The inhibitory effect of Binens bipinnata L. extract on U14 tumour in mice.
The objective of this paper was to study the in vitro and in vivo inhibitory effect of Bidens bipinnata L. extract on growth of cervical carcinoma U14 cells. MTT method was used to determine the inhibitory effect of Bidens bipinnata L. extract on U14 tumour cells, and the effects of Bidens bipinnata L. extract on inhibition rate of solid tumour and life prolongation rate of ascites tumour were observed through the establishment of two animal models of mouse cervical carcinoma U14 solid tumour and ascites tumour. In the in vitro MTT assay, the inhibition rate gradually increased with the increase of dose of Bidens bipinnata L. and the extension of time. Its inhibition rate was 70.44% at a concentration of 80µg/L. Solid tumour inhibition rates in the high- and low-dose groups and cisplatin group were 49.13%, 2.26% and 75.72% respectively; life prolongation rates in each ascites tumour group were 63.63%, 34.86% and 87.34% respectively. The Bidens bipinnata L. extract has a certain inhibitory effect on growth of mouse cervical carcinoma U14.


[Reoperations for early recurrent occlusions following femoropopliteal and femorocrural bypasses].
We analyse the early results of 333 patients who had been operated on because of femoropopliteal occlusions between 1996 and 2000. Most interventions (90.4%) were below knee reconstructions. The rate of crural bypasses was high (40.5%). We examined whether the length and type of the graft influenced the outcome of the primary operation. If below knee bypass was necessary in every operation autologous grafts were preferred either partially or entirely (saphenous vein or arm vein). The number of reocclusions and amputations was significantly higher if the distal anastomosis involved the crural arteries (p < 0.02), or the graft was not autologous (p < 0.01). There was no statistical difference between early results of saphena and arm vein bypasses (p = 0.2). Thirty-six reoperations were performed for early graft failures. Either the patient's general condition or local findings did not allow reoperations in 17 patients with occluded graft, they were treated conservatively. Nine patients died after surgery (2.7%). In the postoperative period 21 major amputations were necessary (6.3%), in six cases the graft was patient. After reoperations 7 patients needed amputations (19.4%), in the 17 patients not reoperated on the second time, 8 amputations were necessary (47%), the difference is significant (p < 0.05). We are convinced about the importance of urgent reoperation in case of early graft occlusion. If the run-off to the distal arteries was doubtful intraoperative angiography was performed. When distal extension of the operation was necessary we tried to use autologous grafts. The amputation rate was significantly lower after reoperations if the cause of graft occlusion was found and corrected compared to simple thrombectomies (p < 0.05).


Ants' navigation in an unfamiliar environment is influenced by their experience of a familiar route.
When displaced experimentally from a food source (feeder) to unfamiliar terrain, ants run off a portion of the homeward vector or its entirety, depending on species and conditions, and then search systematically, turning in loops of ever increasing size. The Australian desert ant Melophorus bagoti runs off a smaller portion of its vector if the test site is more dissimilar to its nest area. Here we manipulated familiarity with the training route between a feeder and the ants' nest to examine its effects when the ants were displaced to a distant site from the feeder. Naïve ants that arrived at an experimentally provided feeder for the first time were compared with experienced ants that had travelled the route for two days. At the unfamiliar test site, naïve ants ran off a longer portion of their vector from path integration than did experienced ants. Naïve ants also spread out in their systematic search slower than did experienced ants. We conclude that as ants learn the views encountered on their familiar route better, they identify more readily unfamiliar views. A scene distant from their nest area may not look as unfamiliar to a naïve ant as it does to an experienced ant.


Effects of polyunsaturated fatty acids on vincristine-resistance in human neuroblastoma cells.
PUFAs such as GLA (n-6) or DHA (n-3) were shown to exert antitumor activity on a human neuroblastoma cell line (NCG) and its VCR-resistant subline (NCG/VCR1, 8.6-fold resistant to VCR) in vitro. The NCG/VCR1 line had markedly decreased intracellular accumulation of [3H]-VCR and an accelerated drug efflux, compared to the NCG. The cytotoxic activity of PUFAs was correlated with the generation of MDA-like products in these cells. When VCR was added simultaneously with GLA or DHA to culture medium, the cytotoxic effect of VCR was about 2-fold enhanced, accompanied by about 1.5-2.0-fold increase of intracellular [3H]-VCR in both cell lines. Fatty acid analysis of membrane phospholipids of the NCG and the NCG/VCR1 cells treated with GLA or DHA showed an increased total PUFAs and SFAs, associated with markedly decreased total MUFAs and an inverted PUFAs/MUFAs ratio. Such phospholipid modification may have altered the membrane physical properties and enhanced the VCR cytotoxicity by increasing intracellular VCR accumulation; however, these PUFAs did not affect the drug efflux sufficiently enough to overcome completely the VCR resistance in the NCG/VCR1 cells. These results indicate that PUFAs partially alleviate the VCR-resistance in human neuroblastoma cells, not directly acting on VCR-resistance mechanism(s).


Amitriptyline and Sexual Function: A Systematic Review Updated for Sexual Health Practice.
Amitriptyline is an old drug but is still prevalently used as the first-line treatment for a variety of common diseases. Surprisingly, knowledge of sexual risks with amitriptyline comes from only one clinical trial and several case reports from three decades ago. In the current study, a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) related to amitriptyline and sexual dysfunction (SD) was performed. The frequency, gender-difference, types, disease-specificity and time course of SD, and the relationship between SD and nonsexual adversity were studied. A total of 14 publications, including 8 qualified randomized clinical trials, were eligible. The frequency of SD in overall, male and female patients was 5.7, 11.9 and 1.7%, respectively. SD was six-fold higher in men than women. The frequency of SD was 6.9% in depressive patients compared with 0.8% in non-depressive patients ( p = .008), and gradually decreased at 8 weeks after treatment ( p = .02). Amitriptyline impacted arousal and libido more than orgasm and ejaculation in male patients but mainly libido in female patients. SD was significantly correlated with insomnia linearly whereas somnolence and nausea dually. Therefore, amitriptyline-associated SD mainly occurs in depressive and male patients, disturbs each phase of the sexual response cycle in men but mainly libido in women, gradually decreases under long-term treatment, and can be predicted by the co-existence of insomnia, somnolence or nausea during treatment. Clinicians should caution and tailor the gender and disease vulnerability of amitriptyline in their practice.


Crystal structure of cyclic tris-(ferrocene-1,1'-di-yl).
The mol-ecular structure of the trinuclear title compound, [Fe3(C10H8)3] {systematic name: tris-[μ-(η(5):η(5))-1,1'-bi-cyclo-penta-dien-yl]tri-iron(II)}, consists of three ferrocene subunits (each with an eclipsed conformation) that are condensed via C-C bonds of the fulvalene moieties into a cyclic trimer. The angles between the planes of the cyclo-penta-dienyl (Cp) rings within the three fulvalene moieties are 76.1 (3), 80.9 (3) and 81.7 (3)°. In the crystal, C-H⋯π inter-actions between neighbouring mol-ecules lead to the cohesion of the structure.


Simulated flying altitude and performance of continuous positive airway pressure devices.
Continuous positive airway pressure (CPAP) is used in air ambulances to treat patients with impaired oxygenation. Differences in mechanical principles between CPAP devices may affect their performance at different ambient air pressures, as will occur in an air ambulance during flight. Two different CPAP systems, a threshold resistor device and a flow resistor device, at settings of 5 and 10 cm H₂O were examined. Static pressure, static airflow, and pressure during simulated breathing were measured at ground level and at three different altitudes [2400 m (7874 ft), 3000 m (9843 ft), and 10,700 m (35,105 ft)]. When altitude increased, the performance of the two CPAP systems differed during both static and simulated breathing pressure measurements. With the threshold resistor CPAP, measured pressure levels were close to the preset CPAP level. Static pressure decreased 0.71 ± 0.35 cm H₂O at CPAP 10 cm H₂O compared to ground level and 35,105 ft (10,700 m). With the flow resistor CPAP, as the altitude increased, CPAP produced pressure levels increased. At 35,105 ft (10,700 m), the increase was 5.13 ± 0.33 cm H₂O at CPAP 10 cm H₂O. The velocity of airflow through the flow resistor CPAP device is strongly influenced by reduced ambient air pressure, leading to a higher delivered CPAP effect than the preset CPAP level. Threshold resistor CPAP devices seem to have robust performance regardless of altitude. Thus, the threshold resistor CPAP device is probably more appropriate for CPAP treatment in an air ambulance cabin, where ambient pressure will vary during patient transport.


Mixed methods systematic review of the literature base exploring working alliance in the chiropractic profession.
The construct of working alliance has been used to operationalise the patient-clinician relationship. Research evidence from the rehabilitation literature has established an association between the construct and several patient outcomes. The aim of this systematic literature review was to study working alliance in the chiropractic discipline. This review followed a mixed method systematic review methodology: EBSCO (The Allied and Complementary Medicine Database), EBSCO (MEDLINE), EBSCO PsycINFO, Web of Science Core Collection, Chiro index, and grey literature were searched for quantitative, qualitative, and mixed methods studies on 17th March 2021. Qualitative appraisal was conducted using the Mixed Methods Appraisal Tool, version 2018. The qualitative component was synthesised via thematic synthesis and explored patients' and chiropractors' perceptions of the nature and role of working alliance. The quantitative component was synthesised via narrative synthesis to examine how the construct has been measured in research and what its effect on clinical outcomes and patient satisfaction is. The findings were integrated in the discussion section. Thirty studies were included. The qualitative component found that both patients and chiropractors consider working alliance as a key factor in the treatment journey. The findings illustrated that the construct includes the bond between a patient and a chiropractor which is underpinned by trust and attentiveness to patients' needs, values and preferences. Qualitative data also suggested that strong working alliance has the potential to improve patients' adherence to treatment and that it is characterised by ongoing negotiation of expectations about the goals of care and the tasks involved in the treatment plan. The quantitative component highlighted that even though working alliance is relevant to the chiropractic discipline, very few studies have quantitatively measured the construct and its effect. The findings of this review emphasise the subjective importance of working alliance in the chiropractic clinical encounter. However, there were not enough homogenous studies measuring the effect of working alliance on clinical outcomes and patient satisfaction to conduct a meta-analysis. Future research should focus on evaluating potential direct and mediated effects on patient outcomes.


[Respiratory failure in pulmonary tuberculosis sequelae].
Patients with respiratory failure based on pulmonary tuberculosis sequelae are second in number among some fifty thousand patients receiving home oxygen therapy in Japan. Its 5 year survival rate is 47% in man and 56% in woman. The prognosis is better in woman than in man and may be dependent, at least partially, on younger age in woman. The influence of arterial blood gases on the prognosis is quite different between tuberculosis sequelae and chronic obstructive pulmonary disease: PaO2 scarcely influence the prognosis while higher PaCO2 is beneficial for tuberculosis sequelae. Patients with hypercapnia have better nutrition as estimated by serum albumin and this fact may cause the longer survival. Pulmonary hypertension is more frequently observed but is less strongly related to arterial blood gases and ventilatory function in tuberculosis sequelae than chronic obstructive pulmonary disease.


Invited review: technical solutions for analysis of milk constituents and abnormal milk.
Information about constituents of milk and visual alterations can be used for management support in improving mastitis detection, monitoring fertility and reproduction, and adapting individual diets. Numerous sensors that gather this information are either currently available or in development. Nevertheless, there is still a need to adapt these sensors to special requirements of on-farm utilization such as robustness, calibration and maintenance, costs, operating cycle duration, and high sensitivity and specificity. This paper provides an overview of available sensors, ongoing research, and areas of application for analysis of milk constituents. Currently, the recognition of abnormal milk and the control of udder health is achieved mainly by recording electrical conductivity and changes in milk color. Further indicators of inflammation were recently investigated either to satisfy the high specificity necessary for automatic separation of milk or to create reliable alarm lists. Likewise, milk composition, especially fat:protein ratio, milk urea nitrogen content, and concentration of ketone bodies, provides suitable information about energy and protein supply, roughage fraction in the diet, and metabolic imbalances in dairy cows. In this regard, future prospects are to use frequent on-farm measurements of milk constituents for short-term automatic nutritional management. Finally, measuring progesterone concentration in milk helps farmers detect ovulation, pregnancy, and infertility. Monitoring systems for on-farm or on-line analysis of milk composition are mostly based on infrared spectroscopy, optical methods, biosensors, or sensor arrays. Their calibration and maintenance requirements have to be checked thoroughly before they can be regularly implemented on dairy farms.


Thermal Imaging of Root Caries In Vivo.
Improved methods are needed to assess the structure and activity of lesions on root surfaces in order to improve clinical decision making. Conventional visual and tactile methods for assessing lesion activity are not reliable, and the clinician is often unable to evaluate if the lesion is progressing or has remineralized. An important marker of an arrested lesion is a highly mineralized surface zone that forms when mineral is deposited in the outer layer of the lesion. In vitro studies have shown that a mineralized surface zone influences the kinetics of water evaporation and the surface temperature while drying. Temperature changes can be monitored by measuring the thermal emission with thermal imaging. Studies have also shown that the depth and severity of demineralization and the thickness of the highly mineralized transparent surface zone on arrested lesions can be measured nondestructively with optical coherence tomography (OCT). Thermal imaging at 8-µm to 13-µm wavelengths was completed on 30 test subjects with a suspected active root caries lesion by monitoring thermal emission from the tooth surfaces during 30 s of air drying. Lesions were also evaluated using cross-polarization OCT (CP-OCT) during lesion dehydration to identify transparent surface zones indicative of arrested lesions and determine if shrinkage occurred during drying. The overall thermal emission recorded during drying was significantly different (P < 0.001) when comparing sound tooth surfaces, lesion areas identified as arrested, and lesion areas identified as active, demonstrating that thermal imaging is a promising approach for the clinical assessment of lesion activity on root surfaces. Ten of the lesions in this study had distinct areas with transparent surface zones that were visible in CP-OCT images. Shrinkage was detected with CP-OCT during drying for 12 lesions. This study confirms that these novel approaches for assessing lesion activity on root surfaces can be implemented in vivo.


[Advances and limitations of liver transplantation in Germany].
Orthotopic liver transplantation (OLT) is now an established therapy for end stage liver disease as well as acute liver failure. Improvements in surgical techniques, meticolous selection of transplant candidates and advances in immunosuppression have markedly increased patient and graft survial. The demand for organ grafts has continuously increased. Living donor organ transplantation omits the problem of organ shortage with prolonged waiting times for OLT and the likelihood of disease progression especially in tumor patients. Advanced liver disease related to chronic viral hepatitis is one of the primary indications for OLT worldwide. Combination therapy with hepatitis B immunoglobulin and lamivudine has been widely adopted as an effective prophylactic treatment regimen against recurrent HBV infection. Reinfection of the allograft is obligate in viremic post transplant patients with HCV infection. However the use of pegylated interferon in combination with ribavirin holds promise for delaying rapid progression of HCV infection in the allograft and the need for retransplantation. Recurrence of PBC, PSC and autoimmune hepatitis affects between 20 % and 30 % grafts at 10 years but appears to have little impact on long-term graft function and survival. In patients with hepatocellular carcinoma fulfilling strict selection criteria for OLT, 5 year survival rates of approximately 75% have been reported.


[Fibrin agglutination of thyroid gland cysts after fine needle puncture].
Tolerance to and efficacy of a fibrin adhesive injected into thyroid cysts after their evacuation by fine needle puncture was investigated in 60 consecutive patients (52 women, 8 men; mean age 50 [18-82] years) with solitary thyroid cysts. The patients were randomly separated into two groups of 30 each. In group A patients the cysts were completely emptied by fine needle puncture under ultrasound control. In group B patients a fibrin adhesive (0.8-1.4 ml) was subsequently injected. 25 of 30 patients in group A had recurring cysts, twelve of which were larger than the original one. There were 13 recurrences in group B (P < 0.005), but only one was of a larger volume. In each group three patients reported a brief period of pain after the evacuation procedure. The described technique has proven to be reliable and well tolerated. Cysts obliterated by fibrin adhesive recurred less frequently and had a smaller volume than those only evacuated by needle puncture.


A compact, versatile low-energy electron beam ion source.
A new compact Electron Beam Ion Source, the Dresden EBIT-LE, is introduced as an ion source working at low electron beam energies. The EBIT-LE operates at an electron energy ranging from 100 eV to some keV and can easily be modified to an EBIT also working at higher electron beam energies of up to 15 keV. We show that, depending on the electron beam energy, electron beam currents from a few mA in the low-energy regime up to about 40 mA in the high-energy regime are possible. Technical solutions as well as first experimental results of the EBIT-LE are presented. In ion extraction experiments, a stable production of low and intermediate charged ions at electron beam energies below 2 keV is demonstrated. Furthermore, X-ray spectroscopy measurements confirm the possibility of using the machine as a source of X-rays from ions excited at low electron energies.


alpha-Interferon therapy for HBV-related glomerulonephritis.
We report a case of a patient with hepatitis B virus (HBV)-related membranous glomerulonephritis (MGN) who showed improvement after interferon-alpha (IFN-alpha) therapy. A 35-year-old man with nephrotic syndrome and HBV antigens received a 24-week course of IFN-alpha. At the end of therapy there was an elevation in the level of plasma aminotransferase and an increase in proteinuria, which were followed by antigen/antibody seroconversion. This "flare-up" before seroconversion suggests an increase in disease activity in the liver and kidney, demonstrating in vivo HBV involvement in MGN.


Discrimination of Three Panax Species Based on Differences in Volatile Organic Compounds Using a Static Headspace GC-MS-Based Metabolomics Approach.
Panax ginseng (Asian ginseng), Panax quinquefolium (American ginseng) and Panax notoginseng (notoginseng) are highly valuable tonic herbs derived from the Panax genus that have similar morphological appearances and odors but different pharmacological activities and clinical indications. Thus, the authentication of these three Panax species is crucial for ensuring the quality, safety and efficacy of medication. In the present study, a static headspace gas chromatography - mass spectrometry (GC-MS) followed by a multivariate statistical analysis was developed to globally characterize the volatile organic compound (VOC) profiles in P. ginseng, P. quinquefolium, and P. notoginseng, and subsequently to discover differentiating chemical markers. Under the optimized conditions, the headspace VOCs of a total of 49 batches of Panax herbs derived from the three Panax species were profiled, and the dataset of sample code, [Formula: see text]-m/z pair and ion intensity was processed by unsupervised principal component analysis (PCA) and by supervised partial least squared discriminant analysis (PLS-DA) to comprehensively compare the chemical differences in Panax across the species. The results demonstrated that Panax herbs derived from three species possess obviously diverse chemical characteristics of VOCs, PCA, and PLS-DA. According to their VOC profiles, 49 tested samples could be clearly differentiated according to species. Chemomarker 1, 2, and 4 might be used as unique chemical markers of P. ginseng, P. notoginseng and P. quinquefolium, respectively. Our findings indicate that static headspace GC-MS-based VOC profiling, combined with multivariate statistical analysis, provide a reliable tool to discriminate between the three Panax species and to identify their differentiation markers, which will be helpful for ensuring their quality, safety and efficacy.


Clinical application of a new hemostatic material using mussel-inspired catecholamine hemostat: A pilot study.
This study aimed to evaluate clinical application of InnoSEAL Plus (a mussel-inspired catecholamine hemostat) as a new hemostatic material for humans. Patients treated with topical hemostatic patches after liver resection were enrolled. They were divided into an experimental group (InnoSEAL Plus group) and two control groups (TachoSil® group and Surgicel Fibrillar® group) for efficacy evaluation. A total of 15 patients were enrolled. Each group had five patients. The 3-minute hemostasis success rate was 80.0% (4/5 patients) in the InnoSEAL Plus group, 80.0% (4/5 patients) in the TachoSil® group, and 40.0% (2/5 patients) in the Surgicel Fibrillar® group, showing no significant difference in the success rate among these groups (p > 0.05). All three groups exhibited 100% success rate for 10-minute hemostasis. Both InnoSEAL Plus and TachoSil® groups had one patient developing adverse events, which were treated easily with drug administrations. InnoSEAL Plus is expected to be functionally not inferior to other conventional hemostatic agents. However, it is necessary to confirm this through multicenter prospective studies in the future.


Effects of Mild Water Stress and Diurnal Changes in Temperature and Humidity on the Stable Oxygen and Hydrogen Isotopic Composition of Leaf Water in Cornus stolonifera L.
In this paper we make comparisons between the observed stable isotopic composition of leaf water and the predictions of the Craig-Gordon model of isotopic enrichment when plants (Cornus stolonifera L.) were exposed to natural, diurnal changes in temperature and humidity in a glasshouse. In addition, we determined the effects of mild water stress on the isotopic composition of leaf water. The model predicted different patterns of diurnal change for the oxygen and hydrogen isotopic composition of leaf water. The observed leaf water isotopic composition followed qualitatively similar patterns of diurnal change to those predicted by the model. At midday, however, the model always predicted a higher degree of heavy isotope enrichment than was actually observed in leaves. There was no effect of mild water stress on the hydrogen isotopic composition of leaf water. For the oxygen isotopic composition of leaf water, there was either no significant difference between control and water-stressed plants or the stressed plants had lower delta(18)O values, despite the enriched stem water isotopic composition observed for the stressed plants.


[Spinal localization of Gorham's syndrome. Case report].
The authors report a case of massive osteolysis of the spine in an eighteen years old boy presenting a T9 collapse without neurological symptoms associated to a right chylothorax which disappeared after 5 days of drainage. MRI showed an increased signal on T1 and T2 weighted sequences. An orthopaedic treatment with a cast was decided as a first attempt. Because on increasing pain and kyphosis, surgery was considered, with posterior segmental fixation with Hartshill rectangle from T4 to L5. The result was satisfactory after 6 months of follow-UP. The vanished bone disease is a rare affection of unknown aetiology. 132 cases were published, 20 with spinal localization. The prognosis is uncertain with a mortality of 16 per cent. The treatment of bony lesions is difficult. Spinal localizations are best treated by segmental fixation extended on normal vertebrae.


Evaluation of in vivo and in vitro toxicological and genotoxic potential of aluminum chloride.
Aluminum and its compounds are common contaminants of water and food, as well as medications and cosmetics. The wide distribution of the element facilitates the demand for detailed studies of its biological and toxicological effects. This work aimed to evaluate the possible genotoxic and toxic activity resulting from in vivo and in vitro exposure to Al. For in vivo analysis, 40 Swiss mice were used, various concentrations of hydrated aluminum chloride were administered orally. They were analyzed for possible genic activity and metal cytotoxicity using a micronucleus test (MN), and for toxicity through histopathological evaluation of the extracted organs. For in vitro analysis, lymphocytes from the peripheral blood of 3 healthy donors were used. These cells were exposed to the same chemical agent in various concentrations. In vivo study revealed a significant increase in the number of MN in all Al concentrations. Furthermore, significant alterations in all the organs evaluated were verified by the presence of irreversible lesions (such as necrosis). Corroborating these findings, a significant increase in the quantity of MN in all concentrations with lymphocytes in vitro. In light of this, we suggest that this metal presents genotoxic potential and is potentially a cause of pathological disorders.


Composition and Stability of Plasma Polymer Films Exhibiting Vertical Chemical Gradients.
Controlling the balance between stability and functional group density in grown plasma polymer films is the key to diverse applications such as drug release, tissue-engineered implants, filtration, contact lenses, microfluidics, electrodes, sensors, etc. Highly functional plasma polymer films typically show a limited stability in air or aqueous environments due to mechanisms like molecular reorganization, oxidation, and hydrolysis. Stabilization is achieved by enhancing cross-linking at the cost of the terminal functional groups such as -OH and -COOH, but also -NH2, etc. To overcome such limitations, a structural and chemical gradient was introduced perpendicular to the surface plane; this vertical gradient structure is composed of a highly cross-linked base layer, gradually changing into a more functional nanoscaled surface termination layer. This was achieved using CO2/C2H4 discharges with decreasing power input and increasing gas ratio during plasma polymer deposition. The aging behavior and stability of such oxygen-functional vertical gradient nanostructures were studied in air and in different aqueous environments (acidic pH 4, neutral pH ≈ 6.2, and basic pH 10). Complementary characterization methods were used, including angle-resolved X-ray photoelectron spectroscopy (ARXPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) as well as water contact angle (WCA) measurements. It was found that in air, the vertical gradient films are stabilized over a period of months. The same gradients also appear to be stable in neutral water over a period of at least 1 week. Changes in the oxygen depth profiles have been observed at pH 4 and pH 10 showing structural and chemical aging effects on different time scales. The use of vertical gradient plasma polymer nanofilms thus represents a novel approach providing enhanced stability, thus opening the possibility for new applications.


Phentolamine Eye Drops Reverse Pharmacologically Induced Mydriasis in a Randomized Phase 2b Trial.
After a dilated eye examination, many patients experience symptoms of prolonged light sensitivity, blurred vision, and cycloplegia associated with pharmacological mydriasis. Phentolamine mesylate ophthalmic solution (PMOS) may expedite the reversal of mydriasis in patients, potentially facilitating return to functional vision and reducing barriers to obtaining dilated eye examinations. The protracted reversal time after pharmacologically induced pupil dilation impairs vision. We tested the hypothesis that PMOS rapidly reduces pupil diameter in this acute indication. In this double-masked placebo-controlled, randomized, two-arm crossover phase 2b trial, we evaluated the effects of one drop of 1% PMOS applied bilaterally in subjects who had their pupils dilated by one of two common mydriatic agents: 2.5% phenylephrine or 1% tropicamide. End points included change in pupil diameter, percent of subjects returning to baseline pupil diameter, and accommodative function at multiple time points. Thirty-one subjects completed the study (15 dilated with phenylephrine and 16 with tropicamide). Change in pupil diameter from baseline at 2 hours after maximal dilation with 1% PMOS was -1.69 mm and was significantly greater in magnitude compared with placebo for every time point beyond 30 minutes (P < .05). At 2 hours, a greater percentage of study eyes given 1% PMOS returned to baseline pupil diameter compared with placebo (29 vs. 13%, P = .03), which was this also seen at 4 hours (P < .001). More subjects treated with PMOS in the tropicamide subgroup had at least one eye returning to baseline accommodative amplitude at 2 hours (63 vs. 38%, P = .01). There were no severe adverse events, with only mild to moderate conjunctival hyperemia that resolved in most patients by 6 hours. Phentolamine mesylate ophthalmic solution at 1% reversed medically induced pupil dilation more rapidly than placebo treatment regardless of which mydriatic was used (adrenergic agonists and cholinergic blockers) with a tolerable safety profile.


Monitoring adverse outcomes of surgery using administrative data.
In this article, we document a stabilization in adverse outcomes associated with hysterectomies, cholecystectomies, and prostatectomies performed between 1972-73 and 1982-83 in Manitoba, Canada. The proportion of surgery performed by high-volume surgeons and by surgical specialists increased slightly over the decade. However, given the already low rates of adverse outcomes, these changes did not translate into significant decreases in the postoperative mortality rate or in the rate of related hospital readmissions. Reducing the proportion of adverse outcomes would be facilitated by identifying institutions with poorer than expected outcomes.


Sources, Fluxes, and Sinks of Nitrogen during Early Reproductive Growth of Maize (Zea mays L.).
A study was designed to (a) identify sources and sinks of N in the maize (Zea mays L.) shoot, by estimating net N fluxes for each of seven parts of the shoot, (b) determine effects of N entering the plant upon fluxes of N absorbed before reproductive growth, and (c) determine the effects of the opaque-2 gene on N fluxes in the maize shoot during early reproductive growth. Plants of a maize hybrid (Pioneer 3369A) and its opaque-2 counterpart (Pioneer L3369) were grown in a greenhouse using nutrient solution/sand culture, with NO(3) (-) as the N source during the vegetative growth phase. Beginning at the time of pollination, the same nutrient regime was continued, except that some plants received no N, and others received 3.75 millimolar (15)N as NO(3) (-)-N.Stalk and leaves were found to be primary N sources for the grain, while shank, husk, and cob acted first as N sinks, then as N sources during reproductive growth. Net fluxes of N for each plant part were estimated by calculating the first derivatives of regression equations used to fit data for N contents of each plant part as functions of time. All parts of the shoot were sinks for exogenous N (absorbed after pollination). Thirty-six days after pollination, the grain contained 60% endogenous N (absorbed before pollination) when 3.75 millimolar NO(3) (-)-N was supplied after pollination. Rates of total N influx to the grain were identical whether or not N was supplied in the nutrient solution during reproductive growth. At 36 days after pollination, less N had accumulated in the grain of the opaque-2 genotype, but otherwise there were no differences in N contents or dry weights of the shoots due to the opaque-2 gene. Absence of N from the rooting medium significantly affected N fluxes throughout the shoot during reproductive growth, but there were no detectable effects of the opaque-2 gene on N fluxes in parts of the plant other than the grain.


Optimal trajectory for the basketball free throw.
Using a theoretical approach, we studied the basketball free throw as a function of angle, speed and spin at release. The ball was constrained to the sagittal plane bisecting the hoop and normal to the backboard, and was permitted to bounce and change spin on both backboard and hoop. Combinations of angle, speed and spin resulting in a successful shot were calculated analytically. Standard deviations for a shooter's angle and speed were used to predict the optimal trajectory for a specific position of release. An optimal trajectory was predicted which had an initial angle and speed of approximately 60 degrees and 7.3 m s(-1) respectively over the domain of spins (-2 to +2 m s(-1) surface speed; -16 to +16 rad s[1]). The effect of air resistance and the sagittal plane constraint on the predicted optimal trajectory were discussed and quantified. The optimal trajectory depended on both the anthropometric characteristics and accuracy of the shooter, but generally a high backspin with an angle and speed combination which sent the ball closer to the far rim of the basket than the near rim was advantageous. We provide recommendations for shooters as a function of the height of ball release.


Specialization on pollen or nectar in bumblebee foragers is not associated with ovary size, lipid reserves or sensory tuning.
Foraging specialization allows social insects to more efficiently exploit resources in their environment. Recent research on honeybees suggests that specialization on pollen or nectar among foragers is linked to reproductive physiology and sensory tuning (the Reproductive Ground-Plan Hypothesis; RGPH). However, our understanding of the underlying physiological relationships in non-Apis bees is still limited. Here we show that the bumblebee Bombus terrestris has specialist pollen and nectar foragers, and test whether foraging specialization in B. terrestris is linked to reproductive physiology, measured as ovarian activation. We show that neither ovary size, sensory sensitivity, measured through proboscis extension response (PER), or whole-body lipid stores differed between pollen foragers, nectar foragers, or generalist foragers. Body size also did not differ between any of these three forager groups. Non-foragers had significantly larger ovaries than foragers. This suggests that potentially reproductive individuals avoid foraging.


Foreign body in the oral cavity mimicking a benign connective tissue tumor.
Foreign bodies may be embedded in the oral cavity either by traumatic injury or iatrogenically. The commonly encountered iatrogenic foreign bodies are restorative materials like amalgam, obturation materials, broken instruments, needles, and impression materials. This paper describes an asymptomatic presentation of a foreign body in the oral mucosa which clinically appeared like a benign connective tissue tumor.


Thyroid autocrine factors: regulation of secretion of insulin-like growth factor binding proteins from sheep thyroid cells by autocrine basic fibroblast growth factor.
The mRNA for basic fibroblast growth factor has been detected in primary cultures of sheep thyroid cells. RNA species of 2.0 kb, 3.3 kb and 7.2 kb have been identified. The effects of this autocrine factor on the production of insulin-like growth factor binding proteins (IGFBPs) have been examined. bFGF enhanced the secretion of IGFBP-2 and, like epidermal growth factor (EGF) and the tumour promoting phorbol ester (TPA), induced the appearance of IGFBP-3. We conclude that bFGF is synthesized by sheep thyroid cells and has autocrine potential since it can regulate the secretion of other thyroid autocrine factors which, in turn, may regulate thyroid growth and function.


Weak organic acid stress triggers hyperphosphorylation of the yeast zinc-finger transcription factor War1 and dampens stress adaptation.
Exposure of Saccharomyces cerevisiae to weak organic acids such as sorbate, propionate, or benzoate rapidly induces the plasma membrane ABC transporter Pdr12, requiring the Zn(II)(2)Cys(6) zinc-finger transcription factor War1. Weak acid stress rapidly triggers War1 phosphorylation but its role for War1 function is not clear yet. Here, we provide new insights into sorbate-induced phosphorylation of War1. A War1 zinc-finger mutant is still hyperphosphorylated in response to sorbate stress, indicating that War1 phosphorylation occurs independently of DNA recruitment. To map and identify phosphoresidues, War1 purified from stressed and unstressed cells was subjected to semiquantitative phosphopeptide mass spectrometry analysis. Remarkably, we show that weak acid stress causes a dramatic hyperphosphorylation of several already prephosphorylated residues. WAR1 alleles harboring combinations of mutations identified phosphoresidues were generated, some of which display altered gel mobility. Certain mutational combinations almost completely abolish stress-induced gel-shift, suggesting alternative phosphorylation. Surprisingly, PDR12 expression levels are similar in these mutants, demonstrating that War1 phosphorylation is not required for PDR12 induction. Strikingly, absence of hyperphosphorylation in response to stress leads to a faster stress adaptation, suggesting that phosphorylation might play a role in stabilizing War1 activity on the promoter elements, hence changing the dynamics and kinetics of the stress response.


[Morphologic evaluation of the effectiveness of local immune reactions in gastric cancer].
Upon the analysis of 50 cases of cancer of the stomach, the authors compared the size and composition of stromal cellular infiltrate, the size of active vascular bed in the tumor, mitotic activity of the tumor cells, the severity of regression in adenocarcinomas and signet ring cell polymorphocellular carcinoma of the stomach. The authors established the necessity of a comprehensive investigation of the tumor parenchyma and specificities of parenchymal blood supply for determination of local immune response in the tumor in relation to its efficiency.


An electromyographic and kinematic study of the scapular stabilisers.
The scapular stabilisers, especially the actions of the force couples around the scapula, have an impact on the biomechanics of the scapula and the orientation of the glenoid. The aim of our study was to determine both the muscle activity and the correlation between the muscle activity ratio of the lower force couple (the serratus anterior lower fibres and the lower trapezius). This was a quantitative cross-sectional study. Muscle activity of the dominant serratus anterior lower fibres and the lower trapezius muscles was collected with surface electromyographic (EMG) sensors and an inertial motion capture system was used to measure the three-dimensional (3D) shoulder flexion in the sagittal plane and abduction in the frontal plane. Graph Pad 5 (Prism, San Diego, CA, USA) was used for the statistical analysis. The confidence level was set at 95% (p < 0.05). Sixteen men and women participated in our study, with a mean (standard deviation) age of 25.4 (± 4.6) years, weight of 80.2 (± 25.1) kg and height of 171.6 (± 10.3) cm. A strong negative correlation was found at the start of the abduction (r = -0.623; p = 0.01) between the muscle activity of the serratus anterior lower fibres and the lower trapezius. The only significant increase in the mean EMG ratio of serratus anterior lower fibres versus the lower trapezius was present at 60% (from baseline) of abduction (p = 0.03). The EMG activity ratio of serratus anterior lower fibres and lower trapezius remains variable in different movement planes.


[Land ecological safety in Poyang Lake Eco-economic Zone: an evaluation based on matter-element model].
Base on the 2001-2007 related statistical data, and by means of matter-element model, an evaluation was conducted on the land ecological safety in Poyang Lake Eco-economic Zone. The land safety in the Eco-economic Zone was relatively fine in 2001, decreased to critical level in 2002-2004, and degraded to unsafe in 2005. From 2006, the safety level returned to critical, indicating a better safety status. This study showed that matter-element model had the advantages of simple calculation, clear indication, and higher accuracy, being able to provide another approach for regional land ecological safety evaluation.


Predictors of Third Trimester Blood Trihalomethanes and Urinary Trichloroacetic Acid Concentrations among Pregnant Women.
Prenatal exposure to disinfection byproducts (DBPs) has been associated with a variety of adverse birth outcomes. However, little is known about predictors of prenatal biomarkers of exposure to DBPs among pregnant women. We aimed to identify predictors of third trimester blood trihalomethanes (THMs) and urinary trichloroacetic acid (TCAA) concentrations, two biomarkers of exposure to DBPs, among pregnant women. Blood samples, urine samples, and questionnaires on individual characteristics and water-use activities were collected from 893 pregnant women in a Chinese cohort study. Maternal blood THM [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and urinary TCAA concentrations were measured. We used multivariable linear regression to identify the predictors of third trimester blood THM and creatinine-adjusted urinary TCAA concentrations. The geometric mean of blood TTHM (sum of TCM, BDCM, DBCM, and TBM) and creatinine-adjusted urinary TCAA concentrations were 51.90 ng/L and 9.66 μg/g creatinine, respectively. Study city was the strongest significant predictors of blood THM and creatinine-adjusted urinary TCAA concentrations. Prenatal body mass index (BMI) was associated with decreased blood THM and decreased creatinine-adjusted urinary TCAA concentrations. Age was associated with increased blood Br-THM (sum of BDCM, DBCM, and TBM) concentrations. Intake of boiled water and passive smoking were associated with lower blood THM concentrations. The predictors of blood THM and urinary TCAA concentrations identified in this study provide potential health implications on how to reduce DBP exposure during pregnancy.


Miocene Mammals and Central American Seaways: Fauna of the Canal Zone indicates separation of Central and South America during most of the Tertiary.
The presence of Miocene mammals of North American affinity in the Panama Canal Zone indicates that Central America was attached to North America. That this attachment was a broad and stable land mass is shown by the close relation of the Panama Miocene herbivores to the widely distributed Miocene herbivore fauna of North America. A continuous connection existed probably throughout the Tertiary, to the west and north of the isthmian region, but the tectonically active isthmus probably was broken up into an archipelago during most of Tertiary time. Between the islands ran the Strait of Panama; from time to time parts of the isthmian area were connected to the stable land to the west, allowing eastward migration of land animals. The mammals of North American affinity in the Cucaracha Formation were found only a few kilometers from the western end of the San Blas Area, a stable land mass in eastern Panama that was separated from South America by the Bolivar Trough during most of the interval between Oligocene and Pliocene time (16). The Strait of Panama was a less stable barrier than the Bolivar Trough; this being so, it is likely that the San Blas Area was inhabited by land animals of North American rather than South American affinity. Thus, the disappearance of the Bolivar seaway in Pliocene time would have allowed, probably for the first time, mingling of the North and South American mammal faunas.


Activation of matrix metalloproteinases-9 after photothrombotic spinal cord injury model in rats.
Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 have been known to play an important role in secondary inflammatory reaction after spinal cord injury (SCI). The aim of this study was to investigate the expression and activity of MMP-2 and MMP-9 and to determine their relationship with disruption of endothelial blood-barrier after photochemically induced SCI in rats. Female Sprague-Dawley rats, weighing between 250 and 300 g (aged 8 weeks) received focal spinal cord ischemia by photothrombosis using Rose Bengal. Expressions and activities of MMP-2 and MMP-9 were assessed by Western blot and gelatin zymography at various times from 6 h to 7 days. Endothelial blood-barrier integrity was assessed indirectly using spinal cord water content. Zymography and Western blot analysis demonstrated rapid up-regulation of MMP-9 protein levels in spinal cord after ischemic onset. Expressions and activities of MMP-9 showed a significant increased at 6 h after the photothrombotic ischemic event, and reached a maximum level at 24 h after the insult. By contrast, activated MMP-2 was not detected at any time point in either the experimental or the control groups. When compared with the control group, a significant increase in spinal cord water content was detected in rats at 24 h after photothrombotic SCI. Early up-regulation of MMP-9 might be correlated with increased water content in the spinal cord at 24 h after SCI in rats. Results of this study suggest that MMP-9 is the key factor involved in disruption of the endothelial blood-barrier of the spinal cord and subsequent secondary damage after photothrombotic SCI in rats.


Enzyme-based flow injection analysis system for glutamine and glutamate in mammalian cell culture media.
We present the setup of a flow injection analysis system designed for on-line monitoring of glutamate and glutamine. These amino acids represent a major energy source in mammalian cell culture. A cycling assay consisting of glutamate dehydrogenase and aspartate aminotransferase produces NADH proportional to the glutamate concentration in the sample. NADH is then measured spectrophotometrically. Glutamine is determined by conversion to glutamate which is fed into the cycling assay. The conversion of glutamine to glutamate is catalyzed by asparaginase. Asparaginase was used in place of glutaminase due to its relatively high reactivity with glutamine and a pH optimum similar to that of glutamate dehydrogenase. The enzymes were immobilized covalently to activated controlled pore glass beads and integrated into the flow injection analysis system. The application of the immobilized enzymes and the technical setup are presented in this paper.


Uneasy promises: sexuality, health, and human rights.
Although attention to the links between health and human rights is growing globally, the full potential of a progressive human rights approach to health has not yet been explored, and it is even more faintly understood in the United States than in the rest of the world. At the same time, global claims for sexual rights, particularly for those identifying as gay, lesbian, transsexual, or bisexual, are increasingly being made as human rights claims. All of these approaches to rights advocacy risk limiting their own transformative impact unless advocates critique their own strategies. Paradoxically, using health as a way to bring attention to nonheteronormative sexualities can be both helpful and potentially dangerous, especially when coupled with human rights. Recognizing sexuality as a critical element of humanity, and establishing a fundamental human right to health, can play a role in broader social justice claims, but the tendency of both public health and human rights advocacy to "normalize" and regulate must be scrutinized and challenged.


Appearance of high-molecular weight sialoglycoproteins recognized by Maackia amurensis leukoagglutinin in gastric cancer tissues: a case report using 2-DE-lectin binding analysis.
Aberrant expression of sialoglycoconjugates has been thought to play an important role in cancer progression. Our previous lectin-histochemical study showed that overexpression of sialoglycoconjugates recognized by alpha2,3-sialic acid-specific Maackia amurensis leukoagglutinin (MAL) was significantly related to the malignancy of gastric cancer. The present study analyzed the sialoglycoproteins in gastric cancer tissues by 2-dimensional electrophoresis (2-DE) in combination with lectin-binding analysis using MAL. Various MAL-positive sialoglycoproteins were detected in cancer tissues but not in non-cancer tissues. The sialoglycoproteins have a high molecular weight of near 200 kDa and over 200 kDa with different pI values for the two. This suggests that the MAL-positive sialoglycoproteins detected in gastric cancer tissues have high molecular weights and may contain different numbers of alpha2,3-linked sialic acid residues in the carbohydrate moiety.


The role of the adrenals in the acute phase response to interleukin-1 and tumor necrosis factor-alpha.
The purpose of this study was to investigate the role of the adrenals, particularly the glucocorticoids, in the acute phase response following daily injections for 5 days of recombinant human interleukin-1 alpha,beta and tumor necrosis factor-alpha (TNF alpha). Adult weight-stable freely fed or pair-fed (to cytokine-injected mice) mice (C57Bl/6J) with and without adrenals were used. Adrenalectomized animals showed a sensitivity to both IL-1 alpha and -1 beta (40 ng IL-1/day) greater than 10-fold higher than that of normal mice (420 ng IL-1/day) in regard to mortality and anorexia. Microscopic examination of tissue specimens from adrenalectomized IL-1 alpha,beta-injected mice did not reveal any histologic alterations in lung, kidney, liver, brain, or gastrointestinal tract to explain the mortality. This mortality was not prevented by physiologic replacement doses of hydrocortisone (10-20 micrograms/day); however, a pharmacological dose of 2.5 mg hydrocortisone/day abolished completely the increased toxicity to IL-1 alpha,beta and the anorectic response to IL-1 alpha,beta and TNF alpha. Increased toxicity (mortality) was not observed in adrenalectomized animals with TNF alpha at the dose interval used (450 ng TNF alpha/day and lower). The hepatic acute phase response (liver weight and RNA and liver protein content) was increased by both IL-1 alpha,beta and TNF alpha in a glucocorticoid-independent way. The cytokine-induced alterations of plasma concentrations of acute phase proteins (serum amyloid P, transferrin, complement C3) were significantly dependent on glucocorticoids, while the decline in plasma albumin was not.(ABSTRACT TRUNCATED AT 250 WORDS)


Time of onset in haemodialysis access-induced distal ischaemia (HAIDI) is related to the access type.
A small portion of haemodialysis patients develop hand ischaemia (HAIDI, haemodialysis access-induced distal ischaemia) in the presence of an arteriovenous access (AVA). It is unknown if the time of onset of ischaemia is related to the type of AVA. This review aims to investigate if a relationship is present between the type of AVA and the time of onset and intensity of HAIDI. Standard databases and reference lists of the pertinent literature were systematically searched. HAIDI was classified as 'acute' (<24 h after routine access construction), 'subacute' (within 1 month) or 'chronic' (>1 month). Location, type and follow-up of AVA were tabulated. Twenty-one studies reporting on surgically or percutaneously corrected HAIDI patients (n = 464) fulfilled the inclusion criteria. Acute HAIDI strongly (88%) correlated with non-autogenous AVA. In contrast, chronic HAIDI was predominantly (91%) observed following autogenous AVA based on the cubital segment of the brachial artery. A simple clinical classification for chronic HAIDI guiding treatment strategies is proposed. Hand ischaemia occurring early after routine access surgery is usually related to grafts and not to autogenous access construction. If patients have several risk factors for acute hand ischaemia (diabetes), nephrologists and vascular surgeons may choose an autogenous AVA. A disadvantage of an autogenous access is its association with chronic hand ischaemia, particularly if constructed with a brachial artery.


Non-traumatic atlanto-axial subluxation: Grisel's syndrome. Two case reports.
Two 8-year-old boys presented with complaints of torticollis and pain on neck turning. Both patients had a history of throat infection. Radiography and computed tomography demonstrated atlanto-axial subluxation. The patients were treated under diagnoses of Grisel's syndrome, unilateral or bilateral subluxation of the atlas on the axis associated with infection in the head or neck. Both patients were treated conservatively with bed rest, muscle relaxants, non-steroid anti-inflammatory agents, and immobilization with a soft cervical collar and cervical halter traction. The torticollis had resolved and reduction of atlanto-axial subluxation was confirmed within 2 weeks in both patients. Early diagnosis of Grisel's syndrome with appropriate antibiotics and a cervical collar, with halter traction if necessary, can achieve good outcome. Surgical treatment for the reduction of atlanto-axial subluxation should be reserved for persistent or recurrent cases.


[Artisan iris-claw IOL implantation in cases of bilateral lens luxation into the vitreous body].
A clinical case of bilateral retropupillary implantation of iris-fixated lenses (Worst iris-claw intraocular lenses) in a patient with bilateral complete native lens dislocation into the vitreous body is presented. Despite native lens in the vitreous, the patient did not develop ocular hypertension in either eye after the surgery during a long-term follow-up period. Visual acuity significantly improved and there was no necessity in removing the dislocated lenses.


Situation analysis of risk factors related to non-communicable diseases in Khon Kaen Province, Thailand.
A descriptive cross-sectional study was carried out in Khon Kaen Province during January 1 to June 30, 2008. The aims were to assess: (1) the prevalence of risk factors for chronic diseases such as cancer, diabetes, blood pressure; and (2) health behaviour and health education needs. There were 338 sample subjects aged between 20-60 years, from urban, semi-urban and rural areas. Some 20.4 % of the sample subjects reported that they were unhealthy (10.4% diagnosed with hypertension, 9.8% with diabetes, and 0.9% with cancer). For history of illness in the family, the most common were diabetes (42%), high blood pressure (16.5 %) and cancer (14.8 %), and 66.9% reported stress within the last 6 months. In terms of risk behavior, 82.3% of males smoked cigarettes but only 1.9% of females. The respective figures for alcohol were 68.4% and 26.6%. The majority (61.2) had low physical activity (sitting or standing, little movement). Almost one third (32%) reported testing positive for Opisthorchis viverrini eggs in stool. For health education needs, 64.2%, 54.7% and 42.6% wanted to learn more about cancer, diabetes and hypertension, respectively. For means of health education delivery, 31.7% want to learn from medical doctors, 20.4% from TV, 16.3% from village's broadcasting and 13.6% from health volunteers. Suitable means to delivery health education are needed to convey knowledge to the population. Community health volunteers may be one of the best sustainable alternative methods to transfer knowledge.


[Diagnosis of floating venous thrombi by spiral CT phlebography].
Evaluation by means of spiral CT as to whether or not a thrombus in a proximal deep vein of the leg is floating or adherent to the vessel wall. Local application of contrast agent into an ipsilateral dorsal foot vein and spiral CT were used to examine 16 consecutive cases with deep venous thrombosis proven at conventional venography; in addition, colour Doppler flow imaging was performed. At conventional venography, 8/16 thrombi appeared to be floating and the remaining 8/16 were adherent to the vessel wall. Spiral-CT showed 15/16 thrombi to be adherent to the vessel wall; the floating thrombus correlated with findings in conventional venography. At colour Doppler flow imaging 3/16 thrombi were considered floating, one of them was discordant to conventional venography. The comparison of conventional venography to spiral-CT demonstrates complete agreement for adherence to vessel wall seen in conventional venography (p = 1,0) and significant discordance in cases with free-floating appearance in conventional venography (p = 0,0002). Adherence of thrombi to the wall of the vessel at conventional venography is in agreement with computed tomography. Conventional venography probably overestimates the prevalence of free floating thrombi.


Cushion form bearings for total knee joint replacement. Part 2: Wear and durability.
Cushion knee prostheses have been designed and constructed to produce larger initial contact areas and thicker theoretical film thicknesses than a conventional UHMWPE (ultra-high molecular weight polyethylene) joint. The compliant bearing had a flat tibial component which imposed fewer biomechanical constraints and allowed greater range of movement. Wear tests were performed in a knee joint simulator and creep tests were carried out in a servo-hydraulic apparatus. Various failure modes of cushion joints that require further study were identified. However, the results showed that adequate durability was achieved from a 20 MPa polyurethane material in joint simulating tests carried out over 0.5, 1.0 and 5.0 million cycles. Most importantly, during these tests, no detectable wear debris was generated. It is believed that this is the first time that the full potential of cushion bearings has been demonstrated in a joint simulator over periods corresponding to about five years of service in vivo.


Graduate Medical Education: Its Role in Achieving a True Medical Education Continuum.
Nearly half a century ago, Lowell T. Coggeshall recommended, through what has come to be known as the Coggeshall Report, that physician education-medical school (or undergraduate medical education [UME]), residency training (or graduate medical education [GME]), and continuing medical education (CME)-be "planned and provided as a continuum." While the dream of a true continuum remains unfulfilled, recent innovations focused on defining and assessing meaningful outcomes at last offer the anchor for the creation of a seamless, flexible, and ongoing pathway for the preparation of physicians. Recent innovations, including a widely accepted competency framework and entrustable professional activities (EPAs), provide key tools for creating a continuum. The competency framework is being leveraged in UME, GME, and CME and is serving as the foundation for the continuum. Learners and those who assess them are increasingly relying on observable behaviors (e.g., EPAs) to determine progress. The GME community in the United States and Canada has played-and continues to play-a leading role in the creation of these tools and a true medical education continuum. Despite some systemic challenges to implementation (e.g., premedical learner formation, time-in-step requirements), the GME community is already operationalizing these tools as a basis for other innovations that are improving transitions across the continuum (e.g., competency-based progression of residents). The medical education community's greatest responsibility in the years ahead will be to build on these efforts in GME-joining together to learn from one another and develop a continuum that serves the public and the profession.


Conservative management of penetrating hypopharyngeal wounds.
To demonstrate the applicability of nonoperative treatment to penetrating hypopharyngeal wounds. A prospective study. An analysis of patients with penetrating hypopharyngeal wounds who were treated nonoperatively at the Hospital Universitario del Valle (Cali, Colombia) during 4 years (beginning January 1990) was performed. Patients older than 13 years with proven lesions produced by penetrating trauma were included. Patients with foreign-body-induced or iatrogenic lesions (orotracheal intubation, endoscopy) or immediate need for surgery (for associated lesions) were excluded. Nonoperative management consisted of nasogastric tube for feeding, suspension of oral intake, and parenteral antibiotics for 7 days. Fourteen patients met the above criteria. Gunshot wounds (n = 11) were the most common trauma. An esophagogram/endoscopy demonstrated the lesions. The only complication in the group consisted of a cervical abscess, which presented in a patient during the first week of treatment. There were no complications such as fistula, leakage, and Horner's syndrome. Conservative management is a good and safe alternative when indicated in penetrating hypopharyngeal wounds.


Racemization of alcohols catalyzed by [RuCl(CO)2(eta(5)-pentaphenylcyclopentadienyl)]--mechanistic insights from theoretical modeling.
Two possible pathways of inner-sphere racemization of sec-alcohols by using the [RuCl(CO)(2)(eta(5)-pentaphenylcyclopentadienyl)] catalyst (1) have been thoroughly investigated by means of density function calculations. To be able to racemize alcohols, catalyst 1 needs to have a free coordination site on the metal. This can be achieved either by a eta(5)-->eta(3) ring slippage or by dissociation of a carbon monoxide (CO) ligand. The eta(5)-->eta(3) ring-slip pathway was found to have a high potential energy barrier, 42 kcal mol(-1), which can be explained by steric congestion in the transition state. On the other hand, CO dissociation to give a 16-electron complex has a barrier of only 22.6 kcal mol(-1). We have computationally discovered a mechanism involving CO participation that does not require eta(5)-->eta(3) ring slippage. The key features of this mechanism are 1) CO-assisted exchange of chloride for alkoxide, 2) alcohol-alkoxide exchange, and 3) generation of an active 16-electron complex through CO dissociation with subsequent beta-hydride elimination as the racemization step. We have found a low-energy pathway for reaction of 1 with potassium tert-butoxide and a pathway for fast alkoxide exchange with interaction between the incoming/leaving alcohol and one of the two CO ligands. We predict that dissociation of a Ru-bound CO ligand does not occur in these exchange reactions. Dissociation of one of the two Ru-bound CO ligands has been found necessary only at a later stage of the reaction. Though this barrier is still quite high, our results indicate that it is not necessary to cross the CO dissociation barrier for the racemization of each new alcohol. Thus, the dissociation of a CO ligand is interpreted as a rate-limiting reaction step in order to create a catalytically active 16-electron complex.


Decreased hemoglobin concentrations, hyperparasitemia, and severe malaria are associated with increased Plasmodium falciparum gametocyte carriage.
To determine factors influencing gametocyte carriage, a cross-sectional study was conducted among 512 patients admitted for Plasmodium falciparum malaria. After adjustments for potential confounders, hemoglobin concentrations were lower in gametocyte carriers 10.5 (+/-2.5) than in patients without gametocytes 12.5 (+/-2.3) (P < 0.0001). Hemoglobin concentrations were negatively correlated with peak gametocyte counts (Spearman's p = -0.37, P < 0.0001) and gametocyte carriage durations (Spearman's p = -(0.30, P < 0.0001). Adjustments for the duration of the malaria episode and other potential confounders did not alter the association (P < 0.0001). After adjustment for potential confounders, the median asexual parasitemia was higher in patients with gametocytes than in patients without gametocytes (P = 0.003). Severe malaria cases were more likely to have gametocytes (65%) than malaria with hyperparasitemia (38%) or mild malaria (31%) (P = 0.0001). These findings suggest that events surrounding anemia and tissue hypoxia stimulate Plasmodium falciparum gametocytogenesis.


Activator protein 1 activity is involved in the regulation of the cell type-specific expression from the proximal promoter of the human profilaggrin gene.
The human profilaggrin gene is expressed in the granular layer during the late stages of terminal differentiation of the epidermis. In in vitro transcription experiments we show that the abundance of the mRNA and the specificity of the expression are regulated primarily at the level of transcription. We found that the 5'-flanking sequences control the transcription in a keratinocyte-specific mode and that as little as 116 base pairs preceding the mRNA initiation site is sufficient to restrict the transcription to epidermal cells in vitro. This specificity depends critically on the presence of an activator protein 1 (AP1) motif at position -77. Binding of c-jun/c-fos heterodimers to this sequence confers high levels of expression to the reporter constructs in cultured epidermal keratinocytes, while having little effect in HeLa cells. The transactivating properties of c-jun are essential in this process. On the other hand, junB and junD, which are involved in transactivating the transcription of earlier epidermal differentiation markers, control profilaggrin expression through a pathway which does not depend on a direct binding at the AP1 site and is not cell-type specific. These data indicate that AP1 factors are involved in a complex, multipathway regulation of the profilaggrin gene expression.


The effect of intra-articular mepivacaine administration prior to carpal arthroscopy on anesthesia management and recovery characteristics in horses.
To evaluate the effects of intra-articular (IA) mepivacaine administration prior to carpal arthroscopy on anesthetic drug requirements, blood pressure support, hemodynamic variables, and quality of recovery in horses. Experimental, analytical, cohort study. Twenty-two horses (n = 11 horses/group). Horses were anesthetized by using the same protocol, but an IA injection of mepivacaine or saline was performed before carpal arthroscopy. End-tidal isoflurane concentration, heart rate, and mean arterial pressure were recorded at specific time points. Quality of recovery was scored by the anesthetist, who was unaware of group assignment. Data were analyzed by using two-way repeated-measures analysis of variance. Mean arterial pressure was higher during joint distension in the control group compared with baseline (7% higher, P = .02) and with the treatment group (10% higher, P = .04). Heart rate was higher in the control group compared with the treatment group during joint distension (8% higher, P = .04) and chip removal (11% higher, P = .03). Heart rate was higher in the control group compared with baseline during chip removal (5.5% higher, P = .04). Two horses in the control group required additional ketamine vs none in the treatment group. Quality of recovery was not different between groups. Intra-articular mepivacaine resulted in fewer detectable reactions to surgical stimulation, with similar recovery scores and blood pressure support requirements. Intra-articular anesthesia prior to arthroscopy can be used safely in the horse and should be considered as a part of balanced anesthetic protocols.


Use of digital tools for preclinical training in complete denture: A pilot study.
Advances in CAD-CAM complete dentures open up opportunities in preclinical laboratory education. A cross-over study was conducted to assess the benefit of digital training in custom tray fabrication. Hypotheses were that digital training improved conceptual skill acquisition and that assessment of digital work helps in the discrimination of students' difficulty. Third-year students were allocated either into group A and took the manual practical classes before the digital ones, or into group B (N = 154). Prior to the sessions, a motor skill test was conducted. The influence on the learning process was evaluated by comparing the groups' results to the manual lab work with a Student's t-test. The effectiveness of the assessment in discriminating manual aptitude and conceptual skill was studied through Spearman's rank coefficient between digital and manual scores in conceptual skill and with a subgroup analysis according to the results of the motor skill test. The level of significance was set up at .05. Students' satisfaction was also assessed with a questionnaire. Students in group B achieved better scores. Spearman's rank coefficient test showed a weak correlation, R = .16. For manual lab work, the most manually skilled students did significantly better. In contrast, for the digital session, the medium manually skilled students did better. More than half of the students (55%) found the manual and digital sessions complementary, without identifying any difference depending on the learning sequence. Digital training improved the students' results in the conventional practical exercise. Assessments of the digital and conventional custom trays were complementary in order to distinguish conceptual and motor skills.


Interferon beta1a treatment modulates TH1 expression in gammadelta + T cells from relapsing-remitting multiple sclerosis patients.
A paradigm exists that multiple sclerosis is causally related to dysregulation of TH1 inflammatory cytokines and TH2 antiinflammatory cytokines. The cytokine source(s) that initiate the imbalances are unknown. In this study, gammadelta, CD4, and CD8 T cell receptor-positive (TCR+) cells were isolated from the blood of 26 definitive relapsing-remitting multiple sclerosis patients prior to interferon beta-1a (IFNbeta1a) therapy and following 8-10 weeks of this therapy. The bioactivities of interferon gamma (IFNgamma), interleukin 10 (IL10), and interleukin 12 (IL12) were determined. The concentrations of IFN-gamma, IL10, and IL12 from each cell type did not change significantly with IFNbeta1a treatment. The IL10 secreted by gammadelta TCR+ cells strongly correlated with the IL12 secreted by the same gammadelta TCR+ cells, supporting the paradigm. Furthermore, IFNbeta1a therapy decreased the gammadelta TCR+ cell secretion of TH1 cytokines after 8-10 weeks of therapy.


Neurogenic heterotopic ossification.
Heterotopic ossification (HO) following neurological injury is defined as soft tissue bone formation which is most often seen after spinal cord or head injury and reported to occur after numerous other neurological insults. It can result in ankylosis of associated joints restricting patient mobility. Lesions present with signs of local inflammation. Evidence of ossification is noted on Technetium 99 bone scan and then on X-ray. Serum alkaline phosphatase may be elevated. Although it resembles the histopathology of myositis ossificans traumatica, its pathogenesis remains unclear. Current research favors exercise of joints to attenuate loss in range of motion. Ethane-1-hydroxy-1, 1-diphosphonic acid, a diphosphonate analogue of pyrophosphate, is the only medical treatment specifically indicated in heterotopic ossification. It has not been as effective as first hoped. Nonsteroidal anti-inflammatory drugs, warfarin, and X-radiation therapy hold promise as treatments. Surgical excision to remove ankylosing ectopic bone has been plagued by reoccurrence. Studies to better elucidate the etiology of HO, accelerate diagnosis of the condition, and accurately determine its risk of reoccurrence are needed. Further controlled studies of the various treatments are also warranted.


The aluminum content of parenteral solutions: current status.
Aluminum contaminates several chemical compounds that are administered intravenously to patients. The most highly contaminated are calcium and phosphate salts, followed by albumin and heparin. Parenteral administration of aluminum bypasses the gastrointestinal tract, which serves as a protective barrier to aluminum entry into the blood. In the past, parenteral administration of aluminum as a contaminant of water used in hemodialysis and of casein hydrolysate, the former source of protein in parenteral nutrition solutions, was associated with a low-turnover osteomalacic bone disease and, in the case of uremic patients, encephalopathy. Groups currently at risk for aluminum accumulation in tissue resulting from parenteral administration include premature infants receiving long-term parenteral nutrition and patients receiving plasmapheresis therapy with albumin. Both groups may develop metabolic bone disease; the pathogenesis may involve aluminum. The Food and Drug Administration is currently considering regulation of aluminum in fluids used for parenteral nutrition. No changes are presently proposed with regard to albumin.


Thermodynamics of base pairing.
The study of the thermodynamics of base pairing is a rapidly expanding field due to its importance for taking advantage of opportunities presented by the growing database of nucleic acid sequences. Both natural and unnatural nucleic acids are being studied. The determination of nearest-neighbor parameters from optical melting data for RNA-DNA and DNA-DNA duplexes with Watson-Crick base pairs is particularly noteworthy. The foundations are also being laid for a theoretical understanding of these thermodynamics.


High-resolution crystal structure of magnesium (MgII)-iron (FeII) hybrid hemoglobin with liganded beta subunits.
The structures of deoxy (alpha(Mg(II))2 beta(Fe(II))2) and CO-liganded (alpha(Mg(II)2(Fe(II)-CO)2) forms of human hemoglobin were determined by X-ray crystallography to a resolution of 1.7 A and 1.9 A, respectively. The deoxy hybrid has virtually the same structure as that of the native deoxy HbA. Both the deoxy and CO-liganded hybrids assumed a T quaternary structure characteristic of native deoxy HbA. No significant structural difference was found between the alpha subunits of the CO-liganded hybrid and deoxy HbA, while in the beta subunit, significant tertiary structural changes were confined to the heme pocket. Baldwin showed by a comparison of COHbA and deoxy HbA that there is a 1.5 A shift of the beta subunit heme into its pocket. This shift was much reduced in alpha(Mg(II))2 beta(Fe(II)-CO)2. On the other hand, when the two structures are compared with superposition of hemes, the nearest neighbors of CO (Fe, E11 Val and E7 His) have shifted nearly to the same positions as those in COHbA. Thus the tertiary structure of the beta subunit of alpha(Mg(II))2 beta(Fe(II)-CO)2 is such that the CO molecule and the neighboring atoms assume nearly the same conformation as those of COHbA, while the block shift of these groups is impeded with respect to the structural invariant portions of the molecule.


Entomological outcomes of cluster-randomised, community-driven dengue vector-suppression interventions in Kampong Cham province, Cambodia.
Cambodia has one of the highest dengue infection rates in Southeast Asia. Here we report quantitative entomological results of a large-scale cluster-randomised trial assessing the impact on vector populations of a package of vector control interventions including larvivorous guppy fish in household water containers, mosquito trapping with gravid-ovitraps, solid waste management, breeding-container coverage through community education and engagement for behavioural change, particularly through the participation of school children. These activities resulted in major reductions in Container Index, House Index, Breteau Index, Pupal Index and Adult Index (all p-values 0.002 or lower) in the Intervention Arm compared with the Control Arm in a series of household surveys conducted over a follow-up period of more than one year, although the project was not able to measure the longer-term sustainability of the interventions. Despite comparative reductions in Adult Index between the study arms, the Adult Index was higher in the Intervention Arm in the final household survey than in the first household survey. This package of biophysical and community engagement interventions was highly effective in reducing entomological indices for dengue compared with the control group, but caution is required in extrapolating the reduction in household Adult Index to a reduction in the overall population of adult Aedes mosquitoes, and in interpreting the relationship between a reduction in entomological indices and a reduction in the number of dengue cases. The package of interventions should be trialled in other locations.


Intrinsic cisplatin resistance in lung and ovarian cancer cells propagating in medium acutely depleted of folate.
Many tumors develop intrinsic and/or acquired resistance to cisplatin. The purpose of the present study was to examine the influence of acute extracellular folate depletion prior to cisplatin treatment on the development of intrinsic cisplatin resistance. Lung and ovarian cancer cells were propagated in medium acutely depleted of folate and subsequently treated with cisplatin. The IC50 level for cisplatin, cell viability, cell proliferation, and global DNA methylation were determined. Gene expression profiling was performed using the Atlas Cancer 1.2 Array. Acute extracellular folate depletion resulted in the development of intrinsic cisplatin resistance. Cells propagating in medium acutely depleted of folate had a survival advantage compared to control cells when exposed to cisplatin, and thymidine supplementation did not reverse the intrinsic cisplatin resistance. cDNA microarray analysis revealed some novel genes associated with the development of intrinsic cisplatin resistance. Our report is the first to demonstrate that acute extracellular folate depletion results in intrinsic cisplatin resistance. If these results are confirmed by in vivo human studies, it would suggest that the folate status of the recipient of cisplatin might have an impact on response to that chemotherapeutic agent.


Differentiation kinetics and globin gene expression by circulating human BFUe in suspension cultures.
We studied the kinetics of erythroid differentiation and the globin synthetic patterns of circulating early erythroid progenitors (erythroid burst-forming units, BFUe) stimulated to differentiate in suspension cultures in the presence of interleukin 3 (IL-3) and erythropoietin. Erythroid progenitor cells present at the onset of culture and on successive days (2-12) thereafter were quantitatively assessed by clonal assays, whereas globin synthesis was measured sequentially in aliquots from the suspension culture. Although BFUe numbers increased to a peak value by day 4, the number of progenitors generating larger bursts was progressively decreasing with a concomitant increase in the number of smaller sized bursts. Erythroid colony-forming units (CFUe) and erythroid clusters were first detected by day 4 and peaked on day 6. Proerythroblasts were morphologically identifiable on day 4, and they progressively increased in number and maturity so that, at culture days 10 and 12, 51% and 59% of the culture cells were erythroblasts, respectively. In keeping with the morphologic changes during the liquid culture, globin mRNA was first detected on day 4. gamma/gamma + beta mRNA ratios were highest on days 4 and 6 and declined thereafter. Our results show that circulating BFUe (at least the majority of them) can differentiate and mature as a cohort in suspension cultures, providing terminal progeny with accelerated kinetics compared to semisolid, clonal cultures. In this system the same cohort of cells can be easily sampled throughout the culture for molecular studies on erythroid differentiation.


Effect of Soil Moisture Regimes on the Glyphosate Sensitivity and Morpho-Physiological Traits of Windmill Grass (Chloris truncata R.Br.), Common Sowthistle (Sonchus oleraceus L.), and Flaxleaf Fleabane [Conyza bonariensis (L.) Cronq.].
The glasshouse study was conducted with the objectives of (i) investigating the effect of soil moisture variations on the control efficiency of glyphosate on windmill grass (Chloris truncata R.Br.), common sowthistle (Sonchus oleraceus L.), and flaxleaf fleabane [Conyza bonariensis (L.) Cronq.], (ii) evaluating the tolerance of tested weed species under soil moisture variations, and (iii) determining the morphological and physiological characteristics of these species to partially explain herbicide tolerance under periods of reduced soil moisture availability (RSM). The species' tolerance to glyphosate increased significantly under reduced soil moisture availability (p < 0.001). The lethal dose to cause herbicide injury or biomass reduction by 50% (LD50) and 80% (LD80) in relation to untreated control for water-stressed plants [i.e., moderate soil moisture availability (MSM) and RSM] was significantly higher than that of plants grown under high soil moisture availability (HSM). The tolerance factor (TF) for C. truncata, S. oleraceus, and C. bonariensis, in terms of biomass reduction under RSM, was 2.6, 2.4, and 2.6, respectively, as compared to HSM. The results showed that the glyphosate sensitivity, especially at the sub-lethal rates, of the three weed species under study decreased as soil moisture availability reduced (p< 0.01). Overall glyphosate efficacy, in relation to the recommended rate, was unaffected, except for C. truncata; the weed survived the highest tested glyphosate rate [750 g active ingredient (a.i.) ha-1] under RSM. There was significant interaction between weed species and soil moisture regimes for weed morpho-physiological traits (p < 0.001), with reduced soil moisture having a more influential impact on the growth of C. bonariensis and S. oleraceus compared to C. truncata. Changes in the leaf characteristics, such as increased leaf thickness, higher leaf chlorophyll content, reduced leaf area, and limited stomatal activity for all the tested weed species under MSM and RSM in relation to HSM, partially explain the tolerance of species to glyphosate at sublethal rates.


Chagas' disease among school students from Chiapas, Mexico: Two cases of Chagasic cardiomyopathy.
Chagas disease is a vector-borne life-threatening illness originally confined to the Americas. Seroprevalence studies have been reported in the Mexican state of Chiapas; nevertheless, no clinical/cardiological studies have been conducted to detect underage cases. The aim of the present work was to detect underage cases in the Mexican state of Chiapas. A serological screening by ELISA was conducted on 1556 blood samples from school pupils; seropositiv- ity was confirmed by indirect ELISA and indirect immunofluorescence. Seropositive cases were clinically assessed in a hospital, and electrocardiographic and echocardiographic studies were performed. Descriptive statistics were used for analysis. Seropositivity was confirmed in three cases in the population under study (0.19%). Cardiological studies confirmed the presence of alterations associated to Chagasic cardiomyopathy in two of the three patients. The conditions for an active transmission of T. cruzi infection are met in the rural localities under study. Additionally, the presence of Chagasic cardiomyopathy in underage patients highlights the relevance of an early detection of cases to provide specific treatment at the onset of the infection and to implement epidemiological surveillance as suggested by PAHO/WHO.


Chemokine-Regulated Recruitment of Antigen-Specific T-Cell Subpopulations to the Liver in Acute and Chronic Hepatitis C Infection.
In hepatitis C virus (HCV) infection, virus-specific CD8+ T cells are recruited to the liver for antiviral activity. Multiple chemokine ligands are induced by the infection, notably interferon-inducible chemokine, CXCL10. In HCV, intrahepatic T cells express chemokine receptors (CCRs), including CXCR3, CXCR6, CCR1, and CCR5, but CCR expression on antigen-specific effector and memory T cells has not been investigated. Paired blood and liver samples were collected from subjects with chronic HCV for flow cytometric analysis of CCR expression on CD8+ T cells. Expression of these CCRs was then examined on HCV-specific CD8+ T-cell subpopulations in the blood from subjects with acute or chronic HCV. Relative to peripheral blood, the liver was enriched with CD8+ T cells expressing CCR2, CCR5, CXCR3, and CXCR6 either singly or in combinations. CXCR3 was preferentially expressed on HCV-specific CD8+ T cells in both acute and chronic phases of infection in blood. Both CXCR3 and CCR2 were overexpressed on HCV-specific CD8+CCR7+CD45RO+ (central memory) cells, whereas effector memory (CD8+CCR7-CD45RO+) cells expressed more CXCR6. CXCR3-mediated signals support the accumulation of HCV-specific CD8+ memory T cells in the infected liver, and emphasize the importance of the CXCL10/CXCR3 trafficking pathway during acute and chronic HCV infection.


Use of stable calcium isotopes (42Ca & 44Ca) in evaluation of calcium absorption in Beijing adolescents with low vitamin D status.
Female adolescent populations with low calcium intakes and sub-optimal vitamin D status are found in northern China. Whether these individuals are able to adapt by enhancing calcium absorption and reducing calcium excretion for maximizing calcium retention is unknown. This study examined the association between true-fractional-calcium-absorption (TFCA), plasma 25-hydroxy-vitamin-D, and urinary calcium excretion among adolescents in Northern China. Twelve healthy girls 9 to 17 years old were recruited from Beijing during a winter. Calcium intake, anthropometry, pubertal status, plasma 25-hydroxyvitamin-Ds (25-OHD), serum calcium, and urinary calcium were determined. TFCA was evaluated by dual stable calcium isotopes. The mean +/- SD calcium intake, 24-hour urinary calcium excretion, plasma 25-OHD and TFCA were 591 +/- 164 mg/day, 79.9 +/- 49.6 mg/day, 30.5 +/- 9.8 nmol/L, and 60.4 +/- 14.4%, respectively. TFCA was inversely correlated with 25-OHD (r = -0.73, p = .008). Urinary calcium was correlated with the onset of menarche (r = 0.63, p = .027). Post-menarcheal girls had a higher urinary calcium output than premenarcheal girls (p = .03). Adolescents from north China with sub-optimal vitamin-D status are able to adapt by enhancing TFCA and reducing urinary calcium excretion to retain calcium for bone development. TFCA was inversely correlated with plasma 25-OHD. Whether a higher efficiency of calcium absorption is sustainable if the shortfall of vitamin D persisting remains to be studied.


Five reasons for the lack of nursing students' motivation to learn public health.
Prevention is better than cure. Public health plays an important role in promoting prevent medicine. To obtain the abilities to provide appropriate nursing services, learning public health is necessary for students who want to become registered nurses. When teachers teach public health to nursing students, it is important to motivate them to learn it. Therefore, we investigated the reasons for the lack of motivation to learn public health by conducting a questionnaire survey. The subjects were female nursing students in 29 vocational schools in Kanagawa and Chiba prefectures of Japan that allow graduation after a 3-year study period. We asked the students whether or not they had completed the subject of public health and analyzed those students who answered affirmatively. We analyzed 1,553 respondents whose average age was 22.6 ± 5.2 years (range, 18 to 45). Using factor analysis, we discovered the 5 reasons that lead to the lack of nursing students' motivation to learn public health: "Difficulties acquiring knowledge of public health," "Inappropriate attitudes of public health teachers," "Thinking lightly about the national examination in the field of public health," "Lack of understanding the importance of learning public health," and "Future plans that do not specialize in public health." Using multiple linear regression analysis, these 5 reasons were significant predictors for the lack of students' motivation. Older students also had significantly less motivation to learn public health than did younger students. When teachers instruct their students, they should teach public health better with the present knowledge.


Comprehensive Analysis of CPA4 as a Poor Prognostic Biomarker Correlated with Immune Cells Infiltration in Bladder Cancer.
Carboxypeptidase A4 (CPA4) has shown the potential to be a biomarker in the early diagnosis of certain cancers. However, no previous research has linked CPA4 to therapeutic or prognostic significance in bladder cancer. Using data from The Cancer Genome Atlas (TCGA) database, we set out to determine the full extent of the link between CPA4 and BLCA. We further analyzed the interacting proteins of CPA4 and infiltrated immune cells via the TIMER2, STRING, and GEPIA2 databases. The expression of CPA4 in tumor and normal tissues was compared using the TCGA + GETx database. The connection between CPA4 expression and clinicopathologic characteristics and overall survival (OS) was investigated using multivariate methods and Kaplan-Meier survival curves. The potential functions and pathways were investigated via gene set enrichment analysis. Furthermore, we analyze the associations between CPA4 expression and infiltrated immune cells with their respective gene marker sets using the ssGSEA, TIMER2, and GEPIA2 databases. Compared with matching normal tissues, human CPA4 was found to be substantially expressed. We confirmed that the overexpression of CPA4 is linked with shorter OS, DSF(Disease-specific survival), PFI(Progression-free interval), and increased diagnostic potential using Kaplan-Meier and ROC analysis. The expression of CPA4 is related to T-bet, IL12RB2, CTLA4, and LAG3, among which T-bet and IL12RB2 are Th1 marker genes while CTLA4 and LAG3 are related to T cell exhaustion, which may be used to guide the application of checkpoint blockade and the adoption of T cell transfer therapy.


The Long-Term Effect of Treatment Using the Transcranial Magnetic Stimulation rTMS in Patients after Incomplete Cervical or Thoracic Spinal Cord Injury.
Repetitive transcranial magnetic stimulation (rTMS) may support motor function recovery in patients with incomplete spinal cord injury (iSCI). Its effectiveness mainly depends on the applied algorithm. This clinical and neurophysiological study aimed to assess the effectiveness of high-frequency rTMS in iSCI patients at the C2-Th12 levels. rTMS sessions (lasting 3-5 per month, from 2 to 11 months, 5 months on average) were applied to 26 iSCI subjects. The motor cortex was bilaterally stimulated with a frequency at 20-25 Hz and a stimulus strength that was 70-80% of the resting motor threshold (15.4-45.5% maximal output) during one therapeutic session. Surface electromyography (sEMG) recordings at rest and during maximal contractions and motor evoked potential (MEP) recordings were performed from the abductor pollicis brevis (APB) and the tibialis anterior (TA) muscles. The same neurophysiological studies were also performed in patients treated with kinesiotherapy only (K group, n = 25) and compared with patients treated with both kinesiotherapy and rTMS (K + rTMS). A decrease in sEMG amplitudes recorded at rest from the APB muscles (p = 0.001) and an increase in sEMG amplitudes during the maximal contraction of the APB (p = 0.001) and TA (p = 0.009) muscles were found in the K + rTMS group. A comparison of data from MEP studies recorded from both APB and TA muscles showed significant changes in the mean amplitudes but not in latencies, suggesting a slight improvement in the transmission of spinal efferent pathways from the motor cortex to the lower spinal centers. The application of rTMS at 20-25 Hz reduced spasticity in the upper extremity muscles, improved the recruitment of motor units in the upper and lower extremity muscles, and slightly improved the transmission of efferent neural impulses within the spinal pathways in patients with C2-Th12 iSCI. Neurophysiological recordings produced significantly better parameters in the K + rTMS group of patients after therapy. These results may support the hypothesis about the importance of rTMS therapy and possible involvement of the residual efferent pathways including propriospinal neurons in the recovery of the motor control of iSCI patients.


Accumulation of nerve growth factor in cerebrospinal fluid and biological activity following neurosurgery.
Perioperative nerve growth factor (NGF) levels in cerebrospinal fluid (CSF) of patients with acoustic neurinoma (14 cases), tentorial meningioma (1 case), or subarachnoid hemorrhage (1 case) were examined. Preoperative NGF levels in CSF were below the level of detection in all patients. However, NGF was found to accumulate transiently in CSF following neurosurgery. Pre- and postoperative CSF obtained from a patient with acoustic neurinoma enhanced the proliferation of astrocytes in neuronal cell cultures derived from embryonic rat cortex grown in serum-free defined medium, and increased choline acetyltransferase activity of cholinergic neurons derived from embryonic rat septal area and brainstem. The effect of postoperative CSF on septal and brainstem neurons was more potent than that of preoperative CSF. These results indicate that NGF and non-NGF-type neurotrophic activities accumulate in the CSF following neurosurgery. These neurotrophic activities are probably important in the regeneration of damaged neural networks in the central nervous system.


What can be the criteria of outpatient-based endoscopic resection for colon polyp?
To investigate whether out-patient based endoscopic mucosal resection (EMR) for colon polyps ≤ 10 mm is safe. Between January 2004 and December 2012, a total of 3015 EMR cases conducted in 1320 patients were retrospectively reviewed. The factors contributing delayed hemorrhage were analyzed. We calculated the probability of delayed bleeding after stratifying conditions of specific risk factors. The size of the polyp (95%CI: 1.096-1.164, P < 0.001) and patients with chronic renal failure (95%CI: 1.856-45.106, P = 0.007) were identified as independent risk factors for delayed bleeding in multivariate analysis. 95%CI for percent of delayed bleeding according to polyp size was determined for the following conditions: size ≤ 10 mm, 0.05%-0.43%; 20 mm ≥ size > 10 mm, 0.54%-2.08%; size > 20 mm, 4.22%-11.41%. 95%CI was determined for the risk of serious immediate bleeding for a polyp ≤ 10 mm was 0.10%-0.56%. Finally, 95%CI for percent of incomplete resection was 0.07%-0.49% in polyps ≤ 10 mm. It seems acceptable to perform outpatient-based EMR for colon polyps ≤ 10 mm.


Tibialis posterior muscle pain effects on hip, knee and ankle gait mechanics.
Tibialis posterior (TP) dysfunction is a common painful complication in patients with rheumatoid arthritis (RA), which can lead to the collapse of the medial longitudinal arch. Different theories have been developed to explain the causality of tibialis posterior dysfunction. In all these theories, pain is a central factor, and yet, it is uncertain to what extent pain causes the observed biomechanical alterations in the patients. The aim of this study was to investigate the effect of experimental tibialis posterior muscle pain on gait mechanics in healthy subjects. Twelve healthy subjects were recruited for this randomized crossover study. Experimental pain was induced by ultrasound-guided injection of 1 mL hypertonic saline into the upper part of the right tibialis posterior muscle with the use of isotonic saline as non-pain-inducing control. Subsequently, kinematic data during three self-paced over ground walking for each condition were collected. Ground reaction forces and external moments were measured from force plates installed in the floor. Painful areas were evaluated using body charts and pain intensity scoring via a verbal numerical rating scale. Decreased hip internal rotation was observed during the pain condition at the end of the stance phase. There were no changes in gait velocity and duration of stand phase between the pain and no pain conditions. Reduced external joint moment was found for external knee rotation and for external hip rotation. The study has demonstrated that induced pain in the TP muscle evokes kinematic alteration in the hip and the knee joints, but not in the ankle, which suggest an underlying early stage joint compensatory mechanism. These findings suggest the need to include those joints in current physical evaluations of tibialis posterior dysfunction.