Effects of sustained inflation pressure during neonatal cardiopulmonary resuscitation of asphyxiated piglets.
Sustained inflation (SI) during chest compression (CC = CC+SI) has been recently shown as an alternative method during cardiopulmonary resuscitation in neonates. However, the optimal peak inflation pressure (PIP) of SI during CC+SI to improve ROSC and hemodynamic recovery is unknown. To examine if different PIPs of SI during CC+SI will improve ROSC and hemodynamic recovery in severely asphyxiated piglets. Twenty-nine newborn piglets (1-3 days old) were anesthetized, intubated, instrumented and exposed to 30-min normocapnic hypoxia followed by asphyxia. Piglets were randomized into four groups: CC+SI with a PIP of 10 cmH2O (CC+SI_PIP_10, n = 8), a PIP of 20 cmH2O (CC+SI_PIP_20, n = 8), a PIP of 30 cmH2O (CC+SI_PIP_30, n = 8), and a sham-operated control group (n = 5). Heart rate, arterial blood pressure, carotid blood flow, cerebral oxygenation, and respiratory parameters were continuously recorded throughout the experiment. Baseline parameters were similar between all groups. There was no difference in asphyxiation (duration and degree) between intervention groups. PIP correlated positively with tidal volume (VT) and inversely with exhaled CO2 during cardiopulmonary resuscitation. Time to ROSC and rate of ROSC were similar between piglets resuscitated with CC+SI_PIP_10, CC+SI_PIP_20, and CC+SI_PIP_30 cmH2O: median (IQR) 75 (63-193) sec, 94 (78-210) sec, and 85 (70-90) sec; 5/8 (63%), 7/8 (88%), and 3/8 (38%) (p = 0.56 and p = 0.12, respectively). All piglets that achieved ROSC survived to four hours post-resuscitation. Piglets resuscitated with CC+SI_PIP_30 cmH2O exhibited increased concentrations of pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α in the frontoparietal cerebral cortex (both p<0.05 vs. sham-operated controls). In asphyxiated term newborn piglets resuscitated by CC+SI, the use of different PIPs resulted in similar time to ROSC, but PIP at 30 cmH2O showed a larger VT delivery, lower exhaled CO2 and increased tissue inflammatory markers in the brain.


Verbal working memory dysfunction in schizophrenia: use of a Brown-Peterson paradigm.
Recent studies of schizophrenia have implicated deficits in processes related to working memory, but the cognitive features of these deficits have been incompletely characterized. We used a modified Brown-Peterson paradigm to compare working memory in patients with schizophrenia and in normal control subjects. Distractor conditions differed in processing demand, increasing in complexity from no distractor to counting backwards (serial threes). We found significant effects of group, of distractor condition, and of a group x distractor condition interaction. The significant interaction was the result of a more rapid decline in the performance of schizophrenic patients with concurrent articulation. In addition, the schizophrenic group also made significantly more intrusion errors. The study suggests that schizophrenic patients exhibit dysfunction of the verbal working memory system due to a diminution in its overall processing resources.


Evolution of duplicated reggie genes in zebrafish and goldfish.
Invertebrates, tetrapod vertebrates, and fish might be expected to differ in their number of gene copies, possibly due the occurrence of genome duplication events during animal evolution. Reggie (flotillin) genes code for membrane-associated proteins involved in growth signaling in developing and regenerating axons. Until now, there appeared to be only two reggie genes in fruitflies, mammals, and fish. The aim of this research was to search for additional copies of reggie genes in fishes, since a genome duplication might have increased the gene copy number in this group. We report the presence of up to four distinct reggie genes (two reggie-1 and two reggie-2 genes) in the genomes of zebrafish and goldfish. Phylogenetic analyses show that the zebrafish and goldfish sequence pairs are orthologous, and that the additional copies could have arisen through a genome duplication in a common ancestor of bony fish. The presence of novel reggie mRNAs in fish embryos indicates that the newly discovered gene copies are transcribed and possibly expressed in the developing and regenerating nervous system. The intron/exon boundaries of the new fish genes characterized here correspond with those of human genes, both in location and phase. An evolutionary scenario for the evolution of reggie intron-exon structure, where loss of introns appears to be a distinctive trait in invertebrate reggie genes, is presented.


Steady-State Oxygen Isotope Effects of N2O Production in Paracoccus denitrificans.
Knowledge of isotopic discrimination, or fractionation, by denitrifying bacteria can benefit agricultural fertilizer management, wastewater treatment, and other applications. However, the complexity of N transformation pathways in the environment and the sensitivity of denitrification to environmental conditions warrant better isotopic distinction between denitrification and other processes, especially for oxygen isotopes. Here, we present a dataset of δ18O measurements in continuous culture of Paracoccus denitrificans. The authors hope that it will be useful in further studies of N2O in the environment.


[Electron immunocytochemistry of lymphocyte surface immunoglobulins in the bursa of Fabricius in the pre- and early postnatal ontogeny of chickens].
The appearance and localization of surface immunoglobulins on B-lymphocytes of the bursa of Fabricius of developing chick embryos and chicks were studied by immuno-electron-cytochemical peroxidase-antiperoxidase (PAP) method. Ultrastructural characteristics of marked and unmarked lymphocytes of the bursa of Fabricius was shown. The increase in the density of reaction product on PAP-complex in the course of lymphocytes differentiation was established.


Spatial stochastic models for cancer initiation and progression.
The multistage carcinogenesis hypothesis has been formulated by a number of authors as a stochastic process. However, most previous models assumed "perfect mixing" in the population of cells, and included no information about spatial locations. In this work, we studied the role of spatial dynamics in carcinogenesis. We formulated a 1D spatial generalization of a constant population (Moran) birth-death process, and described the dynamics analytically. We found that in the spatial model, the probability of fixation of advantageous and disadvantageous mutants is lower, and the rate of generation of double-hit mutants (the so-called tunneling rate) is higher, compared to those for the space-free model. This means that the results previously obtained for space-free models give an underestimation for rates of cancer initiation in the case where the first event is the generation of a double-hit mutant, e.g. the inactivation of a tumor-suppressor gene.


Tracking Systems Used to Monitor the Performance and Activity Profile in Elite Team Sports.
Technology has become established in elite sport in recent years and is used on a regular basis, especially in team sports [...].


[Maternal refusal to consent to a cesarean delivery, stillbirth].
The doctor-lawyer perspective that we discuss is a maternal refusal to consent to a cesarean delivery for a fetal indication in June 2011. Despite repeated information of the risks during a three-week hospitalization for pre-eclampsia, after being assured of the proper understanding of the seriousness of the situation by the patient and spouse, and after consideration to transfer to another hospital, the reiterated refusal led to a late fetal extraction resulting in term stillbirth.


Multi-gene epigenetic silencing of tumor suppressor genes in T-cell lymphoma cells; delayed expression of the p16 protein upon reversal of the silencing.
To understand better T-cell lymphomagenesis, we examined promoter CpG methylation and mRNA expression of closely related genes encoding p16, p15, and p14 tumor suppressor genes in cultured malignant T-cells that were derived from cutaneous, adult type, and anaplastic lymphoma kinase (ALK)-expressing T-cell lymphomas. p16 gene was epigenetically silenced in all but one of the 10 malignant T-cell lines examined, p15 gene silenced in roughly half of the lines, and p14 was the least frequently affected. Extensive methylation of the p16 promoter was seen in six out of 10 cutaneous T-cell lymphoma patient samples and corresponded with lack of p16 protein expression in the cases examined. Treatment of cultured T-cells with the DNA methyltransferase inhibitor, 5-aza-2-deoxy-cytidine, resulted in reversal of the p16 gene silencing. However, expression of p16 protein was delayed in relationship to p16 promoter demethylation and required up to 3 weeks to occur, seemingly reflecting late activation of the p16 gene. These findings indicate that epigenetic silencing affects in T-cell malignancies, often simultaneously, several tumor suppressor genes that impact on key cell functions. The observed differential silencing of p16 and p14, and to a lesser degree p15 gene, indicates that the silencing is governed by precise, promoter region-specific mechanisms. The study provides also further rationale for treatment of at least some types of T-cell lymphomas with DNA methyltransferase inhibitors to target the epigenetically silenced tumor suppressor genes.


Gender associations with selection into Australian Orthopaedic Surgical Training: 2007-2019.
Communities have better health outcomes when their clinicians reflect the diversity of the communities they serve. More than 50% of Australian medical school graduates are female, yet women represent less than 5% of Australian orthopaedic surgeons. Selection into orthopaedic surgical training in Australia is an annual, nation-wide process, based on curriculum vitae (CV), referee reports and performance in multiple mini-interviews (MMI). The influence of applicant gender on these selection scores was examined. The CV, referee reports and MMI scores used for selection for each year from 2007 to 2019 were analysed from the perspective of the applicant's gender. Over the years of the study, male applicants had higher CV scores and referee report scores, which determined the gender proportions invited to interview. By contrast, the interview process and selection from interview did not demonstrate a gender association. We describe the impact of selection tools, utilized over the past 13 years, on the gender diversity of trainees commencing orthopaedic surgery training in Australia. Leaders in postgraduate training should examine commonly used selection procedures to identify and reduce the unconscious biases that may affect their performance and value.


Management and prognostic analysis of patients with gestational trophoblastic neoplasia (GTN) in FIGO stage IV and its special type.
GTN is a group malignant diseases from placental trophoblastic cells. There are very few cases of GTN with FIGO (International Federation of Gynecology and Obstetrics) stage IV all over the world, and the special types (patients with metastatic lesions and with no evidence of GTN neither in genitalia nor in lungs) have rarely been reported. It is necessary to conduct large retrospective studies aimed at exploring the diagnosis, treatment and outcomes of this disease. In this retrospective study, 716 patients with GTN were treated at Zhejiang University School of Medicine Women's Hospital between January 1999 and September 2019; 26 patients were diagnosed as stage IV GTN; Among the 26 stage IV GTN patients, 5 were defined as the special types. The 5-year OS rate of the total 26 FIGO stage IV GTN patients was 69.0%. There was no significant difference of survival rate between stage IV GTN and its special type. And no significant differences in blood type, antecedent pregnancy type, the interval from last known pregnancy, pretreatment serum HCG (human chorionic gonadotropin) level, maximum diameter of tumors, FIGO score, underwent surgery or not and pathological pattern by the outcomes. Age, number of tumor lesions, primary chemotherapy regimen was EMA-CO or EP-EMA protocol and chemoresponse affected the prognosis significantly. Only number of tumor lesions > 8 was independent prognostic factors associated with poorer OS.


Medication Safety Systems and the Important Role of Pharmacists.
Preventable medication-related adverse events continue to occur in the healthcare setting. While the Institute of Medicine's To Err is Human, published in 2000, highlighted the prevalence of medical and medication-related errors in patient morbidity and mortality, there has not been significant documented progress in addressing system contributors to medication errors. The lack of progress may be related to the myriad of pharmaceutical options now available and the nuances of optimizing drug therapy to achieve desired outcomes and prevent undesirable outcomes. However, on a broader scale, there may be opportunities to focus on the design and performance of the many processes that are part of the medication system. Errors may occur in the storage, prescribing, transcription, preparation and dispensing, or administration and monitoring of medications. Each of these nodes of the medication system, with its many components, is prone to failure, resulting in harm to patients. The pharmacist is uniquely trained to be able to impact medication safety at the individual patient level through medication management skills that are part of the clinical pharmacist's role, but also to analyze the performance of medication processes and to lead redesign efforts to mitigate drug-related outcomes that may cause harm. One population that can benefit from a focus on medication safety through clinical pharmacy services and medication safety programs is the elderly, who are at risk for adverse drug events due to their many co-morbidities and the number of medications often used. This article describes the medication safety systems and provides a blueprint for creating a foundation for medication safety programs within healthcare organizations. The specific role of pharmacists and clinical pharmacy services in medication safety is also discussed here and in other articles in this Theme Issue.


Evaluation of Peterson et al.: MAPK cascades don't work in silos: MAP3K cross-activation of MAPKs and the effect of crosstalk on cellular responses.
One snapshot of the peer review process for "Systematic Analysis of the MAPK Signaling Network Reveals MAP3K Driven Control of Cell Fate" (Peterson et al., 2022) appears below.


Mucosa-associated lymphoid tissue lymphoma involving lung and conjunctiva.
A 68-year-old man was found to have tumors of the left lung and left conjunctiva. Thoracoscopic partial lung resection was performed. Histological examination revealed diffuse proliferations of centrocyte-like cells with lymphoepithelial lesions, and a diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma was made. Immunohistochemical study and flow cytometric analysis were also compatible with MALT lymphoma. Conjunctival tumor biopsy was performed and the diagnosis was confirmed. The postoperative course of the patient was uneventful, and he is currently being followed without further treatment.


Update on transient cardiac standstill in cerebrovascular surgery.
Transient cardiac standstill is a complementary procedure used with microsurgery to treat patients with particularly complex aneurysms, such as large or giant cerebral aneurysms. These procedures allow the aneurysms to be decompressed while maintaining a bloodless field and increased surgical exposure. Deep hypothermia combined with circulatory arrest provides cerebroprotection with optimal surgical conditions. However, its disadvantage is the relatively high risk of the procedure, which requires extensive expertise and infrastructure. Thus, its use is typically limited to patients with complex posterior circulation aneurysms. Adenosine-induced transient asystole is an easily applied technique in a variety of clinical situations. Its use requires minimal advanced preparation and no complex logistical coordination with other subspecialties. However, patient-specific dose-response relationships must be determined by exposure, so the relationship may not be known in an emergent situation. Persistent hypotension is a potentially major complication. Rapid ventricular pacing (RVP) has recently been reintroduced into cerebrovascular surgery. It is more predictable than adenosine in response time and, thus, can be used during unanticipated complications, such as aneurysmal rupture. It also induces a shorter period of hypotension compared with adenosine. However, RVP is more invasive and more complex from an anesthesia standpoint. Vascular neurosurgeons should be familiar with these techniques and know their applications and limitations.


Association analysis of a highly polymorphic CAG Repeat in the human potassium channel gene KCNN3 and migraine susceptibility.
Migraine is a polygenic multifactorial disease, possessing environmental and genetic causative factors with multiple involved genes. Mutations in various ion channel genes are responsible for a number of neurological disorders. KCNN3 is a neuronal small conductance calcium-activated potassium channel gene that contains two polyglutamine tracts, encoded by polymorphic CAG repeats in the gene. This gene plays a critical role in determining the firing pattern of neurons and acts to regulate intracellular calcium channels. The present association study tested whether length variations in the second (more 3') polymorphic CAG repeat in exon 1 of the KCNN3 gene, are involved in susceptibility to migraine with and without aura (MA and MO). In total 423 DNA samples from unrelated individuals, of which 202 consisted of migraine patients and 221 non-migraine controls, were genotyped and analysed using a fluorescence labelled primer set on an ABI310 Genetic Analyzer. Allele frequencies were calculated from observed genotype counts for the KCNN3 polymorphism. Analysis was performed using standard contingency table analysis, incorporating the chi-squared test of independence and CLUMP analysis. Overall, there was no convincing evidence that KCNN3 CAG lengths differ between Caucasian migraineurs and controls, with no significant difference in the allelic length distribution of CAG repeats between the population groups (P = 0.090). Also the MA and MO subtypes did not differ significantly between control allelic distributions (P > 0.05). The prevalence of the long CAG repeat (>19 repeats) did not reach statistical significance in migraineurs (P = 0.15), nor was there a significant difference between the MA and MO subgroups observed compared to controls (P = 0.46 and P = 0.09, respectively), or between MA vs MO (P = 0.40). This association study provides no evidence that length variations of the second polyglutamine array in the N-terminus of the KCNN3 channel exert an effect in the pathogenesis of migraine.


Tryptophan supplementation and pH adjustment for optimizing the sporulation of Coniothyrium minitans.
To determine the effect of tryptophan and pH on sporulation of Coniothyrium minitans, the fungus was cultivated using a two-stage, agar plate method in which addition of tryptophan and pH were controlled at the sporulation stage. The spore yield was enhanced by 4 times with 0.1 g tryptophan/l addition after 72 h. The optimal pH values were 4 for mycelia growth and 5.8-6 for sporulation. Mycelia grown at pH 6 had a higher productivity of spore production than did those grown at pH 4.


Impact of MYCN status on response of high-risk neuroblastoma to neoadjuvant chemotherapy.
MYCN-amplification in neuroblastoma is associated with an aggressive clinical phenotype. We evaluated the association of MYCN amplification with tumor response to neoadjuvant chemotherapy. Primary tumor response, assessed by percentage volume change on CT scan and degree of tumor resection, assessed by the operating surgeon, were retrospectively compared in 84 high-risk neuroblastoma patients. There were thirty-four (40%) with MYCN-amplified tumors and fifty (60%) with non-amplified tumors treated at our institution from 1999 to 2016. Metastatic disease response was assessed on MIBG scan by change in Curie score. MYCN-amplification was associated with a greater mean percentage reduction in primary tumor volume after neoadjuvant chemotherapy (72.27% versus 46.83% [non-amplified tumors], p = 0.001). The percentage of patients with a Curie score > 2 at diagnosis who then had a score ≤ 2 after neoadjuvant chemotherapy was not significantly different (8 [61.5%] and 8 [34.8%], respectively, p = 0.37). Twenty-eight (85.7%) patients with MYCN-amplification had ≥90% surgical resection compared to 45 (91.84%) patients with non-amplified tumors (p = 0.303). MYCN-amplification in high-risk neuroblastoma was associated with a better response of the primary tumor to neoadjuvant chemotherapy, but not metastatic sites, than in patients with non-amplified tumors. This did not significantly impact the ability to resect ≥90% of the primary tumor/locoregional disease. Treatment Study LEVEL OF EVIDENCE: Level III.


Policy framework and development strategy for freshwater aquaculture sector in the light of COVID-19 impact in Andaman and Nicobar archipelago, India.
The present study was aimed at understanding the impact of COVID-19 pandemic related restrictions on the freshwater aquaculture sector of Andaman and Nicobar archipelago (ANI). We interviewed the freshwater fish farmers (N = 211) covering all the three districts (North and Middle, South Andaman, Nicobar district) of the archipelago. The results revealed the critical issues faced by the stakeholders such as fish seed unavailability, limitations in feeding, insufficient logistical support, movement related restrictions, lack of inputs, manpower shortages, etc. as the important constraints during lockdown. Our surveys also revealed that there was a significant reduction in the income of the farmers post COVID-19 outbreak (p < 0.001). Possible reform strategies that could promote the sector development and resilience were outlined to recover from the COVID-19 impacts. The study also highlights the significance of effective networking among the stakeholders and necessary preparedness measures to be undertaken by the fish farmers to deal with the exigencies. The study also recommends a policy framework to strengthen the planning and management of freshwater aquaculture sector towards the path of sustainability.


Fine root densities of grasses and perennial sugarcane significantly reduce stream channel erosion in southern China.
Stream Channel (SC) erosion results in immense soil and nutrient losses and eutrophication of downstream lakes and rivers. Among other factors, the lack of vegetation cover within SCs and on adjacent soils can accelerate soil and nutrient losses. The combined impact of perennial sugarcane plantation and grass cover on increasing SC erosion losses have not been previously studied. Current study determined SC erosion and associated nutrient losses and clarified the effect of grass roots within SCs and the ratooned sugarcane grown on adjacent lands in Nala watershed in southern subtropics of China. Six SCs in two sub-watersheds (SW1 and SW2) surveyed after revegetation during 2019 were compared with initial survey conducted in 2017 and 2018. The SC erosion was significantly (P < 0.05) reduced by 84.2% (5.19 ± 2.16 Mg ha-1) in entire watershed in 2019 compared to 2018 (43.9 ± 15.2 Mg ha-1). It notably decreased by 99.23% and 96.50% in SC-1-3 at SW1 and SC2-3 at SW2, respectively. Total N and P losses decreased by 84.9% and 82.5%, respectively, in entire watershed. The decreases in SC erosion and nutrient losses are attributed to increasing vegetative cover (R2 = 0.7543, P < 0.001), and grass root densities of <1 mm (R2 = 0.7543, P < 0.001), 1-2 mm (R2 = 0.7051, P < 0.001) and >2 mm (R2 = 0.5746, P < 0.001). Principal component regression analysis confirmed that root densities of SC grasses, perennial sugarcane, and organic matter had positive impacts on controlling SC erosion and consequent nutrient losses.


Lesion positioning method of a CT-guided surgical robotic system for minimally invasive percutaneous lung.
Robot-assisted puncture has gradually attracted more attention and practical clinical application. The lesion positioning and the needle positioning are the basis to ensure the accuracy of puncture and the key techniques in insertion operation. A lesion positioning method is established which is realized only by the robot-CT system without using external positioning system, and an omnidirectional needle positioning method is also developed and realized by using VRCM, in order to make the puncture needle always keep pointing to the lesion point. A CT-guided surgical robotic system used for minimally invasive percutaneous lung is designed and the physical prototype is manufactured, to perform in-vitro experiments, thereby to validate the effectiveness of the lesion positioning method and the feasibility of omnidirectional needle positioning method. The accuracy of established lesion positioning method based on three non-collinear markers is within 3 mm, which is similar to that of the least squares method based on the five non-coplanar markers, but the positioning efficiency can be improved by about 40%, and the non-collinearity of markers is easier to be satisfied than non-coplanarity in practical applications. The average calculation error of the established positioning method is 0.997 mm. Moreover, the omnidirectional positioning of the puncture needle under the designed surgical robot is feasible. The designed surgical robot has good control accuracy and it can satisfy the requirements for use. The established lesion positioning method can provide a good precision basis for robot-assisted puncture surgery. The suitable insertion point and insertion posture can be determined by the developed omnidirectional needle positioning method. This study can provide theoretical reference for further study of path planning or autonomous positioning.


In vivo evaluation of root canal sealer distribution.
The effectiveness of sealer placement and its distribution in the prepared root canal system by an energized ultrasonic file was evaluated in vivo. One hundred patients had sealer placed into prepared root canals with either the master gutta-percha cone or an ultrasonic file. Before placement of sealer with the file, canals were irrigated, debrided, and flushed with water for 10 s and an energized #20 ultrasonic file at 1.0 mm from the working length. Canals were obturated with gutta-percha using lateral condensation, and evaluations were based on the presence or absence of sealer-filled accessory canals. Chi-square analysis showed that a statistically significant difference existed in the number of radiographically visible accessory canals filled when the ultrasonic file was used to place the sealer.


A case of superior mesenteric artery syndrome characterized by deep forward bending posture in a cross-legged position on the floor.
A 17-year-old healthy male presents with severe epicardial pain and frequent vomiting 1 h after lunch, preferring to sit cross-legged on a stretcher with a deep forward bending posture along with difficulty lying down. SMA syndrome should be considered in the differential diagnosis of patients demonstrating such posture.


Immune Microenvironment Characteristics of Urachal Carcinoma and Its Implications for Prognosis and Immunotherapy.
Urachal carcinoma (UrC) is an exceedingly rare tumor and lacks effective treatment. Herein, we characterized an immune microenvironment characteristic of UrC in detail and identified its implications for prognosis and immunotherapy. In total, 37 resections of UrC were stained for CD20, CD3, CD4, CD8, FOXP3, CD68, HLA-DR, CD163, PD1, and PD-L1, as well as mismatch repair protein including MSH2, MSH6, MLH1, and PMS2 by immunohistochemistry. Intratumoral and peritumoral immune cell densities or the proportion of PD1 and PD-L1 expression alongside MSH2, MSH6, MLH1, and PMS2 status were manually evaluated using the whole slide. UrC patients with the number of tertiary lymphoid structures (TLS) per slide tended to be higher in tumors with dMMR (p = 0.1919), and tumors with higher number of TLS tended to have longer OS (p = 0.0940) and DFS (p = 0.0700). High densities of CD3+ T, CD8+ T, and CD68+ cells were significantly associated with worse OS and DFS (both p<0.05). Increased intratumoral (p = 0.0111) and peritumoral (p = 0.0485) CD8+ T cell densities were significantly associated with PD-L1 expression or increasing proportion of PD-L1 expression on immune cells. Similarly, increased intratumoral (p = 0.0008) and peritumoral (p = 0.063) CD8+ T cell densities were significantly associated with increasing proportion of PD1 expression on immune cells. Tumors with PD-L1 positive expression on immune cells had a significantly increased proportion of PD1 expression (p = 0.0121). High peritumoral CD8+ T cell density (>73.7/mm2) was significantly associated with worse OS (p = 0.0120) and DFS (p = 0.00095). The number of TLS seems to be considered not only as histopathological characteristics in predicting MMR status of UrC, but also as a prognostic or therapeutic biomarker, and we also provide some important suggestions for targeting PD-1/PD-L1 checkpoint in UrC.


Population responses to contour integration: early encoding of discrete elements and late perceptual grouping.
The neuronal mechanisms underlying perceptual grouping of discrete, similarly oriented elements are not well understood. To investigate this, we measured neural population responses using voltage-sensitive dye imaging in V1 of monkeys trained on a contour-detection task. By mapping the contour and background elements onto V1, we could study their neural processing. Population response early in time showed activation patches corresponding to the contour/background individual elements. However, late increased activity in the contour elements, along with suppressed activity in the background elements, enabled us to visualize in single trials a salient continuous contour "popping out" from a suppressed background. This modulated activity in the contour and in background extended beyond the cortical representation of individual contour or background elements. Finally, the late modulation was correlated with behavioral performance of contour saliency and the monkeys' perceptual report. Thus, opposing responses in the contour and background may underlie perceptual grouping in V1.


Synergistic action of laccase treatment and membrane filtration during removal of azo dyes in an enzymatic membrane reactor upgraded with electrospun fibers.
Nowadays, the increasing amounts of dyes present in wastewaters and even water bodies is an emerging global problem. In this work we decided to fabricate new biosystems made of nanofiltration or ultrafiltration membranes combined with laccase entrapped between polystyrene electrospun fibers and apply them for decolorization of aqueous solutions of three azo dyes, C.I. Acid Yellow 23 (AY23), C.I. Direct Blue 71 (DB71) and C.I. Reactive Black 5 (RB5). Besides effective decolorization of the permeate stream, the biosystems also allowed removal of dyes from the retentate stream as a result of enzymatic action. The effect of pH and applied pressure on decolorization efficiencies was investigated, and pH 5 and pressure of 2 bar gave the highest removal efficiencies of 97% for AY23 and 100% for both DB71 and RB5 from permeate solutions while decolorization of retentate for RB5 reached 65% under these conditions. Almost 100% decolorization of all dyes was achieved after three consecutive enzyme membrane cycles. Decolorization was shown to be due to the synergistic action of membrane separation and bioconversion. The biocatalytic action also enabled significant reduction of permeate and retentate toxicity, which is one of the biggest environmental health issues for these types of streams.


"How I Do It:" Non-occlusive High Flow Bypass Surgery.
Giant intracranial aneurysms are a formidable challenge for treatment, considering their grim prognosis. Until lately, endovascular treatment options have been disappointing, and neurosurgical treatment results are by far the most promising. In the neurosurgical treatment of giant intracranial aneurysms, the non-occlusive nature of the ELANA anastomosis technique is a major advantage in flow replacement bypass surgery where large proximal arteries with higher flows need to be replaced or reconstructed. The construction of a deep intracranial anastomosis using the ELANA technique needs less vessel exposure than when using a conventional occlusive technique. This extra advantage facilitates the construction of anastomoses even on the ICA, MCA, ACA, P1, P2, SCA or BA, using the trans-Sylvian route only, without major skull base surgery. Several different types of EC-IC and IC-IC flow replacement bypass are now safely applicable due to the non-occlusive character of this technique.Future improvements of the technique are focused on sutureless applications, graft improvements and Flow Model Simulation. It is clear that not only conventional bypass techniques, but also, and even especially, the ELANA bypass technique, are of great value in the treatment of giant aneurysms.


Immunohistochemical Comparison of Malignancy Between Radial Invasion and Mucosal Extension in Hilar Cholangiocarcinoma.
To compare the cells of mucosal extension (ME) and radial invasion (RI) in hilar cholangiocarcinoma (HCCA) for optimal resection. Forty-six patients underwent surgery for HCCA between 1992 and 2004. Immunohistochemical expressions of p53, Ki-67, matrix metalloproteinase-7 (MMP7), mucin 1 (MUC1), and E-cadherin were assessed at five different sites of the tumour and compared between the recurrence and non-recurrence groups. Expression of E-cadherin was significantly lower in RI cells than in ME cells, and that of MMP7 and MUC1 was significantly higher in RI cells than in ME cells. Ki-67 expression was higher in ME cells than in RI cells. During the 11-year follow-up, recurrence in patients with R0 resection was associated with significantly lower E-cadherin, higher MMP7, and higher Ki-67 expression. Removal of as many RI cells as possible should be a priority in resection of HCCA, followed by removal of ME cells. E-Cadherin appears to be associated with recurrence of HCCA.


A resource on behavioral terminology: an annotated bibliography of on terms articles in the behavior analyst.
An annotated bibliography that summarizes the On Terms articles on behavior-analytic terminology from The Behavior Analyst is provided. Thirty-five articles published between 1979 and 2010 were identified, annotated, and classified using common behavior analysis course-content frameworks.


Pleiotropic QTL on chromosome 19q13 for triglycerides and adiposity: the HERITAGE Family Study.
Motivated by strong correlations between plasma levels of triglycerides (TG) and adiposity traits, we conducted a series of bivariate genome-wide linkage analyses of TG with body mass index (BMI), total fat mass (FAT), percentage of body fat (FATPC), and abdominal subcutaneous fat (ASF). Maximum lod scores of 3.3, 3.0, 2.2 and 2.4, respectively, were found on chromosome 19q13. This linkage region includes the APOE gene, a predictor of variation in lipid-lipoprotein levels, and the hormone-sensitive lipase (LIPE) gene, a key enzyme in the mobilization of fatty acids from triglyceride stores. In addition, the adiposity measures together with the APOE marker showed significant association with TG levels (p = 0.02 to p = 0.03). In summary, these results suggest that one or more QTLs in the 19q13 region jointly influence TG levels and adiposity. Polymorphisms in the APOE gene, and possibly LIPE gene, appear to be strong candidates for the source of this pleiotropic QTL.


HM-chromanone reverses the blockade of insulin signaling induced by high glucose levels in human HepG2 cells.
This study investigated whether (E)-5-hydroxy-7-methoxy-3-(2'-hydroxybenzyl)-4-chromanone (HM-chromanone) could counteract the high glucose level-induced blockade of insulin signaling in human HepG2 cells. Cells were pre-incubated with glucose (5.5 or 33 mM) and then incubated with a medium containing various concentrations of HM-chromanone. Assays for glucose uptake, glycogen synthesis, and glucose production were performed. Western blotting helped elucidate the underlying molecular mechanisms. High glucose concentration (33 mM) significantly increased p-IRS-1ser307 levels and decreased p-Akt levels. However, HM-chromanone significantly decreased p-IRS-1ser307 levels while increasing p-IRS-1tyr612 and Akt levels, which restored insulin signaling disturbed by high glucose concentration. HM-chromanone significantly increased p-AMPK levels, which were reduced by high glucose in HepG2 cells. Knockdown of AMPK using siRNA increased p-IRS-1ser307 and decreased p-Akt levels, even after treatment with HM-chromanone in high glucose concentration-treated cells. HM-chromanone stimulated glycogen synthesis by increasing p-GSK3βser9 and decreasing p-GSser641 levels in HepG2 cells under high glucose concentration; this effect was blocked by AMPK siRNA. HM-chromanone significantly decreased PEPCK, G6Pase, and hepatic glucose production, which were also blocked by AMPK siRNA. These results suggest that HM-chromanone could reverse insulin signaling blockade (induced by high glucose levels) through the activation of AMPK and stimulation of glucose uptake and glycogen synthesis in HepG2 cells.


Association study of apoptosis gene polymorphisms in mitochondrial diabetes: A potential role in the pathogenicity of MD.
Mitochondrial diabetes (MD) is a heterogeneous disorder characterized by a chronic hyperglycemia and is maternally transmitted. Syndromic MD is a subgroup of MD including diabetic microangiopathy and macroangiopathy, in addition to extrapancreatic disorder. MD is caused by genetic mutations and deletions affecting mitochondrial DNA. This mitochondrial damage initiates apoptosis. In this study, we hypothesized that functional polymorphisms in genes involved in apoptotic pathway could be associated with the development of apoptosis in MD disease and increased its risk. Detection of apoptosis was confirmed on muscle biopsies taken from MD patients using the TUNEL method and the Cytochrome c protein expression level. We genotyped then 11 published SNPs from intrinsic and extrinsic apoptotic pathway and assessed the signification of these polymorphisms in 43 MD patients and 100 healthy controls. We found 10 selected polymorphisms (p53 (rs1042522 and rs17878362), BCL2 (rs2279115), BAX (rs1805419), BAK1 (rs210132 and rs2227925), CASP3 (rs1405937), CASP7 (rs2227310), CASP8 (rs1045485) and CASP10 (rs13006529)) with a potential apoptosis effect in MD patients compared to control population. Specifically, SNPs involved in the intrinsic pathway (p53, BCL2, BAK1 and CASP3) presented the highest risk of apoptosis. Our result proved that apoptosis initiated by mtDNA mutations, can be emphasized by a functional apoptotic polymorphisms associated with high expression of cytochrome c protein and more myofibers with apoptosis in syndromic MD subgroup compared with non-syndromic MD subgroup.


How to manage athletes with ventricular arrhythmias.
Young competitive athletes are perceived by the general population to be the healthiest members of society. The possibility that highly trained athletes may have a potentially serious cardiac condition that can predispose to life-threatening tachyarrhythmias or sudden cardiac death seems paradoxical. Thus, differentiating the benign, exercise-induced physiologic changes from true pathologic conditions with risk of sudden death is critical for developing appropriate screening strategies to reduce the risk of these adverse events.


Moexipril does not alter the pharmacokinetics or pharmacodynamics of warfarin.
The potential effect of moexipril, a new converting enzyme inhibitor, on the pharmacokinetics and pharmacodynamics of a single dose of warfarin has been investigated. Ten healthy male volunteers received in a randomised crossover fashion a single oral dose of 50 mg warfarin sodium alone and together with the first dose of 6 days of oral treatment with moexipril 15 mg o.d. Mean oral plasma clearance of (R)-warfarin was 175 ml.h-1 in the absence and 181 ml.h-1 in the presence of moexipril, and the corresponding values for (S)-warfarin were 248 ml.h-1 and 249 ml.h-1. Apparent volume of distribution, peak plasma concentration, time to reach peak concentration and area under the plasma concentration-time curve both of (R)- and (S)-warfarin were not significantly affected. Moexipril did not alter the maximum prothrombin time (20.3 versus 20.1 s, respectively in the absence and presence of moexipril), time to maximum response (48.0 versus 50 h) and area under the prothrombin time versus time curve. The results suggest that a clinically important interaction between moexipril and warfarin is unlikely to occur in patients treated with both drugs.


In vitro interaction of chronic wound bacteria in biofilms.
To use in vitro biofilm models of wound bacterial isolates and compare the biofilms produced for different combinations of wound bacterial species. In vitro biofilms, generated by Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus oralis and Micrococcus luteus in microtitre plates and a constant depth film fermentor (CDFF), were studied. The tested isolates all originated from chronic venous leg ulcers. Biofilms of individual and dual combinations of these species were generated in microtitre plate wells at 37°C for 24-96 hours and also in the CDFF for 7 days. The extent of biofilm formation from these systems was then measured using crystal violet staining and/or total viable counts. All the chronic wound bacteria formed biofilms (both individually and in mixed culture) in these models. In mixed species microtitre plate biofilms, both P. aeruginosa and S. aureus appeared to antagonise biofilm formation by S. oralis and M. luteus, with P. aeruginosa completely inhibiting the growth of these organisms. Similar effects were evident in the CDFF model, when all four bacterial species were added simultaneously, with M. luteus being 'out-competed' by the other organisms present and occurring at numbers at the limits of detection; however, there was an apparent increase in the numbers of S. oralis compared with its single culture equivalent. The study highlighted differences in biofilm formation ability for the tested species in both closed and open model systems. Using dual species biofilms, distinct species antagonism was observed with apparent antagonism of pathogenic species over 'commensal' ones. Such a finding provides insight into possible bacterial interactions during development of 'non-healing' wound biofilms.


Author Correction: Determination of RNA structural diversity and its role in HIV-1 RNA splicing.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Ab initio phasing of X-ray powder diffraction patterns by charge flipping.
Determining crystal structures from powder X-ray diffraction data remains a challenging problem in materials science. By embedding a Le-Bail-like procedure within the recently discovered charge-flipping phasing algorithm, an extremely simple, fast and effective ab initio method has been developed to determine phases directly from indexed powder diffraction patterns. The algorithm solves the degeneracy problem by applying spherical averaging for overlapping Bragg reflections, while solving the phase problem by using the Oszlányi-Süto charge-flipping algorithm. The processes of peak decomposition and phasing are integrated within the same iteration, and a dynamic support is used. The Fienup hybrid input-output algorithm is also incorporated to minimize stagnation. The ability of the algorithm to find structure-factor phases rapidly is found to assist with the fundamental problem of degeneracy (overlapping reflections) which is intrinsic to powder diffraction data. Space-group and chemical-composition information are not needed as inputs, and can be determined from the result. The method is illustrated using several experimental powder patterns of indifferent quality.


E3 Ubiquitin Ligase Nedd4 Promotes Japanese Encephalitis Virus Replication by Suppressing Autophagy in Human Neuroblastoma Cells.
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that causes the most prevalent viral encephalitis in Asia. Since JEV is a neurotropic virus, it is important to identify key molecules that mediate JEV infection in neuronal cells and to investigate their underlying mechanisms. In this study, the critical role of Nedd4, an E3 ubiquitin ligase that is highly expressed in the central nervous system, was examined in JEV propagation. In SK-N-SH neuroblastoma cells, Nedd4 was up-regulated in response to JEV infection. Moreover, down-regulation of Nedd4 resulted in a significant decrease in JEV replication without alterations in virus attachment and internalization or in JEV pseudotyped virus infection, suggesting that Nedd4 participates in the replication but not in the entry stage of JEV infection. Further functional analysis showed that Nedd4 attenuated JEV-induced autophagy, which negatively regulates virus replication during infection. These results suggest that Nedd4 facilitates the replication of JEV by suppressing virus-induced autophagy. Taken together, our results indicate that Nedd4 plays a crucial role in JEV infection of neuronal cells, which provides a potential target for the development of novel treatment to combat JEV infection.


CXCL13 contributes to chronic pain of a mouse model of CRPS-I via CXCR5-mediated NF-κB activation and pro-inflammatory cytokine production in spinal cord dorsal horn.
Complex regional pain syndrome type-I (CRPS-I) causes excruciating pain that affect patients' life quality. However, the mechanisms underlying CRPS-I are incompletely understood, which hampers the development of target specific therapeutics. The mouse chronic post-ischemic pain (CPIP) model was established to mimic CRPS-I. qPCR, Western blot, immunostaining, behavioral assay and pharmacological methods were used to study mechanisms underlying neuroinflammation and chronic pain in spinal cord dorsal horn (SCDH) of CPIP mice. CPIP mice developed robust and long-lasting mechanical allodynia in bilateral hindpaws. The expression of inflammatory chemokine CXCL13 and its receptor CXCR5 was significantly upregulated in ipsilateral SCDH of CPIP mice. Immunostaining revealed CXCL13 and CXCR5 was predominantly expressed in spinal neurons. Neutralization of spinal CXCL13 or genetic deletion of Cxcr5 (Cxcr5-/-) significantly reduced mechanical allodynia, as well as spinal glial cell overactivation and c-Fos activation in SCDH of CPIP mice. Mechanical pain causes affective disorder in CPIP mice, which was attenuated in Cxcr5-/- mice. Phosphorylated STAT3 co-expressed with CXCL13 in SCDH neurons and contributed to CXCL13 upregulation and mechanical allodynia in CPIP mice. CXCR5 coupled with NF-κB signaling in SCDH neurons to trigger pro-inflammatory cytokine gene Il6 upregulation, contributing to mechanical allodynia. Intrathecal CXCL13 injection produced mechanical allodynia via CXCR5-dependent NF-κB activation. Specific overexpression of CXCL13 in SCDH neurons is sufficient to induce persistent mechanical allodynia in naïve mice. These results demonstrated a previously unidentified role of CXCL13/CXCR5 signaling in mediating spinal neuroinflammation and mechanical pain in an animal model of CRPS-I. Our work suggests that targeting CXCL13/CXCR5 pathway may lead to novel therapeutic approaches for CRPS-I.


My paper has been rejected without review. What do I do now?
This column is intended to address the kinds of knotty problems and dilemmas with which many scholars grapple in studying health professions education. In this article, the authors address the question of why papers may be desk rejected (rejected without going out for formal peer review) and describe simple steps for authors to optimize their work so it gets past the desk reject stage.


Case report: Recurrent spontaneous cerebrospinal fluid (CSF) leak.
Obese, middle age, females, and increased intracranial pressure is the commonest predisposing factors for spontaneous cerebrospinal fluid. Here we present a middle-aged female presented 1 year ago with right sided CSF Leak the confirmed by Beta 2 Transferrin and CT scan and repair have been done. Now she presented with the same complains in the left side. Proper management of increased intracranial pressure must be done pre and post skull base repair to prevent recurrence either in the same side or the opposite side.


Accuracy of saliva for SARS-CoV-2 detection in outpatients and their household contacts during the circulation of the Omicron variant of concern.
While nasopharyngeal (NP) swabs are considered the gold standard for severe acute respiratory coronavirus 2 (SARS-CoV-2) real-time reverse transcriptase-polymerase chain reaction (RT-PCR) detection, several studies have shown that saliva is an alternative specimen for COVID-19 diagnosis and screening. To analyze the utility of saliva for the diagnosis of COVID-19 during the circulation of the Omicron variant, participants were enrolled in an ongoing cohort designed to assess the natural history of SARS-CoV-2 infection in adults and children. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa coefficient were calculated to assess diagnostic performance. Overall, 818 samples were collected from 365 outpatients from January 3 to February 2, 2022. The median age was 32.8 years (range: 3-94 years). RT-PCR for SARS-CoV-2 was confirmed in 97/121 symptomatic patients (80.2%) and 62/244 (25.4%) asymptomatic patients. Substantial agreement between saliva and combined nasopharyngeal/oropharyngeal samples was observed with a Cohen's kappa value of 0.74 [95% confidence interval (CI): 0.67-0.81]. Sensitivity was 77% (95% CI: 70.9-82.2), specificity 95% (95% CI: 91.9-97), PPV 89.8% (95% CI: 83.1-94.4), NPV 87.9% (95% CI: 83.6-91.5), and accuracy 88.5% (95% CI: 85.0-91.4). Sensitivity was higher among samples collected from symptomatic children aged three years and older and adolescents [84% (95% CI: 70.5-92)] with a Cohen's kappa value of 0.63 (95% CI: 0.35-0.91). Saliva is a reliable fluid for detecting SARS-CoV-2, especially in symptomatic children and adolescents during the circulation of the Omicron variant.


Constructive quantum interference in a bis-copper six-porphyrin nanoring.
The exchange interaction, J, between two spin centres is a convenient measure of through bond electronic communication. Here, we investigate quantum interference phenomena in a bis-copper six-porphyrin nanoring by electron paramagnetic resonance spectroscopy via measurement of the exchange coupling between the copper centres. Using an analytical expression accounting for both dipolar and exchange coupling to simulate the time traces obtained in a double electron electron resonance experiment, we demonstrate that J can be quantified to high precision even in the presence of significant through-space coupling. We show that the exchange coupling between two spin centres is increased by a factor of 4.5 in the ring structure with two parallel coupling paths as compared to an otherwise identical system with just one coupling path, which is a clear signature of constructive quantum interference.


Deconstructing allostery by computational assessment of the binding determinants of allosteric PTP1B modulators.
Fragment-based drug discovery is an established methodology for finding hit molecules that can be elaborated into lead compounds. However it is currently challenging to predict whether fragment hits that do not bind to an orthosteric site could be elaborated into allosteric modulators, as in these cases binding does not necessarily translate into a functional effect. We propose a workflow using Markov State Models (MSMs) with steered molecular dynamics (sMD) to assess the allosteric potential of known binders. sMD simulations are employed to sample protein conformational space inaccessible to routine equilibrium MD timescales. Protein conformations sampled by sMD provide starting points for seeded MD simulations, which are combined into MSMs. The methodology is demonstrated on a dataset of protein tyrosine phosphatase 1B ligands. Experimentally confirmed allosteric inhibitors are correctly classified as inhibitors, whereas the deconstructed analogues show reduced inhibitory activity. Analysis of the MSMs provide insights into preferred protein-ligand arrangements that correlate with functional outcomes. The present methodology may find applications for progressing fragments towards lead molecules in FBDD campaigns.


Structural alterations in the caudate nucleus and precuneus in un-medicated anorexia nervosa patients.
Anorexia nervosa (AN) is a mental disorder characterized by a preoccupation with thinness and may be associated with brain structural alteration. The aim of the study was to examine the brain structural alteration in AN patients, including subcortical structure volume and cortical thickness. Thirty-five un-medicated AN patients and 20 matched healthy controls underwent structural magnetic resonance imaging brain scans. High resolution structural images were acquired on a SIEMENS 3T scanner and preprocessed using FreeSurfer software. Subcortical structure volume and cortical thickness were compared between the two groups. We found larger percentage of caudate volume relative to total grey matter (GM) volume in the AN group. Reduced cortical thickness at the left precuneus was also observed in AN patients. Moreover, an interaction between group and hemisphere was found, suggesting that cortical thinning was more prominent in the left hemisphere in AN patients. These findings provide further evidence for structural brain abnormalities in patients with AN.


Statistical design-principal component analysis optimization of a multiple response procedure using cloud point extraction and simultaneous determination of metals by ICP OES.
A procedure has been developed for the simultaneous determination of traces amounts of Cd, Cr, Cu, Mn, Ni and Pb from saline oil-refinery effluents and digested vegetable samples using inductively coupled plasma optical emission spectrometry (ICP OES). The procedure is based on cloud point extraction (CPE) of these metals as 2-(bromo-2-pyridylazo)-5-diethyl-amino-phenol (Br-PADAP) complexes into a micellar phase of octylphenoxypolyethoxyethanol (Triton X-114). Optimization of the procedure was performed by response surface methodology (RSM) using a Doehlert design. Principal components (PC) were used to simplify the multiple response analysis. A response surface for the first PC score is useful in determining the optimum conditions for the Cd, Cr, Cu, Mn and Pb determinations whereas the second PC is highly correlated with the Ni response. Improvement factors of 22, 36, 46, 25, 65 and 39, along with limits of detection (3sigma(B)) of 0.081, 0.79, 0.38, 0.83, 0.28 and 0.69 microg L(-1), and precision expressed as relative standard deviation (%R.S.D., n=8, 20.0 microg L(-1)) of 1.5, 2.2, 3.5, 2.6, 2.5 and 2.5 were achieved for Cd, Cr, Cu, Mn, Ni and Pb, respectively. The accuracy was evaluated by spike tests in oil-refinery effluent samples and analysis of a vegetable certified reference material (NIST 1571, orchard leaves). Results found were in agreement with certified values.


The effects of pH oscillation on Lactobacillus rhamnosus batch cultivation.
Inhomogeneous mixing in industrial-sized fermentation processes causes oscillations in process parameters such as temperature or pH value in the cultivation medium, which causes stress to the bacteria being cultivated. In this work, the impact of extracellular pH oscillations on the production of Lactobacillus rhamnosus, a well-studied probiotic bacteria, were investigated by means of a scale-down batch process, simulating inhomogeneous pH values by controlling the pH value of the medium on sinusoidal trajectories. Effects of pH stimulation on the bacteria were assessed by testing storage and freeze-drying stability of harvested cells, two factors relevant for the industrial process. Furthermore, gene expressions of six selected genes, i.e. atpA, fat, cfa, groEL, hrcA, and pstS, known to be related to stress response were monitored. Although storage stability is only slightly negatively affected by pH stimulation of the bacteria, gene expression of four of the studied genes, i.e. fat, hrcA, groEL, and pstS show to correlate with amplitude and frequency of the oscillation.


ROS-Sp1 axis is involved in thermochemotherapy-enhanced sensitivity of pancreatic cancer cells to gemcitabine.
Gemcitabine (GEM)-based chemotherapy represents the first choice for locally unresectable advanced pancreatic cancer, while the benefit is limited due to acquired chemoresistance or drug delivery insufficiency. Hyperthermia treatment potentially improves the clinical efficacy of GEM. However, the underlying mechanism is incompletely revealed. Our study aims to investigate the effect and involved mechanism of thermochemotherapy on cell survival. Pancreatic cancer cells PANC-1 and ASPC-1 were either treated with GEM or thermochemotherapy, then cell viability, apoptosis, migration, invasion, reactive oxygen species (ROS) production, and Sp1 expression were evaluated. The results showed that GEM dose and time-dependently affected cell viability, and 30 μM GEM achieved favorable effect in suppressing cancer cell growth. Meanwhile, hyperthermia preconditioning (43°C for 60 min) 24 h before GEM treatment yielded superior effect than other treatment sequence. GEM caused significant cell apoptosis and proapoptotic genes of both cancer cells, and thermochemotherapy further promoted apoptosis and genes transcription, accompanied by excessive ROS production. Thermochemotherapy was superior to GEM in suppressing cell migration and invasion of pancreatic cancer cells. Meanwhile, GEM significantly reduced Sp1 mRNA and protein and its downstream gene Cox-2, and thermochemotherapy further suppressed their expressions. ROS elimination with N-acetyl-l-cysteine notably neutralizes the suppressive effect of GEM and thermochemotherapy on cell growth and expressions of Sp1 and Cox-2. In conclusion, thermochemotherapy inhibited pancreatic cell viability, migration and invasion, and promoted cell apoptosis by inducing excessive ROS production, which subsequently suppressed Sp1 expression and the downstream Cox-2.


Contribution of dppA to urease activity in Helicobacter pylori 26695.
The gastric pathogen Helicobacter pylori produces urease in amounts up to 10% of its cell protein. This enzyme, which catalyzes the hydrolysis of urea to ammonia and carbon dioxide, protects the bacterium from gastric acid. Urease, a nickel metalloenzyme, requires active uptake of nickel ions from the environment to maintain its activity. NixA is a nickel transport protein that resides in the cytoplasmic membrane. Mutation of nixA significantly reduces but does not abolish urease activity, strongly suggesting the presence of a second transporter. We postulated that the dipeptide permease (dpp) genes that are homologous to the nik operon of Escherichia coli could be a second nickel transporter. The predicted Dpp polypeptides DppA, DppC, and DppD of H. pylori share approximately 40%, 53%, and 56% amino acid sequence identity with their respective E. coli homologs. A mutation in dppA, constructed by insertional inactivation with a chloramphenicol resistance cassette, was introduced by allelic exchange into H. pylori strain 26695. When compared to the parental strain, urease activity was not decreased in a dppA mutant. DppA does not contribute to the synthesis of catalytically active urease in H. pylori 26695 and is likely not a nickel importer in H. pylori.


Influence of deep neuromuscular block on the surgeonś assessment of surgical conditions during laparotomy: a randomized controlled double blinded trial with rocuronium and sugammadex.
During laparotomy, surgeons may experience difficult surgical conditions if the patient's abdominal wall or diaphragm is tense. Deep neuromuscular block (NMB), defined as a post-tetanic-count (PTC) between 0-1, paralyses the abdominal wall muscles and the diaphragm. We hypothesized that deep NMB (PTC 0-1) would improve subjective ratings of surgical conditions during upper laparotomy as compared with standard NMB. This was a double blinded, randomized study. A total of 128 patients undergoing elective upper laparotomy were randomized to either continuous deep NMB (infusion of rocuronium 2 mg ml -1 ) or standard NMB (bolus of rocuronium 10 mg or increased depth of anaesthesia). Surgical conditions were evaluated using a 5-point subjective rating scale (1: extremely poor, 5: optimal) every 30 min. Primary outcome was the average of scores for a patient's surgical conditions. Other outcomes were surgical rating score during fascial closure, episodes of a need to optimize surgical conditions, occurrence of wound dehiscence, and wound infection. Deep compared with standard NMB resulted in better ratings of surgical conditions; median 4.75 (range 3-5) compared with 4.00 (range 1-5) ( P <0.001), respectively. Deep compared with standard NMB resulted in better ratings of surgical conditions during fascial closure ( P <0.001), fewer episodes of need to optimize surgical conditions ( P <0.001), and fewer incidents with sudden movements ( P <0.001). No differences in operating time, occurrence of wound infection, and wound dehiscence were found. Deep NMB compared with standard NMB resulted in better subjective ratings of surgical conditions during laparotomy. NCT02140593.


Topical delivery systems containing clotrimazole for the management of candidiasis: Effect of different excipients and enhanced antifungal activity of nanovesicles.
WHO classified Candida albicans as one of the four critical priority fungi for public health worldwide in 2022. Conventional topical formulations commercially available for the treatment of cutaneous candidiasis are associated with low drug bioavailability at the infection site and the lack of a sustained therapeutic effect. The main objectives of this work were to develop new topical administration systems of clotrimazole (CLT) and study the influence of surfactants on the antifungal inhibitory efficacy. Therefore, the minimum concentration of CLT required to inhibit 50 % of growth (MIC50) was determined, obtaining a value of approximately 15 ng/mL. A non-ionic emulsion type 1, Beeler base cream, hydrogel and liposomes containing CLT were designed, prepared, characterized and their antifungal activity against C. albicans was tested. CLT loaded liposomes were small in size (102 nm), homogeneous (polydispersity index = 0.3) and uncharged (+0.07 mV), showing higher antifungal activity against C. albicans than that of the commercially available cream Canesten®. Furthermore, the antifungal activity of CLT was reduced in combination with surfactants such as Tween-80/Span-80 or Brij-S10. Sodium lauryl sulphate showed a fungicidal effect that disappeared when formulated as part of the Beeler base cream.


Calmodulin-dependent regulation of neurotransmitter release differs in subsets of neuronal cells.
The purpose of this study was to determine whether calmodulin (CaM) plays a role in neurotransmitter release by examining the effect that ophiobolin A (OBA), a CaM antagonist, on neurotransmitter release from clonal rat pheochromocytoma PC12 cells, primary cortical neurons, and primary cerebellar granule cells. OBA inhibited Ca²⁺/CaM-dependent phosphorylation of cAMP response element binding protein in all cell types tested. Moreover, Ca²⁺-dependent release of dopamine and acetylcholine from PC12 cells were remarkably reduced by OBA in a dose-dependent and temporal manner, but neurotransmitter release partially recovered with the addition of CaM in membrane permeabilized PC12 cells. OBA and several synthetic CaM antagonists suppressed Ca²⁺-dependent glutamate release from cerebral cortical neurons, but not from cerebellar granule cells. Myosin Va, a CaM binding protein, localized to synaptic vesicles of PC12 cells and cerebral cortical neurons, but not in cerebellar granule cells. OBA suppressed Ca²⁺-induced myosin Va dissociation from secretory vesicles, and inhibited secretory vesicle motility in PC12 cells. These results suggest that CaM, although not essential, regulates neurotransmitter release in a subset of neurons and secretory cells, and myosin Va is a possible target of OBA in this process.


Left Atrial Appendage Patency at Cardioversion After Surgical Left Atrial Appendage Intervention.
Surgical left atrial appendage (LAA) closure is often incomplete, with patients frequently requiring direct current cardioversion (DCCV) for atrial arrhythmias. Transesophageal echocardiography (TEE) is often performed before DCCV to exclude LAA thrombus. The impact of incomplete surgical LAA closure on patients referred for postoperative DCCV is unknown. We retrospectively reviewed patients undergoing TEE-guided DCCV within 30 days of cardiac surgery and surgical LAA closure. All pre-DCCV TEEs were reviewed to assess LAA patency and the presence of thrombus. Ninety-three patients (mean age 68 years; 61 men [66%]) had a median time from surgery to DCCV of 6 days. Duration of atrial fibrillation was 48 hours or more in 85% (n = 79). On pre-DCCV TEE, a residual communication from the LAA was noted in 37% (n = 34). The rate of LAA patency was higher after suture closure than after surgical excision or staple closure. Thrombus was present in 26 of the 93 patients (28%), including 16 of 34 patients (47%) with incomplete closure of LAA. The strongest risk factor for thrombus was a patent, partially closed LAA (odds ratio 4.36, p = 0.003). Systemically accessible thrombus was present in 19 of the 93 patients (20%), and cardioversion was cancelled owing to thrombus in 15 (16%). Surgical closure of the LAA is often incomplete. Interrogation of the residual LAA after surgical LAA intervention with TEE before DCCV frequently detects thrombus and alters clinical management. Patients undergoing DCCV after surgical LAA intervention require evaluation with TEE for LAA patency and thrombus.


Better adherence to the Chinese Healthy Eating Index is associated with a lower prevalence of metabolic syndrome and its components.
The Chinese Healthy Eating Index (CHEI) was built on Dietary Guidelines for Chinese-2016 and has been confirmed as a valid measuring instrument to evaluate the diet quality of the Chinese population. Studies have shown that healthy dietary patterns were associated with reduced metabolic syndrome (MS) risk. Here, we hypothesized a better adherence to CHEI was effective in preventing MS. Therefore, we performed a cross-sectional study (n = 704; 298 males and 406 females) in Hubei. Dietary data were collected by 3-day 24-hour dietary recalls. MS was diagnosed using Guidelines for the Prevention and Control of type 2 Diabetes in China (2017 edition). Logistic regression and propensity and restricted cubic splines analysis were used to evaluate the associations of CHEI with MS and its components. In a comparison of the adjusted risk of MS in participants in the third and first tertile of CHEI, a 47% lower risk was observed for MS in females, especially for those who were middle-aged. However, no significant association of CHEI was exhibited with MS in males. Propensity analysis validated the findings in females, presenting a 58% lower MS risk and 71% lower risk of central obesity. It exhibited a linear association of CHEI score with MS and abdominal obesity. The associations were consistent after excluding those with prior hypertension or diabetes mellitus. In conclusion, a negative linear association was identified between CHEI score and MS and central obesity, which was pronounced in females.


Inhibition of tumor necrosis factor-alpha secretion by pentoxifylline in advanced cancer patients with abnormally high blood levels of tumor necrosis factor-alpha.
TNF, in addition to its antitumor activity, would play an important role in the pathogenesis of cancer-related severe complications, including ARDS and DIC. Therefore, the modulation of TNF secretion could be important in the supportive care of advanced cancer patients. At present, PTX is the only drug which has been proven to be able to inhibit in vitro the release of TNF. The present study was performed to evaluate the effect of PTX on TNF blood concentrations in disseminated cancer patients with abnormally high TNF values. The study included 14 cancer patients, with initial or conclamate signs of ARDS (n = 8) or DIC (n = 6). PTX was given intravenously at a dose of 300 mg/day for 7 days. Mean serum levels of TNF significantly decreased in response to PTX therapy, and they returned to normal range in 5/14 patients. These preliminary data would suggest that PTX may be considered as a biological response modifier, capable of inhibiting TNF secretion in humans, with a following potential use in the treatment of cancer-related severe complications.


A study on the amount of high-mobility-group chromatin proteins in T-cells at different stages of differentiation.
The amounts of high-mobility-group proteins (HMG) 1 and 2 in different mouse T-cell populations are studied. It is shown that the quantity of HMG 1 and 2 is different in functionally distinct T-cells. The level of these proteins in thymus cells is higher than in cortisone-resistant thymocytes and peripheral T-cells; it increases in the cytotoxic cells generated in mixed lymphocyte culture. The quantity of HMG is negligible in memory T-cells and increases when the latter cells are stimulated again. The differences found in the levels of HMG 1 and 2 could be related to the rate of cell proliferation and to the changes in chromatin structure at each functional stage of differentiating T-cells.


Dipyridamole cardiac imaging.
Dipyridamole cardiac imaging is a useful alternative technique to exercise stress testing in the evaluation of patients with ischemic heart disease. Intravenous dipyridamole is still in the investigational phase, while oral dipyridamole is widely available. The hemodynamic effects of dipyridamole include an increase in coronary blood flow (due to coronary vasodilation) which is in excess of the increase in myocardial oxygen consumption and cardiac output. The disparity in the increase in coronary blood flow relative to the cardiac output results in an increase in myocardial thallium activity and an increase in the myocardial/background activity ratio. The quality of the thallium images is better or similar to that of exercise thallium images. The optimal dose of intravenous dipyridamole is 0.56 mg/kg, and of the oral dose it is 300 to 400 mg, although higher doses may be necessary in some patients. Analysis of the thallium images has been to a large extent based on visual inspection of the planar images. Delayed images are helpful to establish the nature of the perfusion abnormalities (transient or fixed). The process of redistribution is based on disparate rates of washout from the normal and abnormal zones. The sensitivity and specificity of dipyridamole thallium imaging, whether intravenous or oral, have been shown in a number of studies to be quite adequate and comparable to that achieved during exercise thallium imaging. Dipyridamole two-dimensional echocardiography has also been used in the detection of coronary artery disease; transient (new or worsening of preexisting) wall motion abnormalities have been found to be a specific marker of coronary artery disease. Transmural as well as regional coronary steal phenomena have been postulated as the mechanism for dipyridamole-induced regional wall motion abnormalities. Compared to exercise two-dimensional echocardiography, dipyridamole echocardiography provides high-quality studies and in higher proportions of patients. The results of dipyridamole thallium imaging have also been extremely important in identifying high-risk patients after acute myocardial infarction or patients with peripheral vascular disease undergoing elective vascular surgery; the presence of a dipyridamole-induced perfusion abnormality identifies patients at high risk for future cardiac events. Thus, dipyridamole cardiac imaging is helpful in the diagnosis of coronary artery disease and in risk stratification.


Nutritional Wellness for the Busy Health Care Provider: Small Everyday Wins.
When describing health care provider wellness, diet and nutrition are typically not addressed. This, in combination with the lack of decent food and diet resources typically available to the typically busy health care provider, exposes a significant gap in the road to advancing clinician wellness. This article aims to describe the relationship between nutrition and well-being, and potential barriers to optimal nutrition encountered by health care providers in the workplace. Readily available and practical strategies to improve physician diet and nutrition include: mindful eating practices, home meal preparation, food journaling, and mobile applications. From an organizational level, once physicians are making more informed food choices it is the hospital's responsibility to make nutritional options available in the workplace.


5HT3 receptor antagonists do not block nicotine induced hyperactivity in rats.
The effects of 5-HT3 receptor antagonists (ondansetron 0.1 mg kg-1 SC 30 min; bemesetron 0.03 mg kg-1 SC 45 min) on nicotine-induced increases in locomotor activity were measured in male Sprague-Dawley rats. Intermittent daily injections of nicotine (0.3-1.2 mg kg-1 SC 30 min) resulted in increased locomotor activity as measured by photocell counts. The effect of nicotine was not affected by administration of the 5-HT3 receptor antagonists at doses that are reported to block nicotine- and morphine-induced place-preference conditioning. Neither of the 5-HT3 receptor antagonists tested affected activity counts in vehicle treated animals. Nicotine-induced hyperactivity was blocked by the dopamine antagonist haloperidol (0.03 mg kg-1 SC 2 h) and by the nicotinic antagonist mecamylamine (1 mg kg-1 SC 1 min). The effects of a range of doses (0-1 mg kg-1) of the 5-HT3 receptor antagonists ondansetron, bemesetron, granisetron and tropisetron on hyperactivity induced by 0.6 mg kg-1 nicotine were then assessed. Only tropisetron at 1 mg kg-1 attenuated nicotine-induced hyperactivity. To demonstrate the efficacy of the present range of doses of the 5-HT3 receptor antagonists in this study, conditioned taste aversion experiments were conducted. Ondansetron (0.1 mg kg-1) failed to attenuate a conditioned taste aversion to saccharin induced by nicotine (0.6 mg kg-1), but did induce a reduction in saccharin preference in choice tests following three saccharin-ondansetron pairings.(ABSTRACT TRUNCATED AT 250 WORDS)


45Calcium uptake during the transition from reversible to irreversible liver injury induced by D-galactosamine in vivo.
The hepatic uptake of 45calcium (45Ca) was studied in rats after administration of D-galactosamine (3 mmoles per kg, i.v.). In contrast to measurements of the hepatic calcium content, 45Ca uptake served as a dynamic rather than a static indicator of calcium homeostasis during the transition from reversible to irreversible liver injury which occurs between 3 and 4 hr after injection of the hepatotoxin. 45Ca uptake during a 1 hr-labeling period increased from 25 to 100% above control between 3 and 4 hr and subsequently remained at this level. The rise in 45Ca uptake and in hepatic calcium content occurred 2 to 3 hr after the D-galactosamine-induced depletion of UTP, UDP-galactose, UDP-glucose and UDP-glucuronate. The level of UDP-glucuronate was the earliest to recover. The enhanced 45Ca uptake was associated with hepatic glycogen breakdown and with an increased SGPT activity in plasma. Inhibition of RNA polymerase II by alpha-amanitin (0.5 mg per kg, i.p.) and of dolichol-dependent protein glycosylation as well as ganglioside synthesis by tunicamycin (2 mg per kg, i.p.) were used to imitate two of the early actions of D-galactosamine and indicated that an interference with either process can lead to an enhanced uptake of 45Ca into the liver in vivo. Uridine, at a dose replenishing uracil nucleotide pools after their depletion by D-galactosamine, prevented or reversed the rise in 45Ca uptake. The antiinflammatory steroid dexamethasone, injected prior to or simultaneously with D-galactosamine also protected against the loss of calcium homeostasis and the development of liver injury.(ABSTRACT TRUNCATED AT 250 WORDS)


Reduced alpha adrenergic mediated contraction of renal preglomerular blood vessels as a function of gender and aging.
As human males age, a decline in baroreflex-mediated elevation of blood pressure occurs due, at least in part, to a reduction in alpha-1 adrenergic vasoconstrictor function. Alpha adrenergic constriction is mediated by guanosine triphosphate binding Protein (G Protein) coupled signaling pathways. Alpha-1 A/C, B, and D adrenergic receptor expressions, measured by GeneChip array, are not reduced during aging in renal blood vessels of male or female rats. Alpha-1 A GeneChip expression is greater, at all ages studied, in females than in males. Prazosin binding by alpha-1 adrenergic receptors is greater in young adult female rats than in young adult male rats; however, it is reduced with aging in both male and female rats. G alpha q GeneChip expression declines while expression of adrenergic receptor kinase (GRK2) and tyrosine phosphatases (TyrP) increase with aging in male rats. The declines in alpha-1 adrenergic receptor binding and G alpha q expression and also the increases in GRK2 and TyrP expression likely relate to the age-related decline of vasoconstriction in male rats. The information that the expression of alpha-1 A adrenergic receptors is greater in female rats and (GRK2) expression does not increase during aging could relate to the gender differences in vasoconstrictor function with aging. Gene therapy to ameliorate the age-related decline in renal function could possibly reduce the need for renal dialysis. Signaling pathways such as those reviewed herein may provide an outline of the molecular pathways needed to move toward successful renal gene therapy for aging individuals.


A fast and safe technique for sperm preparation in ICSI treatments within a randomized controlled trial (RCT).
Recently a novel method based on horizontal sperm migration in injection dishes has been introduced as an additional tool for preparation of semen sample in assisted reproductive technology (ART) procedures. In the present study, we evaluated both timing and reproductive outcomes in a randomized controlled study including 1034 intra-cytoplasmic sperm injection (ICSI) procedures followed by fresh embryo transfer. Couples enrolled were divided into two sub-groups, namely conventional swim-up method (Group A), and horizontal sperm migration in injection dishes (Group B).No significant differences were found between groups with respect to fertilization rate, implantation success, clinical pregnancy outcomes and ongoing pregnancies. On the contrary, both cleavage and blastocyst rates were statistically higher in Group B, suggesting superior efficiency and safety of this innovative technique also including time-saving and cheaper costs as compared to the classical swim-up sperm preparation.Our data support the interpretation of the horizontal sperm migration as a promising procedure for semen preparation in ART cycles.


Cyclooxygenase-2 Inhibition Provides Lasting Protection Following Germinal Matrix Hemorrhage in Premature Infant Rats.
Germinal matrix hemorrhage (GMH) is a major cause of brain damage in prematurity and has long-lasting neurological implications. The development of brain inflammation contributes to brain injury, leading to a lifetime of neurologic deficits. PAR-1 and 4 receptors are involved with inflammatory pathways after brain hemorrhage in adult models of stroke, of which cyclooxygenase-2 (COX-2) is a potential mediator. We therefore hypothesized a role for PAR-1, 4/ COX-2 signaling following GMH. Postnatal day 7 Sprague-Dawley rats were subjected to GMH induction, which entailed stereotactic collagenase infusion into the ganglionic eminence. Animals were euthanized at two time points: 72 h (short-term) or 4 weeks (long-term). Short-term COX-2 expression was evaluated in the context of PAR-1 (SCH-79797) and PAR-4 (P4pal10) inhibition. Pups in the long-term group were administered the selective COX-2 inhibitor (NS-398); and the neurobehavioral and pathological examinations were performed 4 weeks later. Pharmacological PAR-1, 4 antagonism normalized COX-2 expression following GMH and reduced hydrocephalus. Early inhibition of COX-2 by NS-398 improved long-term neurobehavioral outcomes. COX-2 signaling plays an important role in brain injury following neonatal GMH, possibly through upstream PAR-1, 4 receptor mechanisms.


Exclusive MRI-based tandem and colpostats reconstruction in gynaecological brachytherapy treatment planning.
According to the GYN GEC-ESTRO Recommendations, MRI is needed with the modality of T2 weighted. CT-MR compatible tandem plus colpostats (T/C) (Nucletron) is widely used in cervical brachytherapy. The major challenge of MRI is the lack of dummy catheters. Therefore, an additional imaging modality is usually required. One disadvantage of sliced-based reconstruction is that resolution in longitudinal directions can be affected by the slice thickness. The aim of this study is to present a modified T/C applicator in which the catheter visibility is significantly improved. A modification to the existing T/C applicator has been made available, increasing the catheter entrance diameter. It allows a greater dummy catheter diameter, and consequently it can be filled with more material per unit length. Visibility was studied with different materials. The catheter filled with saline water plus iodine compound was clearly seen in both axial and longitudinal acquisitions. To avoid uncertainties introduced by the slice thickness, a simple procedure is presented using longitudinal acquisitions. The modified applicator plus catheter allows a powerful signal in T2 weighted MRI, using a very simple and accessible material. Also, a method is proposed to solve the problem of the uncertainty derived from slice thickness using few longitudinal acquisitions.


Flexible Carbon Nanotube-Epitaxially Grown Nanocrystals for Micro-Thermoelectric Modules.
Flexible thermoelectric materials have attracted increasing interest because of their potential use in thermal energy harvesting and high-spatial-resolution thermal management. However, a high-performance flexible micro-thermoelectric device (TED) compatible with the microelectronics fabrication process has not yet been developed. Here a universal epitaxial growth strategy is reported guided by 1D van der Waals-coupling, to fabricate freestanding and flexible hybrids comprised of single-wall carbon nanotubes and ordered (Bi,Sb)2 Te3 nanocrystals. High power factors ranging from ≈1680 to ≈1020 µW m-1 K-2 in the temperature range of 300-480 K, combined with a low thermal conductivity yield a high average figure of merit of ≈0.81. The fabricated flexible micro-TED module consisting of two p-n couples of freestanding thermoelectric hybrids has an unprecedented open circuit voltage of ≈22.7 mV and a power density of ≈0.36 W cm-2 under ≈30 K temperature difference, and a net cooling temperature of ≈22.4 K and a heat absorption density of ≈92.5 W cm-2 .


Adynamic bone in patients with chronic kidney disease.
Adynamic bone in patients with chronic kidney disease (CKD) is a clinical concern because of its potential increased risk for fracture and cardiovascular disease (CVD). Prevalence rates for adynamic bone are reportedly increased, although the variance for its prevalence and incidence is large. Differences in its prevalence are largely attributed to classification and population differences, the latter of which constitutes divergent groups of elderly patients having diabetes and other comorbidities that are prone to low bone formation. Most patients have vitamin D deficiency and the active form, 1,25-dihydroxyvitamin D, invariably decreases to very low levels during CKD progression. Fortunately, therapy with vitamin D receptor activators (VDRAs) appears to be useful in preventing bone loss, in part, by its effect to stimulate bone formation and in decreasing CVD morbidity, and should be considered as essential therapy regardless of bone turnover status. Future studies will depend on assessing cardiovascular outcomes to determine whether the risk/reward profile for complications related to VDRA and CKD is tolerable.


Intraocular lens power calculation. A retrospective analysis of its practical value.
Two hundred and two consecutive intraocular lens (IOL) implantations, the lens power being predicted with the SRK-method, are retrospectively analyzed, and the factors possibly influencing the error in IOL power prediction are evaluated. The actual post-operative refraction is compared to the expected refraction for each IOL and to a hypothetical refraction that would have been obtained by a standard-power IOL implant. Axial length measurement and a high pre- and post-operative astigmatic error, along with low- and high power IOL predictions, are the factors that most influence the post-operative refractive error. A similar distribution of post-operative refraction could have been obtained by using a standard-power IOL instead of pre-operative calculation.


Superhydrophobic surfaces: from natural to biomimetic to functional.
Nature is the creation of aesthetic functional systems, in which many natural materials have vagarious structures. Inspired from nature, such as lotus leaf, butterfly' wings, showing excellent superhydrophobicity, scientists have recently fabricated a lot of biomimetic superhydrophobic surfaces by virtue of various smart and easy routes. Whilst, many examples, such as lotus effect, clearly tell us that biomimicry is dissimilar to a simple copying or duplicating of biological structures. In this feature article, we review the recent studies in both natural superhydrophobic surfaces and biomimetic superhydrophobic surfaces, and highlight some of the recent advances in the last four years, including the various smart routes to construct rough surfaces, and a lot of chemical modifications which lead to superhydrophobicity. We also review their functions and applications to date. Finally, the promising routes from biomimetic superhydrophobic surfaces in the next are proposed.


A survey on the occurrence of citrinin in feeds and their ingredients in Russia.
More than 1700 samples of forage grain, sunflower and soy-bean oil-seed meal and cakes, gluten, and compounded feeds were analyzed for citrinin by indirect ELISA with a minimum detectable level of 10 ppb. Out of 829 compounded feeds (rations and concentrates) 8.8 per cent samples were positive and the amount of citrinin ranged between 12 and 182 ppb. Only 4.5% of wheat and 3.6% of barley contained citrinin at 50-998 ppb. 1.9% of maize grain samples were positive at levels of 218-953 ppb. Among the other ingredients the highest incidence (28.9%) at the levels of 14-397 ppb was found for sunflower oil-seed meal and cakes. Three positive cases of 148 processed soy-bean samples contained citrinin in a range of 14-30 ppb.


Edoxaban: a review in nonvalvular atrial fibrillation.
The factor Xa inhibitor edoxaban (Lixiana(®)) is a new direct oral anticoagulant recently approved in the EU for the prevention of stroke and systemic embolic events (SEE) in patients with nonvalvular atrial fibrillation and one or more risk factors. In the large, randomized, double-blind, double-dummy, ENGAGE AF-TIMI 48 trial, oral edoxaban dosages of 30 and 60 mg once daily for a median treatment duration of 907 days in patients with moderate-to-high-risk nonvalvular atrial fibrillation were noninferior to warfarin for the incidence of first stroke or SEE. Both high-dose and low-dose edoxaban were associated with significantly lower rates than warfarin of major bleeding, including intracranial haemorrhage, and death from cardiovascular causes. Edoxaban has a rapid onset of action, a short half-life, few drug interactions and offers the convenience of oral, once-daily, fixed-dose administration, without the need for coagulation monitoring and without regard to food. Therefore, edoxaban is an effective and well tolerated therapeutic option in patients with nonvalvular atrial fibrillation.


Short-term growth hormone or IGF-I administration improves the IGF-IGFBP system in arthritic rats.
Adjuvant-induced arthritis is an experimental model of rheumatoid arthritis that inhibits the GH-IGF-I axis and decreases body weight gain and muscle mass. Although chronic GH or IGF-I treatment increases body weight gain in arthritic rats, muscle resistance to GH and IGF-I is a very common complication in inflammatory diseases. In this study we examine the effect of short-term administration of rhGH and rhIGF-I on liver and muscle IGF-I, IGFBP-3 and -5 as well as on the ubiquitin-ligases MuRF1 and atrogin-1 in the muscle of arthritic rats. Arthritis was induced in adult male Wistar rats by an intradermal injection of 4 mg of Freund's adjuvant. Fifteen days after adjuvant injection, 300 μg/kg of rhGH or 200 μg/kg of rhIGF or saline was administrated 18 and 3h before decapitation. A pair-fed group injected with saline was included in order to discard a possible effect of decreased food intake. Gene expression of IGF-I, GHR, IGFBP-3, IGFBP-5, atrogin-1 and MuRF1 were quantified using RT-PCR. In serum, IGF-I was measured by radioimmunoassay (RIA) and IGFBP-3 by ligand blot. Arthritis decreased serum IGF-I and IGF mRNA in liver (P<0.05), but not in skeletal muscle. In arthritic rats, rhGH increased serum IGF-I and liver IGF-I mRNA similar to the levels of pair-fed rats. Arthritis increased atrogin-1, MuRF1, IGFBP-3 and IGFBP-5 mRNA in muscle (P<0.01). IGFBP-3 mRNA was downregulated by rhIGF-I, but not by rhGH, administration in control and arthritic rats (P<0.05). Administration of rhGH and rhIGF-I increased IGFBP-5 in the gastrocnemius of arthritic rats. Short-term rhGH and rhIGF-I administration was found to increase muscle IGFBP-5 mRNA, whereas only rhIGF-I administration decreased muscle IGFBP-3 mRNA in control and arthritic rats. These data suggest that arthritis does not induce GH or IGF-I resistance in skeletal muscle.


Development of a Simple Dansyl-Based PH Fluorescent Probe in Acidic Medium and Its Application in Cell Imaging.
A simple pH fluorescent probe based on dansyl derivative (Bu-Dns) was synthesized via one-step reaction between dansyl chloride and 4-bromobutan-1-amine hydrobromide. The obtained probe showed good selectivity and sensitivity toward H+ in acidic medium over two pH units (~4-2). At pH > 4, Bu-Dns solution emitted yellow fluorescent light, which became gradually weaker with decreasing pH value. At pH below 2, complete fluorescence quenching occurred. The pH response of Bu-Dns was ascribed to the protonation of dimethylamine group. The lack of influence of metal ion on pH response increases the prevalence of Bu-Dns in the potential detection of pH variation in acidic aqueous media. More importantly, it can sense the intracellular pH change in acidic range.


Retrospective comparison of blood pressure course during preeclamptic and matched control pregnancies.
A decrease in systemic blood pressure by midtrimester of normal pregnancy has been observed by many investigators. To examine the timing of onset of this decline and to study early behavior of blood pressure in pregnancies complicated by preeclampsia, we reviewed the outpatient charts of all patients with preeclampsia who received prenatal care at our clinics during the past 3 years. The 30 patients who met our criteria for preeclampsia were matched for age, race, and parity with normotensive control subjects. We found that in normal pregnancies, decline in blood pressure occurred before the second trimester and blood pressure remained low throughout gestation, rising insignificantly near term. Both systolic and diastolic blood pressures were significantly higher (p less than 0.05) for patients with preeclampsia than for normal control subjects beginning in the first trimester. This difference persisted throughout pregnancy and was also present at the 6-week postpartum visit (p less than 0.025).


[Comparison of surgical outcomes after different surgical approach for middle or lower thoracic esophageal squamous cancer].
To compare outcomes of left and right thoracic incision for middle and lower thoracic esophageal squamous cancer, and to determine reasonable surgical approach for thoracic esophageal squamous carcinoma. One hundred and twenty patients with middle or lower thoracic esophageal squamous cancer who received esophagectomy plus lymphadenectomy between January 2004 and December 2007 were divided into two groups including left(n=60) and right thoracic(n=60) approach. Clinical data were analyzed including the results of surgical resection, lymphadenectomy, postoperative complication, recurrence, and survival. The rate of surgical resection was 91.7%(55/60) in the left approach group and 95%(57/60) in the right approach group. There was no significant difference(P>0.05). But the average number of lymph nodes resected (4.60 vs. 8.32) and metastatic lymph nodes(0.57 vs. 1.33) were both significantly higher in the right approach group(P<0.01). There was no statistical difference in postoperative complications[26.7%(16/60) vs. 31.7%(19/60), P>0.05] between the two groups. However, the incidence of local recurrence was lower[43.3%(26/60) vs. 23.3%(14/60), P<0.05] in the right approach group than that in left-approach group. There was no significant difference in distant metastasis(P>0.05). The resection rate is comparable between left and right approach for thoracic esophageal cancer. However, it is easier to perform systemic lymphadenectomy via right thoracic approach and therefore the local recurrence is reduced and long-term survival improved.


Emergency response to stormwater contamination: A framework for containment and treatment.
This paper presents a Stormwater Emergency Response Framework (SERF) for use in the containment and treatment of stormwater runoff following a hazardous material release. The framework consists of four high level process steps and a decision tree. These resources are intended to assist stormwater managers in fulfilling their emergency response responsibilities within the United States' National Incident Management System. Robust hydraulic and watershed modeling may take weeks to months to develop for a contaminated site, whereas decisions made in the initial hours can have a significant impact on limiting contamination spread. Many web resources are publicly available to assist responders in visualizing stormwater runoff flow paths. A case study provided in this paper also demonstrates how simple calculations may be utilized to estimate peak flows and storage volumes necessary to respond to precipitation events immediately. These calculations are useful for decision makers' allocation of containment and treatment resources within the impacted area. This includes where to deploy available resources to minimize contamination risks to downstream communities and where supplemental resources from outside partners are urgently needed.


Characterization of orthopoxviruses isolated from feline infections in Britain.
The biological properties and genomes of orthopoxviruses isolated from cats in Britain were compared with strains of cowpox virus isolated from cows and their handlers. All the isolates tested produced haemorrhagic pocks and A-type inclusions on the CAM, but did not produce pocks above 40 degrees C. Thus the feline isolates behaved as typical strains of cowpox virus. Differences were found in the heat resistance of the virions and in the character of the A-type inclusion which did not correlate with the host from which the viruses were isolated. Analysis of the genomes with a variety of restriction endonucleases showed very close relationship between all the isolates and also failed to separate feline isolates from cowpox virus. However again minor differences, which may prove to be of epidemiological value were detected. We conclude that the orthopoxvirus currently isolated from domestic cats in Britain is cowpox virus and that there is no evidence that a feline variant or subspecies circulates in Britain.


Clinical and metabolic effects of two lipid emulsions on the parenteral nutrition of septic patients.
We compared the metabolic and clinical effects of two lipid emulsions, long-chain triacylglycerols (LCT) and a mixture of medium- and long-chain triacylglycerols (MCT/LCT), in septic patients. Both groups received total parenteral nutrition (TPN) with a solution enriched with branched-chain amino acids (BCAA). Seventy-two septic patients received TPN with MCT/LCT (group 1) or LCT (group 2). Before starting TPN (basal) and 10 d after (final), various parameters were evaluated. Twenty-six subjects in each group completed the study. Both groups showed an increase in cholestasis enzymes, with no significant changes in lipid parameters. The rise of retinol-binding protein and the recovery of nitrogen balance were significantly greater in group 1. A multivariate analysis of nutritional markers and catabolic parameters showed a better evolution in group 1 (P = 0.002). The MCT/LCT group exhibited a significant increase of insulin levels. Overall mortality and length of stay in the intensive care unit were not affected by the lipid emulsion. In septic patients who received TPN with a solution enriched with BCAAs, the use of an emulsion containing MCT provided them with a greater recovery of their nutrition status than the traditional LCT formula, without influencing the outcome.