Treatment of severe platelet dysfunction and hemorrhage after cardiopulmonary bypass: reduction in blood product usage with desmopressin.
Impairment of platelet function commonly occurs after cardiopulmonary bypass, and may result in substantial bleeding. Because desmopressin acetate (a synthetic analogue of vasopressin) shortens bleeding time in a variety of platelet disorders, a controlled clinical trial of intravenous desmopressin was performed in 39 patients with excessive mediastinal bleeding (greater than 100 ml/h) and a prolonged template bleeding time (greater than 10 minutes) more than 2 hours after termination of cardiopulmonary bypass. Twenty-three desmopressin recipients and 16 control patients (no desmopressin) were similar in surgical procedure, pump time, platelet count, template bleeding time and amount of bleeding before therapy (p = NS). Compared with the control group, the patients receiving desmopressin (20 micrograms; mean 0.3 micrograms/kg) utilized fewer blood products (29 +/- 19 versus 15 +/- 13 units/patient; p less than 0.05), especially platelets (12 +/- 9 versus 4 +/- 7 units/patient; p = 0.004), while achieving a similarly effective reduction in mediastinal bleeding (4.8- and 4.3-fold, p = 0.001 for both). Severe platelet dysfunction was partially corrected within 1 hour after desmopressin infusion, during which interval no blood products were administered: the template bleeding time shortened (from 17 to 12.5 minutes, p less than 0.05), whereas the platelet count remained unchanged (at 96 +/- 35 and 105 +/- 31 X 10(3)/mm3, p = NS). The plasma levels of two factor VIII components increased: procoagulant activity (VIII:C) from 0.97 +/- 0.43 to 1.52 +/- 0.74 units/ml (p less than 0.05) and von Willebrand factor (VIII:vWF) from 1.28 to 1.78 units/ml (p less than 0.05); these increases correlated with the shortening of the bleeding time (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


Regulation of oxidative stress-mediated apoptosis by diallyl sulfide in DMBA-exposed Swiss mice.
Diallyl sulfide, a sulfur-containing volatile compound present in garlic (Allium sativum), exerts anticarcinogenic activity in various rodent tumor models. In the present study, apoptosis-inhibiting effects of diallyl sulfide against a carcinogenic polycyclic aromatic hydrocarbon, 7,12-dimethyl benz(a)anthracene (DMBA), in Swiss albino mice were observed. The animals were given either 250 microg/mouse or 500 mug/mouse of diallyl sulfide for 1 week after a single intragastric dose of 7,12-dimethyl benz(a)anthracene (50 mg/kg body weight). Results showed that diallyl sulfide supplementation effectively protects against 7,12-dimethyl benz(a)anthracene-induced oxidative stress, characterized by restored antioxidant enzyme levels (up to 64%) and lipid peroxidation (up to 25%). Flow cytometric analysis showed a reduction in apoptotic cell population in hypodiploid region in diallyl sulfide-supplemented animals. Inhibition of apoptosis was preceded by decrease in reactive oxygen species levels and restoration of mitochondrial transmembrane potential followed by decreased DNA fragmentation. In 7,12-dimethyl benz(a)anthracene-exposed animals, downregulation approximately 30%) of antiapoptotic Bcl-2 and upregulation (approximately 60%) of pro-apoptotic Bax proteins were observed. These alterations were restored significantly by diallyl sulfide supplementation, indicating inhibition of apoptosis. Thus, these results show that diallyl sulfide provides protection against oxidative damage induced by 7,12-dimethyl benz(a)anthracene in mouse liver and may be an effective chemopreventive and therapeutic agent by modulating expression of cell-growth regulatory proteins.


Xenon-127.
The ventilation perfusion study is of proven value in the diagnosis of patients with lung disease. The technique would be even more useful if the ventilation study could be performed after the perfusion lung scan. Then only those patients with a perfusion defect would require a ventilation study and the study could be performed in the position which best demonstrates the lesion. This cannot be done satisfactorily with 133Xe. Because of its physical properties, 127Xe is the isotope of choice for ventilation studies. With this gas, the ventilation study can be performed after the perfusion lung scan with no interference from the 99mTc. The resolution of lesions within the lung is better with 127Xe than with 133Xe. Finally, the reduced tissue absorption and high photon yield permit the use of small amounts of 127Xe and therefore reduced cost and a smaller radiation dose to the patient.


Does the mean 24-h pulse rate from ambulatory blood pressure monitoring reflect the mean 24-h ventricular rate from Holter electrocardiogram in atrial fibrillation patients?
Ambulatory blood pressure monitoring (ABPM) on the oscillometric method is applicable in patients with atrial fibrillation, but the mean pulse rate is or not similar to the ventricular rate from the Holter in atrial fibrillation patients remains unknown. This study included 228 persistent atrial fibrillation patients who received simultaneous 24-h ABPM and 24-h Holter. The mean 24-h pulse rate and the mean 24-h ventricular rate were calculated, and mVR-mPR was used to reflect the difference between them. The SD of 24-h pulse rate values was calculated as SD-pulse rate. Furthermore, according to the SD-pulse rate, the patients were divided into ≤5, 6-10, 11-15 and >15 bpm subgroups. For the total population, the mean 24-h pulse rate is positively correlated with the mean 24-h ventricular rate, and the Bland-Altman plot showed quite wide 95% limits. As the SD-pulse rate increased, the 24-h mVR-mPR also increased. The mean 24-h mVR-mPR was 0.5 bpm when SD-pulse rate ≤5, 3.5 bpm when SD-pulse rate of 6-10, 7.6 bpm when SD-pulse rate of 11-15, and 12.5 bpm when SD-pulse rate >15 bpm, respectively. Meanwhile, in the SD-pulse rate 0-10 subgroup, the 95% limits were only from -13.8 to 19.7 bpm, while in the >10 subgroup, these values were from -19.5 to 36.5 bpm. The mean 24-h pulse rate should not be used to represent the true ventricular rate for all atrial fibrillation patients. However, when lower the SD-pulse rate, the mVR-mPR becomes smaller.


Environmental contamination by organisms causing urinary tract infection.
We have examined the bedsheets, floor and bedside chairs of 33 patients with urinary tract infections for organisms causing urinary infection. In ten patients the causative organism was recovered from the undersheet, and in two of these it was also recovered from the floor and bedside chair. Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae and Enterococcus faecalis were recovered from sheets, while Group B beta-haemolytic streptococci and Candida tropicalis were also found on floors and chairs.


Innovative, Sugar-Free Oral Hydrogel as a Co-administrative Vehicle for Pediatrics: a Strategy to Enhance Patient Compliance.
Palatability and swallowability in the pediatric population are perceived as true challenges in the oral administration of medication. Pediatric patients have high sensitivity to taste and reduced ability to take solid dosage forms, which can often lead to a poor therapeutic compliance. It is crucial to find new strategies to simplify the oral administration of drugs to children. The present paper reports the development of a new hydrogel vehicle adapted to the pediatric population. Several polymers with similar properties were selected and adjustments were made to obtain the desired characteristics of the final product. The developed formulations were studied for organoleptic properties, rheology, mucoadhesion properties, preservative efficacy, and stability. Physical and chemical compatibilities between the vehicle and several drugs/medicines, at the time of administration, were also studied. Six final formulations with different polymers, odor, and color were chosen, and no known interactions with medications were observed. The proposed new oral vehicles are the first sugar-free vehicle hydrogels designed to make the intake of oral solid forms a more pleasant and safer experience for pediatric patients.


Natural astaxanthin enhanced antioxidant capacity and improved semen quality through the MAPK/Nrf2 pathway in aging layer breeder roosters.
Natural astaxanthin (ASTA) has strong antioxidant properties and has been widely used as a health product to improve human health. However, the effects of ASTA on the reproductive performance of aging roosters have been poorly studied. We aimed to investigate the effects of dietary ASTA on semen quality and antioxidant capacity in aging roosters and to explore the potential mechanism of semen quality change via anti-oxidation defense system. In the present study, 96 53-week-old Jinghong No. 1 layer breeder roosters were fed a corn-soybean meal basal diet containing 0, 25, 50, or 100 mg/kg ASTA for 6 weeks. Semen quality in the ASTA groups remarkably improved than that in the control group, and antioxidant activities, the abilities to scavenge hydroxyl radicals and superoxide anions, increased gradually with ASTA addition (P < 0.05). In addition, the mRNA levels of antioxidant enzymes as well as the mRNA and protein levels of the mitogen-activated protein kinase (MAPK) and nuclear factor-erythroid 2-related factor 2 (Nrf2) were markedly increased in the 50-100 mg/kg ASTA group (P < 0.05). Collectively, these results demonstrate that dietary ASTA may improve semen quality by increasing antioxidant enzyme activities and the ability to scavenge hydroxyl radicals, which may be related to upregulation of the MAPK/Nrf2 pathway.


Novel cross-linked homogeneous polyacrylamide gels with improved separation properties: investigation of the cross-linker functionality.
Polyacrylamide (PAAm) gels were synthesized using cross-linkers with their potential functionality (twice the number of double bonds of a cross-linker) varying from six to sixteen. Improved electrophoretic separation and highly desirable porosity and sieving properties were observed for most of the PAAm gels containing novel cross-linkers. An increase in the potential functionality of cross-linkers used in PAAm gels was an important factor, influencing the pore size and pore size distribution of the network.


Uptake of 11C-L- and D-methionine in brain tumors.
11C-labeled L- and D-methionine uptake was measured in seven patients with brain tumors using positron emission tomography. Tumors accumulated both isomers of the tracer. The strongest uptake occurred in tumors with a high grade of malignancy, while low grade tumors accumulated less activity. The L to D uptake ratio in tumor regions ranged from 0.92-1.25. Conventional 99mTc-DTPA scans revealed blood-brain barrier damage in two patients with no or only slight 11C-methionine accumulation, while one patient with a negative 99mTc-DTPA scan accumulated 11C-methionine in the tumor region. In view of the biochemical pathway of methionine and the present findings, it is concluded that the uptake reflects metabolic activity in brain tissue rather than uptake by diffusion due to disruption of the blood-brain barrier.


Inhibition of p38 MAPK activation attenuates esophageal mucosal damage in a chronic model of reflux esophagitis.
Reflux esophagitis (RE) is one of the common gastrointestinal diseases that are increasingly recognized as a significant health problem. This study was designed to investigate the role of p38 mitogen-activated protein kinase (MAPK) in experimental chronic RE model of rats. Chronic acid RE rats were induced by fundus ligation and partial obstruction of the pylorus and treated with SB203580 (a p38 MAPK inhibitor, i.p., 1 mg/kg/day) for 14 days. Immunohistochemical staining and Western blotting results revealed the activation of p38 MAPK signaling in the esophagus mucosa 14 days post injury. Through gross and histological assessment, we found that inhibition of p38 MAPK activation by SB203580 attenuated esophageal mucosal damage in RE rats. Inhibition of p38 MAPK activation in RE rats attenuated esophageal barrier dysfunction, through enhancing the expression of tight junction proteins and reducing the expression of matrix matalloproteinases-3 and -9. Inhibition of p38 MAPK activation in RE rats reduced CD68-positive cells in esophagus mucosa and mRNA levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in esophagus and protein levels of TNF-α, IL-6, and IL-1β in serum. In addition, we found that inhibition of p38 MAPK activation in RE rats suppressed protein expression of inducible nitric oxide synthase and reduced formation of nitric oxide (NO), 3-nitrotyrosin, and malondialdehyde in esophagus. Inhibition of p38 MAPK activation attenuated esophageal mucosal damage in acid RE rats, possibly by modulating esophageal barrier function and regulating inflammatory cell recruitment, and the subsequent formation of cytokines, NO, and reactive oxygen species.


Procalcitonin Correlates With but Is Not Superior to Other Diagnostic Markers of Bacterial Pneumonia.
Despite extensive research on procalcitonin (PCT)-guided therapy in lower respiratory tract infections, the association between PCT and bacterial pneumonia remains unclear. We evaluated retrospectively the performance of PCT in patients presenting with lower respiratory tract infection symptoms and grouped by seven diagnoses. All patients had microbial testing, chest imaging, and CBC counts within 1 day of PCT testing. Median PCT level in patients diagnosed with bacterial pneumonia was significantly higher than in patients diagnosed with other sources of infections or those not diagnosed with infections. Median PCT levels were not different among patients grouped by type or quantity of pathogen detected. They were significantly higher in patients with higher pathogenicity scores for isolated bacteria, those with abnormal WBC count, and those with chest imaging consistent with bacterial pneumonia. A diagnostic workup that included imaging, WBC count, and Gram stain had an area under the receiver operating characteristic curve of 0.748, and the addition of PCT increased it to 0.778. PCT was higher in patients diagnosed with bacterial pneumonia. Less clear is its diagnostic ability to detect bacterial pneumonia over and above imaging and laboratory data routinely available to clinicians.


Ischaemic stroke after exposure to aflibercept: interaction with vitamin K antagonist and/or direct pharmacodynamic effect?
Vascular endothelial growth factor (VEGF) proteins are involved in the regulation of vascular endothelium, and their inhibition led to the development of a number of drugs used for malignancies or exudative neo-vascular age-related macular degeneration (AMD). We report a case of ischemic stroke in an 87-year-old woman having received intravitreal aflibercept, a new anti-VEGF for AMD. She had been treated with ranibizumab since 2007. In 2013, ranibizumab was replaced with aflibercept, followed by a decrease in the International Normalized Ratio, complicated by a stroke a few days later. The rechallenge was positive. A potential time-dependent interaction between aflibercept and VKA antagonist and/or a direct effect of aflibercept may have contributed to the occurrence of the ischaemic stroke. Currently available data suggest some pharmacokinetic and pharmacodynamic effects of aflibercept by explaining its pro-thrombotic profile.


Modeling osteoinduction in titanium bone scaffold with a representative channel structure.
Optimizing scaffold architecture for perfect osteointegration depends on good understanding of bone ingrowth in the porous space of implants. This study developed an immunoregulatory agent-based model to discover the osteoinduction mechanism in porous scaffolds. Immunoreaction, macrophage polarization, and the corresponding growth factors were combined in the model, and all played critical roles in recruiting osteogenic cells that migrated into the scaffolds. Angiogenesis was also considered in this model. The bone ingrowth predicted by the model coincides with results from published in vivo experiments. Simulation results suggested that the pore architecture affected the diffusion process of chemotactic factors in the scaffolds, subsequently influencing the complex reactions of diverse cells and the osteoinduction location. In flexural pore spaces, bone formation spread from the periphery into the center of scaffolds due to larger M2 phenotype macrophage populations colonizing boundary regions and the distribution of corresponding growth factors concentration. In straight channels, osteogenic cells migrated further inward and osteoinduction initiated in deeper position as a result of the deeper distribution of osteogenic cytokines concentration field.


Balanced by iron. Hereditary hemochromatosis and celiac disease.
We present the case of a healthy 14-year-old adolescent who was referred to our hospital for an incidental alteration of the iron profile (Fe 225 ug/dl, transferrin 186 mg/dl, IST 63.93 %, ferritin 253 ng/ml). The blood count, proteinogram and renal, lipid and liver function tests were in the normal range. Abdominal ultrasound was requested with no findings of interest. The genetic analysis for hereditary hemochromatosis (HH) confirmed that the patient was homozygous for the C282Y mutation.


Professional identity acquisition process model in interprofessional education using structural equation modelling: 10-year initiative survey.
The mandatory interprofessional education (IPE) programme at Gunma University, Japan, was initiated in 1999. A questionnaire of 10 items to assess the students' understanding of the IPE training programme has been distributed since then, and the factor analysis of the responses revealed that it was categorised into four subscales, i.e. "professional identity", "structure and function of training facilities", "teamwork and collaboration", and "role and responsibilities", and suggested that these may take into account the development of IPE programme with clinical training. The purpose of this study was to examine the professional identity acquisition process (PIAP) model in IPE using structural equation modelling (SEM). Overall, 1,581 respondents of a possible 1,809 students from the departments of nursing, laboratory sciences, physical therapy, and occupational therapy completed the questionnaire. The SEM technique was utilised to construct a PIAP model on the relationships among four factors. The original PIAP model showed that "professional identity" was predicted by two factors, namely "role and responsibilities" and "teamwork and collaboration". These two factors were predicted by the factor "structure and function of training facilities". The same structure was observed in nursing and physical therapy students' PIAP models, but it was not completely the same in laboratory sciences and occupational therapy students' PIAP models. A parallel but not isolated curriculum on expertise unique to the profession, which may help to understand their professional identity in combination with learning the collaboration, may be necessary.


Quality of therapeutic drug monitoring guidelines is suboptimal: an evaluation using the Appraisal of Guidelines for Research and Evaluation II instrument.
Although therapeutic drug monitoring (TDM) guidelines are available, systematic evaluations of their methodological quality are scarce. This study aimed to assess the quality of current TDM guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument. We performed a systematic search to identify the relevant TDM guidelines in PubMed, EMBASE, CNKI, Wan Fang Database, CBM, VIP, four main guideline databases (NICE, NGC, GIN, and WHO guideline databases), and official websites of the governments and societies associated with TDM from the inception date to May 2018. Four independent appraisers rated the quality of each TDM guideline using the AGREE II instrument, and the mean score of each AGREE II item was calculated. The overall agreement among the appraisers was evaluated using the intraclass correlation coefficient (ICC). Twenty-eight TDM guidelines satisfied the eligibility criteria from among 12,235 references. The overall agreement among the appraisers was substantial (0.700-0.880). The mean scores for the six AGREE II domains were scope and purpose, 67.7% (95% CI, 64.0-71.4%); stakeholder involvement, 39.8% (95% CI, 33.3-46.3%); rigor of development, 36.0% (95% CI, 28.1-43.9%); clarity and presentation, 61.6% (95% CI, 55.7-67.4%); applicability, 30.6% (95% CI, 26.4-34.8%); and editorial independence, 49.2% (95% CI, 40.0-58.6%). The reviewers recommended only four guidelines, and most of the TDM guidelines were rated as "recommended with modifications." Overall, the quality of TDM guidelines is suboptimal according to the evaluation using the AGREE II instrument. The domains of applicability, rigor of development, stakeholder involvement, and editorial independence of the guidelines need to be reported. In addition, guideline developers closely adhering to the AGREE II instrument and the Grading of Recommendations Assessment Development and Evaluation system are required to draft high-quality and reliable TDM guidelines.


Using differential scanning calorimetry for the development of non-reduced capillary electrophoresis sodium dodecyl sulfate methods for monoclonal antibodies.
Analysis of non-reduced and reduced monoclonal antibodies (mAbs) by capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) is routinely used to detect product size variants and process-related impurities. Levels of high molecular weight (HMW) forms obtained from this method usually trend comparably to those obtained by orthogonal methods such as size-exclusion ultra-high performance liquid chromatography (SE-UHPLC). However, in the presented case study, comparison of CE-SDS data for three IgG1 mAbs (trastuzumab, mAb1, and mAb2) showed a discrepancy between amounts of observed HMW forms in mAb2 compared with its native forms determined by SE-UHPLC (~17% vs. ~0.5%, respectively). SDS chemical denaturation, as measured by differential scanning calorimetry, demonstrated that the high thermal stability of mAb2 caused an unidentified HMW peak observed by non-reduced (NR)-CE-SDS, which was the result of improper denaturing, resulting in a partially folded species. More so, this strategy enabled the rapid identification of optimal SDS concentration and temperature conditions needed for suitable denaturation for mAb2. This case study presents an alternative option for quick optimization of NR-CE-SDS methods when characterizing mAbs or other thermally stable proteins. Also, this strategy can be used to understand basic biophysical mechanisms of protein unfolding and investigate the higher-order structure imparted by specific sequences and understand how these sequences might affect the results of an analytical method such as CE-SDS.


Nerve growth factor-induced loss of cell-associated nerve growth factor receptor in human melanoma A875 cells.
Human A875 melanoma cells are known to express the low-affinity nerve growth factor receptor p75NGFR in a monomeric and a covalently linked probably dimeric form. Kinetic analysis of the association of nerve growth factor (NGF) with its receptor revealed a rapid loss of binding sites at high ligand concentrations. Using cross-linking and immunoprecipitation with an anti-p75NGFR antibody, this was found to be due to a decrease of the high molecular weight form of the receptor. Mechanisms for such a ligand-induced receptor loss are discussed.


In situ determination of Clostridium endospore membrane fluidity during pressure-assisted thermal processing in combination with nisin or reutericyclin.
This study determined the membrane fluidity of clostridial endospores during treatment with heat and pressure with nisin or reutericyclin. Heating (90°C) reduced laurdan (6-dodecanoyl-2-dimethylaminonaphthalene) general polarization, corresponding to membrane fluidization. Pressure (200 MPa) stabilized membrane order. Reutericyclin and nisin exhibit divergent effects on heat- and pressure-induced spore inactivation and membrane fluidity.


Presence of predatory wasps and stinkbugs alters foraging behavior of cryptic and non-cryptic caterpillars on plantain (Plantago lanceolata).
We examined the foraging patterns of two species of caterpillar (Junonia coenia: Nymphalidae and Spilosoma congrua: Arctiidae) that contrast in feeding specialization and crypticity on plantain (Plantago lanceolata) in the absence and presence of two different insect predators [stinkbugs, Podisus maculiventris (Pentatomidae) and wasps, Polistes fuscatus (Vespidae)]. Junonia larvae were quite apparent to human observers, feeding on upper leaf surfaces during daylight, whereas Spilosoma larvae were relatively cryptic, often hiding under leaves and in soil crevices during daylight. In the presence of either predator species, the non-cryptic Junonia caterpillars more quickly left the plant on which they were initially placed and were less apparent than Junonia larvae not exposed to predators. The presence of predators had no detectable influence on where the caterpillars occurred on the plants (new, intermediate-aged or mature leaves, or reproductive stalks). Surprisingly, the predators influenced the behavior of the inherently cryptic Spilosoma: the apparency of these larvae at night increased when wasps had access to the plots during the day. Survivorship of the non-cryptic Junonia was less than 12% when stinkbugs were present compared to 60% in their absence. Although the presence of wasps resulted in a lower relative growth rate for the non-cryptic Junonia larvae, the indirect effect of predators on reduction in survivorship due to alterations in prey growth rate through behavioral changes was less than 3%. After taking into account the decline in caterpillars per plot through predation, we found that both the amount of leaves eaten and the proportion of plants eaten were altered on plots with predators present, which suggests that the caterpillars' increased consumption countered increased maintenance costs due to the presence of predators. Overall, our results indicate that hostplant size, level of predation and type of predator can influence the degree to which these caterpillars react to the presence of insect predators. In contrast, degree of inherent feeding specialization and cryptic behavior seemed to have little effect on the expression of reactive behaviors of these caterpillars to predators.


Human papillomavirus testing and screening.
Cervical cancer is a largely preventable disease through the detection, treatment and follow-up of its precursors. Traditionally, this has been accomplished through screening women with cervical cytology, and referring women with abnormal cytology for colposcopy, histological sampling and treatment. In organized programmes that achieve wide coverage of the target population at frequent intervals, this approach has resulted in a considerable reduction in cervical cancer. Recently, however, the development of reliable and reproducible tests for the detection of human papillomavirus (HPV) infection of the cervix (which is now accepted to be causally associated with the development of almost all cervical cancers) has led to the evaluation of HPV de-oxyribonucleic acid (DNA) testing as either an alternative or adjunctive test to cytology for the detection of cervical cancer and its precursors. There is now a large body of data supporting the clinical utility of HPV DNA testing for the prevention of cervical cancer, particularly in the settings of primary screening of women older than 30 years, in the triage of women with equivocal cytology and for the follow-up of women post-treatment.


Corneal stimulation of MMP-1, -9 and uPA by platelet-activating factor is mediated by cyclooxygenase-2 metabolites.
This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX-2) activity on urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMPs)-1 and -9 induction in cornea following platelet-activating factor (PAF) treatment. Corneal organ cultures were pre-treated with increasing concentrations of COX-2-specific inhibitors NS398 or nimesulide prior to PAF stimulation. To determine the effect of exogenous prostaglandins (PGs) on uPA, MMP-1 and MMP-9 levels, corneas were pre-treated with COX-2 inhibitors followed by the addition of 2.5 microM PGD2, PGE2 or PGF2alpha. The levels of uPA and MMP-9 were assayed by casein and gelatin zymography, respectively. MMP-1 levels were determined by Western Blot analysis. The increase in uPA, MMP-9 and MMP-1 levels detected in corneal organ cultures treated with 100 nM cPAF was blocked by 5 microM NS398 and 10 microM nimesulide, concentrations at which these inhibitors selectively inhibit COX-2 activity. Furthermore, pre-incubation with COX-2 inhibitors, followed by supplementation with PGD2, PGE2 or PGF 2alpha, increases uPA, MMP-9 and MMP-1 levels in corneas similar to and in some cases greater than that produced by cPAF treatment alone. During corneal injury and inflamation, PAF is an important factor in the activation of proteolytic cascades, which could lead to corneal epithelial defects and ultimately ulceration. One important goal in treating these defects is to modulate the activity of enzymes that destroy the extracellular matrix. Our results suggest that COX-2 induction following PAF stimulation and subsequent eicosanoid release may play a crucial role in the induction of uPA, MMP-1 and MMP-9 enzymes. Specific COX-2 inhibition could therefore block the actions of PAF when inflammation is sustained.


Expression of p57KIP2 reduces growth and invasion, and induces syncytialization in a human placental choriocarcinoma cell line, BeWo.
Syncytiotrophoblasts are the major components of the human placenta involved in fetal maternal exchange and hormone secretion. The syncytiotrophoblasts arise from the fusion of villous cytotrophoblasts. The cell cycle suppressor p57KIP2 is known to be an essential molecule for proper trophoblast differentiation during placental formation. We generated p57KIP2-expressing BeWo transfectant cells. Proliferation assay and matrigel invasion assay were used to characterize p57KIP2-expressing BeWo transfectant cells. To reveal the role of p57KIP2 in syncytialization, we proceeded syncytium formation analysis and qRT-PCR for detection of the expression levels Syncytin-1, Syncytin-2 and their receptors. The human choriocarcinoma cell line, BeWo has undetectable levels of p57KIP2 expression. Expression of p57KIP2 reduced cell proliferation rate and extracellular matrix invasion activity. p57KIP2 expressing cells displayed multinucleated cells associated with syncytiotrophoblast differentiation. In the syncytialization event, p57KIP2 was found to potentiate forskolin-induced upregulation of Syncytin-2 in a cAMP-independent manner. These results indicate that the expression of p57KIP2 may act on the proliferation/invasion inhibitory factor and enhance the expression of Syncytin-2, which are associated with syncytialization in cytotrophoblasts.


[Electric stimulation and neuromuscular diseases. Effects on denervated and dystrophic muscle].
The literature on the effects of electrical stimulation on denervated and dystrophic muscles is reviewed. Analysis of the information supplied suggests that denervated muscles of experimental animals may benefit from the treatment that cannot be used on human patients due to technical limitations. However electrical stimulation can be used in the treatment of dystrophic muscles in human.


[Dilatational Tracheotomy in Head and Neck Surgery].
The pre- and postoperative airway management during surgery of head and neck cancer is a clinically relevant and challenging task. Usually an epithelialised tracheostomy is used. The significance of percutaneous dilatational tracheostomy (PDT) in combination with tumour surgery of the head neck area has not yet been fully considered. Within a surgical therapy of head neck tumours, 58 patients were treated with a PDT by Ciaglia or Fantoni at the Department of Otorhinolaryngology, Head and Neck Surgery, Martin-Luther-University Halle during the period from December 2002 to October 2007. The patient data were retrospective analyzed in a pseudonymous way. In a follow-up examination the resulting conditions of the PDT were reviewed. The median of the length of time till decannulation was 12 days. There were no documented disorders or complications after PDT at 25 patients (43%). As serious complications pneumothorax in 2 patients (3,4%), 9 bleedings (15,5%) and 1 infection (1,7%) were recorded. After occurrence of tracheostomy metastases in 2 patients with tracheostomy by Fantoni, this method was no longer used. For the subsequent follow-up examination 33 patients were included. No tracheal stenosis or serious long term complications were determined. Under consideration of the indications and contraindications, the percutaneous dilatational tracheostomy by Ciaglia with associated bronchoscopy is a safe method with low complication rate for the airway management of patients with head neck cancer. Long term complications and disorders after PDT are not to be expected. Tracheotomy according to Fantoni cannot be recommended for this treatment.


Effects of intra-amygdalar dopamine agonists and antagonists on gastric stress lesions in rats.
Microinjections of dopamine (DA, 3 and 30 micrograms) or its agonist apomorphine (3 micrograms) into the central amygdala (CEA) attenuated cold restraint (3 h at 4 degrees C)-induced gastric ulcer formation in rats. Pretreatment with DA antagonists, haloperidol and metoclopramide (both i.p. and intra-amygdalar) reversed the stress ulcer attenuating effect of DA. It is suggested that the CEA is one of the central sites for this DA cytoprotection and that D2 receptors are possibly involved in this effect.


Rabbit muscle and urethral in situ biocompatibility properties of the self-reinforced L-lactide-glycolic acid copolymer 80: 20 spiral stent.
A new type of self-reinforced L-lactide-glycolic acid copolymer, molar ratio 80:20, stent was developed. We evaluated the tissue biocompatibility properties of the new material. Rods made of self-reinforced L-lactide-glycolic acid copolymer were inserted into rabbit dorsal muscles and rods of latex or polyvinylchloride and silicone served as positive and negative controls, respectively. Urethral stents of self-reinforced L-lactide-glycolic acid copolymer and steel were inserted in situ via cystoscopy into the rabbit prostatic urethra. The animals were sacrificed after 2 weeks, 1, 2 and 3 months, respectively. In situ histological analysis was done. Tissue reactions around the implantation types were analyzed histologically and scored semiquantitatively. In addition, macroscopic analysis was done of the urethral in situ stents. In rabbit muscle implantation test tissue reaction to the self-reinforced L-lactide-glycolic acid copolymer stent resembled that of negative control silicone. Less than moderate chronic inflammatory changes gradually subsided after 2 weeks. Foreign materials in the tissue and the reaction to these materials began to disappear after 1 month and at 3 months were completely absent. All rabbits fitted with the stent voided normally postoperatively. Self-reinforced L-lactide-glycolic acid copolymer stents were soft, partially fragmented and easily disintegrated when touched at 2 months, and were almost completely degraded at 3 months. The material did not encroach into the urethral wall macroscopically or microscopically. No calcification on the self-reinforced L-lactide-glycolic acid copolymer stents or bladder stone formation was seen. The new self-reinforced L-lactide-glycolic acid copolymer 80:20 material is safe, highly biocompatible and suited for future clinical use. It is most appropriate for preventing postoperative urinary retention after most minimally invasive thermal treatments for benign prostatic hyperplasia.


Higher abdominal adiposity is associated with higher lean muscle mass but lower muscle quality in middle-aged and older men and women: the Framingham Heart Study.
The objective was to determine if abdominal fat is related to poor muscle health. This cross-sectional study included 428 males and 534 females with appendicular lean mass (ALM, kg) from dual-energy X-ray absorptiometry (DXA), grip strength (kg), and upper extremity muscle "quality" (grip strength/arm lean mass) measured (1996-2001) in the Framingham Offspring Study. Sex-specific linear regressions associated adiposity measures [waist circumference (WC, cm) and visceral adipose tissue (VAT, cm3), and subcutaneous adipose tissue (SAT, cm3)] as Z-scores with each measure of muscle, adjusting for covariates. Models were further stratified by body mass index (BMI, < 30, ≥ 30 kg/m2). Mean (± SD) age was 60 ± 9 years and BMI was 28.9 ± 4.6 kg/m2 (men) and 27.7 ± 5.8 kg/m2, (women). In men, the BMI-stratified analyses showed higher WC was associated with higher ALM (P < 0.0001 each) but with lower muscle quality (P < 0.02) in both BMI groups. Higher SAT was also associated with higher ALM (P = 0.0002) and lower muscle quality (P = 0.0002) in men with BMI < 30, but not in obese men. In women, higher WC, SAT, and VAT were each associated with higher ALM but lower muscle quality, particularly in obese women. Higher SAT (P = 0.05) and VAT (P = 0.04) were associated with higher quadriceps strength in women with BMI < 30 kg/m2 but not in obese women. Higher abdominal fat may be associated with greater lean mass but poorer muscle quality, particularly in obese women. This suggests that adipose tissue may have endocrine influences on muscle, which should be confirmed in longitudinal studies.


Intracranial hypertension: an unusual case due to sinus obstruction by fibrosarcoma.
A case of a skull fibrosarcoma compressing the right lateral sinus is presented as a rare cause of intracranial hypertension.


Gelling by heating.
We exploit the concept of competing interactions to design a binary mixture of patchy particles that forms a reversible gel upon heating. Our molecular dynamics computer simulation of such a system shows that with increasing temperature the relaxation dynamics slows down by more than four orders of magnitude and then speeds up again. The system is thus a fluid both at high and at low temperatures and a solid-like disordered open network structure at intermediate temperature. We further discuss the feasibility of realizing a real material with this reversible behavior.


Haemodiafiltration at increased plasma ionic strength for improved protein-bound toxin removal.
Protein-bound uraemic toxin accumulation causes uraemia-associated cardiovascular morbidity. Enhancing the plasma ionic strength releases toxins from protein binding and makes them available for removal during dialysis. This concept was implemented through high sodium concentrations ([Na+ ]) in the substituate of pre-dilution haemodiafiltration at increased plasma ionic strength (HDF-IPIS). Ex vivo HDF-IPIS with blood tested increasing [Na+ ] to demonstrate efficacy and haemocompatibility. Haemocompatibility was further assessed in sheep using two different HDF-IPIS set-ups and [Na+ ] between 350 and 600 mmol L-1 . Safety and efficacy of para-cresyl sulphate (pCS) and indoxyl sulphate (IS) removal was further investigated in a randomized clinical pilot trial comparing HDF-IPIS to HD and HDF. Compared to [Na+ ] of 150 mmol L-1 , ex vivo HDF-IPIS at 500 mmol L-1 demonstrated up to 50% higher IS removal. Haemolysis in sheep was low even at [Na+ ] of 600 mmol L-1 (free Hb 0.016 ± 0.001 g dL-1 ). In patients, compared to HD, a [Na+ ] of 240 mmol L-1 in HDF-IPIS resulted in 40% greater reduction (48.7 ± 23.6 vs. 67.8 ± 7.9%; P = 0.013) in free IS. Compared to HD and HDF (23.0 ± 14.8 and 25.4 ± 10.5 mL min-1 ), the dialytic clearance of free IS was 31.6 ± 12.8 mL min-1 (P = 0.017) in HDF-IPIS, but [Na+ ] in arterial blood increased from 132 ± 2 to 136 ± 3 mmol L-1 (0 vs. 240 min; P < 0.001). HDF-IPIS is technically and clinically feasible. More effective HDF-IPIS requires higher temporary plasma [Na+ ], but dialysate [Na+ ] has to be appropriately adapted to avoid sodium accumulation.


Multiple intestinal atresia with apple peel syndrome: successful treatment by five end-to-end anastomoses, jejunostomy, and transanastomotic silicone stent.
The association of apple peel bowel with multiple intestinal atresias is a rare event. The authors report a case of a 2.200-g newborn affected by this uncommon condition. The interruptions of small bowel continuity were treated successfully with 5 end-to-end anastomoses and with the construction of 2 ostomies. A gastroduodenal silicone tube (Vygon S.A., Ecouen, France) was used as an intraluminal stent.


Renalase gene polymorphisms in patients with type 2 diabetes, hypertension and stroke.
Renalase is a novel, recently identified, flavin adenine dinucleotide-dependent amine oxidase. It is secreted by the kidney and metabolizes circulating catecholamines. Renalase has significant hemodynamic effects, therefore it is likely to participate in the regulation of cardiovascular function.The aim of our study was to investigate the involvement of renalase gene polymorphisms in hypertension in type 2 diabetes patients. A total of 892 patients and 400 controls were genotyped with three SNPs in the renalase gene. The C allele of rs2296545 SNP was associated with hypertension (P < 0.01). For rs2576178 SNP, frequencies in hypertensive patients differed from controls, but not from normotensive patients. For rs10887800 SNP, the differences in the G allele frequencies were observed in hypertensive patients with stroke, with 66% of patients being GG homozygotes. To confirm observed association we later genotyped 130 stroke patients without diabetes. The OR for risk allele was 1.79 (95% CI 1.33-2.41). In conclusion, the renalase gene polymorphism was associated with hypertension in type 2 diabetes patients. The most interesting result is a strong association of the rs10887800 polymorphism with stroke in patients with and without diabetes. The G allele of this polymorphism might thus be useful in identifying diabetes patients at increased risk of stroke.


The Role of Technology in Ophthalmic Surgical Education During COVID-19.
To describe the effect of COVID-19 on ophthalmic training programs and to review the various roles of technology in ophthalmology surgical education including virtual platforms, novel remote learning curricula, and the use of surgical simulators. COVID-19 caused significant disruption to in-person clinical and surgical patient encounters. Ophthalmology trainees worldwide faced surgical training challenges due to social distancing restrictions, trainee redeployment, and reduction in surgical case volume. Virtual platforms, such as Zoom and Microsoft Teams, were widely used during the pandemic to conduct remote teaching sessions. Novel virtual wet lab and dry lab curricula were developed. Training programs found utility in virtual reality surgical simulators, such as the Eyesi, to substitute experience lost from live patient surgical cases. Although several of these described technologies were incorporated into ophthalmology surgical training programs prior to COVID-19, the pandemic highlighted the importance of developing a formal surgical curriculum that can be delivered virtually. Novel telementoring, collaboration between training institutions, and hybrid formats of didactic and practical training sessions should be continued. Future research should investigate the utility of augmented reality and artificial intelligence for trainee learning.


Effects of root or nerve destruction on vibrotactile sensitivity in trigeminal neuralgia.
Vibrotactile thresholds were determined at 7 frequencies between 25 and 300 Hz at the medial edge of the cheek in 11 patients who had been or were currently being treated for major trigeminal neuralgia, tic douloureux. A control group, comparable in age but without neural pathology, was also tested. Results indicate essentially no difference between normal and affected sides of the face prior to surgery. The drug carbamazepine (Tegretol), commonly used to control pain of trigeminal neuralgia, did not affect vibrotactile thresholds. Infraorbital neurectomy resulted in an initial loss of sensitivity at all frequencies, followed by a gradual return of sensation which reached preoperative levels at approximately one year. The return of sensitivity was followed by the return of neuralgia. Following alcoholic gasserian rhizolysis, low-frequency thresholds were elevated considerably as after neurectomy, but sensation above 100 Hz was lost completely. A return of high-frequency sensitivity accompanied the recurrence of pain in some patients who had been injected up to 13 years prior to testing. The results are discussed in terms of recent anatomical, electrophysiological, and clinical findings.


The effects of antidepressants and electroconvulsive shocks on the functioning of the mesolimbic dopaminergic system: a behavioral study.
The mesolimbic dopaminergic innervation is supposed to be involved in the mechanisms of central effects exerted by various classes of psychotropic drugs. Antidepressants have been found to interact with the brain dopaminergic system as well, although the precise central location of this interaction is unknown. Some data point to the mesolimbic dopaminergic system as a possible target for antidepressant action. The aim of the present experiment was to verify this hypothesis. It was found that a long-term treatment of rats with desipramine, citalopram or electroconvulsive shocks potentiated the dopaminergic mechanisms within the nucleus accumbens, as evidenced by an increase in or the appearance of behavioral effects (exploratory locomotion, an active behavior in the Porsolt test) following microinjections of dopaminergic agonists into this brain area. Similar results obtained with different methods of treatment for depression indicate that the effect of antidepressants and electroshocks on dopaminergic mechanisms within the nucleus accumbens may be linked directly to the mechanism of their antidepressant action.


Lipopolysaccharide potentiates hyperthermia-induced seizures.
Prolonged febrile seizures (FS) have both acute and long-lasting effects on the developing brain. Because FS are often associated with peripheral infection, we aimed to develop a preclinical model of FS that simulates fever and immune activation in order to facilitate the implementation of targeted therapy after prolonged FS in young children. The innate immune activator lipopolysaccharide (LPS) was administered to postnatal day 14 rat (200 μg/kg) and mouse (100 μg/kg) pups 2-2.5 h prior to hyperthermic seizures (HT) induced by hair dryer or heat lamp. To determine whether simulation of infection enhances neuronal excitability, latency to seizure onset, threshold temperature and total number of seizures were quantified. Behavioral seizures were correlated with electroencephalographic changes in rat pups. Seizure-induced proinflammatory cytokine production was assessed in blood samples at various time points after HT. Seizure-induced microglia activation in the hippocampus was quantified using Cx3cr1(GFP/+) mice. Lipopolysaccharide priming increased susceptibility of rats and mice to hyperthemic seizures and enhanced seizure-induced proinflammatory cytokine production and microglial activation. Peripheral inflammation appears to work synergistically with hyperthermia to potentiate seizures and to exacerbate seizure-induced immune responses. By simulating fever, a regulated increase in body temperature from an immune challenge, we developed a more clinically relevant animal model of prolonged FS.


The insanity defense for sex offenders: jury decisions after repeal of Wisconsin's Sex Crimes Law.
After repeal of a Wisconsin statute permitting hospitalization of defendants convicted of sexual crimes, the authors noted an increase in the percentage of sex offenders among persons hospitalized after being found not guilty by reason of insanity. They also found that a greater proportion of hospitalized sex offenders than of other kinds of offenders were diagnosed as nonpsychotic. Illustrating with three case studies, the authors argue that despite trends away from the therapeutic model of corrections, juries continue to make decisions that provide treatment for defendants perceived to need it, even if the legal criteria for those decisions do not appear to be met.


Mucosal adjuvants and long-term memory development with special focus on CTA1-DD and other ADP-ribosylating toxins.
The ultimate goal for vaccination is to stimulate protective immunological memory. Protection against infectious diseases not only relies on the magnitude of the humoral immune response, but more importantly on the quality and longevity of it. Adjuvants are critical components of most non-living vaccines. Although little attention has been given to qualitative aspects of the choice of vaccine adjuvant, emerging data demonstrate that this function may be central to vaccine efficacy. In this review we describe efforts to understand more about how adjuvants influence qualitative aspects of memory development. We describe recent advances in understanding how vaccines induce long-lived plasma and memory B cells, and focus our presentation on the germinal center reaction. As mucosal vaccination requires powerful adjuvants, we have devoted much attention to the adenosine diphosphate (ADP)-ribosylating cholera toxin and the CTA1-DD adjuvants as examples of how mucosal adjuvants can influence induction of long-term memory.


Measuring the value of older people's production: a diary study.
The productive capacity of retired people is usually not valued. However, some retirees produce much more than we might expect. This diary-based study identifies the activities of older people, and suggests some value mechanisms. One question raised is whether it is possible to scale up this diary study into a larger representative study. Diaries kept for one week were collected among 23 older people in the north of Sweden. The texts were analysed with a grounded theory approach; an interplay between ideas and empirical data. Some productive activities of older people must be valued as the opportunity cost of time or according to the market value, and others must be valued with the replacement cost. In order to make the choice between these methods, it is important to consider the societal entitlement. When there is no societal entitlement, the first or second method must be used; and when it exists, the third must be used. An explicit investigation of the content of the entitlement is needed to justify the choice of valuation method for each activity. In a questionnaire addressing older people's production, each question must be adjusted to the type of production. In order to fully understand this production, it is important to consider the degree of free choice to conduct an activity, as well as health-related quality of life.


Paranormal belief, thinking style preference and susceptibility to confirmatory conjunction errors.
This study examines the extent to which belief in extrasensory perception (ESP), psychokinesis (PK) or life after death (LAD), plus need for cognition (NFC) and faith in intuition (FI), predict the generation of confirmatory conjunction errors. An opportunity sample (n = 261) completed sixteen conjunction problems manipulated across a 2 event type (paranormal vs. non-paranormal) × 2 outcome type (confirmatory vs. disconfirmatory) within subjects design. Three Generalised Linear Mixed Models - one per paranormal belief type - were performed. With respondent gender and age controlled for, ESP, PK and LAD beliefs were all associated with the making (vs. non-making) of conjunction errors both generally and specifically for confirmatory conjunctive outcomes. Event type had no impact. Individuals high in NFC were less likely to commit the fallacy. The role thinking style plays in shaping paranormal believers' susceptibility to confirmatory conjunction biases is discussed. Methodological issues and future research ideas are also considered.


Impact of composting strategies on the degradation of nonylphenol in sewage sludge.
Nonylphenol can be present in sewage sludge, and this can limit the use of the sewage sludge to amend soil. Composting is one of the most efficient and economical methods of making sewage sludge stable and harmless. The nonylphenol degradation rates during composting with added bulking agents and with aeration applied were studied. Three organic bulking agents (sawdust, corn stalk, and mushroom residue) were added to sewage sludge, and the effects of the bulking agents used and the amount added on nonylphenol degradation were determined. The highest apparent nonylphenol degradation rate (71.6%) was found for sewage sludge containing 20% mushroom residue. The lowest apparent nonylphenol degradation rate (22.5%) was found for sewage sludge containing 20% sawdust. The temperature of the composting pile of sewage sludge containing 20% sawdust became too high for nonylphenol to be efficiently degraded, and the apparent nonylphenol degradation rate was lower than was found for sewage sludge containing 10% sawdust. Increasing the ventilating time from 5 to 15 min increased the apparent nonylphenol degradation rate from 19.7 to 41.6%. Using appropriate aerobic conditions facilitates the degradation of nonylphenol in sewage sludge, decreasing the risks posed by sewage sludge applied to land. Adding too much of a bulking agent can decrease the amount of the nonylphenol degraded. Increasing the ventilating time and the amount of air supplied can increase the amount of nonylphenol degraded even if doing so causes the composting pile temperature to remain low.


A case of ischemic stroke with hemorrhagic transformation associated with essential thrombocythemia and JAK-2 V617F mutation.
Essential thrombocythemia (ET) is a rare cause of stroke. The V617F mutation in the Janus kinase 2 (JAK2) gene is one of the most typical mutations in ET and has been shown to be a risk factor for stroke, especially in younger people. However, to date, there have been few reports of intracranial thrombotic and hemorrhagic complications in patients with ET. Herein, we present a case of JAK2 gene mutation-associated ET in a patient who developed both ischemic and hemorrhagic stroke, and discuss potential underlying mechanisms. A 45-year-old Chinese male presented to our center with gradually developing weakness of the right limbs for 3 months. A computed tomography scan of the brain showed an area of infarction with hemorrhage in the left subcortical and corona radiata regions. High-resolution magnetic resonance imaging revealed a thrombosis on the surface of the atherosclerotic plaque. Digital subtraction angiography revealed an insect bite-like change in the C1 branch of the left internal carotid artery, which caused up to 50% stenosis. Blood tests showed continued elevation of the platelet and white blood cell counts. After consultation with a hematologist, a bone marrow biopsy was performed, which revealed proliferative bone marrow changes with numerous megakaryocytes and proliferative but mature granulocytes. Further genetic testing revealed a positive JAK2-V617F mutation. Therefore, the diagnosis of ET was confirmed according to the World Health Organization (WHO) 2016 diagnostic criteria. Finally, we decided to administer aspirin and hydroxyurea. The patient remained stroke free and the platelet levels were normal throughout the 1-year follow-up period. JAK2 mutations affect the proliferation and differentiation of blood cells through the JAK, signal transducer and activator of transcription pathway, which leads to changes in platelets and macrophages, and an increase in neutrophil extracellular traps, which may explain the patient's ischemic and hemorrhagic changes. Further investigation of the underlying mechanisms may change the treatment strategy for such patients in the future.


Highly potent and selective heptapeptide antagonists of the neurokinin NK-2 receptor.
Incorporation of D-Pro9 into substance P related peptides is known to enhance neurokinin NK-2 receptor agonist potency and selectivity with respect to other neurokinin receptors. We now report that replacement of D-Trp9 by D-Pro9 in the nonselective neurokinin antagonist [Arg5,D-Trp7,9, Nle11]-SP(5-11) gave a partial agonist with NK-2 receptor selectivity. Further incorporation of Pro10 provided the weak but selective NK-2 antagonist Arg-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (compound 4; NK-2 pKB = 5.9; NK-1 pKB = 4.7; NK-3 pKB less than 4.6). Addition of a suitable lipophilic N-terminal substituent (e.g. Boc, PhCO, cyclohexylcarbonyl) to this compound greatly enhanced NK-2 antagonist activity (compound 10, GR 83074; NK-2 pKB = 8.2), and combined with further optimization of the N-terminal amino acids, provided the extremely potent and selective NK-2 antagonist PhCO-Ala-Ala-D-Trp-Phe-D-Pro-Pro-Nle-NH2 (compound 34, GR 94800; NK-2 pKB = 9.6; NK-1 pKB = 6.4; NK-3 pKB = 6.0). Compounds of this class produced a potent inhibition of NK-2 agonist-induced bronchoconstriction in the anaesthetized guinea-pig.


Fatigue in community-dwelling older adults: A review of definitions, measures, and related factors.
Fatigue is a common age-related symptom among community-dwelling adults aged 65 years and older. Yet, a systematic approach has rarely been applied to review definitions, measures, related factors, and consequences of fatigue in this population. A scoping review was conducted in December 2020 to fill the gap, and 36 articles met the inclusion criteria. Definitions, albeit diverse, included at least one of the following attributes: an early indicator of disablement, subjective, a lack of energy, multidimensional, impaired daily activities, and temporal. A summary of fatigue measures used in this population was provided, including a brief overview, number of items, reliability, and validity. In general, different measures were used with considerable variability in the content. Additionally, most measures had limited information on test-retest reliability and validity. Fatigue-related factors mapped into biological, psychological, social, and behavioral factors. Fatigue consequences were primarily declines in physical and cognitive functions. (100-150 words).


Rapid and efficient detection of genetic polymorphism in wheat through amplification by polymerase chain reaction.
The polymerase chain reaction (PCR) was used to amplify genomic DNA of several wheat genotypes. The oligonucleotides used as primers were the terminal sequences of a gamma-gliadin gene. The electrophoretic analysis of the PCR products showed specific bands which revealed both inter- and intra-specific genetic polymorphism among the examined genotypes. The technique is proposed as a very simple and efficient alternative to RFLP markers.


[Giving up the tobacco habit through the application of the Smoker's Aid Program in the Chantrea Health Centre].
This is a prospective descriptive study of intervention without aleatory assignation, carried out in the Chantrea Health Centre. Its aim is to determine the characteristics of the smokers who are taking part in two interventions by the Smokers' Aid Program (Programa de Ayuda al Fumador-PAF), and to evaluate the factors that influence the latter's success. The characteristics of 100 smokers were analyzed. They were offered one of the two PAF interventions: Minimal Intervention 1 (MN1): they are given a support brochure in the first consultations, contacted by telephone after one month and called to consultation after 6 months to measure CO. Minimal Intervention 2 (MN2): the smoker makes 5 consultations of support in giving up smoking (+ or - nicotine patches) with the doctor, nurse or social worker indiscriminately. The factors that were influential in abandoning the habit with 65 subjects were evaluated. 60% of the subjects were male with an average age of 41 (DE 29). 29% showed a pathology related to tobacco, with no relation found between this and the success of the interventions. Those who chose MN2 (38%) had started tobacco consumption at an earlier age and were more dependent on nicotine. Of the 65 smokers who completed the program, 37% continued not to smoke after 6 months. Those who managed to give up smoking were of a greater average age, had spent more years smoking and belonged above all to the MN1 intervention. Notable successes are achieved if the actions are carried out by the First Aid Team. We find no significant differences between the characteristics of those who give up smoking and those who do not. Not even a serious pathology, related to tobacco, is predictive of success. The smoker's dependence on nicotine must be taken into account in the intervention.


Enhancement of molecular properties in thin films by controlled orientation of molecular building blocks.
We demonstrate the design and formation of thin films having divergent physicochemical properties by using two porphyrin building blocks with high chemical and optical resemblance. A predetermined variation in the molecular design is efficiently transferred and enhanced when constituting a two-dimensional film via control of molecular orientation. Variations of the peripheral substituents on the porphyrin ring resulted in control of the molecular orientation at the surface.


Smartphone-based wearable microfluidic electrochemical sensor for on-site monitoring of copper ions in sweat without external driving.
The directional movement of liquid without exogenous drive can show great potential in portable electrochemical platforms. Herein, we developed a portable electrochemical platform that drove electrolyte flow by surface tension gradient, which can realize collection of electrolyte, flow preconcentration and electrochemical detection of Cu2+. The induced graphene electrodes (LIG) was fabricated using laser direct writing, and flower cluster shaped ZnO nanorods (FC-ZnONRs) were prepared and modified on LIG, which provided a large amount of space for electrolyte to shuttled between the holes of LIG and ZnO, and increased the electrochemical active sites and electrons transport ability. The effect of surface tension gradients driving fluid flow could accelerate preconcentration, shorten detection time (save 300 s of preconcentration time) and enhance electrochemical responses in synergy with the 3D FC-ZnONRs/LIG. The microfluidic system possessed excellent performance for detection of Cu2+ ranged from 1 μg L-1 to 2100 μg L-1 with a low detection limit (LOD) of 0.0368 μg L-1 and high sensitivity of 0.414 μA (μg L-1)-1 cm-2. Additionally, this portable microfluidic system was successfully worn on the skin for analysing Cu2+ in human sweat, and the results showed good consistency with inductively coupled plasma-mass spectrometry (ICP-MS). This novel sensing system provides a sample collection, rapid detection, low cost and easy-to-operate strategy for heavy metal ions analysis in real samples and shows huge application prospects in point-of-care testing.


Family functioning in anorexia nervosa: British and Italian mothers' perceptions.
This study tested the hypothesis that cultural differences would influence individuals' perceptions of family functioning. Mothers of British and Italian children and adolescents with anorexia nervosa completed the Family Assessment Device (FAD). British mothers perceived their families' communication and role definition as less healthy than did the Italian mothers. In contrast, the Italians perceived their families' behavior control methods as less healthy than did the British mothers. The findings might be explained by differences between British and Italian interpretations of the role of "family," particularly giving the British emphasis on independence and the Italian emphasis on family life. It is suggested that these culturally divergent attitudes towards family life might have different influences on anorexia nervosa. Finally, implications for family therapy are discussed, taking into account those characteristics that are more relevant for each cultural group.


Father-absent and father-present families of disturbed and nondisturbed adolescents.
In a study of intact and of father-absent families, male adolescent disturbance in both groups was found to be related to less warm, supportive, and expressive intrafamilial relations; less of a family orientation toward personal growth; and less successful participation in extrafamilial involvement. Disturbance in father-absent boys was not related to negative father-typing by the mother or maternal restrictions, and the findings do not support the assumption of family conditions peculiar to the father-absent home as a factor in adolescent pathology.


The burden of untreated insomnia disorder in a sample of 1 million adults: a cohort study.
Insomnia disorder is a highly prevalent, significant public health concern associated with substantial and growing health burden. There are limited real-world data assessing the burden of insomnia disorder on daytime functioning and its association with comorbidities. The objective of this study was to leverage large-scale, real-world data to assess the burden of untreated insomnia disorder in terms of daytime impairment and clinical outcomes. This United States medical claims database study compares patients diagnosed with insomnia disorder but not receiving treatment ('untreated insomnia' cohort) to patients without an insomnia disorder diagnosis and without treatment ('non-insomnia' cohort). International Classification of Disease, Tenth Revision codes were used as a proxy to represent the three symptom domains (Sleepiness, Alert/Cognition, Mood) of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ), a newly developed and validated tool used in clinical studies to assess daytime functioning in insomnia disorder. Chronic Fatigue (R53.83) and Other Fatigue (R53.83), Somnolence (R40.0) and Disorientation (R41.0) were selected as categories representing one or more IDSIQ domains. Clinical outcomes included cardiovascular events, psychiatric disorders, cognitive impairment and metabolic disorders. Approximately 1 million patients were included (untreated insomnia: n = 139,959; non-insomnia: n = 836,975). Compared with the 'non-insomnia' cohort, the 'untreated insomnia' cohort was more likely to experience daytime impairments, with mean differences in occurrences per 100 patient-years for: (a) fatigue, at 27.35 (95% confidence interval [CI] 26.81, 27.77, p < 0.01); (b) dizziness, at 4.66 (95% CI 4.40, 4.90, p < 0.01); (c) somnolence, at 4.18 (95% CI 3.94, 4.43, p < 0.01); and (d) disorientation, at 0.92 (95% CI 0.77, 1.06, p < 0.01). During the 1-year look-back period, patients in the 'untreated insomnia' cohort were also more likely to have been diagnosed with arterial hypertension (40.9% vs. 26.3%), psychiatric comorbidities (40.1% vs. 13.2%), anxiety (29.2% vs. 8.5%), depression (26.1% vs. 8.1%) or obesity (21.3% vs. 11.1%) compared with those in the 'non-insomnia' cohort. This large-scale study confirms the substantial burden of insomnia disorder on patients in a real-world setting, with significant daytime impairment and numerous comorbidities. This reinforces the need for timely insomnia disorder diagnosis and treatments that improve both sleep, as well as daytime functioning.


[Necrotizing fasciitis caused by group G streptococci].
Necrotizing fasciitis is a soft tissue infection which is highly lethal. Its lethality can only be reduced by early diagnosis and radical débridement. A delayed diagnosis will result in streptococcal toxic shock syndrome. Any surgery neglecting radical débridement up to amputation is inadequate and cannot reduce lethality. This paper reports on two cases of necrotizing fasciitis of the leg caused by group G streptococci.


Lactation outcome in insulin-dependent diabetic women.
To document the incidence and management of breast feeding among women with insulin-dependent diabetes mellitus (IDDM), 30 IDDM mothers and 30 controls were followed from birth of their infants to 6 weeks postpartum. The researchers interviewed the mothers in the hospital and by telephone at 1, 2, and 6 weeks postpartum. Fifty-three percent of the IDDM women and 57% of the general hospital population intended to breast feed. Because of the need for neonatal observation for hypoglycemia, most IDDM mothers were separated from their infants for the first 2 days. After 1 week, as many IDDM mothers as controls nursed. Initially, no differences in breast-feeding problems were found between the groups, but between 2 and 6 weeks postpartum, two IDDM nursing mothers but none of the controls experienced clinically diagnosed mastitis. A daily diet prescription of 31 kcal per kilogram of maternal body weight was associated with IDDM mothers' ability to sustain lactation, in contrast with 25 kcal per kilogram of maternal weight for IDDM mothers who stopped nursing. Six-week postpartum fasting plasma glucose levels of IDDM mothers who exclusively breast fed were significantly lower (4.6 +/- 2.2 mmol/L [82 +/- 40 mg/dl]) than the glucose levels of the women who stopped nursing (8.1 +/- 2.1 mmol/L [145 +/- 37 mg/dl]) or the glucose levels of the IDDM mothers who chose to bottle feed (6.7 +/- 1.7 mmol/L [120 +/- 30 mg/dl]). It appears that adequate maternal calories, blood sugar control, early breast stimulation, and mastitis monitoring are necessary for optimal lactation outcome in insulin-dependent diabetic women.


[Vascular and neural malformations].
The presentation of vascular and neural malformations in an understandable terminology permits accurate diagnosis, proper treatment, individualized prognosis, and also stimulates studies of pathogenesis. The descriptive classification includes: NF 1 and NF 2; hemangiomas, low- and high-flow vascular malformations, combined malformations, and hypertrophy; and syndromes such as, Parkes Weber, Klippel-Trénaunay, Maffuci's, and multiple dysplasia syndromes. Lymphatic malformations are abnormalities of lymphatic development. The list of treatment includes surgical and nonsurgical treatment. Not all vascular malformations can be successfully treated. Coping with NF is a challenge for both, affected individuals and health care professionals. NF is often associated with a myriad of anomalies that present a lot of problems for plastic surgery. In certain cases watchful waiting seems justified but not in cases of severe problems, giant growth, and local complications.


Multi-institutional assessment of the prevalence of neuroendocrine tumors in children undergoing laparoscopic appendectomy for acute appendicitis in the United States.
As non-operative management of acute appendicitis in children has become more common, missed incidental appendiceal pathology can be an unintended consequence. We assessed the prevalence of neuroendocrine tumors in appendectomy specimens from eight US children's hospitals from 2012 to 2021. The prevalence of neuroendocrine tumors (NET) was found to be 1:271, with a median age of 14 years and 62% female. Most tumors were small (median 6 mm; interquartile range [IQR]: 3-10), and no recurrence was noted during the follow-up period (median 22.5 months; IQR: 3-53). The possibility of delayed diagnosis of these tumors should be part of the discussion for non-operative management of pediatric acute appendicitis.


Hepatic angiomyolipoma: identification of an efferent vessel as a hepatic vein by contrast-enhanced harmonic sonography.
Two cases of hepatic angiomyolipoma were studied by contrast-enhanced harmonic sonography. The special tumor hemodynamics, namely the efferent blood flow of the hepatic angiomyolipoma draining into the hepatic vein, were clearly shown on harmonic imaging, and they corresponded well with those seen on angiography and computed tomography during angiography. Benign hepatic tumors were diagnosed preoperatively in both cases according to the hemodynamic findings. Hepatic angiomyolipoma was finally identified histologically. The special tumor hemodynamics might be one of the important characteristics of hepatic angiomyolipoma. Contrast-enhanced harmonic sonography is useful for the detection of special tumor hemodynamics and may facilitate the differential diagnosis from other hepatic tumors, especially malignant liver tumors.


Neutrophil to Lymphocyte Ratio and Periprosthetic Joint Infection: A Systematic Review and Meta-Analysis.
The neutrophil-to-lymphocyte ratio (NLR) has shown promising results as a diagnostic tool for periprosthetic joint infection (PJI) after total joint arthroplasty. We conducted a systematic review and meta-analysis to determine the utility of NLR in the diagnosis of PJI. We searched PubMed, Scopus, and Web of Science from inception up to 2022 and evaluated the quality of the included literature. Based on the 12 eligible studies, NLR levels were significantly higher in patients who had PJI compared to those who had aseptic loosening (standard mean difference (SMD) = 1.05, 95% Confidence Interval (CI) = 0.71 to 1.40, P < .001). In the subgroup analysis according to type of PJI, NLR levels were significantly higher in patients who had either acute (SMD = 1.04, 95% CI = 0.05 to 2.03, P < .001) or chronic PJI (SMD = 1.08, 95% CI = 0.55 to 1.61, P < .001), compared to those who had aseptic loosening. According to type of arthroplasty, NLR levels were significantly higher in patients who had either total knee arthroplasty (SMD = 1.81, 95% CI = 1.48 to 2.13, P < .001) or total hip arthroplasty (SMD = 1.76, 95% CI = 1.54 to 1.98, P < .001) compared to aseptic loosening. The pooled sensitivity of the 12 studies was 0.73 (95% CI, 0.65 to 0.79), and the pooled specificity was 0.75 (95% CI, 0.71 to 0.78). The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of NLR were 2.94 (95% CI = 2.44 to 3.54), 0.35 (95% CI = 0.27 to 0.46), and 8.26 (95% CI = 5.42 to 12.58), respectively. In summary, this meta-analysis indicates that NLR is a reliable marker in the diagnosis of PJI.


Marital status independently predicts survival of patients with upper urinary tract urothelial carcinoma: A population-based study.
To evaluate impact of marital status on survival of patients with upper urinary tract urothelial carcinoma (UTUC). Data of patients diagnosed with UTUC from 2010 to 2015 were identified and retrieved from the Surveillance, Epidemiology, and End Results database. The impact of marital status on overall survival (OS) and cancer-specific survival (CSS) was analyzed using Kaplan-Meier survival curve method and compared with the log-rank test. Multivariate survival analysis of OS and CSS was conducted using the Cox proportional hazards regression model. A total of 4520 eligible patients with UTUC were included in this study. The 5-year OS rates of married patients, never-married patients, and separated, divorced, or widowed (SDW) patients were 47.3%, 43.7%, and 39.2%, respectively (P < 0.001), and the corresponding 5-year CSS rates were 57.7%, 55.2%, and 51.5%, respectively (P = 0.005). In multivariate analyses, marital status was an independent prognostic factor for OS (P < 0.001) and CSS (P = 0.002) of patients with UTUC. Compared to married patients, never married (hazard ratio [HR], 1.187; 95% confidence interval [CI], 1.016-1.386 for OS; HR, 1.102; 95% CI, 0.877-1.385 for CSS) and SDW (HR, 1.205; 95% CI, 1.094-1.327 for OS; HR, 1.309; 95% CI, 1.131-1.514 for CSS) patients showed poor OS and unfavorable CSS. Marital status was an independent prognostic factor for OS and CSS in patients with UTUC. Married patients with UTUC experienced longer OS and a more favorable CSS than their never married and SDW counterparts.


Conjugation of soy protein isolate (SPI) with pectin: effects of structural modification of the grafting polysaccharide.
Recently, there has been a great interest in enhancing the emulsifying properties of soy protein isolate (SPI) by Maillard reaction. As a commonly-used grafting polysaccharide, pectin has proved useful in modifying proteins. However, effects of its structural characteristics on conjugation are still not fully understood. To address this problem, we employed alkaline or/and enzymatic treatments to modify pectin and obtained three modified samples. Structural characteristics of pectin, including the molecular weight, degree of methoxylation and acetylation, and monosaccharide compositions were measured. When conjugated with SPI, pectin with lower molecular weight and less main chains induced higher conjugate yield. Fluorescence intensity and surface hydrophobicity of all conjugates markedly reduced compared to the original SPI, suggesting a more loosened protein structure after Maillard reaction. In this study, the enzymolysis pectin proved an optimum grafting polysaccharide considering the simple preparation procedures and the highest emulsifying properties of its resulting conjugates.


Non-invasive diagnosis of Helicobacter pylori infection: simplified 13C-urea breath test, stool antigen testing, or DNA PCR in human feces in a clinical laboratory setting?
(1) To compare two stool antigen EIAs (HpSA, FemtoLab) and PCR of ureaseA and cagA in feces, with (13)C-urea breath test (UBT). (2) To ascertain whether a simplified UBT (breath collection time = 10 min) is as reliable as the standard assay (30 min). Helicobacter pylori status was recorded in Group 1 (n = 187) by UBT, H. pylori stool antigen, ureA and cagA PCR in feces. UBT with 10, 20 and 30 min sampling was performed in Group 2 patients (n = 283). The sensitivity and specificity of HpSA, FemtoLab, and ureA were 67% and 99%, 90% and 96%, 35% and 98%, respectively. cagA results were positive in 16/48 H. pylori-positive, and in 5/100 H. pylori-negative patients. The results of UBT with a 10- and 30-min sampling strictly overlapped. UBT with 10 min breath collection and FemtoLab stool antigen assay are the most reliable non-invasive tests to diagnose H. pylori infection.


Integrated bioinformatics analysis of differentially expressed genes in the temporomandibular joint internal derangement.
This study aimed to identify significant mechanisms and potential treatments for temporomandibular joint internal derangement (TMJD) through integrated bioinformatics analysis. Gene expression data sets (GSE66864) from the Gene Expression Omnibus (GEO) database were downloaded. Differentially expressed genes (DEGs) were identified both in the treatment groups and in controls by R packages. Network analysis of protein-protein interaction (PPI) and Human Protein Atlas was used to explore DEGs' potential function. DGIdb database was utilized to gain potential drug targets. In conclusion, 126 DEGs were selected for TMJD through bioinformatics analysis. Both GO and Kyoto Encyclopedia of Genes and Genomes analyses combined showed the pathways involved in TMJD. A PPI network was constructed to select the top 10 hub genes, of which five hub genes were chosen for further investigation. Moreover, the microenvironment of immune cells related to hub genes was evaluated by R packages. Macrophages play an important role in inflammation and oral-related tumors. The Human Protein Atlas analysis indicated that the five hub genes are highly related to head and neck cancer. Finally, eight potential drugs were selected for two genes using the DGIdb database. Our integrated bioinformatics analysis identified DEGs in TMJD and provided potential ideas for further research and treatment approaches. However, experimental validation of the hub genes and potential drug targets is still needed. The key mechanisms of the identified genes and their potential roles as biomarkers or drug targets in TMJD require further investigation.


Organization of midbrain dopamine systems and the pathophysiology of Parkinson's disease.
Understanding of the pathophysiology of Parkinson disease (PD) has advanced rapidly over the last two decades through basic and clinical studies using modern neuroanatomical, clinical assessment, neuropathological and functional brain imaging methods. Two interacting processes determine the development of functional impairment, neuronal degeneration with selective denervation of specific regions and compensatory responses, which oppose the effects of denervation. The clinical manifestations of PD, at least in early stages, reflect selective degeneration of dopamine neurons in the substantia nigra projecting through the nigrostriatal pathway to the caudal putamen with compensatory changes in this and related systems. Positron emission tomography with specific ligands for the dopamine system is a powerful tool for analysis of both degenerative and compensatory processes in the pathophysiology of Parkinson disease in vivo and can be used to confirm the diagnosis of dopamine deficient Parkinson disease.


Prophylactic surgery in familial adenomatous polyposis (FAP)--a single surgeon's short- and long-term experience with hand-assisted proctocolectomy and smaller J-pouches.
Prophylactic proctocolectomy with an ileoanal neo-reservoir is the established procedure in non-attenuated familial adenomatous polyposis (FAP). Traditionally, the ileal J-pouch is created by doubling 15 cm of the terminal ileum. Pouch inlet problems are not infrequently encountered in longer pouches. On this rationale, this series reports on the functional outcome and quality of life (QoL) following standardized construction of a shorter J-pouch with a limb of 8-9 cm length. All patients of a single-surgeon series with FAP who underwent hand-assisted laparoscopic proctocolectomy and small ileal pouch-anal anastomosis as the primary procedure between 10/2005 and 04/2010 and responded to the questionnaire were included and retrospectively analyzed. A total of 46 patients (78 %) out of the consecutive series who underwent operation in this period were included in the study. After a mean follow-up of 38 months, 40/46 patients (87 %) did not report any incontinence and 3 patients (6.5 %) complained about occasional nocturnal incontinence (3 failed to answer this question). The mean stool frequency per 24 h was 6.25. No significant difference was encountered between the QoL outcome of our patients versus the German normative population. Comparable results were achieved in a study analyzing the long-term results in FAP patients with a 15-cm pouch. Smaller, 8-9 cm J-pouches show excellent functional results both in short- and in long-term results. The hand-assisted procedure was safe and no conversions were required. QoL is equal to a normative population, as it is in a series of patients with larger J-pouches.


Institutional charges and disparities in outpatient brain biopsies in four US States: the State Ambulatory Database (SASD).
Several groups have demonstrated the safety of ambulatory brain biopsies, with no patients experiencing complications related to early discharge. Although they appear to be safe, the reasons factoring into the selection of patients have not been investigated. We performed a cross-sectional study involving 504 patients who underwent outpatient and 10,328 patients who underwent inpatient brain biopsies and were registered in State Ambulatory Surgery Databases and State Inpatient Databases respectively for four US States (New York, California, Florida, North Carolina). In a multivariate analysis private insurance (OR 2.45, 95 % CI, 1.85, 3.24), was significantly associated with outpatient procedures. Higher Charlson Comorbidity Index (OR 0.16, 95 % CI, 0.08, 0.32), high income (OR 0.37, 95 % CI, 0.26, 0.53), and high volume hospitals (OR 0.30, 95 % CI, 0.23, 0.39) were associated with a decreased chance of outpatient procedures. No sex, or racial disparities were observed. Institutional charges were significantly less for outpatient brain biopsies. There was no difference in the rate of 30-day postoperative readmissions among inpatient and outpatient procedures. The median charge for inpatient surgery was 51,316 as compared to 12,266 for the outpatient setting (P < 0.0001, Student's t test). Access to ambulatory brain biopsies appears to be more common for patients with private insurance and less comorbidities, in the setting of lower volume hospitals. Further investigation is needed in the direction of mapping these disparities in resource utilization.


Plasticity of the adult human small intestinal stoma microbiota.
The human distal small intestine (ileum) has a distinct microbiota, but human studies investigating its composition and function have been limited by the inaccessibility of the ileum without purging and/or deep intubation. We investigated inherent instability, temporal dynamics, and the contribution of fed and fasted states using stoma samples from cured colorectal cancer patients as a non-invasive access route to the otherwise inaccessible small and large intestines. Sequential sampling of the ileum before and after stoma formation indicated that ileostoma microbiotas represented that of the intact small intestine. Ileal and colonic stoma microbiotas were confirmed as distinct, and two types of instability in ileal host-microbial relationships were observed: inter-digestive purging followed by the rapid postprandial blooming of bacterial biomass and sub-strain appearance and disappearance within individual taxa after feeding. In contrast to the relative stability of colonic microbiota, the human small intestinal microbiota biomass and its sub-strain composition can be highly dynamic.


Inhibition of peptide initiation by a low molecular weight RNA from rabbit reticulocytes.
A heat-stable inhibitor of protein synthesis has been isolated from the postribosomal supernatant of rabbit reticulocytes. Its activity is not susceptible to protease treatment but is destroyed by incubation with alkali. Inhibitory activity can be quantitatively recovered in the aqueous phase after phenol extraction and has the ultraviolet absorption spectrum of a nucleic acid. It is concluded that the inhibitor is RNA. The inhibitory activity sediments in the range of 3 S, but it has not been demonstrated whether the inhibitor RNA is a single molecular species. The inhibitory RNA does not affect peptide elongation but rather blocks a step of peptide initiation. It does not interfere with the formation of the ternary complex between initiation factor 2, GTP, and methionyl-tRNAMetf and does not activate a protein kinase phosphorylating initiation factor 2. The inhibitory RNA appears to be a novel type of RNA that inhibits polypeptide initiation at a step involving ribosomal subunits.


Trunk endurance, posterior chain flexibility, and previous history of musculoskeletal pain predict overuse low back and lower extremity injury: a prospective cohort study of 545 Navy Cadets.
To investigate predictors of low back and lower extremity musculoskeletal injury in a cohort of Naval cadets. Prospective Cohort Study METHODS: 545 Naval cadets (Males, n = 394, 72%) were followed-up over eight months. Nine variables were investigated as predictors: history of musculoskeletal symptoms in the last 12 months, ankle dorsiflexion range of motion, sit and reach test, isometric hip abduction and external rotation strength, alignment during the single leg squat test, single leg hop test for distance, prone plank and side plank tests. All injuries that required medical attention were registered. Predictive associations were examined using univariable and multivariable logistic regression analyses. The incidence of all injuries was 7%. Cadets who failed the 60-second plank test (OR = 3.3; 95% CI, 1.2-8.8, P = 0.04), had ≤18 cm in the sit and reach test (OR = 4.0; 95% CI, 1.4-11.2, P = 0.01), or reported pain in the last 12 months in two or more body regions (OR = 2.7; 95% CI, 1.02-7.3, P = 0.04), had greater odds of sustaining an overuse injury. No predictors were identified for acute injuries. Decreased trunk endurance on the prone plank test, reduced posterior chain flexibility on the sit and reach test, and a history of pain reported in two or more sites in the last 12 months were predictors of overuse injuries in Naval cadets. Assessment and intervention of these modifiable risk factors may be clinically relevant in injury screening and prevention.


Selective recognition of oxalate in water: effect of pH on binding strength and sensing mechanisms.
Bicyclic receptors bearing anthracene as a strap were designed for selective oxalate binding in a buffered aqueous solution. The receptors were found to possess two mechanisms of fluorescence response depending on the pH of a buffered solution. Receptor 2 binds oxalate at pH 6.2 showing a 10-fold fluorescence enhancement and a two orders of magnitude selectivity over other anions.


Molecular characterization of the rat insulin enhancer-binding complex 3b2. Cloning of a binding factor with putative helicase motifs.
Cell-specific expression of the rat insulin II gene is in part mediated through an element located in the 5'-flanking region. The element, termed RIPE3b (-126 to -101), confers beta-cell-specific expression in conjunction with an adjacent element RIPE3a (-110 to -86). Here we report the characterization of one of the RIPE3b-binding complexes, 3b2. UV cross-linking analysis demonstrated that it is composed of at least three polypeptides: p58, p62, and p110. Furthermore, a cDNA was isolated via expression screening for binding to RIPE3b. Sequence analysis reveals that the encoded protein, designated Rip-1, possessed putative helicase motifs and a potential transcription activation domain. Overexpression of Rip-1 in cells greatly enhances the 3b2 binding complex, suggesting that Rip-1 is involved in the binding of 3b2.


Coordinate synthesis of azurin I and copper nitrite reductase in Alcaligenes xylosoxidans during denitrification.
The denitrifying bacterium Alcaligenes xylosoxidans synthesises two azurins (Az), which are termed Az I and Az 2. Both function as effective electron donors to copper nitrite reductase (NiR) in vitro. As a first step towards identifying the physiological relevance of these electron transfer proteins in the denitrification process, the gene (azuA) encoding Az I was characterised and its expression with respect to denitrification determined. We show that the azuA gene from A. xylosoxidans is monocistronic and its expression is increased when cells are grown under denitrifying conditions in the presence of nitrate or nitrite. The expression pattern of azuA was similar, though not identical, to that of the monocistronic nirK gene, which encodes copper NiR, and is in accord with both gene products being synthesised when the bacterium denitrifies. Recombinant Az I was exported to the periplasm of the heterologous host Escherichia coli, was synthesised at very high levels (80 mg purified protein per litre) and was fully loaded with copper. Electron donation from reduced recombinant Az to NiR was indistinguishable from the activity determined with the native protein. Taken together, these findings indicate that in A. xylosoxidans azuA expression is coordinated with denitrification and recombinant Az I is processed and matured in the periplasm of E. coli in the same way it is in A. xylosoxidans.


A comparison of short- and long-term outcomes for balloon angioplasty and coronary stent placement.
We sought to compare patient outcomes for coronary stent placement and balloon angioplasty. Since 1994, the number of patients treated only with balloon angioplasty has decreased nationally, whereas the use of coronary stents as an alternative has grown tremendously. The objectives of this study were to compare short- and long-term survival and subsequent revascularization rates for patients undergoing single-vessel balloon angioplasty and coronary stent placement. New York's Coronary Angioplasty Registry was used to identify New York patients undergoing either balloon angioplasty or stent placement between July 1, 1994, and December 31, 1996. Statistical models were used to compare risk-adjusted short- and long-term survival and subsequent coronary artery bypass graft surgery (CABG) and percutaneous coronary interventions (PCIs). No significant differences were found in adjusted in-patient mortality, but patients who had balloon angioplasty were, on average, 1.36 times more likely to have died at any time during the two-year period after the index procedure (p = 0.003). The adjusted in-patient CABG rate was significantly higher for balloon angioplasty (2.72% vs. 1.66%, p<0.0001), and the adjusted two-year CABG rate was also significantly higher for balloon angioplasty (10.81% vs. 7.25%, p<0.001). The adjusted two-year rate for subsequent PCIs was also significantly higher for balloon angioplasty (19.6% vs. 14.3%, p<0.0001). Although measures were taken to eliminate or minimize the effect of selection bias, it should be noted that patients with stents were healthier at hospital admission than patients who had balloon angioplasty. Stent placement is associated with significantly lower risk-adjusted long-term mortality, CABG and subsequent PCI rates, as compared with balloon angioplasty.


Small molecule-assisted assembly of multifunctional ceria nanozymes for synergistic treatment of atherosclerosis.
Considering that intravascular reactive oxygen species (ROS) and inflammation are two characteristic features of the atherosclerotic microenvironment, developing an appropriate strategy to treat atherosclerosis by synergistically regulating ROS and inflammation has attracted widespread attention. Herein, a special molecule, zoledronic acid, containing imidazole and bisphosphonate groups, was selected for the first time to assist the assembly of cerium ions and produce functionalized ceria-zoledronic acid nanocomposites (CZ NCs). It not only serves as a new carrier for different kinds of drugs (e.g. probucol, PB) but also exerts an efficient multienzyme activity to achieve collaborative therapy. More importantly, platelet membrane-coated biomimetic nanoplatform (PCZ@PB NCs) specifically accumulate at inflammatory atherosclerotic lesions, synergistically regulate ROS levels and inflammation, and efficiently inhibit foam cell formation. This novel assembly method can also be applied in the treatment of many other diseases associated with oxidative stress and inflammation.


Malignant tumours of the spermatic cord with contribution of a rare case of lymphosarcoma.
A detailed survey is given to the problem of malignant tumours of the spermatic cord. The authors present their own case of lymphosarcoma of the spermatic cord. They found only three cases of lymphosarcoma of the spermatic cord in the accessible literature. In the treatment of these malignant tumours they prefer to make radical operation - hemicastration with total extirpation of the spermatic cord - followed by radiotherapy.


Pharmacokinetics and pharmacodynamics of Phor21-betaCG(ala), a lytic peptide conjugate.
Phor21-betaCG(ala), a 36-amino acid peptide comprised of a lytic peptide (Phor21) conjugated to a modified 15-amino acid segment of the beta-chain of chorionic gonadotropin (betaCG(ala)), selectively kills cancer cells that over-express luteinizing hormone/chorionic gonadotropin (LH/CG) receptors by disrupting cellular membrane structure. These studies were designed to further characterize its in-vitro inhibition and in-vivo destruction of prostate cancer cells, biostability and pharmacokinetics to determine its pharmacokinetic and pharmacodynamic profile. Inhibitory effects of Phor21-betaCG(ala) were tested in PC-3 and Caco-2 cells as well as in nude mice bearing PC-3 cells transfected with the luciferase gene (PC-3.luc). Plasma stability, protease hydrolysis and pharmacokinetics of Phor21-betaCG(ala) were measured by using liquid chromatography mass spectrometry (LC/MS/MS). Phor21-betaCG(ala) selectively inhibited proliferation in-vitro and in-vivo metastases of PC-3 cells. Phor21-betaCG(ala) was relatively stable in mouse, rat, dog and human plasma. Its degradation was partially due to protease hydrolysis and thermodynamic catalysis. Intravenous administration of Phor21-betaCG(ala) showed its blood C(max) and AUC(0-->infinity) around the in-vitro effective levels. In the tested rodents, Phor21-betaCG(ala) displayed a moderate volume of distribution at steady state (Vd(ss)) and slow clearance (Cl) in the rodents. In conclusion, Phor21-betaCG(ala) displayed promising in-vitro and in-vivo anti-cancer activity with favourable pharmacokinetics, and may offer a novel approach to metastatic cancer chemotherapy.


Vitamin A deficiency alters the pulmonary parenchymal elastic modulus and elastic fiber concentration in rats.
Bronchial hyperreactivity is influenced by properties of the conducting airways and the surrounding pulmonary parenchyma, which is tethered to the conducting airways. Vitamin A deficiency (VAD) is associated with an increase in airway hyperreactivity in rats and a decrease in the volume density of alveoli and alveolar ducts. To better define the effects of VAD on the mechanical properties of the pulmonary parenchyma, we have studied the elastic modulus, elastic fibers and elastin gene-expression in rats with VAD, which were supplemented with retinoic acid (RA) or remained unsupplemented. Parenchymal mechanics were assessed before and after the administration of carbamylcholine (CCh) by determining the bulk and shear moduli of lungs that that had been removed from rats which were vitamin A deficient or received a control diet. Elastin mRNA and insoluble elastin were quantified and elastic fibers were enumerated using morphometric methods. Additional morphometric studies were performed to assess airway contraction and alveolar distortion. VAD produced an approximately 2-fold augmentation in the CCh-mediated increase of the bulk modulus and a significant dampening of the increase in shear modulus after CCh, compared to vitamin A sufficient (VAS) rats. RA-supplementation for up to 21 days did not reverse the effects of VAD on the elastic modulus. VAD was also associated with a decrease in the concentration of parenchymal elastic fibers, which was restored and was accompanied by an increase in tropoelastin mRNA after 12 days of RA-treatment. Lung elastin, which was resistant to 0.1 N NaOH at 98 degrees, decreased in VAD and was not restored after 21 days of RA-treatment. Alterations in parenchymal mechanics and structure contribute to bronchial hyperreactivity in VAD but they are not reversed by RA-treatment, in contrast to the VAD-related alterations in the airways.