Reduced Morbidity Motivated Adoption of Infant and Young Child Feeding Practices after Nutrition Education Intervention in Rural Malawi.
This study assessed caregivers' knowledge and practices and factors that influence the adoption of improved infant and young child feeding (IYCF) practices after nutrition education in Kasungu and Mzimba districts among 198 caregivers. Mixed-methods convergent-parallel design, including knowledge tests, focus group discussions, and in-depth interviews in the intervention areas, was used to collect quantitative and qualitative data. Data were analyzed using count regression and content analysis, which showed that knowledge increased among caregivers after nutrition education. The knowledge about diet diversification for young children as well as about hygienic practices when preparing food and during feeding improved in addition. Enhanced health among children motivated caregivers to apply improved IYCF practices. The study was based on the caregivers' reports. Long-term effects of exposure to nutrition education are unknown. However, the nutrition education that focused on the child's health benefits motivated mothers to adopt improved IYCF practices.


Chronic caffeine treatment causes changes in cardiac adenosine receptor function in rats.
Caffeine exerts a number of cardiovascular effects via antagonism of adenosine A1 and A2a receptors, and chronic caffeine intake has been suggested to be a preventable risk factor for cardiovascular disease. We attempted, therefore, to determine the effects of chronic caffeine treatment on adenosine receptor function and the heart rate and blood pressure of anaesthetized rats. Rats were given two weeks of drinking water containing either caffeine (0.2%) or tap water alone. Rats were then anaesthetized and blood pressure and heart rate was assessed, as well as cardiovascular responses to adenosine receptor agonists and antagonists. Following 2 weeks caffeine treatment, both the resting blood pressure and heart rate of the treated rats were significantly increased compared to the non-caffeine treated (147 +/- 5 compared to 161 +/- 3 mm Hg). Negative chronotropic responses to A1 receptor agonist N6 cyclopentyladenosine occurred at lower concentrations in caffeine-treated rats than control (2.5-fold decrease in the ED50 of bradycardic responses to N6 cyclopentyladenosine), whilst vasodilator and reflex tachycardic responses to A2a receptor agonist CGS 21680 were unchanged. A shorter duration of caffeine- treatment resulted in moderate increases in heart rate and bradycardic responses to N6 cyclopentyladenosine. In summary, we found changes in resting heart rate and blood pressure in caffeine-treated rats which were concurrent with changes in adenosine receptor function.


Fluorescence Enhancement of Unconstrained GFP Chromophore Analogues Based on the Push-Pull Substituent Effect.
Unlike the high fluorescence quantum yield of the naturally occurring green fluorescence protein (GFP, Φf ∼ 0.8), the GFP chromophore, a benzylidenedimethylimidazolinone (BDI) dye, is nearly nonfluorescent (Φf < 0.001) in common solutions at room temperature. While many efforts have been devoted into the BDI chromophore engineering for fluorescence recovery, limited success has been achieved for structurally unconstrained GFP chromophore analogues (uGFPc). Herein we report a rational design of uGFPc toward an unprecedentedly high fluorescence quantum efficiency of 0.60 in hexane. This is achieved by a combined ortho-CN and meta-dimethylamino substituent electronic effect that largely suppresses the Z → E photoisomerization (the τ torsion) reaction, which is the major nonradiative decay channel of uGFPc. The structural design relied on the assumptions that the τ torsion of the meta-amino-substituted BDI systems leads to a zwitterionic twisted intermediate state (1p*) and that destabilizing the 1p* state by an electron-withdrawing CN substituent at the ortho or para position could slow down the τ torsion. The observed CN position effect conforms to the design concept. The push-pull substitution of BDI also leads to sensitive fluorescence-quenching responses to electron donors such as trimethylamine and to H-bond donors such as methanol.


Six-day canine kidney preservation. Hypothermic perfusion combined with isolated blood perfusion.
Successful 6-day kidney preservation was obtained with a combination of perfusion techniques. Canine kidneys were preserved by hypothermic continuous perfusion in a Gambro machine with albumin perfusate. On day 3 the hypothermic preservation was interrupted by a normothermic perfusion for 3 hr. This intermediate perfusion was performed in a heart-lung machine filled with heparinized blood from non-related dogs. The preserved kidneys were autotransplanted in subsequently nephrectomized dogs. Nine of 11 animals with such preserved kidneys survived in a healthy condition. In the control group with hypothermic perfusion only, one of 8 dogs survived after implantation. In this dog a high serum creatinine concentration was measured after implantation. Kidney function was assessed by determining glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and filtration fraction (FF) during the intermediate blood perfusion in the experimental group and at 1 hr after implantation in both groups. A low FF (less than 0.27) indicated the presence of active functioning tubules in the intermediate blood-perfused group. In this group the GFR, ERPF, and FF values returned to normal within 10 days after implantation. These results show that it is possible to prevent irreversible preservation damage by normothermic blood perfusion. Histological observation indicated that the isolated blood perfusion had a beneficial effect, especially on the tubules of the preserved kidney.


Abdominal wall hernias: cross-sectional imaging signs of incarceration determined with sonography.
The aim of this study was to determine with sonography whether distinct cross-sectional imaging signs exist that may differentiate between incarcerated and nonincarcerated abdominal wall hernias. The sonographic appearance of 149 consecutive abdominal wall hernias was prospectively investigated and correlated with subsequent surgical results. Commercially available 4- to 10-MHz linear transducers and 2- to 5-MHz curved transducers were used to evaluate the hernias. Surgery revealed 126 nonincarcerated and 23 incarcerated hernias. The sonographic signs suggestive of incarceration that we identified included free fluid in the hernia sac, which was observed in 91% of the incarcerated hernias and in 3% of the nonincarcerated hernias; bowel wall thickening in the hernia, which was detected in 88% of the incarcerated hernias and in none of the nonincarcerated hernias; fluid in the herniated bowel loop, which was detected in 82% of the incarcerated hernias and in 3% of the nonincarcerated hernias; and dilated bowel loops in the abdomen, which occurred in 65% of the incarcerated hernias and in none of the nonincarcerated hernias. These imaging findings allowed the identification of incarceration in all 23 cases and led to a false-positive result in two of 126 nonincarcerated hernias. Cross-sectional imaging signs indicating hernial incarceration included free fluid in the hernial sac, bowel wall thickening in the hernia, fluid in the herniated bowel loop, and dilated bowel loops in the abdomen. Sonography is an appropriate cross-sectional imaging modality for detecting these signs that are helpful in diagnosing patients with atypical clinical presentations.


Transition between the stick and slip states in a simplified model of magnetic friction.
We introduce a simplified model of magnetic friction and investigate its behavior using both numerical and analytical methods. When resistance coefficient γ is large, the movement of the system obeys the thermally activated process. In contrast, when γ is sufficiently small, the slip and stick states behave as separate metastable states, and the lattice velocity depends on the probability that the slip state appears. We evaluate the velocities in both cases using several approximations and compare the results with those of numerical simulations.


Influence of Insect Growth Regulators on Stephanitis pyrioides (Hemiptera: Tingidae) Eggs and Nymphs.
The azalea lace bug, Stephanitis pyrioides (Scott) (Hemiptera: Tingidae), is an important insect pest of azaleas (Rhododendron L. spp.) in the USA. Stephanitis pyrioides feeds on azalea foliage and causes extensive chlorosis, which reduces the aesthetic value and marketability of these plants. Because the use of neonicotinoid insecticides has been dramatically reduced or discontinued, growers and landscape managers are seeking alternative tools or strategies to control this insect. Although insect growth regulators (IGRs) are known for their activity against immature insect stages, their activity against egg hatching has not been addressed thoroughly, specifically against S. pyrioides. Thus, a series of experiments was conducted to understand the ovicidal activity of IGRs using novaluron, azadirachtin, pyriproxyfen, and buprofezin against S. pyrioides. The number of newly emerged young instars was significantly lower when leaves implanted with eggs were sprayed on both sides with novaluron, azadirachtin, and buprofezin compared to nontreated and pyriproxyfen treatments. When IGRs plus adjuvant were applied to the adaxial surface of the leaves, the densities of the newly emerged nymphs were significantly lower under the novaluron treatment compared to the nontreated leaves. However, there was no significant difference in the number of nymphs that emerged in the absence of adjuvant. Furthermore, close monitoring revealed reduced levels of egg hatching in the presence of adjuvant with novaluron compared to its absence. The data show that the survival of S. pyrioides first instars was not affected by exposure to dried IGR residues.


Technical Note: High temporal resolution characterization of gating response time.
Low temporal latency between a gating ON/OFF signal and the LINAC beam ON/OFF during respiratory gating is critical for patient safety. Here the authors describe a novel method to precisely measure gating lag times at high temporal resolutions. A respiratory gating simulator with an oscillating platform was modified to include a linear potentiometer for position measurement. A photon diode was placed at linear accelerator isocenter for beam output measurement. The output signals of the potentiometer and diode were recorded simultaneously at 2500 Hz with an analog to digital converter for four different commercial respiratory gating systems. The ON and OFF of the beam signal were located and compared to the expected gating window for both phase and position based gating and the temporal lag times extracted. For phase based gating, a real-time position management (RPM) infrared marker tracking system with a single camera and a RPM system with a stereoscopic camera were measured to have mean gate ON/OFF lag times of 98/90 and 86/44 ms, respectively. For position based gating, an AlignRT 3D surface system and a Calypso magnetic fiducial tracking system were measured to have mean gate ON/OFF lag times of 356/529 and 209/60 ms, respectively. Temporal resolution of the method was high enough to allow characterization of individual gate cycles and was primary limited by the sampling speed of the data recording device. Significant variation of mean gate ON/OFF lag time was found between different gating systems. For certain gating devices, individual gating cycle lag times can vary significantly.


Effect of exercise training on glucose homeostasis in normal and insulin-deficient diabetic rats.
The effect of 8-wk of treadmill training on plasma glucose, insulin, and lipid concentrations, oral glucose tolerance, and glucose uptake in the perfused hindquarter of normal and streptozocin-treated, diabetic Sprague-Dawley rats was studied. Diabetic rats with initial plasma glucose concentrations of 200-450 mg/dl and control rats were divided into trained and sedentary subgroups. Training resulted in lower plasma free fatty acid concentrations and increased triceps muscle citrate synthase activity in both the control and diabetic rats; triglyceride concentrations were lowered by training only in the diabetic animals. Oral glucose tolerance and both basal and insulin-stimulated glucose uptake in hindquarter skeletal muscle were impaired in the diabetic rats, and plasma glucose concentrations (measured weekly) gradually increased during the experiment. Training did not improve the hyperglycemia, impaired glucose tolerance, or decreased skeletal muscle glucose uptake in the diabetic rats, nor did it alter these parameters in the normal control animals. In considering our results and those of previous studies in diabetic rats, we propose that exercise training may improve glucose homeostasis in animals with milder degrees of diabetes but fails to cause improvement in the more severely insulin-deficient, diabetic rat.


Application of the Ribosomal DNA ITS2 Region of Physalis (Solanaceae): DNA Barcoding and Phylogenetic Study.
Recently, commercial interest in Physalis species has grown worldwide due to their high nutritional value, edible fruit, and potential medicinal properties. However, many Physalis species have similar shapes and are easily confused, and consequently the phylogenetic relationships between Physalis species are poorly understood. This hinders their safe utilization and genetic resource conservation. In this study, the nuclear ribosomal ITS2 region was used to identify species and phylogenetically examine Physalis. Eighty-six ITS2 regions from 45 Physalis species were analyzed. The ITS2 sequences were aligned using Clustal W and genetic distances were calculated using MEGA V6.0. The results showed that ITS2 regions have significant intra- and inter-specific divergences, obvious barcoding gaps, and higher species discrimination rates (82.2% for both the BLASTA1 and nearest distance methods). In addition, the secondary structure of ITS2 provided another way to differentiate species. Cluster analysis based on ITS2 regions largely concurred with the relationships among Physalis species established by many previous molecular analyses, and showed that most sections of Physalis appear to be polyphyletic. Our results demonstrated that ITS2 can be used as an efficient and powerful marker in the identification and phylogenetic study of Physalis species. The technique provides a scientific basis for the conservation of Physalis plants and for utilization of resources.


[Opinion: prevention and health services research from the point of view of the German Forum on Disease Prevention and Health Promotion].
The article presents the point of view of the German Forum on Disease Prevention and Health Promotion that health promotion and prevention and health care research are not only similar as to their self-concept, structure and future tasks, but that health promotion and prevention need the systematic support of health care research to improve its policy impact. Furthermore, the article informs about the latest developments and the current state of disease prevention in Germany, presents a survey of the structure and work of the German Forum on Disease Prevention and Health Promotion and lists desirable topics for future studies in the field of health services research.


Expression and regulation of 1-acyl-sn-glycerol- 3-phosphate acyltransferases in the epidermis.
Phospholipids are a major class of lipids in epidermis, where they serve as a source of free fatty acids that are important for the maintenance of epidermal permeability barrier function. The phospholipid biosynthetic enzyme, 1-acyl-sn-glycerol-3-phosphate acyltransferase (AGPAT), catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, the major precursor of all glycerolipids. We identified an expression pattern of AGPAT isoforms that is unique to epidermis, with relatively high constitutive expression of mouse AGPAT (mAGPAT) 3, 4, and 5 but low constitutive expression of mAGPAT 1 and 2. Localization studies indicate that all five isoforms of AGPAT were expressed in all nucleated layers of epidermis. Furthermore, rat AGPAT 2 and 5 mRNAs increased in parallel with both an increase in enzyme activity and permeability barrier formation late in rat epidermal development. Moreover, after two methods of acute permeability barrier disruption, mAGPAT 1, 2, and 3 mRNA levels increased rapidly and were sustained for at least 24 h. In parallel with the increase in mRNA levels, an increase in AGPAT activity also occurred. Because upregulation of mAGPAT mRNAs after tape-stripping could be partially reversed by artificial barrier restoration by occlusion, these studies suggest that an increase in the expression of AGPATs is linked to barrier requirements.


[Histopathological changes produced in organs by platelet activating factor].
This experiment was conducted to investigate the effect of platelet activating factor (PAF) on the pathological changes in organs using 10 mice (C3H/HeN). Ten mice were divided into two groups of acute and chronic experiment groups. In acute experiment, each mice received iv bolus injection of PAF 2.5 micrograms.kg-1 and in chronic experiment daily ip injection of PAF 7.5 micrograms.kg-1 for 7 days. Histopathology was observed with light microscopy after one hour or after 7 days by haematoxylin and eosin stain. In acute experiment, congestion of the lung, liver, kidney and spleen in all cases, right ventricular dilation in 2 cases and villous necrosis in the small intestine in 4 cases were observed. In chronic experiment, hyaline thrombus with congestion of the lung in 3 cases and congestion of the liver and kidney in all cases were observed. Splenomegaly with increased macrophage was observed, but no necrosis in the small intestine was observed. Marked findings were villous necrosis in the small intestine in acute experiment and hyaline thrombus in the lung as well as splenomegaly in chronic experiment.


Rifampin inhibits prostaglandin E2 production and arachidonic acid release in human alveolar epithelial cells.
Rifampin, a potent antimicrobial agent, is a major drug in the treatment of tuberculosis. There is evidence that rifampin also serves as an immunomodulator. Based on findings that arachidonic acid and its metabolites are involved in the pathogeneses of Mycobacterium tuberculosis infections, we investigated whether rifampin affects prostaglandin E(2) (PGE(2)) production in human alveolar epithelial cells stimulated with interleukin-1beta. Rifampin caused a dose-dependent inhibition of PGE(2) production. At doses of 100, 50, and 25 microg/ml, it inhibited PGE(2) production by 75%, 59%, and 45%, respectively (P < 0.001). Regarding the mechanism involved, rifampin caused a time- and dose-dependent inhibition of arachidonic acid release from the alveolar cells. At doses of 100, 50, 25, and 10 mug/ml, it significantly inhibited the release of arachidonic acid by 93%, 64%, 58%, and 35%, respectively (P < 0.001). Rifampin did not affect the phosphorylation of cytosolic phospholipase A(2) or the expression of cyclooxygenase-2. The inhibition of PGE(2), and presumably other arachidonic acid products, probably contributes to the efficacy of rifampin in the treatment of tuberculosis and may explain some of its adverse effects.


Biphasic growth in fish II: empirical assessment.
In [Quince, et al., 2008. Biphasic growth in fish I: Theoretical foundations. J. Theor. Biol., doi:10.1016/j.jtbi.2008.05.029], we developed a set of biphasic somatic growth models, where maturation is accompanied by a deceleration of growth due to allocation of energy to reproduction. Here, we use growth data from both hatchery-raised and wild populations of a large freshwater fish (lake trout, Salvelinus namaycush) to test these models. We show that a generic biphasic model provides a better fit to these data than the von Bertalanffy model. We show that the observed deceleration of somatic growth in females varies directly with gonad weight at spawning, with observed egg volumes roughly 50% of the egg volumes predicted under the unrealistic assumption of perfectly efficient energy transfer from somatic lipids to egg lipids. We develop a Bayesian procedure to jointly fit a biphasic model to observed growth and maturity data. We show that two variants of the generic biphasic model, both of which assume that annual allocation to reproduction is adjusted to maximise lifetime reproductive output, provide complementary fits to wild population data: maturation time and early adult growth are best described by a model with no constraints on annual reproductive investment, while the growth of older fish is best described by a model that is constrained so that the ratio of gonad size to somatic weight (g) is fixed. This behaviour is consistent with the additional observation that g increases with size and age among younger, smaller breeding females but reaches a plateau among older, larger females. We then fit both of these optimal models to growth and maturation data from nineteen wild populations to generate population-specific estimates of 'adapted mortality' rate: the adult mortality consistent with observed growth and maturation schedules, given that both schedules are adapted to maximise lifetime reproductive output. We show that these estimates are strongly correlated with independent estimates of the adult mortality experienced by these populations.


[Where do people with mental disorders are looking for help?].
This article presents and discusses the concept of "pathway to psychiatric care". According to literature review, only few people, who meet criteria for mental disorders, reach psychiatrists. Therefore it is important to identify institutions where people with mental disorders look for help. On the basis of World Health Organization programme "Pathway study" authors present institutions in different countries all over the world, which are involved in helping people with mental disorders. In all European centers taken part in the "Pathway study" most of the people who reached psychiatrists had been consulted in primary healthcare first. Project "Pathway study" has been the first research programme related with this topic. It has initiated similar studies in different centers all over the world. Results of those studies show, where outside psychiatric institutions, it is possible to diagnose and treat mentally ill people.


Maternal caffeine intake, blood pressure, and the risk of hypertensive complications during pregnancy. The Generation R Study.
Caffeine intake has been suggested to be associated with the risk of hypertension. Less is known about the associations of caffeine intake on maternal cardiovascular adaptations during pregnancy. We examined the associations of caffeine intake in different trimesters of pregnancy with repeatedly measured blood pressure and the risks of pregnancy-induced hypertension and pre-eclampsia in a population-based cohort of 7,890 pregnant women. In each trimester caffeine intake and systolic and diastolic blood pressure were assessed by questionnaires and physical examinations, respectively. Information about hypertensive complications was obtained from medical records. Our longitudinal analyses revealed no significant differences for both systolic and diastolic blood pressure. The cross-sectional analyses showed that higher caffeine intake tended to be associated with higher systolic blood pressure in first and third trimester (P trend <0.05), but not in second trimester. Caffeine intake was not consistently associated with diastolic blood pressure levels, or the risk of pregnancy-induced hypertension. As compared to women with caffeine intake of <2 units/day, those using 2-3.9 units/day had a lower risk of pre-eclampsia (odds ratio 0.63 (95% confidence interval: 0.40, 0.96)). Higher caffeine intake during pregnancy seems to be associated with elevated systolic blood pressure levels in first and third trimester, but not with diastolic blood pressure levels. We did not find evidence of significant adverse associations of caffeine intake on maternal cardiovascular adaptations during pregnancy. The unexpected finding of a possible protective association with moderate caffeine intake deserves further investigation.


Dividing the Archaeal Way: The Ancient Cdv Cell-Division Machinery.
Cell division in most prokaryotes is mediated by the well-studied fts genes, with FtsZ as the principal player. In many archaeal species, however, division is orchestrated differently. The Crenarchaeota phylum of archaea features the action of the three proteins, CdvABC. This Cdv system is a unique and less-well-studied division mechanism that merits closer inspection. In vivo, the three Cdv proteins form a composite band that contracts concomitantly with the septum formation. Of the three Cdv proteins, CdvA is the first to be recruited to the division site, while CdvB and CdvC are thought to participate in the active part of the Cdv division machinery. Interestingly, CdvB shares homology with a family of proteins from the eukaryotic ESCRT-III complex, and CdvC is a homolog of the eukaryotic Vps4 complex. These two eukaryotic complexes are key factors in the endosomal sorting complex required for transport (ESCRT) pathway, which is responsible for various budding processes in eukaryotic cells and which participates in the final stages of division in Metazoa. There, ESCRT-III forms a contractile machinery that actively cuts the membrane, whereas Vps4, which is an ATPase, is necessary for the turnover of the ESCRT membrane-abscission polymers. In contrast to CdvB and CdvC, CdvA is unique to the archaeal Crenarchaeota and Thaumarchaeota phyla. The Crenarchaeota division mechanism has often been suggested to represent a simplified version of the ESCRT division machinery thus providing a model system to study the evolution and mechanism of cell division in higher organisms. However, there are still many open questions regarding this parallelism and the division mechanism of Crenarchaeota. Here, we review the existing data on the role of the Cdv proteins in the division process of Crenarchaeota as well as concisely review the ESCRT system in eukaryotes. We survey the similarities and differences between the division and abscission mechanisms in the two cases. We suggest that the Cdv system functions differently in archaea than ESCRT does in eukaryotes, and that, unlike the eukaryotic case, the Cdv system's main function may be related to surplus membrane invagination and cell-wall synthesis.


Combination of pembrolizumab and pelareorep promotes anti-tumour immunity in advanced pancreatic adenocarcinoma (PDAC).
We previously reported activity of pelareorep, pembrolizumab and chemotherapy. Patients developed new T-cell clones and increased peripheral T-cell clonality, leading to an inflamed tumour. To evaluate a chemotherapy-free regimen, this study assesses if pelareorep and pembrolizumab has efficacy by inducing anti-tumour immunological changes (NCT03723915). PDAC patients who progressed after first-line therapy, received iv pelareorep induction with pembrolizumab every 21-days. Primary objective is overall response rate. Secondary objectives included evaluation of immunological changes within tumour and blood. Clinical benefit rate (CBR) was 42% amongst 12 patients. One patient achieved partial response (PR) and four stable disease (SD). Seven progressed, deemed non-responders (NR). VDAC1 expression in peripheral CD8+ T cells was higher at baseline in CBR than NR but decreased in CBR upon treatment. On-treatment peripheral CD4+ Treg levels decreased in CBR but not in NR. Analysis of tumour demonstrated PD-L1+ cells touching CD8+ T cells, and NK cells were more abundant post-treatment vs. baseline. A higher intensity of PD-L1 in tumour infiltrates at baseline, particularly in CBR vs. NR. Finally, higher levels of soluble (s)IDO, sLag3, sPD-1 observed at baseline among NR vs. CBR. Pelareorep and pembrolizumab showed modest efficacy in unselected patients, although potential immune and metabolic biomarkers were identified to warrant further evaluation.


The treatment of patellar instability by lateral release.
A simple procedure of using a Smillie knife to release the lateral patellar retinaculum and the capsule in the unstable patella syndrome is described. The syndrome includes recurrent dislocation, recurrent subluxation and acute dislocation of the patella. Arthroscopy, to exclude any other pathology such as chondromalacia patellae, is performed before proceeding to closed lateral release. The results of this procedure are as good as those after more major surgical procedures. In a small percentage of patients a second operation such as tibial tubercle transfer or patellectomy may be necessary, especially in patients with an underlying congenital abnormality; but in many patients this type of major surgery has proved unnecessary.


Issues of design and methodology in long-term followup studies.
Beginning with Vaillant, followup studies of schizophrenia have devoted increasing attention to issues of design and methodology. The major advances and elements are described here and include: (1) conceptual framework, (2) design, (3) sample representativeness, (4) sample description, (5) data source and quality, (6) measures, (7) reliability, (8) diagnosis, (9) comparison groups, (10) assessment independence, (11) outcome, (12) missing subjects/bias testing, and (13) statistical techniques.


Monitoring pulse pressure variation during lung resection surgery.
Although pulse pressure variation (PPV) is an effective dynamic parameter widely used to predict the increase in cardiac output after the administration of fluids in abdominal surgery, its use in thoracic surgery is controversial. A study was designed to describe the behaviour of PPV during lung resection surgery. A prospective observational study was conducted on adult patients scheduled for lung resection surgery. Patients with bleeding greater than 200cc, or those who required vasopressors during data collection, were excluded. The PPV values were collected during different phases: in bipulmonary ventilation (T1), after the start of single lung ventilation, and the opening of the thorax (T2), at the end of the procedure prior to the restoration of the bipulmonary ventilation (T3), and after the closure of the thorax in bipulmonary ventilation (T4). The correlation coefficient of the PPV values at the different times was calculated. The study included 50 consecutive patients. The mean values and standard deviations of PPV in the different phases were: T1, 11.14% (6.67); T2 6.24% (3.21, T3 5.68% (3.19), and T4 7.84% (4.61). The repeated ANOVA measurements found significant differences between the mean values of PPV in the different phases (P<.001). The correlation between the PPV values during T1 and T2 (PPVT1 and PPVT2) was r=0.868 ([P<.001], r2=0.753), while between T3 and T4 (PPVT3 and PPVT4) the correlation was r=0.616 ([P<.001], r2=0.379) between the PPV values in T3 and T4. PPV presents a predictable behaviour in the course of lung resection surgery, characterised by a decrease of almost half at the beginning of the unipulmonary ventilation and opening of the thorax. It then remains stable throughout the surgery when there are no changes in the intravascular blood volume.


Endophytic fungal pre-treatments of seeds alleviates salinity stress effects in soybean plants.
In the present study, four endophytic fungi (GM-1, GM-2, GM-3, and GM-4) were tested for their ability to improve soybean plant growth under salinity stress conditions. The seed germination and plant growth were higher in seeds pretreated with endophytic fungal cultures than their controls. The positive influence of fungi on plant growth was supported by gibberellins analysis of culture filtrate (CF), which showed wide diversity and various concentrations of GAs. Specifically, GA4, GA7, GA8, GA9, GA12, and GA20 were found in fungal CFs. Under salinity stress conditions, GM-1 significantly enhanced the length and fresh weight of soybean plants relative to other fungal treatments. GM-1 effectively mitigated the adverse effects of salinity by limiting lipid peroxidation and accumulating protein content. GM-2, GM-3, and GM-4 also counteracted the salinity induced oxidative stress in soybean plants through reduction of lipid peroxidation and enhancement of protein content, maintaining the length and fresh weight of shoots. The activities of the antioxidant enzymes catalase, superoxide dismutase and peroxidase were inhibited in salinity exposed plants, while GM-1 significantly enhanced these antioxidant enzyme activities in plants under salt stress. GM-1 treatment also showed lower levels of abscisic acid and elevated levels of salicylic acid in plants under salinity stress. Hence, GM-1 was identified as Fusarium verticillioides (teleomorph Gibberella moniliformis) isolate RK01 based on its DNA sequence homology. These results suggest that endophytic fungal (F. verticillioides) pre-treatment of soybean seeds would be an effective method to promote soybean plant growth under salinity stress conditions.


Antigenic markers of hepatocellular carcinoma.
One hundred thirty-five hepatocellular carcinomas were examined for the presence of antigenic tumor markers by the avidin-biotin-peroxidase complex method. Ninety-seven were from the US and 38 came from Argentina. The following markers were tested: alpha-fetoprotein (AFP), alpha-1-antitrypsin (AAT), hepatitis B surface antigen (HBsAg), hepatitis B core antigen (HBcAg), hepatitis D delta antigen (HD delta Ag), and Mallory's bodies (MB). In the US cases, AFP was present in 43%, AAT in 41%, HBsAg in 17%, and MB in 48%. Both HBcAg and HD delta Ag were absent. In the cases from Argentina, AFP was found in 26% and AAT in 18%. None of the other antigens were seen. Thirteen US tumors expressed three antigens and two four antigens simultaneously. This study reveals in humans a heterogenous expression of antigens by neoplastic hepatocytes with geographic differences, possibly due to multiple factors such as alcohol consumption or prevalence of hepatitis B infection.


Lovastatin. A preliminary review of its pharmacodynamic properties and therapeutic use in hyperlipidaemia.
Lovastatin is the first of a new class of cholesterol lowering drugs that competitively inhibit HMG-CoA reductase. This new drug decreases cholesterol synthesis and apolipoprotein B concentrations, and increases LDL receptor activity without adverse effects on other products in the cholesterol pathway. In patients with heterozygous familial or polygenic (non-familial) hypercholesterolaemia, oral lovastatin 20 to 40 mg twice daily reduces plasma total cholesterol and LDL-cholesterol concentrations by 25 to 40% over a period of several weeks. Lovastatin also produces decreases in plasma triglyceride and VLDL-cholesterol concentrations, although to a lesser extent. In addition, small though significant increases in HDL-cholesterol concentrations have been observed. Combined administration of lovastatin with other lipid-lowering drugs results in further reductions in plasma total and LDL-cholesterol concentrations beyond those seen with either drug alone. From findings in short term studies, lovastatin appears to be well tolerated with a low incidence of side effects. However, liver function tests and eye examinations for possible lens opacities are advised, and further long term studies in larger groups of patients are necessary before the side effect profile of lovastatin will be clearly established. As would be expected at this relatively early stage of its clinical 'life,' lovastatin has not yet been studied in a manner that would determine its effect on cardiovascular mortality during long term administration. Nevertheless, if the substantial improvements to patients' lipid and lipoprotein profiles observed in short term studies are maintained during long term administration, then lovastatin will have an important role in the pharmacological management of hyperlipidaemia.


Listening to fluoxetine: a hot message from the FLAME trial of poststroke motor recovery.
The fluoxetine for motor recovery after acute ischemic stroke study was a double blind, placebo-controlled trial examining the effects of fluoxetine in patients five- to 10 days after an ischemic stroke. The study found motor improvement to 90 days poststroke, measured as the change in the Fugl-Meyer score, was significantly greater in the fluoxetine group as compared with the placebo group, and that this finding was significant after adjusting for depression. Patients randomized to fluoxetine also had less disability (modified Rankin Scale 0-2). The study adds to the weight of data suggesting that viable strategies exist to improve patient outcomes by initiating a restorative agent, days after stroke injury is fixed. Stroke remains among the leading causes of human disability. Currently, a minority of patients can access approved reperfusion therapies, and among those so treated a substantial fraction derives limited benefit. Therapies that target restorative events have a time window measured in days-weeks and so hold the potential to help many patients with stroke.


Partial mixed neuropathy of the fourth lumbar spinal nerve misdiagnosed as "shin splints."
A case of anteromedial leg pain diagnosed and treated for 10 years as "shin splints" (medial tibial stress syndrome) is described. A history and examination was performed focused on anatomy, biomechanics, and peripheral nerves. Detailed sensory testing was performed in the painful area, and imaging was obtained to confirm the diagnosis. The clinical investigation was consistent with dynamic stenosis of the left L4-5 intervertebral foramen, causing a mixed partial mononeuropathy of the L4 spinal nerve that presented as pain and hypersensitivity in the anteromedial shin. Manual therapy maneuvers intended to open the intervertebral foramen led to resolution of the pain and sensory deficits. After three additional treatments performed within a month, resolution was maintained for >3 years. This case highlights how concepts from preclinical studies, coupled with basic anatomical, neurological, and biomechanical investigations, can be critical for accurate diagnosis and treatment for a case previously considered unresponsive to care.


Additional Telemedicine Rounds as a Successful Performance-Improvement Strategy for Sepsis Management: Observational Multicenter Study.
Sepsis is a major health care problem with high morbidity and mortality rates and affects millions of patients. Telemedicine, defined as the exchange of medical information via electronic communication, improves the outcome of patients with sepsis and decreases the mortality rate and length of stay in the intensive care unit (ICU). Additional telemedicine rounds could be an effective component of performance-improvement programs for sepsis, especially in underserved rural areas and hospitals without ready access to critical care physicians. Our aim was to evaluate the impact of additional daily telemedicine rounds on adherence to sepsis bundles. We hypothesized that additional telemedicine support may increase adherence to sepsis guidelines and improve the detection rates of sepsis and septic shock. We conducted a retrospective, observational, multicenter study between January 2014 and July 2015 with one tele-ICU center and three ICUs in Germany. We implemented telemedicine as part of standard care and collected data continuously during the study. During the daily telemedicine rounds, routine screening for sepsis was conducted and adherence to the Surviving Sepsis Campaign's 3-hour and 6-hour sepsis bundles were evaluated. In total, 1168 patients were included in this study, of which 196 were positive for severe sepsis and septic shock. We found that additional telemedicine rounds improved adherence to the 3-hour (Quarter 1, 35% vs Quarter 6, 76.2%; P=.01) and 6-hour (Quarter 1, 50% vs Quarter 6, 95.2%; P=.001) sepsis bundles. In addition, we noted an increase in adherence to the item "Administration of fluids when hypotension" (Quarter 1, 80% vs Quarter 6, 100%; P=.049) of the 3-hour bundle and the item "Remeasurement of lactate" (Quarter 1, 65% vs Quarter 6, 100%, P=.003) of the 6-hour bundle. The ICU length of stay after diagnosis of severe sepsis and septic shock remained unchanged over the observation period. Due to a higher number of patients with sepsis in Quarter 5 (N=60) than in other quarters, we observed stronger effects of the additional rounds on mortality in this quarter (Quarter 1, 50% vs Quarter 5, 23.33%, P=.046). Additional telemedicine rounds are an effective component of and should be included in performance-improvement programs for sepsis management.


Interaction between intra-oral cinnamaldehyde and nicotine assessed by psychophysical and physiological responses.
Cinnamaldehyde and nicotine activate the transient receptor potential subtype A1 (TRPA1) channel, which may cause burning sensations. This study investigated whether cinnamaldehyde modulates nicotine-induced psychophysical and physiological responses in oral tissues. Healthy non-smokers (n = 22) received, in a randomized, double-blind, crossover design, three different gums containing 4 mg of nicotine, 20 mg of cinnamaldehyde, or a combination thereof. Assessments of orofacial temperature and blood flow, blood pressure, heart rate, taste experience, and intra-oral pain/irritation area and intensity were performed before, during, and after a 10-min chewing regime. Cinnamaldehyde increased the temperature of the tongue and blood flow of the lip, and was associated with pain/irritation, especially in the mouth. Nicotine increased the temperature of the tongue and blood flow of the cheek, and produced pain/irritation in the mouth and throat. The combination of cinnamaldehyde and nicotine did not overtly change the psychophysical or physiological responses. Interestingly, half of the subjects responded to cinnamaldehyde as an irritant, and these cinnamaldehyde responders reported greater nicotine-induced pain/irritation areas in the throat. Whether sensitivity to cinnamaldehyde can predict the response to nicotine-induced oral irritation remains to be determined. A better understanding of the sensory properties of nicotine in the oral mucosa has important therapeutic implications because pain and irritation represent compliance issues for nicotine replacement products.


Differences in clinical course in zidovudine-treated asymptomatic HIV-infected men associated with T-cell function at intake.
Declining CD4+ T-cell numbers and anti-CD3-induced T-cell responsiveness are prognostic markers for progression of HIV infection. We investigated the effect of long-term (2-year) zidovudine treatment on these immunological markers in a group of nine asymptomatic p24-antigenaemic men, five of whom progressed to AIDS. A group of 10 untreated HIV-infected men, five of whom progressed to AIDS, was studied as a control. At intake, 1 year before the start of treatment, CD4+ T-cell numbers in the groups were not significantly different. However, at that time progressors already exhibited an extremely low anti-CD3-induced T-cell responsiveness compared with non-progressors. In all people T-cell responsiveness and the number of CD4+ T-cells had improved 6 months after the start of zidovudine treatment. However, CD4+ T-cell numbers were not persistently elevated, and restoration of T-cell responsiveness was of only short duration. Our results show that zidovudine treatment in the asymptomatic phase of HIV infection did not result in a sustained improvement in T-cell function. Furthermore, they suggest that differences in clinical course among zidovudine-treated asymptomatics may be caused by heterogeneity of this group with respect to T-cell functional capacity at the start of treatment.


The Integration of Electrical Signals Originating in the Root of Vascular Plants.
Plants have developed different signaling systems allowing for the integration of environmental cues to coordinate molecular processes associated to both early development and the physiology of the adult plant. Research on systemic signaling in plants has traditionally focused on the role of phytohormones as long-distance signaling molecules, and more recently the importance of peptides and miRNAs in building up this communication process has also been described. However, it is well-known that plants have the ability to generate different types of long-range electrical signals in response to different stimuli such as light, temperature variations, wounding, salt stress, or gravitropic stimulation. Presently, it is unclear whether short or long-distance electrical communication in plants is linked to nutrient uptake. This review deals with aspects of sensory input in plant roots and the propagation of discrete signals to the plant body. We discuss the physiological role of electrical signaling in nutrient uptake and how nutrient variations may become an electrical signal propagating along the plant.


A risk profile of street youth in northern California: implications for gender-specific human immunodeficiency virus prevention.
To assess human immunodeficiency virus (HIV) risk behaviors of street youth and to determine whether risk behaviors differ by gender or housing status. Using systematic street-based sampling in four Northern California cities, we recruited 429 street youth (mean age = 19.2 years). Participants completed a structured interview which was used to assess sexual and drug HIV risk behaviors. The majority of youth were heterosexual (85%), white (77%), male (68%), and currently without any type of stable housing (75%). Although 60% of the sample had had vaginal sex in the past 30 days, only 44% used a condom the last time they had sex. About one-third (32%) of the sample reported ever injecting drugs, and almost all reported lifetime use of multiple drugs including D-lysergic acid diethylamide (96%), marijuana (90%), alcohol (81%), cocaine (70%), and speed (70%). Compared to males, females were equally likely to use injection and noninjection drugs, but were more likely to be sexually active (P < .001), were more likely to have been diagnosed with a sexually transmitted disease (P = .005), and were less likely to report consistent condom use (P = .003) or intent to use condoms consistently in the future (P = .005). Compared with those with stable housing, youth who were currently without such housing reported higher rates of injection, and other drug use; females without stable housing were less likely to have used condoms the last time they had vaginal intercourse. The high level of HIV risk behavior in this street-based sample of youth, particularly females and youth without stable housing, suggests an urgent need for gender-specific prevention efforts and an increased range of housing options.


Treatment of paralytic lagophthalmos by loading the lid with a gold plate and lateral canthopexy.
Various methods of managing patients with lagophthalmos secondary to paralysis of the facial nerve have been reported. While addition of a gold plate facilitates displacement of the upper eyelid downwards, coaptation of the lid margin is often incomplete because of coexisting ectropion of the lower lid. The outcome obtainable from loading the lid with a gold plate alone is often unsatisfactory. To manage the deformity by combining the loading of the lid with gold plate and lateral canthopexy is technically simple. Morbidity is minimal as it can be done under local anaesthesia. Adequacy of coaption of the palpebral margin could be assessed immediately. We have managed a total of seven (mainly elderly) such patients between 1999 and 2000 in our hospitals. The outcome was generally satisfactory and there were no complications.


Beyond the Debye length in high ionic strength solution: direct protein detection with field-effect transistors (FETs) in human serum.
In this study, a new type of field-effect transistor (FET)-based biosensor is demonstrated to be able to overcome the problem of severe charge-screening effect caused by high ionic strength in solution and detect proteins in physiological environment. Antibody or aptamer-immobilized AlGaN/GaN high electron mobility transistors (HEMTs) are used to directly detect proteins, including HIV-1 RT, CEA, NT-proBNP and CRP, in 1X PBS (with 1%BSA) or human sera. The samples do not need any dilution or washing process to reduce the ionic strength. The sensor shows high sensitivity and the detection takes only 5 minutes. The designs of the sensor, the methodology of the measurement, and the working mechanism of the sensor are discussed and investigated. A theoretical model is proposed based on the finding of the experiments. This sensor is promising for point-of-care, home healthcare, and mobile diagnostic device.


Palladium-Catalyzed Cyclization Reaction of Oxime Acetates and Aryl Iodides: Syntheses of 2-Imidazolines.
A novel and versatile method for the synthesis of 2-imidazolines has been developed via the Pd-catalyzed cyclization reaction of readily available homoallenyl oxime acetates with aryl iodides. This protocol is performed under mild reaction conditions and needs no additives or ligands.


HF ultrasound vs PET-CT and telethermography in the diagnosis of In-transit metastases from melanoma: a prospective study and review of the literature.
Over the past several years the incidence of cutaneous melanoma has rapidly increased. This tumor develops often in-transit metastases that significantly reduce patient survival at 5 years. To improve prognosis and quality of life in patients with melanoma metastases, a mini invasive procedure like electrochemotherapy (ECT) is adopted to remove superficial tissue lesions. To detect the melanoma metastases, high frequency (HF) ultrasound (US) is used. This technique, though, can be time-consuming and it needs an expert operator and a high performing machine. Therefore, we asked whether the US could be replaced or integrated with other less time-consuming techniques such as 18-FDG positron emission tomography/computed tomography (PET-CT) and telethermography (TT). Fifteen patients (4 males and 11 females - age range: 63-91) affected whit advanced stage melanoma were enrolled. They presented 52 in-transit metastases as detected by the three techniques used, HF-US, PET/CT and TT within 30 days before ECT. All the 52 lesions were detected by HF-US (100%), 24/52 were detected by PET-CT (42,6%) and 15/52 were detected by TT (27,7%). PET-CT reported 3.7% false positives, while no false positive were reported by TT. As US detected 100% lesions, compared to the other two techniques used, US, along with clinical examination, has still to be considered as gold standard in the diagnosis of metastatic lesions. US, associated with an exhaustive anamnesis and accurate clinical examination, cannot be replaced by either PET-CT or TT. When US performing devices and experienced operators are not available, though, it is highly recommended to integrate US with at least one of the other techniques. Under certain circumstances, as in the case of obese and non-collaborating patients or in patients with lymphatic stasis, these techniques should be integrated to obtain exact in-transit metastases evaluation.


Canal-centering ability: An endodontic challenge.
During instrumentation of the root canal, it is important to develop a continuously tapered form and to maintain the original shape and position of the apical foramen. However, the presence of curvatures may cause difficulty in root canal instrumentation. The ability to keep the instruments centered is essential to provide a correct enlargement, without excessive weakening of the root structure. Several studies have shown that Ni-Ti instruments remain significantly more centered and demonstrated less canal transportation than stainless steel files. Considerable research has been undertaken to understand the several factors related to an instrument's canal-centering ability. In this article, we have discussed the influence of various parameters such as alloys used in the manufacture of instruments, instrument cross-section, taper, and have given tips on canal-centering ability.


Nanovesicles-Mediated Drug Delivery for Oral Bioavailability Enhancement.
Bioavailability is an eternal topic that cannot be circumvented by peroral drug delivery. Adequate blood drug exposure after oral administration is a prerequisite for effective treatment. Nanovesicles as pleiotropic oral vehicles can solubilize, encapsulate, stabilize an active ingredient and promote the payload absorption via various mechanisms. Vesicular systems with nanoscale size, such as liposomes, niosomes and polymersomes, provide a versatile platform for oral delivery of drugs with distinct nature. The amphiphilicity of vesicles in structure allows hydrophilic and lipophilic molecule(s) either or both to be loaded, being encapsulated in the aqueous cavity or the inner core, respectively. Depending on high oral transport efficiency based on their structural flexibility, gastrointestinal stability, biocompatibility, and/or intestinal epithelial affinity, nanovesicles can markedly augment the oral bioavailability of various poorly absorbed drugs. Vesicular drug delivery systems (VDDSs) demonstrate a lot of preferences and are becoming more prominent of late years in biomedical applications. Equally, these systems can potentiate a drug's therapeutic index by ameliorating the oral absorption. This review devotes to comment on various VDDSs with special emphasis on the peroral drug delivery. The classification of nanovesicles, preparative processes, intestinal transport mechanisms, in vivo fate, and design rationale were expounded. Knowledge on vesicles-mediated oral drug delivery for bioavailability enhancement has been properly provided. It can be concluded that VDDSs with many merits will step into an energetic arena in oral drug delivery.


Best of Both Worlds? Fixation of Distal Femur Fractures with the Nail-Plate Construct.
Distal femoral fractures are a significant injury sustained by low- and high-energy trauma. Common treatment practices are lateral locking plate or intramedullary nail fixation, with disadvantages including risk of non and malunion and limited post-operative weightbearing status. Combining both techniques as a nail-plate construct (NPC) theoretically achieves enhanced fixation to allow immediate weightbearing. The aim of this study is to examine radiographic union, malunion and patient-reported outcomes in distal femur NPC fixation. Single-center retrospective study including all patients >18 years who sustained distal femur fractures treated with NPC. Primary outcomes were radiographic union, malunion and patient reported outcome measures at minimum 1-year follow-up. Secondary outcome measures included post-operative mobility, length of stay and complications. Relevant variables of normality are reported as mean with standard deviation. Subgroup analysis of patients aged <65 and ≥65 years are provided. Sixteen patients were included in the study. Rate of radiographic union was 100%. There was no case of malunion. All patients were allowed to bear full weight immediately post-operatively. Mean length of stay was 9.50 days, with 37.5% of patients discharged directly home. The majority (85.7%) of patients returned to pre-injury mobility. Early post-operative complications occurred in three patients. Three patients returned to theater. The mean EQ-5D-5L index value was 0.713, with 71.4% describing no problems with self-care and 85.7% reporting no or slight problems with usual daily activities. The NPC provided stable fixation permitting full weightbearing post-operatively with no cases of non or malunion. Return to pre-injury mobility and activity are encouraging. Based on these results we support the use of nail-plate construct fixation in the management of distal femur fractures.


Photocatalytic Deoxygenation of Sulfoxides Using Visible Light: Mechanistic Investigations and Synthetic Applications.
The photocatalytic deoxygenation of sulfoxides to generate sulfides facilitated by either Ir[(dF(CF3)ppy)2(dtbbpy)]PF6 or fac-Ir(ppy)3 is reported. Mechanistic studies indicate that a radical chain mechanism operates, which proceeds via a phosphoranyl radical generated from a radical/polar crossover process. Initiation of the radical chain was found to proceed via two opposing photocatalytic quenching mechanisms, offering complementary reactivity. The mild nature of the radical deoxygenation process enables the reduction of a wide range of functionalized sulfoxides, including those containing acid-sensitive groups, in typically high isolated yields.


Involvement of level I neck lymph nodes in advanced squamous carcinoma of the larynx.
This study was performed to evaluate the incidence of metastasis at level I in patients with squamous laryngeal cancer. One hundred consecutive patients with squamous carcinoma of the larynx were submitted to surgical treatment including radical neck dissection. The tumor stage was T3 or T4, and the neck stage was N1-N2c. Lymph node metastases were pathologically confirmed in 80 patients. Metastases were concentrated within level II in 59% of cases, level III in 17% of cases, level IV in 11% of cases, and level V in 6% of cases. Only 2 patients (2%) had detectable tumors in the lymph nodes of the submandibular triangle (level IB). This study shows that patients with laryngeal cancer rarely present metastases at the submandibular triangle, even in advanced local disease with cervical metastasis staged as N1 to N2c. Therefore, dissection of the submandibular triangle is indicated only in the presence of clinical, radiographic, or cytologic evidence of metastatic disease at level I.


Associations between Drug Use and Sexual Risk Behaviours among Men Who Have Sex with Men in Japan: Results from the Cross-Sectional LASH Study.
This study assessed drug use patterns among men who have sex with men (MSM) in Japan, and evaluated their potential associations with sexual risk behaviours. Between September and October 2016, study subjects were recruited through a cross-sectional survey (LASH: Love Life and Sexual Health) using a geosocial networking application for MSM. Of the participants, 25.4% (1756/6921) reported ever having used drugs, and 11.3% (780/6921) reported having done so in the past six months. Those who used drugs were more likely to have greater knowledge of HIV/sexually transmitted infections (STIs). Drug use in the past six months was independently associated with each of the following sexual risk behaviours in the same period: (i) six or more sexual partners (adjusted odds ratio [aOR] = 2.70, 95% confidence interval [CI]: 2.30-3.17); (ii) condomless anal intercourse (aOR = 2.88, 95% CI: 2.43-3.42); (iii) group sex (aOR = 2.60, 95% CI: 2.22-3.05); and (iv) sex work (aOR = 2.30, 95% CI: 1.67-3.16). These results suggest that MSM in Japan who use drugs are more likely to report sexual risk behaviours, while also having greater knowledge of HIV/STIs. Supporting MSM to minimise the harm from drug use may be helpful in reducing HIV transmission among this priority population.


Laparoscopic expertise increases hospital volume of adrenal surgery.
The laparoscopic approach is preferred for most adrenal tumors but technical challenges limit its use. We evaluated the effects of the availability of laparoscopic expertise on the volume of the adrenal surgery at a tertiary care hospital. Patients undergoing adrenalectomy 5 years before and 5 years after an advanced laparoscopic program was established were retrospectively reviewed. The average annual volume increased from 2 cases during the first period to 15 cases during the 5 years (1999-2003) after laparoscopic expertise became available. The average distance of travel to the hospital was significantly greater for the latter patients and significantly more patients were referred from outside of a 30-mile radius. Although the average statewide annual number of adrenalectomies has not significantly changed, the proportion of adrenalectomies performed at our institution rose. Offering a laparoscopic approach has altered physicians' referral patterns and has significantly increased the volume of adrenal surgery at the institution.


A randomized trial between different suture materials (polydioxanone vs. poliglecaprone 25) and different suturing techniques (running subcuticular suture alone vs. with running horizontal mattress) in prevention of hypertrophic scar development in median sternotomy wound.
Hypertrophic scar development after median sternotomy wound in cardiac surgery patients is quite common in surgical practice and becomes a major concern nowadays. To compare cosmetic outcome between different suture materials and different suture techniques for skin closure in median sternotomy wound. A randomized clinical trial was conducted in 80 patients who underwent cardiac surgery in Thammasat University Hospital, Thailand. In respect of the materials and the techniques used to suture the skin, the patients were randomly allocated to four groups. In group 1, the skin was closed with subcuticular running 4-0 Poliglecaprone 25 (Monocryl). In group 2, the skin was closed with subcuticular running 4-0 Polydioxanone (PDS). In group 3, the skin was closed with subcuticular running 4-0 Poliglecaprone 25 (Monocryl) and running horizontal mattress 6-0 Nylon. In group 4, the skin was closed with subcuticular running 4-0 Polydioxanone (PDS) and running horizontal mattress 6-0 Nylon. Postoperative evaluation was performed at 2 and 6 weeks, 3 and 6 months follow-up visits. The scar was analyzed in three parts: upper, middle and lower one third of the sternal wound. The outcome measures for surgical wound were width, height and overall appearance of the scar using the Vancouver scar scale (VSS). A linear visual analogue score (VAS) was preformed to assess pain and itch. At 6 months, there were no significant differences between 4 groups ofpatients in every parameters (width, height, VSS, pain score and itch score) at three different wound sites (upper middle and lower). There was a statistically significant and progressive increase in scar stretching, height and total VSSfrom top to bottom of the sternum with the same pattern in all groups ofpatients (p<0. 05). At 6 months, scar showed a statistically significant difference in width when compares to6 weeks and 3 months (p<O.001).Female had a statistically significant difference ofscar stretching at upper two third of the sternum (p<0. 05). Female scar width was approximately 2folds greater than male patient. Duringfollow-up in group 3, two patients died postoperatively due to multi-organ failure and one patient developed wound infection. There were no significant differences in cosmetic outcomes between different suture materials and different suture techniques.


Retaining hospital workers: a rapid methodology to determine incentive packages.
As efforts are made to increase the production of new human resources for health, simultaneous attention must be placed on retaining existing health workers in hospitals and other health facilities for as long as possible to increase access to healthcare services. The US Agency for International Development (USAID)'s CapacityPlus project is designing a rapid retention survey tool using the discrete choice experiment, a powerful, quantitative method to determine the relative importance health workers place on different characteristics related to their choice of employment. The user-friendly tool will allow human resource managers to rapidly assess retention preferences to better pinpoint the bundle of incentives and interventions that would most cost-effectively motivate health workers to take up posts in underserved facilities. The results of the survey can be used locally to create evidence-based incentive packages or to advocate with policy-makers and other decision-makers regarding the most favorable national retention policies and strategies for implementation.


A case-control study of non-alcoholic fatty liver disease in breast cancer.
Patients with breast cancer sometimes present with increased liver enzymes during follow-up period that may be consistent with hepatic steatosis. This effect known as non-alcoholic fatty liver disease may be associated with the malignancy itself, drugs or some other well-known risk factors that may induce steatosis. We studied the influences of primary disease and treatment on steatosis in patients with breast cancer. There were four groups of patients in our study. Group 1: 40 newly diagnosed, previously untreated breast cancer; Group 2: 45 cases of breast cancer treated with systemic therapy; Group 3: 40 cases of ovarian cancer; Group 4: 40 healthy women. Hepatic steatosis was evaluated by sonography by two radiologist, independently. We also evaluated major risk factors, biochemical findings, and influences of treatment on hepatic steatosis. We detected steatosis in 63%, 72%, 77%, and 48% of patients in groups 1, 2, 3, and 4, respectively. There was a statistically significant difference only between groups 3 and 4 (P = 0.045). However, grade 2 and 3 steatosis were more frequent in breast cancer patients (group 1 and 2), compared with mild steatosis in ovarian cancer patients and healthy women. Although a good correlation was found between tamoxifen use and chemotherapy on development of non-alcoholic fatty liver disease, no association of hepatic steatosis with transaminase levels was found, which might be of help for earlier detection of steatosis. AST/ALT ratio was found to have no impact on the rate of hepatic steatosis, contrary to the literature. Hepatic steatosis, excluding patients with grade 1 steatosis, which may be a normal variant, were more readily detected in patients with breast cancer. This effect was aggravated by use of tamoxifen, but not the chemotherapy. Non-alcoholic fatty liver disease in patients with breast cancer may be associated with the primary tumor itself or some well-known risk factors such as obesity, hyperlipidemia, and diabetes mellitus, which needs to be explored.


Nanochannel Implants for Minimally-Invasive Insertion and Intratumoral Delivery.
Novel approaches to achieve local, intratumoral drug delivery have the dual benefit of reducing systemic toxicity while enhancing efficacy for malignant cells. We have developed a new implantable system combining a next-generation BioNEMS nanofluidic membrane with parallel nanochannels that offers controlled release of biomolecules. Based on concentration-driven diffusive transport, nanochannel membranes provide a "drug agnostic" delivery mechanism. Integrating this nanotechnology within a small implantable capsule permits multipurpose functionality and compatibility with different therapeutic approaches as well as diagnostic imaging capability. A minimally-invasive, percutaneous trocar delivery mechanism enables serial implantation throughout a target tissue volume. In this manuscript, we demonstrate that this platform is capable of sustained delivery for chemotherapy, radiosensitization, immunomodulation, and imaging contrast, among others. This platform's utility was established through release of doxorubicin, OX86, FGK45, and Magnevist. Further proof-of-concept experiments demonstrated successful in vivo implantation and intratumoral release of antibodies and contrast agents, as well as the platform's MR-compatibility and capability as a radiopaque fiducial. These results provide strong evidence for a flexible, multifunctional nanofluidic implant capable of broadening local delivery utility in the clinic.


Reliability analysis for radiographic measurement of limb length discrepancy: full-length standing anteroposterior radiograph versus scanogram.
Patients with limb length discrepancy (LLD) often have associated angular deformities requiring a standing full-length radiograph of the lower limb in addition to a scanogram. The purpose of our study was to determine the intraobserver and interobserver reliability of measuring LLD with both techniques, using computed radiography. The LLD was measured on 70 supine scanograms and standing anteroposterior radiographs of the lower extremity by 5 blinded observers on 2 separate occasions. Intraclass correlation coefficient (ICC) and mean absolute difference (in millimeters) was calculated to assess intraobserver and interobserver reliability and found to be excellent for both radiographic techniques. Intraobserver ICC and mean absolute difference was 0.975 to 0.995 and 1.5 to 2.6 mm for scanogram and 0.939 to 0.996 and 1.5 to 4.6 mm for the standing radiograph, respectively. Repeated measurements for both radiographic studies were within 5 mm of the first measurement greater than 90% and within 10 mm greater than 95% of times. Interobserver ICC and mean absolute difference was 0.979 and 2.6 mm for scanogram and 0.968 and 3.0 mm for the standing radiograph. The reliability was excellent irrespective of age, sex, and underlying diagnosis other than Blount disease, which had good reliability. A standing anteroposterior radiograph of the lower extremity should be the imaging modality of choice when evaluating patients with limb length inequality who may have angular deformities because it allows a comprehensive evaluation of the extremity and is as reliable as a scanogram for measuring LLD. This approach may decrease the radiation exposure and financial burden involved in assessing patients with unequal limb lengths.


BRMS1 gene expression may be associated with clinico-pathological features of breast cancer.
Our aim is to investigate whether or not the breast cancer metastasis suppressor 1 (BRMS1) gene expression is directly linked to clinico-pathological features of breast cancer. Following a stringent inclusion and exclusion criteria, case-control studies with associations between BRMS1 and breast cancer were selected from articles obtained by way of searches conducted through an electronic database. All statistical analyses were performed with Stata 12.0 (Stata Corp, College Station, TX, U.S.A.). Ultimately, 1,263 patients with breast cancer were found in a meta-analysis retrieved from a total that included 12 studies. Results of our meta-analysis suggested that BRMS1 protein in breast cancer tissues was significantly lower in comparison with normal breast tissues (odds ratio, OR = 0.08, 95% confidence interval (CI) = 0.04-0.15). The BRMS1 protein in metastatic breast cancer tissue was decreased than from that was found in non-metastatic breast cancer tissue (OR = 0.20, 95%CI = 0.13-0.29), and BRMS1 protein in tumor-node-metastasis (TNM) stages 1 and 2 was found to be higher than TNM stages 3 and 4 (OR = 4.62, 95%CI = 2.77-7.70). BRMS1 protein in all three major types of breast cancer was lower than that of control tissues respectively. We also found strong correlations between BRMS1 mRNA levels and TNM stage and tumor size. The results our meta-analysis showed that reduction in BRMS1 expression level was linked directly to clinico-pathological features of breast cancer significantly; therefore, suggesting the loss of expression or reduced levels of BRMS1 is potentially a strong indicator of the metastatic capacity of breast cancer with poor prognosis.


Dependence of turbulent Rayleigh-Taylor instability on initial perturbations.
The dependency of the self-similar Rayleigh-Taylor bubble acceleration constant alpha(b)(identical with [(amplitude)/2] x (displacement) x (Atwood number)) on the initial perturbation amplitude h(0k) is described with a model in which the exponential growth of a small amplitude packet of modes makes a continuous nonlinear transition to its "terminal" bubble velocity proportional, variant Fr[equal to(Froude number)(1/2)]. Then, by applying self-similarity (diameter proportional, variant amplitude), alpha(b) is found to increase proportional to Fr and logarithmically with h(0k). The model has two free parameters that are determined from experiments and simulations. The augmentation of long wavelength perturbations by mode coupling is also evaluated. This is found to decrease the sensitivity of alpha(b) on the initial perturbations when they are smaller than the saturation amplitude of the most unstable modes. These results show that alpha(b) can vary by a factor of 2-3 with initial conditions in reasonable agreement with experiments and simulations.


[Levels of manganese in biological media: value, samplings, physiopathological variations. Bibliographic review].
The great diversity of methods for manganese analysis in biological materials (serum, plasma, whole blood, urine, spinal fluid and hair) reveals the difficulty in measuring extremely small quantities of this element. An examination of these methods demonstrate that the most used one is flameless atomic absorption spectrometry. This review offers a comparison of the different instrument settings. Authors' recommendations for the collecting of samples are reported in detail. A description of the preliminary steps, the handling of the specimen samples, the preparation of the standards, procedures used, analytical criteria and perturbations is also included. Normal values and their physiological and pathological variations are also described.


Elasticity of canine vocal fold tissue.
Stress-strain curves were obtained from vocalis muscle tissue that was kept viable in an aerated Krebs-Ringer solution after excision of the larynx from live dogs. Results are compared to similar curves obtained from dead tissue and suggest that vocal fold elasticity depends on the level of strain, the elapsed time after elongation, the condition of the tissue, and the choice of rest length for strain computation. Tables of Young's moduli for various conditions are given.


Insect Artifacts Are More than Just Altered Bloodstains.
The bases for forensic entomology are that insects and their arthropod relatives can serve as evidence in criminal, medical and civil legal matters. However, some of the very same species that provide utility to legal investigations can also complicate crime scenes by distorting existing body fluid evidence (e.g., bloodstains, semen, saliva) and/or depositing artifacts derived from the insect alimentary canal at primary or secondary crime scenes. The insect contaminants are referred to as insect stains, artifacts, specks or spots, and are most commonly associated with human bloodstains. This review will discuss the different types of insect artifacts that have been described from crime scenes and laboratory experiments, as well as examine insect contaminates (non-blood based artifacts, transfer patterns, meconium, and larval fluids) that have received little research or case attention. Methods currently used for distinguishing insect stains from human body fluids will also be discussed and compared to presumptive tests used for identification of human body fluids. Since all available methods have severe limitations, areas of new research will be identified for the purpose of development of diagnostic techniques for detection of insect artifacts.


Evaluation of Euroimmun Anti-Zika Virus IgM and IgG Enzyme-Linked Immunosorbent Assays for Zika Virus Serologic Testing.
With the emerging Zika virus (ZIKV) epidemic, serologic diagnosis relies on a labor-intensive IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA) and confirmation by a plaque reduction neutralization test (PRNT). To streamline serologic testing, several commercial assays have been developed. Our aim was to compare the commercial Euroimmun anti-ZIKV IgM and IgG assays to the reference MAC-ELISA and PRNT currently in use. Serum specimens submitted to Public Health Ontario Laboratory, Canada, were tested for IgM and IgG using the Euroimmun assays and the results were compared with those from MAC-ELISA. The PRNT was performed on positive or equivocal specimens using either MAC-ELISA or Euroimmun assays, MAC-ELISA-inconclusive specimens, and a convenience sample of specimens negative by both assays (cohort 1). Another set of specimens selected on the basis of PRNT results was subsequently tested by the Euroimmun assays (cohort 2). MAC-ELISA was positive, equivocal, negative, and inconclusive in 57/223, 15/223, 147/223, and 4/223 specimens, respectively. Among the 76 specimens that were MAC-ELISA positive, equivocal, or inconclusive, 30 (39.5%) were Euroimmun IgM and/or IgG positive or equivocal. Among the 147 MAC-ELISA-negative specimens, 136 (92.5%) were Euroimmun IgM and IgG negative. The sensitivity of the combined Euroimmun IgM/IgG against the PRNT was 83% (cohort 1) and 92% (cohort 2), whereas the specificity was 81% (cohort 1) and 65% (cohort 2). The combined Euroimmun IgM/IgG showed good specificity (92.5%) but suboptimal sensitivity (39.5%) compared with that of the MAC-ELISA. However, the sensitivity of the combined Euroimmun IgM/IgG against the PRNT was significantly higher (83 to 92%). More studies are needed before commercial assays are implemented for routine ZIKV serologic diagnosis.


Synthesis and antitubercular screening of some novel 4H-1,4- benzothiazines and their sulfones under environment benign solvent free conditions as future anti-tubercular agents.
Some novel analogs of 4H-1,4-benzothiazines were synthesized under environmentally benign solvent free conditions by one pot oxidative cyclocondensation of substituted 2- aminobenzenthiols with compounds having active methylene group and then converted in to sulfones. These compounds were examined as antitubercular agents against Mycobacterium tuberculosis H37Rv using REMA plate method. The best results have MICs from 6.4 to 8.8 μg/mL, comparable to phenothiazines. IR, NMR and mass spectral investigations are included for structural elucidation.


Using an optical scanner and data base program to manage a family medicine teaching program.
This article describes the value of optically scannable forms and off-the-shelf software in improving administration of a required multi-site, third-year family medicine preceptorship. Formerly, a small preceptorship administrative staff manually handled nearly 1,000 evaluation forms per year. The process was slow, cumbersome, expensive, and inflexible. Optically scannable forms are now used and data bases are created, from which a series of administrative reports are easily generated. This system has reduced management time and cost, eliminated errors, and allowed staff to create both standardized and specialized reports as needed.


Pathophysiology of Gastroesophageal Reflux Disease.
Gastroesophageal reflux disease pathophysiology is multifactorial and linked to a misbalance between the aggressiveness of the refluxate into the esophagus or adjacent organs and the failure of protective mechanisms associate or not to a defective valvular mechanism at the level of the esophagogastric junction incapable of dealing with a transdiaphragmatic pressure gradient. Antireflux mechanisms include the lower esophageal sphincter and abdominal esophagus, the diaphragm, the angle of His, the Gubaroff valve, and the phrenoesophageal membrane. Protective mechanisms include esophageal motility, saliva production, and epithelial protection. Disruption of this balance occurs most commonly due to the presence of a hiatal hernia, esophageal dysmotility, a rise in abdominal pressure (obesity), and decrease in thoracic pressure (chronic lung diseases).


Stress hormones and the immunological responses to heat and exercise.
This review focuses on the response of "stress" hormones to heat, exercise (single or repeated bouts), and combinations of these stimuli, with particular reference to their impact upon immune function. Very hot conditions induce a typical stress response, with secretion of catecholamines and cortisol. The catecholamines induce a demargination of leukocytes, and cortisol subsequently causes cells to migrate to lymphoid tissue. Sustained exercise, even in a thermally comfortable environment, induces a larger hormonal response than moderate thermal stress. With moderate exercise, increases in leukocyte numbers are related mainly to plasma norepinephrine concentrations, but with more intense exercise epinephrine concentrations assume a major importance. As exercise continues, plasma cortisol levels also rise, inducing an influx of neutrophils from bone marrow and an efflux of other leukocyte subsets. A combination of exercise and heat stress augments both hormonal and leukocyte responses. But these changes seem to be reversed if temperatures are clamped by exercising in cold water. If a second bout of exercise is performed with an inter-test interval of 30-45 min, neither hormone concentrations nor immune responses show any great cumulative effect under temperate conditions. However, in a hot environment the second exercise bout induces a larger and more persistent neutrophilia. Training influences these various responses mainly by decreasing the stress imposed when exercising at a given absolute work-rate.


Covalently bound pH-indicator dyes at selected extracellular or cytoplasmic sites in bacteriorhodopsin. 1. Proton migration along the surface of bacteriorhodopsin micelles and its delayed transfer from surface to bulk.
The kinetics of the light-induced release and uptake of protons was monitored with the optical pH-indicator fluorescein covalently bound to various sites on the extracellular and cytoplasmic surfaces of bacteriorhodopsin. Selective labeling was achieved by reacting (iodoacetamido)fluorescein with the single cysteine residues in bacteriorhodopsin introduced at the desired positions by site-directed mutagenesis. All measurements were performed with bacteriorhodopsin micelles in phospholipid/detergent mixtures in 150 mM KCl at 22 degrees C, pH 7.3. Neither the replacements by cysteine nor the subsequent labeling affected the absorption spectrum of bacteriorhodopsin and the rise times of the M intermediate. Only the decay of M was altered for some bacteriorhodopsin mutants with cysteine residues on the cytoplasmic side. The proton release time detected with fluorescein attached to the extracellular surface (the proton release side) at position 72 (in the loop connecting helices B and C) or 130 (DE loop) was 22 +/- 4 microseconds, clearly faster than that measured with pyranine in the aqueous bulk phase (125 +/- 10 microseconds for wild-type and all mutants studied). For bacteriorhodopsin mutants labeled at positions 35, 101, 160, 229, and 231 in the cytoplasmic loop region (the proton uptake side), the released proton was observed with a time of 61 +/- 4 microseconds. This was about 3-fold slower than the release time on the extracellular side, but still significantly faster than that measured with pyranine in the bulk phase. These results suggest that the released protons are retained on the micellar surface and move more rapidly along this surface to the cytoplasmic side than from the surface to the bulk medium.(ABSTRACT TRUNCATED AT 250 WORDS)


Disparities in Confidence to Manage Chronic Diseases in Men.
Chronic diseases are highly prevalent among men in the United States and chronic disease management is problematic for men, particularly for racial and ethnic minority men. This study examined the association between health information seeking and confidence to manage chronic diseases among men. Study data were drawn from the 2007 Health Tracking Household Survey and analyzed using multiple binary logistic regressions. The analytical sample included 2,653 men, 18 years and older with a chronic illness. Results: Health information seeking was not associated with confidence to manage chronic illnesses. African-American men had lower odds than White men to agree to take actions to prevent symptoms with their health. Hispanic men had lower odds than White men to agree to tell a doctor concerns they have, even when not asked. Racial and ethnic minority men with a chronic condition appear to be less confident to manage their health compared to white men. Chronic disease management needs greater exploration to understand the best ways to help racial and ethnic minority men successfully manage their chronic condition.


Preparation of injectable hydrogels from temperature and pH responsive grafted chitosan with tuned gelation temperature suitable for tumor acidic environment.
In this present work, stimuli responsive polymers that can respond to the temperature and pH of the environment were prepared. A series of temperature responsive diblock copolymers based on poly(ethylene glycol) methyl ether (mPEG) and ε-caprolactone (CL) were synthesized. Subsequently, the diblock copolymers were grafted onto chitosan, a pH responsive biopolymer. These chitosan-graft-(mPEG-block-PCL) (chitosan-g-(mPEG-b-PCL)) graft copolymers were structurally characterized by 1H NMR and FTIR and their sol-gel phase transitions were analyzed by the test tube inversion method as well as dynamic rheological measurements. These chitosan-g-(mPEG-b-PCL) graft copolymers demonstrated tunable temperature and pH responsive sol-gel phase transitions that correspond well with body temperature and pH of acidic tumor microenvironments. Gelation temperature (Tgel) decreased with increasing pH of the system, increasing PCL composition in the diblock copolymers, increasing solution concentration and decreasing grafting content of the diblock copolymers on chitosan. The graft copolymer hydrogels successfully showed the sustained release of both doxorubicin and curcumin for up to 2 weeks. The designed system was based on chitosan-g-(mPEG-b-PCL) graft copolymers, of which chitosan showed pH responsive properties and mPEG-b-PCL acted as a temperature sensitive moiety. In addition, mPEG and PCL are recognized as biocompatible polymers and chitosan has been engaged in various pharmaceutical research. Thus, this system could be considered an alternative choice for drug delivery applications.


Unveiling anticancer, antimicrobial, and antioxidant activities of novel synthesized bimetallic boron oxide-zinc oxide nanoparticles.
Bimetallic nanoparticles have received much attention recently due to their multifunctional applications, and synergistic potential at low concentrations. In the current study, bimetallic boron oxide-zinc oxide nanoparticles (B2O3-ZnO NPs) were synthesized by an eco-friendly, and cost-effective method through the utilization of gum arabic in the presence of gamma irradiation. Characterization of the synthesized bimetallic B2O3-ZnO NPs revealed the successful synthesis of bimetallic NPs on the nano-scale, and good distribution, in addition to formation of a stable colloidal nano-solution. Furthermore, the bimetallic B2O3-ZnO NPs were assessed for anticancer, antimicrobial and antioxidant activities. The evaluation of the cytotoxicity of bimetallic B2O3-ZnO NPs on Vero and Wi38 normal cell lines illustrated that bimetallic B2O3-ZnO NPs are safe in use where IC50 was 384.5 and 569.2 μg ml-1, respectively. The bimetallic B2O3-ZnO NPs had anticancer activity against Caco 2 where IC50 was 80.1 μg ml-1. Furthermore, B2O3-ZnO NPs exhibited promising antibacterial activity against E. coli, P. aeruginosa, B. subtilis and S. aureus, where MICs were 125, 62.5, 125 and 62.5 μg ml-1 respectively. Likewise, B2O3-ZnO NPs had potential antifungal activity against C. albicans as unicellular fungi (MIC was 62.5 μg ml-1). Moreover, B2O3-ZnO NPs displayed antioxidant activity (IC50 was 102.6 μg ml-1). In conclusion, novel bimetallic B2O3-ZnO NPs were successfully synthesized using gum arabic under gamma radiation, where they displayed anticancer, antimicrobial and antioxidant activities.


Elevated arsenic level in fasting serum via ingestion of fish meat increased the risk of hypertension in humans and mice.
There has been a shortage of human studies to elucidate the association between serum arsenic levels and the prevalence of hypertension. This study multidirectionally investigated associations among arsenic exposure, dietary ingestion, and the risk of hypertension by combined human epidemiological and mouse experimental studies. This study focused on the total arsenic level in fasting serum, a biomarker of arsenic exposure. Associations among ingestion frequencies of 54 diet items of Japanese food separated into six categories, total arsenic level in fasting serum, and the prevalence of hypertension were investigated in 2709 general people in Japan. Logistic regression analysis demonstrated a dose-dependent association between serum arsenic level and hypertension and a positive association between the ingestion of fish meat and hypertension. Further analysis showed that the latter association was fully mediated by increased fasting serum arsenic levels in humans. Similarly, oral exposure to the putative human-equivalent dose of arsenic species mixture with the same ratios in a common fish meat in Japan increased systolic blood pressure and arsenic levels in fasting serum in mice. This interdisciplinary approach suggests that fish-meat ingestion is a potential risk factor for arsenic-mediated hypertension. Because the increased consumption of fish meat is a recent global trend, health risks of the increased ingestion of arsenic via fish meat should be further investigated.


How the science of practice will improve evidence-based care.
This review article analyzes the present evidence-based medicine (EBM) algorithm, compares it to the science of practice (SOP) algorithm, and demonstrates how the SOP can evolve from a quality assurance and quality improvement tool into a clinical research tool. Using appropriately constructed prospective observational databases (PODs), the SOP algorithm can be used to draw causal inferences from nonrandomized data, perform innovative comparative effectiveness research, and generate reliable information that can be used to guide treatment decisions.


Construction and Preclinical Evaluation of a 124/131I-Labeled Radiotracer for the Detection of Mesothelin-Overexpressing Cancer.
Mesothelin is a molecular biomarker of many types of solid cancers, which may represent a highly promising new target in the development of cancer-targeted diagnostic agents. A human anti-mesothelin antibody with a low molecular weight, ET210sc, was applied; this antibody has potent affinity and can penetrate tissue quickly and stably without causing immunoreactions. We developed a new 124/131I-labeled radiotracer of ET210sc. The 124/131I-labeled ET210sc radiotracer showed excellent radiochemical quality (with over 99% radiolabeling yield, 0.07 GBq/μmol specific activity) and remarkable stability in phosphate-buffered saline (>95% at 3 days). The radiotracer retained its potent affinity (dissociation constant, Kd = 0.101 nM). The radiotracer specifically bound to mesothelin-positive cells in vitro. Interestingly, the radiotracer exhibited significant positive-to-negative tumor uptake ratios (1.5:1) 3 days postinjection. The estimated absorbed doses of each organ (e.g., 0.704 mGy/MBq for the rectum; 0.341 mGy/MBq for the spleen) met the medical safety standards for further clinical applications. Our findings provide an initial proof of concept for the potential use of 124/131I-labeled ET210sc radiotracers to detect mesothelin-overexpressing cancer. 124I-ET210sc is proposed to be an ideal imaging agent for further clinical applications.


Robust Vector BOTDA Signal Processing with Probabilistic Machine Learning.
This paper presents a novel probabilistic machine learning (PML) framework to estimate the Brillouin frequency shift (BFS) from both Brillouin gain and phase spectra of a vector Brillouin optical time-domain analysis (VBOTDA). The PML framework is used to predict the Brillouin frequency shift (BFS) along the fiber and to assess its predictive uncertainty. We compare the predictions obtained from the proposed PML model with a conventional curve fitting method and evaluate the BFS uncertainty and data processing time for both methods. The proposed method is demonstrated using two BOTDA systems: (i) a BOTDA system with a 10 km sensing fiber and (ii) a vector BOTDA with a 25 km sensing fiber. The PML framework provides a pathway to enhance the VBOTDA system performance.


Penguin egg-white and polar fish blood-serum proteins.
The development of, and findings in, a long-term research program on penguin proteins and polar fish blood proteins are described. Two of the egg-white proteins from the Adelie penguin (Pygoscelis adeliae) have unique properties: a glycoprotein named penalbumin that is a major constituent with some characteristics similar to ovalbumin, and an ovomucoid with strong inhibitory capacity for subtilisin as well as for bovine trypsin and alpha-chymotrypsin. The antifreeze glycoproteins from Antarctic fish (Trematomus borchgrevinki and Dissostichus mawsoni) and an Arctic fish (Boreogadus saida) appear to function noncolligatively by lowering the freezing temperature without affecting the melting point. Current evidence indicates that the antifreeze glycoprotein functions at the ice-solution interface, either on the ice surface or in a transition layer between the solution and the ice.


Gain and subsequent loss of lung function after lung volume reduction surgery in cases of severe emphysema with different morphologic patterns.
Surgical lung volume reduction improves lung function and dyspnea in advanced emphysema to a variable degree. Because long-term results with this procedure are scant, we prospectively investigated lung function over several years after lung volume reduction surgery with regard to emphysema morphology. Bilateral video-assisted thoracoscopic lung volume reduction surgery was performed in severely symptomatic patients with marked hyperinflation caused by advanced nonbullous emphysema. Emphysema heterogeneity was visually graded on chest computed tomography. Symptoms and lung function were assessed before the operation and 3, 6, and then every 6 months after the operation. A total of 115 patients with a median forced expiratory volume in 1 second of 0.73 L (27% of predicted value) underwent lung volume reduction surgery. Follow-up extended over a median of 37 months. Median forced expiratory volume in 1 second significantly increased within 6 months after the operation by 37% in homogeneous (n = 27), by 38% in intermediately heterogeneous (n = 37), and by 63% in markedly heterogeneous emphysema (n = 51, P <.05 vs. other morphologies). Maximal forced expiratory volume in 1 second was reached within 6 months after lung volume reduction surgery and decreased in the first postoperative year by 0.16 L per year in homogeneous, by 0.19 L per year in intermediately heterogenous, and by 0.32 L per year in markedly heterogeneous emphysema (P <.01 vs. other morphologies). The decline in forced expiratory volume in 1 second over subsequent years decelerated according to an exponential decay and was similar for all morphologic types (median annual decrease of 0.09 L [9%]). Lung volume reduction surgery improves lung function in severe homogeneous and, to an even greater extent, heterogeneous emphysema. Forced expiratory volume in 1 second peaks within 6 months postoperatively. The subsequent decline is most rapid in the first year and slows down in succeeding years according to an exponential decay. Therefore, long-term functional results of lung volume reduction surgery may be more favorable than expected from linear extrapolations of short-term observations.


The effect of ultraviolet functionalization of titanium on integration with bone.
Titanium implants are used as a reconstructive anchor in orthopedic and dental diseases and problems. Recently, ultraviolet (UV) light-induced photocatalytic activity of titanium has earned considerable and broad interest in environmental and clean-energy sciences. This study determines whether UV treatment of titanium enhances its osteoconductive capacity. Machined and acid-etched titanium samples were treated with UV for various time periods up to 48h. For both surfaces, UV treatment increased the rates of attachment, spread, proliferation and differentiation of rat bone marrow-derived osteoblasts, as well as the capacity of protein adsorption, by up to threefold. In vivo histomorphometry in the rat model revealed that new bone formation occurred extensively on UV-treated implants with virtually no intervention by soft tissue, maximizing bone-implant contact up to nearly 100% at week 4 of healing. An implant biomechanical test revealed that UV treatment accelerated the establishment of implant fixation 4 times. The rates of protein adsorption and cell attachment strongly correlated with the UV dose-responsive atomic percentage of carbon on TiO2, but not with the hydrophilic status. The data indicated that UV light pretreatment of titanium substantially enhances its osteoconductive capacity, in association with UV-catalytic progressive removal of hydrocarbons from the TiO2 surface, suggesting a photofunctionalization of titanium enabling more rapid and complete establishment of bone-titanium integration.


Adenosine inhibits neutrophil degranulation in activated human whole blood: involvement of adenosine A2 and A3 receptors.
Adenosine, acting via A2 receptors, is a potent inhibitor of neutrophil oxidative burst, but its effects and mechanisms of action on neutrophil degranulation have been less well characterized. We, therefore, investigated the effects of adenosine and its receptor-specific analogues on neutrophil degranulation in stimulated human whole blood. Adenosine dose-dependently inhibited the LPS- and TNF-alpha-induced release of the azurophilic granule proteins bactericidal/permeability-increasing protein, elastase, and defensins to approximately the same extent, with a maximum inhibition of 70 to 80% and an IC50 ranging from 14 to 24 microM. The inhibitory effects of adenosine were partially blocked by the A2 receptor antagonist 3,7-dimethyl-1-propargylxanthine, the A1/A2 antagonist 8(p-sulfophenyl)theophyline, and the A1/A3 antagonist xanthine amine congener, but not by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine. The highly selective A3 agonist N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide and the nonselective agonist 2-chloroadenosine reduced degranulation more potently than the A1 agonist N6-cyclopentyladenosine. The inhibitory effects of N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide and 2-chloroadenosine were strongly reversed by xanthine amine congener, but were not affected by 8(p-sulfophenyl)theophyline. In addition, the adenosine kinase inhibitor GP515 attenuated degranulation via an adenosine-mediated mechanism. These data indicate that adenosine acts via A2 as well as A3 receptors to inhibit neutrophil degranulation and add to the anti-inflammatory potential of adenosine and adenosine-regulating agents in neutrophil-mediated tissue injury.