Hypotensive effect of selective laser trabeculoplasty in patients with medically uncontrolled primary open-angle glaucoma.
Glaucoma is a chronic, progressive disease of the optic nerve which if left untreated can lead to blindness at end stages. A decrease of intraocular pressure (IOP) has proven to slow down the progression of the disease. IOP decrease can be achieved by medical, laser and surgical treatment. The aim of this study was to evaluate the response of patients with medically uncontrolled primary open angle glaucoma to selective laser trabeculoplasty (SLT). The study involved baseline characteristics recorded for each of 35 patients (48 eyes) in whom, despite being under full medication we could not achieve a satisfactory IOP. Patients, who had pressure above 25 mmHg under the maximal medication therapy, were not included into the study and were referred for surgical treatment. IOP was measured on admission, 1 hour, 7 days, 1, 3, 6 and 12 months after SLT. We considered satisfactory surgical result if IOP was decreased more than 20% of the initial value. Also, we investigated the influence of baseline IOP on SLT outcome after 12 months. Patient inclusion criteria were inability to reach target IOP with maximal medical therapy. Exclusion criteria were congenital glaucoma, any type of angle closure glaucoma, advanced-stage glaucoma, eyes with previous laser or surgical glaucoma applications and patients with baseline IOP > 25 while fully medicated. Patients who could not be followed for at least 12 months were also excluded. The mean age of our patients was 73 ± 12 years. The mean baseline IOP was 20.48 mmHg (SD = 1.91), and the mean change in IOP from baseline of the treated eye after one year was 4.47 mmHg (SD = 2.12). In eyes with a higher baseline IOP the reduction of pressure at the end of the study was significantly higher. Satisfactory effect of IOP reduction after one year was achieved in 64.58% of eyes. The IOP reduction did not show to be dependent as regarding age and gender. SLT effectively lowers IOP in patients with primary open-angle glaucoma, and the intervention is not followed by significant complications. Our results confirm that the IOP reduction is more significant if the initial value is higher. Our first reliable results of IOP reduction were confirmed one month after the procedure so that the procedure should not be repeated before one month has elapsed.The study is limited by a small number of eyes, which is insufficient to make a complete case analysis.


New product development and at-home medical tests.
The COVID-19 pandemic has impacted every aspect of life and continues to affect individuals and organizations in ways no one anticipated. In an attempt to cope with alternative lifestyle patterns, many companies have formulated products and services to mitigate behavioral adjustments. Specifically, the healthcare industry has increased efforts to cope with the ramifications of this infectious disease. A focus on creating and distributing at-home testing has become a priority as companies attempt to expedite the approval, production and commercialization of tests. This paper addresses the dynamics of producing, distributing, and evaluating at-home medical tests.


A frequency view of colour: measuring the human sensitivity to square-wave spectral power distributions.
We have measured the chromatic threshold sensitivity to stimuli with spectral composition determined by a periodic function of energy over wavelength. This approach is analogous to frequency studies of spatial vision for the study of colour. A device was constructed permitting the synthesis of illuminants over the entire visible range (400-700 nm) in which phase, frequency and amplitude can be independently controlled. We have used 12 frequencies of square-wave functions (from 0.5 to 3.6 cycles/300 nm) and seven values of phase (between 0 degrees and 180 degrees) to obtain the contrast sensitivity function of the chromatic system in three normal trichromats. The results show maximum sensitivity around 1.5 cycles/300 nm and a high-frequency cut-off at 3.6 cycles/300 nm. These empirical values are compared with the predictions obtained from three current psychophysical models of opponent-colour process.


Characterization of knitted polymeric scaffolds for potential use in ligament tissue engineering.
Different scaffolds have been designed for ligament tissue engineering. Knitted scaffolds of poly-L-lactic acid (PLLA) yarns and co-polymeric yarns of PLLA and poly(glycolic acid) (PLGA) were characterized in the current study. The knitted scaffolds were immersed in medium for 20 weeks, before mass loss, molecular weight, pH value change in medium were tested; changes in mechanical properties were evaluated at different time points. Results showed that the knitted scaffolds had 44% porosity. There was no significant pH value change during degradation, while there was obvious mass loss at initial 4 week, as well as smooth molecular weight drop of PLLA. PLGA degraded more quickly, while PLLA kept its integrity for at least 20 weeks. Young's modulus increased while tensile strength and strain at break decreased with degradation time; however, all of them could maintain the basic requirements for ACL reconstruction. It showed that the knitted polymeric structures could serve as potential scaffolds for tissue-engineered ligaments.


[Transsphenoidal surgery of craniopharyngioma: form palliative surgery to radical removal].
The paper presents basic principles of transsphenoidal craniopharyngioma surgery. Stages of methodology development. Steps of methodology development of such operations in the Institute are described--from palliative interventions to the high-tech modern radical surgery with the use of anterior extended approach. Additional stereotactic irradiation provides reliable control of the disease for a long period. The article mainly describes operative technique and contains preliminary analysis of the surgical results showing effectiveness and safety of endoscopic removal of craniopharyngioma.


Intravenous desensitization to beta-lactam antibiotics.
Patients allergic to penicillin (PCN) often require treatment with beta-lactam antibiotics for life-threatening bacterial infections. In this article, we review our experience with rapid intravenous desensitization for patients who gave a history of PCN allergy and who had hypersensitivity demonstrated by skin tests. Skin testing was performed with both prick and intradermal techniques and with the recommended antibiotic as well as PCN G, penicilloyl polylysine, and a minor determinant mixture. Patients were transferred to the intensive care unit, and desensitization was performed with a buret technique that required minimal preparation and was easily applied to any antibiotic. Fifteen desensitizations in 12 patients were associated with no immediate reactions. One patient developed a delayed reaction consisting of a pruritic rash and angioedema. A second patient developed a more serious delayed serum sickness-like illness with fever, rash, eosinophilia, abnormal liver function tests, and urinary abnormalities. These reactions did not necessitate stopping the antibiotic, although the latter patient required corticosteroids to suppress his symptoms. Rapid intravenous desensitization is a rapid, safe, and effective technique for patients demonstrating hypersensitivity to beta-lactam antibiotics who require therapy with these medications.


Mental health nursing and the prenatal diagnosis of a congenital anomaly; a narrative of experience.
Many parents find out that their unborn baby has a difference in their health, development, or genetics. This news is often unexpected and can be distressing and traumatic, which can lead to anxiety. There is a gap in support for parents. This paper offers a story of the lived experience of the first-author, a mental health nurse who was told that her baby had a difference late in pregnancy. The narrative moves through the anxiety and difficulties faced when falling between gaps in the systems. This paper identifies the need for more support for parents who receive a prenatal diagnosis. This support is within the mental health nurse scope of practice across a range of settings and services. People who have been given a psychiatric diagnosis have been excluded from other studies that explore the experience of the unexpected news of a congenital anomaly. Research in this area is indicated. Mental health nurses are well-positioned to address the gap in psychosocial support for parents who have received a prenatal diagnosis. As clinicians who are recognized to deliver federally funded pregnancy support counselling, psychosocial support is within the mental health nurse scope of practice. Some parents will require a higher level of support, assessment and intervention when they experience reactive mental illness or pre-existing mental illness is exacerbated. Furthermore, people who have received a psychiatric diagnosis have been excluded from studies that explore the experience of receiving a prenatal diagnosis. This exclusion has resulted in a gap in knowledge. Introduction Expectant parents who receive a prenatal diagnosis of a congenital anomaly often experience shock, distress and a heightened risk of mental illness. Aim This paper aimed to highlight the gap in psychosocial support for parents who receive a prenatal diagnosis through the personal narrative of a mental health nurse who received a third-trimester diagnosis. Method The first-author reviewed her medical records and photos to recall moments of the experience and prompt reflection. Findings The narrative moved through the shock, guilt and subsequent pathological anxiety that followed a prenatal diagnosis at 32-week gestation and the option to terminate. Discussion The gap in psychosocial supports for parents who receive a prenatal congenital anomaly diagnosis raises the risk to parental mental health and potentially confounds the risk to the baby. Mental health nurses are well-positioned as service providers to fill this gap. Implications for Practice The provision of psychosocial support after a prenatal diagnosis is within the mental health nurse scope of practice. This support may be provided through pregnancy support counselling, innovative nurse-led perinatal mental health services or as additional support to a parent with the lived experience of mental illness who receives a prenatal diagnosis of a congenital anomaly.


Genome-wide analysis of long noncoding RNA profile in human gastric epithelial cell response to Helicobacter pylori.
Long noncoding RNAs (lncRNAs) are an important class of pervasive genes, and their misregulation has been shown in various types of diseases. However, the relationship between lncRNAs and the immune response to pathogen infection has been rarely reported. Helicobacter pylori is a major human pathogenic bacterium that causes gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue lymphoma, and gastric cancer. The regulatory mechanism of the H. pylori-induced immune response is not yet clear. In the present study, we identified nonoverlapping signatures of a small number of lncRNAs that were aberrantly expressed in H. pylori-infected gastric epithelial cells using microarray analysis followed by bioassays. From microarray data, we found that 23 lncRNAs were upregulated and 21 were downregulated. Five lncRNAs, XLOC_004562, XLOC_005912, XLOC_000620, XLOC_004122, and XLOC_014388, were further evaluated using quantitative reverse transcription-PCR, and the results matched well with microarray data. In addition, XLOC_004122 and XLOC_014388 were decreased in gastric mucosal tissues of H. pylori-positive patients. Differentially expressed lncRNAs may play a partial or key role in the immune response to H. pylori, and this may provide potential targets for the future treatment of H. pylori-related diseases.


High Prevalence of Apical Periodontitis in Patients With Inflammatory Bowel Disease: An Age- and Gender- matched Case-control Study.
Deep carious lesions cause pulpitis, pulpal necrosis and, finally, apical periodontitis (AP). Root canal treatment (RCT) is the treatment of choice for AP, changing the tooth into a root-filled tooth (RFT). Several studies have linked AP and RFT to systemic diseases. Likewise, previous studies have also found an association among inflammatory bowel disease (IBD) and periodontal disease. This study aims to analyze the frequency of AP and RCT in IBD patients and healthy control subjects. An age- and gender-matched case-control study design was used. The study group (SG) included 54 IBD patients (28 with Crohn´s disease, 26 with ulcerative colitis). Another 54 healthy subjects without IBD and age- and gender-matched were included in the control group (CG). The radiographic records were analyzed, and periapical radiolucencies were diagnosed as AP, using the periapical index (PAI). The statistical analysis was carried out using the Student t test, χ 2 test, and multivariate logistic regression. The presence of 1 or more teeth with radiolucent periapical lesions (RPLs) was found in 19 patients (35.2%) in the study group and in 9 subjects (16.7%) in the control group (P = 0.03). No differences were found among the 2 groups neither in the amount of teeth with AP nor in the number of RFTs (P > 0.05). However, multivariate logistic regression analysis adjusting for number of teeth and number of RFTs showed that patients with IBD have RPLs with higher likelihood than control patients (odds ratio, 5.7; confidence interval 95%, 1.7-19.1; P = 0.0048). Subjects with inflammatory bowel disease have higher prevalence of apical periodontitis. An oral health protocol should be established to address the higher prevalence of inflammatory oral processes.


A CD4-like molecule can be expressed in vivo in human parathyroid.
The expression of several epitopes of CD4, a molecule usually restricted to a subset of T-lymphocytes, was observed after immunofluorescent labeling of frozen-cut sections of human parathyroid. Seven samples obtained from three subjects presenting adenomas and from seven renal insufficiency patients with secondary or tertiary hyperplasia were found to express this molecule. Dot enzyme-linked immunosorbent assay, polyacrylamide gel electrophoresis, and Western blotting were used to characterize this peptide in cytosol and membrane fractions of these glands. These studies confirmed, in the parathyroids found positive in immunofluorescence, the presence of a protein with a mol wt similar to that of lymphocyte-derived CD4.


Highlights from Faraday Discussion: From optical to THz control of materials, London, UK, May 2022.
The Faraday Discussion 'From optical to THz control of materials' was held in London, UK, and online on the 23rd, 24th, and 25th May 2022. The meeting brought together established and early-career scientists, postgraduate students, scientific editors, and industrial researchers in the field of spectroscopy and materials science from over ten different countries interested in exploring the physical properties of materials at ultrafast timescales driven by optical and THz excitations. This conference report provides highlights of this meeting and we give summaries of the presentations including the introductory lecture, all the papers discussed, and the concluding remarks.


Low Back Pain Perceptions and Coping Strategies in Pre-Professional Dancers: A Qualitative Study.
Low back pain (LBP) is a common health problem in pre-professional dancers which could hamper the dancers' professional career. However, pre-professional dancers are not often studied, although they may have their own pain perceptions and coping strategies towards LBP. Considering the biopsychosocial nature of LBP, it is important to increase the understanding of these perceptions and coping strategies. The aim of this qualitative research study was to explore the dancers' perceptions about LBP and their coping strategies when they suffered from LBP. Eighteen pre-professional dancers with and without LBP from different dance schools in Belgium were included in this study. Participants were invited for an in-depth online video interview. These in-depth interviews were based on a topic list. Afterwards, the interview transcripts were analyzed thematically. Two primary themes emerged from the data: 1) perceptions of LBP and 2) coping strategies which dancers applied when they suffered from LBP. The perceptions about LBP were related to two different themes: "it's all about the body" and "it's all about the psychosocial and contextual factors." In addition, the coping strategies were divided into "active coping strategies" and "passive coping strategies," whereas the most popular coping strategies were stretching exercises and passive coping strategies such as massages or heating cream. Although LBP has clearly been shown to be a biopsychosocial phenomenon, this qualitative study showed that dancers mainly considered biomedical factors as contributing factors to LBP. Additionally, instead of relying on coping strategies aimed at directly improving pain or trying to treat LBP on the basis of a single-cause diagnosis, it is important to consider the biopsychosocial origin of LBP in the management plans.


Transoesophageal echocardiographic evaluation of pulmonary vein anatomy in patients undergoing ostial radiofrequency catheter ablation for atrial fibrillation: a comparison with magnetic resonance angiography.
A detailed definition of pulmonary vein (PV) anatomy is of great importance in patients undergoing radiofrequency catheter ablation for atrial fibrillation. In fact, it is known that variations in the number and anatomy of the PV ostia are more frequent than thought. The aim of this study was to assess the usefulness of transoesophageal echocardiography (TOE) in defining the exact PV anatomy by comparing it with magnetic resonance angiography (MRA), which is proven to be very accurate. Forty-five consecutive patients (39 male, 6 female, mean age 50 + or - 6 years) affected by drug-refractory atrial fibrillation underwent radiofrequency catheter ablation. They were all studied with MRA and then with TOE in order to exclude intra-atrial thrombi and to assess PV anatomy. TOE visualised the superior PVs in 100% of cases and the right and left inferior PVs in 98% and 94% of cases, respectively. Only 19 patients (42%) showed typical PV anatomy, with two left and two right distinct PV ostia. In 14 patients (31%), one or two intermediate right PVs and in 12 patients (27%) a common left trunk were detected. The concordance with MRA was high (95%). TOE is accurate in assessing PV anatomy and in showing anatomic variations in the PV ostia compared with MRA. Anomalous pulmonary venous drainage is more frequent than expected. TOE can provide functional Doppler information, thus being particularly useful in the follow-up after radiofrequency catheter ablation.


Eichhornia crassipes (Mart.) Solms: A Comprehensive Review of Its Chemical Composition, Traditional Use, and Value-Added Products.
Eichhornia crassipes (Mart.) Solms, commonly known as water hyacinth, is one of the world's most invasive aquatic plants of the Pontederiaceae family occurring in tropical and subtropical regions of the world. Although, E. crassipes causes significant ecological and socioeconomic issues such as a high loss in water resources, it has multipurpose applications since it is famous for many industrial applications such as bioenergy, biofertilizer production, wastewater treatment (absorption of heavy metals), and animal feed. Furthermore, E. crassipes is rich in diverse bioactive secondary metabolites including sterols, alkaloids, phenolics, flavonoids, tannins, and saponins. These secondary metabolites are well known for a wide array of therapeutic properties. The findings of this review suggest that extracts and some isolated compounds from E. crassipes possess some pharmacological activities including anticancer, antioxidant, anti-inflammatory, antimicrobial, skin whitening, neuroprotective, and hepatoprotective activities, among other biological activities such as allelopathic, larvicidal, and insecticidal activities. The present review comprehensively summarizes the chemical composition of E. crassipes, reported to date, along with its traditional uses and pharmacological and biological activities.


Memantine in the preventive treatment of refractory migraine.
To assess the efficacy and tolerability of memantine(MEM)in the preventive treatment of refractory migraine. Glutamate is of importance in migraine pathophysiology and may be related to progression from episodic to chronic migraine. Furthermore, individuals with chronic pain often report cognitive problems. MEM has the potential to address both issues, justifying this pilot study. We included subjects with refractory migraine (episodic migraine with 8-14 days of headache per month or transformed migraine, who had previously failed at least 2 trials of adequate preventive therapy). Other preventive drugs were allowed if the patient had been on a stable dose for more than 30 days. MEM dose ranged from 10 mg to 20 mg per day. The treatment phase lasted 3 months. The primary endpoint was number of days with headache at month 3. Cognitive performance was assessed with the trail making tests A and B (TMT-A and B). Statistical analyses were performed on the intent-to-treat (ITT) population, using data subjected to the last observation carried forward algorithm.We also conducted per protocol analyses. In the ITT population (n = 28), monthly headache frequency was reduced from 21.8 days at baseline to 16.1 (P < .01) at 3 months. The mean number of days with severe pain was reduced from 7.8 to 3.2 at 3 months (P < .01). The mean disability scores were significantly reduced at 3 months, compared with baseline (36.6 vs 54.9, P < .01). There was a significant reduction in the time to complete TMT-A at termination vs baseline (28.4 vs 23.2,P = .02) and also TMT-B (70.1 vs 50.4,P = .04). Side effects were present in 37.5% of the patients; 5.5% dropped out the study because of poor tolerability. Most adverse events were mild. This study offers preliminary evidence for the use of MEM in the prevention of refractory migraine.Double-blind studies are now required.


Identification of a novel locus that regulates expression of toxin genes in Clostridium perfringens.
A novel gene that regulates the alpha-toxin (plc), kappa-toxin (colA), and theta;-toxin (pfoA) genes was identified using toxin-negative mutant strains of Clostridium perfringens. The cloned 3.2-kb fragment contained the virX gene encoding a 51-amino acid polypeptide of unknown function that seemed to be responsible for the activation of toxin genes. The virX knock out mutant of wild-type strain 13 showed a reduced expression of the plc, colA, and pfoA genes, which was complemented by the transformation of the intact virX gene. Deletion and site-directed mutagenesis studies suggested that the virX gene acts as a regulatory RNA rather than as a peptide regulator. The virX locus found in this study might play a part in the signal transduction to regulate toxin production in C. perfringens.


MRI/TRUS data fusion for prostate brachytherapy. Preliminary results.
Prostate brachytherapy involves implanting radioactive seeds (I125 for instance) permanently in the gland for the treatment of localized prostate cancers, e.g., cT1c-T2a N0 M0 with good prognostic factors. Treatment planning and seed implanting are most often based on the intensive use of transrectal ultrasound (TRUS) imaging. This is not easy because prostate visualization is difficult in this imaging modality particularly as regards the apex of the gland and from an intra- and interobserver variability standpoint. Radioactive seeds are implanted inside open interventional MR machines in some centers. Since MRI was shown to be sensitive and specific for prostate imaging whilst open MR is prohibitive for most centers and makes surgical procedures very complex, this work suggests bringing the MR virtually in the operating room with MRI/TRUS data fusion. This involves providing the physician with bi-modality images (TRUS plus MRI) intended to improve treatment planning from the data registration stage. The paper describes the method developed and implemented in the PROCUR system. Results are reported for a phantom and first series of patients. Phantom experiments helped characterize the accuracy of the process. Patient experiments have shown that using MRI data linked with TRUS data improves TRUS image segmentation especially regarding the apex and base of the prostate. This may significantly modify prostate volume definition and have an impact on treatment planning.


Designing a B Cell-Based Vaccine against a Highly Variable Hepatitis C Virus.
The ability to use structure-based design and engineering to control the molecular shape and reactivity of an immunogen to induce protective responses shows great promise, along with corresponding advancements in vaccine testing and evaluation systems. We describe in this review new paradigms for the development of a B cell-based HCV vaccine. Advances in test systems to measure in vitro and in vivo antibody-mediated virus neutralization include retroviral pseudotype particles expressing HCV E1E2 glycoproteins (HCVpp), infectious cell culture-derived HCV virions (HCVcc), and surrogate animal models mimicking acute HCV infection. Their applications have established the role of broadly neutralizing antibodies to control HCV infection. However, the virus has immunogenic regions in the viral envelope glycoproteins that are associated with viral escape or non-neutralizing antibodies. These regions serve as immunologic decoys that divert the antibody response from less prominent conserved regions mediating virus neutralization. This review outlines the immunogenic regions on E2, which are roughly segregated into the hypervariable region 1 (HVR1), and five clusters of overlapping epitopes designated as antigenic domains A-E. Understanding the molecular architecture of conserved neutralizing epitopes within these antigenic domains, and how other antigenic regions or decoys deflect the immune response from these conserved regions will provide a roadmap for the rational design of an HCV vaccine.


[Power, status and valency in healthy and ill partners].
Using the degree of identification and projection (self concept/concept of self as perceived by others--Giessen-test) it was possible to develop a new approach to power, status and valency in couple relationships by means of deriving theoretical probabilities from those three core variables. The anticipated scores were validated using a number of reference scores of typical clinical samples and putting them in relationship to the standardized marital couples.


Absence of calcitriol-mediated nongenomic actions in isolated intestinal cells of the damara mole-rat (Cryptomys damarensis).
Calcitriol [1,25(OH)2D3] actions on intestinal calcium transport involve genomic and nongenomic pathways. Whether nongenomic 1,25(OH)2D3-mediated actions are employed was investigated using isolated intestinal epithelial cells of naturally vitamin D-deficient underground-dwelling damara mole-rats (Cryptomys damarensis). 1,25(OH)2D3-mediated nongenomic pathways of intestinal calcium uptake, measured by opening of 1,25(OH)2D3-activated voltage-sensitive Ca2+ channels (VSCC), did not occur. Rapid (1 min) 45Ca2+ transmembrane influx in intestinal cells was not significantly increased by the addition of 1,25(OH)2D3 (at concentrations from 10(-12) to 10(-6) nM), when compared to opening of VSCC in the presence of a depolarizing (elevated K+) buffer. Furthermore, even after 30 min calcium uptake was not significantly enhanced by the hormone. These findings support earlier reports that duodenal calcium absorption is independent of vitamin D and is a highly adaptive feature of a subterranean existence.


OTSC assisted EFTR for the treatment of GIST: 40 cases analysis.
To verify the safety and efficacy of over-the-scope clip (OTSC)-assisted endoscopic full-thickness resection (EFTR) for the excision of stromal tumors. Forty patients with gastric stromal tumors treated in the Department of Gastroenterology, Binzhou Medical University Hospital from December 2015 to March 2017 were included in this study. The surgical procedures included marking the lesion boundaries, cutting open the top surface of the lesion, installing an OTS, sucking the lesion into the transparent cap of the anatomical clip which was then released, application of an endoloop for EFTR, and confirming the complete resection and pathological examination of the lesion. Statistical analysis of the tumor site and size, operation time, success rates, complications, pathological examination results, and follow-up status was performed. The average operation duration was 38.40 ± 24.9 min. Three cases had an incomplete resection, but the lesion was later found to have fallen off together with the OTSC. Therefore, the treatment success rate was 100%. Postoperative pathological examination revealed leiomyomas in four cases and stromal tumors in the remaining 36 cases. OTSC-assisted EFTR is safe and effective for resection of gastrointestinal stromal tumors, especially for those <20 mm in size.


The corticotopic organization of the human basal forebrain as revealed by regionally selective functional connectivity profiles.
The cholinergic basal forebrain (CBF), comprising different groups of cortically projecting cholinergic neurons, plays a crucial role in higher cognitive processes and has been implicated in diverse neuropsychiatric disorders. A distinct corticotopic organization of CBF projections has been revealed in animal studies, but little is known about their organization in the human brain. We explored regional differences in functional connectivity (FC) profiles within the human CBF by applying a clustering approach to resting-state functional magnetic resonance imaging (rs-fMRI) data of healthy adult individuals (N = 85; 19-85 years). We further examined effects of age on FC of the identified CBF clusters and assessed the reproducibility of cluster-specific FC profiles in independent data from healthy older individuals (N = 25; 65-89 years). Results showed that the human CBF is functionally organized into distinct anterior-medial and posterior-lateral subdivisions that largely follow anatomically defined boundaries of the medial septum/diagonal band and nucleus basalis Meynert. The anterior-medial CBF subdivision was characterized by connectivity with the hippocampus and interconnected nodes of an extended medial cortical memory network, whereas the posterior-lateral subdivision was specifically connected to anterior insula and dorsal anterior cingulate components of a salience/attention network. FC of both CBF subdivisions declined with increasing age, but the overall topography of subregion-specific FC profiles was reproduced in independent rs-fMRI data of healthy older individuals acquired in a typical clinical setting. Rs-fMRI-based assessments of subregion-specific CBF function may complement established volumetric approaches for the in vivo study of CBF involvement in neuropsychiatric disorders.


An immunofluorescence study of light chain in pemphigus.
Immunofluorescence studies were made on light (L) chain of immunoglobulins in patients with pemphigus. These patients fell into two groups: a subcorneal bulla group, consisting of 10 patients with Senear-Usher syndrome, and one with pemphigus foliaceus, and a suprabasal bulla group consisting of 8 patients with pemphigus vulgaris. In the former group there was deposition of L chains of either type alone in the intercellular spaces of the upper epidermis: kappa type alone in 9 and lambda type alone in 2 patients. Deposition of L chains of both types was observed in the intercellular spaces of the lower epidermis in all patients of the latter group. No significant difference existed between groups as to the titre of circulating intercellular antibodies of either type. Some comments are made on the significance of the L chain of immunoglobulins in a pemphigus.


Synthesis and histamine H2-agonistic activity of ring-substituted phenyl analogues of impromidine.
Analogues of the H2-agonist impromidine, characterized by a substituted phenyl ring instead of the 5-methyl-4-imidazolyl group, were prepared and tested for their H2-agonistic and H1-antagonistic activity at the guinea-pig atrium and ileum, respectively. The compounds were synthetized via successive aminolysis of diphenyl benzoylcarbonimidate and final acid hydrolysis of the benzoylguanidines. The substituents (mono- or disubstitution with F, Cl, Br, CF3, Me, Et, NO2, NMe2, NEt2, PhCH2) were mainly selected according to the structure-activity relationships known from potent cardiohistaminergics such as arpromidine. While in the arpromidine series substitution of the phenyl ring, in particular halogenation, proved to be very useful for increasing potency, in the series of title compounds, except for the m-fluoro analogue 5g, these variations resulted in a decrease in H2-agonistic activity in the isolated guinea-pig right atrium up to 1.5 orders of magnitude related to the parent compound 5a, which is 10 times more potent than histamine.


Environment-assisted quantum walks in photosynthetic energy transfer.
Energy transfer within photosynthetic systems can display quantum effects such as delocalized excitonic transport. Recently, direct evidence of long-lived coherence has been experimentally demonstrated for the dynamics of the Fenna-Matthews-Olson (FMO) protein complex [Engel et al., Nature (London) 446, 782 (2007)]. However, the relevance of quantum dynamical processes to the exciton transfer efficiency is to a large extent unknown. Here, we develop a theoretical framework for studying the role of quantum interference effects in energy transfer dynamics of molecular arrays interacting with a thermal bath within the Lindblad formalism. To this end, we generalize continuous-time quantum walks to nonunitary and temperature-dependent dynamics in Liouville space derived from a microscopic Hamiltonian. Different physical effects of coherence and decoherence processes are explored via a universal measure for the energy transfer efficiency and its susceptibility. In particular, we demonstrate that for the FMO complex, an effective interplay between the free Hamiltonian evolution and the thermal fluctuations in the environment leads to a substantial increase in energy transfer efficiency from about 70% to 99%.


Engineered holliday junctions as single-molecule reporters for protein-DNA interactions with application to a MerR-family regulator.
Protein-DNA interactions are essential for gene maintenance, replication, and expression. Characterizing how proteins interact with and change the structure of DNA is crucial in elucidating the mechanisms of protein function. Here, we present a novel and generalizable method of using engineered DNA Holliday junctions (HJs) that contain specific protein-recognition sequences to report protein-DNA interactions in single-molecule FRET measurements, utilizing the intrinsic structural dynamics of HJs. Because the effects of protein binding are converted to the changes in the structure and dynamics of HJs, protein-DNA interactions that involve small structural changes of DNA can be studied. We apply this method to investigate how the MerR-family regulator PbrR691 interacts with DNA for transcriptional regulation. Both apo- and holo-PbrR691 bind the stacked conformers of the engineered HJ, change their structures, constrain their conformational distributions, alter the kinetics, and shift the equilibrium of their structural dynamics. The information obtained maps the potential energy surfaces of HJ before and after PbrR691 binding and reveals the protein actions that force DNA structural changes for transcriptional regulation. The ability of PbrR691 to bind both HJ conformers and still allow HJ structural dynamics also informs about its conformational flexibility that may have significance for its regulatory function. This method of using engineered HJs offers quantification of the changes both in structure and in dynamics of DNA upon protein binding and thus provides a new tool to elucidate the correlation of structure, dynamics, and function of DNA-binding proteins.


Cerium Oxide Nanoparticle Administration to Skeletal Muscle Cells under Different Gravity and Radiation Conditions.
For their remarkable biomimetic properties implying strong modulation of the intracellular and extracellular redox state, cerium oxide nanoparticles (also termed "nanoceria") were hypothesized to exert a protective role against oxidative stress associated with the harsh environmental conditions of spaceflight, characterized by microgravity and highly energetic radiations. Nanoparticles were supplied to proliferating C2C12 mouse skeletal muscle cells under different gravity and radiation levels. Biological responses were thus investigated at a transcriptional level by RNA next-generation sequencing. Lists of differentially expressed genes (DEGs) were generated and intersected by taking into consideration relevant comparisons, which led to the observation of prevailing effects of the space environment over those induced by nanoceria. In space, upregulation of transcription was slightly preponderant over downregulation, implying involvement of intracellular compartments, with the majority of DEGs consistently over- or under-expressed whenever present. Cosmic radiations regulated a higher number of DEGs than microgravity and seemed to promote increased cellular catabolism. By taking into consideration space physical stressors alone, microgravity and cosmic radiations appeared to have opposite effects at transcriptional levels despite partial sharing of molecular pathways. Interestingly, gene ontology denoted some enrichment in terms related to vision, when only effects of radiations were assessed. The transcriptional regulation of mitochondrial uncoupling protein 2 in space-relevant samples suggests perturbation of the intracellular redox homeostasis, and leaves open opportunities for antioxidant treatment for oxidative stress reduction in harsh environments.


Morphology studies of the human fetal cochlea in turner syndrome.
Turner syndrome (TS) is the most frequent sex chromosome abnormality, and sensorineural hearing loss is common. We aimed to determine whether there are consistent morphologic cochlear abnormalities during gestational development that could be associated with TS. The histology of nine fetal temporal bones of TS autopsied after spontaneous abortion was studied. Gross morphologic examination of the TS cochleae failed to reveal a pattern of structural abnormalities that would explain the development of sensorineural hearing loss. Mondini-like cochlear dysplasia was observed in one 13-wk-old TS fetus. We could not demonstrate a consistent pattern of cochlear malformations.


Fever, pulmonary haemorrhage, and acute renal failure in a young girl.
Leptospirosis is rarely reported in children. It is easily treated with antibiotics but can be fatal if treatment is delayed. A 12-year-old girl was diagnosed with Weil syndrome, a severe form of leptospirosis, 10 days after returning from Mainland China. She presented with fever, hypotension, jaundice, and acute renal failure. She had used well water for bathing and swum in freshwater.


Prospective evaluation of red man syndrome in patients receiving vancomycin.
The incidence of red man syndrome (RMS) and its relationship to histamine were investigated in patients receiving vancomycin or an aminoglycoside (control). During the 60-min infusions, patients were observed for signs or symptoms consistent with RMS, including pruritus, erythema, angioedema, and cardiovascular depression. Four blood samples were obtained at 30-min intervals for determination of histamine concentrations. One (3.4%) of 29 vancomycin- and none of 8 aminoglycoside-treated patients had documented RMS. The mean maximum changes in blood pressure and heart rate were not significant and were similar between groups. Increases in histamine concentrations to > 1 ng/mL occurred only in 25% (2/8) of the aminoglycoside patients. Vancomycin induced minimal changes in histamine concentrations despite the occurrence of RMS. From these observations, it appears that RMS is not closely associated with histamine release, and elevated histamine concentrations do not predict RMS. Further investigation is needed to elucidate other mediators of RMS.


Reserve cells in human uterine cervical epithelium are derived from müllerian epithelium at midgestational age.
The role of endocervical reserve cells in squamous metaplasia and neoplasia is still debated. Their origin in the cervix is open to speculation and it is unclear how they are targeted during carcinogenesis. To further understand the primary characteristics of reserve cells, we phenotyped them in the developing human cervix. In 13 perinatal autopsies of fetuses between 16 and 40 weeks of gestation, the human fetal cervix was evaluated in serial sections. Immunostaining comprised a panel of antibodies for cytokeratins, p63, and bcl-2; then, the sections were stained with Alcian blue and periodic acid-Schiff before and after diastase treatment. Reserve cells are first identified at approximately 20 weeks of gestation. They are first noted under müllerian-type columnar cells lining the developing uterine cavity. There is considerable overlap in the expression profiles of müllerian cells and reserve cells for p63, bcl-2, and cytokeratins 5, 8, and 18 at this stage of development, with increasing gestational age expression localized to respective cell compartments. Eventually, the phenotype of these cells correspond fully with that described for adult reserve cells and endocervical cells. Müllerian epithelial cells are the stem cell for endocervical reserve cells and endocervical columnar cells. They have the capacity to transform into both endocervical columnar and squamous-type epithelium in the endocervix during early cervical development.


Melatonin and vitamin E alleviate homocysteine-induced oxidative injury and apoptosis in endothelial cells.
A relationship exists between hyperhomocysteinemia and cardiovascular diseases, although the underlying mechanisms are still incompletely defined. One possibility involves a homocysteine (Hcy)-induced increased oxidative stress. Melatonin (Mel) and vitamin E (vitE) are important anti-oxidants. The main purpose of this study was (1) to compare the effect of treatments with Mel, vitE or both, on Hcy-induced apoptosis in human umbilical vein endothelial cells (HUVECs), and (2) to investigate the underlying mechanisms. Cell proliferation assay was carried out by Water Soluble Tetrazolium-1 (WST-1) assay kit. Apoptotic index was calculated by TUNEL Assay. Anti-oxidant parameters were studied by measurement of reactive oxygen species (ROS) and lipid peroxidation (LPO) levels. mRNA and protein expression levels of apoptotic and anti-apoptotic genes and proteins were studied by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting experiments respectively. The results showed that treatments with Mel, vitE or Mel + vitE suppressed Hcy-induced cell death, with a higher efficiency for the Mel and Mel + vitE treatments. Our results suggests that the mechanisms by which these anti-oxidants protected endothelial cells include the decrease in ROS and LPO levels, an increase in cell migration, the downregulation of pro-apoptotic proteins Cas 3, Cas 9, Cyt C and Bax and the upregulation of anti-apoptotic protein Bcl 2. Collectively, these results revealed the protective role of vitE and Mel against Hcy-induced cell apoptosis, which may add insight into therapeutic approaches to Hcy-induced damages.


Live discharge from hospice care: psychosocial challenges and opportunities.
Hospice social workers face many challenges in attempts to replicate or supplement the holistic support and unique services hospice provides for individuals discharged alive. This discontinuity in care can impact the types of supports needed by individuals and caregivers, which may or may not be accessible within their community. Patients and families who have access to community-based palliative care programs following a discharge generally tend to navigate the process with fewer challenges. This qualitative study (N = 24) explored both the challenges of the live discharge process and the opportunities within social work practice in the US. Results from this study emphasize the need for a framework to better approach a live discharge to ensure appropriate supports are accessible for all patients and caregivers. Specifically, results highlight both the concrete and psychosocial challenges in live discharges as a result of tension between current eligibility requirements and individual feelings and needs. Social workers also provided suggestions to improve the live discharge process, including attention to communication and preparation. This paper outlines specific challenges of live discharge from hospice, a framework for understanding presented challenges, and implications for policy and practice.


Polygenic inheritance of breast cancer: Implications for design of association studies.
Susceptibility to breast cancer is likely to be the result of susceptibility alleles in many different genes. In particular, one segregation analysis of breast cancer suggested that disease susceptibility in noncarriers of BRCA1/2 mutations may be explicable in terms of a polygenic model, with large numbers of susceptibility polymorphisms acting multiplicatively on risk. We considered the implications for such a model on the design of association studies to detect susceptibility polymorphisms, in particular the efficacy of utilizing cases with a family history of the disease, together with unrelated controls. Relative to a standard case-control association study with cases unselected for family history, the sample size required to detect a common disease susceptibility allele was typically reduced by more than twofold if cases with an affected first-degree relative were selected, and by more than fourfold if cases with two affected first-degree relatives were utilized. The relative efficiency obtained by using familial cases was greater for rarer alleles. Analysis of extended families indicated that the power was most dependent on the immediate (first-degree) family history. Bilateral cases may offer a similar gain in power to cases with two affected first-degree relatives. In contrast to the strong effect of family history, varying the ages at diagnosis of the cases across the range of 35-65 years did not strongly affect the power to detect association. These results indicate that association studies based on cases with a strong family history, identified for example through cancer genetics clinics, may be substantially more efficient than population-based studies.


High-performance liquid chromatography analysis of black currant (Ribes nigrum L.) fruit phenolics grown either conventionally or organically.
Black currants (Ribes nigrum L.) contain a diverse range of phenolics and possess a high antioxidant activity, which makes them an interesting target for the functional food industry. In this study, phenolic profiles of organically and conventionally grown black currant fruits, collected from commercial farms within a climatically similar area, were compared. Compounds were identified using UV/vis and mass spectroscopy techniques and quantified with high-performance liquid chromatography equipped with UV/vis detection. Several different conjugates of hydroxycinnamic acids, flavonols, and anthocyanins were quantified. Statistically significant differences between farms were found for almost all compounds. Differences between the highest and the lowest measured values of major phenolic compounds of different phenolic classes ranged from 24 to 77%. Principal component analysis quite effectively separated farms from each other but did not cluster them according to cultivation technique. Thus, it was concluded that the biochemical quality of organically grown black currant fruits does not differ from those grown conventionally.


[Methotrexate therapy of rheumatoid arthritis. An open observation study of 110 patients with median length of treatment of 17.8 month].
Effects and side-effects of treating patients with rheumatoid arthritis with methotrexate given as weekly pulse-treatment are examined in an open observation study. One hundred and ten consecutive patients with active rheumatoid arthritis entered the study. Six criteria of remission were registered as effect variables. Median length of treatment at the time of investigation was 17.8 months. At this point, 34 patients were in complete remission, with a median effect score of five point five out of six possible points. Twenty-nine were in partial remission and 47 (42.7%) had not improved. The median effect score for all patients was three point 6 (95% confidence limits (2-4). Methotrexate treatment was stopped in 24 patients, in 15 of these because of a combination of side-effects and lack of therapeutic response. Prednisone treatment could be discontinued in 20 out of 57 patients during the course of methotrexate treatment. Side-effects were registered in 67 cases (62.7%), and led to treatment being discontinued in 21 cases. Nearly half the side-effects consisted of dyspepsia and rises in amino-transferase levels (48 of 67 patients). Consistently raised amino-transferase levels were found in five cases, all returned to normal after methotrexate was stopped. Serious side-effect were registered in four cases, consisting of two cases of short-term pancytopenia following overdosage and two cases of severe hypoxia following methotrexate-induced alveolitis.


The ethical implications of stratifying by race in pharmacogenomics.
Many predict that pharmacogenomics is poised to deliver on the promises of the genomic revolution in ushering an era of personalized medicine. However, questions have emerged over whether the field will deliver a truly individualized medicine or if population-based therapies that build on conventional notions of racial biology will prevail. At the heart of this issue is the challenge of knowing which axes of stratification are appropriate in identifying population differences and to what extent is race and/or ethnicity an appropriate method of comparison in studies of genetic variation. These questions make plain that in addition to the development of technical tools to identify salient gene variants associated with drug response, serious consideration over how best to characterize populations in human genetic variation research must be given in order to realize the putative benefits of tailored therapeutics.


QUANTUM DOT SINGLE MOLECULE TRACKING REVEALS A WIDE RANGE OF DIFFUSIVE MOTIONS OF MEMBRANE TRANSPORT PROTEINS.
Single particle tracking (SPT) provides information about the microscopic motions of individual particles in live cells. We applied SPT to study the diffusion of membrane transport proteins in cell plasma membranes in which individual proteins are labeled with quantum dots at engineered extracellular epitopes. Software was created to deduce particle diffusive modes from quantum dot trajectories. SPT of aquaporin (AQP) water channels and cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels revealed several types of diffusion. AQP1 was freely mobile in cell membranes, showing rapid, Brownian-type diffusion. The full-length (M1) isoform of AQP4 also diffused rapidly, though the diffusion of a shorter (M23) isoform of AQP4 was highly restricted due to its supermolecular assembly in raft-like orthogonal arrays. CFTR mobility was also highly restricted, in a spring-like potential, due to its tethering to the actin cytoskeleton through PDZ-domain C-terminus interactions. The biological significance of regulated diffusion of membrane transport proteins is a subject of active investigation.


A Natural Benzofuran from the Patagonic Aleurodiscus vitellinus Fungus has Potent Neuroprotective Properties on a Cellular Model of Amyloid-β Peptide Toxicity.
Alzheimer's disease (AD) is characterized by amyloid plaques that form due to an increase in amyloid-β peptide (Aβ) aggregation. One strategy in the search of new treatments for AD focuses on compounds that decrease Aβ accumulation. Compounds containing a benzofuran ring have been described to play an important role in decreasing Aβ-induced toxicity; however, only synthetic benzofurans have been tested thus far. The aim of the present study was to examine the in vitro neuroprotective properties of fomannoxin (Fx), a natural benzofuran isolated from cultures of the Andean-Patagonian fungi Aleurodiscus vitellinus, and evaluate its effect on Aβ peptide. We tested the effect of Fx at a wide concentration range (10-11-10-4 M) in PC-12 cells, and found the compound did not alter cellular viability. Fx also showed a concentration-dependent effect on the Aβ-induced toxicity in PC12 cells, showing viability above 100% at 10-6 M. We then measured the effect of Fx (10-7-10-5 M) on the frequency of cytosolic Ca2+ transients in rat hippocampal neurons at both acute and chronic (24 h) times. Acute incubation with Fx increased the frequency of cytosolic Ca2+ transients to values around 200%, whereas chronic incubation with Fx increased the frequency of Ca2+ transients. Finally, the Aβ-induced decrease in intracellular Ca2+ transients was prevented when Fx (10-6 M) was co-incubated with Aβ (5×10-6 M). The results suggest a potent neuroprotective effect of this naturally occurring benzofuran against Aβ peptide toxicity that could be mediated by an interference with it binding to plasma membrane, and lead Fx as new chemical entity to develop pharmacological tools against Aβ peptide neurotoxicity.


Advanced hepatocellular carcinoma with MET-amplified contained excellent response to crizotinib: a case report.
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. Several novel therapeutic strategies have been developed to prolong the survival of patients with advanced HCC. However, therapeutic decision-making biomarkers owing to the extensive heterogeneity of HCC. Next-generation sequencing (NGS) is generally used in treatment decisions to help patients benefit from genome-directed targeting. A 56 year-old male with type-B hepatitis for more than 20 years was admitted to our department and underwent laparoscopic left lateral hepatic lobectomy for hepatocellular carcinoma. Unfortunately, the tumor recurred 1 year later. Despite multiple treatments, the tumor continued to progress and invaded the patient's 5th thoracic vertebras, leading to hypoesthesia and hypokinesia below the nipple line plane 2 years later. NGS revealed MET amplification, and crizotinib, an inhibitor of MET, was recommended. After administration for a month, tumor marker levels decreased, and the tumor shrunk. The patient has remained in remission since that time. We report that a patient with high MET amplification benefited from its inhibitor, which was recommended by NGS. This indicates the potential clinical decision support value of NGS and the satisfactory effect of MET inhibitors.


Keratoderma-like T cell dyscrasia: A report of 13 cases and its distinction from mycosis fungoides palmaris et plantaris.
Atypical epitheliotropic T cell lymphocytic infiltrates are commonly encountered in routine and consultative dermatopathology practices and typically do not represent mycosis fungoides. Other conditions can mimic certain light microscopic and phenotypic findings encountered in mycosis fungoides, comprising a diverse spectrum of conditions including the lymphomatoid drug reaction, collagen vascular disease, viral hypersensitivity reactions and cutaneous T cell dyscrasia. To examine biopsies obtained from cutaneous T cell dyscrasia localized to the palms and soles and to evaluate whether it exhibits a morphologic and pathogenetic continuum with mycosis fungoides plantaris et palmaris. We examined 13 biopsies showing an epidermotropic superficial lymphocytic infiltrate from thirteen patients who presented with a palmar and/or plantar keratoderma without other sites of cutaneous involvement. Conventional light microscopy, immunophenotyping and clonality studies were carried out. The clinical features were recorded. Biopsies showed a variably dense, superficial, angiocentric CD4 or CD8 dominant lymphocytic infiltrate accompanied by a non-destructive pattern of epidermotropism. Low-grade cerebriform atypia along with variable diminution in the expression of CD7 and CD62L was noted. In three cases, statins were suspected to be the cause. Due to lack of familiarity with the entity, treatment interventions were inconsistent and not aggressively pursued. There was no evidence of disease progression to mycosis fungoides in any case. The limitations of this study include the lack of long-term follow up and information on the nature of the therapeutic interventions and responses to treatment. The spectrum of cutaneous lymphoid dyscrasias should be expanded to include cases manifesting as palmo-plantar keratoderma. These cases are to be distinguished from mycosis fungoides palmaris et plantaris. As with other forms of cutaneous lymphoid dyscrasia, the lesions tend to be persistent. The course however, is indolent in most cases.


Synthesis and in vitro evaluation of quaternary ammonium derivatives of chlorambucil and melphalan, anticancer drugs designed for the chemotherapy of chondrosarcoma.
To enhance affinity for malignant cartilaginous tumors (chondrosarcomas), quaternary ammonium (QA) conjugates of chlorambucil and melphalan were prepared by linking the QA moiety to nitrogen mustards via an amide bond. They exhibited closely similar and sometimes more favorable values than their parent compounds. In the cell lines tested, the two QA conjugates displayed appreciable cytotoxicity, the QA conjugate of chlorambucil even showing an enhanced efficiency against chondrosarcoma compared with chlorambucil.


The Saliva Exposome for Monitoring of Individuals' Health Trajectories.
There is increasing evidence that environmental, rather than genetic, factors are the major causes of most chronic diseases. By measuring entire classes of chemicals in archived biospecimens, exposome-wide association studies (EWAS) are being conducted to investigate associations between a myriad of exposures received during life and chronic diseases. Because the intraindividual variability in biomarker levels, arising from changes in environmental exposures from conception onwards, leads to attenuation of exposure-disease associations, we posit that saliva can be collected repeatedly in longitudinal studies to reduce exposure-measurement errors in EWAS. From the literature and an open-source saliva-metabolome database, we obtained concentrations of 1,233 chemicals that had been detected in saliva. We connected salivary metabolites with human metabolic pathways and PubMed Medical Subject Heading (MeSH) terms, and performed pathway enrichment and pathway topology analyses. One hundred ninety-six salivary metabolites were mapped into 49 metabolic pathways and connected with human metabolic diseases, central nervous system diseases, and neoplasms. We found that the saliva exposome represents at least 14 metabolic pathways, including amino acid metabolism, TCA cycle, gluconeogenesis, glutathione metabolism, pantothenate and CoA biosynthesis, and butanoate metabolism. Saliva contains molecular information worthy of interrogation via EWAS. The simplicity of specimen collection suggests that saliva offers a practical alternative to blood for measurements that can be used to characterize individual exposomes. https://doi.org/10.1289/EHP1011.


Ionic-liquid-bifunctional wrapping of ultrafine SnO2 nanocrystals into N-doped graphene networks: high pseudocapacitive sodium storage and high-performance sodium-ion full cells.
Sodium ion batteries are in great need of electrode materials with high specificity and rate capability being developed. The sluggish reaction kinetics of SnO2-based materials has impeded their applications as anodes of SIBs. Designing electrode materials with high pseudocapacitive contribution can increase the near-surface faradaic reaction, which helps to improve their kinetics and achieve high rate capability. Here, we designed a high-pseudocapacitance sodium storage anode SnO2/N-rGO by downsizing the particle size of SnO2 and constructing an N-doped graphene wrapped structure. The ultrafine structure of SnO2 ensures the high faradaic near-surface reaction, while the N-doped graphene matrix guarantees the superior electron and Na+ diffusion. Meanwhile, the wrapped N-doped graphene acts as a buffer layer to alleviate the volumetric changes of the active SnO2. The obtained ultrafine SnO2/N-graphene composite exhibits a high capacity of 607.6 mA h g-1 at 50 mA g-1 with an impressive rate capability (261.8 mA h g-1 at 2 A g-1) in Na+ half-cells. Furthermore, a good performance with a capacity of 133.3 mA h g-1 at 2.4 A g-1 in Na+ full-cells can also be achieved, which makes it a promising anode material for SIBs.


Perceptions of psychiatry of old age amongst psychiatry registrars in Australia and New Zealand.
To assess the perceptions of psychiatry registrars of their training experience in Psychiatry of Old Age (POA), and whether factors such as clinical exposure and stage of training correlate with these perceptions. Royal Australian and New Zealand College of Psychiatrists (RANZCP) registrars were surveyed in September 2009. Demographic information, POA exposure and responses to 14 statements related to registrar experience were collected. From 978 surveys sent, 226 responses were complete enough to be analysed. Themes that emerged included a high level of enjoyment of a POA rotation, favourable views of supervision, the challenging nature of managing medical co-morbidities and concerns regarding the teaching of cognitive assessment. In general, type or duration of POA exposure and demographic variables were not correlated with a significant difference in perceptions of the field. These data may be useful in addressing a shortfall of trainees in POA, which has implications for the health of older Australasians. It may inform service providers and the RANZCP of factors that could be modified or optimised to encourage registrars to consider subspecialty training in the area.


Cytotoxicity and proinflammatory cytokine expression induced by interim resin materials in primary cultured human dental pulp cells.
Acrylic resin materials for interim restoration may adversely affect pulp tissue during the polymerization phase. The purpose of this in vitro study was to determine the cytotoxic and proinflammatory cytokine production effects induced by interim resin materials in primary cultured human dental pulp cells (hDPCs). Five interim resin materials were evaluated: 3 types of chemically activated products, 1 light-activated product, and 1 computer-aided design and computer-aided manufacturing (CAD-CAM) product. After obtaining eluates from interim resin materials that either were in the process of polymerizing or were already polymerized, these extracts were cocultured with hDPCs under serially diluted conditions (50%, 25%, 12.5%, 6.25%, and 3.125%) for 24 hours with positive (1% phenol) and negative (distilled water) controls. A cell viability assay with tetrazolium was used to evaluate toxic effects on the cells, and images of both live and dead cells were captured using confocal microscopy. Proinflammatory cytokine levels were measured using cytokine antibody arrays. All experiments were independently repeated 3 times, and data were analyzed using 1-way ANOVA and post hoc Tukey honest significant differences test (α=.05). Cell viabilities less than 70% were observed from the eluates of the 3 chemically activated products under the 50% conditions. Among the chemically activated products, the adverse effects were significantly greater with eluates derived from the polymerizing phase compared than those that had already polymerized, as shown by confocal microscopy images of live and dead cells. However, the light-activated and CAD-CAM-fabricated products did not adversely affect the hDPCs. Significantly increased levels of proinflammatory cytokines were not detected in 12.5% of extract from polymerizing compared with distilled water control. The 50% eluates derived from chemically activated interim resin during the polymerizing phase were cytotoxic to hDPCs and may adversely affect pulp tissue. Recommendations such as excess washing are necessary during fabrication.


[Clinical studies on effect of cefbuperazone on surgical infections].
We conducted clinical studies on the efficacy and safety of cefbuperazone (CBPZ) on surgical infections with the following results. 1) In evaluable 32 patients, CBPZ was evaluated to be clinically effective in 23 (71.9%) and the efficacy rate was better in those who were administered 4 g/day of CBPZ (87.5%, 14/16) than in those who were given 2 g/day (57.1%, 8/14). 2) Antibacterial activity of CBPZ was evaluated in 41 isolated bacterial strains. Pathogen eradication rate by bacterial species was 75.6% (31/41). CBPZ exerted excellent antibacterial effects on Escherichia coli (100%, 8/8) and anaerobic bacteria such as Bacteroides (88.9%, 8/9). Resistant bacteria to CBPZ were Enterococcus faecalis and Pseudomonas aeruginosa. 3) No serious side effects were noted in any of the 34 patients who entered in this study. Abnormal laboratory test results were noted in 2 patients (5.9%) and they were transient elevation of transaminases and alkaline phosphatase. From the results shown above, CBPZ appears to be a highly useful antibiotic for the treatment of surgical infection.


Expression of cancer/testis antigens in salivary gland carcinomas with reference to MAGE-A and NY-ESO-1 expression in adenoid cystic carcinoma.
Cancer/testis antigens (CTAs) are detected in cancer cells but not in healthy normal tissues, with the exception of gametogenic tissues. CTAs are highly immunogenic proteins, and thus represent ideal targets for cytotoxic T-lymphocyte-mediated specific immune therapy. The aim of this study was to screen CTA expression in various types of salivary gland carcinoma and to clarify clinicopathological significance of MAGE-A and NY-ESO-1 expression in adenoid cystic carcinomas (AdCCs) of the salivary gland, which is one of the most common salivary gland carcinomas, and usually has a fatal outcome. We used immunohistochemistry to examine the expression of four CTAs (MAGE-A, NY-ESO-1, CT7, and GAGE7) in various types of salivary gland carcinoma (n = 95). When carcinoma cases were divided into low-grade and intermediate/high-grade types, NY-ESO-1 and CT7 were expressed more frequently in intermediate/high-grade carcinomas. We then focused on MAGE-A and NY-ESO-1 expression in a large cohort of adenoid cystic carcinomas (AdCCs) (n = 46). MAGE-A and NY-ESO-1 were frequently expressed in AdCC; specifically, MAGE-A was expressed in >60% of the AdCC cases. MAGE-A expression and tumour site (minor salivary gland) were identified as independent risk factors for locoregional tumour recurrence. These findings suggest that CTAs may be expressed in a variety of salivary gland carcinomas, especially in those with higher histological grades. In addition, MAGE-A, which is frequently expressed in AdCC cases, may be a useful prognostic factor for poorer locoregional recurrence-free survival.


4'-demethylepipodophyllotoxin 9-(4,6-o-2-thenylidene-beta-D-glucopyranoside) (NSC-122819; VM-26) and 4'-demethylepipodophyllotoxin 9-(4.6-0-ethylidene-beta-D-glucopyranoside) (NSC-141540; VP-16-213) in childhood cancer: preliminary observations.
We evaluated the responses of 39 children with cancer who, after failure to respond to conventional chemotherapeutic agents, received either or both of two epipodophyllotoxins: 4'-demethylepipodophyllotoxin 9-(4,6-o-2-thenylidene-beta-D-glucopyranoside) (NSC-122819) and 4'-demethylepipodophyllotoxin 9-(4,6-o-ethylidene-beta-D-glucopyranoside) (NSC-141540). Seventeen patients has acute lymphocytic leukemia (ALL). 12 had acute nonlymphocytic leukemia (ANLL), and ten had solid tumors. Initially, the patients in each disease category were randomized to receive 50 mg/m2/dose of NSC-122819 intravenously (iv) twice weekly or 75 mg/m2/dose iv of NSC-141540 twice weekly for 4 weeks. Drug dosages and schedules of administration were adjusted during the course of the study. Although objective responses were not detected in the heterogeneous group of solid tumor patients, definite clinical responses were obtained in nine of the 29 patients with acute leukemia. The responses to the two epipodophyllotoxins were noted in patients with ALL as well as in patients with ANLL. Toxic side-effects included nausea, vomiting, diarrhea, fever, alopecia, leukopenia, and thrombocytopenia. These results, the first reported with both NSC-122819 and NSC-141540 in childhood cancer, indicate that the epipodophyllotoxins are well tolerated and may be effective against acute leukemia.


C-reactive proteins and chronic disease: what role does nutrition play?
The following review provides an update on C-reactive proteins (CRPs) and how they are related to chronic diseases and diet. Emphasis is placed on the mechanism that is involved in the infection/stress-induced formation of CRPs. CRPs' role as biomarkers for coronary heart disease is discussed. This review also discusses the roles that obesity, diabetes, smoking, and synthetic hormones play in increasing serum CRP concentrations. It also summarizes information about how dietary manipulation and exercise can decrease CRP concentrations. The dietary components that seem to lead to a decrease in CRPs include omega-3 fatty acids (fish oil), vitamin E, and moderate amounts of alcohol. Aspirin intake is also discussed as a method that can be used to decrease CRP concentrations.


Through-space spin-spin coupling in van der Waals dimers and CH/pi interacting systems. An ab initio and DFT study.
The through-space J(HH) and J(CH) spin-spin coupling constants of model van der Waals dimers (involving methane, ethylene, and benzene), and of selected compounds showing the CH/pi interaction, have been investigated by means of DFT and ab initio calculations. In the range of intermolecular separations for which the interaction is stabilizing, weak couplings (0.1-0.3 Hz) are predicted for J(CH), while the corresponding J(HH) couplings are much smaller. The relative contributions (Fermi-contact, spin-orbit, and spin-dipole) are strongly dependent on the geometry of the dimers and on the distance; the non-negligible values of J(CH) for pi systems stem largely from an incomplete cancellation of spin-orbit terms. The results obtained for the larger molecules, that is, acetonitrile@calix[4]arene 5, the imine 6, and the aryl ester 7 are consistent with those on the model dimers. For 7, the occurrence of a through-space mechanism for the transmission of coupling is established by examining trends in the magnitude of couplings as a function of the number of intervening covalent bonds.


Exposure to difenoconazole, diclofop-methyl alone and combination alters oxidative stress and biochemical parameters in albino rats.
The herbicides diclofop-methyl and the fungicide difenoconazole are widely used in agriculture and may lead to serious toxicity risks. However, limited studies have been done to evaluate differences in the metabolic effects of these herbicides. Difenoconazole (10 mg/kg) and Diclofop-methyl (1 mg/kg) were orally administrated individually (Groups 1 and 2 respectively) as well as combined (G3) to rats for 28 days. In all treated groups, alanine aminotransferase (ALT) and urea were significantly higher than the control group. Plasma creatinine was also significantly higher in groups G1 and G2 than control. Significant inhibition in gamma glutamyltransferase (γGT) was observed in all treated groups, in addition to significant inhibition of plasma acetylcholinesterase enzyme (AChE) in G3 (p < 0.01). There was no effect in aspartate aminotransferase (AST) and albumin. Total plasma triiodothy-ronine (T3) hormone was significantly higher in groups G2 and G3 (p < 0.01), but significantly lower in G1 group as compared to control. Thyroxin (T4) was significantly lower in all treated groups than control. Cholesterol level was significantly lower in G3 than control, and a total protein (TP) was significantly higher in all treated groups than control. No differences were observed in glucose levels. Malondialdehyde (MDA) and superoxide dismutase (SOD), an oxidative stress biomarker, was significantly increased in all treated groups comparing to control. Sulphur containing protein (SH-protein) was significantly lower in G1 than control. No significant changes were observed for GST in all treatments. The significant differences in measured biomarkers after application of diclofop-methyl, difenoconazole individually and combined indicate that the investigated pesticides may have potentially harmful effects on humans and the surrounding environment. We suggest that larger studies be conducted to better understand the toxicity mechanisms of these pesticides.


Rapid surface uplift and crustal flow in the Central Andes (southern Peru) controlled by lithospheric drip dynamics.
The high flux magmatism, crustal shortening/extension and plateau formation in Cordilleran orogenic systems have been explained by removal of lithosphere (lower crust and the sub-arc mantle lithosphere) that develops beneath the magmatic arc and hinterland regions. However, the primary role of this process driving surface uplift, and crustal deformation is not well understood. Here, reconciling geodynamic model predictions with lithospheric structure and paleoelevation estimates, we suggest that viscous drip-type lithospheric removal from beneath the Central (Peruvian) Andes can explain several tectonic features: (1) "double humped" shaped/axisymmetric topographic profile and rapid surface rise (up to 1.2 km in ~ 4.31 Myrs); (2) thicker crust associated with the lower surface elevation of the Altiplano plateau (Lake Titicaca region) (negative residual topography) and higher topography and thinner crust of Western and Eastern Cordilleras (positive residual topography); and (3) faster wave speed (colder)/sub-Moho anomaly underlying the Altiplano, surrounded by slower speed anomalies on both western arc-forearc areas and parts of the eastern Cordillera and Sub-Andes. Our results emphasize the important role of lithospheric drip and associated mantle dynamics in the transient evolution of Andean orogeny controlling surface uplift and crustal flow and thickening.


Silent cerebral infarction and cognitive function following TAVI: an observational two-centre UK comparison of the first-generation CoreValve and second-generation Lotus valve.
To compare the incidence of silent cerebral infarction and impact on cognitive function following transcatheter aortic valve implantation (TAVI) with the first-generation CoreValve (Medtronic, Minneapolis, Minnesota, USA) and second-generation Lotus valve (Boston Scientific, Natick Massachusetts, USA). A prospective observational study comprising a 1.5 T cerebral MRI scan, performed preoperatively and immediately following TAVI, and neurocognitive assessments performed at baseline, 30 days and 1 year follow-up. University hospitals of Leeds and Leicester, UK. 66 (80.6±8.0 years, 47% male) patients with high-risk severe symptomatic aortic stenosis recruited between April 2012 and May 2015. Incidence of new cerebral microinfarction and objective decline in neurocognitive performance. All underwent cerebral MRI at baseline and immediately following TAVI, and 49 (25 Lotus, 24 CoreValve) completed neurocognitive assessments at baseline, 30 days and 1 year. There was a significantly greater incidence of new cerebral microinfarction observed following the Lotus TAVI (23 (79%) vs 22 (59%), p=0.025) with a greater number of new infarcts per patient (median 3.5 (IQR 7.0) vs 2.0 (IQR 3.0), p=0.002). The mean volume of infarcted cerebral tissue per patient was equivalent following the two prostheses (p=0.166). More patients suffered new anterior (14 (48%) vs 2 (5%), p=0.001) and vertebrobasilar (15 (52%) vs 7 (19%), p=0.005) lesions following Lotus. Lotus was associated with a decline in verbal memory and psychomotor speed at 30 days. However, performance longitudinally at 1 year was preserved in all neurocognitive domains. There was a higher incidence of silent cerebral microinfarction and a greater number of lesions per patient following Lotus compared with CoreValve. However, there was no objective decline in neurocognitive function discernible at 1 year following TAVI with either prosthesis.


Brain and spinal cord lesions in the newborn rat.
Previous studies involving the induction of central nervous system lesions in animals have required complex, expensive equipment including sterotaxis and an operating microscope. This study describes a technique for producing telencephalic (forebrain) lesions in the developing rat by the use of copper wire. In addition, a nonvisual method of producing spinal cord transections in the young rat is discussed. Both techniques have a high succes rate and minimal mortality.


Clinical utilisation of the "G.T. MSRS", the rating scale for mixed states: 35 cases report.
The knowledge of the clinical features of the mixed states and of the symptoms of the "mixity" of mood disorders is crucial: to mis-diagnose or mis-treat patients with these symptoms may increase the suicide risk and make worse the evolution of mood disorders. The rating scale "G.T. MSRS" has been designed to improve the clinical effectiveness of both psychiatrists and GPs by enabling them to make an early "general" diagnosis of mixed states. This study presents some cases in which the "G.T. MSRS" scale has been used, in order to demonstrate its usefullness.


[A genomic study of adult-onset idiopathic hypoparathyroidism in Chinese by targeted next-generation sequencing].
Several genes have been recognized to be associated with non-surgical hypoparathyroidism. Data about gene mutations in adult-onset hypoparathyroidism patients is lacking. This study was designed to screen gene mutation in adult-onset hypoparathyroidism in Chinese through the targeted next-generation sequencing (NGS). We recruited 17 patients with adult-onset hypoparathyroidism who were regularly followed or newly diagnosed at our centre during the past one year. Nine of them developed hypercalciuria during the treatment with calcium and vitamin D. Eight of them were newly diagnosed with no treatment. Targeted NGS was performed to screen 11 related genes, including AIRE, AP2S1, CASR, CLDN16, FAM111A, GATA3, GCM2, PTH, TBCE, TBX1 and TRPM6. A novel homozygosis mutation of GCMB gene[c.130G>A (p.G44S)]was identified which was predicted to be deleterious by PolyPhen2. The patient was a 36-year-old woman who suffered from paroxysmal carpopedal spasms for ten years. Before treatment, the serum calcium and phosphorus was 1.48 mmol/L and 2.29 mmol/L, respectively.Parathyroid hormonel (PTH) concentration was lower than 3.0 ng/L. Intracranial calcification and cataract were also identified. She developed hypercalciuria during treatment with calcium and vitamin D. She had no physical deformity or family history of hypoparathyroidism. In this study, the genetic defect was only identified in 1 patient (5.9%). In adult-onset hypoparathyroidism without other diagnostic clues, the gene mutation screening as the first choice to clarify the etiology was not recommended.


[Heart failure in acute myocardial infarction].
Heart failure during the immediate period of an acute myocardial infarction constitutes a major insult to this pathology; since, once installed, it is associate to ventricular dysfunction and expansion of the left ventricle. It can appear either early or delayed. Subsequent to the acute insult, the myocardium is subjected to diverse changes in its anatomical conformation and to diastolic and systolic alterations, which will affect the hemodynamic constants of the patient. Changes in the parietal ventricular architecture as well as at the neurohumoral level will also occur. The clinical signs of heart failure are: dyspnea, pallor, tachycardia, diaphoresis, cold skin, oliguria, somnolence, and gallop, which can be observed at the very beginning of the coronary occlusion. Its clinical identification, through in-hospital studies supported by adequate hemodynamic monitoring, is of utter relevance since it will lead to appropriate and fast treatment. The groups of patients with acute myocardial infarction with high risk for the development of cardiac failure are: patients with extensive Q wave infarction, diabetic, patients over 65 years of age, and those with a history of previous myocardial infarction(s). The cornerstone of treatment must be focused on reducing the myocardial ischemia, which can be achieved through the use of modern therapeutics and, given the case, pharmacological agents, coronary intervention procedures, or cardiac surgery must be taken into account. At present it is known that angiotensin converting enzyme inhibitors, betablockers, inotropics, are useful to improve ventricular function in patients with acute myocardial infarction.


[Systemic sclerosis and occupational difficulties: Results of a prospective study].
Between 9000 and 14000 people have systemic sclerosis (ScS) in France. The work is often affected. Our study aims to assess the frequency of professional difficulties (DP) of scleroderma patients, identify these DP, the symptoms involved and the solutions used. A heteroquestionnaire was offered to scleroderma patients the Lille University Hospital. Data were cross-checked with the clinical database of the National Observatory of scleroderma patients. We used 104 questionnaires of which 84% are women. A total of 62.5%, (95% CI [52.5 to 71.8]) patients had experienced DP related to SSc, 55% reported symptoms worsened at work, 41% lower efficiency and a 19% job loss. Symptoms responsible for their DP were mainly asthenia, Raynaud syndrome, arthralgias and finger ulcerations. Only 40% of patients in difficulty were initiating steps with the county home for disabled people and 45% in informing their doctor at work (MT). The MT information absence was related to a misunderstanding of possible aid in 45% of cases, 57% of patients had not found a solution, 41% of them have lost their jobs and 31% of patients in the cohort experienced a drop in income. The impact of SSc the work is important. The aid job retention devices are under-used due to lack of knowledge of steps to take and the role of MT. Taking into account the symptoms responsible for PD must be improved to participate in this retention.


Matrix-matched quantitative analysis of trace-elements in calcium carbonate shells by laser-ablation ICP-MS: application to the determination of daily scale profiles in scallop shell (Pecten maximus).
A micro-scale method has been developed for analysis of trace-element concentration profiles in the calcium carbonate shell of the Great Scallop (Pecten maximus). UV laser ablation at 266-nm coupled with ICP-MS detection was used to analyse daily calcite striae of shell samples to obtain high temporal resolution of trace element incorporation. Analysis of scallop shells was carefully examined to determine the quality of calcium carbonate ablation and calibration. An accurate external calibration method based on matrix matching was developed. Twelve sodium-free enriched calcium carbonate standards containing up to twenty-four elements were prepared, by co-precipitation with aqueous ammonia and NH(4)HCO(3), and subsequently back-calibrated in the laboratory. These CaCO(3) standards were found to be homogenous and their use enabled sensitive quantitative analysis (detection limits of a few ng g(-1)) over a wide range of concentrations (0.1 to 500 microg g(-1)). Use of these CaCO(3) standards was also evaluated by analysis of three calcium-rich certified reference materials. Because calibration was consistent with the certified results, this analytical method is a sensitive tool for analysis of environmental calcium carbonate matrices. Repeated analysis of scallop shell samples collected simultaneously at the same location showed that the trace elements are homogeneously distributed along a stria. The reliability of such in-situ records of biogenic calcium carbonate (scallop shells) is apparent from the inter-individual and inter-annual reproducibility of the trace element profiles.


Alpha-synuclein (SNCA) polymorphisms exert protective effects on memory after mild traumatic brain injury.
Problems with attention and short-term learning and memory are commonly reported after mild traumatic brain injury (mTBI). Due to the known relationships between α-synuclein (SNCA), dopaminergic transmission, and neurologic deficits, we hypothesized that SNCA polymorphisms might be associated with cognitive outcome after mTBI. A cohort of 91 mTBI patients one month after injury and 86 healthy controls completed a series of cognitive tests assessing baseline intellectual function, attentional function, and memory, and was genotyped at 13 common single nucleotide polymorphisms (SNPs) in the SNCA gene. Significant differences in two memory measures (p=0.001 and 0.002), but not baseline intellectual function or attentional function tasks, were found between the mTBI group and controls. A highly significant protective association between memory performance and SNCA promoter SNP rs1372525 was observed in the mTBI patients (p=0.006 and 0.029 for the long and short delay conditions of the California Verbal Learning Tests, respectively), where the presence of at least one copy of the A (minor) allele was protective after mTBI. These results may help elucidate the pathophysiology of cognitive alterations after mTBI, and thus warrant further investigation.


Relationship of conjunctival impression cytology with clinical and biochemical assessment of vitamin A status of preschoolers.
Comparison of conjunctival impression cytology (CIC) with ocular signs and vitamin A levels was done based upon a national nutrition survey involving 427 randomly selected subjects aged 6 months to 6 years. Medical nutritionists looked for ocular signs and performed conjunctival impressions. Imprints were submitted to the Institute of Ophthalmology, University of the Philippines-Philippines General Hospital, for analysis. Fixing, staining and reading of all imprints was performed in accordance with the procedures of the International Centre for Epidemiologic and Preventive Ophthalmology (ICEPO). Comparison of the biochemical determination of serum vitamin A (SVA) with CIC results revealed that irrespective of SVA levels, more than 50% of the subjects were noted to have abnormal CIC results. The highest proportion of abnormal imprints was seen among those with low SVA. The relationship, however, was found not to be significant. Of the 247 subjects examined, 95% had a normal clinical and biochemical assessment of vitamin A; of these, 50.2% had abnormal cytology imprints while 45.3% had normal imprints. Using sensitivity and specificity analyses, CIC was compared with SVA levels. The computed sensitivity, specificity and positive predictive value (PPV) were 60.5, 45.2 and 60.0%, respectively. The lack of significant difference in mean serum retinol levels between normal and abnormal CIC groups may partly explain the low sensitivity and PPV of the CIC. In this study population, CIC failed to identify children with subclinical vitamin A deficiency as established by biochemical examination.


Chlamydophila pneumoniae in horses: a seroepidemiological survey in Italy.
We tested 731 sera from apparently healthy light horses against Chlamydophila pneumoniae, by a microimmuno-fluorescence (MIF) test. To verify cross-reactions with other species of chlamvdiae, all sera with an antibody titre > or = 32 to C. pneumoniae were tested against both C. psittaci and C. abortus. Antibodies to C. pneumoniae were detected in 194 out of 731 (26.5%) samples tested, with antibody titres ranging from 32 to 1024. No antibody titre > or = 32 was detected in sera to C. abortus. Only few sera with a high antibody titre to C. pneumoniae reacted weakly with C. psittaci at the dilution of 1:32.


Induction of cell death in neuroblastoma by inhibition of cathepsins B and L.
A specific irreversible inhibitor of both cathepsins B and L, Fmoc-Tyr-Ala-CHN(2) (FYAD) induced apoptosis of neuroblastoma cells but not other tumor cells. Cysteine protease inhibitors that were not efficient inhibitors of both proteases did not cause death of any cell line tested. Apoptosis was preceded by accumulation of large electron dense vesicles and multivesicular bodies in the cytoplasm. Exposure of cells to the cathepsin D inhibitor, pepstatin, failed to rescue cells from FYAD-induced death. These results indicate that inhibition of cathepsins B and L may provide a unique mechanism for selectively inducing death of neuroblastoma with limited toxicity to normal cells and tissues.


Excitonic effects in a time-dependent density functional theory.
Excited state properties of one-dimensional molecular materials are dominated by many-body interactions resulting in strongly bound confined excitons. These effects cannot be neglected or treated as a small perturbation and should be appropriately accounted for by electronic structure methodologies. We use adiabatic time-dependent density functional theory to investigate the electronic structure of one-dimensional organic semiconductors, conjugated polymers. Various commonly used functionals are applied to calculate the lowest singlet and triplet state energies and oscillator strengths of the poly(phenylenevinylene) and ladder-type (poly)(para-phenylene) oligomers. Local density approximations and gradient-corrected functionals cannot describe bound excitonic states due to lack of an effective attractive Coulomb interaction between photoexcited electrons and holes. In contrast, hybrid density functionals, which include long-range nonlocal and nonadiabatic corrections in a form of a fraction of Hartree-Fock exchange, are able to reproduce the excitonic effects. The resulting finite exciton sizes are strongly dependent on the amount of the orbital exchange included in the functional.


Profile of Trypanosoma cruzi infection in a tropical medicine reference center, Northern Italy.
Chagas disease (CD) is endemic in Central and South America, Mexico and even in some areas of the United States. However, cases have been increasingly recorded also in non-endemic countries. The estimated number of infected people in Europe is in a wide range of 14000 to 181000 subjects, mostly resident in Spain, Italy and the United Kingdom. Retrospective, observational study describing the characteristics of patients with CD who attended the Centre for Tropical Diseases (Negrar, Verona, Italy) between 2005 and 2013. All the patients affected by CD underwent chest X-ray, ECG, echocardiography, barium X-ray of the oesophagus and colonic enema. They were classified in the indeterminate, cardiac, digestive or mixed category according to the results of the screening tests. Treatment with benznidazole (or nifurtimox in case of intolerance to the first line therapy) was offered to all patients, excluding the ones with advanced cardiomiopathy, pregnant and lactating women. Patients included were 332 (73.9% women). We classified 68.1% of patients as having Indeterminate Chagas, 11.1% Cardiac Chagas, 18.7% as Digestive Chagas and 2.1% as Mixed Form. Three hundred and twenty-one patients (96.7%) were treated with benznidazole, and most of them (83.2%) completed the treatment. At least one adverse effect was reported by 27.7% of patients, but they were mostly mild. Only a couple of patients received nifurtimox as second line treatment. Our case series represents the largest cohort of T. cruzi infected patients diagnosed and treated in Italy. An improvement of the access to diagnosis and cure is still needed, considering that about 9200 infected people are estimated to live in Italy. In general, there is an urgent need of common guidelines to better classify and manage patients with CD in non-endemic countries.


Reduction of cell size induced by enod40 in Arabidopsis thaliana.
An extensive analysis of organ and cell size was performed in three different Arabidopsis lines transformed with the early nodulin gene enod40 under control of the CaMV35S promoter. All three transgenic lines presented a significant decrease in the mean size of both epidermal internode and leaf mesophyll cells. Flow cytometric and image analysis of enod40-transfected protoplasts prepared from wild-type Arabidopsis cell suspensions showed that transient expression of the gene resulted in reduced forward light scattering (a factor correlated with particle size) and cell size. The direct administration of ENOD40 peptide to fresh protoplasts also resulted in reduced forward scattering with respect to the control and to the administration of unrelated peptides. As far as is known this is the first report documenting a biological effect of enod40 at the cellular level in non-legume plants.


Impact of the COVID-19 Pandemic on the Severity of Diabetic Ketoacidosis Presentations in a Tertiary Pediatric Emergency Department.
More severe presentations of diabetic ketoacidosis (DKA) have been reported during the coronavirus disease 2019 (COVID-19) pandemic, possibly due to avoidance of healthcare settings or reduced access to care. To date, no studies have utilized statistical process control to relate temporal COVID-19 events with DKA severity. Our objectives were (1) to determine whether the severity of pediatric DKA presentations changed during COVID-19 and (2) to temporally relate changes in severity with regional pandemic events. This study was a retrospective chart review of 175 patients younger than 18 years with DKA presenting to a pediatric emergency department in the United States between 5/1/2019 and 8/15/2020. As part of our ongoing clinical standard work in ED management of DKA, DKA severity measures, including presenting pH, the proportion of PICU admissions, and admission length of stay, were analyzed using statistical process control. During COVID-19, we found special cause variation with a downward shift in the mean pH on DKA presentation from 7.2 to 7.1 for all patients. The proportion of DKA patients requiring PICU admission increased from 34.2% to 54.6%. Changes temporally corresponded to the statewide bans on large events (3/11/2020), school closures (3/13/2020), and a reduction in our institution's emergency department volumes. Admission length of stay was unchanged. Pediatric DKA presentations were more severe from March to June 2020, correlating with regional COVID-19 events. Future quality improvement interventions to reduce delayed presentations during COVID-19 surges or other natural disasters should target accessibility of care and public education regarding the importance of timely care for symptoms.


Restaging after neoadjuvant chemoradiation in rectal cancers: is histology the key in patient selection?
Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer. However, there is no clarity regarding the necessity for restaging scans to rule out systemic progression of disease post chemoradiation with existing literature being divided on the need for the same. Data from a prospectively maintained database was retrospectively analysed. All locally advanced rectal cancers (node positive/T4/T3 with threatened or involved CRM) were included. Biopsy proof of adenocarcinoma and CT scan of abdomen and chest were mandatory. Grade of tumor and response to CTRT on restaging magnetic resonance imaging (MRI) were documented. Out of 119 patients subjected to CTRT, 72 underwent definitive total mesorectal excision while 13 patients progressed locoregionally on restaging MR pelvis and 15 other patients progressed systemically while the rest defaulted. Patients with poorly differentiated (PD) cancers were compared to those with well/moderately differentiated (WMD) tumors. PD tumors had a significantly higher rate of local progression (32.1% vs. 5.6% %, P=0.0011) and systemic progression (35.7% vs. 6.9%, P=0.0008) as compared to WMD tumors. Only one-third (9/28) of PD patients underwent TME while the rest progressed. Selecting poorly differentiated tumors alone for restaging CECT abdomen and thorax will be a cost effective strategy as the rate of progression is very high. Also patients with PD tumors need to be consulted about the high probability of progression of disease.


Direct interaction of TrkA/CD44v3 is essential for NGF-promoted aggressiveness of breast cancer cells.
CD44 is a multifunctional membrane glycoprotein. Through its heparan sulfate chain, CD44 presents growth factors to their receptors. We have shown that CD44 and Tropomyosin kinase A (TrkA) form a complex following nerve growth factor (NGF) induction. Our study aimed to understand how CD44 and TrkA interact and the consequences of inhibiting this interaction regarding the pro-tumoral effect of NGF in breast cancer. After determining which CD44 isoforms (variants) are involved in forming the TrkA/CD44 complex using proximity ligation assays, we investigated the molecular determinants of this interaction. By molecular modeling, we isolated the amino acids involved and confirmed their involvement using mutations. A CD44v3 mimetic peptide was then synthesized to block the TrkA/CD44v3 interaction. The effects of this peptide on the growth, migration and invasion of xenografted triple-negative breast cancer cells were assessed. Finally, we investigated the correlations between the expression of the TrkA/CD44v3 complex in tumors and histo-pronostic parameters. We demonstrated that isoform v3 (CD44v3), but not v6, binds to TrkA in response to NGF stimulation. The final 10 amino acids of exon v3 and the TrkA H112 residue are necessary for the association of CD44v3 with TrkA. Functionally, the CD44v3 mimetic peptide impairs not only NGF-induced RhoA activation, clonogenicity, and migration/invasion of breast cancer cells in vitro but also tumor growth and metastasis in a xenograft mouse model. We also detected TrkA/CD44v3 only in cancerous cells, not in normal adjacent tissues. Collectively, our results suggest that blocking the CD44v3/TrkA interaction can be a new therapeutic option for triple-negative breast cancers.