Aminoethyl-isothiourea inhibits leukocyte production of reactive oxygen species and proinflammatory cytokines induced by streptococcal cell wall components in human whole blood.
The incidence of severe invasive disease caused by serogroup A streptococci (GAS) is increasing, and to elucidate the role of streptococcal cell wall components in the inflammatory response, human whole blood was stimulated with lipoteichoic acid (LTA, 0.005-50 microg/mL) and peptidoglycan (10 and 100 microg/ml) from Streptococcus pyogenes. Both stimulants increased dose dependently the leukocyte release of cytokines many thousand fold: tumor necrosis factor alpha (0 to 158,000+/-4,900 pg/mL), interleukin (IL)-1beta (85+/-56 to 31,000+/-4,600 pg/mL), IL-6 (30+/-11 to 34,800+/-15,000 pg/mL), and IL-8 (300+/-150 to 29,000+/-14,000 pg/mL). Intracellular leukocyte levels of reactive oxygen species (ROS) as measured by flow cytometry increased 15-20 fold, from 25 to 400-500 mean fluorescence intensity. Aminoethyl-isothiourea (AE-ITU), a relatively selective inhibitor of the inducible nitric oxide synthase (iNOS) and a ROS scavenger, reduced the cytokine production by 70-100%, and intracellular leukocyte ROS levels by 50-70% (all P < 0.05). The non-selective NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME) did not affect intracellular ROS levels, but it caused a moderate selective inhibition of IL-8 production. Leukocyte NO production (measured up to 36 h) was not enhanced by LTA, peptidoglycan, inactivated streptococci, or cytokine combinations. The mechanisms for the anti-inflammatory effects of AE-ITU may be through a reduction of intracellular ROS levels, or through a direct effect on signal transduction, whereas NO modulation is an unlikely mechanism.


[Option of the surgical mode for breast cancer based on the effect of neoadjuvant chemotherapy].
Neoadjuvant chemotherapy has become standard treatment for breast cancer patients to avoid mastectomy in larger tumors. Neoadjuvant chemotherapy permits more breast-conserving surgery to be performed. The treatment outcome is favorable in women whose tumors show a complete pathological response. Histological grade, HER-2, p53, and hormone receptor status are significant predictive factors of a good pathological response to neoadjuvant chemotherapy. In addition, computed tomography and/or magnetic resonance imaging are useful tools in determining the optimal resection area for breast cancer.


Efficacy of a dehydrated steinernematid nematode against black cutworm (Lepidoptera: Noctuidae) and diamondback moth (Lepidoptera: Plutellidae).
We compared the ability of in vitro-produced, commercially formulated with in vivo-produced, nonformulated Steinernema carpocapsae (Weiser) Poinar. All strain to infect and kill larvae of black cutworm, Agrotis ipsilon (Hufnagel), and diamondback moth, Plutella xylostella (L.). In vitro-produced nematodes formulated in wettable dispersible granules, which were stored dry, were rehydrated in water for 0-72 h before application. Against black cutworms, the efficacy of nematodes was (from most to least effective): in vivo > in vitro rehydrated for 72 h > in vitro rehydrated for 48 h > in vitro rehydrated for 24 h > dehydrated (0 h). Nematodes rehydrated for 72 h in water or moist soil were equally effective against black cutworm larvae, and both were significantly more effective than nematodes without rehydration. These results indicated that nematodes in the wettable dispersible granule formulation required time to rehydrate in the soil before infecting black cutworm larvae. Nematode treatments described above were applied to radish plants held at 100 or 75% RH and tested against diamondback moth larvae. At 100% RH, nematode efficacy was (from most to least effective): in vitro rehydrated for 72 h > in vivo > in vitro rehydrated 48 h > in vitro rehydrated 24 h > dehydrated (0 h). The efficacy of all treatments was lower at 75% than at 100% RH, and the ranking of in vivo and in vitro nematodes rehydrated for 72 h was reversed. The nematodes in the wettable dispersible granule formulation were effective for foliar treatments when humidity was high and nematodes were rehydrated for at least 48 h before application. The data show that nematode infectivity was reduced unless nematodes were rehydrated.


Application of dynamic contrast enhanced ultrasound in distinguishing focal-type autoimmune pancreatitis from pancreatic ductal adenocarcinoma.
To explore the value of dynamic contrast enhanced ultrasound (DCE-US) in preoperative differential diagnosis of focal-type autoimmune pancreatitis (AIP) and pancreatic ductal adenocarcinoma (PDAC). From May 2016 to March 2020, patients with biopsy and histopathologically confirmed focal-type AIP (n = 9) were retrospectively included. All patients received contrast enhanced ultrasound (CEUS) examinations one week before surgery/biopsy. Dynamic analysis was performed by VueBox® software (Bracco, Italy). Eighteen cases of resection and histopathologically proved PDAC lesions were also included as control group. B mode ultrasound (BMUS) features, CEUS enhancement patterns, time intensity curves (TICs) and CEUS quantitative parameters were obtained and compared between AIP and PDAC lesions. After injection of ultrasound contrast agents, most focal-type AIP lesions displayed hyper-enhancement (2/9, 22.2%) or iso-enhancement (6/9, 66.7%) during arterial phase of CEUS, while most of PDAC lesions showed hypo-enhancement (88.9%) (P < 0.01). During late phase, most of AIP lesions showed iso-enhancement (8/9, 88.9%), while most of PDAC lesions showed hypo-enhancement (94.4%) (P < 0.001). Compared with PDAC lesions, TICs of AIP lesions showed delayed and higher enhancement. Among all CEUS perfusion parameters, ratio of PE (peak enhancement), WiAUC (wash-in area under the curve), WiR (wash-in rate), WiPI (wash-in perfusion index, WiPI = WiAUC/ rise time), WoAUC (wash-out area under the curve), WiWoAUC (wash-in and wash-out area under the curve) and WoR (wash-out rate) between pancreatic lesion and surrounding normal pancreatic tissue were significantly higher in AIP lesions than PDAC lesions (P < 0.05). DCE-US with quantitative analysis has the potential to make preoperative differential diagnosis between focal-type AIP and PDAC non-invasively.


Electrostatic Assembly of Platinum Nanoparticles along Electrospun Polymeric Nanofibers for High Performance Electrochemical Sensors.
A novel polyacrylonitrile (PAN) nanofibrous membrane conjugated with platinum nanoparticles (PtNPs) was fabricated by electrospinning and electrostatic assembly techniques. In this procedure, PAN was electrospun with 3-aminopropyltriethoxysilane (APS) together as precursor materials. First, amine groups were introduced onto PAN nanofibers, and then the as-prepared negative-charged platinum nanoparticles (PtNPs) were conjugated onto the surface of the amino-modified PAN nanofibers uniformly by the electrostatic interaction-mediated assembly. The fabricated PAN-PtNPs hybrid nanofibrous membrane was further utilized to modify the glassy carbon electrodes and was used for the fabrication of a non-enzymatic amperometric sensor to detect hydrogen peroxide (H₂O₂). The electrochemical results indicated that, due to the uniform dispersion of PtNPs and the electrostatic interaction between amine groups and PtNPs, the fabricated PAN-PtNPs nanofibrous membrane-based electrochemical sensor showed excellent electrocatalytic activity toward H₂O₂, and the chronoamperometry measurements illustrated that the fabricated sensor had a high sensitivity for detecting H₂O₂. It is anticipated that the strategies used in this work will not only guide the design and fabrication of functional polymeric nanofiber-based biomaterials and nanodevices, but also extend their potential applications in energy storage, cytology, and tissue engineering.


Anti-angiogenic effect of pyridoxal 5'-phosphate, pyridoxal and pyridoxamine on embryoid bodies derived from mouse embryonic stem cells.
We previously demonstrated anti-angiogenic activity of pyridoxal 5'-phosphate (PLP) and pyridoxal (PL) using in vitro and ex vivo angiogenesis models and anti-colon tumor effect of vitamin B(6) in mice. There is growing evidence that endothelial progenitor cells (EPCs) in circulation contribute to tumor-induced angiogenesis. It is of importance to clarify whether EPC differentiation is involved in the mechanism of anti-angiogenic effect of vitamin B(6). In this study, we investigated the effect of vitamin B(6) on angiogenesis in embryonic stem cell-derived embryoid bodies (EBs). PLP suppressed angiogenesis in EBs at >or=100 microM. Among the vitamin B(6) compounds at the concentration of 200 microM, PL, as well as PLP, was the most effective suppressor of vasculogenesis, while pyridoxine was inactive. These results were consistent with their effects in rat aorta and endothelial cell assays. Interestingly, pyridoxamine (PM), which had no effect in rat aorta and endothelial cell assays, also exerted a significant suppressive effect in this model. This study demonstrated an inhibitory effect of PM on vasculogenesis in this EB model as well as PLP and PL, and suggests that suppression of EPC differentiation is at least in part responsible for the mechanism of the anti-angiogenesis effect of vitamin B(6).


Exact asymptotic analysis for metapopulation dynamics on correlated dynamic landscapes.
We compute the mean patch occupancy for a stochastic, spatially explicit patch-occupancy metapopulation model on a dynamic, correlated landscape, using a mathematically exact perturbation expansion about a mean-field limit that applies when dispersal range is large. Stochasticity in the metapopulation and landscape dynamics gives negative contributions to patch occupancy, the former being more important at high occupancy and the latter at low occupancy. Positive landscape correlations always benefit the metapopulation, but are only significant when the correlation length is comparable to, or smaller than, the dispersal range. Our analytical results allow us to consider the importance of spatial kernels in all generality. We find that the shape of the landscape correlation function is typically unimportant, and that the variance is overwhelmingly the most important property of the colonisation kernel. However, short-range singularities in either the colonisation kernel or landscape correlations can give rise to qualitatively different behaviour.


The modifying effects of green tea polyphenols on acute colitis and inflammation-associated colon carcinogenesis in male ICR mice.
Reactive oxygen species (ROS) have been implicated as mediators of intestinal inflammation and carcinogenesis. Although green tea polyphenols (GTP) have anticancer property as antioxidants they also generate ROS in vitro. In this study, we investigated the modifying effects of GTP on dextran sulfate sodium (DSS)-induced acute colitis and on 1,2-dimethylhydrazine (DMH) and DSS-induced colon carcinogenesis in male ICR mice. At sacrifice after 6 days, the colon shortening induced by 2% DSS was unchanged by 0.1% and 0.25% GTP, but increased by 0.5% and 1% GTP-containing diet. The expression of interleukin-1beta and macrophage-migration inhibitory factor in the DSS + 0.1% GTP group were lower than the DSS alone group, whereas the expression levels were increased in the DSS + 0.5% GTP and DSS + 1% GTP groups when compared with the DSS alone group. In a subsequent experiment to determine the effects of 0.01-1% GTP on inflammation-associated colon carcinogenesis induced by DMH/DSS, 0.5 and 1% doses of GTP failed to prevent the development of multiple colon tumors, rather, they tended to increase it. Our results thus indicate that the modifying effects of GTP on DSS-induced acute colitis and DMH/DSS-induced colon carcinogenesis depends upon its dosage and the expression of proinflammatory cytokines.


Implications of SARS-CoV-2 on current and future operation and management of wastewater systems.
While researchers have acknowledged the potential role of environmental scientists, engineers, and industrial hygienists during this pandemic, the role of the water utility professional is often overlooked. The wastewater sector is critical to public health protection and employs collection and treatment system workers who perform tasks with high potential for exposures to biological agents. While various technical guidances and reports have initially provided direction to the water sector, the rapidly growing body of research publications necessitates the constant review of these papers and data synthesis. This paper presents the latest findings and highlights their implications from a water and wastewater utility operation and management perspective. PRACTITIONER POINTS: Extrapolation from SARS-CoV-1 and MERS-CoV, as well as other surrogates, has helped predicting SARS-CoV-2 behavior and risk management. Data from treated wastewater effluent suggest that current processes are sufficient for SARS-CoV-2 control. Scientific evidence supports the possibility of fecal-oral transmission for SARS-CoV-2. Limited evidence supports the potential survival of infective SARS-CoV-2 on surfaces and in aerosols and the efficacy of control measures at reducing transmission. Protective practices and PPE can protect workers from SARS-CoV-2 and other pathogens found in wastewater.


Factors affecting expressed emotion in parents of ill and normal children.
In order to examine their relationship to Expressed Emotion, family environment and marital relationships were measured in the parents of disruptive, obsessive-compulsive, and normal children. Satisfactory family and martial environment were found to be related to low Expressed Emotion, while achievement orientation in mothers and greater family conflict were found to be significantly related to high Expressed Emotion.


Amino acid carryover in the subzonal space of mouse fertilized ova affects subsequent transport kinetics.
SummaryWe have investigated whether culture in glycine-containing medium affects subsequent glycine transport by the specific transport system, GLYT1, which is the sole glycine transporter in fertilized mouse ova. When fertilized ova were maintained for 6 h in culture with a physiological level of glycine (1 mM), subsequent transport of radiolabelled glycine was decreased by 40% compared with fertilized ova that had been maintained in glycine-free medium. Kinetic measurements showed that the apparent glycine affinity was decreased after culture with glycine (Km increased from 0.20 to 0.41 mM), but maximal transport rate was unchanged (similar Vmax of 20 and 23 fmol/fertilized ovum/min). These findings could have reflected activation of GLYT1 by prolonged substrate starvation, similar to some other amino acid transport systems. However, our findings were instead consistent with the alteration in glycine transport being due to trapping of glycine within the zona pellucida resulting in competitive transport inhibition even after ova were removed from glycine-containing media. First, even very brief exposures to glycine resulted in decreased subsequent glycine transport rates, with a maximal effect apparent within ~6 min. Second, extensive washing (at least six) reversed the effect. Third, the effect was absent when zona-free fertilized ova were used. Thus, it appears that components of the external environment of preimplantation embryos may continue to affect transport kinetics for a period even after embryos are removed from environments that contain them.


A Novel ZRS Mutation in a Chinese Patient with Preaxial Polydactyly and Triphalangeal Thumb.
Preaxial polydactyly (PPD; OMIM 603596), which is characterized as having supernumerary fingers, is an unusual congenital hand abnormality. Triphalangeal thumb (TPT; OMIM 190600) is identified by an extra phalangeal bone and is often found in association with PPD. When in combination, the disease is referred to as PPD type II (PPD II; OMIM 174500). Previous studies have demonstrated that variations in the zone of polarizing activity regulatory sequence (ZRS; chr7:156,583,796-156,584,569; hg19) region are associated with PPD II. In this study, our patient was diagnosed with PPD II, having bilateral thumb duplication and unilateral TPT (on the right hand). Further investigation of possible causative genes identified a de novo heterozygous ZRS mutation (ZRS 428T>A). This novel mutation was neither found in 200 normal controls nor reported in online databases. Moreover, the bioinformatics program Genomic Evolutionary Rate Profiling (GERP) revealed this site (ZRS428) to be evolutionarily highly conserved, and the 428T>A point mutation was predicted to be deleterious by MutationTaster. In conclusion, the affected individual shows bilateral thumb duplication, but unilateral TPT making this case special. Thus, our findings not only further support the important role of ZRS in limb morphogenesis and expand the spectrum of ZRS mutations, but also emphasize the significance of genetic diagnosis and counseling of families with digit number and identity alterations as well.


Neoadjuvant and Adjuvant Chemotherapy of Cervical Cancer.
Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided.


Anti-inflammatory Silent Agonists.
The traditional view of nicotinic acetylcholine receptors (nAChRs) is that they strictly exert their functions via their well-known ion channel activity. With the identification of the cholinergic anti-inflammatory pathway and the critical involvement of the α7 nAChR, an alternate modality of function has emerged for the receptor involving metabotropic-like activity. The new emerging pharmacology for the receptor includes ligands termed silent agonists, which exert little or no ionotropic activity, yet are capable of modulating cellular inflammatory responses.


Surgical results of video-assisted minimally invasive direct coronary artery bypass.
A video-assisted minimally invasive direct coronary artery bypass procedure is defined as a combination of video thoracoscopic internal mammary artery harvest and direct coronary bypass grafting through a minithoracotomy without cardiopulmonary bypass. We reviewed our experience with this procedure and examined its efficacy. Since November 1995, 110 patients have undergone a minimally invasive direct coronary artery bypass procedure in our institution. Seventy (64%) of them underwent a video-assisted minimally invasive operation (group 1). As a control group (group 2), we reviewed the results in 37 patients who underwent conventional single or double coronary artery bypass grafting using an internal mammary artery graft between 1993 and 1995 and could have been candidates for minimally invasive direct coronary artery bypass grafting. There were two hospital deaths (2.9%) in group 1 and one hospital death (2.7%) in group 2. There were no significant differences in mortality or morbidity between the two groups. The number of patients who needed postoperative positive inotropic agents was significantly greater in group 2, and this group also had a significantly longer mean postoperative intubation time and mean hospital stay than group 1. The surgical results of video-assisted direct coronary artery bypass procedures were better than those of conventional coronary artery bypass grafting in this review. A long-term follow-up for graft patency is needed.


Fractal Morphology and Breakage of DLCA and RLCA Aggregates.
Latex aggregates, formed in 1 M McIlvaine buffer solution and 0.2 M NaCl solution, have been characterized in terms of aggregate size distribution and fractal morphology. This was achieved using three sizing techniques (image analysis, laser scattering, and electrical sensing) in which size distributions and fractal properties of the aggregates were measured. Estimates of fractal dimensions were made using the two-slope method based on dimensional analysis and the small-angle light scattering method. Aggregate suspensions were prepared using both water and a mixture of heavy water/ water as the solvent. The latter essentially eliminated sedimentation, which was observed after one day of aggregation when water alone was used as a solvent. Latex aggregates formed by diffusion-limited colloid aggregation (DLCA) and reaction-limited colloid aggregation (RLCA) had fractal dimensions close to 1.8 and 2.1, respectively. As observed through image analysis, DLCA aggregates possessed a loose tenuous structure, whereas RLCA aggregates were more compact. Disruption of both DLCA and RLCA aggregates has been investigated in laminar flow and turbulent capillary flow. The shear forces introduced by a laminar shear device with a shear rate up to 1711 s(-1) were unable to bring about aggregate breakup; shearing facilitates aggregate growth in the case of DLCA. However, latex aggregates were significantly disrupted after passage through a turbulent capillary tube at 95209 s(-1). Copyright 2000 Academic Press.


Reproducibility of plasma and urinary sex hormone levels in premenopausal women over a one-year period.
Although endogenous sex steroid hormones in premenopausal women may be associated with the risk of breast cancer and other illnesses, direct evidence to support this hypothesis is limited in large part by methodological issues in the conduct of relevant studies. One major unresolved issue is whether a single blood sample (such as is available in most epidemiological studies), collected in a specific phase of the menstrual cycle, reflects long-term levels in that phase. To address this issue, two sets of blood and urine samples were obtained from 87 premenopausal women over a 1-year period in both the follicular and luteal phases. Plasma estradiol, estrone, and estrone sulfate were measured in the blood samples obtained in both phases, whereas progesterone and urinary 2- and 16a-hydroxyestrone were measured in luteal-phase samples only. For all of the women combined, intraclass correlation coefficients (ICCs) ranged, with one exception, from 0.52 to 0.71 for the plasma estrogens and the urinary estrogen metabolites. The sole exception was for estradiol in the luteal phase (ICC = 0.19); inclusion of only women who were ovulatory in both cycles and who collected each sample 4-10 days before their next period resulted in a substantially higher ICC for estradiol in the luteal phase (ICC = 0.62; 95% confidence interval, 0.43-0.78). These data indicate that, for several plasma and urinary sex hormones, a single follicular- or luteal-phase measurement in premenopausal women is reasonably representative of hormone levels in that phase for at least a 1-year period.


Astrocytes, HIV and the Glymphatic System: A Disease of Disrupted Waste Management?
The discovery of the glial-lymphatic or glymphatic fluid clearance pathway in the rodent brain led researchers to search for a parallel system in humans and to question the implications of this pathway in neurodegenerative diseases. Magnetic resonance imaging studies revealed that several features of the glymphatic system may be present in humans. In both rodents and humans, this pathway promotes the exchange of interstitial fluid (ISF) and cerebrospinal fluid (CSF) through the arterial perivascular spaces into the brain parenchyma. This process is facilitated in part by aquaporin-4 (AQP4) water channels located primarily on astrocytic end feet that abut cerebral endothelial cells of the blood brain barrier. Decreased expression or mislocalization of AQP4 from astrocytic end feet results in decreased interstitial flow, thereby, promoting accumulation of extracellular waste products like hyperphosphorylated Tau (pTau). Accumulation of pTau is a neuropathological hallmark in Alzheimer's disease (AD) and is accompanied by mislocalization of APQ4 from astrocyte end feet to the cell body. HIV infection shares many neuropathological characteristics with AD. Similar to AD, HIV infection of the CNS contributes to abnormal aging with altered AQP4 localization, accumulation of pTau and chronic neuroinflammation. Up to 30% of people with HIV (PWH) suffer from HIV-associated neurocognitive disorders (HAND), and changes in AQP4 may be clinically important as a contributor to cognitive disturbances. In this review, we provide an overview and discussion of the potential contributions of NeuroHIV to glymphatic system functions by focusing on astrocytes and AQP4. Although HAND encompasses a wide range of neurocognitive impairments and levels of neuroinflammation vary among and within PWH, the potential contribution of disruption in AQP4 may be clinically important in some cases. In this review we discuss implications for possible AQP4 disruption on NeuroHIV disease trajectory and how HIV may influence AQP4 function.


Glycyrrhizic acid inhibits leukemia cell growth and migration via blocking AKT/mTOR/STAT3 signaling.
Glycyrrhizic acid (GA) is the bioactive compound of licorice and has been used as an herbal medicine because of its anti-viral, anti-cancer, and anti-inflammatory properties. This study was designed to investigate the effects of GA on leukemia cells growth, migration, and the mechanisms underlying the anti-cancer activities of GA. MTT test was used to detect the effect of GA on TF-1 leukemia cell growth. Wound closure assay and Transwell were adopted to assess the effect of GA on TF-1 migration and invasion. Migration and invasion related proteins including AKT and mTOR were detected by western blot assay. We further used western blot and immunofluorescence assay to evaluate the effect of GA on STAT3 phosphorylation in vitro. We also evaluated the anti-tumor effect of GA in TF-1 tumor bearing BALB/c mice model. The present study showed GA significant inhibit of TF-1 proliferation in a dose and time-dependent manner. GA could remarkably inhibit TF-1 cell migration and invasion; meanwhile effectively suppress AKT, mTOR, and STAT3 phosphorylation in TF-1 cells. GA in 100 mg/kg/ could inhibit the tumor growth in vivo and down-regulated AKT, mTOR, and STAT3 phosphorylation in TF-1 tumor tissues. Our findings suggest that GA is a promising therapeutic agent for leukemia that targets the AKT/mTOR/STAT3 pathway.


[Chylothorax - case report].
Chylothorax is the occurrence of lymph in the pleura due to damage or obstruction of the thoracic duct. High content of triglycerides and the presence of chylomicrons make the diagnosis of chylothorax. Its aetiology can be divided in traumatic and non-traumatic. Traumatic rupture occurs after accidents or surgery. Within non-traumatic aetiology, lymphoma is the most common and in the presence of a chylothorax of unknown origin this should be the first suspicion, being non-Hodgkin type the most frequent. The authors present a case report of a patient with chylothorax due to non-Hodgkin lymphoma, discuss the particularities of chylothorax as well as the investigation and its treatment options.


Effects of Extreme Prematurity on Numerical Skills and Executive Function in Kindergarten Children: An Application of Partially Ordered Classification Modeling.
Although mathematics disabilities (MD) are common in extremely preterm/extremely low birth weight (EPT/ELBW) children, little is known about the nature of these problems. In this study partially ordered set (POSET) models were applied to classify 140 EPT/ELBW kindergarten children (gestational age <28 weeks and/or birth weight <1000 g) and 110 normal birth weight (NBW) controls into profiles of numerical and cognitive skills. Models based on five numerical skills and five executive function and processing speed skills provided a good fit to performance data. The EPT/ELBW group had poorer skills in all areas than NBW controls but the models also revealed substantial individual variability in skill profiles. Weaknesses in executive function were associated with poorer mastery of numerical skills. The findings illustrate the applicability of POSET models to research on MD and suggest distinct types of early numerical deficits in EPT/ELBW children that are related to their impairments in executive function.


Beta2-integrin-induced p38 MAPK activation is a key mediator in the CD14/TLR4/MD2-dependent uptake of lipopolysaccharide by hepatocytes.
The liver is the main organ that clears circulating lipopolysaccharide (LPS), and hepatocytes are a major cell type involved in LPS uptake. Little is known about the mechanisms for LPS internalization in hepatocytes and what signaling pathways are involved. We show here that LPS uptake is initiated after formation of a multi-receptor complex within lipid rafts. We find that essential components for LPS uptake are CD14, TLR4, MD2, and the beta2-integrin CD11b/CD18. Activation of p38 MAPK is also essential for the initiation of LPS uptake, and interestingly, we show that this activation is not through TLR4 signaling by MyD88 but through activation of TIRAP via CD11b/CD18. However, TLR4/MD2 remain essential components at the cell surface as part of the LPS receptor complex. We therefore suggest novel roles for TLR4/MD2, CD11b/CD18, TIRAP, and p38 MAPK in LPS uptake by hepatocytes.


Template learning of cellular neural network using genetic programming.
A new learning algorithm for space invariant Uncoupled Cellular Neural Network is introduced. Learning is formulated as an optimization problem. Genetic Programming has been selected for creating new knowledge because they allow the system to find new rules both near to good ones and far from them, looking for unknown good control actions. According to the lattice Cellular Neural Network architecture, Genetic Programming will be used in deriving the Cloning Template. Exploration of any stable domain is possible by the current approach. Details of the algorithm are discussed and several application results are shown.


The nitrendipine-sensitive Ca2+ channel in chick muscle cells and its appearance during myogenesis in vitro and in vivo.
The nitrendipine-sensitive Ca2+ channel of chick skeletal myotubes in culture has been studied using both the 45Ca2+ flux technique and [3H]nitrendipine binding experiments. Ca2+ uptake is insensitive to nitrendipine when chick myotubes in culture are polarized. Whereas depolarization reveals a new component of 45Ca2+ influx which is inhibited by nitrendipine. Half-maximal inhibition occurs at a nitrendipine concentration of 0.7 nM. This value is similar to the dissociation constant Kd = 0.4 nM found in [3H]nitrendipine binding experiments. During myogenesis in vitro the nitrendipine receptor is absent in myoblasts and appears in parallel with the fusion process. Two stages of increased binding have been observed in vivo. The first one, which occurs during embryonic life, has the same properties as in the in vitro development. The second stage occurs near hatching and corresponds to a large increase in the number of nitrendipine receptors. This increase is accompanied by a decrease of affinity of nitrendipine for its receptor by a factor of 4 to 10. Chronic denervation produces a further increase in the number of nitrendipine receptors which reaches a factor of about 2 at 15 days of denervation. Results are discussed in relation to the particular localization of these channels in transverse tubules and with the innervation.


Inhibition of recombinant Pneumocystis carinii dihydropteroate synthetase by sulfa drugs.
Forty-four sulfa drugs were screened against crude preparations of recombinant Pneumocystis carinii dihydropteroate synthetase. The apparent Michaelis-Menten constants (Km) for p-aminobenzoic acid and 7,8-dihydro-6-hydroxymethylpterin pyrophosphate were 0.34 +/- 0.02 and 2.50 +/- 0.71 microM, respectively. Several sulfa drugs, including sulfathiazole, sulfachlorpyridazine, sulfamethoxypyridazine, and sulfathiourea, inhibited dihydropteroate synthetase approximately as well as sulfamethoxazole, as determined by the concentrations which cause 50% inhibition and/or by Ki. For all sulfones and sulfonamides tested, unsubstituted p-amino groups were necessary for activity, and sulfonamides containing an N1-heterocyclic substituent were found to be the most effective inhibitors. Folate biosynthesis in isolated intact P. carinii was approximately equally sensitive to inhibition by sulfamethoxazole, sulfachlorpyridazine, sulfamethoxypyridazine, sulfisoxazole, and sulfathiazole. Two of these drugs, sulfamethoxypyridazine and sulfisoxazole, are known to be less toxic than sulfamethoxazole and should be further evaluated for the treatment of P. carinii pneumonia.


Assessment of clinical technologies. Importance for provision and use.
The author contends that the diffusion and use of modern medical technologies has had a profound impact on the hospital environment, the doctor-patient relationship, and the humanity of the patient. On these grounds the author argues for a rigorous, comprehensive, and ongoing assessment of diagnostic and therapeutic technologies. He stresses the importance of developing standards by which to judge the human and economic impact of particular technologies. These studies would decrease the inappropriate use of medical technology and would provide guidelines to improve current use.


Reflections, memories, and sources 'The cleanest man on earth': Harcourt Whipple Ellis and the NLA Australian newspapers.
The National Library of Australia (NLA) Australian Newspapers project went public in July 2008, but many historians and researchers are as yet unaware of its existence, or of its great potential for their research. This article will demonstrate the revolutionary potential of this project for the history of medicine in Australia. Using the case ofa largely-forgotten Western Australian chemist, dentist, and optician, Harcourt Whipple Ellis, a search of the NLA Australian Newspapers project produces a substantial amount of information on his at times scandalous career, a general physical description, a verbatim quotation, and many other witnesses statements attributed to him. These newspaper articles flesh out' Ellis, and also provide valuable insights into early-twentieth-century life in Perth.


Lumbar epidurography with multi-orifice and single orifice epidural catheters.
The spread of iohexol in the epidural space was studied using two types of epidural catheter. Twenty pre-menopausal women undergoing hysterectomy received lumbar epidural analgesia via either multi-orifice or single orifice catheters. Twenty-four hours after surgery, iohexol was injected before catheter removal with the patient lying supine. Whereas there was no significant difference in the total number of vertebral segments covered by dye or the total number of segments reached above or below the level of epidural insertion, spread was more even to the right and left of midline using the single orifice catheters. Sacral spread of dye was only observed when a single orifice catheter was used. Epidural catheter design affects the distribution of solutions in the epidural space, with single orifice epidural catheters producing more even distribution of dye with sacral extension.


A Synthetic Gene Circuit for Self-Regulating Delivery of Biologic Drugs in Engineered Tissues.
We engineered a synthetic transcription system based on nuclear factor kappa-light-chain-enhancer of activated B cells signaling that can attenuate the effects of the inflammatory cytokine interleukin (IL)-1α in a self-regulating manner. This system responds in a time- and dose-dependent manner to rapidly produce therapeutic levels of IL-1 receptor antagonist (IL-1Ra). The use of lentiviral gene therapy allows this system to be utilized through different transduction methods and in different cell types for a variety of applications. Broadly, this approach may be applicable in developing autoregulated biologic systems for tissue engineering and drug delivery in a range of disease applications.


[Phenotypic variability in 47, XXX patients: Clinical report of four new cases].
The 47, XXX karyotype has a frequency of 1 in 1000 female newborns. However, this karyotype is not usually suspected at birth or childhood. These patients are usually diagnosed during adulthood when they develop premature ovarian failure or infertility, because the early phenotype doesn t have any specific features. The study describes four cases and the clinical variability of the 47, XXX karyotype.


Effects of continuous infusion fentanyl citrate on cerebrovascular and systemic prostanoids in postsurgical newborn piglets.
Newborns admitted to the intensive care unit undergo multiple painful procedures. Fentanyl citrate (FC) is one of the most commonly used drugs for pain relief in the newborn. Although it has been reported that one of the biological effects of fentanyl is hemodynamic stability, the response of systemic and/or cerebrovascular prostanoids to FC infusions have not been studied. To examine the effects of continuous intravenous (IV) infusion of FC on systemic and cerebrovascular prostanoid concentrations, two groups of spontaneously breathing newborn piglets (1-3 days old) were studied. The study group (n = 6) and the control group (n = 8) were respectively given a loading dose of 30 micrograms/kg IV over 15 minutes, immediately followed by a continuous IV infusion of 10 micrograms/kg/hr for 6 hours, or a placebo (PB) solution of 5% dextrose in a similar fashion. Cerebrospinal fluid (0.5 mL) from cisterna magna puncture and blood samples (1.0 mL) from the sagittal sinus vein and carotid artery were collected serially before and after FC or PB infusion for drug and PG determinations. FC was measured by high pressure liquid chromatography (HPLC), and the prostanoids were measured using enzyme immunoassay (EIA) kits. FC infusion induced marked elevations in 6-ketoPGF1 alpha (300%, p < 0.001) and TXB2 (150%, p < 0.001) at 30 minutes, and remained elevated up to 2 hours of infusion. In addition, systemic 6-ketoPGF1 alpha increased by 180% (p < 0.001) and PGE2 concentrations fell dramatically at 30 minutes (87%, p < 0.001) and did not return to normal levels during the infusion time (83% to 81%, p < 0.001 to p < 0.01). CSF 6-ketoPGF1 alpha and TXB2 levels increased by 152% and 80%, respectively (p < 0.001), but PGE2 decreased by 76% (p < 0.001), at 6 hours of infusion. An inverse relationship existed between FC, and sagittal sinus PGE2 levels (r = 0.46, p < 0.03) and systemic PGE2 levels (r = 0.602, p < 0.02). The data suggest FC is rapidly transported across the blood brain barrier and the effects on cerebrovascular prostanoids, particularly PGE2 is rapid and prolonged. PGE2 appears to be the primary responsive prostanoid. The magnitude of the response, as evidenced by the early and sharp reductions in systemic and cerebrovascular concentrations, suggest vasoconstriction, with possible adverse effects on organ blood flow and metabolic activity. However, further studies are required to evaluate the effects on organ blood flow and metabolism.


American Burn Association Burn Prevention Framework.
In February 2020, burn prevention experts from a variety of professional backgrounds gathered for a national Burn Prevention Summit. Through lively discussion and debate, this group came to a consensus on several core burn prevention concepts in order to create a framework for burn prevention program planning. The resulting document includes components of a successful program, a five-step process for program planning, best practices in messaging, and general advice from the summit attendees. This framework is designed for both novice professionals who are new to burn prevention programming development and experienced professionals who would like to strengthen existing programming.


The discovery of phenylketonuria: the story of a young couple, two retarded children, and a scientist.
In the 1920s, a little girl 3 years of age was brought from China to the United States by her American mother. Although the child was beautiful, her mind was not developing. The grief-stricken mother had consulted doctors in China, but they could neither diagnose the problem nor provide treatment. Morning and night the same questions occupied her mind: "What is the matter with my little girl? What is causing it? Is there any doctor, anywhere, who can cure her?" In the United States, she also went from doctors to psychologists to clinics looking for someone who could help. Finally, she went to the Mayo Clinic in Rochester, Minnesota. When she had answered all of the doctor's questions, and all the tests were finished, they still could not tell her what was wrong. There was nothing they could do. The disease from which the little girl suffered was unknown at that time. The mother was Pearl Buck. In her book, The Child Who Never Grew,(1) she described her first infant: "I remember when she was only 3 months old she lay in her basket on the sun deck of a ship. I had taken her there for the morning air. The people who promenaded on deck often stopped to look at her, and my pride grew as they spoke of her unusual beauty and of the intelligent look of her deep, blue eyes. I do not know at what moment the growth of her intelligence stopped, nor to this day why it did." This is a classical description of the disease, phenylketonuria (PKU). A perfect infant seems to develop normally for several months, then the development slows and at some point seems to stop. "Look at Mommy-look at Daddy!" the parents say as they try to coax the treasured smiles. Instead, the child drifts into a dream world and into irreversible mental retardation. All Pearl Buck's devotion and determination was of no avail in finding the cause of her child's retardation. It was to be another mother with the same commitment to her beautiful but retarded children, who approximately 10 years later followed the same path until she found a special doctor who unlocked the secret of the fate of these children. When 1 of the authors (W.R.C.) visited Miss Buck at her Pennsylvania home in 1960, she talked about how her daughter, Carol, then a grown person, had recently been diagnosed as having PKU, as a result of screening tests at the New Jersey Vineland Training School for the Mentally Retarded. During my visit and without disclosing the reason, Pearl Buck was invited to sniff a vial of phenylacetate crystals (the odor of stale urine samples from PKU patients). Immediately she recalled that Carol, as a child, had the same unusual odor. She was relieved that the prophesy of the last words in her book had come true: "What has been, need not forever continue to be so. It is too late for some of our children, but if their plight can make people realize how unnecessary much of the tragedy is, their lives, thwarted as they are, will not have been meaningless." These could be the words of Borgny Egeland, the mother of the children through whom the mystery of PKU was brought to light. Or they could express the conviction of the physician and biochemist, Asbjörn Fölling, who believed that "what was not known could be known." Through the discovery of PKU in these children, hope has been given to thousands of other children and to their grateful parents ().


Cellular signalling of non-synonymous single-nucleotide polymorphisms of the human μ-opioid receptor (OPRM1).
There is significant variability in individual responses to opioid drugs, which is likely to have a significant genetic component. A number of non-synonymous single-nucleotide polymorphisms (SNPs) in the coding regions of the μ-opioid receptor gene (OPRM1) have been postulated to contribute to this variability. Although many studies have investigated the clinical influences of these μ-opioid receptor variants, the outcomes are reported in the context of thousands of other genes and environmental factors, and we are no closer to being able to predict individual response to opioids based on genotype. Investigation of how μ-opioid receptor SNPs affect their expression, coupling to second messengers, desensitization and regulation is necessary to understand how subtle changes in receptor structure can impact individual responses to opioids. To date, the few functional studies that have investigated the consequences of SNPs on the signalling profile of the μ-opioid receptor in vitro have shown that the common N40D variant has altered functional responses to some opioids, while other, rarer, variants display altered signalling or agonist-dependent regulation. Here, we review the data available on the effects of μ-opioid receptor polymorphisms on receptor function, expression and regulation in vitro, and discuss the limitations of the studies to date. Whether or not μ-opioid receptor SNPs contribute to individual variability in opioid responses remains an open question, in large part because we have relatively little good data about how the amino acid changes affect μ-opioid receptor function. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.


The effect of ASA, ticagrelor, and heparin in ST-segment myocardial infarction patients with prolonged transport times to primary percutaneous intervention.
To investigate the effects of early upstream antithrombotic therapy administration (ATTA) in ST-segment elevation myocardial infarction (STEMI) patients with prolonged transport times to primary percutaneous intervention (PPCI) on major clinical outcomes. It remains unclear whether early upstream administration of aspirin, ticagrelor, and unfractionated heparin (UFH) confers additional benefits compared with in-hospital administration. Between 2015 and 2018, we performed PPCI in 709 included consecutive STEMI patients. We compared 482 STEMI patients who received aspirin, ticagrelor, and UFH loading in a non-PCI capable spoke hospital before transfer (NPHT) versus 227 prehospital triage setting (PTS) STEMI patients who received in-ambulance aspirin, followed by ticagrelor and UFH in the hub catheterization laboratory. The primary outcome was the presence of a pre-PPCI TIMI flow 2-3 in the infarct related artery (IRA). The secondary outcomes included definite acute stent thrombosis and hemorrhagic complications. The median times from ticagrelor and heparin administration to angiography in the NPHT group and the PTS group were 80.5 min (Interquartile Range (IQR) 68.5-94) and 10 min (IQR 5-15) respectively (p < .0001). Using inverse probability of treatment weighting to minimize heterogeneity between groups, we showed significant differences for the primary outcome (44.6 versus 18.5%, p < .0001) and for definite acute stent thrombosis (0.6 versus 2.6%, p = .03), with no difference in the combined in-hospital BARC 2-5 bleeding events (1.9 versus 3.5%, p = .18) in the NPHT versus the PTS group, respectively. In this single-center retrospective cohort study, after adjusting for baseline covariates, early upstream ATTA with aspirin, ticagrelor, and UFH was associated with greater pre-PPCI TIMI flow and less definite acute stent thrombosis in STEMI patients, without increased bleeding risk.


Immunostimulatory activities of mono- or diglycosylated alpha-galactosylceramides.
We examined the effects of 2"- or 3"-monoglycosylated alpha-galactosylceramides (alpha-GalCers) and 2",3"-diglycosylated alpha-GalCers on allogeneic MLR and the proliferation of murine spleen cells. It was found that their ceramide portions greatly affect their immunostimulatory activities, and that the 3"-hydroxyl group plays a more important role in the immunostimulatory effects of alpha-GalCer derivatives than the 2"-hydroxyl group.


Long-term-video monitoring EEG and 18F-FDG-PET are useful tools to detect residual disease activity in anti-LGI1-Abs encephalitis: A case report.
The use of CD20-depleting monoclonal antibodies has shown to improve the long-term outcome of patients with anti-leucine-rich glioma-inactivated protein 1 antibodies (anti-LGI1-Abs) encephalitis after first-line immunotherapy, but currently predictive markers of treatment response and disease activity are lacking. A 75-year-old man presented cognitive impairment and faciobrachial dystonic seizures (FBDS), with mild abnormalities at electroencephalography (EEG), normal brain magnetic resonance and cerebrospinal fluid (CSF) analysis. Anti-LGI1-Abs were detected in serum and CSF, and corticosteroids and intravenous immunoglobulins were administered. Despite partial cognitive improvement, 18F-fluoridesoxyglucose-positron emission tomography (18F-FDG-PET) showed the persistence of temporo-mesial hypermetabolism, and FBDS were still detected by long-term monitoring video EEG (LTMV EEG). Rituximab was therefore administered with FBDS disappearance, further cognitive improvement, and resolution of 18F-FDG-PET temporo-mesial hypermetabolism. Our experience supports the use of 18F-FDG-PET and LTMVEEG as useful tools to measure disease activity, evaluate treatment response and guide therapeutic decisions in the long-term management of anti-LGI1-antibody encephalitis.


Isolated internal carotid artery dissection in a long-distance runner.
We present a case of internal carotid artery dissection (ICAD) in the precranial segment, which caused binocular visual impairment in a 49-year-old man during a marathon race. The incident lasted 3 h, after which the symptoms resolved. Imaging tests showed internal carotid artery dissection. No ophthalmologic changes were identified. After 6 weeks of ineffective non-invasive treatment the patient underwent vascular surgery - stent implantation into the damaged artery. Detailed diagnostic tests and adequate treatment allowed us to achieve a good clinical result. Upon the suspicion of ICAD it is recommended to extend standard Doppler ultrasound performed with a linear transducer and evaluate the proximal segment of the internal carotid artery with a curved transducer as well.


Significance of the genetic relationships deduced from partial nucleotide sequencing of infectious bursal disease virus genome segments A or B.
The rapid genomic characterization of infectious bursal disease virus (IBDV) requires determining which partial nucleotide (nt) sequences derived from IBDV segments A or B would produce phylogenetic information as significant as sequencing the whole corresponding segments. Long nt coding sequences of 27 IBDV segments A (aa 20-991) and 21 segments B (aa 7-stop codon) were retrieved from databanks and used to compute reference phylogenetic trees using Neighbor Joining (NJ) and Parsimony (P): clusters appearing in the NJ and P reference trees with a bootstrap value greater than 80% were considered as significant (Whole Segment Clusters, WSC). The sequences were then cut into overlapping regions. These were used to compute phylogenetic trees which were compared with reference ones. Of the partial sequences, the VP2 gene best represented IBDV segment A (10 out of 13 WSC were conserved), and the 5' two thirds of segment B best represented segment B (5 to 6 conserved WSC out of 6). Implementation of the Plato programme finally demonstrated that the region encoding VP2 variable domain (vVP2, segment A) is the only region of IBDV genome with a significantly different evolution rate, which result is consistent with vVP2 being subjected to a high selection pressure.


A heterotrimetallic Ir(III), Au(III) and Pt(II) complex incorporating cyclometallating bi- and tridentate ligands: simultaneous emission from different luminescent metal centres leads to broad-band light emission.
Di- and tri-nuclear metal complexes incorporating gold(III), iridium(III) and platinum(II) units linked via a 1,3,5-triethynylbenzene core are reported, together with the corresponding mononuclear complexes as models. The gold(III) and platinum(II) units comprise tridentate, cyclometallating, C^N^C and N^N^C-coordinating ligands, respectively, with the Ar-C≡C- directly bound to the metal at the fourth coordination site. The iridium moiety is an Ir(ppy)2(acac) unit bound to the triethynylbenzene through a phenyl substituent at the 3-position of the acac ligand. The multinuclear compounds are prepared, using a modular synthetic strategy, from the monometallic complexes. All of the compounds are luminescent in solution at room temperature, and their photophysical properties were studied. The triplet excited state energies of the mononuclear complexes lie in the order Au > Ir > Pt. Consistent with this order, energy transfer from Au to Ir and from Au to Pt is observed, leading to quenching of the Au emission in the gold-containing multinuclear complexes. Energy transfer from Ir to Pt occurs at a rate that only partially quenches the Ir-based emission. As a result, the dinuclear Ir-Pt and trinuclear Au-Ir-Pt complexes display broad emission across most of the visible region of the spectrum.


[Video-assisted thoracoscopic surgery].
We describe our experience with video-assisted thoracoscopic surgery (VATS). Twenty-nine patients were operated on with this technique for various anterior thoracic spinal lesions. There were 6 cases of disc herniation with simple resection, 6 with acute thoracic fractures requiring anterior grafting and stabilization, 7 old fractures and malunions treated by corporectomy, grafting and anterior stabilization in 3, 4 with spinal metastases that were resected and stabilized, 3 with a paravertebral spinal tumor (2 schwannomas and 1 chondroblastoma), and 3 osteoid osteomas that were resected with anterior grafting in one case. Indications for these procedures are specified and the technical considerations discussed for each group of pathologies. We had three complications: one conversion to thoracotomy in a case of spinal metastasis, one pleural effusion, and one incomplete resection of a thoracic disc herniation. We emphasize the need for minimally invasive approaches in spinal surgery.


Assessment of chemoselective neoglycosylation methods using chlorambucil as a model.
To systematically assess the impact of glycosylation and the corresponding chemoselective linker upon the anticancer activity/selectivity of the drug chlorambucil, herein we report the synthesis and anticancer activities of a 63-member library of chlorambucil-based neoglycosides. A comparison of N-alkoxyamine-, N-acylhydrazine-, and N-hydroxyamine-based chemoselective glycosylation of chlorambucil revealed sugar- and linker-dependent partitioning among open- and closed-ring neoglycosides and corresponding sugar-dependent variant biological activity. Cumulatively, this study represents the first neoglycorandomization of a synthetic drug and expands our understanding of the impact of sugar structure upon product distribution/equilibria in the context of N-alkoxyamino-, N-hydroxyamino-, and N-acylhydrazine-based chemoselective glycosylation. This study also revealed several analogues with increased in vitro anticancer activity, most notably D-threoside 60 (NSC 748747), which displayed much broader tumor specificity and notably increased potency over the parent drug.


Prevention of adipose tissue depletion during food deprivation in angiotensin type 2 receptor-deficient mice.
Angiotensin (Ang) II is produced locally in various tissues, but its role in the regulation of tissue metabolism is still unclear. Recent studies have revealed the role of type 2 Ang II receptor (AT2R) in the control of energy homeostasis and lipid metabolism. The contribution of the AT2R to adaptation to starvation was tested using AT2R-deficient (AT2R (y)(/-)) mice. Fasted AT2R (y)(/-) mice exhibited a lower loss of adipose tissue weight associated to a decreased free fatty acid (FFA) release from stored lipids than the controls. In vitro studies show that Ang II causes an AT1R-mediated antilipolytic effect in isolated adipocytes. AT1R expression is up-regulated by fasting in both genotypes, but the increase is more pronounced in AT2R (y/-) mice. In addition, the increased muscle beta-oxidation displayed in AT2R (y/-) mice on a fed state, persists after fasting compared with wild-type mice. In liver from fed mice, AT2R deficiency did not modify the expression of genes involved in fatty acid oxidation. However, in response to fasting, the large increase of the expression of this subset of genes exhibited by wild-type mice, was impaired in AT2R (y/-) mice. Taken together, decreased lipolytic capacity and increased muscle fatty acid oxidation participate in the decreased plasma FFA observed in fasted AT2R (y/-) mice and could account for the lower FFA metabolism in the liver. These data reveal an important physiological role of AT2R in metabolic adaptations to fasting.


Common dermatoses. Part II.
Skin diseases are an essential part of primary care medicine. Most dermatologic care is delivered in an outpatient setting. The initial evaluation is usually performed by the primary care physician. Women account for nearly 60% of all visits for dermatologic complaints.


Experimental study of myocardial bridges.
Myocardial bridges were reproduced in dogs by transfer of a fragment of the left ventricular wall above the upper portion of the anterior interventricular artery. The viability of this bridge was shown by coronarography, anatomic, histologic and electron microscopic studies, illustrating the vascular patency and the integrity of blood vessels and neighbouring myocardium in the cases postoperatively heparinized. The experimental model efficiency was also proved by ECG examinations revealing ischemic distresses induced by compression of the bridge against the underlying artery.


Hunter versus CIE color measurement systems for analysis of milk-based beverages.
The objective of our work was to determine the differences in sensitivity of Hunter and International Commission on Illumination (CIE) methods at 2 different viewer angles (2 and 10°) for measurement of whiteness, red/green, and blue/yellow color of milk-based beverages over a range of composition. Sixty combinations of milk-based beverages were formulated (2 replicates) with a range of fat level from 0.2 to 2%, true protein level from 3 to 5%, and casein as a percent of true protein from 5 to 80% to provide a wide range of milk-based beverage color. In addition, commercial skim, 1 and 2% fat high-temperature, short-time pasteurized fluid milks were analyzed. All beverage formulations were HTST pasteurized and cooled to 4°C before analysis. Color measurement viewer angle (2 vs. 10°) had very little effect on objective color measures of milk-based beverages with a wide range of composition for either the Hunter or CIE color measurement system. Temperature (4, 20, and 50°C) of color measurement had a large effect on the results of color measurement in both the Hunter and CIE measurement systems. The effect of milk beverage temperature on color measurement results was the largest for skim milk and the least for 2% fat milk. This highlights the need for proper control of beverage serving temperature for sensory panel analysis of milk-based beverages with very low fat content and for control of milk temperature when doing objective color analysis for quality control in manufacture of milk-based beverages. The Hunter system of color measurement was more sensitive to differences in whiteness among milk-based beverages than the CIE system, whereas the CIE system was much more sensitive to differences in yellowness among milk-based beverages. There was little difference between the Hunter and CIE system in sensitivity to green/red color of milk-based beverages. In defining milk-based beverage product specifications for objective color measures for dairy product manufacturers, the viewer angle, color measurement system (CIE vs. Hunter), and sample measurement temperature should be specified along with type of illuminant.


Efficacy of Intra-arterial Indocyanine Green Videoangiography in Hemangioblastoma Surgery: A Case Report.
Intravenous indocyanine green (ICG) videoangiography is reportedly useful for vascular neurosurgery, and for treating hemangioblastoma due to its high vascularity. Videoangiography obtained after intra-arterial ICG injection has emerged as a more useful option than that after intravenous injection. This report offers the first description of a case of hemangioblastoma successfully treated using intra-arterial ICG videoangiography, and describes the efficacy of this technique. A 20-year-old man presented with progressive cerebellar ataxia and dysphagia. Magnetic resonance imaging (MRI) revealed an enhanced solid tumor in the medulla oblongata. Digital subtraction angiography (DSA) showed a highly vascularized tumor. Surgery was performed to remove the tumor in a hybrid operating room. A catheter was introduced into the vertebral artery (VA) for intra-arterial ICG videoangiography. Superficial feeders and drainers were identified and flow dynamic changes in the tumor were assessed by intra-arterial ICG videoangiography. The tumor was removed after confirming lack of flow in the drainer. Intra-arterial ICG videoangiography was more useful than intravenous ICG videoangiography in hemangioblastoma surgery for identifying feeders and drainers and assessing flow dynamics in the tumor. Use of Flow 800 made these findings simpler and easier to evaluate.


Immobilization of pectin fragments on solid supports: novel coupling by thiazolidine formation.
As a prerequisite to solid-phase and sequence analyses and for the study of the fine structure of pectin, we have developed oriented and chemoselective methodologies to couple model pectin fragments onto a solid support. Polyethylene glycol polyacrylamide (PEGA) resins were selected due to their excellent swelling properties in a wide range of solvents, including water, and their easy accessibility to enzymes. Following appropriate derivatization of amino-terminated PEGA resins, oligomers of alpha-D-galacturonic acid (GalA), up to the trimer, were anchored to the support through their reducing end. In addition to reductive amination, the strategies included the formation of an oxime bond, a glycosyl hydrazide, and a pyroglutamyl ring. Further, we developed a new immobilization approach based on the formation of a thiazolidine ring. All methods proved efficient and did not require modification of the GalA oligomers prior to coupling. In addition, very mild conditions and few steps for derivatization of the support were required. Immobilization by thiazolidine ring and oxime bond formation were the preferred methods, given the stability of the linkages formed, their compatibility with aqueous solvents, the few number of steps required, and their potential for application to larger pectin fragments. Thiazolidine and pyroglutamyl anchoring were developed further by the insertion of a disulfide bond which allowed release of the saccharides under mild, selective conditions.


Design and Optimization of Febuxostat-loaded Nano Lipid Carriers Using Full Factorial Design.
This work aims to develop nanostructured lipid carriers (NLCs) to improve the oral bioavailability of febuxostat (FEB). High shear homogenization, a well-known technique, followed by bath sonication with slight modifications was used to prepare FEB-loaded NLCs using oleic acid as liquid lipid and stearic acid as solid lipid. A total of 3² full factorial design was utilized to examine the effect of 2 independent variables, namely, X1 (liquid to solid lipid ratio) and X2 (surfactant concentration) on the Y1 (particle size) and Y2 (% entrapment efficiency) of the drug. The prepared NLCs were evaluated for particle size, polydispersity index, zeta potential, and (%) entrapment efficiency. The drug's highest solubility was found in the stearic (solid lipid) and oleic acid (liquid lipid), which were further chosen for NLC preparation. Result of the present study showed an increase in entrapment efficiency and a decrease in particle size with the increase in liquid lipid to solid lipid ratio. With increased surfactant concentration, a small particle size is observed. The optimized formulation's particle size and (%) entrapment efficiency was found to be 99 nm and 80%, respectively. The formulations' zeta potential and polydispersity index were found within the range. Compared to plain drug suspension, the optimized formulation showed higher drug release, which may be due to the presence of the higher amount of liquid lipid. The particles shown in the transmission electron microscopy were round in shape and have smooth surface. Stability studies showed that the NLC formulation can be stored for a longer time period under room condition. FEB-loaded NLC were successfully prepared using full 3² factorial design, and can be further used for oral delivery of FEB for gout treatment.


A comparison of knee joint motion patterns between men and women in selected athletic tasks.
Women have higher non-contact anterior cruciate ligament injury rate than men do in sport activities. Non-contact anterior cruciate ligament injuries frequently occur in sports requiring cutting tasks. Alternated motor control strategies have identified as a potential risk factor for the non-contact anterior cruciate ligament injuries. The purpose of this study was to compare the patterns of knee kinematics and electromyographic activities in running, side-cutting, and cross-cutting between men and women recreational athletes. Three-dimensional kinematic data of the knee and electromyographic data of selected muscles across the knee joint were collected for 11 men and 9 women recreational athletes in running, side-cutting, and cross-cutting. Regression analyses with dummy variables for comparison of knee motion patterns between men and women. Women tend to have less knee flexion angles, more knee valgus angles, greater quadriceps activation, and lower hamstring activation in comparison to men during the stance phase of each of the three athletic tasks. Literatures suggest these alternated knee motion patterns of women tend to increase the load on the anterior cruciate ligament. Women on average may have certain motor control strategies that may alter their knee motion patterns. Women's altered knee motion patterns may tend to increase the load on the anterior cruciate ligament in the selected athletic tasks, which may contribute to the increased anterior cruciate ligament injury rate among women. Non-contact anterior cruciate ligament injuries frequently occur in sports. Altered motor control strategies and lower extremity motion patterns are likely to play an important role in non-contact anterior cruciate ligament injuries. Non-contact anterior cruciate ligament injuries may be prevented by correcting altered motor control strategies and associated lower extremity motion patterns through certain training programs.


Quantification of Degradation Products Formed during Heat Sterilization of Glucose Solutions by LC-MS/MS: Impact of Autoclaving Temperature and Duration on Degradation.
Heat sterilization of glucose solutions can lead to the formation of various glucose degradation products (GDPs) due to oxidation, hydrolysis, and dehydration. GDPs can have toxic effects after parenteral administration due to their high reactivity. In this study, the application of the F0 concept to modify specific time/temperature models during heat sterilization and their influence on the formation of GDPs in parenteral glucose solutions was investigated using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Glucose solutions (10%, w/v) were autoclaved at 111 °C, 116 °C, and 121 °C for different durations. The GDPs glyoxal, methylglyoxal, glucosone, 3-deoxyglucosone/3-deoxygalactosone, 3,4-dideoxyglucosone-3-ene, and 5-hydroxymethylfurfural were quantified after derivatization with o-phenylenediamine by an optimized LC-MS/MS method. For all GDPs, the limit of detection was <0.078 μg/mL, and the limit of quantification was <0.236 μg/mL. The autoclaving time of 121 °C and 15 min resulted in the lowest levels of 3-DG/3-DGal and 5-HMF, but in the highest levels of GO and 2-KDG. The proposed LC-MS/MS method is rapid and sensitive. So far, only 5-HMF concentrations are limited by the regulatory authorities. Our results suggest reconsidering the impurity limits of various GDPs, especially the more toxic ones such as GO and MGO, by the Pharmacopoeias.


SigF, a new sigma factor required for a motility system of Myxococcus xanthus.
A new sigma factor, SigF, was identified from the social and developmental bacterium Myxococcus xanthus. SigF is required for fruiting body formation during development as well as social motility during vegetative growth. Analysis of gene expression indicates that it is possible that the sigF gene is involved in regulation of an unidentified gene for social motility.


Pathogenesis of uteroplacental acute atherosis: An update on current research.
Uteroplacental acute atherosis is a type of arterial vascular disease that affects the placenta during pregnancy and predominates in the maternal spiral arteries in the decidua basalis layer of the pregnant uterus. This condition is characterized by fibrin-like necrosis of the blood vessel walls, the accumulation of macrophages containing fat (foam cells), and the infiltration of macrophages around blood vessels. Uteroplacental acute atherosis is rare in normal pregnancy but occurs more frequently in patients with pregnancy complications, including preeclampsia, spontaneous preterm labor, preterm prelabor rupture of membranes, mid-trimester spontaneous abortion, fetal death, and small-for-gestational age. It is believed that the mechanisms underlying the development of uteroplacental acute atherosis are related to the incomplete physiological transformation of spiral arteries, placental inflammation, abnormal lipid metabolism, and oxidative stress. In this review, we describe the pathogenesis of uteroplacental acute atherosis to provide reference guidelines for the future prevention and treatment of uteroplacental acute atherosclerotic disease.


Application of direct-infusion ESI-MS/MS for toxicological screening.
Direct-infusion ESI-MS/MS is a powerful approach for the identification of substances in complex mixtures. The aim of this work was to investigate its applicability to the toxicological screening of blood samples. A simple protein precipitation was used, followed by a 15 min infusion of the extract in the mass spectrometer. The application of the procedure to commercial quality controls and authentic post-mortem blood samples demonstrated that the direct-infusion ESI-MS/MS approach enables the simultaneous identification of substances that require different chromatographic conditions. However, poor sensitivity was observed for benzodiazepine, amphetamines and opiate compounds. Considering the facile implementation and positive performance of direct-infusion ESI-MS/MS, this approach may to be a valuable complementary technique for systematic toxicological analysis procedures.


The role of the general practitioner and the orthodontist in the provision of orthodontic care.
Orthodontics is a small branch of dentistry but one of the oldest and most widespread of dental specialties. It is characterized by long-term treatment objectives which are related to dentofacial morphology and function, growth, facial balance and maturation. Owing to the lack of baseline data it has not been included in the recommendations of the FDI for a stepwise procedure towards 'Health for All by the Year 2000'. Serious efforts should be made to allow inclusion of orthodontics by overcoming this data problem. It is strongly recommended that an internationally acceptable index for orthodontic purposes at the community level be developed. Problems of integration of orthodontic services within oral health care programmes are most significant at medium resource levels when priorities have to be established among many highly desirable dental services. In upper resource levels with less caries and periodontal disease than before the general practitioner should be aware of the rapidly increasing needs for service among elderly people due to improved oral health in adults. For the sake of efficiency, control and quality orthodontic treatment should preferably be carried out by appropriately educated orthodontists, even if the case appears simple in the beginning. Simple cases treated by specialists consume fewer resources than are needed for a system of effective communication and delegation to the general practitioner. Continuing education of all practitioners and other members of the dental team should be carried out in personnel categories and across the boundaries between them.


[Nocturia and nocturnal polyuria in the elderly. Treatment essential for increasing patients' quality of life and decreasing the risk of injury].
Nocturia, i.e. nocturnal voiding episodes, is a symptom which can occur at all ages, but there is an age-related increase in both men and women. Both health and quality of life are deteriorated by nocturia. Sleep is disturbed, with daytime sleepiness and reduced well-being as consequences. The risk of fall injuries is increased among elderly persons who need to get up several times at night for toilet visits. Nocturia is associated with an increase in nocturnal urine output, and an increased number of nocturnal voids indicates a shift of urine output from the daytime to the night. One of the aims of the treatment of nocturia is therefore to normalise the circadian rhythm of diuresis.


An Algorithm for Fitting Sphere Target of Terrestrial LiDAR.
The sphere target played a vital role in terrestrial LiDAR applications, and solving its geometrical center based on point cloud was a widely concerned problem. In this study, we proposed a newly finite random search algorithm for sphere target fitting. Based on the point cloud data and the geometric characteristics of the sphere target, the algorithm realized the target sphere fitting from the perspective of probability and statistics with the help of parameter estimation. Firstly, an initial constraint space was constructed, and the initial center and radius were determined by finite random search. Then, the optimal spherical center and radius were determined gradually through continuous iterative optimization. We tested the algorithm with the simulated and realistic point cloud. Experimental results showed that the proposed algorithm could be effectively applied to all kinds of point cloud fitting. When the coverage rate was bigger than 30%, the fitting accuracy could reach within 0.01 mm for all kinds of point clouds. When the coverage rate was less than 20%, the fitting accuracy can reach ±1 mm, although it was reduced to a certain extent.


Metabolic and nutritional needs to normalize body mass index by doubling the admission body weight in severe anorexia nervosa.
Anorexia nervosa exhibits one of the highest death rates among psychiatric patients and a relevant fraction of it is derived from undernutrition. Nutritional and medical treatment of extreme undernutrition present two very complex and conflicting tasks: (1) to avoid "refeeding syndrome" caused by a too fast correction of malnutrition; and (2) to avoid "underfeeding" caused by a too cautious refeeding. To obtain optimal treatment results, the caloric intake should be planned starting with indirect calorimetry measurements and electrolyte abnormalities accurately controlled and treated. This article reports the case of an anorexia nervosa young female affected by extreme undernutrition (BMI 9.6 kg/m(2)) who doubled her admission body weight (from 22.5 kg to 44 kg) in a reasonable time with the use of enteral tube feeding for gradual correction of undernutrition. Refeeding syndrome was avoided through a specialized and flexible program according to clinical, laboratory, and physiological findings.


Rasch-transformed raw scores and Two-way ANOVA: a simulation analysis.
This article demonstrates, through the exposition of underestimated variable effects or spurious interaction effects, the inherent inadequacy of untransformed 0-1 raw scores for analysis via Two-Way analysis of variance (ANOVA). The pioneering work in this field, conducted in the 1990's by Dr. Susan Embretson of the University of Kansas, USA, is highlighted, and the eminent suitability of Rasch transformations of 0-1 raw scores for analysis via Two-Way ANOVA is also demonstrated. In this study Monte Carlo techniques or simulations are utilized to determine the precise psychometric conditions under which differences between raw scores and Rasch transformations of those raw scores are detectable via Two-Way ANOVA. This study partially replicates Dr. Embretson's studies, and also defines the extent of underestimation and spuriousness which ensue when uniform or skewed distributions of item difficulties are used instead of normal distributions, and misfitting raw data are utilized instead of fitting data.


Diabetic retinopathy management by Australian optometrists.
To survey the current diabetic retinopathy screening and management practices of Australian optometrists following the release of the 1997 National Health Medical Research Council Diabetic Retinopathy Management Guidelines. Cross-sectional national survey, primary care setting. 1000 Australian optometrists across different states. A self-administered questionnaire was sent to 1000 optometrists across all states during 2007/2008. Use of retinal camera, screening practices/attitudes and behaviour in diabetic retinopathy management. 568 optometrists (57%) responded to the survey. Patients' unpreparedness to drive post dilation (51%) and the fear of angle closure glaucoma (13%) were the two main barriers to optometrists not performing dilated ophthalmoscopy. Those who had strong desire to screen for diabetic retinopathy were more likely to use a retinal camera (p<0.005). Use of a retinal camera was significantly associated with an increased confidence in detecting clinical signs of diabetic retinopathy including macular oedema (P<0.001). Optometrists who read the guidelines at least once were 2.5-times (P<0.001) more likely to have confidence in detecting macular oedema than those who had never read the guidelines. Although they may be confident in diagnosis, and may use retinal cameras for screening, nearly 60% of optometrists would not refer patients with macular oedema to an ophthalmologist. Despite their self-reported desire for involvement in diabetic retinopathy, the management of macular oedema by Australian optometrists needs improvement. The use of retinal cameras and promotion of the 2008 NHMRC guidelines should be encouraged to improve overall optometric diabetic retinopathy management, particularly with macular oedema.


Determinants of Clinical Outcomes After Infectious Scleritis.
The aims of this study were to describe the clinical course of microbial infectious scleritis and identify factors associated with poor visual outcomes. Data from 26 eyes of 26 patients with culture-proven bacterial or fungal scleritis presenting at a single tertiary center from January 1, 2007, to July 1, 2021, were reviewed. Thirty-six variables were analyzed for associations with poor vision [best-corrected visual acuity (BCVA) <20/200] or loss of vision (no light perception vision or requirement for enucleation or evisceration) at final visit. The mean age at initial presentation was 67.1 ± 14.0 (range: 34-92) years with a mean follow-up of 2.1 ± 2.2 (0.05-8.45) years. The mean presenting logarithm of minimal angle of resolution (logMAR) BCVA was 1.3 ± 1.0 (∼20/400) and mean final logMAR BCVA was 1.6 ± 1.2 (∼20/800). Fourteen eyes (53.8%) exhibited poor vision and 7 (26.9%) had loss of vision at final follow-up. History of necrotizing scleritis and poor presenting vision were associated with poor final vision (OR = 19.1; P = 0.017 and OR = 7.5; P = 0.047, respectively), whereas fungal scleritis was associated with loss of vision (odds ratio [OR] = 30.3, P = 0.013). Subconjunctival antimicrobial treatment was inversely associated with loss of vision (OR = 0.06, P = 0.023). There was no difference in vision between medical and combined medical-surgical management, although infection resolution time was shorter for combined intervention (16.8 ± 10.6 vs. 53.7 ± 33.8 days; P = 0.005). Infectious scleritis is often successfully treated, but loss of vision or eye removal is common. Poor baseline vision, history of necrotizing scleritis, and fungal etiology were prognostic for worse clinical outcomes. Surgical intervention was associated with quicker resolution compared with medical treatment alone.


Commentary. The diseases of Alexander the Great.
The accompanying articles that speculate that Alexander the Great had a traumatic carotid dissection or congenital cervical scoliosis demonstrate the difficulties in retrospective diagnosis as a historical enterprise. The extant primary sources were written centuries after Alexander's death and are ambiguous in their original languages, and even more so in translation. Thus we cannot be certain what illness Alexander actually had. Furthermore, anachronistic diagnosis removes Alexander from the medical context of this time, telling us little of historical significance about him. Such investigations also illustrate the more general limits that the absence of context imposes on the study of ancient history.


The minimal clinically important difference of the motricity index score.
The Motricity Index (MI) can predict motor function after rehabilitation, but its minimal clinically important difference (MCID) has not been established. The primary study aim was to estimate the MCID value of the MI arm score. Between 2017 and 2018, 173 participants hospitalized with confirmed ischemic stroke were recruited into an observational rehabilitation study. Participants with motor weakness as measured by the Fugl-Meyer upper-extremity (FM-UE) and MI with complete baseline and follow-up assessments at 3 months were included in this analysis. The longitudinal recovery of the MI arm score was anchored to having a poor outcome based on the FM-UE recovery (<9) longitudinally. Results reported include the area-under-curve (AUC), along with sensitivity, specificity, and optimal cut-points based on maximizing the Youden statistic. Sixty-nine patients (median [IQR] age 70 [18] years; 48% male; 54% white) were included in the final analysis. Mean ± standard deviation outcome scores at 3-months were: MI arm: 83.19 ± 22.80; FM-UE: 53.04 ± 17.26. For the primary results, the MI arm score optimal MCID cutoff for observed recovery was 13 points with a sensitivity of 80% (95% Confidence Interval (CI)(67.6%, 92.4%)) and a specificity of 69.0% (95% CI (52.1, 85.8%)), and the AUC was 0.8082 (0.7007, 0.9157). This was the first study to report the MCID of the MI arm score, as anchored to the FM-UE recovery between acute evaluation and 3-months. The estimated optimal MCID of improvement in the MI arm score was 13 points.


New artificial dielectric metamaterial and its application as a terahertz antireflection coating.
We describe a novel artificial dielectric material that has applications at millimeter and submillimeter wavelengths. The material is manufactured from layers of metal mesh patterned onto thin polypropylene sheets, which are then bonded together using a hot pressing process to provide planar rugged discs that can be reliably cycled to cryogenic temperatures. The refractive index of this material can be tuned by adjusting the geometry and spacing of the metal mesh layers. We demonstrate its usage by designing and characterizing a broadband antireflection coating for a Z-cut crystalline quartz plate. The coating was fabricated and applied to the quartz using the hot press technique and characterized using a Fourier transform spectrometer. The performance is shown to be in good agreement with a high frequency structure simulator and transmission line modeling results.


Potential risks, benefits of progestins in birth control pills outlined.
Progestins in oral contraceptives (OCs) produce potential complications, as well as noncontraceptive benefits, according to Robert A. Hatcher, MD, MPH, professor of gynecology and obstetrics, Emory University Medical School. Hatcher told CTU that lowering the progestin content in an OC may decrease complications, but could also decrease the benefits experienced by women. "The extent to which that will happen remains to be seen," he said. Hatcher cited the following potential complications of progestins in OC: hypertension; decreased levels of high density lipoproteins; acne; oily skin; headaches between pill cycles; dilated leg veins; pelvic congestion syndrome; thrombosis of superficial leg veins; gallstones; Monilia vaginitis; cholestatic jaundice; and depression, fatigue, and decreased libido. Progestins, according to Hatcher, also produce these noncontraceptive benefits: protection against PID; decreased dysmenorrhea; decreased menstrual blood loss, decreased iron deficiency anemia; protection against endometrial cancer; protection against fibrocystic breast disease, and fibroadenomas of the breast; decreased bleeding from fibroids; decreased growth of fibroids. When ovulation is suppressed, Hatcher emphasized, additional benefits that may occur include the following: decreased risk of functional ovarian cysts; elimination of mittleschmerz pain; decreased rick of ovarian cancer; protection against endometriosis.


A method for calculating the mean absorption time of drugs undergoing reversible and first-pass metabolism.
A method has been derived for calculating the mean absorption time of an oral drug and its interconversion metabolite which is generated from the drug systemically and presystemically. The method evolves from the convolution integral and requires plasma AUC and AUMC values after separate intravenous administration of the drug and its interconversion metabolite and oral administration of the drug. It can also be used to calculate the mean input time of a drug undergoing reversible metabolism and administered by any other extravascular route. Results of a simulation study using both errorless and errant data indicate that, when the absorption rate constant of a drug or its interconversion metabolite is not much larger than the apparent elimination rate constant, the proposed method performs satisfactorily. However, when the absorption rate constant of a drug or its interconversion metabolite is much larger than the apparent elimination rate constant, the proposed method appears to be inaccurate.


Clinical Evaluation and Treatment of Soft Tissue Tumors.
Soft tissue sarcomas are uncommon and frequently missed on examination, resulting in delays in diagnosis and, occasionally, inappropriate treatment. Sarcoma staging, the process of defining the local extent of tumor and potential distant spread, involves a thorough history and physical examination, directed imaging, and biopsy. Biopsy is a complicated procedure in approximately 20% of cases and should be performed only by experienced personnel and at a center with a multidisciplinary team familiar with the treatment of patients with soft tissue sarcomas. The goal of surgery is to obtain tumor-free margins. In conjunction with radiation therapy, surgery can then provide local disease control in more than 90% of patients. The role of chemotherapy in nonmetastatic disease is unclear and is of marginal efficacy in patients with metastases. Although most tumors recur within 2 to 5 years, long-term clinical and radiographic surveillance is necessary.


Superior Electrocatalytic Activity of a Robust Carbon-Felt Electrode with Oxygen-Rich Phosphate Groups for All-Vanadium Redox Flow Batteries.
A newly prepared type of carbon felt with oxygen-rich phosphate groups is proposed as a promising electrode with good stability for all-vanadium redox flow batteries (VRFBs). Through direct surface modification with ammonium hexafluorophosphate (NH4 PF6 ), phosphorus can be successfully incorporated onto the surface of the carbon felt by forming phosphate functional groups with -OH chemical moieties that exhibit good hydrophilicity. The electrochemical reactivity of the carbon felt toward the redox reactions of VO(2+) /VO2 (+) (in the catholyte) and V(3+) /V(2+) (in the anolyte) can be effectively improved owing to the superior catalytic effects of the oxygen-rich phosphate groups. Furthermore, undesirable hydrogen evolution can be suppressed by minimizing the overpotential for the V(3+) /V(2+) redox reaction in the anolyte of the VRFB. Cell-cycling tests with the catalyzed electrodes show improved energy efficiencies of 88.2 and 87.2 % in the 1(st) and 20(th) cycles compared with 83.0 and 81.1 %, respectively, for the pristine electrodes at a constant current density of 32 mA cm(-2) . These improvements are mainly attributed to the faster charge transfer allowed by the integration of the oxygen-rich phosphate groups on the carbon-felt electrode.


The relationship between professional identity and burnout among occupational therapists.
ABSTRACT Health professionals have been identified as a high risk group for job-related stress and burnout. This study builds on the existing literature to examine the links between burnout and the development of professional values as well as the broad scope of occupational therapy, which may act as a hindrance to establishing a concise and well recognized professional identity. One hundred and twenty six occupational therapists completed the Maslach Burnout Inventory and the Professional Identity Questionnaire. The factors that contribute to the relationship between a lack of professional identity in the field of occupational therapy and the levels of burnout among occupational therapists are identified and implications for establishing a strong and healthy workforce in occupational therapy are discussed.


TanGeoMS: tangible geospatial modeling system.
We present TanGeoMS, a tangible geospatial modeling visualization system that couples a laser scanner, projector, and a flexible physical three-dimensional model with a standard geospatial information system (GIS) to create a tangible user interface for terrain data. TanGeoMS projects an image of real-world data onto a physical terrain model. Users can alter the topography of the model by modifying the clay surface or placing additional objects on the surface. The modified model is captured by an overhead laser scanner then imported into a GIS for analysis and simulation of real-world processes. The results are projected back onto the surface of the model providing feedback on the impact of the modifications on terrain parameters and simulated processes. Interaction with a physical model is highly intuitive, allowing users to base initial design decisions on geospatial data, test the impact of these decisions in GIS simulations, and use the feedback to improve their design. We demonstrate the system on three applications: investigating runoff management within a watershed, assessing the impact of storm surge on barrier islands, and exploring landscape rehabilitation in military training areas.


[Risk factors for road traffic injury in agricultural vehicle drivers].
Objective: To examine the risk factors for road traffic injury in agricultural vehicle drivers. Methods: A total of 103 drivers (who had suffered agricultural vehicle road traffic injury within the past year based on the road traffic injury registrar from the Traffic Management Bureau) who were involved in the annual agricultural vehicle inspection from December 2014 to January 2015 were randomly sampled from the Yixing Agricultural Vehicle Station as the case group for this study. Based on a 1∶2 assignment ratio and matched for sex, age, and education, a total of 206 drivers who had not suffered any agricultural vehicle road traffic injury within the past year were selected as the control group. The general information, vehicle information, driving information, driving behavior, and accident details of the agricultural vehicle drivers were analyzed. Results: The incidence rate of road traffic injury was 7.24% given the 103 agricultural vehicle drivers who had suffered agricultural vehicle road traffic injury in the past year. Univariate logistic regression analysis showed that drinking, debt, pressure, history of car accident, history of drunk driving, smoking and phone use during driving, fatigue driving, and driving with illness were the risk factors for road traffic injury in agricultural vehicle drivers (OR=2.332, 2.429, 19.778, 5.589, 8.517, 2.125, 3.203, 10.249 and 5.639, respectively) . Multivariate logistic regression analysis also demonstrated that pressure, history of car accident, history of drunk driving, fatigue driving, and driving with illness were the risk factors for road traffic injury in agricultural vehicle drivers (OR=12.139, 11.184, 6.729, 5.939, and 6.544, respectively) . Conclusion: Pressure, history of car accident, history of drunk driving, fatigue driving, and driving with illness are the major risk factors for road traffic injury in agricultural vehicle drivers.


Different axoneme patterns in cilia and flagella of the same animal.
In eel fish ependymal cilia have a '9 + 2' axoneme with doublets bearing two dynein arms, while sperm flagella have a '9 + 0' axoneme, with doublets bearing only the row of inner arms. On this basis, the possibility that in the same animal a different genetic system regulates the flagellar and ciliary axoneme assembly is discussed.


Direct in Situ TEM Observation of Modification of Oxidation by the Injected Vacancies for Ni-4Al Alloy Using a Microfabricated Nanopost.
Vacancy injection and selective oxidation of one species in bimetallic alloy at high temperature is a well-known phenomenon. However, detailed understanding of the behavior of the injected vacancies and consequently their effect on oxidation remains elusive. The current research examines the oxidation of high-purity Ni doped with 4.1 at. % Al using in situ transmission electron microscopy (TEM). Experiments are performed on nanoposts fabricated from solution-annealed bulk material that are essentially single crystal samples. Initial oxidation is observed to occur by multisite oxide nucleation, formation of an oxide shell followed by cavity nucleation and growth at the metal/oxide interface. One of the most interesting in situ TEM observations is the formation of a cavity that leads to the faceting of the metal and subsequent oxidation occurring by an atomic ledge migration mechanism on the faceted metal surface. Further, it is directly observed that metal atoms diffuse through the oxide layer to combine with oxygen at the outer surface of the oxide. The present work indicates that injection of vacancies and formation of cavity will lead to a situation where the oxidation rate is essentially controlled by the low surface energy plane of the metal, rather than by the initial terminating plane at the metal surface exposed to the oxidizing environment.


Cell-Free Circulating Epigenomic Signatures: Non-Invasive Biomarker for Cardiovascular and Other Age-Related Chronic Diseases.
The burden of cardio-vascular and other age-related non-communicable diseases are rapidly increasing worldwide. Majority of these chronic ailments are curable, if diagnosed at early stages. Candidate biomarkers of early detection are therefore essential for identification of high-risk individuals, prompt and accurate disease diagnosis, and to monitor therapeutic response. The functional significance of circulating nucleic acids that recapitulate specific disease profiles is now well established. But subtle changes in DNA sequence may not solely reflect the differentiation of gene expression patterns observed in diverse set of diseases as epigenetic phenomena play a larger role in aetiology and patho-physiology. Unlike genetic markers, knowledge about the diagnostic utility of circulating epigenetic signatures: methylated DNA; micro RNA and modified histones are deficient. Characterization of these novel entities through omics-based molecular technologies might prompt development of a range of laboratory-based strategies, thereby accelerating their broader translational purpose for early disease diagnosis, monitoring therapeutic response and drug resistance. However, largest opportunity for innovation lies in developing point-of-care tests with accurate diagnostic and higher prognostic score that is applicable for screening of high-risk populations.