Phenotypic characterization of circulating tumor cells in the peripheral blood of patients with small cell lung cancer.
To evaluate the phenotypic heterogeneity of circulating tumor cells (CTCs) based on the expression of proliferative, apoptotic and Epithelial-to-Mesenchymal Transmission (EMT) markers during front-line treatment in patients with small cell lung cancer (SCLC) and to evaluate their clinical relevance. CTCs from 108 chemotherapy-naïve patients with SCLC were analyzed by double immunofluorescence staining using anti-Ki67, anti-M30, anti-Vimentin along with anti-CKs antibodies. In 83 patients CTCs were also enumerated using the CellSearch. Sequential samples were available from 76 and 48 patients after one-treatment cycle and on disease progression (PD), respectively, for immunofluorescence and from 50 and 36 patients after one-cycle and on PD, respectively, for CellSearch. At baseline, 60.2% of the patients had detectable CTCs by either method. Both proliferative (CK67+) and non-proliferative (Ki67-), apoptotic (M30+) and non-apoptotic (M30-) as well as EMT (Vim+) CTCs were present in the same patient. Among 22 patients without detectable CTCs by CellSearch, CK+/Ki67+ and CK+/Vim+ CTCs could be detected in 6 (27.3%) and 6 (27.3%) patients, respectively. One-chemotherapy cycle reduced both the incidence of detection (p<0.001) and the absolute number (p<0.001) of CTCs; conversely, on PD both the incidence of detection and the number of CTCs were significantly increased (p = 0.002 and p = 0.04, respectively). Multivariate analysis revealed that the increased number of Vim+ CTCs at baseline and of non-apoptotic CTCs on PD could be emerged as independent prognostic factors associated with decreased OS(p = 0.009 and p = 0.023, respectively). CK+/Ki67+, CK+/M30+ and CK+/Vim+ CTCs represent distinct subpopulations of CTCs in patients with SCLC, can be detected even in the absence of detectable CTCs by CellSearch; CK+/Ki67+ and CK+/Vim+ CTCs are associated with unfavorable clinical outcome.


Kindler syndrome with severe mucosal involvement in a large Palestinian pedigree.
Kindler syndrome (KS) is a rare autosomal recessive disease of skin fragility, photosensitivity and progressive poikiloderma. Mucous membranes may also be involved. KS is caused by mutations in the FERMT1 gene encoding kindlin-1. We report the clinical and molecular features of the largest kindred with KS to date, comprising 18 affected family members (age range: 12-63 years) from the Gaza Strip. All the affected family members were clinically examined. In addition a skin biopsy for immunofluorescence testing was obtained from the index case. Molecular analysis of the FERMT1 gene was performed on genomic DNA extracted from peripheral blood of 5 patients. All patients presented skin and eye photosensitivity, cutaneous atrophy, dyschromia and poikiloderma, oral cavity involvement, dysphagia and constipation with anal fissures. In addition, nail dystrophy and digit webbing were observed in most of them. Ocular manifestations detected in all patients comprised ectropion and keratoconjunctivitis, with early development of symblepharon in 17 out of 18 cases and blindness in one. Of note, 17 out of 18 affected family members also suffered from urethral strictures since childhood. Diagnosis was supported by immunofluorescence findings and definitely confirmed by FERMT1 sequencing which identified the homozygous frame-shift mutation c.137_140delTAGT. The high rate of mucosal involvement, its early onset and progressive course are noticeable features of our kindred. Also noteworthy is the lack of muco-cutaneous malignancies, despite the sunny habitat.


[Temporary and permanent NiTi stents in percutaneous surgery for ureteropelvic segment stricture].
A total of 18 roentgenoendoscopic percutaneous interventions for strictures of the ureteropelvic segment (UPS) have been made by the authors from the beginning of 2004: in 15 (83.3%) females and 3 (16.7%) males aged 16-48 years. Recurrent strictures developed in 11 (61.1%) patients after operations by Kuchere, Pristlay, Andersen-Hines, in 7 (38.9%) patients the strictures were primary. UPS bougieurage and endotomy were made in 3 and 15 patients, respectively. UPS intubation with a PVC tube was made in 2 cases, with a permanent NiTi stent-crown--in 5 cases, temporary stent--in 9 cases, in 2 cases intubation was not made. Complete recovery of UPS passability and significant reduction of hydronephrosis were seen in 15 (83.3%) patients, insignificant effect was registered in 3 patients (one case of PVC tube intubation, one case of NiTi temporary stent, one case of no intubation). Efficacy in patients with permanent stent was 100%, in patients with temporary stent--88.9%, in patients with a PVC tube and without intubation--in 50%. Novel techniques of intubation with permanent and temporary stents with shape memory after percutaneous correction of UPS stricture are promising in the treatment of patients with this pathology of the upper urinary tract and may become an operation of choice.


Analysis of AKAP7γ Dimerization.
A-kinase anchoring proteins (AKAPs) constitute a family of scaffolding proteins that contribute to spatiotemporal regulation of PKA-mediated phosphorylation events. In particular, AKAP7 is a family of alternatively spliced proteins that participates in cardiac calcium dynamics. Here, we demonstrate via pull-down from transfected cells and by direct protein-protein association that AKAP7γ self-associates. Self-association appears to be an isoform specific phenomenon, as AKAP7α did not associate with itself or with AKAP7γ. However, AKAP7γ did associate with AKAP7δ, suggesting the long isoforms of the AKAP can form heterodimers. Surface plasmon resonance found that the AKAP7γ self-association occurs via two high affinity binding sites with K D values in the low nanomolar range. Mapping of the binding sites by peptide array reveals that AKAP7γ interacts with itself through multiple regions. Photon counting histogram analysis (PCH) of AKAP7γ-EGFP expressed in HEK-293 cells confirmed that AKAP7γ-EGFP self-associates in a cellular context. Lastly, computational modeling of PKA dynamics within AKAP7γ complexes suggests that oligomerization may augment phosphorylation of scaffolded PKA substrates. In conclusion, our study reveals that AKAP7γ forms both homo- and heterodimers with the long isoforms of the AKAP and that this phenomenon could be an important step in mediating effective substrate phosphorylation in cellular microdomains.


Disentangling the roles of chance, abiotic factors and biotic interactions among epiphytic bryophyte communities in a tropical rainforest (Yunnan, China).
Epiphytes offer an appealing framework to disentangle the contributions of chance, biotic and abiotic drivers of species distributions. In the context of the stress-gradient theory, we test the hypotheses that (i) deterministic (i.e., non-random) factors play an increasing role in communities from young to old trees, (ii) negative biotic interactions increase on older trees and towards the tree base, and (iii) positive interactions show the reverse pattern. Bryophyte species distributions and abiotic conditions were recorded on a 1.1 ha tropical rainforest canopy crane site. We analysed co-occurrence patterns in a niche modelling framework to disentangle the roles of chance, abiotic factors and putative biotic interactions among species pairs. 76% of species pairs resulted from chance. Abiotic factors explained 78% of non-randomly associated species pairs, and co-occurrences prevailed over non-coincidences in the remaining species pairs. Positive and negative interactions mostly involved species pairs from the same versus different communities (mosses versus liverworts) and life forms, respectively. There was an increase in randomly associated pairs from large to small trees. No increase in negative interactions from young to old trees or from the canopy to the base was observed. Our results suggest that epiphytic bryophyte community composition is primarily driven by environmental filtering, whose importance increases with niche complexity and diversity. Biotic interactions play a secondary role, with a very marginal contribution of competitive exclusion. Biotic interactions vary among communities (mosses versus liverworts) and life forms, facilitation prevailing among species from the same community and life form, and competition among species from different communities and life forms.


The Bidirectional Relationship between Sleep and Immunity against Infections.
Sleep is considered an important modulator of the immune response. Thus, a lack of sleep can weaken immunity, increasing organism susceptibility to infection. For instance, shorter sleep durations are associated with a rise in suffering from the common cold. The function of sleep in altering immune responses must be determined to understand how sleep deprivation increases the susceptibility to viral, bacterial, and parasitic infections. There are several explanations for greater susceptibility to infections after reduced sleep, such as impaired mitogenic proliferation of lymphocytes, decreased HLA-DR expression, the upregulation of CD14+, and variations in CD4+ and CD8+ T lymphocytes, which have been observed during partial sleep deprivation. Also, steroid hormones, in addition to regulating sexual behavior, influence sleep. Thus, we hypothesize that sleep and the immune-endocrine system have a bidirectional relationship in governing various physiological processes, including immunity to infections. This review discusses the evidence on the bidirectional effects of the immune response against viral, bacterial, and parasitic infections on sleep patterns and how the lack of sleep affects the immune response against such agents. Because sleep is essential in the maintenance of homeostasis, these situations must be adapted to elicit changes in sleep patterns and other physiological parameters during the immune response to infections to which the organism is continuously exposed.


Analysis of yield of retinal imaging in a rural diabetes eye care model.
The aim of this study is to analyze the yield of retinal images obtained in a rural diabetes eye care model. An analysis of a sample of nonmydriatic fundus photography (NMFP) of posterior segment ophthalmic images, obtained by an indigenous equipment (3 nethra-Forus Royal), was done in a district-wide rural diabetic retinopathy (DR) screening program; a trained optometrist did the initial image grading. DR and diabetic macular edema (DME) were classified based on international DR and DME severity scale. The agreement between the optometrist and retina specialist was very good (κ = 0.932; standard error = 0.030; 95% confidence interval = 0.874-0.991). Posterior segment images of 2000 eyes of 1000 people with diabetes mellitus (DM) were graded. The mean age of the participants was 55.7 ± 11.5 standard deviation years. Nearly 42% of the screened participants (n = 420/1000) needed referral. The most common referable posterior segment abnormality was DR (8.2%). The proportion of people with any form of DR was seen in 110/1225 eyes, and sight-threatening DR was seen in 35/1225 eyes. About 62% of posterior segment images were gradable. The reasons for ungradable posterior segment images (34%) were small pupil, unfocused/partially available field of images, and cataract. A NMFP model was able to detect referable posterior segment abnormalities in a rural diabetes eye care program. Reasons found for ungradability of images in the present study can be addressed while designing future DR screening programs in the rural areas.


Possible involvement of GTP-binding proteins in 1 alpha,25-dihydroxyvitamin D3 induction of tissue transglutaminase in mouse peritoneal macrophages.
Induction of transglutaminase was analyzed based on increases in the maximal enzymic activity and in the Northern blots of mRNA during culture of mouse resident peritoneal macrophages with active forms of hydrophobic vitamins and steroid hormones. The enzyme was induced by 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25-(OH)2D3) or retinoic acid but not by steroid hormones. The induction by 1 alpha,25-(OH)2D3 was characterized by its slow onset and marked synergism with retinoic acid induction. The induction was enhanced by protein kinase activators such as cholera toxin and phorbol 12-myristate 13-acetate but largely inhibited by pertussis toxin treatment of cells. It is suggested that pertussis toxin-linked and protein kinase-related signaling would mediate the 1 alpha,25-(OH)2D3-induced enzyme gene expression.


Evaluation of cerebral glioma using 3T diffusion kurtosis tensor imaging and the relationship between diffusion kurtosis metrics and tumor cellularity.
Purpose To evaluate the clinical utility of diffusion kurtosis tensor imaging in the characterization of cerebral glioma and investigate correlations between diffusion and kurtosis metrics with tumor cellularity. Materials and Methods A group of 163 patients (age: 40.5 ± 11.5 years) diagnosed with cerebral glioma underwent diffusion kurtosis tensor imaging with a 3 T scanner. Diffusion and kurtosis metrics were measured in the solid part of tumors, and their abilities to distinguish between tumor grades was evaluated. In addition, we analyzed correlations between the metrics and tumor cellularity. Results Mean kurtosis (MK) revealed a significant difference between each pair of tumor grades ( P < 0.05) and produced the best performance in a receiver operating characteristics analysis (area under the curve [AUC] = 0.89, sensitivity/specificity = 83.3/90). In contrast, mean diffusivity (MD) revealed a significant difference only for tumor grade II versus IV ( P < 0.05). No significant differences between grades were detected with fractional anisotropy (FA; P > 0.05). Thus, kurtosis metrics exhibited a positive and strong correlation with tumor cellularity, while MD exhibited a negative or weak correlation with tumor cellularity. Conclusion Diffusion kurtosis metrics, particularly MK, demonstrated superior performance in distinguishing cerebral glioma of different grades compared with conventional diffusion metrics, and were closely associated with tumor cellularity.


A new amphiphilic derivative, N-{[4-(lactobionamido)methyl]benzylidene}-1,1-dimethyl-2-(octylsulfanyl)ethylamine N-oxide, has a protective effect against copper-induced fulminant hepatitis in Long-Evans Cinnamon rats at an extremely low concentration compared with its original form alpha-phenyl-N-(tert-butyl) nitrone.
An amphiphilic alpha-phenyl-N-(tert-butyl) nitrone (PBN) derivative, N-{[4-(lactobionamido)methyl]benzylidene}-1,1-dimethyl-2-(octylsulfanyl)ethylamine N-oxide (LPBNSH), newly synthesized from its original form PBN in hopes of clinical use, was intraperitoneally administered to Long-Evans Cinnamon (LEC) rats every 2 days at the concentrations of 0.1, 0.5, 1.0, and 2.0 mg/kg. We found that LPBNSH protected against copper-induced hepatitis with jaundice in LEC rats at concentrations of 0.1 and 0.5 mg/kg, which were extremely low compared with that of PBN. It also effectively prevented the loss of body weight, reduced the death rate, and suppressed the increase in serum aspartate aminotransferase and alanine aminotransferase values arising from fulminant hepatitis with jaundice at the same concentrations. Similar results were observed when PBN was administered at the concentration of 150 mg/kg. Immunohistochemical analysis of 8-hydroxy-2'-deoxyguanosine and measurement of thiobarbituric acid-reactive substances in the liver showed that LPBNSH largely suppressed the formation of these oxidative products at same concentrations. No difference in the abnormal accumulation of copper in the liver between the LPBNSH administered and control groups was observed. From these results, it was concluded that LPBNSH exhibited liver-protective effects against fulminant hepatitis with jaundice at ca. 1/1000, 500 the molar concentration of PBN and, therefore, was clinically promising.


A test of three methods for estimating stature from immature skeletal remains using long bone lengths.
In this study, the accuracy of three methods for stature estimation of children from long bone lengths was investigated. The sample utilized consists of nine identified immature skeletons (seven males and two females) of known cadaver length, aged between 1 and 14 years old. Results show that stature (cadaver length) is consistently underestimated by all three methods (from a minimum of 2.9 cm to a maximum of 19.3 cm). The femur/stature ratio provided the least accurate estimates of stature, and predictions were not significantly improved by the other two methods. Differences between true and estimated stature were also greatest when using the length of lower limb bones. Given that the study sample children grew in less than optimal environmental conditions, compared with the children that contributed to the development of the methods, they are stunted and have proportionally shorter legs. This suggests that stature estimation methods are not universally applicable and that environmental differences within a population (e.g., socioeconomic status differences) or differing levels of modernization and social and economic development between nations are an important source of variation in stature and body proportions of children. The fallibility of stature estimation methods, when they do not consider such variation, can be somewhat minimized if stature is estimated from the length of upper limb bones.


Wavy and rough cracks in silicon.
Single-crystal silicon exhibits a strong preference to cleave along a few certain planes, but in experiments we observe wavy cracks with almost no evidence of a preferred fracture direction. Furthermore, we find that the fracture surface is an anisotropic and self-affine fractal over five decades in length scale in the direction of the crack with a roughness exponent of 0.78. In our experiments a 1-4 cm wide strip of single-crystal silicon is heated to 378 degrees C and lowered into a 20 degrees C water bath at speeds of 0.2-5 cm/s. The thermal gradient produces cracks that, depending on the speed, are straight, wavy with amplitude 0.1-0.5 cm and wavelength 0.3-1 cm, or multibranched. The transition from one mode of fracture to another is discontinuous and hysteretic.


Electrochemical trifluoroalkylation/annulation for the synthesis of CF3-functionalized tetrahydroquinolines and dihydroquinolinones.
Tuning the electronic structure of protecting groups on the nitrogen atom of substrates has emerged as an effective strategy to achieve the tandem trifluoromethylation/C(sp2)-H annulation using Langlois' reagent as the CF3 source for the electrochemical synthesis of functionalized tetrahydroquinolines and dihydroquinolinones.


Adsorbed polymer and NOM limits adhesion and toxicity of nano scale zerovalent iron to E. coli.
Nanoscale zerovalent iron (NZVI) is used for groundwater remediation. Freshly synthesized bare, i.e. uncoated NZVI is bactericidal at low mg/L concentration, but the impact of surface modifiers and aging (partial oxidation) on its bactericidal properties have not been determined. Here we assess the effect that adsorbed synthetic polymers and natural organic matter (NOM) and aging (partial oxidation) have on the bactericidal properties of NZVI to the gram-negative bacterium, Escherichia coli. Exposure to 100 mg/L of bare NZVI with 28% Fe(0) content resulted in a 2.2-log inactivation after 10 min and a 5.2-log inactivation after 60 min. Adsorbed poly(styrene sulfonate) (PSS), poly(aspartate) (PAP), or NOM on NZVI with the same Fe(0) content significantly decreased its toxicity, causing less than 0.2-log inactivation after 60 min. TEM images and heteroaggregation studies indicate that bare NZVI adheres significantly to cells and that the adsorbed polyelectrolyte or NOM prevents adhesion, thereby decreasing NZVI toxicity. The 1.8-log inactivation observed for bare NZVI with 7% Fe(0) content was lower than the 5.2-log inactivation using NZVI with 28% Fe(0) after 1 h; however, the minimum inhibitory concentration (MIC) after 24 h was 5 mg/L regardless of Fe(0) content. The MIC of PSS, PAP, and NOM coated NZVI were much higher: 500 mg/L, 100 mg/L, and 100 mg/L, respectively. But the MIC was much lower than the typical injection concentration used in remediation (10 g/L). Complete oxidation of Fe(0) in NZVI under aerobic conditions eliminated its bactericidal effects. This study indicates that polyelectrolyte coatings and NOM will mitigate the toxicity of NZVI for exposure concentrations below 0.1 to 0.5 g/L depending on the coating and that aged NZVI without Fe(0) is relatively benign to bacteria.


Quality of Life, Sexual Functioning, and Physical Functioning Following Perineal Reconstruction with the Lotus Petal Flap.
Lotus petal flaps (LPF) may be used for the reconstruction of extralevator abdominoperineal defects that cannot be closed primarily. Limited data are available on how perineal reconstruction with the LPF impacts on patients' quality of life (QoL), sexual functioning, and physical functioning. A cross-sectional study was performed following perineal reconstruction with the LPF. The QoL of patients having undergone LPF reconstruction was compared with a control group in which perineal defects were closed without flaps. Sexual and physical functioning (presence of perineal herniation and range of motion [ROM] of the hip joints) could only be evaluated in the LPF group. Psychometrically sound questionnaires were used. Physical functioning was evaluated subjectively with binary questions and objectively by physical examination. Of the 23 patients asked to participate, 15 (65%) completed the questionnaires and 11 (47%) underwent physical examination. In the control group, 16 patients were included. There were no significant differences in QoL between the LPF and control groups. Within the LPF group, 33% of patients were sexually active postoperatively compared with 87% preoperatively. No perineal herniation was found. The ROM of the hip joints was bilaterally smaller compared with the generally accepted values. Conclusions should be made with care given the small sample size. Despite a supposedly larger resection area in the LPF group, QoL was comparable in both groups. Nonetheless, reconstruction seemed to affect sexual function and physical function, not hampering overall satisfaction.


Interactions between Sirt1 and MAPKs regulate astrocyte activation induced by brain injury in vitro and in vivo.
Astrocyte activation is a hallmark of traumatic brain injury resulting in neurological dysfunction or death for an overproduction of inflammatory cytokines and glial scar formation. Both the silent mating type information (Sirt1) expression and mitogen-activated protein kinase (MAPK) signal pathway activation represent a promising therapeutic target for several models of neurodegenerative diseases. We investigated the potential effects of Sirt1 upregulation and MAPK pathway pharmacological inhibition on astrocyte activation in vitro and in vivo. Moreover, we attempted to confirm the underlying interactions between Sirt1 and MAPK pathways in astrocyte activation after brain injury. The present study employs an interleukin-1β (IL-1β) stimulated primary cortical astrocyte model in vitro and a nigrostriatal pathway injury model in vivo to mimic the astrocyte activation induced by traumatic brain injury. The activation of GFAP, Sirt1, and MAPK pathways were detected by Western blot; astrocyte morphological hypertrophy was assessed using immunofluorescence staining; in order to explore the neuroprotective effect of regulation Sirt1 expression and MAPK pathway activation, the motor and neurological function tests were assessed after injury. GFAP level and morphological hypertrophy of astrocytes are elevated after injury in vitro or in vivo. Furthermore, the expressions of phosphorylated extracellular regulated protein kinases (p-ERK), phosphorylated c-Jun N-terminal kinase (p-JNK), and phosphorylated p38 activation (p-p38) are upregulated, but the Sirt1 expression is downregulated. Overexpression of Sirt1 significantly increases the p-ERK expression and reduces the p-JNK and p-p38 expressions. Inhibition of ERK, JNK, or p38 activation respectively with their inhibitors significantly elevated the Sirt1 expression and attenuated the astrocyte activation. Both the overproduction of Sirt1 and inhibition of ERK, JNK, or p38 activation can alleviate the astrocyte activation, thereby improving the neurobehavioral function according to the modified neurological severity scores (mNSS) and balance latency test. Thus, Sirt1 plays a protective role against astrocyte activation, which may be associated with the regulation of the MAPK pathway activation induced by brain injury in vitro and in vivo.


Perinatal toxicity of cyfluthrin in mice: developmental and behavioral effects.
The present study was undertaken to evaluate the teratogenic and behavioral effects of perinatal exposure to cyfluthrin (Synthetic Pyrethroid) on mice offspring. Humans are exposed to this compound as it is widely used in various household insecticide formulations and in public health programmes. Pregnant females were exposed to 16 mg/kg (low dose) and 32 mg/kg (high dose) body weight cyfluthrin daily by oral intubation from gestation day 14 through parturition and lactation up to weaning. On 18th day of gestation, 50% females were euthanized for teratological studies and the remaining were allowed to deliver their pups normally. The fetuses were weighed and observed for gross external malformations and routine teratological examination was done. The neonates were observed for neuromotor reflexes (surface righting, tail hang reflex and pivoting) from day 1 up to day 7 after birth. Movement and exploratory behavior of weanlings were observed using 'open-field' and 'hole-board.' The fetuses did not show any external malformation. Skeletal aberrations observed included poor ossification of the skull and phalanges and short ribs. Surface righting and pivoting were significantly affected by the high dose. Both doses produced significant changes in the locomotion, exploration, and rearing frequencies in the open-field. The study indicates that cyfluthrin when administered at the above-mentioned doses did not elicit significant teratogenicity but both the doses caused significant difference in behavioral activities.


Scattering of circularly polarized light in laser Doppler anemometry.
Laser Doppler anemometry is based on light scattered from small particles in a fluid. When measurements are made near a surface the reflections from the surface may decrease the SNR of the Doppler bursts. This paper discusses a method to separate scattered light from reflected light by means of circularly polarized light. The relations describing the scattering of circularly polarized light are given and scattering diagrams are calculated for various Mie parameters and refractive indices. It is shown which collection angles, particle diameters and refraction indices should be used in LDA to efficiently quench the reflections from surfaces.


Successful autologous bone marrow transplantation in second remission of malignant histiocytosis.
This report describes an 18-year-old man with disseminated malignant histiocytosis (MH). The patient initially attained complete remission (CR1) with conventional chemotherapy and then relapsed 14 months later. In second complete remission (CR2) 2 years and 8 months after initial diagnosis, an autologous bone marrow transplantation (ABMT) was undertaken following conditioning with the BEAM regimen. Bone marrow collected in CR2 was incubated with mafosfamide at a dose adjusted to the individual sensitivity of normal CFU-GM according to our current protocol. At the time of writing, 4 years post-transplant, this patient remains disease free. This is the first report of ABMT with marrow treated in vitro by mafosfamide in MH.


Determinants of self-rated health in a representative sample of a rural population: a cross-sectional study in Greece.
Self-rated health (SRH) is a health measure related to future health, mortality, healthcare services utilization and quality of life. Various sociodemographic, health and lifestyle determinants of SRH have been identified in different populations. The aim of this study is to extend SRH literature in the Greek population. This is a cross-sectional study conducted in rural communities between 2001 and 2003. Interviews eliciting basic demographic, health-related and lifestyle information (smoking, physical activity, diet, quality of sleep and religiosity) were conducted. The sample consisted of 1,519 participants, representative of the rural population of Tripoli. Multinomial regression analysis was conducted to identify putative SRH determinants. Among the 1,519 participants, 489 (32.2%), 790 (52%) and 237 (15.6%) rated their health as "very good", "good" and "poor" respectively. Female gender, older age, lower level of education and impaired health were all associated with worse SRH, accounting for 16.6% of SRH variance. Regular exercise, healthier diet, better sleep quality and better adherence to religious habits were related with better health ratings, after adjusting for sociodemographic and health-related factors. BMI and smoking did not reach significance while exercise and physical activity exhibited significant correlations but not consistently across SRH categories. Our results support previous findings indicating that people following a more proactive lifestyle pattern tend to rate their health better. The role of stress-related neuroendocrinologic mechanisms on SRH and health in general is also discussed.


Methods of defining best practice for population health approaches with obesity prevention as an example.
Childhood obesity has reached a crisis stage and has become a population health issue. The few traditional systematic reviews that have been done to identify best practice provide little direction for action. The concept of evidence-based practice has been adopted in health care, and in medicine in particular, to determine best practice. Evidence-based medicine has its origins in the scientific method and for many researchers this concept means strict adherence to standards determining internal validity in order to justify a practice as evidence based. Practitioners addressing population health face challenges in identifying criteria for determining evidence, in part because of the nature of population health with its goal of shifting the health of whole populations. As well, the type of evidence provided by more traditional critical appraisal schema is limiting. Expanded approaches in finding and defining evidence have been proposed that use: expert panels; broad and inclusive search and selection strategies; appraisal criteria that incorporate context and generalizability. A recent synthesis of 147 programmes addressing childhood overweight and obesity provides a concrete example of using a broader approach to identify evidence for best practice (Flynn et al. 2006). Incorporating evaluation and population health frameworks as criterion components in addition to traditional methodological rigour criteria, this synthesis has identified programmes that provide contextual information that can be used to populate what Swinburn et al. (2005) have described as the 'promise table'. Using this approach a range in 'certainty of effectiveness' and a range in 'potential for population impact' are integrated to identify promising strategies. The exercise can provide direction for agencies and practitioners in taking action to address obesity.


Excision of a Nasal Dermoid Sinus Cyst via Open Rhinoplasty Approach and Primary Reconstruction Using Tutoplast-Processed Fascia Lata.
Nasal dermoid sinus cysts are the most common congenital midline nasal lesion, accounting for 1% to 3% of all dermoid cysts, and 4% to 12% of all head and neck dermoids. Selection of the appropriate reconstruction technique, after dermoid resection, is important for treatment. Here we describe the successful management of a case with a nasal dermoid sinus cyst using an open rhinoplasty approach, and primary reconstruction using Tutoplast-processed fascia lata and crushed septal cartilage.


Bioinspired Functionalized Melanin Nanovariants with a Range of Properties Provide Effective Color Matched Photoprotection in Skin.
Melanin and related polydopamine hold great promise; however, restricted fine-tunabilility limits their usefulness in biocompatible applications. In the present study, by taking a biomimetic approach, we synthesize peptide-derived melanin with a range of physicochemical properties. Characterization of these melanin polymers indicates that they exist as nanorange materials with distinct size distribution, shapes, and surface charges. These variants demonstrate similar absorption spectra but have different optical properties that correlate with particle size. Our approach enables incorporation of chemical groups to create functionalized polyvalent organic nanomaterials and enables customization of melanin. Further, we establish that these synthetic variants are efficiently taken up by the skin keratinocytes, display appreciable photoprotection with minimal cytotoxicity, and thereby function as effective color matched photoprotective agents. In effect we demonstrate that an array of functionalized melanins with distinct properties could be synthesized using bioinspired green chemistry, and these are of immense utility in generating customized melanin/polydopamine like materials.


Approaches to open fullerenes: a 1,2,3,4,5,6-hexaadduct of C60.
Complete saturation of a single six-membered ring on fullerene C60 has been achieved. The critical step in this first synthesis of a fully characterized 1,2,3,4,5,6-hexaadduct consisted of a remarkable double 5-exo-trig addition of alkoxyl radicals promoted by lead tetraacetate. Two possible opening pathways ([2 + 2 + 2] retrocycloadditions) for the newly synthesized compound were explored using quantum mechanical calculations. We found that the oxa bridges in the hexaadduct prevent ring opening through the retro[2 + 2 + 2] mechanism due to the high activation barrier and endothermicity of the reaction.


Characterization of cross-reactive norovirus-specific monoclonal antibodies.
Noroviruses (NoVs) commonly cause acute gastroenteritis outbreaks. Broadly reactive diagnostic assays are essential for rapid detection of NoV infections. We previously generated a panel of broadly reactive monoclonal antibodies (MAbs). We characterized MAb reactivities by use of virus-like particles (VLPs) from 16 different NoV genotypes (6 from genogroup I [GI], 9 from GII, and 1 from GIV) coating a microtiter plate (direct enzyme-linked immunosorbent assay [ELISA]) and by Western blotting. MAbs were genotype specific or recognized multiple genotypes within a genogroup and between genogroups. We next applied surface plasmon resonance (SPR) analysis to measure MAb dissociation constants (Kd) as a surrogate for binding affinity; a Kd level of <10 nM was regarded as indicating strong binding. Some MAbs did not interact with the VLPs by SPR analysis. To further assess this lack of MAb-VLP interaction, the MAbs were evaluated for the ability to identify NoV VLPs in a capture ELISA. Those MAbs for which a Kd could not be measured by SPR analysis also failed to capture the NoV VLPs; in contrast, those with a measurable Kd gave a positive signal in the capture ELISA. Thus, some broadly cross-reactive epitopes in the VP1 protruding domain may be partially masked on intact particles. One MAb, NV23, was able to detect genogroup I, II, and IV VLPs from 16 genotypes tested by sandwich ELISA, and it successfully detected NoVs in stool samples positive by real-time reverse transcription-PCR when the threshold cycle (CT) value was <31. Biochemical analyses of MAb reactivity, including SPR analysis, identified NV23 as a broadly reactive ligand for application in norovirus diagnostic assays.


Fast and accurate quantitative detection of Helicobacter pylori and identification of clarithromycin resistance mutations in H. pylori isolates from gastric biopsy specimens by real-time PCR.
Rapid identification of patients infected with clarithromycin-resistant Helicobacter pylori without the need for culture can help to avoid useless prescriptions of clarithromycin. We developed and tested a routine real-time quantitative PCR assay dedicated to that purpose. One hundred ninety-six consecutive gastric biopsy specimens were examined by culture, histology performed by a trained physician, and rapid PCR with the LightCycler apparatus. Infection was defined as (i) positivity of culture, (ii) positivity of histology, or (iii) positivity of PCR if confirmed by positivity of a concomitant indirect test (serology or urea breath test). Susceptibility to clarithromycin was tested by E-test and PCR. The prevalence of infection was 33.7% (66 of 196 samples). The sensitivities of culture, histology, and PCR were 90.9% (60 of 66 samples), 87.9% (58 of 66 samples), and 97.0% (64 of 66 samples), respectively. The specificity of PCR was 94.6% (123 of 130 samples). The linearity of the PCR results was achieved over a 6-log range of input DNA, and we were able to accurately quantify as few as 300 bacteria and to qualitatively detect as few as 30 bacteria per DNA sample. For clarithromycin susceptibility testing, there was 98.2% (55 of 56 samples) concordance between E-test and PCR. Forty-eight strains were clarithromycin susceptible, and 9 strains were clarithromycin resistant. The single discrepancy concerned a culture which was a mixture of mutant and wild type, with a susceptible-to-resistant ratio of 11.5: the resistant population was detected by E-test but not by PCR. Our PCR assay is accurate for fast detection of H. pylori as well as of clarithromycin resistance and is also able to objectively determine bacterial density.


Microarray expression profiling and co-expression network analysis of circulating LncRNAs and mRNAs associated with neurotoxicity induced by BPA.
A growing body of evidence has shown bisphenol A (BPA), an estrogen-like industrial chemical, has adverse effects on the nervous system. In this study, we investigated the transcriptional behavior of long non-coding RNAs (lncRNAs) and mRNAs to provide the information to explore neurotoxic effects induced by BPA. By microarray expression profiling, we discovered 151 differentially expressed lncRNAs and 794 differentially expressed mRNAs in the BPA intervention group compared with the control group. Gene ontology analysis indicated the differentially expressed mRNAs were mainly involved in fundamental metabolic processes and physiological and pathological conditions, such as development, synaptic transmission, homeostasis, injury, and neuroinflammation responses. In the expression network of the BPA-induced group, a great number of nodes and connections were found in comparison to the control-derived network. We identified lncRNAs that were aberrantly expressed in the BPA group, among which, growth arrest specific 5 (GAS5) might participate in the BPA-induced neurotoxicity by regulating Jun, RAS, and other pathways indirectly through these differentially expressed genes. This study provides the first investigation of genome-wide lncRNA expression and correlation between lncRNA and mRNA expression in the BPA-induced neurotoxicity. Our results suggest that the elevated expression of lncRNAs is a major biomarker in the neurotoxicity induced by BPA.


Single-Cell Mechanical Characteristics Analyzed by Multiconstriction Microfluidic Channels.
A microfluidic device composed of variable numbers of multiconstriction channels is reported in this paper to differentiate a human breast cancer cell line, MDA-MB-231, and a nontumorigenic human breast cell line, MCF-10A. Differences between their mechanical properties were assessed by comparing the effect of single or multiple relaxations on their velocity profiles which is a novel measure of their deformation ability. Videos of the cells were recorded via a microscope using a smartphone, and imported to a tracking software to gain the position information on the cells. Our results indicated that a multiconstriction channel design with five deformation (50 μm in length, 10 μm in width, and 8 μm in height) separated by four relaxation (50 μm in length, 40 μm in width, and 30 μm in height) regions was superior to a single deformation design in differentiating MDA-MB-231 and MCF-10A cells. Velocity profile criteria can achieve a differentiation accuracy around 95% for both MDA-MB-231 and MCF-10A cells.


The toxicological application of transcriptomics and epigenomics in zebrafish and other teleosts.
Zebrafish (Danio rerio) is one of a number of teleost fish species frequently employed in toxicology. Toxico-genomics determines global transcriptomic responses to chemical exposures and can predict their effects. It has been applied successfully within aquatic toxicology to assist in chemical testing, determination of mechanisms and environmental monitoring. Moreover, the related field of toxico-epigenomics, that determines chemical-induced changes in DNA methylation, histone modifications and micro-RNA expression, is emerging as a valuable contribution to understanding mechanisms of both adaptive and adverse responses. Zebrafish has proven a useful and convenient model species for both transcriptomic and epigenetic toxicological studies. Despite zebrafish's dominance in other areas of fish biology, alternative fish species are used extensively in toxico-genomics. The main reason for this is that environmental monitoring generally focuses on species native to the region of interest. We are starting to see advances in the integration of high-throughput screening, omics techniques and bioinformatics together with more traditional indicator endpoints that are relevant to regulators. Integration of such approaches with high-throughput testing of zebrafish embryos, leading to the discovery of adverse outcome pathways, promises to make a major contribution to ensuring the safety of chemicals in the environment.


Cosmeceuticals based on Rhealba(®) Oat plantlet extract for the treatment of acne vulgaris.
Recent evidence suggests that acne vulgaris begins as an inflammation in and around the sebaceous gland and alterations in the lipid content of sebum, which drive hyperproliferation and increased desquamation of keratinocytes within sebaceous follicles. This prevents sebum drainage, causing the formation of microcomedones, which spontaneously regress or become acne lesions when the pilosebaceous unit is further blocked by the accumulation of corneocytes. These conditions are favourable for the proliferation of Propionibacterium acnes, which further aggravates acne by enhancing abnormal desquamation, sebum production and inflammation. Also, skin fragility due to inflammation or irritation by anti-comedogenic agents can worsen the situation. Rhealba(®) Oat plantlet extract (Pierre Fabre Dermo Cosmetique) soothes and restores fragile skin in acne by reducing inflammation and inhibits bacterial adhesion of Propionibacterium acnes. Cosmeceuticals combining Rhealba(®) Oat plantlet extract and hydro-compensating actives, which are available with or without anti-comedogenic hydroxy acids, provide a balanced, multifaceted approach for acne patients.


Prevalence, causes, and consequences of masked hypertension: a meta-analysis.
Masked hypertension (MH) is a relatively newly detected condition of which little is known. More information about MH may help to improve overall antihypertensive health care. We aimed to investigate the prevalence, potential causes, and associated consequences of MH. We searched published literature using MEDLINE, EMBASE, and the Cochrane database completed with references cited in reviews and original study articles. We restricted our research to articles written in the English, German, French, and Spanish language. Studies were included only when the prevalence of MH was reported, office blood pressure (BP) values were given, and methods of BP measurements were described in detail. All data were extracted independently by two readers with a standardized protocol and data-collection form. The prevalence of MH averaged 16.8% (95% confidence interval 13.0-20.5%). The MH prevalence was 7% for children and 19% for adults. MH prevalences did not differ significantly when determined with self or ambulatory BP measurement (21.1% vs. 16.8%; P = 0.42). Subjects with MH had significantly higher left ventricular mass index (LVMI) values than normotensives (110 vs. 98 g/m2; P < 0.01) but similar values as sustained hypertensives (109 g/m2). In addition, patients with MH were more often smokers than normotensives (mean difference 18%; P < 0.03). MH strikes about a quarter of the patients who were initially classified as normotensives (based on office BP measurements) and of treated hypertensives. Patients with MH seem to have a similar cardiovascular risk as sustained hypertensives but they may remain undetected. The presence of MH seems to be a matter of a coincidently low office BP value not related to certain subject characteristics although the chance of its presence may be increased by smoking and antihypertensive treatment.


Expression of the Epstein-Barr virus gp350/220 gene in rodent and primate cells.
The gene encoding the Epstein-Barr virus envelope glycoproteins gp350 and gp220 was inserted downstream of the cytomegalovirus immediate-early, Moloney murine leukemia virus, mouse mammary tumor virus, or varicella-zoster virus gpI promoters in vectors containing selectable markers. Host cell and recombinant vector systems were defined which enabled the isolation of rodent or primate cell clones which expressed gp350/220 in substantial quantities. Continued expression of gp350/220 required maintenance of cells under positive selection for linked markers and periodic cloning. gp350/220 expressed in various host cells varied slightly in electrophoretic mobility, probably reflecting differences in glycosylation. Insertion of a stop codon into the gp350/220 open reading frame, upstream of the putative membrane anchor sequence, resulted in efficient secretion of truncated gp350 and gp220 from rat pituitary (GH3) cells. gp350/220 expressed in mammalian cells is highly immunogenic and elicits virus-neutralizing antibodies when administered to mice.


Observer-based stabilization for switched positive system with mode-dependent average dwell time.
This paper concerns the exponential stabilization problem for a class of switched positive systems. The switching signal satisfies mode-dependent average dwell time (MDADT) and the state variables are partially unmeasurable. A further explanation of mode-dependent average dwell time is included. By employing a set of quasi-time variables, which is first proposed for switched systems with MDADT, new stability results are obtained for the switched nonlinear systems and the underlying linear systems. Observer-based stabilization controllers, both for single-input case and multi-input case, are designed such that the closed-loop system converges exponentially. The designed observers and controllers are both mode-dependent and quasi-time-dependent, which is proved to be less conservative than the ones only mode-dependent. A simplified design strategy is provided to reduce the computation burden. Illustrative examples are provided to demonstrate the effectiveness of the results.


Race-Based Differences in ST-Segment-Elevation Myocardial Infarction Process Metrics and Mortality From 2015 Through 2021: An Analysis of 178 062 Patients From the American Heart Association Get With The Guidelines-Coronary Artery Disease Registry.
Systems of care have been developed across the United States to standardize care processes and improve outcomes in patients with ST-segment-elevation myocardial infarction (STEMI). The effect of contemporary STEMI systems of care on racial and ethnic disparities in achievement of time-to-treatment goals and mortality in STEMI is uncertain. We analyzed 178 062 patients with STEMI (52 293 women and 125 769 men) enrolled in the American Heart Association Get With The Guidelines-Coronary Artery Disease registry between January 1, 2015, and December 31, 2021. Patients were stratified into and outcomes compared among 3 racial and ethnic groups: non-Hispanic White, Hispanic White, and Black. The primary outcomes were the proportions of patients achieving the following STEMI process metrics: prehospital ECG obtained by emergency medical services; hospital arrival to ECG obtained within 10 minutes for patients not transported by emergency medical services; arrival-to-percutaneous coronary intervention time within 90 minutes; and first medical contact-to-device time within 90 minutes. A secondary outcome was in-hospital mortality. Analyses were performed separately in women and men, and all outcomes were adjusted for age, comorbidities, acuity of presentation, insurance status, and socioeconomic status measured by social vulnerability index based on patients' county of residence. Compared with non-Hispanic White patients with STEMI, Hispanic White patients and Black patients had lower odds of receiving a prehospital ECG and achieving targets for door-to-ECG, door-to-device, and first medical contact-to-device times. These racial disparities in treatment goals were observed in both women and men, and persisted in most cases after multivariable adjustment. Compared with non-Hispanic White women, Hispanic White women had higher adjusted in-hospital mortality (odds ratio, 1.39 [95% CI, 1.12-1.72]), whereas Black women did not (odds ratio, 0.88 [95% CI, 0.74-1.03]). Compared with non-Hispanic White men, adjusted in-hospital mortality was similar in Hispanic White men (odds ratio, 0.99 [95% CI, 0.82-1.18]) and Black men (odds ratio, 0.96 [95% CI, 0.85-1.09]). Race- or ethnicity-based disparities persist in STEMI process metrics in both women and men, and mortality differences are observed in Hispanic White compared with non-Hispanic White women. Further research is essential to evolve systems of care to mitigate racial differences in STEMI outcomes.


Adherence to the Mediterranean Diet Is Associated with Health-Related Quality of Life and Anthropometric Measurements in University Professors.
The main objective of this study was to assess the relationship between Mediterranean diet (MD) adherence and health-related quality of life (HRQOL) according to the anthropometric measurements of teaching and research staff (TRS) at the University of Granada (UGR), Spain. This diagnostic, non-experimental, cross-sectional, and observational study was performed on university lecturers (65 women and 62 men) using a correlational descriptive methodology. The lecturers' anthropometric measurements were taken, while MD adherence was determined using the PREvention with MEDiterranean diet (PREDIMED) questionnaire. The Short Form Health Survey (SF-36) was used for measuring HRQOL. Better results for body composition were associated with improvements in the physical and mental dimensions and MD adherence. Statistically significant differences were found between sexes, with men showing higher values for weight, height, waist circumference, BMI, waist/hip ratio (WHR), muscle mass, and systolic and diastolic pressure than women. Similarly, MD adherence was positively correlated with vitality (r = 0.233; p = 0.009), social functioning (r = 0.229; p = 0.008), and the mental component summary (r = 0.205; p = 0.021). The regression model determined that the mental component summary (β = 0.239, p = 0.041), diastolic pressure (PD) (β = -0.473, p < 0.000), fat percentage (FP) (β = -0.241, p = 0.004), and age (β = -0.231, p = 0.022) significantly predicted MD adherence. The results obtained in this study suggest that healthy dietary patterns such as the MD and an optimum body composition contribute to an improved HRQOL.


The ONSTEP inguinal hernia repair technique: initial clinical experience of 693 patients, in two institutions.
Experience with a novel hernioplasty procedure--the ONSTEP approach--for inguinal hernia repair in a large series of patients performed by two surgeons at two institutions is described, focusing in particular on the duration of surgery, the time taken to return to normal activities, chronic pain, complication and recurrence rates. Adult patients underwent inguinal hernia repair using the ONSTEP approach. The hernia defect was repaired using a PolySoft™ hernia patch. Patients were followed up for 1 year for pain, complications and recurrences. A total of 693 patients underwent ONSTEP inguinal hernia repair. The mean duration of surgery (± SD) was 17 ± 6 min; the time to discharge from hospital was less than 24 h in all patients; and the mean time to return to normal daily activities was 6.1 ± 3.0 days. The overall complication rate was 1.0 % and the overall recurrence rate was 0.6 %. Residual pain was present in 4 patients at 6 months and was cured by removal of the memory ring in 3 patients and disappeared spontaneously in one case, so that there was no case of chronic pain at 1 year. The ONSTEP inguinal hernia repair technique described is simple, quick to perform, produces consistent results and is associated with very low overall complication, chronic pain and recurrence rates. It may offer an alternative to both Lichtenstein and laparoscopic inguinal hernia repair.


Improving the Test-Retest Reliability of Resting State fMRI by Removing the Impact of Sleep.
Resting state functional magnetic resonance imaging (rs-fMRI) provides a powerful tool to examine large-scale neural networks in the human brain and their disturbances in neuropsychiatric disorders. Thanks to its low demand and high tolerance, resting state paradigms can be easily acquired from clinical population. However, due to the unconstrained nature, resting state paradigm is associated with excessive head movement and proneness to sleep. Consequently, the test-retest reliability of rs-fMRI measures is moderate at best, falling short of widespread use in the clinic. Here, we characterized the effect of sleep on the test-retest reliability of rs-fMRI. Using measures of heart rate variability (HRV) derived from simultaneous electrocardiogram (ECG) recording, we identified portions of fMRI data when subjects were more alert or sleepy, and examined their effects on the test-retest reliability of functional connectivity measures. When volumes of sleep were excluded, the reliability of rs-fMRI is significantly improved, and the improvement appears to be general across brain networks. The amount of improvement is robust with the removal of as much as 60% volumes of sleepiness. Therefore, test-retest reliability of rs-fMRI is affected by sleep and could be improved by excluding volumes of sleepiness as indexed by HRV. Our results suggest a novel and practical method to improve test-retest reliability of rs-fMRI measures.


Proliferation of activated CD1d-restricted NKT cells is down-modulated by lymphocyte activation gene-3 signaling via cell cycle arrest in S phase.
Upon antigenic stimulation, CD1d-restricted NKT cells quickly secrete large amounts of cytokines. This prompt response demonstrates that CD1d-restricted NKT cells may potentially prove to be useful therapeutic agents for the treatment of many diseases. Despite the clinical importance of CD1d-restricted NKT cells, the regulating mechanisms of this unique T cell population remain to be defined. We found murine LAG-3 is inducible on CD1d-restricted NKT cells as the result of a variety of stimulants such as concanavalin A (con A) and anti-CD3. Also, antigen-specific CD1d stimulation can elicit LAG-3 in CD1d-restricted NKT cells. Moreover, ectopic LAG-3 expression on CD1d-restricted NKT cells results in cell cycle arrest in the S phase. These results show that LAG-3 signaling on activated CD1d-restricted NKT cells may down-modulate NKT cell proliferation.


Fetus in fetu: a fetiform teratoma.
Examination of a retroperitoneal fetus in fetu, diagnosed preoperatively, revealed previously unreported histologic findings in the vascular pedicle and membranous capsule that indicated that these structures are not "umbilical cord" or "amnion." These findings include nervous innervation of both structures and a well-defined lamina elastica interna and vaso vasorum in the artery of the vascular pedicle. Thus, strong support is provided for the theory that many examples of fetus in fetu are remarkably complex, well differentiated, highly organized teratomas. Additional arguments that favor the identity of fetus in fetu and teratoma are presented.


The diagnostic gap in diarrhoeal aetiology.
It is well established that rotaviruses of group A are the most important cause of severe diarrhoea in children. The causes of most cases of infectious diarrhoea still remain unidentified, however, and there must be other viruses to be found. 'Novel' rotaviruses have recently been discovered, mainly in animals (serogroups B and C in pigs and humans, D in birds, and one or more further groups in sheep and other mammals). Except for the group B virus which has caused widespread outbreaks of quite severe diarrhoea in adults in China (still not reported from outside China) these novel rotaviruses are rarities in the human and probably represent uncommon zoonotic infections. We speculate that the Chinese virus might have arisen by reassortment of genetic segments of animal group B viruses or perhaps by mutation, and so became infectious for man. The problem of identifying and determining the importance of small round viruses is reviewed. It seems likely that the group of small, round structured viruses, including Norwalk and the viruses of plainly calicivirus morphology, are all representatives of a whole group of enteric caliciviruses. Until they can be more easily cultivated it will be difficult to make diagnostic reagents available to all. Astroviruses and genuine parvoviruses have been found by many people in many countries. Astroviruses are probably more important as pathogens in lambs than in children or calves; parvoviruses can only be established as significant in epidemics. The coronavirus-like particles, first found in Vellore and Bristol, are still enigmatic and their role in diarrhoea is uncertain. Toroviridae, recently discovered as causes of diarrhoea in ungulates, do not seem to be at all important as causes of diarrhoea in humans. Possibly fruitful approaches to future searches are outlined: firstly to make more extensive use of immuno-electron microscopy; and secondly to try to improve existing tissue culture systems to make them more sensitive to enteric viruses.


Water harvesting techniques and supplemental irrigation impact on sorghum production.
In general, rain-fed agriculture is practised in many areas in western Sudan. Therefore, it is imperative to adopt appropriate rainwater harvesting and reuse technique(s) by promoting soil and water management research to sustain crop productivity. Sorghum (Sorghum bicolor L.) is a primary stable crop of Sudan. Extensive field experiments were conducted to study the effect of water harvesting techniques (WHTs) and supplemental irrigation (SI) on infiltration rate (IR), soil moisture content (SMC), growth and productivity of sorghum during two rainy seasons (2012 and 2013). The results showed that the WHTs and SI affected the soil physical properties, growth and productivity parameters of sorghum. The results indicated that the tied-ridging with SI (TRwSI) produced the highest values of accumulative IR, SMC and sorghum productivity (115 mm, 13% and 4000 kg h(-1) , in season 2012, respectively, whereas in season 2013 the values were 145 mm, 10% and 5000 kg h(-1) , for accumulative IR, SMC and sorghum productivity, respectively. Basin with SI (BwSI) ranked second, next to TRwSI in the both seasons. Hence, water harvesting and SI are expected to play a significant role in terms of sustainable agricultural and socio-economic development in western Sudan and similar areas.


Intelligent Task Caching in Edge Cloud via Bandit Learning.
Task caching, based on edge cloud, aims to meet the latency requirements of computation-intensive and data-intensive tasks (such as augmented reality). However, current task caching strategies are generally based on the unrealistic assumption of knowing the pattern of user task requests and ignoring the fact that a task request pattern is more user specific (e.g., the mobility and personalized task demand). Moreover, it disregards the impact of task size and computing amount on the caching strategy. To investigate these issues, in this paper, we first formalize the task caching problem as a non-linear integer programming problem to minimize task latency. We then design a novel intelligent task caching algorithm based on a multiarmed bandit algorithm, called M-adaptive upper confidence bound (M-AUCB). The proposed caching strategy cannot only learn the task patterns of mobile device requests online, but can also dynamically adjust the caching strategy to incorporate the size and computing amount of each task. Moreover, we prove that the M-AUCB algorithm achieves a sublinear regret bound. The results show that, compared with other task caching schemes, the M-AUCB algorithm reduces the average task latency by at least 14.8%.


High-Rate Hydrogen Generation by Direct Sunlight Irradiation with a Triruthenium Complex.
Herein we report a biomimetic triruthenium catalyst that, when under direct sunlight irradiation, facilitates high-rate H2 production from formic acid (FA) dehydrogenation. The system consists of 2 μmol of catalyst and 6 μmol of tri- o-tolylphosphine in 1 mL of dimethylformamide (DMF) and 4 mL of FA/triethylamine (TEA; 5:2). With 0.4 mM catalyst loaded, a high turnover frequency of 1.15 × 106 h-1 was detected when under direct sunlight irradiation. In an experiment with 0.2 mM catalyst loaded, more than 140 L of H2 (280 L of H2 + CO2) was produced, and a turnover number of approximately 2.78 × 106 was obtained within 5 h without decline in H2 generation activity, making it suitable for high-rate H2 production.


Positron emission tomographic study in Alzheimer's disease and Pick's disease.
Positron Emission Tomography has been used to compare patients with Alzheimer's disease and 3 patients with biopsy-proved Pick's disease to age-matched volunteers. In Alzheimer's disease, there was a trend to a decrease of the metabolism parallel to the severity of the affection. The hypometabolism was predominant in the temporo-parieto-occipital and the middle temporal regions. In 2 cases of Pick's disease with a classical "frontal syndrome", there was an important fronto-temporal hypometabolism, very suggestive of the diagnosis owing to both its location and intensity. A third patient presented with a slowly progressive dysphasia. A left perisylvian hypometabolism was observed before any evident anatomical abnormality. The clinical symptoms evolved to a dementia and the hypometabolism extended to both frontal lobes.


Occult pneumonia in a child.
We describe the case of a 10-year-old boy who presented with high fever, vomiting and diarrhoea. There were no respiratory symptoms and auscultation and percussion of the lungs were normal. The combination of the clinical picture with a high C reactive protein value prompted us to perform a diagnostic work-up. A chest radiograph showed abscess formation in a lobar pneumonia in the right upper lobe and intravenous antibiotic therapy was started. The patient recovered and treatment was continued with oral antibiotics. Radiologically confirmed pneumonia in a febrile patient without respiratory symptoms is described as occult pneumonia. An increased number of leucocytes and/or an increased C reactive protein value can predict occult pneumonia in febrile children. This case highlights the diagnostic challenge of pneumonia in febrile children without respiratory symptoms and reminds clinicians to consider occult pneumonia in the differential diagnosis of fever without source.


Uterine deletion of Gp130 or Stat3 shows implantation failure with increased estrogenic responses.
Leukemia inhibitory factor (LIF), a downstream target of estrogen, is essential for implantation in mice. LIF function is thought to be mediated by its binding to LIF receptor (LIFR) and recruitment of coreceptor GP130 (glycoprotein 130), and this receptor complex then activates signal transducer and activator of transcription (STAT)1/3. However, the importance of LIFR and GP130 acting via STAT3 in implantation remains uncertain, because constitutive inactivation of Lifr, Gp130, or Stat3 shows embryonic lethality in mice. To address this issue, we generated mice with conditional deletion of uterine Gp130 or Stat3 and show that both GP130 and STAT3 are critical for uterine receptivity and implantation. Implantation failure in these deleted mice is associated with higher uterine estrogenic responses prior to the time of implantation. These heightened estrogenic responses are not due to changes in ovarian hormone levels or expression of their nuclear receptors. In the deleted mice, estrogen-responsive gene, Lactoferrin (Ltf), and Mucin 1 protein, were up-regulated in the uterus. In addition, progesterone-responsive genes, Hoxa10 and Indian hedgehog (Ihh), were markedly down-regulated in STAT3-inactivated uteri. These changes in uteri of deleted mice were reflected by the failure of differentiation of the luminal epithelium, which is essential for blastocyst attachment.


Dynamics of Calcium during In vitro Microspore Embryogenesis and In vivo Microspore Development in Brassica napus and Solanum melongena.
Calcium is widely known to have a role as a signaling molecule in many different processes, including stress response and activation of the embryogenic program. However, there are no direct clues about calcium levels during microspore embryogenesis, an experimental process that combines a developmental switch toward embryogenesis and the simultaneous application of different stressing factors. In this work, we used FluoForte, a calcium-specific fluorescent vital dye, to track by confocal microscopy the changes in levels and subcellular distribution of calcium in living rapeseed (B. napus) and eggplant (S. melongena) microspores and pollen grains during in vivo development, as well as during the first stages of in vitro-induced microspore embryogenesis in rapeseed. During in vivo development, a clear peak of cytosolic Ca2+ was observed in rapeseed vacuolate microspores and young pollen grains, the stages more suitable for embryogenesis induction. However, the Ca2+ levels observed in eggplant were dramatically lower than in rapeseed. Just after in vitro induction, Ca2+ levels increased specifically in rapeseed embryogenic microspores at levels dramatically higher than during in vivo development. The increase was observed in the cytosol, but predominantly in vacuoles. Non-embryogenic forms such as callus-like and pollen-like structures presented remarkably different calcium patterns. After the heat shock-based inductive treatment, Ca2+ levels progressively decreased in all cases. Together, our results reveal unique calcium dynamics in in vivo rapeseed microspores, as well as in those reprogrammed to in vitro embryogenesis, establishing a link between changes in Ca2+ level and subcellular distribution, and microspore embryogenesis.


Relationships among growth and different NOR phenotypes in a specific stock of rainbow trout (Oncorhynchus mykiss).
Growth is one of the most important aspects in the genetic improvement of cultured fish species. Consequently, genetic parameters related to this feature and their response to selection have been the focus of most research in this area. Such research indicates that, in general, there is enough additive genetic variance related to growth, justifying the use of selection. Based on the usefulness of cytogenetic and molecular markers in the fish culture, the aim of the present work was to analyze the possible relationships among cytogenetic characteristics, specifically the NOR phenotypes, and the increase in length and weight in specimens of the rainbow trout (Oncorhynchus mykiss), resultant from directed mating between homozygous females and heterozygous males according to their NOR phenotypic patterns. The equations of the relationship between length and weight of the analyzed specimens followed the model Wt = a Lt(b), showing b values higher than 3, determinant of a positive allometric growth. The results showed that the different NOR phenotypes were not related with the growth values for length and weight in any statistical test.


Liver Transplant for Patients With Preexisting Portal Vein Thrombosis: A Single-Center Experience.
Portal vein thrombosis is not uncommon in liver cirrhosis patients. Previously, portal vein throm-bosis had been considered as a contraindication to liver transplant because of technical challenges for adequate restoration of portal inflow followed by high morbidity and mortality. However, alternative options for portal vein thrombosis during liver transplant have been introduced, and portal vein thrombosis is now no longer considered as an absolute contraindication for liver transplant. Herein, we introduce our ex-periences and outcomes of liver transplant for patients with portal vein thrombosis. Between March 2014 and June 2018, 65 patients underwent liver transplant at our institution, with 13 (20%) having portal vein thrombosis preoperatively. The characteristics and management of these patients were reviewed retrospectively, and outcomes were compared with those of patients without portal vein thrombosis. The type of portal vein thrombosis included Yerdel grade 1 in 7 patients (53.8%), grade 2 in 4 patients (30.8%), grade 3 in 1 patient (7.7%), and grade 4 in 1 patient (7.7%). For restoration of portal inflow, eversion thrombectomy was performed in 11 patients (84.6%), renoportal bypass in 1 patient (7.7%) with grade 4 portal vein thrombosis, and superior mesenteric vein jump graft in 1 patient (7.7%) with grade 2 portal vein thrombosis. There was no portal vein-related morbidity except for 1 patient who needed portal vein stent because of stricture. Outcomes after liver transplant were comparable among patients with and without portal vein thrombosis. Although the surgical procedure has a technical complexity, liver transplant is no longer a contraindication for patients with portal vein thrombosis because of various alternative options, allowing similar outcomes among patients with and without portal vein thrombosis.


Fetomaternal immunotolerance.
Implantation of mammalian conceptus in uterine cavity is the result of evolutionary adaptation, through high level of physiological procedures to ensure its success. However the majority of pregnancy losses occur before or during implantation. It is expected that exploring and defining the molecular and physiological road map during the crucial time of implantation will enable us to decode and effectively treat fertility defects. Immunological, hormonal and molecular factors participate in the feto-maternal cross talk during implantation and designate the effectiveness of the process. The atypical expression of major histocompatibility complex and other protein-antigens, such as Fas/FasL and petformin in human trophoblast, the modified function of cellular constituents of the feto-maternal interface, as well as the specific role of some hormones and cytokines, represent substantive parameters of feto-maternal immunotolerance during implantation.


Screening for Learning and Memory Mutations: A New Approach.
We describe a fully automated, live-in 24/7 test environment, with experimental protocols that measure the accuracy and precision with which mice match the ratio of their expected visit durations to the ratio of the incomes obtained from two hoppers, the progress of instrumental and classical conditioning (trials-to-acquisition), the accuracy and precision of interval timing, the effect of relative probability on the choice of a timed departure target, and the accuracy and precision of memory for the times of day at which food is available. The system is compact; it obviates the handling of the mice during testing; it requires negligible amounts of experimenter/technician time; and it delivers clear and extensive results from 3 protocols within a total of 7-9 days after the mice are placed in the test environment. Only a single 24-hour period is required for the completion of first protocol (the matching protocol), which is strong test of temporal and spatial estimation and memory mechanisms. Thus, the system permits the extensive screening of many mice in a short period of time and in limited space. The software is publicly available.


[Characteristics of adolescent offenders receiving services in juvenile centers in Québec (Centres jeunesse du Québec, CJQ)].
This study aims at establishing a comparative psychological profile of male and female adolescents at the moment of the application of measures in juvenile centers in Québec (centres jeunesse du Québec, CJQ) as well as their family and social characteristics. The study compares 213 adolescents (12-17 years old) receiving services in CJQ in accordance with the juvenile offenders act (Loi sur les jeunes contrevenants), with 213 adolescents from high schools of impoverished neighbourhoods. Results reveal serious problems of adaptation, external disorders and interiorized disorders and a regular substance abuse among many juvenile offenders. These problems are much more frequent in CJQ than within the juvenile population. The situation of these adolescents is worrisome, given that a high prevalence of depression and sexual victimisation is also observed in females. Finally, families whose adolescent receives services in CJQ have less financial, personal and social resources, as well as more difficulty exercising their parental role compared to parents in the general population. In conclusion, recommendations are proposed concerning psychosocial services necessary for these adolescents and their families.


Implementing a Cardiac Skills Orientation and Simulation Program.
Patients with cardiac morbidities admitted for cardiac surgical procedures require perioperative nurses with a high level of complex nursing skills. Orienting new cardiac team members takes commitment and perseverance in light of variable staffing levels, high-acuity patient populations, an active cardiac surgical schedule, and the unpredictability of scheduling patients undergoing cardiac transplantation. At an academic medical center in Boston, these issues presented opportunities to orient new staff members to the scrub person role, but hampered efforts to provide active learning opportunities in a safe environment. As a result, facility personnel created a program to increase new staff members' skills, confidence, and proficiency, while also increasing the number of staff members who were proficient at scrubbing complex cardiac procedures. To address the safe learning requirement, personnel designed a simulation program to provide scrubbing experience, decrease orientees' supervision time, and increase staff members' confidence in performing the scrub person role.


Costs and funding for published medical education research.
The Institute of Medicine has called for increased rigor of education research and funding to support educational innovation. However, funding for medical education research is scarce. The costs of conducting studies in medical education and how such research is currently funded have not been systematically evaluated. To determine how medical education research studies that were recently published were funded and to approximate the costs of conducting these studies. We conducted a cross-sectional survey of first authors of medical education studies published from September 1, 2002, to December 31, 2003. Original medical education research studies conducted at US institutions and published in 13 prominent peer-reviewed journals were included. For each study we measured duration, percentage of the authors' total work commitment ("percentage effort") devoted to the study, resources used and their costs, attainment of funding, and the first author's estimated cost of conducting the study. The cost of each study was calculated by multiplying the percentage effort of each author for the duration of the study by the national median salary for each author, according to specialty and academic rank, and then adding the costs of resources used. Responses were received from authors of 243 (84%) of 290 identified medical education studies. The median calculated cost of conducting the 243 studies was 24,471 dollars (interquartile range [IQR], 11,531 dollars-63 808 dollars). The median authors' estimate of study cost was 10,000 dollars (IQR, 4000 dollars-25 000 dollars). Some funding was obtained for 72 (29.6%) of the studies. Of studies that were funded, the median amount of funding was 15,000 dollars (IQR, 5000 dollars-66,500 dollars). The median calculated cost of funded studies was 37,315 dollars (IQR, 18,731 dollars-82,393 dollars). Private foundation grants were the most common funding source (n = 30 [41.7%]). Factors independently associated with attaining funding were training in grant writing (odds ratio, 2.05; 95% confidence interval, 1.11-3.79) and number of medical education studies published by the first author (odds ratio, 2.4; 95% confidence interval, 1.24-4.63). The majority of published medical education research is not formally funded, and the studies that do receive support are substantially underfunded. To realize the Institute of Medicine's directive and to improve the quality of medical research, policy reform that increases funding for medical education scholarship will likely be required.


CASPER plus (CollAborative care in Screen-Positive EldeRs with major depressive disorder): study protocol for a randomised controlled trial.
Depression accounts for the greatest disease burden of all mental health disorders, contributes heavily to healthcare costs, and by 2020 is set to become the second largest cause of global disability. Although 10% to 16% of people aged 65 years and over are likely to experience depressive symptoms, the condition is under-diagnosed and often inadequately treated in primary care. Later-life depression is associated with chronic illness and disability, cognitive impairment and social isolation. With a progressively ageing population it becomes increasingly important to refine strategies to identity and manage depression in older people. Currently, management may be limited to the prescription of antidepressants where there may be poor concordance; older people may lack awareness of psychosocial interventions and general practitioners may neglect to offer this treatment option. CASPER Plus is a multi-centre, randomised controlled trial of a collaborative care intervention for individuals aged 65 years and over experiencing moderate to severe depression. Selected practices in the North of England identify potentially eligible patients and invite them to participate in the study. A diagnostic interview is carried out and participants with major depressive disorder are randomised to either collaborative care or usual care. The recruitment target is 450 participants. The intervention, behavioural activation and medication management in a collaborative care framework, has been adapted to meet the complex needs of older people. It is delivered over eight to 10 weekly sessions by a case manager liaising with general practitioners. The trial aims to evaluate the clinical and cost effectiveness of collaborative care in addition to usual GP care versus usual GP care alone. The primary clinical outcome, depression severity, will be measured with the Patient Health Questionnaire-9 (PHQ-9) at baseline, 4, 12 and 18 months. Cost effectiveness analysis will assess health-related quality of life using the SF-12 and EQ-5D and will examine cost-consequences of collaborative care. A qualitative process evaluation will be undertaken to explore acceptability, gauge the extent to which the intervention is implemented and to explore sustainability beyond the clinical trial. Results will add to existing evidence and a positive outcome may lead to the commissioning of this model of service in primary care. ISRCTN45842879 (24 July 2012).


Autologous bone marrow-derived mononuclear cell therapy in three patients with severe asthma.
Despite recent advances in understanding its pathophysiology and development of novel therapies, asthma remains a serious public health issue worldwide. Combination therapy with inhaled corticosteroids and long-acting β2-adrenoceptor agonists results in disease control for many patients, but those who exhibit severe asthma are often unresponsive to conventional treatment, experiencing worse quality of life, frequent exacerbations, and increasing healthcare costs. Bone marrow-derived mononuclear cell (BMMC) transplantation has been shown to reduce airway inflammation and remodeling and improve lung function in experimental models of allergic asthma. This is a case series of three patients who presented severe asthma, unresponsive to conventional therapy and omalizumab. They received a single intravenous dose of autologous BMMCs (2 × 107) and were periodically evaluated for 1 year after the procedure. Endpoint assessments included physical examination, quality of life questionnaires, imaging (computed tomography, single-photon emission computed tomography, and ventilation/perfusion scan), lung function tests, and a 6-min walk test. All patients completed the follow-up protocol. No serious adverse events attributable to BMMC transplantation were observed during or after the procedure. Lung function remained stable throughout. A slight increase in ventilation of the right lung was observed on day 120 after BMMC transplantation in one patient. All three patients reported improvement in quality of life in the early post-procedure course. This paper described for the first time the effects of BMMC therapy in patients with severe asthma, providing a basis for subsequent trials to assess the efficacy of this therapy.


Paravertebral brachial plexus blockade in cats: a cadaver study.
Objectives The aims of this study were to describe the paravertebral brachial plexus (PBP) blockade in cats, and compare the spread of bupivacaine-methylene blue solution (BMS) using two volumes of injection into the PBP. Methods Six cadavers (4.4 ± 1.8 kg) randomly received 0.15 ml/kg (LOW) or 0.2 ml/kg (HIGH) per injection of BMS into the PBP. The first injection was made ventral to the transverse process of the sixth cervical vertebra (nerves C6 and C7) at the emergence of nerve roots. A second injection was performed at the edge of the cranial border of the scapula and directed ventrally towards the first rib (C8 and T1). Cadavers were dissected and the presence of BMS in contact with the nerves (success rate) and length of staining were evaluated for each nerve (C6/C7/C8/T1). Length of target nerves in contact with BMS was measured and <15 mm was considered fair, ⩾15 mm sufficient and >40 mm excessive. Complications (aspiration of blood, staining of pleural space and/or spinal cord) were recorded. Paired t-test, Mann-Whitney U-test and χ2 test were used for statistical analysis when appropriate ( P <0.05). Results Eleven hemilateral brachial plexuses were injected. Aspiration of blood occurred during one injection. Inadvertent pleural or spinal staining was not observed. Success rates (positive nerve staining) in the LOW and HIGH groups, respectively, were as follows: C6: 83% and 80%; C7: 66% and 100%; C8: 66% and 100%; T1: 50% and 60% ( P >0.05). Median (range) length of nerve staining was 22 mm (15-39 mm) for LOW and 21 mm (13-35 mm) for HIGH ( P >0.05). Excessive nerve staining was not recorded. Conclusions and relevance This study describes the PBP blockade in cats with acceptable nerve staining and minimal complications. Success rate and length of nerve staining were not significantly different between the LOW and HIGH groups.


Synthesis and anxiolytic activity of N-substituted cyclic imides (1R*,2S*,3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3- bicyclo[2.2.1]heptanedicarboximide (tandospirone) and related compounds.
A series of cyclic imides bearing a omega-(4-aryl and 4-heteroaryl-1-piperazinyl)alkyl moieties was synthesized and tested in vivo for anxiolytic activity. The in vitro binding affinities of these compounds were also examined for 5-HT1A receptor sites. Structure-activity relationships within these series are discussed. One of these compounds, (1R*,2S*,-3R*,4S*)-N-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-2,3- bicyclo[2.2.1]heptanedicarboximide (1: tandospirone), was found to be equipotent with buspirone in its anxiolytic activity and more anxio-selective than buspirone and diazepam. Tandospirone (1) is currently undergoing clinical evaluation as a selective anxiolytic agent.


Nephrotoxicity: a rational approach to target cell injury in vitro in the kidney.
1. The kidney is a complex organ in which there is cellular heterogeneity. Many nephrotoxic chemicals target preferentially for discrete cell types, but adjacent, morphologically different cells are unaffected. This selectivity has made the assessment of nephrotoxicity in vivo (and the study of underlying mechanisms) difficult. Discrete renal injury can, however, be exploited in vitro, to study the interactions between the toxic compound and the target cell. 2. Several in vitro models have been used to study the potential interaction between the target cells and chemicals, including perfusion of the isolated kidney, renal slices, freshly isolated fragments, primary cultures and continuous cell lines. Where appropriate, isolated organelles and purified enzymes can also be used. 3. The target cell toxicity in vivo of adriamycin, 2-bromoethanamine and hexachlorobutadiene N-acetyl cysteine conjugate is selectively maintained towards glomerular epithelial, medullary interstitial and proximal tubular cells, respectively, in vitro, showing that the "in vivo-in vitro gap" can be bridged. Characteristics unique to each of these renal cell types, such as the selective uptake of a toxin, enzyme systems for generating biologically reactive intermediates, and the presence of lipid droplets (rich in polyunsaturated fatty acid) and peroxidase activity have been identified, and one or more of these may explain the mechanisms of selective injury in discrete regions of the kidney.


Exaggerated response of systolic blood pressure to cycle ergometer.
The aim of this study is to exam the effects of exercise modes on the systolic blood pressure and rate-pressure product during a gradually increasing exercise load from low to high intensity. Fifteen apparently healthy men aged 19 to 23 performed the graded exercise tests on cycle ergometer (CE) and treadmill (TM). During the low-to-maximal exercises, oxygen uptake (VO2), heart rate (HR), systolic blood pressure (SBP) and rate-pressure product were measured. CE had a significantly lower maximum VO2 than TM (CE vs. TM: 48.51±1.30 vs. 55.4±1.19 mL/kg/min; p<0.001). However, CE showed a higher maximum SBP (SBPmax) at the all-out exercise load than TM (CE vs. TM: 170±2.4 vs. 154±1.7 mmHg; p<0.001). During the low-to-maximal intensity increment, the slope of the HR with VO2 was the same as VO2 increased in times of the graded exercise test of CE and TM (CE vs. TM: 2.542±0.100 vs. 2.506±0.087; p=0.26). The slope of increase on SBP accompanied by VO2 increase was significantly higher in CE than in TM (CE vs. TM: 1.669±0.117 vs. 1.179±0.063; p<0.001). The SBP response is stronger in CE than in TM during the graded exercise test. Therefore, there is a possibility that CE could induce a greater burden on workloads to cardiovascular system in humans than TM.


Investigation into the diffusion of water into HEMA-co-MOEP hydrogels.
Cross-linked homopolymers and copolymers of 2-hydroxyethyl methacrylate, HEMA, and ethylene glycol methacrylate phosphate, MOEP, have been synthesized, and the diffusion of water into these systems has been investigated. Only polymers with 0-20 mol % MOEP exhibited ideal swelling behavior as extensive fracturing occurred in the systems with greater than 20 mol % MOEP as the polymers began to swell during water sorption. Gravimetric studies were used in conjunction with magnetic resonance imaging of the diffusion front to elucidate the diffusion mechanism for these systems. In the case of the cross-linked HEMA homopolymer gels, the water transport mechanism was determined to be concentration-independent Fickian diffusion. However, as the fraction of MOEP in the network increased, the transport mechanism became increasingly exponentially concentration-dependent but remained Fickian until the polymer consisted of 30 mol % MOEP where the water transport could no longer been described by Fickian diffusion.


Glycoprotein IIb/IIIa combination therapy in acute myocardial infarction: tailoring therapies to optimize outcome.
Numerous randomized trials have unequivocally shown that fibrinolytic therapy in the treatment of ST-segment elevation myocardial infarction substantially reduces mortality when administered within 12 hours of symptom-onset. Although fibrinolytic therapy initially restores antegrade flow in the infarct vessel in the majority of patients, sustained tissue-level reperfusion occurs in only approximately 25% of patients. Thrombin and platelets are two additional constituents of a coronary thrombus that contribute to the tendency for vessel reocclusion after initially successful reperfusion. Therefore, adjunctive therapy with potent antithrombins and antiplatelets is essential in the successful treatment of a coronary thrombus. Recent studies including GUSTO-V and ASSENT-III have studied the use of combination drug therapy with glycoprotein IIb/IIIa inhibition and reduced-dose fibrinolytics in the treatment of acute myocardial infarction. These studies demonstrated that combination therapy reduces reinfarction rates. However, this therapy is associated with increased bleeding complications especially in elderly patients. This article reviews the results and clinical implications of these major trials of combination drug therapy in acute myocardial infarction and provides recommendations for tailoring their use in clinical practice.


Self-assembly in a model colloidal mixture of dimers and spherical particles.
We investigate the structure of a dilute mixture of amphiphilic dimers and spherical particles, a model relevant to the problem of encapsulating globular "guest" molecules in a dispersion. Dimers and spheres are taken to be hard particles, with an additional attraction between spheres and the smaller monomers in a dimer. Using the Monte Carlo simulation, we document the low-temperature formation of aggregates of guests (clusters) held together by dimers, whose typical size and shape depend on the guest concentration χ. For low χ (less than 10%), most guests are isolated and coated with a layer of dimers. As χ progressively increases, clusters grow in size becoming more and more elongated and polydisperse; after reaching a shallow maximum for χ≈50%, the size of clusters again reduces upon increasing χ further. In one case only (χ=50% and moderately low temperature) the mixture relaxed to a fluid of lamellae, suggesting that in this case clusters are metastable with respect to crystal-vapor separation. On heating, clusters shrink until eventually the system becomes homogeneous on all scales. On the other hand, as the mixture is made denser and denser at low temperature, clusters get increasingly larger until a percolating network is formed.


Asteriquinones from Aspergillus sp. GZWMJZ-258 and Their Derivatives.
A new asteriquinone, ochrindole F (1), and five previously reported analogues (2-6) were isolated from the culture of the fungus Aspergillus sp. GZWMJZ-258, an endophyte of Garcinia multiflora. The structure of compound 1 was determined by a spectroscopic analysis. Furthermore, eight new derivatives (7-14) were synthesized from major metabolites 2 and 3. These compounds showed selective antiproliferative activity against the human acute myeloid leukemia (AML) cell line MV4-11, among which compound 12 showed the strongest activity with an IC50 value of 0.14 μM and the highest selectivity with a selectivity index greater than 710. An initial probe of the mechanism of action showed that compounds 12 and 14 could inhibit the expression of FLT-3 in the MV4-11 cell line.


Laparoscopic Surgery for a Patient With Multiple Liver Metastases of Unknown Origin Concomitant With Gallbladder Tumor.
The liver is the digestive organ where metastatic adenocarcinoma of unknown primary site is most often observed. A 74-year-old man was diagnosed with a growing gallbladder tumor and multiple liver tumors limited to the left lateral sector. Liver tumors were suggested to be primary or secondary adenocarcinoma with no relation to the gallbladder tumor. Also for diagnostic purposes, laparoscopic full-thickness resection of the gallbladder, laparoscopic lateral sectionectomy and lymph node sampling were performed. The final histopathological diagnosis was hyperplastic polyp of the gallbladder and metastatic poorly differentiated adenocarcinoma of the liver. Liver tumors were suspected to originate from the stomach, duodenum, or small intestine; however, the primary sites could not be identified. The patient has been closely followed up without any chemotherapy 3 months after surgery. Laparoscopic surgery can be strongly recommended for patients with multiple liver tumors of unknown origin concomitant with a gallbladder tumor.


Usefulness of Contrast-Enhanced Endoscopic Ultrasound (CH-EUS) to Guide the Treatment Choice in Superficial Rectal Lesions: A Case Series.
Large rectal lesions can conceal submucosal invasion and cancer nodules. Despite the increasing diffusion of high-definition endoscopes and the importance of an accurate morphological evaluation, a complete assessment in this setting can be challenging. Endoscopic ultrasound (EUS) plays an established role in the locoregional staging of rectal cancer, although this technique has a tendency toward the over-estimation of the loco-regional (T) staging. However, there are still few data on contrast-enhanced endoscopic ultrasound (CH-EUS), especially if this ancillary technique may increase the accuracy for predicting invasive nodules among large rectal lesions. Consecutive large (≥20 mm) superficial rectal lesions with high-definition endoscopy, characterized by focal areas suggestive for invasive cancer/2B type according to JNET classification, were considered for additional standardized evaluation via CH-EUS with Sonovue ©. From 2020 to 2023, we evaluated 12 consecutive superficial rectal lesions with sizes ranging from 20 to 180 mm. This evaluation provided additional elements to support the therapeutic decision made. Lesions were treated with surgical (3/12) or endoscopic treatment (9/12) according to their morphology and CH-EUS evaluation. Contrast-enhanced endoscopic ultrasound can provide an additional evaluation for large and difficult-to-classify rectal lesions. In our experience, CH-EUS staging corresponded to the final pathological stages in 9/12 (75%) lesions, improving the distinction between T1 and T2 lesions. Larger prospective studies and randomized trials should be conducted to support and standardize this approach.


Nasal nerve ablation, nasal swell body and inferior turbinate reduction for nasal obstruction and congestion relief.
Nasal obstruction and congestion can occur because of turbinate and septal variations with or without rhinitis. A combined treatment for nasal obstruction and congestion was examined retrospectively in cases where the nasal swell body was addressed with inferior turbinectomy, with or without posterior nasal nerve ablation. A 940 nm laser was utilised for contact (nasal swell body, septum and inferior turbinate) and non-contact (posterior nasal nerve) ablation. Total Nasal Symptoms Score, visual analogue scale pain score, complications and procedure location (office vs operating theatre) were recorded. All 242 patients underwent nasal swell body reduction with inferior turbinate reduction, and 150 had posterior nasal nerve ablation also. No laser complications were observed. An 80 per cent reduction in medication usage was noted. Total Nasal Symptoms Score decreased by 73 per cent; rhinorrhoea and congestion scores decreased by 54 per cent and 81 per cent respectively. Crusting, epistaxis and infections were minimal, and resolved within two weeks. Nasal swell body with inferior turbinate reduction, with or without posterior nasal nerve ablation, is a new method of treating nasal obstruction and congestion. Laser posterior nasal nerve ablation can be utilised as a complementary tool to deliver anatomical obstruction relief.


Numerical study on the lubrication performance of compression ring-cylinder liner system with spherical dimples.
The effects of surface texture on the lubrication performance of a compression ring-cylinder liner system are studied in this paper. By considering the surface roughness of the compression ring and cylinder liner, a mixed lubrication model is presented to investigate the tribological behaviors of a barrel-shaped compression ring-cylinder liner system with spherical dimples on the liner. In order to determine the rupture and reformulation positions of fluid film accurately, the Jacoboson-Floberg-Olsson (JFO) cavitation boundary condition is applied to the mixed lubrication model for ensuring the mass-conservative law. On this basis, the minimum oil film thickness and average friction forces in the compression ring-cylinder liner system are investigated under the engine-like conditions by changing the dimple area density, radius, and depth. The wear load, average friction forces, and power loss of the compression ring-cylinder liner system with and without dimples are also compared for different compression ring face profiles. The results show that the spherical dimples can produce a larger reduction of friction in mixed lubrication region, and reduce power loss significantly in the middle of the strokes. In addition, higher reduction percentages of average friction forces and wear are obtained for smaller crown height or larger axial width.