Mapping spatial pattern in biodiversity for regional conservation planning: where to from here?
Vast gaps in available information on the spatial distribution of biodiversity pose a major challenge for regional conservation planning in many parts of the world. This problem is often addressed by basing such planning on various biodiversity surrogates. In some situations, distributional data for selected taxa may be used as surrogates for biodiversity as a whole. However, this approach is less effective in data-poor regions, where there may be little choice but to base conservation planning on some form of remote environmental mapping, derived, for example, from interpretation of satellite imagery or from numerical classification of abiotic environmental layers. Although this alternative approach confers obvious benefits in terms of cost-effectiveness and rapidity of application, problems may arise if congruence is poor between mapped land-classes and actual biological distributions. I propose three strategies for making more effective use of available biological data and knowledge to alleviate such problems by (1) more closely integrating biological and environmental data through predictive modeling, with increased emphasis on modeling collective properties of biodiversity rather than individual entities; (2) making more rigorous use of remotely mapped surrogates in conservation planning by incorporating knowledge of heterogeneity within land-classes, and of varying levels of distinctiveness between classes, into measures of conservation priority and achievement; and (3) using relatively data-rich regions as test-beds for evaluating the performance of surrogates that can be readily applied across data-poor regions.


Ketone bodies, glycolysis, and KATP channels in the mechanism of the ketogenic diet.
The ketogenic diet (KD) has shown remarkable efficacy in the treatment of drug-resistant childhood epilepsy. Our understanding of how the KD produces its anticonvulsant and antiepileptogenic effects remains incomplete, which is perhaps not surprising for a biological manipulation as sweeping as dietary change. Several hypotheses focus on ketone bodies, fuel molecules that circulate at millimolar concentrations in the blood of patients on a KD, as causative agents. Here I consider some recent evidence for one such hypothesis, involving a possible role for altered glycolysis and consequent activation of a class of potassium channels called K(ATP)channels.


Treatment of itching; a preliminary report on results with a new oral antipruritic.
A new antipruritic, trimeprazine, was used in the treatment of itching associated with a variety of dermatologic disorders in 215 patients.Good to excellent relief of itching was experienced by 71 per cent of the patients, fair relief by 15 per cent and poor relief by 14 per cent.Side effects included mild and transient drowsiness or dizziness that cleared spontaneously; six cases of drowsiness that necessitated discontinuance of the drug; three cases of drowsiness that was controlled by reduction of the dosage; and one case of generalized eruption that cleared upon discontinuance of the drug.


Self-Assembly of Amphiphiles into Vesicles and Fibrils: Investigation of Structure and Dynamics Using Spectroscopy and Microscopy Techniques.
Amphiphiles are a class of molecules which are known to assemble into a variety of nanostructures. The understanding and applications of self-assembled systems are based on what has been learned from biology. Among the vast number of self-assemblies, in this article, we have described the formation, characterization, and dynamics of two important biologically inspired assemblies: vesicles and fibrils. Vesicles, which can be classified into several categories depending on the sizes and components, are of great interest due to their potential applications in drug delivery and as nanoscale reactors. The structure and dynamics of vesicles can also mimic the complex geometry of the cell membrane. On the other hand, the self-assembly of proteins, peptides, and even single amino acids leads to a number of degenerative disorders. Thus, a complete understanding of these self-assembled systems is necessary. In this article, we discuss recent work on vesicular aggregates composed of phospholipids, fatty acids, and ionic as well as nonionic surfactants and single amino acid-based fibrils such as phenylalanine and tyrosine. Beside the characterization, we also emphasize the excited-state dynamics inside the aggregates for a proper understanding of the organization, reactivity, and heterogeneity of the aggregates.


Dialysis-related Amyloidosis: Is It Gone or Should It Be?
The prevalence and severity of dialysis-related amyloidosis (DRA) appear to have decreased significantly over the last two decades, although recent, large-scale epidemiological studies show that DRA continues to occur. Recent experimental findings have documented a direct cellular toxicity of β2microglobulin (β2m) fibrils but the mechanisms of β2m fibrillogenesis remain incompletely understood. Although a high plasma concentration of β2m is still considered as a prerequisite for developing DRA, other factors have been clearly incriminated such as older age at dialysis onset and longer dialysis vintage, or suspected effects such as proinflammatory effects of bioincompatible dialysis techniques. Improved dialysis technology has definitely played a role in delaying the onset of the disease, although the respective contributions of high-flux biocompatible membranes, use of convective mode, and ultrapure dialysate remain imperfectly defined. Importantly, DRA still does exist and no current dialytic modality seems able to fully prevent it. Awaiting further progress in the understanding of DRA pathogenesis, the use of biocompatible high-flux membranes and ultrapure dialysate is strongly recommended in order to minimize or delay its onset. Convective regimens may provide an additional benefit.


Trypanocidal and cell swelling activity of 20-deoxysalinomycin.
The naturally occurring polyether ionophore salinomycin was previously found to display promising anti-proliferative activity against bloodstream forms of Trypanosoma brucei. Here, we report the evaluation of 20-deoxysalinomycin, a naturally occurring homolog to salinomycin, for trypanocidal and cell swelling activity. The concentration of 20-deoxysalinomycin required to reduce the growth rate of bloodstream-form trypanosomes by 50% was determined to be 0.12 μM and found to be 8 times more trypanocidal than that of salinomycin. Moreover, 20-deoxysalinomycin and salinomycin displayed similar cytotoxic activity against human HL-60 cells. Measured as the ratio of cytotoxic to trypanocidal activity, 20-deoxysalinomycin thus exhibits a four-fold higher selectivity compared to salinomycin. The stronger trypanocidal activity of 20-deoxysalinomycin is attributed to an enhanced ability to induce cell swelling in trypanosomes. The findings support 20-deoxysalinomycin as a useful lead in the rational development of new and improved anti-trypanosomal drugs.


X-ray absorption of bromonaphthalene dissolved in supercritical fluid xenon.
The results of Br K-edge X-ray absorption measurements of 1-bromonaphthalene dissolved in supercritical fluid Xe are reported. As the pressure of Xe confined in a high-pressure cell is increased, the absorption spectrum of bromonaphthalene gradually appears, showing that Xe in the supercritical fluid state solvates the bromonaphthalene molecule. The spectrum of the dissolved sample shows a remarkable difference from that of the pure liquid sample in the near-edge region of the X-ray absorption spectrum, reflecting the interaction of the solute material with solvent Xe. Ab initio full multiple-scattering calculations can reproduce the spectral features qualitatively. A large value of the Debye-Waller factor must be introduced to give the best fit, corresponding to a large degree of spatial disorder and violent thermal vibration of the Xe atoms around the Br atom.


The sock electrode array: a tool for determining global epicardial activation during unstable arrhythmias.
The conventional technique for mapping the sequence of epicardial activation uses a hand-held electrode moved over the heart to record from a number of epicardial sites one at a time, and requires 5-15 minutes to record from 50 or more sites distributed over the entire ventricular epicardium. This method is inadequate for arrhythmias that are transient or vary from beat to beat. To overcome these limitations the "sock electrode array," a contour-fitting sock containing 26 or 52 electrodes, has been developed. The nylon mesh sock is pulled over the heart and permits simultaneous recording of potentials from electrodes distributed over the entire ventricular epicardium. The electrograms are recorded and converted to digital form for computer generation of isochronous maps. Most of the epicardial activation sequence derived from the sock electrode were compared to those obtained by the hand-held electrode in six normal dogs during sinus rhythm and ventricular pacing. The sequence of local activation times acquired by both methods showed similar areas of early and late activation and comparable isochronous maps. The hand-held electrode technique required 10-15 minutes for data acquisition and another 15-30 minutes for analysis. The sock electrode array allowed electrograms from 26 epicardial electrodes to be recorded simultaneously during one cardiac cycle and computer generated isochronous maps could be displayed within 10 minutes. This method allows rapid recording and analysis of epicardial electrical phenomena and should meet the time constraints imposed during the intraoperative study of ventricular tachyarrhythmias in patients.


Prostaglandin F2 alpha levels in human cerebrospinal fluid in normal and pathological conditions.
Prostaglandin F2 alpha concentrations in cerebrospinal fluid (CSF) from normal human subjects and patients with various pathological disorders of the central nervous system (CNS) were measured by radioimmunoassay. The mean PGF2 alpha level in 54 controls with no evidence of organic CNS disease was 67 pg/ml (range: 25-150 pg/ml). A significant increase of PGF2 alpha levels was demonstrated in most samples from patients with CNS diseases. Extremely high values were found in patients with stroke and subarachnoid hemorrhage when samples were collected shortly after the cerebral attack. With the regression of clinical symptoms and radiological findings a decrease of PGF2 alpha levels was demonstrated in this group of patients. In 32 patients with cerebral transient ischemic attacks a mean PGF2 alpha concentration of 170 pg/ml (range: 35-355 pg/ml) was found. Increased PGF2 alpha levels were found in patients with epilepsy when samples were collected within a few days after a convulsion. PGF2 alpha levels of four patients with slow progredient forms of multiple sclerosis without clinical symptoms at the time of sample collection were not different from normal controls while the mean PGF2 alpha level of all other patients with multiple sclerosis was 152 pg/ml (range: 55-325 pg/ml). Moreover, increased values could be demonstrated in patients with cerebral tumors and inflammatory processes.


Distinct Features of Doublecortin as a Marker of Neuronal Migration and Its Implications in Cancer Cell Mobility.
Neuronal migration is a critical process in the development of the nervous system. Defects in the migration of the neurons are associated with diseases like lissencephaly, subcortical band heterotopia (SBH), and pachygyria. Doublecortin (DCX) is an essential factor in neurogenesis and mutations in this protein impairs neuronal migration leading to several pathological conditions. Although, DCX is capable of modulating and stabilizing microtubules (MTs) to ensure effective migration, the mechanisms involved in executing these functions remain poorly understood. Meanwhile, there are existing gaps regarding the processes that underlie tumor initiation and progression into cancer as well as the ability to migrate and invade normal cells. Several studies suggest that DCX is involved in cancer metastasis. Unstable interactions between DCX and MTs destabilizes cytoskeletal organization leading to disorganized movements of cells, a process which may be implicated in the uncontrolled migration of cancer cells. However, the underlying mechanism is complex and require further clarification. Therefore, exploring the importance and features known up to date about this molecule will broaden our understanding and shed light on potential therapeutic approaches for the associated neurological diseases. This review summarizes current knowledge about DCX, its features, functions, and relationships with other proteins. We also present an overview of its role in cancer cells and highlight the importance of studying its gene mutations.


Cam morphology but neither acetabular dysplasia nor pincer morphology is associated with osteophytosis throughout the hip: findings from a cross-sectional study in UK Biobank.
To examine whether acetabular dysplasia (AD), cam and/or pincer morphology are associated with radiographic hip osteoarthritis (rHOA) and hip pain in UK Biobank (UKB) and, if so, what distribution of osteophytes is observed. Participants from UKB with a left hip dual-energy X-ray absorptiometry (DXA) scan had alpha angle (AA), lateral centre-edge angle (LCEA) and joint space narrowing (JSN) derived automatically. Cam and pincer morphology, and AD were defined using AA and LCEA. Osteophytes were measured manually and rHOA grades were calculated from JSN and osteophyte measures. Logistic regression was used to examine the relationships between these hip morphologies and rHOA, osteophytes, JSN, and hip pain. 6,807 individuals were selected (mean age: 62.7; 3382/3425 males/females). Cam morphology was more prevalent in males than females (15.4% and 1.8% respectively). In males, cam morphology was associated with rHOA [OR 3.20 (95% CI 2.41-4.25)], JSN [1.53 (1.24-1.88)], and acetabular [1.87 (1.48-2.36)], superior [1.94 (1.45-2.57)] and inferior [4.75 (3.44-6.57)] femoral osteophytes, and hip pain [1.48 (1.05-2.09)]. Broadly similar associations were seen in females, but with weaker statistical evidence. Neither pincer morphology nor AD showed any associations with rHOA or hip pain. Cam morphology was predominantly seen in males in whom it was associated with rHOA and hip pain. In males and females, cam morphology was associated with inferior femoral head osteophytes more strongly than those at the superior femoral head and acetabulum. Further studies are justified to characterise the biomechanical disturbances associated with cam morphology, underlying the observed osteophyte distribution.


Renal brush border enzyme-cleavable linkages for low renal radioactivity levels of radiolabeled antibody fragments.
We previously demonstrated that Fab fragments labeled with 3'-[(131)I]iodohippuryl N(ε)-maleoyl-l-lysine ([(131)I]HML) showed low renal radioactivity from early postinjection time, due to a liberation of m-[(131)I]iodohippuric acid by the action of renal brush border enzymes. Since there are lots of enzymes on renal brush border membrane, peptide linkages other than the glycyl-l-lysine were evaluated as the cleavable linkages to explore the chemical design. In this study, we evaluated four peptide linkages with a general formula of m-iodobenzoyl-glycyl-X (X: l-tyosine O-methyl, l-asparagine, l-glutamine, and N(ε)-Boc-l-lysine). In vitro studies using renal brush border membrane vesicles (BBMVs) demonstrated that 3'-[(125)I]iodohippuryl O-methyl-l-tyrosine (2c) liberated the highest amount of m-[(125)I]iodohippuric acid among the four substrates and the change in the linkage structure altered enzyme species responsible for the hydrolysis reaction. To further assess the applicability of the linkage, a radioiodination reagent containing a glycyl-tyrosine linkage, 3'-[(125)I]iodohippuryl O-((2-maleimidoethyl)carbamoyl)methyl-l-tyrosine (HMT, 12c), was designed, synthesized, and subsequently conjugated to an Fab fragment. [(125)I]HMT-Fab exhibited renal radioactivity levels similar to and significantly lower than [(125)I]HML-Fab and directly radioiodinated Fab, while the blood clearance rates of the three were similar. The analyses of urine for 24 h postinjection of [(125)I]HMT-Fab showed that m-[(125)I]iodohippuric acid was excreted as the major radiometabolite. The findings indicated that glycyl-tyrosine linkage is also available to reduce renal radioactivity levels of radioiodinated Fab fragments, due to liberation of m-iodohippuric acid by the action of enzymes present on renal brush border membrane. These findings suggest that an appropriate selection of peptide linkages would allow the liberation of a designed radiolabeled compound from covalently conjugated polypeptides to prepare radiolabeled polypeptides of low renal radioactivity levels. For the selection of the most appropriate peptide linkage, the in vitro system using BBMVs would be useful to narrow the candidates to just a few.


The role of interferon in immediate hypersensitivity and autoimmune diseases.
We have presented evidence showing that interferon can enhance the IgE-mediated release of histamine. We have also shown that immune interferon is present in the circulation of patients with certain autoimmune diseases. Furthermore, there is a positive correlation between active systemic lupus erythematosus and interferon levels. Systemic lupus erythematosus is characterized by immune hyperactivity. The continuous presence of type II, immune interferon in the circulation of these patients may, on one hand, contribute to the immunological aberrations, while on the other hand, protect against viral infections. At the present time we are looking for interferon in the circulation of patients with other autoimmune disorders.


Outcomes of segmentectomy for cT1bN0M0 lung adenocarcinoma and squamous cell carcinoma: a possible association with pathological invasion.
We evaluated the clinical benefit of segmentectomy for patients with cT1bN0M0 lung cancer. We retrospectively reviewed the medical records of 178 patients who underwent lobectomy or segmentectomy for cT1bN0M0 lung adenocarcinoma and squamous cell carcinoma from January 1995 to December 2005. We investigated the association of surgical outcomes with the presence of pathological invasion. The median follow-up period was 93.4 months. Of 178 patients, 37 were scheduled for segmentectomy, but 6 of these patients were switched to receive lobectomy due to surgical N1 or N2 in 3 patients and insufficient surgical margins in 3 patients. In total, 31 patients underwent segmentectomy, and 147 underwent lobectomy. The 5-year overall survival (OS) was similar between the patients who underwent lobectomy (5-year OS, 81.6%) and segmentectomy (5-year OS, 77.4%, P = 0.73). Among pN0 patients without pathological invasion, there was no difference in OS between patients who underwent lobectomy (5-year OS, 89.9%) and segmentectomy (5-year OS, 88.9%, P = 0.80). In contrast, among pN0 patients with pathological invasion, OS was greater in patients who underwent lobectomy (5-year OS, 80.9%) than in those who underwent segmentectomy (5-year OS, 54.6%; P = 0.19). Moreover, a significantly higher rate of local and local + distant recurrence was observed in patients who underwent segmentectomy (45%) than in those who underwent lobectomy (15%) in this group (P = 0.02). The results of our study suggest that segmentectomy may not be recommended for cT1b tumours if pathological invasion is suspected before surgery.


Quantitative Thermal Synthesis of Cu(I) Coordination Polymers That Exhibit Thermally Activated Delayed Fluorescence.
As a new environmentally friendly route for synthesizing thermally activated delayed-fluorescence (TADF) Cu(I) complexes, we successfully and quantitatively synthesized strongly emissive Cu(I) coordination polymers [Cu2I2(PR3)2(n,n'-bpy)]∞ (CuIR-n, R = Ph, Tol; n = 3, 4; bpy = bipyridine) via the quick thermal reaction of three starting materials (CuI, PR3, and bpy organic ligands) for 1 h in the absence of a solvent. Powder X-ray diffraction and thermogravimetric analyses revealed that melting of the organic ligands significantly promoted the coordination polymerization reaction, and the stoichiometry of three starting materials was crucial to quantitatively affording CuIR-n. Notably, the photophysical properties of CuIR-n obtained by the thermal reaction were almost the same (emission wavelength, quantum yield, and lifetime) as that obtained by generally used solution reactions, probably because CuIR-n was thermally stable enough to prevent the thermal damage and to improve the crystallinity in the heating process. The emission origin of CuIR-n was assignable to TADF at 298 K and phosphorescence at 77 K originating from the metal-to-ligand charge-transfer excited state effectively mixed with the halide-to-ligand charge transfer ((M+X)LCT) state. Thus, the thermal reaction in the melted ligand could be a promising environmentally friendly method for producing TADF Cu(I) luminophores.


Frailty: a term with many meanings and a growing priority for community nurses.
The question of exactly what frailty is and what that may mean for patients is extremely complex. This is a very conceptual problem requiring a broad and long-term solution. It is not a disease or a condition that can be treated in isolation. Frailty is a collection of contributing factors that culminate in an individual being susceptible to poorer outcomes following health-care interventions and minor illness. The solution to such a complex problem lies in engaging and empowering staff to understand and champion frailty. Once better understood, it will be possible to educate and enable this workforce to recognise the signs of frailty, poor prognosis and patients requiring more specialised palliative care. Informing staff working within a health-care economy of this issue must be the first step in a shift towards managing patients with frailty more appropriately, and streaming their care towards the correct care pathways sooner. This article discusses what frailty is, what it may mean for patients, and attempts to expand on why the construct of frailty is a prevalent issue for community nurses. The link between frailty and mortality is discussed and how targeted appropriate advanced care planning may be used to address this demographic challenge.


Plasma levels of adhesion molecules ICAM-1 and VCAM-1 in athletes with sickle cell trait with or without alpha-thalassemia during endurance exercise and recovery.
The aim of the study was to examine the effects of endurance exercise on circulating vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) in sickle cell trait (SCT) athletes with or without alpha-thalassemia. Five athletes with SCT, 7 athletes with both SCT and alpha-thalassemia (SCTAT) and 8 control athletes (CONT) performed an incremental test on cycloergometer followed 72 hours later by a 60-min endurance exercise with a workload set at 70% P(peak) (peak power). We assessed levels of sICAM-1, sVCAM-1 and TNF-alpha at rest, immediately after endurance exercise and 1, 2, and 24 hours of recovery. Although, CONT and SCTAT groups exhibited similar basal plasma levels of adhesion molecules and TNF-alpha, SCT group had higher sVCAM-1 basal concentrations. No significant variation in sVCAM-1, sICAM-1 and TNF-alpha was measured following endurance exercise. Consequently, sVCAM-1 remained elevated in the SCT group after exercise and during the recovery period. In conclusion, our findings support the concept that SCT athletes might be at risk for microcirculatory disturbances, but these adhesive processes were not further impaired in response to endurance exercise. In addition, alpha-thalassemia co existing trait may be protective both at rest and after endurance exercise in SCT subjects.


Peritonitis as the First Presentation of Disseminated Listeriosis in a Patient on Peritoneal Dialysis-a Case Report.
Infections with Listeria monocytogenes are uncommon but serious, with mortality rate approaching 30% in cases of systemic involvement despite first-line therapy. They are usually caused by ingestion of contaminated foods, but spontaneous infections have also been described. Listeria monocytogenes is a rare cause of peritonitis, and most of the published cases are in patients with cirrhosis and ascites. There are a few reported cases of Listeria peritonitis associated with peritoneal dialysis (PD), primarily isolated peritonitis.If detected early, Listeria peritonitis can be successfully treated with ampicillin, alone or in combination with gentamicin. Vancomycin has been listed as a second-line agent. However, it has been associated with treatment failure.In this case report, we present a patient who developed disseminated listeriosis, with peritonitis as the first manifestation of disseminated infection. This case illustrates the importance of having a high index of suspicion for L. monocytogenes if patients deteriorate despite empiric therapy for PD-associated peritonitis and serves as a further example demonstrating the inadequate coverage of vancomycin for L. monocytogenes.


RNAi versus small molecules: different mechanisms and specificities can lead to different outcomes.
The methodology of RNA interference (RNAi) arrived on the scene of mammalian systems research in 2001. Since that time, there has been widespread use of this technology in both academic and industrial settings. RNAi and small molecules were initially considered as equivalent methods for inhibiting protein activity within cells, but as our understanding of the mechanism of RNAi has improved, it has become apparent that differences in their cellular mechanisms have unexpected consequences. There can be profound differences in the phenotypic outcomes of treatment with RNAi versus small molecules. This review discusses the similarities, as well as the predicted differences between RNAi and small molecule effects on therapeutic paradigms and drug discovery.


Effect of steam treatment of alperujo on the composition, enzymatic saccharification, and in vitro digestibility of alperujo.
The solid waste from two-phase olive oil extraction or "alperujo" was submitted to steam treatment at high pressure or temperature, 200 degrees C for 5 min, in the presence and absence of mild acid catalyst. This treatment made easier the separation of the solid and liquid fractions. Besides the recovery of certain valuable components from the liquid fraction (the antioxidant hydroxytyrosol, low molecular weight oligosaccharides, glucose, mannitol, etc.), the major components of the solid residue could be also exploited. In this study, changes in composition of alperujo due to steam treatment were determined. The process reduced appreciably the hemicellulose concentrations (75-88%), removed a substantial portion of Klason lignin and protein (50%), and led to an extensive solubilization of alperujo (55-67%). Cellulose was very resistant to autohydrolysis and acid-catalyzed hydrolysis, so the solid residue was enriched in fat (13-18 g/100 g of dry steam-treated alperujo) and cellulose (15-25 g/100 g of dry and defatted steam-treated alperujo). The steam-treated material can be efficiently saccharified with commercial cellulase. The best hydrolysis yields were attained, up to 80%, when the treated material was post-treated with NaOH. The possibility of using this steam-treated alperujo in animal feeding was evaluated by an in vitro digestibility test, using the pepsin-cellulase method. The treatment affected positively the nutritional characteristics of alperujo with an increase in its in vitro (dry and organic matter) digestibility (8-10% higher than untreated material). In vitro digestibility and cellulose accessibility to enzymatic hydrolysis were improved by the alkali post-treatment.


EU pharmacovigilance regulatory requirements of anticancer biosimilar monoclonal antibodies.
An increasing number of innovative oncology monoclonal antibodies (mAbs) have been introduced into the global market, and biosimilar versions have now also been approved in Europe. Being complex to develop and difficult to manufacture, the biosimilar is a drug similar but not identical in physicochemical characteristics, efficacy, and safety to an original biological drug already approved in the European Union, for which marketing exclusivity rights have expired. Generally, the safety monitoring of biosimilars follows the same requirements that apply to all biologicals, even if specific pharmacovigilance measures exist and some of them are still being debated. The manufacturing process, immunogenicity, traceability, and extrapolation of indication are keywords which may impact on the achievement of additional knowledge about the safety of a biosimilar mAb. In this article, we aim to discuss elements that play a central role in the pharmacovigilance legislation of biosimilar mAbs.


Casuistry and its communitarian critics.
Communitarian critics have derided case-based reasoning for ignoring the need to arrive at a shared hierarchy of goods prior to case resolution. They claim that such a failure means that casuistry depends on either a naive metaphysical realism or an ethical conventionalism. Casuistry does embrace a certain unobjectionable moral realism and can require appeals to narrative histories, but despite this dependence on the surrounding culture, casuists possess a way to remain critical of society through the concept of practical wisdom and the use of a moral taxonomy. Therefore, casuistry's viability depends upon the existence and employment of this Aristotelian virtue. Furthermore, the casuistry that emerges is a sophisticated type of communitarianism rather than a free-standing method.


Ellipticity-tunable attosecond XUV pulse generation with a rotating bichromatic circularly polarized laser field.
We propose and theoretically demonstrate a method to generate attosecond XUV pulses with tunable ellipticity from aligned molecules irradiated by a bichromatic counterrotating circularly polarized (BCCP) driving laser field. By rotating the BCCP field, the attoseond XUV pulse varies from being left elliptically polarized to right elliptically polarized. The rotation of the BCCP field can be easily achieved by adjusting the relative phases between the two circularly polarized components. This scheme will benefit a broad range of applications, including the exploration of chiral-sensitive properties of the light-matter interaction and time-resolved imaging of magnetic structures.


Intimate partner violence, psychopathology and the women with schizophrenia in an outpatient clinic South-South, Nigeria.
Women with schizophrenia are a vulnerable risk group for intimate partner violence (1PV). There are few surveys that highlight the pattern, prevalence and association of IPV with psychopathology in these vulnerable group of women in South-South Nigeria. The aim of the study was to survey the forms, prevalence and association of Intimate partner violence with psychopathology. The study was a cross-sectional survey of 77 female patients diagnosed with schizophrenia who were outpatients at the Federal Neuro-psychiatric Hospital, Calabar, Cross-River State in South-South region of Nigeria. A total of 58 out of 77 (75 %) reported at least a form of IPV, Verbal abuse was the most prevalent form of IPV reported by participants (73 %, n = 56). Women who were younger were more likely to report verbal and sexual assault at p < 0.05. A shorter length of intimate relationship was significantly associated with sexual assault at p < 0.05. Sexual assault, verbal and physical abuse were significantly associated with higher mean score on the Brief Psychiatric Rating Scale at p = 0.01. The study highlighted the high rate of various forms of IPV among women with schizophrenia. Sexual assault, verbal and physical abuse were strongly associated with psychopathology. There is a need to identify risk of IPV among this vulnerable group by routine enquiry by clinicians' and plan therapy accordingly. Holistic management is needed in management of victims in their care.


Clinical significance of a false lumen pathway through the arch in acute type A aortic dissection and its influence on cervical branch compromise.
Upon onset of acute type A aortic dissection, the aortic true lumen generally becomes fixed around the supra-aortic branches in the greater curvature and Botallo's ligament in the lesser curvature of the aortic arch. Therefore, the pathways of the false lumen through the arch can be categorized as anterior, bilateral and posterior. We investigated the relationship between a false lumen pathway through the arch and cervical branch compromise, stratified by primary tear location. Sixty-four consecutive patients with acute type A aortic dissection underwent emergency surgery at our institution between March 2005 and October 2013. Of these, 40 cases (63%) were DeBakey type I, 15 cases (23%) were type II and 9 cases (14%) were type III-D (retrograde type A). We conducted a retrospective review of preoperative computed tomographic angiography using three-dimensional image post-processing tools for 43 cases, excluding 15 cases with type II and 6 cases with type I for which preoperative digital image data were not available. Of the 43 cases, 14, 18 and 11 revealed anterior, bilateral and posterior pathways, respectively. Twenty-one cases (49%) showed a primary intimal tear in the ascending aorta (8 anterior, 12 bilateral and 1 posterior), 12 cases (28%) showed a primary intimal tear in the aortic arch (5 anterior, 3 bilateral and 4 posterior) and 10 cases (23%) showed a primary intimal tear in the descending aorta (1 anterior, 3 bilateral and 6 posterior). Twelve of the 14 anterior pathway cases (86%) had a total of 26 supra-aortic branch compromises, 13 of the 18 bilateral pathway cases (72%) had a total of 20 supra-aortic branch compromises, while only 4 of the 11 posterior pathway cases (36%) had a total of four supra-aortic branch compromises. None of the 11 posterior pathway cases had a dissection extending into all 3 supra-aortic branches. Posterior pathway cases generally showed primary tear locations in the arch or descending aorta, and cervical branch compromise was rare. Aortic dissections tended to extend into the cervical branches through the anterior side of the aortic arch. A false lumen pathway through the arch was strongly associated with cervical branch compromise in acute type A aortic dissections.


COVID-19 Pandemic: Survey of future use of personal protective equipment in optometric practice.
The aim of this project was to evaluate which personal protective equipment (PPE) eye care practitioners (ECP) will use during the next months and also what they will ask the patient to use in clinical practice. A social-media survey was carried out, asking 257 optometrists and opticians in Germany, Austria and Switzerland (i) which PPE they intended to use in the future (after lockdown and before herd immunity and / or vaccine availability) and (ii) what they would ask the patient to do in terms of this. 75 % of the ECPs planned on wearing masks during refractions and 69 % when fitting contact lens. 62 % of the ECPs also expected their patients to wear masks in these tasks. This number is higher than for distance tasks such as fitting frames. Around 90 % of the ECPs would, in addition to hand washing, disinfect their hands and around 80 % expected their patients to do so too. Less than one third of ECPs favoured wearing safety spectacles, gloves and / or protective facial shields. 73 % planed on disinfecting frames after they would have been tried on by customers. In summary, most ECPs planed on continuing to use higher standards of PPE. Those, who intended to wear masks themselves, would ask their patients to also do so, combined with hand disinfection.


Intravenous immunoglobulin therapy induces neutrophil apoptosis in Kawasaki disease.
To investigate the effect of high-dose intravenous immunoglobulin (IVIg) on neutrophil apoptosis in Kawasaki disease (KD), we studied the in vitro spontaneous and IVIg-induced apoptosis of neutrophils by analyzing a proportion of annexin V-positive cells and cells with fragmented DNA. The mean number of peripheral neutrophils in the post-IVIg phase decreased significantly (P < 0.01) compared with that in the pre-IVIg phase. The mean proportion of spontaneous apoptotic neutrophils in the post-IVIg phase was significantly higher (P < 0.01) than that in the pre-IVIg phase, and there was a significantly positive correlation (P < 0.01) with the reduction ratio of the circulating neutrophil counts from the pre-IVIg through the post-IVIg phases. IVIg induced a dose-dependent increase in the proportion of apoptotic neutrophils in the pre-IVIg phase. As a result, the present study demonstrated a novel action in which high-dose IVIg therapy decreased the number of circulating neutrophils by accelerating their apoptosis in KD.


Informed consent and research with stored biological samples.
To report practical experience in obtaining consent for a retrospective study conducted at the Brazilian National Cancer Institute (INCA). The study involved review of medical records and analysis of paraffin blocks of patients surgically treated for colon cancer between 2000 and 2004. Attempts to obtain informed consent were made in compliance with the resolution 196/96 of the Brazilian National Health Council and determination of INCA Research Ethics Committee. At scheduled appointments, we could approach only four patients for consent during three months. After attempting contact by phone, an information sheet summarizing the content of informed consent, two copies of the consent form and a prepaid return envelope were then mailed to the patients. Of the 155 consent forms mailed, 115 were returned (74%). Of these, 111 patients gave consent to participate in the study, one refused consent, and we were informed that three patients had died. The time course of return of these forms ranged from 2 to 89 days (median: 10 days). Attempts to contact patients by phone were successful in 60 out of 160 cases (37.5%). The Research Ethics Committee waived the requirement of consent for those who had died or not responded. Overall mailing cost was R$ 1,004.40. Obtaining consent from patients by phone and mail for a retrospective clinical study is feasible. Most patients responded to contact and gave consent to participate. However, the process entails costs and risks that cannot be overlooked.


African American Cancer Survivors' Perspectives on Cancer Clinical Trial Participation in a Safety-Net Hospital: Considering the Role of the Social Determinants of Health.
Although there has been an increase focus on recruitment of minority populations at safety-net hospitals into cancer clinical trials, there is still a paucity of research exploring minority participation in cancer clinical trials at safety-net settings. The study utilized a multi-level, qualitative approach to assess the clinical and non-clinical facilitators and barriers to African American participation in cancer clinical trials at a safety-net hospital. From June 2018 to July 2019, cancer survivors (n = 25) were recruited from a cancer center at a safety-net hospital in the southeastern USA and participated in a 60-min focus group. Data was coded and analyzed to identify the most prominent themes. Most participants were female (78%), with a mean age of 56 years. The majority were diagnosed with breast cancer (68%) and disabled or unemployed (55%). Major themes identified were (1) lack of understanding of cancer clinical trials, (2) perceptions and fears of cancer clinical trials, and (3) preferred role and characteristics of patient navigator. The barriers and facilitators to enrollment in cancer clinical trials were more pronounced in the safety-net setting, given the overdue burden of social determinants of health. Study findings yield important insights and essential practices for recruiting and engaging underrepresented Black cancer patients into cancer clinical trials, specifically for safety-net settings. Including patient navigators may help traverse potential barriers to cancer clinical trial participation and will allow for the attention to social determinants of health, and ultimately increase the number of African Americans participating in cancer clinical trials.


Helix aspersa gelatin as an emulsifier and emulsion stabilizer: functional properties and effects on pancreatic lipolysis.
Emulsions are widely used in food and pharmaceutical applications for the encapsulation, solubilization, entrapment, and controlled delivery of active ingredients. In order to fulfill the increasing demand for clean label excipients, natural polymers could be used to replace the potentially irritative synthetic surfactants used in emulsion formulation. In the present study, we have studied the properties of oil-in-water emulsions prepared with land snail gelatin (LSG) as the sole emulsifying agent, extracted and described for the first time. LSG was evaluated in terms of proximate composition, oil and water holding capacity, emulsifying and foaming properties, color and amino acid composition. Emulsions of trioctanoylglycerol (TC8) and olive oil were made at different gelatin/oil ratios and changes in droplet-size distribution were determined. The superior emulsifying properties of LSG, the susceptibility of gelatin protein emulsions increasing flocculation on storage, and the coalescence of gelatin emulsions following centrifugation were demonstrated. Furthermore, the effect of LSG on the activity of turkey pancreatic lipase (TPL) was evaluated through the pH-stat methodology with TC8 and olive oil emulsions. The LSG affected the TPL activity in a concentration-dependent way. Our results showed that LSG, comparably to gum arabic, increases the pancreatic lipase activity and improves its stability at the oil-water interface.


[Clinical significance of virulence-related genes of type III secretion system of Pseudomonas aeruginosa].
To study the clinical significance of virulence genes exo U and exo S of type III secretion system (TTSS) of Pseudomonas aeruginosa (PA). One hundred and eighty-nine clinical isolates of PA were collected from five hospitals. The incidence of virulence genes exo U and exo S in PA were determined with PCR. Minimum inhibitory concentration of anti-bacterial drug for PA was determined with microdilution method. The clinical features and outcomes of 60 hospitalized patients colonized or infected with exo U+/exo S- positive or exo U-/exo S+ positive PA isolated from sputum were analyzed retrospectively. Data were processed with chi-square test. Among the 189 PA isolates, 85.2% (161/189) harbored TTSS genes, including exo U-/exo S+ type (120 isolates), exo U+/exo S- type (31 isolates), exo U-/exo S- type (7 isolates), and exo U+/exo S+ type (3 isolates). 72.0% (72/100) isolates from sputum and 81.5% (44/54) isolates from blood belonged to exo U-/exo S+ genotype. Compared with those of TTSS-negative isolates, the antimicrobial resistance of TTSS-positive isolates to cefoperazone/sulbactam, ceftazidime, amikacin, and cefepime were lower (with χ² value respectively 10.1, 16.1, 9.3, 33.8, P values all below 0.01). The antimicrobial resistance to all examined drug between exo U-/exo S+ type and exo U+/exo S- type isolates was close (with χ² values from 0.08 to 2.04, P values all above 0.05). Patients detected with exo U+/exo S- positive PA isolated from sputum were significantly associated with PA infection, and they usually had history of tracheal intubation, ICU hospitalization, and combined use of drugs for anti-infection treatment. Patients detected with exo U-/exo S+ positive PA isolated from sputum were significantly associated with PA colonization, which had basic lung disease and better outcome than the former infection type. The TTSS exists in most clinical isolates of PA. Detection of exo U or exo S of PA isolated from sputum is helpful for the analysis of clinical features and outcome of patients.


[Our experience of eribulin treatment in advanced breast cancer].
The clinical outcomes, including adverse events, in 40 advanced breast cancer patients treated with eribulin were analyzed to confirm the effectiveness and safety of this treatment. The objective response rate (ORR) in patients was 35.0%. The median overall survival and time to treatment failure (TTF) in these patients was 479 and 63 days, respectively. Cases wherein eribulin was used as early-line treatment experienced significantly longer TTF compared to the cases wherein eribulin was used as late-line treatment; however, there was no difference in this value according to the breast cancer subtype. Moreover, subtype analysis revealed no significant difference in adverse events. We observed no difference in the benefit or tolerability of eribulin treatment among different breast cancer subtypes. However, our results suggest that a significant therapeutic effect can be expected when using eribulin as early-line treatment.


[Interdisciplinary home hospitalization program of Marília-SP: material resource costs].
This study estimated the mean total direct cost of some production factors (material resources), including consumption materials, diets, medication and solutions used by two patient groups during hospitalization in the Interdisciplinary Home Hospitalization Program (PROIID) of Marília-SP, Brazil. The sample consisted of 27 patients with a diagnosis of cerebral vascular accident (CVA) and 18 with Neoplasm. Data were collected from the moment of hospitalization until the patients left the program. The mean total direct cost amounted to R$ 52.72 for each patient with CVA and of R$ 65.13 for those with Neoplasm. For both patient groups, the sub-category of material--diets accounted for the highest percentage of costs.


Medicare modernization and diffusion of endoscopy in FFS medicare.
To examine how FFS Medicare utilization of endoscopy procedures for colorectal cancer (CRC) screening changed after implementation of the Medicare Prescription Drug, Improvement, and Modernization Act (MMA) in 2006, which provided subsidized drug coverage and expanded the geographic availability of Medicare managed care plans across the US. Using secondary data from 100% FFS Medicare enrollees, we analyzed endoscopy utilization during two intervals, 2001-2005 and 2006-2009. We examined change in predictors of county-level endoscopy utilization rates based on a conceptual model of market supply and demand with spillovers from managed care practices. The equations for each period were estimated jointly in a spatial lag regression model that properly accounts for both place and time effects, allowing robust assessment of changes over time. All Medicare FFS enrollees with both Parts A and B coverage who were age 65+, remained alive and living in the same state over the interval were included in the analyses. The later interval used a new cohort defined the same as the earlier interval. 100% Medicare denominator files were also used, providing county of address to use for county-level aggregation. The outcome variable was defined as county-level proportion of enrollees who ever used endoscopy over the interval. Endoscopy utilization by FFS Medicare increased, and became more accessible across the US. Medicare managed care plan spillovers onto FFS Medicare endoscopy utilization changed over time from a significant negative (restraining) effect in the early period to no significant effect by the later period. The MMA eased budget constraints for seniors, making endoscopic CRC screening more affordable. The MMA policies also strengthened managed care business prospects, and enrollments in Medicare managed care escalated. The change in managed care spillover effects reflects the gradual acceptance of endoscopic CRC screening procedures, as they emerged as the gold standard during the period.


Providencia stuartii, a hospital pathogen: potential factors for its emergence and transmission.
The emergence of Providencia stuartii as a hospital pathogen in a burn unit was demonstrated by routine infection surveillance. The organism was initially recognized in a burn wound and subsequently in urine or sputum. Compared to controls, those patients harboring P. stuartii were similar in age and percentage of body surface burned and were more likely to have been in one of the two burn unit rooms, (p less than 0.02). Infection with P. stuartii was independent of duration in the Intensive Care Unit or Burn Unit, and of number of visits to hydrotherapy or operating rooms (OR). Once patients were colonized with P. stuartii they had greater morbidity than non-colonized patients as evidenced by longer stays in the unit and increased visits to the OR for debridement. P. stuartii was isolated from air samples (5/14) more commonly than from the hands of personnel. In vitro tests suggested that extensive use of parenteral gentamicin and replacement of the antibacterial topical cream sulfamylon by silver sulfadiazine favored the emergence of P. stuartii over Pseudomonas aeruginosa as the predominant colonizing organism.


High frequency of mas oncogene activation detected in the NIH3T3 tumorigenicity assay.
In four independent transfection experiments performed with high molecular weight DNA isolated from a human ovarian carcinoma, oncogenic NIH3T3 cells contained an activated mas gene in the in vivo tumorigenicity assay. Varying from 1.8 to 3.5 kb upstream of the coding region of the mas gene, the DNA sequences in the transfectants diverged from those present in the ovarian tumor, as determined by restriction enzyme mapping. Because these upstream sequences were different in at least 5 nude mouse tumors studied, we suppose that another as yet not identified structural alteration in the mas gene of the original ovarian tumor is responsible for the transforming activity of the gene.


Elevated liver enzymes in hospitalized patients with COVID-19 in Singapore.
Liver dysfunction in patients with COVID-19 (coronavirus disease 2019) has been described. However, it is not clear if the presence of abnormal liver function tests at presentation was related to underlying undiagnosed liver disease, or a result of the viral infection.We retrospectively examined the first 554 consecutive polymerase chain reaction positive SARS-CoV-2 patients admitted from February 2020 to April 2020 to our academic medical centre. We reviewed their clinical data, chest radiography and laboratory studies obtained within 24 hour of admission.Despite similar hemodynamic parameters, we found significant aspartate transaminase elevation (64 ± 141 vs 35 ± 23 U/L, P < .001) in those with pneumonia compared to those without. Elevated liver enzymes were seen in 102 patients (18.4%). They presented with higher temperatures (38.5 ± 0.9 vs 37.5 ± 0.8 degC, P = .011), higher total white cell counts (6.95 ± 2.29 vs 6.39 ± 2.19 x109/L, P = .021), serum ferritin (240 ± 274 vs 165 ± 198 ng/ml, P = .002) and lactate dehydrogenase (632 ± 912 vs 389 ± 107 U/L, P < .001). These patients were more likely to require intensive care (6.9% vs 2.7% P = .036) and mechanical ventilation (5.9% vs 2.2%, P = .046). Migrant workers from dormitories had a higher rate of baseline liver function test abnormalities (88/425 vs 14/129, P = .01), which were more likely to persist at the time of discharge.Despite relatively mild COVID-19 disease, there was a significant prevalence of liver dysfunction, particularly amongst migrant workers. Elevated liver enzymes were associated with more severe disease, despite similar haemodynamic characteristics. Future studies should explore whether pre-existing liver disease may predispose to more severe COVID-19 disease.


A neuroanatomical account of mental time travelling in schizophrenia: A meta-analysis of functional and structural neuroimaging data.
Mental time travel (MTT) abilities could be particularly compromised in schizophrenic patients due to a deficit of the cognitive processes at the basis of remembering the past and imaging the future: constructive processes, theory of mind and self-awareness. Accordingly, we assumed that the neural circuits typically associated with MTT in healthy people might be partially compromised in chronic schizophrenic patients. To quantitatively and anatomically test our hypothesis, we run two meta-analyses using the Activation Likelihood Estimate method: (i) a neurofunctional meta-analysis on MTT in healthy subjects, (ii) a morphometrical meta-analysis on chronic schizophrenia. The results of the two meta-analyses were overlapped in order to identify the candidate regions involved in MTT deficit in schizophrenia. A significant overlap was found in the vmPFC, in the precuneus, in the hippocampus and in the insular cortex. We assume that MTT deficits in schizophrenic patients may be the results of a complex dysfunctional interaction between the system underlying the creation of self-representation, the constructive system and the salience attribution network.