was significantly higher in group B than in group A (44% vs 27%, P = 0.0004), there was no difference in grade B/C postoperative pancreatic fistula rate (group A: 5.9% vs group B: 14.1%). The length of in-hospital stay in group B was significantly shorter than group A (13 vs 24 days, P < 0.0001). There were no differences in postoperative morbidity and mortality between subgroups that were consisted of patients with small pancreatic duct diameter. This retrospective single-center study showed that nonstented duct-to-mucosa anastomosis was a safe procedure and was associated with a shortened in-hospital stay.


Linear free energy relationship analysis of retention factors in cerasome electrokinetic chromatography intended for predicting drug skin permeation.
The retention factors of neutral, positively charged, and negatively charged solutes were determined in a liposome electrokinetic chromatography (EKC) system, where cerasome was used as the investigated liposome. The Abraham linear free energy relationship (LFER) for neutral and ionized solutes gave a good account of the retention factors (N = 71, R(2) = 0.814, and SD = 0.29 log units). It was shown that the calculated retention factors for 16 neutral acids were about four times higher than those of the corresponding anions, whereas the calculated retention factors for neutral bases were less than those for the corresponding cations by a factor of 0.36. The LFER equation for neutral species, anions, and cations was compared with those for partition from water into a number of solvents and for n-octanol-water distribution coefficients. It was shown that the cerasome EKC system is substantially different to the other systems and consequently it could be a very useful additional model system, possibly for predicting skin permeation. It was further shown that there are considerable advantages in the use of Abraham LFERs that can encompass not only neutral molecules but also ionic species.


Minimally invasive oxygen-ozone therapy for lumbar disk herniation.
Oxygen-ozone therapy is a minimally invasive treatment for lumbar disk herniation that exploits the biochemical properties of a gas mixture of oxygen and ozone. We assessed the therapeutic outcome of oxygen-ozone therapy and compared the outcome of administering medical ozone alone with the outcome of medical ozone followed by injection of a corticosteroid and an anesthetic at the same session. Six hundred patients were treated with a single session of oxygen-ozone therapy. All presented with clinical signs of lumbar disk nerve root compression, with CT and/or MR evidence of contained disk herniation. Three hundred patients (group A) received an intradiscal (4 mL) and periganglionic (8 mL) injection of an oxygen-ozone mixture at an ozone concentration of 27 micro g/mL. The other 300 patients (group B) received, in addition, a periganglionic injection of corticosteroid and anesthetic. Therapeutic outcome was assessed 6 months after treatment by using a modified MacNab method. Results were evaluated by two observers blinded to patient distribution within the two groups. A satisfactory therapeutic outcome was obtained in both groups. In group A, treatment was a success (excellent or good outcome) in 70.3% and deemed a failure (poor outcome or recourse to surgery) in the remaining 29.7%. In group B, treatment was a success in 78.3% and deemed a failure in the remaining 21.7%. The difference in outcome between the two groups was statistically significant (P <.05). Combined intradiscal and periganglionic injection of medical ozone and periganglionic injection of steroids has a cumulative effect that enhances the overall outcome of treatment for pain caused by disk herniation. Oxygen-ozone therapy is a useful treatment for lumbar disk herniation that has failed to respond to conservative management.


Sequence-specific detection of MicroRNAs by signal-amplifying ribozymes.
The rational and straightforward design of hairpin ribozymes that can be sequence-specifically induced by external oligonucleotides is described. Due to intrinsic signal amplification, their sensitivity is at least an order of magnitude increased compared to standard molecular beacons. We applied this system to the detection of microRNAs, a recently discovered class of small endogenous RNA molecules that are involved in gene regulation. We show that the cognate microRNA can reliably and sensitively be detected at low concentrations in a mix of other microRNA sequences. These probes may be useful in applications that require direct detection of minute amounts of small DNAs or RNAs.


Development of food group composites and nutrient profiles for the MyPyramid Food Guidance System.
To identify food selections in each MyPyramid food group or subgroup reflective of typical consumption patterns by Americans, and the nutrient intake that can be expected from consuming a specified amount of these foods from each group, in a low-fat and no-added-sugars form. An analytical process to identify food consumption choices within each food group and subgroup using national food consumption surveys, and to identify the expected nutrient content of each group using food composition databases. Relative consumption of foods within each food group; nutrient content for each food group and subgroup (energy plus 27 nutrients). Disaggregated foods from consumption surveys into component ingredients. Combined similar ingredients into "item clusters" and determined relative consumption of each. Calculated a consumption-weighted nutrient profile for each food group. Consumption-weighted food intake selections and nutrient profiles were developed for all MyPyramid food groups and subgroups. This analytical process derived food group and subgroup composites which estimate typical food choices within each MyPyramid food group. These were used to assess the adequacy of the MyPyramid food intake patterns as they were being iteratively developed.


The Nasal Complex of a Semiaquatic Artiodactyl, the Moose (Alces alces): Is it a Good Evolutionary Model for the Ancestors of Cetaceans?
Among Cetartiodactyla, cetaceans are the only obligate aquatic dwellers. Given morphological similarities between cetacean relatives such as Indohyus (the best represented Eocene raoellid artiodactyl) with other, later artiodactyls, any crown artiodactyl that engages in aquatic behaviors is of interest as an evolutionary model for the adaptations that accompanied the origins of cetaceans. The American moose (Alces alces) is the only non-cetacean artiodactyl to engage in aquatic foraging and, other than Hippopotamus, is distinctive in its diving behaviors. This study surveyed the soft and hard tissue nasal morphology of Alces alces to assess phylogenetic polarity and the presence of adaptations for diving and feeding in fresh water habitats. A fresh dissection of the facial musculature and nasal cavity was performed on one subadult male individual and osteological analyses were also performed on dry crania. This species was analyzed alongside fossil crania of Cervalces (its presumed ancestor), other cervids (e.g., Odocoileus virginianus, the white tail deer; Dama dama, the fallow deer), a bovid (Bos taurus, domestic cattle), and a carnivoran (Ursus americanus, the American black bear). A fresh dissection of the facial musculature and nasal anatomy of one fallow deer specimen was also performed for comparison with the moose. Results indicate that Alces alces exhibited a primitive configuration of maxillolabial muscles and, like Dama, exhibited a series of subcutaneous fibrous tissues connecting these muscles to skin. Alces and Dama, however, both exhibited autapomorphies in the soft tissue anatomy of the external nares. The former possessed a series of muscles that act to constrict the anterior nares, likely during diving. Extremely large fibrofatty pads that were perforated by muscle tendon supported their alar fold. Internally, a double-scrolled maxilloturbinal occupied nearly the entire volume of the anterior nasal cavity and protruded beyond the rim of the piriform aperture in dry crania. Dama had long, thin muscles taking origin on their nasal conchae and inserting onto the alar fold. Yet, despite these anterior nasal autapomorphies, the ethmoturbinal patterns of all observed cervids and the one bovid all appeared primitive with a posteroinferiorly oriented array of ethmoturbinals in close contact with a relatively straight cribriform plate, a macrosmatic condition. These differed from the curved cribriform plate of Ursus whose posterior nasal anatomy appeared hyper-macrosmatic. Indohyus exhibits no skeletal sign of a fleshy proboscis such as an enlarged piriform aperture or shortened nasal bones. Thus, there is little evidence that the early ancestors of cetaceans engaged in prolonged bouts of diving for aquatic foods but more probably were surface swimmers traveling between terrestrial food sources or fleeing predators. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 302:667-692, 2019. © 2018 Wiley Periodicals, Inc.


[Effects of nutritional status on the multiple sclerosis disease: systematic review].
To review the available scientific literature about the effects of nutritional status on the multiple sclerosis disease. A systematic review of the scientific literature in the Medline (PubMed), Scopus, Cochrane Library and Web of Science databases through November 2016. Search equation: ("Multiple Sclerosis"[Mesh] OR "Multiple Sclerosis"[Title/Abstract] OR "Disseminated Sclerosis"[Title/Abstract] OR "Multiple Sclerosis Acute Fulminating"[Title/Abstract]) AND ("Nutritional Status"[Mesh] OR "Nutritional Status"[Title/Abstract] OR "Nutrition Status"[Title/Abstract]). The quality of the selected articles was discussed using the STROBE questionnaire. The search was completed through experts inquiry and additional review of the bibliographic references included in the selected papers. The concordance between authors (Kappa index) had to be higher than 80% for inclusion in this review. Of the 160 references recovered, after applying inclusion and exclusion criteria, 29 articles were selected for review. Concordance between evaluators was 100.00%. The most studies established vitamin D levels. Others focused their research on finding out which nutrient deficits might be related to the multiple sclerosis development. Vitamin D may influence multiple sclerosis improvement. Sunlight and physical activity would be important factors, with nutritional status, in the course of this disease. It is necessary to produce new specific works that will delve into the subject to find out more about the relationship between nutritional status and multiple sclerosis.


Depressed hypothalamic CRF immunoreactivity in 15 day old thiouracil-treated rats.
Depression of thyroid status with thiouracil has been shown to delay the response of the hypothalamus-pituitary-adrenal axis to stress in young rats. In vivo and in vitro bioassay studies have indicated that the hypothalamus is the main site of axis alteration in 15 day old animals. The present study has found a significantly depressed hypothalamic content of immunoassayable corticotropin-releasing factor (CRF) in thiouracil treated young rats.


KDI tripeptide from laminin: a novel approach to treat neurodegenerative disorders.
The excessive release of glutamate following brain injury is responsible for the phenomenon of glutamate excitotoxicity, mediated through glutamate receptors, resulting in apoptotic cell death. KDI ameliorates excitotoxicity and regenerates damaged nerve cells.


Effect of fiber from fruits and vegetables on metabolic responses of human subjects. III. Zinc, copper, and phosphorus balances.
Intakes and excretions of zinc, copper, and phosphorus were determined for 12 men when they consumed a diet low in fiber and when they consumed a diet containing fiber from fruits and vegetables (high-fiber diet). All subjects consumed both diets for 26 days each. The low-fiber diet was supplemented with copper so that it was equivalent to the high-fiber diet in this respect. Mean daily intakes on the low- and high-fiber diets, respectively, were: zinc, 13.2 and 12.6 mg; copper, 1.8 and 1.6 mg; phosphorus, 1.639 and 1.690 g. Mean daily balances on the low- and high-fiber diets, respectively, were: zinc, +3.5 and -0.9 mg; copper, +0.2 and -0.4 mg; phosphorus, +0.361 and +0.292 g. Zinc and copper balances differed significantly on the two diets (P less than 0.001 and P less than 0.005, respectively, but phosphorus balances did not. The fiber supplied by the fruits and vegetables contained more lignin and cellulose and less hemicellulose than would an equivalent amount of fiber from bran. The bran would supply more magnesium, zinc, and copper than this particular diet containing fruits and vegetables.


Transurethral electrovaporization of the prostate in benign prostatic hyperplasia. Evaluation of results using different urodynamic parameters.
We studied the obstruction-relieving capabilities of transurethral electrovaporization of the prostate (TVP) in 32 symptomatic patients with benign prostatic hyperplasia (BPH). Urodynamic studies with pressure-flow analysis were performed before and 6 months after treatment. All 32 patients showed significant improvement of both subjective and objective obstruction parameters. There were few postoperative irritative symptoms and one patient required recatheterization. In conclusion, TVP is a promising modification of performing transurethral resection of the prostate, and it is indeed capable of relieving bladder outflow obstruction.


[A case report of urinary tract infection and meningitis caused by methicillin-resistant Staphylococcus aureus (MRSA) after transurethral resection of the prostate].
We present a case of meningitis that developed following a urinary tract infection caused by methicillin-resistant Staphylococcus aureus (MRSA) after transurethral resection of the prostate. The patient, a 69-year-old man with diabetes mellitis, underwent transurethral resection of the prostate following a diagnosis of benign prostatic hypertrophy. On the 4 th day after surgery, high fever occurred immediately after the removal of the indwelling urethral catheter. Cultures of urine and blood revealed MRSA. On the 6 th day after surgery, severe lumbago was evident and MRSA was isolated from cerebrospinal fluid. Separate administration of arbekacin or vancomycin, to which the isolated MRSA was sensitive, was not effective. Combined therapy with fosfomycin, vancomycin and human immunoglobulin effectively relieved the inflammation. Although it is generally reported that the pathogenicity of MRSA is low in the urinary tract, this case suggests that a urinary tract infection caused by MRSA can advance to sepsis and meningitis.


Acute measles encephalitis of the delayed type: neuroradiological and immunological findings.
A case of delayed acute measles encephalitis in an immunosuppressed child is reported. Detailed immunological studies have shown defective humoral immunity (defective IgA, IgG2 and IgG3) and decreased natural killer activity. Neuroradiological examination by magnetic resonance imaging revealed several high signal lesions on T2-weighted images in the gray matter without clinical or pathological correlation. The implications of these findings are discussed.


Epithelioid sarcoma: clinical, MR imaging and pathologic findings.
To report and describe the MR imaging features of eight new cases of this rare soft tissue sarcoma and correlate them with the clinical and histologic findings. DESIGN AND PATIENTS. Retrospective analysis was carried out for the MR imaging characteristics and histologic findings of eight patients with pathologically proven epithelioid sarcoma and the literature was reviewed. Findings were correlated in each case with the patient's clinical presentation and eventual outcome. The patients, whose primary tumors ranged from 2.5 cm to 19 cm in maximum dimension, were 1 to 90 years of age. Tumors involved the extremities ( n=5), the scalp ( n=2) and the paraspinal muscles ( n=1). Five tumors presented as well-defined, frequently painful, deeply situated masses and three as subcutaneous nodules or cutaneous ulcers with no palpable mass. Four patients had associated regional lymphadenopathy and one had distant metastases at diagnosis. MR imaging showed tumor infiltration of adjacent tissues in seven patients. Signal characteristics reflected varying degrees of cellularity, and the presence of necrosis, hemorrhage, fibrosis, hyalinization and inflammation. Bone marrow involvement was demonstrated in one patient. Clinical outcomes were generally poor. Epithelioid sarcoma is an aggressive soft tissue sarcoma with a varied clinical presentation, growth pattern, MR signal characteristics and histologic picture. The tumor favors the distal extremities and is commonly infiltrative and accompanied by enlarged regional lymph nodes. This neoplasm may present as an intramuscular mass but should also be suspected in patients with ulcerating cutaneous nodules with or without regional lymphadenopathy.


Electron microscopic observations in in situ and microinvasive bronchogenic squamous cell carcinoma.
Seventeen cases of resected in situ and microinvasive bronchogenic squamous cell carcinoma were studied by light and electron microscopy. No definite secretory differentiation was found in any case. Examination of the tumour cells in the basal layer for electron density of cytoplasm, intercellular spaces, and degree of development of cytoplasmic processes showed a variety of cells ranging from type I, where the cytoplasm was dark, development of cytoplasmic processes was good, and the intercellular spaces were large, to type III, where cytoplasmic processes and intercellular spaces were less well developed and the cells were mostly of clear cell type. The tendency to invasion was greater in type III than type I and there was also more marked cellular atypia, more extensive dissolution of basement membrane, a larger number of mitotic figures per 3000 cells in the basal layer, and greater enlargement of nuclear and cytoplasmic areas. A good rank correlation coefficient was obtained. Small dense-core granules were observed in some cases. These finding suggest the strong possibility that cell kinetics and cellular morphology are related to the development of squamous cell carcinoma.


Beyond immunization: travelers' infectious diseases. 1--Diarrhea.
Travelers' diarrhea is the most common illness in persons traveling from resource-rich to resource-poor regions of the world. The fear of developing diarrhea while traveling is common among travelers to any part of the developing world. This concern is realistic; 40 to 60% of travelers to these countries may develop diarrhea. Diarrheal diseases represent one of the five leading causes of death worldwide. Morbidity and mortality are significant even in the United States where diarrhea is more often than not a "nuisance disease" in the normally healthy individual.


Does cessation of progesterone supplementation during early pregnancy in patients treated with recFSH/GnRH antagonist affect ongoing pregnancy rates? A randomized controlled trial.
The aim of this study was to assess whether the cessation of progesterone (P) supplementation during early pregnancy after GnRH antagonist cycles is not inferior to its continuation in terms of pregnancy rates beyond 12 weeks of gestation There were 200 patients, with a positive β-hCG test (followed by a doubling in β-hCG levels 48 h later) after a fixed recombinant FSH (recFSH)/GnRH antagonist protocol for IVF/ICSI and a Day-3 fresh embryo transfer (ET), participated in this randomized controlled study. All patients received luteal support, with 200 mg vaginal P being administered three times daily for 14 days, beginning on the day of ET until the second β-hCG test, 16 days post-ET. In the control group (n = 100) the administration of P was continued until 7 weeks of gestation. In the study group (n = 100), vaginal P was discontinued on the 16th day post-ET RESULTS: The ongoing pregnancy rate beyond 12 weeks, the primary outcome measure, did not differ between the study and control groups (82 versus 73%, P = 0.175; difference 9%, 95% CI: -2.6 to 20.3). There were also no significant differences observed between the study and control group in terms of abortion before or after 7 weeks of gestation [(9 versus 12%, P = 0.645) and (8 versus 10%, P = 0.806), respectively]. The same was true for bleeding episodes (14 versus 19%, P = 0.446). After recFSH/GnRH antagonist cycles, the withdrawal of P supplementation in early pregnancy, with normally increasing β-hCG levels on the 16th day post-ET, had no significant clinical impact in terms of ongoing pregnancy rates beyond 12 weeks.


Immunogenicity of FaB fragment of protein-315 for BALB/cmice.
Immunogenicity of Protein-315 and its Fab fragment (Fab-315) for isologous and heterologous strains of mice was investigated by comparing the characteristics of the anti-idiotypic response produced in BALB/c and A/J mice. The ability of these anti-idiotypic antisera to compete with DNP-lys for the ligand-binding site of Protein-315 were analyzed by comparing their hapten inhibition curves. The anti-idiotypic responses of BALB/c mice to Protein-315 and to Fab-315 were similar to one another with regard to antibody specificity and sensitivity to inhibition by hapten, suggesting that both forms were equally immunogenic in inbred BALB/c mice. This observation indicates that the Fc portion of Protein-315 is not essential for the induction of anti-idiotypic response. Both BALB/c and A/J mice recognized the same antigenic determinants on Fab-315 since the anti-idiotypic antibodies produced by these animals were indistinguishable with regard to their interaction with Protein-315, Fv-315, and sensitivity to hapten inhibition. On the other hand, the response of A/J mice to Protein-315 was remarkably different from that of BALB/c mice since it was found that Protein-315 seemed to be more immunogenic in A/J mice than in BALB/c mice. The data also indicated that Protein-315 was more immunogenic than Fab-315 in stimulating the anti-idiotypic response in A/J mice. A/J antiserum to Protein-315 was found to have antibodies specific for the ligand-binding site as well as those specific for other antigenic determinations on the Fc portion. These findings suggest that the Fc portion of Protein-315 may either act as a haptenic determinatant to provoke directly the antibody response or as a carrier determinant to enhance the anti-Fab response in A/J mice.


Estimating the critical duration for temporal summation of standard achromatic perimetric stimuli.
To estimate the critical duration of temporal summation for achromatic Goldmann III stimuli under the conditions of standard automated perimetry (SAP) and quantify response variability for short-duration stimuli. Contrast thresholds were gathered using the method of constant stimuli for seven circular (0.48° diameter) incremental stimuli of varying duration (sum-of-frames equivalent: 8.3-198.3 ms), at an eccentricity of 8.8° along the four principal meridians of the visual field in two healthy, psychophysically experienced observers. Stimuli were presented on a high-resolution cathode ray tube display with a background luminance of 10 cd/m(2). Psychometric functions were fitted using a probit model and nonparametric local-linear analysis. The critical duration was estimated using iterative two-phase regression analysis, the results also being compared with values produced using previously published methods of analysis. The median critical duration estimated using iterative two-phase regression analysis was 27.7 ms (IQR 22.5-29.8). A slight steepening of the psychometric function slope (lower variability) was observed for longer stimulus durations, using both probit and local-linear analysis techniques, but this was not statistically significant. Critical duration estimates in this study are substantially shorter than those previously reported for a Goldmann III stimulus, under the conditions of SAP. Further work is required to firmly establish the relationship between measurement variability and the degree of local temporal and spatial summation.


Myocardial redox state during coronary artery bypass grafting assessed with microdialysis.
Microdialysis allows the biochemical analysis of interstitial fluids of nearly every organ as a bedside procedure. This technique could be useful to reveal data about the myocardial metabolism during cardiopulmonary bypass in human coronary artery bypass graft (CABG) surgery. In 17 patients undergoing CABG a myocardial microdialysis catheter (CMA 70, CMA/Microdialysis AB, Sweden) was inserted in the apical region of the beating heart. Microdialysis measurements were performed at timed intervals before, during, and after cardiopulmonary bypass (CPB). The concentrations of lactate and pyruvate were analyzed semi-continuously. During CPB the myocardial lactate-pyruvate-ratio (LPR) rose from an initial 11 (8-15) to 33 (29-41) ( P<0.01). After CPB the LPR decreased to 4 (3-7) at the end of observation ( P<0.05). The pyruvate concentration showed an immediate increase from 34 (30-42) microM at the end of CPB to 181 (147-234) microM after removal of the cross-clamp with subsequent increase during reperfusion ( P<0.01). Plasma lactate and pyruvate showed no essential changes during the study. Using the microdialysis technique it was possible to analyze myocardial metabolic changes during CABG. The course of myocardial LPR as a sensitive indicator of the myocardial redox state showed profound changes during and after CPB. We propose the microdialysis technique as an additional monitoring tool in CABG.


Freeze-thaw-induced changes of the zona pellucida explains decreased rates of fertilization in frozen-thawed mouse oocytes.
Frozen-thawed oocytes have a reduced rate of fertilization (48.8%) when compared with unfrozen controls (97%). In this study we have used zona-drilling to bypass the zona pellucida and investigate whether the decreased rate of fertilization is due to freezing-induced changes in the zona pellucida which prevent sperm penetration. After zona drilling the fertilization rate of frozen-thawed oocytes (87.8%) was the same as for zona-intact unfrozen controls (88%), indicating that freeze-thaw-induced changes at the level of the zona pellucida were responsible for the decreased rate of fertilization. To determine whether the changes were occurring during the manipulations before and after freezing or the complete freeze-thaw cycle, oocytes were exposed to the complete set of manipulations normally experienced during cryopreservation and appropriate control groups. A small but significant decrease in the rate of fertilization (82.8%) was apparent in oocytes exposed to the manipulations before and after freezing compared with controls (92.2%). The freeze-thaw-induced changes in the zona pellucida therefore occur primarily during the complete freeze-thaw cycle itself and not the manipulations before and after freezing and are responsible for the decreased rate of fertilization observed in frozen-thawed oocytes.


Isolated Robin sequence in siblings: review of current concepts.
Robin sequence is a condition that includes the triad of micrognathia, glossoptosis and upper airway obstruction, although many authors now consider that cleft palate is also an important part of the sequence. It can be classified as isolated, syndromic or associated with other anomalies without an identifiable syndrome. A possible genetic cause for isolated Robin sequence is yet under preliminary investigation, and the finding of siblings with the same condition, as are the two children we present in this work, is extremely rare, with only nine similar cases previously described. Our article includes the description of the treatment plan and outcome for both children. We review the current concepts and trends of epidemiology, genetics, diagnosis and different treatment options available. We conclude that in cases of failure of more conservative measures in the first weeks, mandibular distraction osteogenesis may be a good and rational option for the management of isolated Robin sequence, as is currently supported in recent literature, providing a reliable way of avoiding tracheostomy.


Polymorphic cytochromes P450 and drugs used in psychiatry.
1. The cytochrome P450 monooxygenases, CYP2D6, CYP2C19, and CYP2C9, display polymorphism. CYP2D6 and CYP2C19 have been studied extensively, and despite their low abundance in the liver, they catalyze the metabolism of many drugs. 2. CYP2D6 has numerous allelic variants, whereas CYP2C19 has only two. Most variants are translated into inactive, truncated protein or fail to express protein. 3. CYP2C9 is expressed as the wild-type enzyme and has two variants, in each of which one amino acid residue has been replaced. 4. The nucleotide base sequences of the cDNAs of the three polymorphic genes and their variants have been determined, and the proteins derived from these genes have been characterized. 5. An absence of CYP2D6 and/or CYP2C19 in an individual produces a poor metabolizer (PM) of drugs that are substrates of these enzymes. 6. When two drugs that are substrates for a polymorphic CYP enzyme are administered concomitantly, each will compete for that enzyme and competitively inhibit the metabolism of the other substrate. This can result in toxicity. 7. Patients can be readily phenotyped or genotyped to determine their CYP2D6 or CYP2C19 enzymatic status. Poor metabolizers (PMs), extensive metabolizers (EMs), and ultrarapid metabolizers (URMs) can be identified. 8. Numerous substrates and inhibitors of CYP2D6, CYP2C19, and CYP2C9 are identified. 9. An individual's diet and age can influence CYP enzyme activity. 10. CYP2D6 polymorphism has been associated with the risk of onset of various illnesses, including cancer, schizophrenia, Parkinson's disease, Alzheimer's disease, and epilepsy.


IL-2-induced IL-5 synthesis, but not proliferation, of human CD4+ T cells is suppressed by FK506.
Regulation of T cell IL-5 synthesis was investigated using human Th cell clones. Immunosuppressant FK506 suppressed IL-5 synthesis of T cells activated through TCR in a dose-dependent manner. IL-5 gene transcription and protein synthesis were also induced in the same T cell clones upon stimulation with IL-2 and were suppressed by FK506 in a dose response similar to that induced by TCR stimulation. In contrast to TCR stimulation, neither activating protein-1, nuclear factor-AT (NF-AT), nor NF-kappaB binding activity was significantly up-regulated by IL-2 stimulation. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell clones was transcribed upon either TCR or IL-2 stimulation and was clearly down-regulated by FK506, indicating that the approximately 500-bp human IL-5 gene segment located 5' upstream of the coding region contained FK506-sensitive enhancer elements. Our present findings clearly indicate that FK506-sensitive signaling molecules are involved in T cell IL-5 production induced by both TCR and IL-2 stimulation and suggest that IL-2 receptor signal leading to IL-5 gene transcription is transduced by a unique FK506-sensitive pathway other than the Ca2+-dependent signal transduction pathway, such as the calcineurin-NF-AT system.


The role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in Alzheimer's disease: therapeutic implications.
Alzheimer's disease is a complex neurodegenerative disorder, with aging, genetic and environmental factors contributing to its development and progression. The complexity of Alzheimer's disease presents substantial challenges for the development of new therapeutic agents. Alzheimer's disease is typified by pathological depositions of beta-amyloid peptides and neurofibrillary tangles within the diseased brain. It has also been demonstrated to be associated with a significant microglia-mediated inflammatory component, dysregulated lipid homeostasis and regional deficits in glucose metabolism within the brain. The peroxisome proliferator-activated receptor-gamma (PPARgamma) is a prototypical ligand-activated nuclear receptor that coordinates lipid, glucose and energy metabolism, and is found in elevated levels in the brains of individuals with Alzheimer's disease. A recently appreciated physiological function of this type of receptor is its ability to modulate inflammatory responses. In animal models of Alzheimer's disease, PPARgamma agonist treatment results in the reduction of amyloid plaque burden, reduced inflammation and reversal of disease-related behavioural impairment. In a recent phase II clinical trial, the use of the PPARgamma agonist rosiglitazone was associated with improved cognition and memory in patients with mild to moderate Alzheimer's disease. Thus, PPARgamma may act to modulate multiple pathophysiological mechanisms that contribute to Alzheimer's disease, and represents an attractive therapeutic target for the treatment of the disease.


Heat tolerance in Drosophila subobscura along a latitudinal gradient: Contrasting patterns between plastic and genetic responses.
Susceptibility to global warming relies on how thermal tolerances respond to increasing temperatures through plasticity or evolution. Climatic adaptation can be assessed by examining the geographic variation in thermal-related traits. We studied latitudinal patterns in heat tolerance in Drosophila subobscura reared at two temperatures. We used four static stressful temperatures to estimate the thermal death time (TDT) curves, and two ramping assays with fast and slow heating rates. Thermal death time curves allow estimation of the critical thermal maximum (CT(max)), by extrapolating to the temperature that would knock down the flies almost "instantaneously," and the thermal sensitivity to increasing stressful temperatures. We found a positive latitudinal cline for CT(max), but no clinal pattern for knockdown temperatures estimated from the ramping assays. Although high-latitude populations were more tolerant to an acute heat stress, they were also more sensitive to prolonged exposure to less stressful temperatures, supporting a trade-off between acute and chronic heat tolerances. Conversely, developmental plasticity did not affect CT(max) but increased the tolerance to chronic heat exposition. The patterns observed from the TDT curves help to understand why the relationship between heat tolerance and latitude depends on the methodology used and, therefore, these curves provide a more complete and reliable measurement of heat tolerance.


Improving the quality of medical care: building bridges among professional pride, payer profit, and patient satisfaction.
Physicians today are confronted with increasing demand to ensure and improve care of their patients. A variety of approaches claim to provide solutions to the problems of health care delivery. These approaches represent different perspectives on optimal care and the best method for improving care. By summarizing recent reviews and debates in this field, this article critically reflects on the value of some of the approaches that have gained popularity during the last decades: evidence-based medicine and clinical practice guidelines, professional development, assessment and accountability, patient empowerment, and total quality management. Evidence regarding the impact and feasibility of the various approaches is mixed or simply lacking. In particular, the health care community lacks an understanding of which approaches are most appropriate for what types of improvement in what settings and of the determinants of successful performance change. Given the complexity of improvement and change in patient care, it is not realistic to expect that one approach can solve all the problems in health care delivery. None of the popular models for improving clinical performance appear to be superior. Therefore, bridges must be built and models must be integrated to be truly effective.


Permutation tests for the correlation among genetic distances and measures of heterosis.
It is often found that heterosis tends to increase with genetic distance of the parents, though the correlation is not usually very close. It is therefore important to test the null hypothesis that the correlation is zero. The present work shows that standard procedures tend to yield too liberal tests, owing to the lack of independence among genetic distances and among heterosis estimates. A valid alternative is to use a permutation test, which was first suggested by Mantel [(1967) Cancer Res 27: 209--220). This test is well-known among plant breeders and geneticists, who often use it to test the correlation among two distance matrices. Its use is not restricted to the comparison of distance matrices. This is demonstrated in the present work, using two published datasets on marker-based genetic distances of maize inbreds or populations and heterosis of their crosses. It is shown that the test is also applicable in the presence of missing data.


UV filters for hair protection.
Synopsis Hair damage, caused by sunlight, and the possibility to protect hair against sunlight by means of cosmetic formulations was studied. For this, five UV-filters were tested: benzophenone-3 (UV-A/UV-B); benzophenone-4 (UV-A/UV-B); phenylbenzimidazole sulfonic acid (UV-B); butylmethoxydibenzoylmethane (UV-A); octyl dimethyl PABA (UV-B). The stability of the UV-filters was tested as pure substances as well as in two cosmetic formulations: a setting lotion and a shine spray. The degree of decolouration and stress strain behaviour were determined. The benzophenones had the best protection ability both on colour and on morphology. Stability data and UV-spectra are discussed.


Notch Signaling Target Genes are Directly Correlated to Esophageal Squamous Cell Carcinoma Tumorigenesis.
Notch signaling is an important cellular pathway which affects the development and function of many organs. It plays critical roles in maintaining of progenitor stem cell population as well as balancing cell proliferation, survival, differentiation and apoptosis. It has been shown that notch signaling is aberrantly activated during the carcinogenesis of a variety of human cancers. In this study we aimed to explore activation of this signaling pathway in esophageal squamous cell carcinoma (ESCC) through expressional analysis of notch signaling target genes. The mRNA expression of HEY1 and HEY2 was comparatively analyzed by real-time PCR in tumor and related margin normal tissues of 50 ESCC patients. Comparative quantitative real-time PCR indicates the overexpression of HEY1 and HEY2 in 54 and 30% of ESCC samples, respectively. Overexpression of HEY1 was significantly associated with stage of the tumor (p = 0.048) and tumor location (p = 0.008). HEY2 overexpression was also significantly correlated to node metastasis of tumor cells (p = 0.043). Overexpression of HEY1 and HEY2 in ESCC is correlated to different indices of poor prognosis and it is extrapolated that such overexpression is important in progression and development of ESCC tumorigenesis. To the best of our knowledge, this is the first report introducing aberrant activation of notch signaling target genes in ESCC, where it plays roles in development and progression of the malignancy and may be considered in therapeutic modalities to restrict ESCC progression.


[Cefditoren: a reality for the treatment of community infections].
Cefditoren, a third-generation cephalosporin, is the oral β-lactam more active against the main community-acquired respiratory tract pathogens (including resistance phenotypes such as penicillin-resistant Streptococcus pneumoniae and ampicillin-resistant Haemophilus influenzae), similar to cefotaxime. Data obtained from clinical trials and later evidence on efficacy and safety, support that cefditoren is an suitable option for the treatment of mild-to moderate community respiratory and urinary tract infections, particularly in regions where non-susceptible phenotipes to common oral antibiotics are prevalent.


Reduced plantarflexor specific torque in the elderly is associated with a lower activation capacity.
Previous studies have reported a decrease in muscle torque per cross-sectional area in old age. This investigation aimed at determining the influence of agonists muscle activation and antagonists co-activation on the specific torque of the plantarflexors (PF) in recreationally active elderly males (EM) and, for comparison, in young men (YM). Twenty-one EM, aged 70-82 years, and 14 YM, aged 19-35 years, performed isometric maximum voluntary contractions (MVC). Activation was assessed by comparing the amplitude of interpolated supramaximal twitch doublets at MVC, with post-tetanic doublet peak torque. Co-activation of the tibialis anterior (TA) was evaluated as the ratio of TA-integrated EMG (IEMG) activity during PF MVC compared to TA IEMG during maximal voluntary dorsiflexion. Triceps surae muscle volume (VOL) was assessed using magnetic resonance imaging (MRI), and PF peak torque was normalised to VOL (PT/VOL) since the later approximates physiological cross-sectional area (CSA) more closely than anatomical CSA. Also, physical activity level, assessed by accelerometry, was significantly lower (21%) in the elderly males. In comparison to the YM group, a greater difference in PT (39%) than VOL (19%) was found in the EM group. PT/VOL and activation capacity were respectively lower by 25% and 21% in EM compared to YM, whereas co-activation was not significantly different. In EM PT/VOL correlated with activation (R(2)=0.31, P<0.01). In conclusion, a reduction in activation capacity may contribute significantly to the decline in specific torque in the plantar flexors of elderly males. The hypothesis is put forward that reduced physical activity is partialy responsible for the reduced activation capacity in the elderly.


Coal particle combustion studied by holography.
The application of holography to the study of burning coal particles in free flight was examined. Resolution to about 3 microm was attained in the combustion zone of a flat flame burner. Both size and velocity of particles up to 75 microm in diameter were measured holographically. Holographic interferometry was also used. Basic combustion events in coal were recorded and are presented here which have not been observed previously. A comparison of images produced by in-line and off-axis holography also resulted from the study.


Three-dimensional electrospun nanofibrous scaffolds displaying bone morphogenetic protein-2-derived peptides for the promotion of osteogenic differentiation of stem cells and bone regeneration.
Tissue scaffolds with three-dimensional (3D) nanofibrous biomimetic structures have attracted attention in the field of bone regeneration. In recent years, emerging strategies based on electrospinning technologies have facilitated the preparation of 3D nanofibrous scaffolds. Based on these developments, in this study, 3D scaffolds possessing both nanofibrous morphologies and interconnected pores were fabricated for their potential in bone tissue engineering. By combining homogenizing, freeze-drying, and thermal crosslinking techniques, nano-hydroxyapatite/PLLA/gelatin (nHA/PLA/GEL) 3D nanofibrous scaffolds were prepared using pre-fabricated electrospun nanofibers. Then, utilizing a polydopamine (pDA)-assisted coating strategy, bone morphogenetic protein-2 (BMP-2)-derived peptides were further immobilized onto the 3D scaffolds to obtain the resulting nano-hydroxyapatite/PLLA/gelatin-peptide (nHA/PLA/GEL-PEP) 3D nanofibrous scaffolds capable of sustained release. Bone mesenchymal stem cells (BMSCs) were cultured on the 3D nanofibrous scaffolds, then relative cell viability, alkaline phosphatase (ALP) activity, and gene expression assays were performed to study the effects of the scaffolds on cell growth and osteogenic differentiation in vitro. Furthermore, the ability of bone formation in vivo was evaluated using a rat cranial bone defect model. In vitro and in vivo results demonstrated that the 3D nanofibrous scaffolds incorporated with nHA and BMP-2 peptides exhibited favorable biocompatibility and osteoinductivity. Therefore, these nanofibrous scaffolds have excellent potential in bone regenerative medicine.


Reliability (internal consistency) of the job content questionnaire on job stress among office workers of a multinational company in Kuala Lumpur.
This small, cross-sectional study assessed the reliability of 3 scales from the Job Content Questionnaire (JCQ)-decision latitude, psychological job demand, and social support-in a group of office workers in a multinational company in Kuala Lumpur. A universal sample of 30 white-collar workers from a department of the company self-administered the English version of the JCQ comprising 21 core items selected from the full recommended version of 49 items on-site. Reliability (internal consistency) was evaluated using Cronbach's alpha coefficients for each scale. Corrected item-total correlation was presented for each and every item. Cronbach's alpha coefficients were acceptable for decision latitude (.76) and social support (.79) but slightly lower for psychological job demand (.64). Values for all item-total correlations for all 3 scales were greater than .3. In conclusion, this study suggests that the JCQ is a reliable scale for assessing job stress in this group of workers.


A novel method for purification of plasma fibronectin.
Plasma fibronectin was purified from a gelatin-affinity chromatography column by elution with glucose. This procedure was effective only if the gelatin was particulate when it was attached to the Sepharose 4B. Glucose could not elute fibronectin from the gelatin if the gelatin was melted before it was attached to the Sepharose 4B. This new purification technique has the advantage of using very mild conditions for the isolation of plasma fibronectin.


Combination of transcatheter arterial embolization and percutaneous ethanol injection for hepatocellular carcinoma: comparison of efficacies of doxorubicin and epirubicin in transcatheter arterial embolization.
We administered a combination of transcatheter arterial embolization (TAE) and percutaneous ethanol injection (PEI) (ie, pretreatment with TAE and subsequent PEI) to treat 56 patients with multiple lesions (number of nodules < or = 3) or a single large (diameter > or = 3 cm) encapsulated lesion of hepatocellular carcinoma. The TAE included doxorubicin (40 mg) in 32 cases and epirubicin (mean, 82 mg) in the remaining 24 cases, and the efficacies of the two were compared. The therapeutic efficacy was evaluated on the basis of the survival rate and recurrence-free survival rate revealed by clinical follow-up. Both rates showed significant differences between the doxorubicin and epirubicin groups, with both being superior in the epirubicin group. It was surmised that epirubicin is a useful chemotherapeutic agent in TAE for patients with hepatocellular carcinoma.


Region-specific alterations in astroglial TWIK-related acid-sensitive K+-1 channel immunoreactivity in the rat hippocampal complex following pilocarpine-induced status epilepticus.
In the present study, we performed an analysis of tandem of P domains in a weak inwardly rectifying K+ channel (TWIK)-related acid-sensitive K+ (TASK)-1 channel immunoreactivity in the rat hippocampal complex following pilocarpine-induced status epilepticus (SE). In control animals, TASK-1 immunoreactivity was strongly detected in astrocytes in the hippocampal complex. One day after SE, TASK-1 immunoreactivity in astrocytes was markedly reduced only in the molecular layer of the dentate gyrus. One week after SE, loss of astrocytes was observed in the molecular layer of the dentate gyrus. At this time point, TASK-1 immunoreactive cells were detected mainly in the subgranular region. These cells had bipolar, elongated cell bodies with fusiform-shaped nuclei and showed vimentin immunoreactivity. Four weeks after SE (when spontaneous seizure developed), typical reactive astrogliosis was observed in the dentate gyrus and the CA1 region. Almost no astrocytes in the molecular layer showed TASK-1 immunoreactivity, whereas astrocytes in the CA1 region showed strong TASK-1 immunoreactivity. These findings indicate that, after SE, TASK-1 immunoreactivity was differentially altered in astrocytes located in different regions of the hippocampal complex, and these changes were caused by astroglial degeneration/regeneration. Therefore, alteration in TASK-1 immunoreactivity may contribute to acquisition of the properties of the epileptic hippocampal complex.


Does compliance with radiation therapy differ in African-American patients with early-stage breast cancer?
The worse outcomes in African-American (AA) breast cancer patients have been attributed to a variety of factors, including compliance/variations with treatment. We evaluated a large cohort of AA patients treated with breast conservation therapy (BCT) in an effort to determine if compliance with radiation or if choice of chemotherapy regimen could be a contributing factor for the worse outcomes reported in AA patients. Our two cohorts consisted of 221 AA and 2170 white patients treated with BCT. Chart reviews were conducted to document dates of treatment, treatment breaks, dose delivered, and chemotherapy delivered. The data were analyzed to detect differences between the two cohorts. The median radiation dose delivered (including cone-down) was 64 Gy in both cohorts (p = 0.9910). The median number of treatment days was: AA, 45 (range 21-71 days) versus white, 45 (range 14-90 days; p = 0.8465). The chemotherapy regimens administered were: adriamycin/cytoxan (17% AA versus 19% white, respectively), adriamycin/cytoxan/taxol (13% versus 5%), cytoxan/methotrexate/5-FU (53% versus 59%), cytoxan/methotrexate/5-FU/vincristine (0% versus 3%), cytoxan/adriamycin/5-FU (12% versus 11%), high dose/transplant (0% versus 1%), and other (4% versus 5%), p = 0.113. Our large institutional series suggests that compliance with radiation therapy, once patients are seen in consultation and simulated, does not differ significantly between AA and white patients. In our large cancer center environment, AA patients referred for radiation therapy appear to receive the same radiation doses in a comparable time frame to white patients. Further exploration of compliance for adjuvant chemotherapy regimens in AA patients is warranted.


Magnetic resonance imaging in animal models of epilepsy-noninvasive detection of structural alterations.
Small animal magnetic resonance imaging (MRI) has opened a window through which brain abnormalities can be observed over time in rodents noninvasively. We review MRI studies done during epileptogenesis triggered by status epilepticus in rat. Most of these studies have used quantitative T2, diffusion, and/or volumetric MRI. The goal has been to identify the distribution and severity of structural lesions during the epileptogenic process, that is, soon after status epilepticus, during epileptogenesis, and after the appearance of spontaneous seizures. Data obtained demonstrate that MRI can be used to associate the development of brain pathology with the evolution of clinical phenotype. MRI can also be used to select animals to preclinical studies based on the severity and/or distribution of brain damage, thus making the study population more homogeneous, for example, for assessment of novel antiepileptogenic or neuroprotective treatments. Importantly, follow-up data collected emphasize interindividual differences in the dynamics of development of abnormalities that could have remained undetected in a typical histologic analysis providing a snapshot to brain pathology. A great future challenge is to take advantage of interanimal variability in MRI in the development of surrogate markers for epilepsy or its comorbidities such as memory impairment. Understanding of molecular and cellular mechanisms underlying changes in various MRI techniques will help to better understand complex progressive pathological processes associated with epileptogenesis and epilepsy.


Purification and some properties of phosphoenolpyruvate carboxylase from Brevibacterium flavum and its aspartate-overproducing mutant.
Phosphoenolpyruvate (PEP) carboxylases (PC) were purified from a wild strain and an aspartate-producing mutant of Brevibacterium flavum to electrophoretic homogeneity. The molecular weights of the enzymes were determined to be 4.1 X 10(5) by the gel-filtration technique. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the enzyme gave only one protein band with a molecular weight of 1.07 X 10(5). The enzyme was labile and stabilized by substrate PEP, activators, metallic cofactors, an allosteric inhibitor and ammonium sulfate. The mechanism for the PC reaction was rapid equilibrium random Bi Bi with a dead end complex, enzyme-bicarbonate-Pi. The KmS for PEP and bicarbonate were 2.5 and 0.63 mM, respectively, and the apparent KmS were not affected by the secondary substrate concentrations. Dissociation constants for Pi of enzyme-Pi and the dead end complex were 5.0 and 16 mM, respectively. Aspartate inhibition was completely competitive with both the substrates, PEP and bicarbonate, with an inhibitor constant of 0.044 mM. An activator, acetyl-CoA, did not alter the apparent Km for bicarbonate but decreased that for PEP. The activator constants for the enzyme-PEP complex and free enzyme were 6.3 and 40 microM, respectively. Double reciprocal plots of reaction rate against PEP concentration were not linear at lower PEP concentrations. Hill coefficients for PEP were 1.6 in the absence of any effectors, 1.0 in the presence of acetyl-CoA, and 2.3 in the presence of aspartate. As to the mutant enzyme, only the inhibitor constant for aspartate was increased, being 0.18 mM, but other constants, coefficients, as described above, and specific activity were almost the same as those of the wild-type enzyme.


Zapateado technique as an injury risk in Mexican folkloric and Spanish dance: an analysis of execution, ground reaction force, and muscle strength.
Zapateado is a repetitive percussive footwork in dance. This percussive movement, and the differences in technique, may be risk factors for injury. A survey on zapateado dance students found a rate of 1.5 injuries/1,000 exposures. Knee injuries are more frequent than in Spanish dancers than folkloric dancers. The aim of this research was to study the relationship between technique and ground reaction force between zapateado on Spanish and Mexican folkloric dancers. Ten female dance students (age 22.4 ± 4 yrs), six Spanish dancers and four Mexican folkloric dancers, were considered. Each student performed zapateado with a flat foot, wearing high-heeled shoes during 5 seconds on a force platform. Videotapes were taken on a lateral plane, and knee and hip angles in each movement phase were measured with Dartfish software. Additionally, knee and ankle flexor and extensor strength was measured with a dynamometer. Ground reaction forces were lower for Spanish dancers than Mexican folkloric dancers. Spanish dancers had less knee flexion when the foot contacted to the ground than did Mexican folkloric dancers. On Spanish dancers, the working leg had more motion in relation to hip and knee angles than was seen in folkloric dancers. The ankle extensors were stronger on folkloric dancers, and there were no differences for the other muscle groups. Knee flexion at foot contact and muscle strength imbalance could be risk factors for injuries. It is suggested that the technique in Spanish dance in Mexico be reviewed, although more studies are required to define more risk factors.


Electronic excitation energies in dimers between radical ions presenting long, multicenter bonding.
The formation of long, multicenter dimers between radical ions is usually monitored through UV-vis spectroscopy given the characteristic low-energy absorption band that they exhibit, not observed for the parent monomers. In this work, the performance of CASPT2, RASPT2, and TD-DFT methods for obtaining excitation energies of the long, multicenter bonded π-[TCNE]2(2-) and π-[TTF]2(2+) dimers has been addressed (TCNE = tetracyanoethylene; TTF = tetrathiafulvalene). The impact of the active space on the vertical electronic transitions computed at the RASPT2 and CASPT2 levels has been tested against experimentally observed absorption bands. Analogous tests have been carried out for a wide variety of density functionals within the TD-DFT formalism. Our calculations show that whereas CASPT2 predicts very accurate excitation energies for the π-[TCNE]2(2-), the mean absolute error for π-[TTF]2(2+) is higher for CASPT2 than for TD-DFT calculations, whenever pure density functionals or low % HF exchange hybrid functionals are used. Hybrid functionals with high % HF exchange (and thus RSH functionals) conduct to large errors on the excitation energies in both dimers. Furthermore, vertical electronic transitions are also obtained for 100 configurations extracted from a 45 ps molecular dynamics (CPMD) simulation aimed at providing an accurate description of the thermal fluctuation effects of a π-[TCNE]2(2-) dimer in dichloromethane. These thermal effects explain the shape of the experimental UV-vis spectrum, where the lowest HOMO → LUMO absorption presents a broad band and the following HOMO-1 → LUMO absorption exhibits a narrower band.


Influence of spleen meridian herbs on the harmonic spectrum of the arterial pulse.
Pulse analysis is a powerful method in Chinese medicine. We suggest that the effect of herbal medicine is to redistribute the blood to organs and meridians. In this report, by injecting extracts into rats and then analyzing the blood pressure wave measured at the caudate arteries, we studied eight important spleen meridian related herbs: They were Semen Lablab, Fructus Amomi Globosi, Rhizoma Atractylodis Macrocephalae, Rhizoma Atractylodis, Tuber Pinelliae, Radix Codonopsitis, Pericarpium Aurantii and Rhizoma Polygonati. All eight herbs increased the intensity of the 3rd harmonic (C3) of the pressure pulse which is correlated to the spleen and spleen meridian, as described in traditional Chinese medical literature. All of them also increased the 2nd harmonic (which is correlated to the kidney and the kidney meridian) as well as decreased the heart load (DC term of pressure wave, C0). Tuber Pinelliae, Radix Codonopsitis, Pericarpium Aurantii and Rhizoma Polygonati decreased the 1st harmonic (correlated to the liver meridian) significantly, while Rhizoma Atractylodis Macrocephalae only decreased C1 slightly. Except for Semen Lablab, all the others decreased the intensity of the 5th (stomach meridian) and the 7th harmonics. The effects of kidney herbs: Cortex Eucommiae and Radix Achyranthis were also shown for comparison.


Models of invasion of enteric and periodontal pathogens into epithelial cells: a comparative analysis.
Bacterial invasion of epithelial cells is associated with the initiation of infection by many bacteria. To carry out this action, bacteria have developed remarkable processes and mechanisms that co-opt host cell function and stimulate their own uptake and adaptation to the environment of the host cell. Two general types of invasion processes have been observed. In one type, the pathogens (e.g., Salmonella and Yersinia spp.) remain in the vacuole in which they are internalized and replicate within the vacuole. In the other type, the organism (e.g., Actinobacillus actinomycetemcomitans, Shigella flexneri, and Listeria monocytogenes) is able to escape from the vacuole, replicate in the host cell cytoplasm, and spread to adjacent host cells. The much-studied enteropathogenic bacteria usurp primarily host cell microfilaments for entry. Those organisms which can escape from the vacuole do so by means of hemolytic factors and C type phospholipases. The cell-to-cell spread of these organisms is mediated by microfilaments. The investigation of invasion by periodontopathogens is in its infancy in comparison with that of the enteric pathogens. However, studies to date on two invasive periodontopathogens. A actinomycetemcomitans and Porphyromonas (Bacteroides) gingivalis, reveal that these bacteria have developed invasion strategies and mechanisms similar to those of the enteropathogens. Entry of A. actinomycetemcomitans is mediated by microfilaments, whereas entry of P. gingivalis is mediated by both microfilaments and microtubules. A. actinomycetemcomitans, like Shigella and Listeria, can escape from the vacuole and spread to adjacent cells. However, the spread of A. actinomycetemcomitans is linked to host cell microtubules, not microfilaments. The paradigms presented establish that bacteria which cause chronic infections, such as periodontitis, and bacteria which cause acute diseases, such as dysentery, have developed similar invasion strategies.


Anogenital neoplasia in AIDS.
We review the recent literature on anogenital neoplasms in AIDS, with emphasis on cancers associated with HPV infection. Immune reactivity to HPV as well as novel immunotherapeutic and preventative strategies are discussed. Many AIDS-associated neoplasms are associated with HPV infection. Whether cervical cancer is truly an AIDS-associated neoplasm has recently been questioned, while the association of anal cancer with AIDS in both males and females is more convincing. Recent reports cast doubt on the efficacy of HAART therapy for HPV-induced anogenital neoplasms, despite efficacy in improving disease caused by other infectious agents. We include here new data on humoral and cellular immune responses to HPV. VLP serology has been reported to be associated with outcome of cervical cancer. VLP seropositivity has been reported to be a favorable prognostic sign in women with HPV 16 positive cervical carcinoma. Several investigators have questioned the immunogenicity of the oncogenic HPV type 16 compared with other HPV types. It has recently been found that in HIV-infected patients, lymphoproliferative cellular immune responses (CMI) to HPV 16 peptides are not associated with CD4 counts, whereas responses to recall antigens and mitogens are associated with CD4 counts. CD4 + T cells may not be responsible for protective cellular immune responses to HPV. VLP serology and CMI responses may be the future intermediate surrogate biomarkers for HPV-associated anogenital neoplasia trials. Several new therapeutic vaccine strategies for management of HPV-induced neoplasia are reviewed. Most anogenital neoplasms occurring with increased frequency in patients with HIV/AIDS are associated with HPV infections. Current treatment strategies are not effective in clearing anogenital HPV infection and need improvement. Immunotherapy with novel vaccines will provide both prevention and therapy for these common malignancies.


[TWELVE WEEKS OF PHYSICAL EXERCISE INTERVAL WITH SURCHARGE IMPROVES THE ANTHROPOMETRIC VARIABLES OF OBESE MORBID AND OBESE WITH COMORBIDITIES CANDIDATES TO BARIATRIC SURGERY].
for the morbid obesity the bariatric surgery is effective, but to major preoperative weight it might increase morbidity and mortality, for such a motive it is necessary to implement programs that improve this condition. to determine the effects of a program of physical exercise interval on the anthropometric profile of the morbidly obese and obese with comorbidities candidates to bariatric surgery. three men and twenty-five women between 18 and 60 years old candidates to bariatric surgery, with morbid obesity (n = 16) or obese and comorbidities (type-II diabetes mellitus, hypertension, dyslipidemia, insulin resistance) (n = 12), they were subjected to a program of physical exercise with interval overload of three months duration (36 sessions). Before and 72 hours after the last intervention session was evaluated on fasting (≥ 12 hours): body weight, body mass index (BMI), waist contour (WC) and contour hip. the average age corresponds to 36.96 years, prior to intervention the weight had an average of 102.66 ± 15.96 kg, BMI of 40.84 ± 4.94, the WC 114.22 ± 10.35 cm and the contour hip 126.84 ± 10.65 cm. After twelve weeks of intervention showed significant decreases in weight variables (p = 0.000), BMI (p = 0.001), WC (p = 0.000) and hip contour (0.000). twelve weeks of interval exercise improved preoperative anthropometric conditions, without presenting risks in health and with high adherence to the program, which is why it may be recommended for this type of treatment.


Alterations in the phosphoproteomic profile of cells expressing a non-functional form of the SHP2 phosphatase.
The phosphatase SHP-2 plays an essential role in growth factor signaling and mutations in its locus is the cause of congenital and acquired pathologies. Mutations of SHP-2 are known to affect the activation of the RAS pathway. Gain-of-function mutations cause the Noonan syndrome, the most common non-chromosomal congenital disorder. In order to obtain a holistic picture of the intricate regulatory mechanisms underlying SHP-2 physiology and pathology, we set out to characterize perturbations of the cell phosphorylation profile caused by an altered localization of SHP-2. To describe the proteins whose activity may be directly or indirectly modulated by SHP-2 activity, we identified tyrosine peptides that are differentially phosphorylated in wild type SHP-2 cells and isogenic cells expressing a non-functional SHP-2 variant that cannot dephosphorylate the physiological substrates due to a defect in cellular localization upon growth factor stimulation. By an iTRAQ based strategy coupled to mass spectrometry, we have identified 63 phosphorylated tyrosine residues in 53 different proteins whose phosphorylation is affected by SHP-2 activity. Some of these confirm already established regulatory mechanisms while many others suggest new possible signaling routes that may contribute to the modulation of the ERK and p38 pathways by SHP-2. Interestingly many new proteins that we found to be regulated by SHP-2 activity are implicated in the formation and regulation of focal adhesions.


Relationship between the movements of the lumbar spine and hip.
Movements of the lumbar spine and hips were measured in 20 healthy subjects using an electromagnetic tracking device. Movement sensors were attached to the L1 spinous process, the sacrum and the thighs. Each subject was requested to perform the following movements of the trunk: forward and backward bending, lateral bending and twisting. The ratio of the maximum magnitude of spine movement to that of the hip was determined. Angle-angle plot and cross-correlation were used to examine the relationship between the movements of the spine and hip. It was shown that during forward and backward bending of the trunk, the overall contributions of the lumbar spine and hip were similar, but the spine had a greater contribution to the early stage of the movement. Lateral bending of the trunk was found to be primarily accomplished by movement of the spine, whereas the hips were the predominate sources of movement for twisting. Moreover, it was shown that in the sagittal and horizontal planes, the movement patterns of the spine and hip were in phase, whereas in the coronal plane, the spine generally moved earlier than the hips. It is concluded that clinical examination of the back should include kinematic measures of both the lumbar spine and hips.


Autoradiographic study of retrocorneal membranes.
Fibrous membranes in the posterior cornea occur in failed transplants. The purpose of these studies was to investigate the role of corneal endothelium in the formation of these membranes. The corneal cellular components of rabbit corneas were labeled with tritiated thymidine. Labeled rabbit corneal stroma was replaced with unlabeled tissue (pre-Descemet's lamellar graft), leaving only labeled endothelium. Weeks later small unlabeled penetrating grafts, without endothelium, were placed inside this lamellar graft. The surrounding labeled host endothelial cells were found in a fine retrograft membrane and in the scar of grafts. The experiment demonstrated that host endothelial cells participate in the formation of retrograft membranes, but it does not exclude other origin of fibroblasts.


A wettability gradient as a tool to study protein adsorption and cell adhesion on polymer surfaces.
A new method for preparing a wettability gradient on polymer surfaces was developed. Low density polyethylene sheets were treated in air with corona from a knife-type electrode whose power gradually increases along the same length. The polymer surfaces oxidized gradually with the increasing power and the wettability gradient was created on the surfaces as evidenced by the measurement of water contact angles, Fourier-transform infrared spectroscopy in the attenuated total reflectance mode, and electron spectroscopy for chemical analysis. The wettability gradient surfaces prepared were used to investigate the interactions of model protein and cells in terms of the surface hydrophilicity/hydrophobicity of polymeric materials.


Chronic pain. Characteristics, assessment, and treatment plans.
Management of chronic pain is not a simple task. Pain is a complex, multifaceted perceptual experience. For effective management, the physician needs the patient's cooperation and personal commitment. Many chronic pain patients become preoccupied with their pain and gradually lose interest in social activities, or they may use their pain to avoid anxiety-producing situations. Chronic pain therapy instituted by the primary care physician demands a coordinated approach using pharmacologic and nonpharmacologic treatment methods. When necessary, appropriate treatment by subspecialty physicians and by psychologists and other paramedical personnel should be coordinated.


Livable communities for adults with disabilities.
In 2004, the National Council on Disability (NCD) commissioned the Center for Home Care Policy and Research to research and prepare a report on the topic of "livable communities" for adults with disabilities. The following is a summary of the major findings in the report and the priority action steps that communities should take to become more livable for people with disabilities. The report was published by the National Council on Disability in December 2004. The National Council on Disability is an independent federal agency making recommendations to the President and Congress to enhance the quality of life for all Americans with disabilities and their families. The full report, entitled Livable Communities for Adults with Disabilities, includes numerous examples of communities that have made improvements in their livability for people with disabilities. It is available on the Council's website, www.ncd.gov.


Accumulation and phytotoxicity of microcystin-LR in rice (Oryza sativa).
Irrigation with eutrophic water containing microcystins-LR (MC-LR) poses a potential risk to crops. However, the accumulation of MC-LR in rice grains and the mechanism of MC-LR-induced inhibition in rice roots are not understood. In this study, we detected the accumulation of MC-LR in rice grains collected from Taihu Lake region. MC-LR could accumulate in rice grains, but the risk evaluation suggested that MC-LR levels in rice grains from Taihu Lake region may not pose a threat to human health currently. In addition, MC-LR with low concentrations did not affect the growth of rice roots. However, MC-LR with high concentrations impeded the rice root morphogenesis by inhibiting root elongation, crown root formation, and lateral root development from primordia. Treatment with high concentrations of MC-LR stimulated the production of reactive oxygen species (ROS) and inhibited the production of nitric oxide (NO) in rice roots. Exogenous NO treatment reversed the inhibition of rice root growth under MC-LR stress. These results indicated that ROS and NO played important roles in the development of rice roots in responding to MC-LR stress.


Use of the dynamic vapor sorption meter to measure skin hydration properties, in vitro.
Maintaining an adequate skin moisture balance is important for retaining soft, pliable, healthy-looking skin. This report describes the use of the dynamic vapor sorption (DVS) meter to quantify water content of skin in vitro under a variety of conditions. It is the only instrument that couples an ultra-sensitive Cahn microbalance (resolution=0.1 microg) with an environmental system where both humidity and temperature are controlled. This feature is important since the skin's water content is influenced by changes in the relative humidity. In every experiment, the temperature was held constant at 25 degrees C, and the starting relative humidity (RH) was set to 0% RH. The RH was programmed to step in 10% increments ending at 90% RH. The RH was incremented to the next level only when the mass change was less than 0.005%/min. A hysteresis was observed for all skin sorption/desorption experiments completed. Glycerin and the sodium salt of pyrrolidone carboxylic acid (NaPCA) both enhanced the % water content of skin. NaPCA was a more effective humectant at high relative humidities (above 60% RH); while glycerin performed better at humidities below 40% RH. Washing the skin with sodium lauryl sulfate (SLS) reduced the skin's ability to absorb water more so than washing with Tween 80, a milder surfactant. Vaseline petroleum jelly enhanced the water-retention properties of untreated skin. The DVS can effectively be used to study the sorption and desorption properties of skin. We have shown that the amount of water absorbed is influenced by the RH, the presence of humectants and/or occlusive agents, and surfactant harshness.


The interaction of activated factor VII with tissue factor: insight into the mechanism of cofactor-mediated activation of activated factor VII.
The structure solution of the complex of tissue factor (TF) and activated factor VII (FVIIa) and extensive mutagenesis analysis of the FVIIa protease domain have recently provided a detailed, novel insight into the function of the extrinsic activation complex. This overview relates the functional data to the known molecular interactions defined by crystallography, arriving at a hypothesis of how FVIIa is 'switched on' through specific contacts with TF. Combining these findings with the results of mutational analysis of TF, a picture emerges whereby multiple domains of both cofactor and enzyme provide contacts for the assembly of macromolecular substrate.


Stigma, sexual risks, and the war on drugs: Examining drug policy and HIV/AIDS inequities among African Americans using the Drug War HIV/AIDS Inequities Model.
The relationship between drug policy and HIV vulnerability is well documented. However, little research examines the links between racial/ethnic HIV disparities via the Drug War, sexual risk, and stigma. The Drug War HIV/AIDS Inequities Model has been developed to address this dearth. This model contends that inequitable policing and sentencing promotes sexual risks, resource deprivation, and ultimately greater HIV risk for African-Americans. The Drug War also socially marginalizes African Americans and compounds stigma for incarcerated and formerly incarcerated persons living with HIV/AIDS. This marginalization has implications for sexual risk-taking, access to health-promoting resources, and continuum of care participation. The Drug War HIV/AIDS Inequities Model may help illuminate mechanisms that promote increased HIV vulnerability as well as inform structural intervention development and targeting to address racial/ethnic disparities.


Pediatric Pulmonology year in review 2018: Asthma, physiology/pulmonary function testing, and respiratory infections.
Pediatric Pulmonology publishes original research, reviews, and case reports related to a wide range of children's respiratory disorders. In our "Year in Review" series, we summarize publications in our major topic areas from 2018, in the context of selected literature in these areas from other journals relevant to our discipline. This review covers selected articles on asthma, physiology/lung function testing, and respiratory infections.


Quantitative assessment of human-induced impacts based on net primary productivity in Guangzhou, China.
Urban expansion and land cover change driven primarily by human activities have significant influences on the urban eco-environment, and together with climate change jointly alter net primary productivity (NPP). However, at the spatiotemporal scale, there has been limited quantitative analysis of the impacts of human activities independent of climate change on NPP. We chose Guangzhou city as a study area to analyze the impacts of human activities on NPP, as well as the spatiotemporal variations of those impacts within three segments, using a relative impact index (RII) based on potential NPP (NPPp), actual NPP (NPPact), and NPP appropriation due to land use/land cover change (NPPlulc). The spatial patterns and dynamics of NPPact and NPPlulc were evaluated and the impacts of human activities on NPP during the process of urban sprawl were quantitatively analyzed and assessed using the RII. The results showed that NPPact and NPPlulc in the study area had clear spatial heterogeneity, between 2001 and 2013 there was a declining trend in NPPact while an increasing trend occurred in NPPlulc, and those trends were especially significant in the 10-40-km segment. The results also revealed that more than 91.0% of pixels in whole study region had positive RII values, while the lowest average RII values were found in the > 40-km segment (39.03%), indicating that human activities were not the main cause for the change in NPP there; meanwhile, the average RII was greater than 65.0% in the other two, suggesting that they were subjected to severe anthropogenic disturbances. The RII values in all three segments of the study area increased, indicating an increasing human interference. The 10-40-km buffer zone had the largest slope value (0.5665), suggesting that this segment was closely associated with growing human disturbances. Particularly noteworthy is the fact that the > 40-km segment had a large slope value (0.3323) and required more conservation efforts. Based on the above results, we suggest that continuous efforts may be necessary to improve the intensity of protection and management in the urban environment of Guangzhou.


Proposal for a future delivery market for transplant organs.
Improvements in surgical procedures and immunosuppressive practices have greatly increased the range and success rate of organ transplants. Unfortunately, supply does not meet demand, and demand is increasing. This paper documents the current level of unsatisfied demand for several transplantable organs, and argues that the extant system of altruistic organ donation is unlikely ever to provide adequate supply because of lack of incentives to donate and the ambiguity surrounding property rights over transplantable organs. A greater reliance on markets would help attenuate these problems. However, unorganized private spot markets for human organs are likely to be both inefficient and inequitable, and are perceived as morally offensive. A feasible alternative is an organized, publicly operated future delivery market, wherein an individual can contract, for valuable consideration, with a government agency for delivery of a specific organ upon death. The implementation of such a market would encounter difficult (but not intractable) problems such as price determination, the selection of a medium of exchange, and contractual issues, particularly the role of minors in such a system. Finally, it is argued that such a market is superior to the much-discussed compulsory expropriation alternative.


Hysteretic behavior of the hepatic microsomal glucose-6-phosphatase system.
Carbamyl-P:glucose and PPi:glucose phosphotransferase, but not inorganic pyrophosphatase, activities of the hepatic microsomal glucose-6-phosphatase system demonstrate a time-dependent lag in product production with 1 mM phosphate substrate. Glucose-6-P phosphohydrolase shows a similar behavior with [glucose-6-P] less than or equal to 0.10 mM, but inorganic pyrophosphatase activity does not even at the 0.05 or 0.02 mM level. The hysteretic behavior is abolished when the structural integrity of the microsomes is destroyed by detergent treatment. Calculations indicate that an intramicrosomal glucose-6-P concentration of between 20 and 40 microM must be achieved, whether in response to exogenously added glucose-6-P or via intramicrosomal synthesis by carbamyl-P:glucose or PPi:glucose phosphotransferase activity, before the maximally active form of the enzyme system is achieved. It is suggested that translocase T1, the transport component of the glucose-6-phosphatase system specific for glucose-6-P, is the target for activation by these critical intramicrosomal concentrations of glucose-6-P.


The rat platelet 97-kDa Ca2+ATPase isoform is the sarcoendoplasmic reticulum Ca2+ATPase 3 protein.
We recently showed that human and rat platelets express two types of SERCAs (Sarco Endoplasmic Reticulum Ca2+ATPases): a 100-kDa SERCA2b isoform and a 97-kDa SERCA isoform. Here, we explored the possibility that the rat 97-kDa isoform is identical to the SERCA3 protein. For this purpose, we first attempted to detect SERCA3 mRNA in rat platelet total RNA by reverse transcription-polymerase chain reaction using SERCA3-specific primers, and demonstrated the presence of this mRNA species by sequencing the amplification product. We then searched for a relationship between the expression of the SERCA3 mRNA and of the 97-kDa protein using either rat aortic smooth muscle cells, previously found not to express the 97-kDa SERCA isoform (negative model), or platelets of spontaneously hypertensive rats (SHR), which overexpress this isoform (overexpression model) but express the 100-kDa SERCA2b isoform normally. No expression of SERCA3 mRNA was detectable by analysis of smooth muscle cell RNA, but comparison by reverse transcription-polymerase chain reaction of the SERCA2b and SERCA3 mRNAs from the platelets of normotensive (Wistar-Kyoto, WKY) rats and SHR clearly demonstrated a 238 +/- 43% increase in the expression of the SERCA3 mRNA in SHR platelets only. Last, by comparative Western blotting of WKY rat and SHR platelet membranes using a recently developed polyclonal anti-SERCA3 antibody, we established that the 97-kDa SERCA and the SERCA3 protein are identical, as immunostaining of the 97-kDa protein revealed a 230 +/- 25% increase in the expression of this protein in SHR versus WKY rat platelets. It is concluded that the 97-kDa platelet SERCA isoform, which is up-regulated in SHR, is the SERCA3 protein. As far as we know, this constitutes the first demonstration of the actual presence of this Ca2+ATPase isoform in normal cells, in addition to the artificial transfection systems.


"Covalent-Assembly"-Based Fluorescent Probe for Detection of a Nerve-Agent Mimic (DCP) via Lossen Rearrangement.
The highly selective and sensitive fluorescence "light-up" probe, 5'-(dimethylamino)-2'-formyl-N-hydroxy-[1,1'-biphenyl]-2-carboxamide(PTS), has been fabricated for the nerve-agent mimic diethyl chlorophosphate (DCP). The probe is designed by combining two novel strategies of "covalent assembly" and Lossen rearrangement. Formation of a phosphoryl intermediate from DCP and a hydroxamic acid group in PTS yields an isocyanate that quickly undergoes Lossen rearrangement to produce an aniline that condenses intramolecularly to a fluorescent phenanthridine system. PTS shows superior properties to probe DCP, such as rapid response (within 100 s), low detection limit (10.4 nM), specificity, and excellent linearity (R2 = 0.9993) in the range from 2 to 16 μM. More importantly, its application of detecting DCP vapor has also been achieved with satisfying results.


Unusual sudden cardiac death from an anomalous left coronary artery from the right sinus of Valsalva.
A left coronary artery arising from the right sinus of Valsalva is a rare congenital coronary anomaly. We report a case of a 5-year-old boy with an anomalous left coronary artery from the right sinus of Valsalva whose presenting sign was cardiac arrest. There is no reported instance of a child <9 years of age without other congenital cardiac defects having died suddenly with this coronary anomaly. The transthoracic echocardiogram demonstrated normal origins of the coronary arteries, but on autopsy, an anomalous origin of the left main coronary artery from the right sinus of Valsalva was found.