Functional Diversity of Macropinocytosis.
Eukaryotic cells are capable of internalizing different types of cargo by plasma membrane ruffling and forming vesicles in a process known as endocytosis. The most extensively characterized endocytic pathways are clathrin-coated pits, lipid raft/caveolae-mediated endocytosis, phagocytosis, and macropinocytosis. Macropinocytosis is unique among all the endocytic processes due to its nonselective internalization of extracellular fluid, solutes, and membrane in large endocytic vesicles known as macropinosomes with unique susceptibility toward Na+/H+ exchanger inhibitors. Range of cell types capable of macropinocytosis and known to play important role in different physiological processes, which include antigen presentation, nutrient sensing, migration, and signaling. Understanding the physiological function of macropinocytosis will be helpful in filling the gaps in our knowledge and which can be exploited to develop novel therapeutic targets. In this chapter, we discuss the different molecular mechanisms that initiate the process of macropinocytosis with special emphasis on proteins involved and their diversified role in different cell types.


Reconnaissance soil geochemical survey of Gibraltar.
The extreme density of population of Gibraltar, situated at the southern tip of Spain, exerts considerable pressure on land use and thus future planning is of utmost importance. An initial reconnaissance soil geochemical survey of Gibraltar was based on 120 surface samples (0-15 cm) taken from a wide range of exposed, either bare soil or vegetated sites, to provide the optimum geographical distribution. The 'total' elemental concentrations of 26 elements (Li, Na, K, Be, Mg, Ca, Sr, Ba, Al, La, Ti, V, Cr, Mo, Mn, Fe, Co, Ni, Cu, Ag, Zn, Cd, Pb, P, S, As) were determined by nitric/percholric acid digestion followed by inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. The reconnaissance data shows that the spatial distribution of various elements depended on previous and present land use. Most elements (Ca, Cr, Mg and Mn excluded) exhibited relatively high concentrations in civilian and natural soils. Trends have been established for many elements, and concentrations exceeding guideline values have been found in certain areas of Gibraltar. This reconnaissance of Gibraltar is at present being followed by a more detailed baseline geochemical survey, which will establish the extent and magnitude of the variations in major and trace elements in soils and dusts, assess the impact of industrial, commercial and urban development on the geochemical landscape and to make recommendations concerning sustainable development.


Characteristics of self-management support (SMS) interventions and their impact on Quality of Life (QoL) in adults with chronic diseases: An umbrella review of systematic reviews.
To provide an overview of types and characteristics of self-management support (SMS) interventions in adults with chronic disease and to assess the impact on the patient reported outcome Quality of Life (QoL). An umbrella review of systematic reviews was conducted. We searched PubMed, Embase, Web of Science, CINAHL and the Cochrane Library from January 2016 to November 2020 for reviews on SMS interventions for chronic diseases, assessing the impact on the patient reported outcome QoL. Quality assessment was based on the JBI Critical Appraisal Checklist for Systematic reviews and Research Syntheses tool. 28 reviews were included. The extensive literature review revealed a variety of SMS interventions. The most frequently cited target group for the interventions were individuals with diabetes. Interventions primarily took place in the home setting. Interventional components that were often incorporated were education, eHealth and mHealth technologies, and coaching techniques. Telephone communication was regularly reported as a type of intervention follow-up. The impact on QoL was mixed and no firm conclusions can be drawn. However, our review revealed a beneficial effect of education. Interventions including educational components seem promising for supporting self-management and showed a beneficial effect on QoL. More research is needed to explore where, by whom and how interventions are ideally delivered.


Highly conductive Co3Se4 embedded in N-doped 3D interconnected carbonaceous network for enhanced lithium and sodium storage.
Traditional cobalt selenides as active materials in lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs) would suffer from drastic volume expansions and large stacking effects, leading to a low cycling stability. In this work, we utilized a facile template method for preparing Co3Se4@N-CN (CSNC) that encapsulated Co3Se4 nanoparticles into 3D interconnected nitrogen-doped carbon network (N-CN). Satisfactorily, it possesses excellent cycling stability with enhanced lithium and sodium energy storage capacity. As an anode material in LIBs, CSNC exhibited a prominent reversible discharge performance of 1313.5 mAh g-1 after 100 cycles at 0.1 A g-1 and 835.6 mAh g-1 after 500 cycles at 1.0 A g-1. Interestingly, according to the analysis from cyclic voltammetry, the in-situ generated Se might provide extra capacity that leaded to a rising trend of capacity. When utilized as an anode in SIBs, CSNC delivered an outstanding capacity of 448.7 mAh g-1 after 100 cycles at 0.1 A g-1 and could retain 328.9 mAh g-1 (77.2% of that of 0.1 A g-1) even at a high current density of 5.0 A g-1. The results demonstrate that CSNC is a superior anode material in LIBs and SIBs with great promise. More importantly, this strategy opens up an effective avenue for the design of transition metal selenide/carbonaceous composites for advanced battery storage systems.


Ginsenosides in endometrium-related diseases: Emerging roles and mechanisms.
Ginsenosides, agents extracted from an important herb (ginseng), are expected to provide new therapies for endometrium-related diseases. Based on the molecular types of ginsenosides, we reviewed the main pharmacological effects of ginsenosides against endometrium-related diseases (e.g., endometrial cancers, endometriosis, and endometritis). The mechanism of action of ginsenosides involves inducing apoptosis of endometrium-related cells, promoting autophagy of endometrium-related cells, regulating epithelial-mesenchymal transition (EMT) in endometrium-related cells, and activating the immune system to kill cells associated with endometrial diseases. We hope to provide a theoretical foundation for the treatment of endometrium-related diseases by ginsenosides.


Differences in aortic vortex flow pattern between normal and patients with stroke: qualitative and quantitative assessment using transesophageal contrast echocardiography.
The flow in the aorta forms a vortex, which is a critical determinant of the flow dynamics in the aorta. Arteriosclerosis can alter the blood flow pattern of the aorta and cause characteristic alterations of the vortex. However, this change in aortic vortex has not yet been studied. This study aimed to characterize aortic vortex flow pattern using transesophageal contrast echocardiography in normal and stroke patients. A total of 85 patients who diagnosed with ischemic stroke and 16 normal controls were recruited for this study. The 16 normal control subjects were designated as the control group, and the 85 ischemic stroke patients were designated as the stroke group. All subjects underwent contrast transesophageal echocardiography (TEE), and particle image velocimetry was used to assess aortic vortex flow. Qualitative and quantitative analyses of vortex flow morphology, location, phasic variation, and pulsatility were undertaken and compared between the groups. In the control group, multiple irregularly-shaped vortices were observed in a peripheral location in the descending thoracic aorta. In contrast, the stroke group had a single, round, merged, and more centrally located aortic vortex flow. In the quantitative analysis of vortex, vortex depth, which represents the location of the major vortex in the aorta, was significantly higher in the control group than in the stroke group (0.599 ± 0.159 vs. 0.522 ± 0.101, respectively, P = 0.013). Vortex relative strength, which is the pulsatility parameter of the vortex itself, was significantly higher in the stroke group than in the control group (0.367 ± 0.148 vs. 0.304 ± 0.087, respectively, P = 0.025). It was feasible to visualize and quantify the characteristic morphology and pulsatility of the aortic vortex flow using contrast TEE, and aortic vortex pattern significantly differed between normal and stroke patients.


Pregabalin and Amitriptyline as Monotherapy or as Low-Dose Combination in Patients of Neuropathic Pain: A Randomized, Controlled Trial to Evaluate Efficacy and Safety in an Eastern India Teaching Hospital.
The main objective is to compare efficacy and safety of pregabalin and amitriptyline monotherapy with their low-dose combination in patients of neuropathic pain (NeuP). In this parallel-group, open-label interventional study at the Neurology Outpatient Department of Bankura Sammilani Medical College, a total of 147 patients were randomly allocated into three groups and were prescribed the following drugs - Group P (n = 42) pregabalin 150 mg once daily, Group A (n = 34), amitriptyline 25 mg once daily, and Group Z (n = 37) = pregabalin (75 mg) + amitriptyline (10 mg) as combination once daily. They were followed up after 4, 8, and 12 weeks. Efficacy was assessed by NeuP symptom inventory score (NPSI) and safety was assessed by treatment-emergent adverse events. Final assessment was done on 92 patients (P = 31, A = 31, Z = 30). Males were predominant (71.7%). NPSI score significantly decreased in every group from baseline (P < 0.0001). There was no difference of NPSI score between groups at any level of follow-up. Percentage of adverse drug reactions were maximum (44.9%) in amitriptyline monotherapy group and lowest in combined group. However, amitriptyline monotherapy was the cheapest treatment option among these three. Combining pregabalin and amitriptyline at low doses proved to be equally effective but more tolerable compared to individual higher dosage monotherapy. However, if tolerability is good, amitriptyline monotherapy can be an attractive choice in economically challenged group of patients.


Over-expression of the Zea mays phytoglobin (ZmPgb1.1) alleviates the effect of water stress through shoot-specific mechanisms.
Water deficit limits plant growth and development by interfering with several physiological and molecular processes both in root and shoot tissues. Through their ability to scavenge nitric oxide (NO), phytoglobins (Pgbs) exercise a protective role during several conditions of stress. While their action has been mainly documented in roots, it is unclear whether Pgb exercises a specific and direct role in shoot tissue. We used a Zea mays root-less system to assess how over-expression or down-regulation of ZmPgb1.1 influences the behavior of shoots exposed to polyethylene glycol (PEG)-simulated water deficit. Relative to their WT and ZmPgb1.1 down-regulating counterparts, PEG-treated shoots over-expressing ZmPgb1.1 exhibited a reduced accumulation of ROS and lipid peroxidation. These effects were ascribed to lower transcript levels of Respiratory Burst Oxidase Homolog (RBOH) genes encoding the ROS generating enzyme complex NADPH oxidase, and a more active antioxidant system. Furthermore, over-expression of ZmPgb1.1 attenuated the reduction in osmotic potential and relative water content experienced during water stress, an observation also demonstrated at a whole plant level, possibly through the retention of the expression of three aquaporins involved in water transfer and implicated in drought tolerance. Pharmacological treatments modulating NO and ethylene levels revealed that the ZmPgb1.1 action was mediated by ethylene synthesis and response, with NO acting as an upstream intermediate. Collectively we provide substantial evidence that ZmPgb1.1 exercises a direct role in shoot tissue, independent from that previously reported in roots, which confers tolerance to water stress.


A comprehensive review about immune responses and exhaustion during coronavirus disease (COVID-19).
Coronavirus disease (COVID-19) is a viral infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The infection was reported in Wuhan, China, in late December 2019 and has become a major global concern due to severe respiratory infections and high transmission rates. Evidence suggests that the strong interaction between SARS-CoV-2 and patients' immune systems leads to various clinical symptoms of COVID-19. Although the adaptive immune responses are essential for eliminating SARS-CoV-2, the innate immune system may, in some cases, cause the infection to progress. The cytotoxic CD8+ T cells in adaptive immune responses demonstrated functional exhaustion through upregulation of exhaustion markers. In this regard, humoral immune responses play an essential role in combat SARS-CoV-2 because SARS-CoV-2 restricts antigen presentation through downregulation of MHC class I and II molecules that lead to the inhibition of T cell-mediated immune response responses. This review summarizes the exact pathogenesis of SARS-CoV-2 and the alteration of the immune response during SARS-CoV-2 infection. In addition, we've explained the exhaustion of the immune system during SARS-CoV-2 and the potential immunomodulation approach to overcome this phenomenon. Video Abstract.


Preparing the health-care system to pay for new Alzheimer's drugs.
Biogen's announcement last fall that it will seek U.S. Food and Drug Administration approval for its Alzheimer's disease (AD) treatment, aducanumab, 7 months after the drug was declared a failure, buoyed patients and families, but put health payers and policymakers on alert. Whether aducanumab succeeds, other disease-modifying therapies for AD will follow, and the health-care system is unprepared for the reimbursement and access challenges. Novel AD therapies are much needed, but we cannot assume substantial cost offsets. With forethought and preparation, however, the health-care system can accommodate new AD drugs. First, we urge the use of cost-effectiveness of new Alzheimer's treatments as a starting point for setting value-based prices. Second, payments for new AD therapies should ideally incorporate a performance warranty, which helps apportion risk associated with initial therapy value estimates between drug manufacturers and payers. Third, we urge consideration of "subscription" payment agreements to address system affordability issues.


The Frequency and Topology of Pseudoorthologs.
Phylogenetics has long relied on the use of orthologs, or genes related through speciation events, to infer species relationships. However, identifying orthologs is difficult because gene duplication can obscure relationships among genes. Researchers have been particularly concerned with the insidious effects of pseudoorthologs-duplicated genes that are mistaken for orthologs because they are present in a single copy in each sampled species. Because gene tree topologies of pseudoorthologs may differ from the species tree topology, they have often been invoked as the cause of counterintuitive results in phylogenetics. Despite these perceived problems, no previous work has calculated the probabilities of pseudoortholog topologies or has been able to circumscribe the regions of parameter space in which pseudoorthologs are most likely to occur. Here, we introduce a model for calculating the probabilities and branch lengths of orthologs and pseudoorthologs, including concordant and discordant pseudoortholog topologies, on a rooted three-taxon species tree. We show that the probability of orthologs is high relative to the probability of pseudoorthologs across reasonable regions of parameter space. Furthermore, the probabilities of the two discordant topologies are equal and never exceed that of the concordant topology, generally being much lower. We describe the species tree topologies most prone to generating pseudoorthologs, finding that they are likely to present problems to phylogenetic inference irrespective of the presence of pseudoorthologs. Overall, our results suggest that pseudoorthologs are unlikely to mislead inferences of species relationships under the biological scenarios considered here.[Birth-death model; orthologs; paralogs; phylogenetics.].


Effects of multigenerational cadmium exposure of insects (Spodoptera exigua larvae) on anti-oxidant response in haemolymph and developmental parameters.
Biochemical and organismal indices of metal tolerance were studied in Spodoptera exigua exposed to a cadmium-contaminated diet for one or many (33 or 61) generations. Reduced and oxidised glutathione, protein thiols, total anti-oxidant capacity level, glutathione transferase activity, and Cd accumulation were assayed in the haemolymph of the last instar larvae. The cadmium concentration in the whole larval body as well as larval survival, larval duration time and last instar body weight were also measured. Elevated cadmium concentration in the whole body, higher mortality and longer duration of the larval stage in one-generation exposed insects in comparison with those exposed for many generations suggest that metal tolerance builds over time. For the larvae from multigeneration metal treatment, the higher cadmium concentration in larval haemolymph positively correlated with glutathione oxidation and total anti-oxidant capacity. One-generation exposed insects had lower metal concentration in haemolymph than did 33-generation exposed insects.


Psychological factors in the choice of psychiatry as a career.
A survey of psychiatrists and non-psychiatrists in a medical faculty examined questions bearing on two hypotheses, that psychiatrists choose their career either to heal themselves or to heal their families. The results provided some support for the psychiatrist as a "wounded healer". The findings did not appear to be an artifact of more psychiatrists having been in therapy. The results were the same whether or not psychiatrists specialized in psychotherapy.


Accuracy of subcostal two-dimensional echocardiography in prospective diagnosis of total anomalous pulmonary venous connection.
Since reparative surgery without cardiac catheterization has been advocated for certain lesions such as total anomalous pulmonary venous connection (TAPVC), it is important to assess the accuracy of two-dimensional (2-D) echocardiography in the prospective diagnosis of this lesion. Abandoning traditional cardiac catheterization and angiography would be justified only if all surgically relevant anatomic features could be consistently displayed noninvasively. Consequently, we reviewed our experience with TAPVC to determine the suitability of subcostal 2-D echocardiography as the sole prospective diagnostic tool. Over a 5-year period, of 2444 infants under 2 years of age who underwent subcostal 2-D echocardiography, 38 were diagnosed as having TAPVC as the only major cardiac defect. There were no false-negative or false-positive cases during the time of the study. Drainage sites were diagnosed correctly in 36 (95%). Of the five cases of mixed-type TAPVC, the second drainage site was missed by 2-D echocardiography in two cases.


Window Approach in Conventional Phototherapy to Protect Non-lesional Skin.
We propose the use of protective coverings-gloves, socks, or clothing, with windows cut out into them, to ensure that the phototherapy targets only the affected areas.


Inelastic electron scattering observation using energy filtered transmission electron microscopy for silicon -- germanium nanostructures imaging.
This paper presents a new technique using energy filtered TEM (EFTEM) for inelastic electron scattering contrast imaging of Germanium distribution in Si-SiGe nanostructures. Comparing electron energy loss spectra (EELS) obtained in both SiGe and Si single crystals, we found a spectrum area strongly sensitive to the presence of Ge in the range [50-100 eV]. In this energy loss window, EELS spectrum shows a smooth steeply shaped background strongly depending on Ge concentration. Germanium mapping inside SiGe can thus be performed through imaging of the EELS background slope variation, obtained by processing the ratio of two energy filtered TEM images, respectively, acquired at 90 and 60 eV. This technique gives contrasted images strongly similar to those obtained using STEM Z-contrast, but presenting some advantages: elastic interaction (diffraction) is eliminated, and contrast is insensitive to polycrystalline grains orientation or specimen thickness. Moreover, since the extracted signal is a spectral signature (inelastic energy loss) we demonstrate that it can be used for observation and quantification of Ge concentration depth profile of SiGe buried layers.


Infantile hypertrophic pyloric stenosis: the changing trend in treatment in a Danish county.
From 1950 to 1984, 679 patients were treated for infantile hypertrophic pyloric stenosis (IHPS) in the County of Funen, Denmark. Medical treatment was performed in 114 patients and pyloromyotomy in 565. A pyloric tumor was palpated in 80% and a barium meal examination was performed in 24% of the patients. A shift toward intravenous fluid and general anesthesia is seen during the study period. Complications occurred in 17% of medically treated patients and in 8% of surgically treated patients. Six deaths occurred among the medically treated and four among the surgically treated patients. During the study period, a shift toward centralization and surgical treatment took place.


A fractal analysis of cell images.
Methods of digital image analysis have been adapted to measure the fractal dimension of cellular profiles. The fractal dimension is suggested as a useful measure of the complexity of a contour. Three methods produce similar results when applied to constructed, near-ideal fractal figures. Comparison of the measurements for a variety of image types indicates the measurement accuracy in each case and may help in interpreting the results when applied to real, non-ideal cell images of unknown fractal dimension. Two of the methods are currently adopted as appropriate for use on neuronal contours. A correlation exists between the complexity of these contours and the magnitude of the estimated fractal dimension.


Efficient electroporation of liposomes doped with pore stabilizing nisin.
Liposomes have a long history as passive and active drug carriers. Recently, a few methods have been realized to control the release from liposomes, including heating, ultrasound and laser. We report on a new approach to drive release from liposomes using electric fields. Liposomes were manufactured containing a high concentration of (quenched) 5-6 carboxyfluorescein dye. Nisin, a well-known amphiphilic peptide lantibiotic that works by stabilizing pores formed in cell membranes, was mixed in solution inside or outside the liposomes. The liposomes were then electroporated using a range of voltages, and assayed for increases in fluorescence due to release of dye. Release was measured against positive and negative controls, with positive control release driven by a strong detergent. Our results demonstrate that the addition of nisin significantly reduces the electric field required to release the contents of liposomes, from 2000 V/m to approximately 200 V/m. This result proves that, in principle, electroporation (EP) of liposomes doped with small amounts of amphiphilic pore stabilizing peptides may be a practical means to drive release of liposomal contents in vivo. Drug delivery from liposomes doped with amphiphilic peptides using EP is feasible. This technique could be developed into a potent adjuvant to tumor ablation using irreversible EP.


Septations in chronic spinal cord injury cavities contain axons.
Human spinal cord injury (SCI) can result in progressive degeneration that may continue for many years and lead to the formation of highly septated cystic cavities. This hallmark feature has been reproduced in experimental models, but neither its pathogenesis nor clinically relevant features have been fully elucidated. Here, we show for the first time in a rodent model of chronic SCI that the septations spanning cavities contain axons.


Paediatric Emergency Department preparedness in Nigeria: A prospective cross-sectional study.
Paediatric emergency medicine (PEM) is poorly developed in low and middle-income countries. The magnitude of challenges facing Paediatric Emergency Departments (PEDs) in Nigeria has not been well described. This study aimed to assess paediatric emergency care preparedness across PEDs in Nigeria. This was a prospective cross-sectional study that utilized a self-administered questionnaire and a check list to assess three key domains (managerial, medication and equipment) in tertiary care PED facilities that were recruited across Nigeria. Preparedness scores and other institutional attributes were compared between zones and regions. Thirty-four tertiary-level PEDs across Nigeria were included. The mean number of patient visits over the 30-day period prior to data collection was 253.2 (±261.2). The mean (SD) managerial, medication and equipment performance scores of the included PEDs were 42.9% (±14.3%), 50.7% (±22.3%) and 43.9% (±11.8%) respectively. The mean (SD) total performance score was 46.9% (±15.3%). Only 13 PEDs had a total performance score of >50%. There was a statistically significant higher mean equipment score (p = 0.029) in the Southern region (47.6 ± 3.1) compared to the Northern region (38.9 ± 2.3) of the country. This study reports a global but remediable deficiency in emergency care preparedness amongst PEDs in tertiary care facilities in Nigeria. This study highlights the need for training of PED managers in basic and advanced life support and for the improvement in medication and equipment procurement across Nigeria.


Preoperative multiple endocrine neoplasia type 1 diagnosis improves the surgical outcomes of pediatric patients with primary hyperparathyroidism.
Primary hyperparathyroidism (PHPT) is uncommon in children. The surgical management of PHPT in children has evolved over the past two decades. A retrospective study of patients who underwent parathyroidectomy for PHPT diagnosed at age < 18 years and managed at a tertiary referral center for endocrine and familial disorders. Thirty-eight patients met eligibility criteria (1981-2012). Median age at PHPT diagnosis was 15 years. Two-thirds of patients were symptomatic (68%, n=26), most commonly from nephrolithiasis. Twenty-six (68%) patients underwent a standard cervical exploration while 32% underwent a focused unilateral parathyroidectomy. Multiple endocrine neoplasia type 1 (MEN1) was diagnosed preoperatively in 22/26 patients. Patients with a preoperative diagnosis of MEN1 were more likely to undergo a complete initial operation (≥ 3 gland parathyroidectomy with transcervical thymectomy, 13/22, 59% vs. 0/4, 0%; P=0.03) and less likely to have recurrent disease (10/22, 45% vs. 3/4, 75%; P<0.001) during follow up than patients diagnosed postoperatively. Children with PHPT should raise suspicion for MEN1. Preoperative MEN1 evaluation helped guide the extent of initial parathyroidectomy and was associated with lower rates of recurrence in sporadic and familial PHPT in pediatric patients. Management should occur at a high volume center with experienced clinicians and genetic counseling services.


Role of hexokinase in controlling the glucose metabolism flux: a study of its flux control coefficient in different tissues.
Flux control coefficients of hexokinase for glucose metabolism in different rat tissues have been determined, showing that the hepatocyte cytosolic hexokinase is the only one which plays an important role in the control of the glucose-input flux studied among the different tissues. Explanation of these results are given in terms of the kinetics features of hexokinase and the metabolic role of glucose in these tissues.


Systematic Genetic Analysis of the SMPD1 Gene in Chinese Patients with Parkinson's Disease.
To examine the association between the sphingomyelin phosphodiesterase 1, acid lysosomal (SMPD1) gene, and Parkinson's disease (PD) in Han Chinese from Central South part of Mainland China, we performed systematic genetic analysis in 502 Chinese Han patients with PD and 637 gender-, age-, and ethnicity-matched normal controls from Central South part of the Mainland China. We identified 11 single nucleotide variants and Leu-Ala (Val) repeat variants in the SMPD1 gene in our large cohort. Two novel missense variants, c.638A > C (p.H213P) and c.1673T > C (p.L558P), and a rare known missense variant, c.1805G > A (p.R602H, rs370129081), were identified in three sporadic PD cases. None of these three variants were observed in controls. Additionally, case-control analysis showed association between Leu-Ala (Val) repeat variants in SMPD1 and Chinese Han patients with PD (P = 0.015, χ (2) = 8.451). Our data provide supportive evidence that some genetic variants in SMPD1 increase the risk of PD in the Chinese Han population.


[Characterisation of a CTX-M-15-producing Shigella sonnei in a Spanish patient who had not travelled abroad].
One hundred and seven Shigella spp. strains were isolated in our laboratory during the years 2000 to 2010. One Shigella sonnei harboured the genes that coded the β-lactamases TEM-1 and CTX-M-15, identifying the structure, ISEcp1+bla(CTX-M-15)+orf477, in their genetic environment. The strain also carried a class 2 integron with the gene cassettes dfrA1+sat+aadA1. A plasmid group IncI1 ST31 (CC-31) was detected and its mobilization by conjugation was demonstrated. We describe for the first time a S. sonnei strain producing a CTX-M-15 β-lactamase recovered from a Spanish patient who had not travelled abroad.


A variant peptide of buffalo colostrum β-lactoglobulin inhibits angiotensin I-converting enzyme activity.
β-lactoglobulin is a rich source of bioactive peptides. The LC-MS separated tryptic peptides of buffalo colostrum β-lactoglobulin (BLG-col) were computed based on MS-MS fragmentation for de novo sequencing. Among the selected peptides (P1-P8), a variant was detected with methionine at position 74 instead of glutamate. The sequences of two peptides were identical to hypocholesterolemic peptides whereas the remaining peptides were in accordance with buffalo milk β-lactoglobulin. Comparative sequence analysis of BLG-col to milk β-lactoglobulin was carried out using CLUSTALW2 and a molecular model for BLG-col was constructed (PMDB ID-PM0076812). The synthesized variant pentapeptide (IIAMK, m/z-576 Da) was found to inhibit angiotensin I-converting enzyme (ACE) with an IC(50) of 498 ± 2 μM, which was rationalized through docking simulations using Molgrow virtual docker.


Allelic loss on chromosomes 8 and 9 correlates with clinical outcome in locally advanced clear cell carcinoma of the kidney.
We correlated allelic loss on chromosomes 8p, 9p and 14q with clinical outcome in locally advanced conventional renal cell carcinoma. We analyzed radical nephrectomy specimens from 72 stage P3N0 conventional renal cell carcinomas by microsatellite loss of heterozygosity (LOH) analyses directed at chromosomes 3p, 8p, 9p and 14q (2 primers per chromosome). All patients were treated with surgery only. LOH results were correlated with disease-free survival using the Kaplan-Meier method. We detected LOH on chromosome 3p in 60 of 64 (94%), on chromosome 8p in 19 of 59 (32%), on 9p in 21 of 67 (31%) and on 14q in 18 of 70 (26%) informative cases. Of the 72 patients 24 (33%) had recurrence during followup. On univariate analysis patients with tumors demonstrating LOH on chromosomes 8p and 9q were at high risk for recurrence (p = 0.01). The correlation of recurrence with LOH approached significance for the individual chromosomes 8p and 9p (p = 0.10 and 0.14, respectively). No correlation was observed of LOH on chromosome 14q with recurrence (p = 0.42). The correlation of tumor grade with risk of relapse also approached significance (p = 0.12). On multivariate analysis LOH on chromosome 8p was a more powerful predictor of recurrence than tumor grade. When combinations of LOH on chromosomes were tested, LOH on chromosomes 8p and 9p was the most powerful predictor of recurrence (p = 0.006). LOH on chromosomes 8p or 9p may provide prognostic significance in patients with locally advanced renal cell carcinoma.


Genomic epidemiology of the Los Angeles COVID-19 outbreak and the early history of the B.1.43 strain in the USA.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused global disruption of human health and activity. Being able to trace the early outbreak of SARS-CoV-2 within a locality can inform public health measures and provide insights to contain or prevent viral transmission. Investigation of the transmission history requires efficient sequencing methods and analytic strategies, which can be generally useful in the study of viral outbreaks. The County of Los Angeles (hereafter, LA County) sustained a large outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To learn about the transmission history, we carried out surveillance viral genome sequencing to determine 142 viral genomes from unique patients seeking care at the University of California, Los Angeles (UCLA) Health System. 86 of these genomes were from samples collected before April 19, 2020. We found that the early outbreak in LA County, as in other international air travel hubs, was seeded by multiple introductions of strains from Asia and Europe. We identified a USA-specific strain, B.1.43, which was found predominantly in California and Washington State. While samples from LA County carried the ancestral B.1.43 genome, viral genomes from neighboring counties in California and from counties in Washington State carried additional mutations, suggesting a potential origin of B.1.43 in Southern California. We quantified the transmission rate of SARS-CoV-2 over time, and found evidence that the public health measures put in place in LA County to control the virus were effective at preventing transmission, but might have been undermined by the many introductions of SARS-CoV-2 into the region. Our work demonstrates that genome sequencing can be a powerful tool for investigating outbreaks and informing the public health response. Our results reinforce the critical need for the USA to have coordinated inter-state responses to the pandemic.


Pedagogical Strategies for the Enhancement of Medical Education.
Clearly, memory and learning are essential to medical education. To make memory and learning more robust and long-term, educators should turn to the advances in neuroscience and cognitive science to direct their efforts. This paper describes the memory pathways and stages with emphasis leading to long-term memory storage. Particular stress is placed on this storage as a construct known as schema. Leading from this background, several pedagogical strategies are described: cognitive load, dual encoding, spiral syllabus, bridging and chunking, sleep consolidation, and retrieval practice.


Increase in the cholinergic cardiac plexus in sympathetically aneural chick hearts.
Embryonic chick hearts were made sympathetically aneural by removal of premigratory neural crest over somites 10-20. The cholinergic cardiac plexus was assessed at 12 to 15 days of incubation using morphological and biochemical techniques. The cholinergic innervation to the heart was increased by 50 to 100% due to both hypertrophy and hyperplasia of the ganglion cells as well as their terminals. The additional cells were an expansion of the normal population of cholinergic neurons in the heart rather than from some extra source. The expanded population of neurons did not express an adrenergic phenotype in response to the absence of adrenergic cardiac innervation.


A Scoping Review on Arginine in Caries Prevention.
Emerging science on arginine or arginine formulations has driven the need to examine the research in the field. The scoping study objectives were (1) to identify the extent, range, and type of evidence on the role of arginine or arginine formulations in caries prevention and (2) to explore the future scope of research on arginine-containing caries-preventive agents. A systematic search was performed in PubMed, Scopus, and Web of Science. In vitro studies, clinical trials, narrative reviews, systematic reviews and or meta-analysis, and umbrella reviews or meta-evaluation examining arginine or arginine formulations for caries prevention were included. The data-charting process involved extracting variables followed by evidence synthesis. Arginine variants investigated up to date were discussed to explore future scope of research. Thirty-nine articles were included for review from 105 identified citations comprising of in vitro studies, clinical trials, and reviews. Most articles studied 1.5% arginine-fluoride toothpaste. Most studies were from Asia, followed by North America, with fewest studies from Europe and South America. Arginine or arginine formulations demonstrated a superior caries-preventive effect compared with their matched controls (including fluorides); however, the evidence is with high risk of bias. Until now, three arginine variants have been investigated with l-arginine monohydrochloride as the least explored variant. The evidence on the caries-preventive effect of arginine or arginine formulations has a high risk of bias. High-quality clinical trials are needed to assess the caries-preventive potential of arginine in commercial formulations. The role of l-arginine monohydrochloride in caries prevention can further be explored by incorporating in self-applied and professionally applied caries-preventive agents.


Comparison of intravaginal 6.5mg (0.50%) prasterone, 0.3mg conjugated estrogens and 10μg estradiol on symptoms of vulvovaginal atrophy.
The objective is to compare the effect of intravaginal dehydroepiandrosterone (DHEA, prasterone), conjugated equine estrogens (CEE) and estradiol (E2) on moderate to severe dyspareunia and/or vaginal dryness. In a review of available data, independent prospective, randomized, double-blind and placebo-controlled Phase III 12-week clinical trials involved daily administration of 6.5mg (0.50%) prasterone, daily (21days on/7days off) 0.3mg CEE, twice weekly 0.3mg CEE or 10μg E2 daily for 2 weeks followed by twice weekly for 10 weeks. Vulvovaginal atrophy (VVA) symptoms were evaluated by questionnaires. The total severity score of dyspareunia decreased from baseline by 1.27 to 1.63 units with prasterone treatment, 1.4 with CEE and 1.23 in one statistically significant study with E2 (combined symptoms). Decreases over placebo ranged from 0.35 to 1.21 with prasterone, 0.7 to 1.0 with CEE and 0.33 for the E2 study. The total decreases in vaginal dryness severity ranged from 1.44 to 1.58 units for prasterone, 1.1 unit for CEE and 1.23 unit for E2. The decreases over placebo of vaginal dryness intensity ranged from 0.30 to 0.43 unit for prasterone, 0.40 unit for CEE and 0.33 for the E2 study with combined symptoms. Daily 6.5mg (0.50%) prasterone appears to be at least as efficacious as 0.3mg CEE or 10μg E2 for treatment of the VVA symptoms. In summary, the beneficial effects on the VVA symptomatology can be obtained by the addition of a small amount of intravaginal prasterone to compensate for the low serum concentration of prasterone observed in the majority of women after menopause without concerns about systemic effects.


PbII-catalyzed transformation of aromatic nitriles to heptanitrogen anions via sodium azide: a combined experimental and theoretical study.
Under hydrothermal conditions, an open-chain N7 3- anion stabilized in a metal-organic framework (MOF) was achieved for the first time via the in situ reaction of 4-fluorobenzonitrile and sodium azide with Pb2+ ion as catalyst. The anion with C 2h symmetry in the MOF was studied by FT-IR, single-crystal XRD and theoretical calculations. Thermal analysis results demonstrated the stability of the anion in the MOF below 430 °C and a high energy content of 8.61 kJ g-1. The anion is also a good reducing agent. It can easily react with basic KMnO4 solution. Moreover, the present study indicates that the Pb2+ ion activates the azide rather than nitrile in the in situ reaction of nitriles with azides to form polynitrogen and this mechanism is a distinct contradiction with the previous results in which the nitrile reacts with azide in the presence of transition metal ions. Our findings may open a new avenue towards the synthesis and capture of polynitrogen compounds.


The complete mitochondrial genome of the Chinese water snake Myrrophis (Enhydris) chinensis (Gray, 1842) (Reptilia: Homalopsidae).
Myrrophis (Enhydris) chinensis, also known as the Chinese water snake, has been used for medicinal purposes, such as the treatment of ailments involving fever, headache, and joint pain. The complete mitochondrial genome of M. chinensis was assembled using next-generation sequencing. The mitochondrial genome was 17,302 bp in length and contained 37 genes, including 13 protein-coding, 22 transfer RNA (tRNA), 2 ribosomal RNA genes, and 2 non-coding control regions (D-loop). The light chain of replication origin was found between tRNA-Asn and tRNA-Cys in the WANCY gene cluster, which is consistent with published mitogenomes of Homalopsidae. The phylogenetic tree supported the monophyly of Homalopsidae species and implied that M. chinensis is the closest related species to Myanophis thanlyinensis. The mitochondrial genome of M. chinensis provides fundamental data for exploring mitochondrial genome evolution in snakes (Homalopsidae).


Efficacy vs. effectiveness research in psychotherapy: implications for clinical hypnosis.
Empirically supported therapy (EST) has become a major focus and trend for mental health practice. When hypnosis is involved, this may mean satisfying a standard that is entirely too narrow in its emphasis. In this article "efficacy"-based research in clinical practice is contrasted with "effectiveness" -focused research, and they are discussed from the perspective of hypnosis. When clinicians can consider trans-theoretical factors as well as those that are treatment-enhancing, possibilities for improved treatment outcome increase. The "effectiveness" perspective also serves as a counter point for hypnosis in contrast with the dubious efficacy-based gold standard currently proposed for therapy in general, and hypnosis in particular.


Limbic system, basal ganglia, and dopaminergic neurons. Executive and regulatory neurons and their role in the organization of behavior.
Mesencephalic dopaminergic neurons appear to be involved in the organization of the behavioral response. They seem to facilitate the functioning of the integrative structures they innervate and to have a coordinated functioning, thus regulating the information transfer between these structures. In the present paper these two aspects have been investigated by behavioral and neurochemical approaches. Experimental studies were focused on the dopaminergic innervation of the nucleus accumbens.


The secrets of successful staffing. Focus on hiring the right people, providing a good environment and letting employees know you care.
Competent medical providers? That's a given. Success also hinges on the right support staff. Here's how to find them--and keep them.


Report on evaluation of hydron film as burn wound dressing.
Hydron Burn Dressing, an amalgam of Polyethylene Glycol-400, and Polyhydroxyethyl methacrylate formed directly on the burn wound has been used in 50 cases with comparable control areas on the same patients which were managed by Polybactrin spray and exposure. The 4-layer film was found to be easily applicable in indoor patients and was pain-free during application and reduced pain after application in superficial burns. It was found to be translucent, pliable, less liable to crack and did not peel off once dried. The rate of infection was found to be 12.5 per cent more than the controls but the healing time was shorter by 2.8 days. Patient's comfort and compliance was better than the scab of the control areas.


Oxidative damage, aging and anti-aging strategies.
The last two decades brought remarkable insight into the nature of normal aging in multicellular organisms. However, we are still far away from realizing extension of maximum lifespan in humans. An important modulator of lifespan is oxidative damage induced by reactive species, such as reactive oxygen species (ROS). Studies from yeast, Caenorhabditis and Drosophila primarily focused on (1) reduced generation or (2) elimination of ROS but have two principal shortcomings: (1) dietary restriction and single gene mutations are often associated with physiological impairments and (2) overexpression of components of the antioxidant system extend lifetime only under stress-induced conditions. Recent results from Drosophila indicate the involvement of an endogenous repair and elimination system for oxidatively damaged proteins in the process of aging. This system includes methionine sulfoxide reductase A (MSRA) and the carbonyl reductase Sniffer, the protein-ubiquitin ligase Parkin and the chaperone Hsp22. In this review we summarize different anti-aging strategies and discuss a synergistic interaction between protection against free radicals and specific repair/elimination of oxidative damage in lifespan extension primarily using the model system Drosophila. To achieve lifespan extension, available experiments are often methodically grouped into (1) caloric restriction, (2) single gene mutation, and (3) overexpression of genes. Here we summarize different strategies by a more causal classification: (1) prevention of ROS generation, (2) reducing free ROS level, and (3) repair and elimination of ROS-damaged proteins.


Photoacoustic generation for a spherical absorber with impedance mismatch with the surrounding media.
Pressure generation in a spherical absorber due to energy deposition from pulsed lasers is studied. For a variety of conditions, analytical solutions are derived that allow quick computation of exact results. For the special case of identical acoustic impedance, the pressure transient spreads to the surrounding medium by a single compressive pulse followed by a tensile pulse at the end of illumination. For the general case of impedance mismatch, the pressure transient is in the form of a series of dampened compressive and tensile pressure pulses. In this paper both the amplitude ratio and the sign of consecutive pressure pulses are determined analytically, and are shown to be dependent upon the impedance mismatch. For laser pulses of duration much less than the absorber's characteristic oscillation time, a stress confinement limit is reached for most of the absorber, but a sharp tensile stress in the core region of the sphere is predicted. This region of high stress is defined by r < or =r(c), and we show that r(c) is proportional to the laser pulse duration tau(0). Upon further shortening of the laser pulse duration, the strength of this tensile stress continues to increase while its spatial distribution is sharpened. This observation has relevance to a number of experiments where laser-induced pressure transients cause the absorber to fracture.


Heavy metal distribution in chicks of two heron species from Korea.
This study presents concentrations of iron, manganese, zinc, copper, lead, and cadmium in tissues of black-crowned night heron (Nycticorax nycticorax) (n = 8) and grey heron (Ardea cinerea) (n = 9) chicks from Pyeongtaek heronry, Gyeonggi-do, Korea, 2001. Iron (respectively, 45.8 +/- 24.0 microg/wet g, 155 +/- 123 microg/wet g), zinc (38.3 +/- 5.34 microg/wet g, 50.9 +/- 14.0 microg/wet g), and copper (9.93 +/- 2.26 microg/wet g, 30.2 +/- 12.9 microg/wet g) concentrations in feathers, manganese concentrations in livers (3.26 +/- 0.68 microg/ wet g, 1.50 +/- 0.58 microg/wet g), kidneys (1.43 +/- 0.27 microg/wet g, 0.84 +/- 0.34 microg/wet g), and bones (1.34 +/- 0.50 microg/wet g, 3.17 +/- 1.31 microg/wet g) were different between black-crowned night heron and grey heron chicks. Lead concentrations in bones (0.11 +/- 0.04 microg/wet g, 0.61 +/- 0.42 microg/wet g) and cadmium concentrations in liver (13.5 +/- 2.30 microg/wet kg, 10.3 +/- 1.59 microg/wet kg), kidney (6.61 +/- 2.54 microg/wet kg, 2.31 +/- 1.29 microg/wet kg), and muscle (5.25 +/- 5.91 microg/wet kg, 1.37 +/- 0.90 microg/wet kg) differed between chicks of the two heron species. The differences of heavy metal concentrations in tissues in herons and egrets were reported to other similar studies. Heavy metal concentrations for both heron species were at background levels. In both species, lead concentrations were higher in livers than in bones and cadmium concentrations were higher in livers than in kidneys. We suggest that it is not chronic exposure but acute exposure to lead and cadmium contamination around breeding site that leads to these observations. Therefore, lead and cadmium concentrations in tissues can be used as a bioindicator of acute local contamination.


Learning, teaching, and training in microsurgery: A systematic review.
Numerous microsurgical training techniques and materials have been developed to reduce animal use and training costs. This systematic review aimed to catalog the available microsurgery learning methods on non-living material in order to define an educational program. The PubMed database was searched for English and French articles related to the initial learning of microsurgery with inert, non-living, or digital material and containing the keywords "microsurgery", "non-living", "simulation" and "virtual reality". Among the 488 articles found, 82 were included. This work reports the main microsurgery learning supports. They were classified according to the material used: inert material, cadaveric animal tissues, human cadaver model, virtual reality, and digital technologies. The educational program proposes here is a two-step program that uses non-living material (basic and deepening) before progressing to living models. This initial learning phase teaches basic microsurgical skills (precision, tremor management, and magnification). Then, frequent home training sessions help to maintain the acquired skills. Ethical, organizational, and economic constraints limit access to animal models. Therefore, inert models seem to be ideal support for initial microsurgical learning. The multiplicity of models described makes it possible to achieve progressive learning depending on which models are available.


Closed chest catheter ablation of an accessory pathway in a patient with permanent junctional reciprocating tachycardia.
This report describes a 23 year old woman with a lifelong history of permanent junctional reciprocating tachycardia refractory to conventional antiarrhythmic medications who was successfully treated with closed chest, transvenous selective ablation of a posteroseptal bypass tract. Two 100 J (stored) direct-current shocks were delivered to the region of the os of the coronary sinus using a quadripolar catheter positioned in the coronary sinus. At a 2 month follow-up interval, the patient is asymptomatic without recurrence of the tachycardia. It is concluded that in patients with permanent junctional reciprocating tachycardia, selective catheter ablation of a posteroseptal accessory pathway is a feasible alternative to a difficult pharmacologic regimen or to ablative surgery.


Psychotropics and the Microbiome: a Chamber of Secrets….
The human gut contains trillions of symbiotic bacteria that play a key role in programming different aspects of host physiology in health and disease. Psychotropic medications act on the central nervous system (CNS) and are used in the treatment of various psychiatric disorders. There is increasing emphasis on the bidirectional interaction between drugs and the gut microbiome. An expanding body of evidence supports the notion that microbes can metabolise drugs and vice versa drugs can modify the gut microbiota composition. In this review, we will first give a comprehensive introduction about this bidirectional interaction, then we will take into consideration different classes of psychotropics including antipsychotics, antidepressants, antianxiety drugs, anticonvulsants/mood stabilisers, opioid analgesics, drugs of abuse, alcohol, nicotine and xanthines. The varying effects of these widely used medications on microorganisms are becoming apparent from in vivo and in vitro studies. This has important implications for the future of psychopharmacology pipelines that will routinely need to consider the host microbiome during drug discovery and development.


Monoclonal antibody recognized hemocyte subpopulations in juvenile and adult Lymnaea stagnalis: functional characteristics and lectin binding.
The mouse monoclonal antibody LS1 recognizes a membrane epitope present on circulating hemocytes of the gastropod mollusc Lymnaea stagnalis. In both juvenile and adult pond snails, LS1+ (LS1 positive) hemocytes have the morphology of immature cells. The percentage of LS1+ hemocytes is higher in juveniles (ca. 39%) than it is in adults (ca. 14%). Functional characteristics of LS1+ hemocytes and lectin binding to these cells were studied. In both age groups, the proliferative activity, as measured by the incorporation of deoxybromouridine, is much higher for LS1+ hemocytes than it is for LS1- (LS1 negative) cells. LS1+ hemocytes are phagocytically less active and have a lower lysosomal enzyme (peroxidase) content as compared to hemocytes that lack the epitope. Histochemical staining of the total population of circulating hemocytes shows that the lectins DBA, BS-l-A4 and BS-l-B4, PNA, SBA and ECA do not react with the hemocytes. LTA, APA, WGA, Con A and LCA bind to all hemocytes. RCA and STA recognize surface carbohydrate moieties present on subpopulations of hemocytes only. The LS1+ hemocyte population virtually lacks the carbohydrate residues recognized by STA, whereas the LS1- population never shows binding of RCA. Our results support the findings that the LS1 epitope is a membrane marker of less differentiated hemocytes in both juvenile and adult L. stagnalis. Furthermore, they suggest a correlation between the presence of the LS1 epitope and the absence of STA binding, whereas absence of the LS1 marker may correlate with the presence of a sugar recognized by RCA.


Thiamine is a substrate of organic cation transporters in Caco-2 cells.
The aim of this study was to characterize the intestinal absorption of thiamine, by investigating the hypothesis of an involvement of Organic Cation Transporter (OCT) family members in this process. [(3)H]-T(+) uptake was found to be: 1) time-dependent, 2) Na(+)- and Cl(-)-dependent, 3) pH-dependent, with uptake increasing with a decrease in extracellular pH and decreasing with a decrease in intracellular pH, 4) inhibited by amiloride, 5) inhibited by the thiamine structural analogues oxythiamine and amprolium, 6) inhibited by the unrelated organic cations MPP(+), clonidine, dopamine, serotonin, 7) inhibited by the OCT inhibitors decynium22 and progesterone. Moreover, the dependence of [(3)H]-T(+) uptake on phosphorylation/dephosphorylation mechanisms was also investigated and [(3)H]-T(+) uptake was found to be reduced by PKA activation and protein tyrosine phosphatase and alkaline phosphatase inhibition. In conclusion, our results are compatible with the possibility of thiamine being transported not only by ThTr1 and/or ThTr2, but also by members of the OCT family of transporters (most probably OCT1 and/or OCT3), thus sharing the same transporters with several other organic cations at the small intestinal level.


Orphan devices: yesterday is history; tomorrow is mystery: towards a European orphan device directive?
Regulatory and economic frameworks stimulated the research and development of orphan drugs, but very little has been done for devices necessary for the in-vivo diagnosis, prevention and treatment of life-threatening conditions with a low prevalence/incidence. A general public consultation in Europe has shown a positive attitude towards an "orphan device" directive. The United States of America have a Humanitarian Use Device exemption, but Europe is still waiting for such a stimulating framework. Post-marketing surveillance ("materio-vigilance") will be necessary for follow-up, patient-reported outcome measures (quality of life versus survival) needed and off-label use data available for patient-safety reasons. The marketing period for devices is shorter than for medicinal products. Incentives are necessary to stimulate research and development of such "orphan devices" especially when surgical intervention is the only option.


Gray and white matter brain abnormalities in first-episode schizophrenia inferred from magnetization transfer imaging.
Neuroimaging studies suggest that schizophrenia is associated with gray and possibly white matter changes. It is unclear whether these changes are present at illness onset or which brain structures are selectively affected. New imaging methods such as magnetization transfer imaging may be more sensitive than conventional volumetric imaging to the subtle structural brain changes in schizophrenia. High-resolution volumetric T1-weighted images and magnetization transfer images were acquired from 30 patients (29 with first-episode schizophrenia and 1 with schizophreniform psychoses) and 30 control subjects. Images were processed using voxel-based morphometry, which allows whole-brain analysis. Compared with controls, the magnetization transfer ratio (an index of signal loss derived from magnetization transfer imaging) was reduced bilaterally in the medial prefrontal cortex (right greater than left), insula (left greater than right), and white matter incorporating the fasciculus uncinatus (left greater than right) in the patient group. Analysis of the T1-weighted images did not reveal significant volumetric differences between patients and controls. Gray and white matter abnormalities are present in schizophrenia at illness onset. The magnetization transfer ratio is sensitive to these abnormalities, which cannot be explained by detectable atrophy in our patient group.


High density lipoproteins--correlation with cardiovascular disease in hemodialysis patients.
1) HDL levels are low in hemodialysis patients. 2) Lipid abnormalities do not correlate with the presence of CVD in hemodialysis patients. 3) Smoking may not effect blood lipid levels in hemodialysis patients. 4) Nandrolone decanoate may not play a role in CVD in hemodialysis patients. 5) Longer time on hemodialysis does not result in a decrease in triglyceride or increase in HDL levels.


The linear mitochondrial plasmid pClK1 of the phytopathogenic fungus Claviceps purpurea may code for a DNA polymerase and an RNA polymerase.
Plasmid pClK1, a linear mitochondrial plasmid of Claviceps purpurea, was completely sequenced. The sequence contains two long open reading frames (ORF1, 3291 bp; ORF2, 2910 bp), and at least four smaller ORFs. The potential polypeptide derived from ORF1 shows homology to the family B type DNA polymerases. The product of ORF2 has significant homology to the mitochondrial RNA polymerase of yeast and RNA polymerases from bacteriophages. ORF1 and ORF2 show homology to URF3 and URF1 of the maize plasmids S1 and S2, respectively. No homology to any published protein sequence was found for the smaller ORFs. The origin of the terminal protein attached to the 5' ends of pClK1 remains open; several alternatives for its origin are discussed. The sequence data as a whole confirm the virus-like character of pClK1 already postulated from structural properties. Thus pClK1 together with S plasmids of maize and several other linear plasmids make up a distinct class of DNA species of plants and fungi probably derived from a common virus-like ancestor.


Genetic and pharmacological inhibition of METTL3 alleviates renal fibrosis by reducing EVL m6A modification through an IGF2BP2-dependent mechanism.
N6 -methyladenosine (m6A) is of great importance in renal physiology and disease progression, but its function and mechanism in renal fibrosis remain to be comprehensively and extensively explored. Hence, this study will explore the function and potential mechanism of critical regulator-mediated m6A modification during renal fibrosis and thereby explore promising anti-renal fibrosis agents. Renal tissues from humans and mice as well as HK-2 cells were used as research subjects. The profiles of m6A modification and regulators in renal fibrosis were analysed at the protein and RNA levels using Western blotting, quantitative real-time polymerase chain reaction and other methods. Methylation RNA immunoprecipitation sequencing and RNA sequencing coupled with methyltransferase-like 3 (METTL3) conditional knockout were used to explore the function of METTL3 and potential targets. Gene silencing and overexpression combined with RNA immunoprecipitation were performed to investigate the underlying mechanism by which METTL3 regulates the Ena/VASP-like (EVL) m6A modification that promotes renal fibrosis. Molecular docking and virtual screening with in vitro and in vivo experiments were applied to screen promising traditional Chinese medicine (TCM) monomers and explore their mechanism of regulating the METTL3/EVL m6A axis and anti-renal fibrosis. METTL3 and m6A modifications were hyperactivated in both the tubular region of fibrotic kidneys and HK-2 cells. Upregulated METTL3 enhanced the m6A modification of EVL mRNA to improve its stability and expression in an insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2)-dependent manner. Highly expressed EVL binding to Smad7 abrogated the Smad7-induced suppression of transforming growth factor-β (TGF-β1)/Smad3 signal transduction, which conversely facilitated renal fibrosis progression. Molecular docking and virtual screening based on the structure of METTL3 identified a TCM monomer named isoforsythiaside, which inhibited METTL3 activity together with the METTL3/EVL m6A axis to exert anti-renal fibrosis effects. Collectively, the overactivated METTL3/EVL m6A axis is a potential target for renal fibrosis therapy, and the pharmacological inhibition of METTL3 activity by isoforsythiaside suggests that it is a promising anti-renal fibrosis agent.


The relationship between preoperative needle electromyography findings and muscle power restoration after surgery in severe carpal tunnel syndrome patients.
Needle electromyography provides essential information about the functional aspects of the muscle. But little attention has been given in the literature to needle electromyography examinations in carpal tunnel syndrome. We examined the relationship between preoperative needle electromyography findings and functional recovery of the abductor pollicis brevis (APB) muscle in severe carpal tunnel syndrome patients. The subjects of this study were 49 patients, 58 hands, who fit the following 5 criteria: (1) idiopathic carpal tunnel syndrome; (2) pre-op MMT grade of the APB muscle was M0 or M1; (3) APB-CMAP (compound muscle action potential) was not evoked in a median nerve conduction study; (4) needle electromyography of the APB muscle had been done; (5) underwent carpal tunnel release only. The patients were divided into two groups according to the results of pre-op needle electromyography: voluntary motor unit potential of the APB muscle was evoked [MUP(+) group]or not [MUP(-) group]. We evaluated APB muscle strength at one year after surgery, and patient satisfaction and functional evaluations (CTSI-FS) at more than one year after. The APB muscle recovery rate to M3 or higher was 100% in the MUP(+) group, and 57% in the MUP(-) group. Patient satisfaction was also high and functional recovery was sufficient in the MUP(+) group. No patients requested a second opponensplasty. Our findings suggest that post-op restoration of thumb function relates to whether or not the MUP ofthe APB muscle is evoked. Single-stage opponensplasty may be unnecessary if the MUP of the APB muscle is; evoked. Needle electromyography is therefore useful in consideration for opponensplasty. Level Ⅲ, case-control study.


OK432 inhibits experimental hepatic metastasis of colon adenocarcinoma ACL-15 in F344 rats.
The effect of OK432 on hepatic metastasis, induced by inoculating 1 x 10(6) ACL-15 cells from a rat colon adenocarcinoma cell line into the ileocolic vein of male F344 rats, was investigated in this study. Metastases were detected 14 days after inoculation in the control rats, however, pretreatment 3 days prior to the tumor cell inoculation with an anti-asialoGM1 antibody, which eliminates natural killer (NK) cell activity in vitro, increased the number of hepatic metastases, shortened the survival time, and decreased the NK activity of the nonparenchymal liver cells (NPC). In contrast, pretreatment with OK432 2 days prior to tumor inoculation significantly decreased the number of hepatic metastases, prolonged the survival time, and augmented the NK activity of the NPC, although treatment with OK432 3 or 7 days after inoculation did not decrease the number of hepatic metastases. Moreover, NPC from the OK432-pretreated rats had a marked antitumor effect against ACL-15 cells in the Winn's neutralization test. The results of this study indicate that pretreatment with OK432 before tumor cell inoculation inhibits hepatic metastasis in this experimental model, possibly by augmentating liver-associated NK activity.


Potent inhibitors of the MAP kinase p38.
The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines TNF-alpha and IL-1. We have developed a novel series of potent p38 inhibitors that could lead to new methods of treatment for inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease.


Release of [3H]acetylcholine from rat hippocampal slices: effect of septal lesion and of graded concentrations of muscarnic agonists and antagonists.
To establish the existence and sensitivity of presynaptic muscarinic receptors on central cholinergic neurons, the electrically evoked release of [3H]ACh from hippocampal slices was measured after medial septal lesion or in the presence of graded concentrations of muscarinic agonists and antagonists. One week after septal lesion, the evoked release of [3H]ACh was abolished, indicating that septo-hippocampal cholinergic fibres are the source of this release. The muscarinic agonists, Oxotremorine, carbamylcholine and arecoline reduced the rate of evoked release of [3H]ACh with an ED50 similar to the ED50 required to displace specific [3H]quinuclidinyl benzilate (QNB) binding as found by Yamamura and Snyder. However, the antagonists QNB, antropine and scopolamine were 10 times weaker in increasing the rate of [3H]ACh release than in displacing [3H]QNB binding. Results suggest that the lower affinity of muscarinic antagonists to presynaptic receptors prevents the demonstration of the specific labelling of these receptors with [3H]QNB.


Quantum dot-induced epigenetic and genotoxic changes in human breast cancer cells.
The staggering array of nanotechnological products, found in our environment and those applicable in medicine, has stimulated a growing interest in examining their long-term impact on genetic and epigenetic processes. We examined here the epigenomic and genotoxic response to cadmium telluride quantum dots (QDs) in human breast carcinoma cells. QD treatment induced global hypoacetylation implying a global epigenomic response. The ubiquitous responder to genotoxic stress, p53, was activated by QD challenge resulting in translocation of p53, with subsequent upregulation of downstream targets Puma and Noxa. Consequential decrease in cell viability was in part prevented by the p53 inhibitor pifithrin-alpha, suggesting that p53 translocation contributes to QD-induced cytotoxicity. These findings suggest three levels of nanoparticle-induced cellular changes: non-genomic, genomic and epigenetic. Epigenetic changes may have long-term effects on gene expression programming long after the initial signal has been removed, and if these changes remain undetected, it could lead to long-term untoward effects in biological systems. These studies suggest that aside from genotoxic effects, nanoparticles could cause more subtle epigenetic changes which merit thorough examination of environmental nanoparticles and novel candidate nanomaterials for medical applications.


Dopamine and cAMP-regulated phosphoprotein 32 kDa (DARPP-32) and survival in breast cancer: a retrospective analysis of protein and mRNA expression.
Dopamine and cAMP regulated phosphoprotein 32 kDa (DARPP-32) also known as phosphoprotein phosphatase-1 regulatory subunit 1B and encoded by the PPP1R1B gene is an inhibitor of protein phosphatase-1 and protein kinase A. DARPP-32 is expressed in a wide range of epithelial cells and some solid tumours; however, its role in breast cancer is only partially defined. DARPP-32 expression was determined using immunohistochemistry in two independent cohorts of early stage invasive breast cancer patients (discovery n = 1352; validation n = 1655), and 112 HER2 positive breast cancer patients treated with trastuzumab and adjuvant chemotherapy. PPP1R1B mRNA expression was assessed in the METABRIC cohort (n = 1980), using artificial neural network analysis to identify associated genes. In the discovery cohort, low nuclear expression of DARPP-32 was significantly associated with shorter survival (P = 0.041), which was independent of other prognostic variables (P = 0.019). In the validation cohort, low cytoplasmic and nuclear expression was significantly associated with shorter survival (both P = 0.002), with cytoplasmic expression independent of other prognostic variables (P = 0.023). Stronger associations with survival in oestrogen receptor (ER) positive disease were observed. In patients treated with trastuzumab, low nuclear expression was significantly associated with adverse progression-free survival (P = 0.031). In the METABRIC cohort, low PPP1R1B expression was associated with shortened survival of ER positive patients. Expression of CDC42 and GRB7, amongst others, were associated with PPP1R1B expression. This data suggests a role for DARPP-32 as a prognostic marker with clinical utility in breast cancer.


Topographic correspondence of contrast echocardiographic perfusion mapping and myocardial infarct extent after varying durations of coronary occlusion.
After acute coronary occlusion, the extent of dysfunction exceeds the extent of infarction by a variable amount. Contrast echocardiography has been shown to be a good predictor of the extent of acute infarction after permanent occlusion. We used hydrogen peroxide contrast echocardiography to study the temporal and topographic relationship between contrast enhancement and tissue viability during acute myocardial infarction in 32 dogs undergoing 1, 2, 3, or 4 hours of circumflex occlusion before reperfusion. To account for changes in collateral blood flow, contrast studies were performed by aortic root injection immediately before reperfusion. The area, circumference, and transmural extent of the region at risk in vivo by contrast echocardiography were statistically unchanged regardless of the duration of occlusion before reperfusion. Echo contrast defect analysis of the risk region predicted the area, circumference, and transmural extent of infarcts reperfused at 2 or more hours (r = 0.81, 0.84, 0.71, respectively). For the 1-hour occlusion group, contrast defect analysis predicted the circumference at risk but markedly overestimated the area and transmural extent of infarction. These data indicate that the circumferential extent of infarction can be identified by contrast echo and is fixed by 1 hour of occlusion. Infarction progression transmurally within the circumferential boundaries had nearly reached the transmural contrast extent by 2 hours of occlusion in this model. Assuming the development of a similar high contrast agent safe for human injection, aortic root contrast echocardiography could be useful to predict myocardium at risk of infarction early after occlusion. Late after occlusion it could be of value to predict the presence of still viable myocardial layers within the dysfunctional infarct region.


[The audible alarm on scopes, a tool for patients and caregivers].
Sound alarms on scopes alert the caregiver to a situation or event that he or she must take into account. Errors in thresholds, reading or interpretation of signals can lead to a significant number of "false sound alarms". Monitors are essential, but they also have deleterious effects on the caregivers because of the numerous sound stimulations.


Hypotension during induction of anaesthesia is neither a reliable nor a useful quality measure for comparison of anaesthetists' performance.
Identification of statistically reliable outcomes for comparison among anaesthetists is challenging. Time-weighted intraoperative mean arterial pressure <65 mm Hg (AUC 65 ) is associated with increased odds for myocardial damage. We explored retrospectively whether such hypotension before incision was statistically reliable for peer comparison. We retrieved electronic data between 2006 and 2015 at a tertiary care, academic hospital in the USA for patients at risk for myocardial damage (inpatient after surgery, ASA physical status ≥III, ≥50 yr of age, and case duration ≥60 min). We determined the percentage of anaesthetists comparable based on caseload and case-mix. The AUC 65 was compared amongst anaesthetists supervising ≥100 cases involving at-risk patients during the last 12 months. Only 14.1% [95% confidence interval (CI) 13.6-14.5%] of cases involved patients who were 'at risk' during the 10 yr study period. A yearly average of 49 ( sd 6) anaesthetists supervised ≥100 cases of any type, of whom only 52% (95% CI 47.1-56.0%) supervised ≥100 cases involving at-risk patients. Thus, nearly half the anaesthetists would have been excluded from peer comparison. During the last 12 months, there were two outliers among 34 evaluable anaesthetists ( P <0.05, controlling for false discovery). However, their contribution to total hypotension amongst cases for all patients was small, because hypotension was widely distributed (e.g. 80% of hypotension attributable to 61.8% of anaesthetists, 95% CI 59.8-63.7%). There was no relationship between the AUC 65 and propofol induction dose. The AUC 65 of time-weighted pre-incision hypotension is not a suitable metric for comparing anaesthetists. There were few at-risk patients, half the anaesthetists were not evaluable because of their case-mix and caseload, and hypotension was widely distributed.


The dynamic role of beta-catenin in synaptic plasticity.
In addition to its role in development and cell proliferation, β-catenin has been implicated in neuronal synapse regulation and remodeling. Here we review basic molecular and structural mechanisms of synaptic plasticity, followed by a description of the structure and function of β-catenin. We then describe a role for β-catenin in the cellular processes underlying synaptic plasticity. We also review recent data demonstrating that β-catenin mRNA and protein phosphorylation are dynamically regulated during fear memory consolidation in adult animals. Such alterations are correlated with a change in the association of β-catenin with cadherin, and deletion of the β-catenin gene prevents fear learning. Overall, the extant data suggest that β-catenin may function in mediating the structural changes associated with memory formation. This suggests a general role for β-catenin in synaptic remodeling and stabilization underlying long-term memory in adults, and possible roles for dysfunction in the β-catenin pathway in disorders of memory impairment (e.g. Alzheimer's Disease) and in disturbances in which emotional memories are too strong or resistant to inhibition (e.g. fear learning in Posttraumatic Stress Disorder). Further understanding of the β-catenin pathway may lead to better appreciation for the structural mechanisms underlying learning and memory as well as provide novel therapeutic approaches in memory related disorders. This article is part of a Special Issue entitled 'Anxiety and Depression'.


Epoxyalkanoyls as novel ACE inhibitors.
The epoxyalkanoyl derivatives were designed and synthesized as ACE inhibitors. Coupling of unsaturated carboxylic acids with amino acids and following epoxidation with dimethyldioxirane gave the epoxyalkanoyls with high yield. The inhibitory activity of synthesized compounds on angiotensin converting enzyme was IC50 values of 0.06-5.5 microM.


Characterisation of the flavour profile from Graciano Vitis vinifera wine variety by a novel dual stir bar sorptive extraction methodology coupled to thermal desorption and gas chromatography-mass spectrometry.
The aim of this work was to develop a new analytical technique for the study of the organoleptic compounds (flavour profile) of the Graciano Vitis vinifera wine variety. The cv. Graciano is a singular variety of red grapes with its origins in La Rioja and Navarra (northern Spain). This variety transfers an intense red colour, aroma and high acidity to musts and provides greater longevity and, consequently, a better capacity for ageing wine. A new dual-stir bar sorptive extraction approach coupled with thermal desorption (TD) and GC-MS has been used to extract the volatile and semivolatile compounds. In this extraction step, the optimal values for the experimental variables were obtained through the Response Surface Methodology (RSM). Full scan chromatogram data were evaluated with two deconvolution software tools, and the results were compared. The volatile and semivolatile components were identified with an MS match ≥80%. As a result, the flavour metabolome of the Graciano Vitis vinifera wine variety was obtained, and 205 metabolites were identified using different databases. These metabolites were grouped into esters, acids, alcohols, nitrogen compounds, furans, lactones, ketones, aldehydes, phenols, terpenes, norisoprenoids, sulphur compounds, acetals and pyrans. The majority of the metabolites observed had already been reported in the literature; however, this work also identified new, previously unreported metabolites in red wines, which may be characteristic of the Graciano variety.


Symptom Burden and End-of-Life Treatment Preferences in the Very Old.
End-of-life (EOL) treatment preferences among the very old (age 85+) may differ from preferences in younger aged populations because of high levels of symptom burden and disability and high risk of mortality. It is unclear if symptom burden or level of disability is more important for such preferences. To investigate whether distress from daily symptom burden was an independent correlate of EOL treatment preferences over two years of follow-up in people with median age 86 (participants) and 88 (reported by proxies) at baseline. The End of Life in Very Old Age is an ancillary study to the Health, Aging and Body Composition study. At baseline in Year 15 of Health, Aging and Body Composition, 1038 participants and 189 proxies reported levels of symptom distress every quarter, as well as 0-8 EOL treatment preferences elicited once each year. At baseline, the mean (SD) count of EOL treatment preferences was 4.2 (2.1) in participants, and 2.9 (2.3) in proxies. EOL treatment preference was not associated with symptom distress. By contrast, black race, male gender, and reported ease walking a quarter mile were independently associated with more aggressive EOL treatment preferences. Preferences for more aggressive EOL treatment were not related to daily symptom distress but were significantly more likely to be endorsed among those with better mobility, suggesting that disability is an independent predictor of EOL treatment preferences in the very old.


Transection rate at different areas of scalp during follicular unit extraction/excision (FUE).
Although the follicular unit excision/extraction (FUE) is regarded an easy procedure to perform, however, there are various factors which affect the outcome. The hair transection is dependent of various factors and the donor site characteristics affect largely. To know the difference in transection rate on various areas of scalp during FUE. The study was conducted in 10 patients undergoing FUE after obtaining informed consent. In each patient, 1 row was marked with intervening 1 cm2 . The row contained five boxes of 1 cm2 . Harvesting of FUs was performed using 0.9 mm serrated punch. The procedures were performed with the patient in supine position with the surgeon sitting on head side. The harvested FUs were checked under microscope. Any transection was calculated. All the data was collected and analyzed statistically. The total number of FUs and hair were more in center zone as compared to the sides. Whereas, the transection rate was lowest in the mid-occipital zone as compared to the sides. Similarly, the FUs: hair ratio was more in the sides 1:1.85 as compared to 1:1.62 in central zone. The right and left sides also showed some variations. The transection was more on right side (17.7%) of the patient as compared to the left side (16.3%) CONCLUSION: The hair transection was more on sides than in the mid-occipital area.


Design and synthesis of thiourea compounds that inhibit transmembrane anchored carbonic anhydrases.
A library of 32 novel glycoconjugate thiourea-bridged benzene sulfonamides have been synthesized from the reaction of glycosyl isothiocyanates with a panel of simple benzene sulfonamides comprising either a free amine or hydrazide. All compounds were investigated for their ability to inhibit the enzymatic activity of five human carbonic anhydrase (hCA) isozymes: hCA I, II and membrane-associated isozymes IX, XII and XIV. A physicochemical feature of the free sugar thioureido glycoconjugates was high water solubility (> 20 mg/mL), as well many of these compounds exhibited a desirable potency and CA isozyme selectivity profile. From this library several inhibitors displayed excellent potency-selectivity profiles for transmembrane anchored CAs over off-target CA I and II. These molecules provide potential dual-acting candidates for the development of inhibitors that target the extracellular CAs (IX, XII and XIV)-either directly as free sugars (membrane impermeable) or indirectly as acetylated prodrugs, becoming free sugars upon esterase hydrolysis.


Targeted Ablation Using Laser Nanosurgery.
Laser-mediated dissection methods have been used for many years to micro-irradiate biological samples, but recent technological progress has rendered this technique more precise, powerful, and easy to use. Today pulsed lasers can be operated with diffraction limited, sub-micrometer precision to ablate intracellular structures. Here, we discuss laser nanosurgery setups and the instrumentation in our laboratory. We describe how to use this technique to ablate cytoskeletal elements in living cells. We also show how this technique can be used in multicellular organisms, to micropuncture and/or ablate cells of interest and finally how to monitor a successful laser nanosurgery.


Tolerability of transvaginal ultrasonography as an ovarian cancer screening test.
To evaluate the acceptability of transvaginal ultrasonography as a screening tool. Prospective survey of women attending for screening within a randomised controlled trial. University Hospital in Teesside. 54 women completed a questionnaire immediately after their first transvaginal ultrasound scan. 52 of 54 (96%) questionnaires were suitable for full analysis. The women were unlikely to find the scan was painful, 47 vs three (p<0.001), or embarrassing 45 vs five (p<0.001). Women were more likely to find both a smear, 42 vs eight (p<0.001) and a mammogram, 47 vs two (p<0.001) was more uncomfortable than transvaginal ultrasonography. Transvaginal ultrasonography is an acceptable tool for screening for ovarian cancer. It is better tolerated than other screening tools such as cervical smear and mammography.


Bovine superoxide dismutase in Fanconi anaemia. Therapeutic trial in two patients.
Bovine superoxide dismutase (SOD) (Peroxinorm, Grünenthal Stolberg) was injected intramuscularly or subcutaneously in a daily dose of 4 mg over a period of six weeks into two patients with Fanconi anaemia. The effects (measured by the decrease of chromosome aberrations in blood lymphocytes and the increase in blood cells in venous blood) were evident but temporary. The hypothetical mode of action of SOD and the failure of a prolonged therapeutic effect are discussed.


Light people: Nobel Laureate Prof. Eric Betzig.
Super-resolution microscopy illuminated the hazy molecular world like a beacon, bringing significant changes to the fields of biology, optics and chemistry. Eric Betzig, who shared the 2014 Nobel Prize of Chemistry with Stefan Hell and William Moerner, is one of the inventors of this fantastic scientific tool. Working originally on near field optics, Dr. Betzig made a series of stunning achievements at Bell Labs before turning 35. Yet he quit, seemingly at the top of his game, to become a hands-on dad and joined the machinery business. Eventually, he missed science so much that he made a comeback and wowed everyone instantly with his work. He defies the conventional definition of "persistence" by demonstrating an alternative route to success. Plain-speaking and earnest, Dr. Betzig is sometimes honest to almost a fault, and always believes in doing practical things. He puts his heart and soul into everything he does, because he says he wants to truly live rather than simply pass through life. In science work, he is meticulous, yet he embraces risks and believes they can bring the best out of oneself. In life, he is a loving father who is always ready to take time from his busy research work to take his children to school or tennis lessons, and a caring teacher who never forgets to command the hard work of his postdocs. Please join us for a glimpse of the Nobel laureate Eric Betzig and his extraordinary life.


Recent advances in electric analysis of cells in microfluidic systems.
Microfluidics offers an ideal platform to integrate cell-based assays with electric measurements. The technological advances in microfluidics, microelectronics, electrochemistry, and electrophysiology have greatly inspired the development of microfluidic/electric devices that work with a low number of cells or single cells. The applications of these microfluidic systems range from the detecting of cell culture density to the probing of cellular functions at the single-cell level. In this review, we introduce the recent advances in the electric analysis of cells on a microfluidic platform, specifically related to the quantification and monitoring of cells in static solution, on-chip patch-clamp measurement, and examination of flowing cells. We also point out future directions and challenges in this field.


[Experimental study of hepatic bloodflow to the effect of cryoablation].
To investigate the bloodflow of hepetatic artery to the effect of cryoablation. Twenty dogs were divided into four groups randomly according to hepatic artery blood flow: completely occlusion of the hepatic artery(A), partial occlusion of the hepatic artery(B), increasing the hepatic artery blood flow(C) ,and no occlusion(D). Two areas of necrosis near portal hepatis (a)and far from it (b)were created in each of the 20 dog livers. Ultrasound was used to measure the blood flow. After cryoablation, the animals were euthanized, the livers were examined and the cryoablation areas were separated into two halves the maximum diameter of necrosis was assessed by vital staining for nicotinamide adenine dinucleotide (NADH) diaphorase and Triphenyl tetrazolium chloride (TTC) staining. The peak speed and volflow of hepatic artery from group A to group D measured by ultrasound were 0 cm/s and 0 mL/min, (22.8+/-0.6) cm/s and (31.4+/-0.9) mL/min, (99.6+/-1.6) cm/s and (70.4+/-1.5) mL/min and (69.5+/-0.7) cm/s and (52.6+/-1.2) mL/min, respectively. The mean longest diameter of ice-ball in areas a from group A to group D were (4.5+/-0.4) cm,(3.5+/-0.1) cm,(2.0+/-0.3) cm,(2.6+/-0.2) cm and the areas b were (4.6+/-0.3) cm,(3.6+/-0.2) cm,(1.9+/-0.1) cm,(2.6+/-0.2) cm; the mean longest necroseis diameter in TTC staining in areas a were (4.0+/-0.3) cm,(2.7+/-0.2) cm, (2.0+/-0.2) cm, (2.3+/-0.1) cm, and in areas b were (3.9+/-0.3) cm, (2.6+/-0.3) cm, (2.1+/-0.1) cm,(2.5+/-0.2) cm; the mean longest necroseis diameter in NADH staining in areas a were (4.1+/-0.4) cm,(2.6+/-0.2) cm,(2.1+/-0.2) cm,(2.3+/-0.3) cm, in areas b were (4.0+/-0.3) cm, (2.7+/-0.3) cm,(2.1+/- 0.1) cm,(2.4+/-0.2) cm. The bloodflow of hepetatic artery can affect the cryoablation rate. When the bloodflow increases, the cryoablation rate decreases.


Effects of an internal transcription unit and its orientation on retrovirus titre and expression.
Using the retroviral vector pMsp, constructs were produced with different coding sequences under the control of the Herpes simplex virus type 1 (HSV) thymidine kinase (tk) promoter, with the internal coding sequence in the same or reverse orientations with respect to long terminal repeat (LTR)-driven transcription and with or without an internal tk polyadenylation (polyA) signal. Following introduction of these constructs into ecotropic or amphotropic packaging cell lines by transfection or infection, it was found that, most consistently, those constructs in which the internal coding sequence/polyA signal component was inserted in the same orientation as LTR-driven transcription produced lower titres of virus than those in which this component was inserted in the reverse orientation. Also, in a construct containing a coding sequence in the same orientation as LTR-driven transcription, but lacking an internal polyA signal, virus titre was much greater than in the corresponding construct possessing the internal polyA signal. Additionally, although functional assays have previously demonstrated expression of the inserted sequences, transcription from the internal tk promoter was inefficient in all these constructs.


Purothionin from wheat endosperm reversibly blocks myogenic differentiation of chick embryonic muscle cells in culture.
Purothionin from wheat endosperm is a cysteine-rich, basic polypeptide of about 5000 Da, which modifies membrane permeability of cultured mammalian cells. This peptide was found to block fusion of chick embryonic muscle cells in culture but allows proliferation and alignment. A purothionin concentration of 6 micrograms/ml (1.2 microM) was necessary for the complete prevention of myotube formation. Under similar conditions, incorporation of [35S]methionine occurred normally but the synthesis of muscle-specific proteins including creatine kinase and acetylcholine receptor was strongly inhibited. In addition, purothionin blocked the uptake of 86Rb+, immediately after its addition to the cultured myoblasts. No such effects were found with the purothionin chemically modified with acetic or succinic anhydride. Thus, the basic residues in purothionin appear to be associated with the inhibition of myogenic differentiation. These results suggest that purothionin exerts its regulatory effect on the transition from proliferative to differentiative myoblasts by interfering with membrane permeability or intercellular contact and recognition, which are necessary for the initiation of muscle differentiation.


New approaches in the therapy of breast cancer--introduction.
Interaction of academic medical research centers with the pharmaceutical and biotechnology industries is essential for progress in exploring new avenues for therapy of breast cancer. This special issue of Breast Cancer Research and Treatment reports the proceedings of a conference held by the Lombardi Cancer Center, Georgetown University, on progress toward development of new therapies for breast cancer. These chapters are organized to present the following topics: immunotherapy, tumor growth pathways and their inhibition, and tumor-host interaction pathways and their inhibition.


Synthesis of Ag@Silica Nanoparticles by Assisted Laser Ablation.
This paper reports the synthesis of silver nanoparticles coated with porous silica (Ag@Silica NPs) using an assisted laser ablation method. This method is a chemical synthesis where one of the reagents (the reducer agent) is introduced in nanometer form by laser ablation of a solid target submerged in an aqueous solution. In a first step, a silicon wafer immersed in water solution was laser ablated for several minutes. Subsequently, an AgNO3 aliquot was added to the aqueous solution. The redox reaction between the silver ions and ablation products leads to a colloidal suspension of core-shell Ag@Silica NPs. The influence of the laser pulse energy, laser wavelength, ablation time, and Ag(+) concentration on the size and optical properties of the Ag@Silica NPs was investigated. Furthermore, the colloidal suspensions were studied by UV-VIS-NIR spectroscopy, X-Ray diffraction, and high-resolution transmission electron microscopy (HRTEM).


Post-translational modifications in Pseudomonas aeruginosa revolutionized by proteomic analysis.
Pseudomonas aeruginosa is an opportunistic pathogen that causes severe infections in vulnerable individuals. It is known that post-translational modifications (PTMs) play a key role in bacterial physiology. Their characterization is still challenging and the recent advances in proteomics allow large-scale and high-throughput analyses of PTMs. Here, we provide an overview of proteomic data about the modified proteins in P. aeruginosa. We emphasize the significant contribution of proteomics in knowledge enhancement of PTMs (phosphorylation, N-acetylation and glycosylation) and we discuss their importance in P. aeruginosa physiology.


Perseverative negative thinking predicts depression in people with acute coronary syndrome.
Depression is common in people who have experienced recent Acute Coronary Syndrome (ACS), and predicts worse medical outcomes. Mechanisms underpinning the development of depression and its association with poor medical outcomes are unclear however. The aim of this study was to investigate the role of perseverative negative thinking (e.g. worry and rumination) in predicting depression in people with recent ACS. Adults attending specialist inpatient and outpatient cardiology services who had recently experienced ACS were invited to participate in this observational prospective cohort study. Questionnaire assessments were completed within 6months of index ACS (baseline), then 2months and 6months later. 169 participants (131 male (78%), median age 68 (±16) years) completed baseline questionnaires, and 111 completed follow-ups. After controlling for the effects of key covariates, baseline rumination was a significant predictor of depression at 6months, accounting for 2% of the variance in depression. This association was partially mediated by poor problem-solving ability and lack of social support. Neither worry nor rumination at baseline were significant predictors of quality of life at 6months. Rumination is a significant independent predictor of depression, and this association may be partially explained by deficits in problem-solving ability and reduced social support. Both rumination and problem solving may provide useful targets for the development of evidence-based interventions to reduce depression among people with coronary heart disease.


Analysis of nonexponential fluorescence decay data by a method of moments.
A method of moments is presented for the analysis of convoluted fluorescence decay data when the impulse response function is given by f(t) = alpha exp (-At - Bt1/2). Examples of this method are given using both simulated and measured fluorescence decays. It is also shown that this method, used with moment index displacements, will correct for light-scatter leakage, zero-point time shifts, and slow lamp drift.


Efficacy of endoscopic closure of acute perforations of the gastrointestinal tract.
Acute perforations of the gastrointestinal tract are rare, severe complications of endoscopy that usually require surgical repair. Endoscopic repair of perforations would reduce the need for surgeries; we evaluated the efficacy and safety of endoscopic closure of acute perforations of the gastrointestinal tract by using a new clip device. We conducted a prospective, international, multicenter study of 36 consecutive patients (15 male) with acute iatrogenic perforations (5 esophageal, 6 gastric, 12 duodenal, and 13 colonic perforation). Endoscopic repair was performed by using the Over-the-Scope-Clip according to a standardized operating procedure. Primary end point was successful closure, which was determined as endoscopic successful closure without leakage (detected by water-soluble contrast x-ray analysis), and absence of adverse events within 30 days after the procedure. Immediate closure was endoscopically successful in 33 patients (92%). One patient developed an esophageal perforation while the cap was introduced, and in 2 patients the perforations did not close; these 3 patients were successfully treated with surgery. None of the patients had leakage of soluble contrast on the basis of contrast x-ray. One patient with a closed colonic perforation deteriorated clinically within 6 hours after the procedure. Despite surgery, the patient died within 36 hours. The remaining 32 patients had successful endoluminal closures; the overall success rate was 89% (95% confidence interval, 75%-96%). The mean endoscopic closure time was 5 minutes 44 seconds ± 4 minutes 15 seconds. The Over-the-Scope-Clip is effective for endoluminal closure of acute iatrogenic perforations. It allows patients to avoid surgery, and 89% of patients had successful closures without adverse events.


Changes in visual field advantage for facial recognition: the development of a general processing strategy.
During the recognition of tachistoscopically presented faces, subjects initially showing a LVF advantage decrease and then increase that advantage; subjects with an initial RVF advantage shift to a LVFA. We examined whether these shifts result from increasing familiarity with specific faces or rather from the development of a more general facial processing strategy. This was accomplished by changing the set of faces presented for recognition during testing. Across trials, the VFA of initially RVF advantaged subjects showed a linear trend, that of LVF advantaged S's a quadratic trend. These trends don't differ from those of subjects tested with one set of faces, suggesting that subjects were learning a general strategy for facial recognition.