Mutations and polymorphic BRCA variants transmission in breast cancer familial members.
We previously showed that about 80% of breast cancer patients at high risk to carry mutation in BRCA genes presented at least one polymorphism in these genes which resulted potentially harmful by in silico analysis. In the present paper, the genealogic transmission of those polymorphic coding and noncoding variants of BRCA genes in family's members has been investigated. Thirty families, enrolled within the Genetic Counselling Program of our Institute, with probands and at least one-first degree relative (n = 67 family members) available, have been studied for both BRCA1 and BRCA2 pathological mutation and polymorphic variants' transmission. Ten and 6 probands carried Mendelian transmitted mutations in BRCA1 and BRCA2, respectively. Polymorphic coding and noncoding variants were transmitted in each family's relatives with a frequency ranging from 42 to 100%, with similar rate for each SNP in mutated and nonmutated families with the only exception of BRCA1 K1183R significantly more frequent in mutated families (P = 0.004); conversely, this SNP and BRCA2 N372H, were more frequently present in breast cancer relatives belonging to families in which pathological BRCA mutations were not present. Furthermore, specific haplotypes were transmitted in all relatives as BRCA1 871Leu-1038Gly, present in both BRCA mutated and nonmutated families, while BRCA2 289His-991Asp-IVS14+53 C>T present only in BRCAX families suggesting the harmful role of these SNPs. In conclusion, analysis of SNPs maps and modality of their transmission could identify further susceptibility markers and provide a basis for a better DNA-based cancer classification.


Caffeic acid phenethyl ester suppresses monocyte adhesion to the endothelium by inhibiting NF-κB/NOX2-derived ROS signaling.
Caffeic acid phenethyl ester (CAPE), one of the major polyphenols, exhibits anti-oxidative, anti-bacterial, and anti-cancer properties. Atherosclerosis is a chronic inflammatory disease, the progression of which is closely related to the accumulated adhesion of inflammatory monocytes/macrophages to the endothelium. We herein determined whether CAPE and its derivatives suppressed THP-1 cell adhesion to human umbilical vein endothelial cells (HUVEC). Of the four polyphenols tested, CAPE significantly suppressed the 12-O-tetradecanoylphorbol 13-acetate (TPA)-elicited expression of cluster for differentiation (CD) 11b, 14, and 36, and this was accompanied by the inhibition of THP-1 cell adhesion to HUVEC. CAPE also suppressed the activation of TPA-elicited nuclear factor-κB (NF-κB) and accumulation of NADPH oxidase 2 (NOX2)-derived reactive oxygen species (ROS), but did not affect extracellular signal-regulated kinase (ERK) phosphorylation. Taken together, these results demonstrated that CAPE suppressed THP-1 cell adhesion to HUVEC through, at least in part, the NF-κB, NOX2, and ROS-derived signaling axis.


Isotopic Effects on Intermolecular and Intramolecular Structure and Dynamics in Hydrogen, Deuterium, and Tritium Liquids: Normal Liquid and Weakly and Strongly Cooled Liquids.
Differences in properties such as phase-transition temperature and transport coefficients among liquids of different isotopic compositions, hydrogen, deuterium, and tritium, should originate from their differently pronounced nuclear quantum effects (NQEs) rather than from any subtle difference in the electronic interaction potentials. Accurate and efficient determination of structural and dynamical isotopic effects in the quantum liquids still remains as one of the challenging problems in condensed-phase physics. With a recently developed nonempirical real-time molecular dynamics method which describes nonspherical molecules with the NQEs, we computationally realized and investigated dynamical and quantum isotopic effects of not only traditionally studied isotopes, hydrogen, and deuterium but also a lesser known radioisotope, tritium, in broad thermodynamic conditions from normal liquid to weakly and strongly cooled liquids, which have been hindered by rapid crystallization in spite of numerous experimental attempts at supercooling. Reproducing the previously reported experimental isotope dependence on the bond length and vibrational frequencies of hydrogen, deuterium, and tritium liquids, we further demonstrate that distinctive isotope effects appear in their intermolecular and intramolecular structure and dynamics not only at lower temperature but also at higher temperature, which none has so far been able to obtain quantitative results for realistic systems. Rationalization of their physical origins and the obtained physical insights will help future experimental searching and monitoring intermolecular and intramolecular dynamics and structures of these isotopes not only in normal liquid but also in supercooled liquid.


Microarray analyses of gene expression during adventitious root development in Pinus contorta.
In order to investigate the gene expression pattern during adventitious root development, RNA of Pinus contorta hypocotyls, pulse-treated with the auxin indole-3-butyric acid and harvested at distinct developmental time points of root development, was hybridized to microarrays containing 2,178 cDNAs from Pinus taeda. Over the period of observation of root development, the transcript levels of 220 genes changed significantly. During the root initiation phase, genes involved in cell replication and cell wall weakening and a transcript encoding a PINHEAD/ZWILLE-like protein were up-regulated, while genes related to auxin transport, photosynthesis, and cell wall synthesis were down-regulated. In addition, there were changes in transcript abundance of genes related to water stress. During the root meristem formation phase the transcript abundances of genes involved in auxin transport, auxin responsive transcription, and cell wall synthesis, and of a gene encoding a B-box zinc finger-like protein, increased, while those encoding proteins involved in cell wall weakening decreased. Changes of transcript abundance of genes related to water stress during the root meristem formation and root formation phase indicate that the plant roots had become functional in water transport. Simultaneously, genes involved in auxin transport were up-regulated, while genes related to cell wall modification were down-regulated. Finally, during the root elongation phase down-regulation of transcripts encoding proteins involved in cell replication and stress occurred. Based on the observed changes in transcript abundances, we suggest hypotheses about the relative importance of various physiological processes during the auxin-induced development of roots in P. contorta.


In vivo determination of radiation dose in kidneys and bladder during renogram: a new approach.
The radiation dose absorbed by a patient from a radiopharmaceutical is usually calculated with the help of the equations published by the Society's Medical Internal Radiation Dose (MIRD) Committee and the use of a Reference Man. However, the (MIRD) estimations are based on the assumption that the patient is a normal subject with the characteristics of the Reference Man. This is not always true particularly in some pathological situations which present large deviations from normal. The purpose of this paper is to determine the dose in kidneys and bladder, during renograms, on the basis of real data. A protocol is formulated by means of which the processing of the frames acquired in the various stages of the renogram enables the determination of the kidney and bladder mass as well as the time distribution of radioactivity in these organs. Our results are in accordance with MIRD estimations for normal cases, whereas very significant deviations are observed in pathological ones. This is due to the fact that the mass of the 'source' and 'target' organs as well as the biodistribution of the radiopharmaceuticals are essential in the dose determination and large deviations are expected between estimated and real doses when in some pathological cases the mass of kidney is particularly reduced or its clearance retarded.


[Can vesicoureteral reflux be predicted in infants with urinary infection?].
To look forward for a formulae able to predict the presence of vesicoureteral reflux (VUR) in the first urinary tract infection (UTI) in infants. We had studied all the diagnosticated first UTI in breast-fed babies in our hospital along 21/2 years. All had been subjects of a renal ultrasound scan, VCUG and CRP test. We have analyzed the result by diagnosis test and logistic regression. We have studied 267 infants aged between 2 days and 24 months old.17,33% manifested UTI caused by germs different than E Coli, 40 subjects presented anomalies in the ultrasound scan and 108 manifested VUR. Oostenbruck s score had been useless in detecting VUR subjects. In the multivariable analysis the two variables of anomalies in the ultrasonographic scan and non E Coli caused UIT were the only ones to presented statistical significance to sign the presence of VUR and of the likeness of VUR of grade > or = 3. The negative probability coefficients for infants with ultrasonographics anomalies and/or UTI non E Coli produced were of 0,78 (IC 0,67-0,90) for all degrees of VUR, 0,25 (IC 0,10-0,52) for VUR with degree > or = 3 and 0 (IC 0-0,67) for VUR with degree > or = 4. We deduced that in children younger of 24 months old that suffer their first UTI the indication to proceeded with a VCUG could be limited to the subjects with present anomalies in the renal ultrasound scan and/or UTI non E Coli, thought there will precised more studies to confirm this findings.


Effectiveness of Basic Life Support Training for Middle School Students.
Bystander cardiopulmonary resuscitation improves survival after out-of-hospital cardiac arrest. This study aimed to assess the effectiveness of a basic life support (BLS) educational course given to 110 middle school children, using a pretest posttest design. In the pretest, students were asked to demonstrate BLS on a manikin to simulate a real-life scenario. After the pretest, a BLS training course of two sessions was provided, followed by posttest on the same manikin. Students were assessed using an observational sheet based on the American Heart Association's BLS guidelines. In the pretest, students showed significant weakness in the majority of guidelines. In the posttest, they demonstrated significant improvement in their BLS skills. BLS training in the middle school was effective, considering the lack of previous skills. It is recommended that BLS education be compulsory in the school setting.


A surgically treated pulmonary sclerosing haemangioma that clinically and radiologically mimicked a thrombosed pulmonary artery aneurysm.
We report the case of a 70-year-old woman with a surgically treated pulmonary sclerosing haemangioma that clinically and radiologically mimicked a thrombosed pulmonary artery aneurysm. She underwent intravenous thrombolytic therapy because of acute pulmonary embolism in the bilaterally segmental arteries. The pulmonary embolism had almost disappeared except for a nodular lesion in the middle lobe branch of the pulmonary artery, and a thrombosed pulmonary artery aneurysm with thrombus was suspected in the CT image. The patient underwent a video-assisted thoracoscopic middle lobectomy. The final pathological diagnosis was sclerosing haemangioma. She had experienced no recurrence for 1 year after surgery, and we continue to take great care during her follow-up.


High-pressure injection injury of the finger.
The high-pressure injection injuries are unusual injuries and the extent of tissue damage is often under estimated. They represent potentially disabling forms of trauma and have disastrous effects on tissues if not treated promptly. We present a case of high pressure injection injury to the finger from lubricant oil. The patient presented late with necrosis of volar tissue of left index finger. The patient was aggressively managed in stages, with delayed flap cover, with satisfactory functional and aesthetic outcome.


Collisional stability of 40K immersed in a strongly interacting Fermi gas of 6Li.
We investigate the collisional stability of a sample of 40K atoms immersed in a tunable spin mixture of 6Li atoms. In this three-component Fermi-Fermi mixture, we find very low loss rates in a wide range of interactions as long as molecule formation of 6Li is avoided. The stable fermionic mixture with two resonantly interacting spin states of one species together with another species is a promising system for a broad variety of phenomena in few- and many-body quantum physics.


Strategies for endovascular mitral valve repair.
Technological advances have recently enabled mitral valve repair to be performed using endovascular techniques and thus open the possibility of nonsurgical treatment of mitral valve disease. While balloon valvotomy has been applied to mitral stenosis for over 20 years, a number of devices aimed at correcting mitral regurgitation are currently in preclinical and clinical development. While some of these, such as edge-to-edge repair, are catheter adaptations of established surgical techniques, others represent true departures from the current surgical paradigms of correcting mitral regurgitation. This review will summarize the current status of percutaneous transcatheter techniques for mitral valve repair. Included are balloon mitral valvotomy, indirect annuloplasty, direct annuloplasty, ventricular shape change, and edge-to-edge repair. These techniques certainly represent a new interdisciplinary paradigm between cardiac surgery and interventional cardiology and may be the next frontier in minimally-invasive cardiac surgery.


Poor working conditions and the capacity of nurses to provide moral care.
The capacity of nurses to uphold exemplary standards of care is being increasingly compromised by the poor conditions under which they are expected to work. Historically nurses have somehow managed to provide ethical and therapeutically effective care to patients even when circumstances have pressured them to do otherwise. There is, however, a limit to what nurses can endure - and to what it is reasonable to expect them to endure - when working in environments that are hostile to moral excellence. Social justice demands that the 'nurse question' be re-examined with a view toward challenging and changing the status quo.


Role of targeted therapy in the treatment of advanced prostate cancer.
Over the past decade, the treatment of advanced prostate cancer has developed significantly, and perhaps the most dramatic shift came in 2004 with the demonstration that docetaxel-based chemotherapy significantly improved overall survival in patients with castration-resistant prostate cancer. This led to a significant expansion of the role of chemotherapy in the management of prostate cancer. In addition, there is now considerable progress being made in the development of more effective antiandrogens, cytochrome P17 inhibitors, novel chemotherapy regimens, targeted therapies, and immunotherapies that can complement existing therapies and may soon become integrated into the treatment paradigm. Progress in our understanding of molecular signalling pathways that play an important role in prostate cancer has stimulated the investigation of targeted therapies, including antiangiogenic agents, bone-targeted agents, and specific inhibitors of key signalling molecules and chaperone proteins. For the most part, targeted agents are being combined with chemotherapy, similar to the approach taken in other solid tumours. Various therapeutic vaccine strategies also appear to have potential in the treatment of advanced prostate cancer. However, the development of new approaches to the treatment of prostate cancer presents many challenges that will demand collaboration and consensus building with respect to biomarkers for patient selection, clinical endpoints, and trial designs.


Bioinspired and Biomimetic AgNPs/Gentamicin-Embedded Silk Fibroin Coatings for Robust Antibacterial and Osteogenetic Applications.
With the progressively increasing demand for orthopedic Ti implants, the balance between two primary complications restricting implant applications is needed to be solved: the lack of bone tissue integration and biomedical device-associated infections (BAI), where emergence of multiresistance bacteria make it worse. Notably, a combination of silver nanoparticles (AgNPs) and a kind of antibiotic can synergistically inhibit bacterial growth, where a low concentration of AgNPs has been confirmed to promote the proliferation and osteogenesis of osteoblasts. In this work, we built AgNPs/gentamicin (Gen)-embedded silk fibroin (SF)-based biomimetic coatings on orthopedic titanium by a facile dipping-drying circular process and with the assistance of polydopamine (PD). Ag+ was reduced to AgNPs by SF under ultraviolet (UV) irradiation, and then they were detected by transmission electron microscope (TEM) images and UV-visible (UV-vis) analyses. Intriguingly, the addition of Gen highly improved the reduction efficiency of Ag+. The antibacterial efficiency of SF-based coatings was examined by challenging them with pathogenic Staphylococcus aureus (S. aureus) bacteria which produced biofilms, and consequently, we found that low concentration loading, durable release of Ag+ (28 days), and 10-fold improvement of antibacterial efficiency were achieved for our novel AgNPs- and Gen-embeded silk fibroin coatings. In bacteria and a cells cocultured system, AgNPs/Gen-embedded coatings strongly inhibited adhesion and proliferation of S. aureus, simultaneously improving cell adhesion and growth. To investigate cytocompatibility and osteogenic potential, different coatings were cultured with MC3T3 cells; AgNPs/Gen-embedded coatings showed generally acceptable biocompatibility (cell adhesion, proliferation, and viability) and accelerated osteoblast maturation (alkaline phosphatase production, matrix secretion, and calcification). Expectantly, this novel biofunctional coating will have promising applications in orthopedic and dental titanium implants thanks to its excellently antibacterial, biocompatible, and osteogenic activities.


Differentiation of human and animal strains of Streptococcus dysgalactiae by pulsed-field gel electrophoresis.
The genetic diversity among 54 human isolates and 33 animal isolates belonging to the species Streptococcus dysgalactiae (20 alpha-haemolytic Streptococcus dysgalactiae, 23 Streptococcus equisimilis, 43 group G streptococci and one group L streptococcus) was evaluated by macrorestriction analysis of chromosomal DNA with SmaI and resolution by pulsed-field gel electrophoresis. This technique revealed a high degree of intraspecies polymorphism, leading to the differentiation of 80 distinct banding patterns, and identified the presence of two major clusters, one containing isolates of human origin and the other isolates of animal origin. These results suggest than human and animal isolates of S.dysgalactiae are genetically distinct, and support the recent proposal of the subspecies S. dysgalactiae subsp. equisimilis for human isolates. The heterogeneity revealed within isolates from the same host type indicates that pulsed-field gel electrophoresis is a powerful epidemiological tool for studying S. dysgalactiae infections.


Human blood neutrophils generate ROS through FcγR-signaling to mediate protection against febrile P. falciparum malaria.
Blood phagocytes, such as neutrophils and monocytes, generate reactive oxygen species (ROS) as a part of host defense response against infections. We investigated the mechanism of Fcγ-Receptor (FcγR) mediated ROS production in these cells to understand how they contribute to anti-malarial immunity. Plasmodium falciparum merozoites opsonized with naturally occurring IgG triggered both intracellular and extracellular ROS generation in blood phagocytes, with neutrophils being the main contributors. Using specific inhibitors, we show that both FcγRIIIB and FcγRIIA acted synergistically to induce ROS production in neutrophils, and that NADPH oxidase 2 and the PI3K intracellular signal transduction pathway were involved in this process. High levels of neutrophil ROS were also associated with protection against febrile malaria in two geographically diverse malaria endemic regions from Ghana and India, stressing the importance of the cooperation between anti-malarial IgG and neutrophils in triggering ROS-mediated parasite killing as a mechanism for naturally acquired immunity against malaria.


The longitudinal changes of the visual field in an Asian population with primary angle-closure glaucoma with and without an acute attack.
To investigate the longitudinal changes of visual field (VF) in Asian patients with primary angle-closure glaucoma (PACG) occurring with and without an acute attack. In this retrospective case series, 87 consecutive patients diagnosed with bilateral PACG during the period from 2000 to 2010 were included. The eyes of the enrolled patients were categorized into 2 groups: PACG with 1 documented episode of an acute episode in the affected eye (APACG); PACG without a previous documented acute episode in the fellow eye (CPACG). The historical change in the VF in both groups was assessed every 3 months for >2 years. Of the 174 eyes included in the study, 87 eyes belonged to the APACG group, and 87 eyes belonged to the CPACG group. The mean deviation (MD) in the APACG group decreased significantly from -6.22 to -6.73 dB between the 6- and 9-month follow-up periods (P=0.03). There were significant differences between the 2 groups in the MD index from the 9- to 24-month follow-up. The corrected pattern standard deviation (CPSD) in the APACG group increased significantly from 3.61 to 3.71 dB between the 6- and 9-month follow-up periods (P=0.04). The CPSD index was higher in the APACG group than in the CPACG group from the 9- to 24-month follow-up, which was a statistically significant difference. Glaucomatous VF damage in Asian patients with APACG was detected after a 6-month follow-up period, despite the presence of laser peripheral iridotomy in this population. In the patients with CPACG, there was no significant difference in the MD and CPSD during the follow-up period. Patients with APACG would benefit from regular monitoring of the decline in the VF.


Molecular Docking and Dynamics Simulations of Ammi visnaga L. Constituents as Antimelanogenic, Anti-Inflammatory and Anticoagulant Agents.
In this study, anti-melanogenic, anti-inflammatory and anti-coagulant potentials of eighteen selected constituents of Ammi visnaga L. were investigated by Induced Fit Docking (IFD) and molecular dynamic simulation with Schrödinger software. The binding free energies of the selected natural compounds were computed by means of ΔG MM-GBSA studies. Anti-melanogetic activity of the constituent against agaricus bisporus tyrosinase, Priestia megaterium tyrosinase and Homo sapiens tyrosinase were evaluated. The result showed that apiumetin had more negative binding free energy against three tyrosinase enzymes than cognate ligands, tropolone and kojic acid. Docking analysis was also performed to predict the constituents with anti-inflammatory activity against human Tumor necrosis factor, Cyclooxygenase-2, Prostaglandin D2 11-ketoreductase AKR1C3 and Prostaglandin reductase PTGR2. The results showed that pyranocoumarins (visnadin, dihydrosamidin, samidin) have more negative binding free energy against Cyclooxygenase-2 and Prostaglandin D2 11-ketoreductase receptors than cognate drugs, rofecoxib and indomethacin. In addition, docking analysis shows that pyranocoumarins, apiumetin and cimifugin have more negative binding free energy against Vitamin K epoxide reductase than S-warfarin drug, predicting that they have anticoagulant activity. Furthermore, the constituents and their cognate drugs were subjected to 100 ns MD Simulation to predict their stability at the active sites of the enzymes.


Adaptability of Napiergrass (Pennisetum purpureum Schumach.) for Weed Control in Site of Animals Buried after Foot-and-Mouth Disease Infection.
After the infection of foot-and-mouth disease outbreaks in Miyazaki, Japan, in 2010, cattle and swine were slaughtered and buried in a site of 100 ha, where weed control is difficult and costly since lands are unlevelled and prohibited to be plowed for 3 years. To consider the adaptability of napiergrass (Pennisetum purpureum Schumach.) to the animal burial site for weed control, two napiergrass varieties, normal Wruk wona (WK) and dwarf late-heading variety (DL), were transplanted, compared with sowing of maize (MZ) and sorghum (SR) in both burial (BU) and neighboring bordered area (BO) in mid-June 2011. Even though several weed control methods were subjected to lands, MZ and SR failed to be established stably at only 1/3-1/2 due to the suppression of growth by indigenous weeds, while WK and DL successfully established as high as 82-91% and 73-85%, respectively, in 2011. The poor establishment of MZ and SR after sowing tended to be increased with the year from establishment. Plant dry matter yield and cellulose concentration were the highest in WK in 2011, while overwintering ability was constantly higher in DL in the 3 years. It is necessary to consider the utilization of forage plants on the animal burial site.


Optimal trajectory and insertion accuracy of sacral alar iliac screws.
The aim of this study was to analyse the optimal trajectories for sacral alar iliac screws (SAISs) in a Japanese patient population and the clinical assessment of insertion accuracies. The ideal trajectories of SAISs, starting from 2 mm medial to the apex of the lateral sacral crest on the midline between S1 and S2 dorsal foramina, were measured in 80 consecutive spinal disease patients (40 males and 40 females; average age: 67.4 ± 8.1 years) using three-dimensional computed tomographic image software. Following these anatomic analyses, accuracies of 32 inserted SAISs in consecutive patients, who underwent long spinal posterior fusion, were investigated clinically. Lateral angulations of optimal SAIS trajectories in males (left: 37.9; right: 37.7) were significantly larger than those than in females (left: 32.8; right: 32.4). Caudal SAIS angulations for females (left: 33.4; right: 33.9) were significantly larger than those in males (left: 27.5; right: 28.0). The 32 SAISs (100 mm long and 9 mm in diameter) assessed clinically were accurately inserted on optimal trajectories. The optimal trajectories of SAISs in a Japanese patient population are more lateral in males and more caudal in females. This study examines the clinical safety and accuracy of SAIS insertion on these optimal trajectories.


Determination of Fatty Acid Profile in Processed Fish and Shellfish Foods.
Seafood products are a crucial dietary source of n-3 polyunsaturated fatty acids (n-3 PUFA), which are essential for human health. However, the presence of these n-3 PUFA may be subject to changes related to different processing methods. The aim of this study was to determine the fatty acid composition, focusing on n-3 PUFA, in different processed fish and shellfish products of both EU and non-EU origin. The products were purchased from supermarkets and ethnic food shops in Messina (Italy). Gas chromatography with a flame-ionization detector (GC-FID) was used for analysis. Based on the fatty acid profile, the atherogenicity index (AI), thrombogenicity index (TI), and flesh lipid quality index (FLQ) were determined: 0.13-1.04 (AI), 0.19-0.89 (TI), and 0.41-29.90 (FLQ). The percentages of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids fell within the following ranges: 13.55-50.48%, 18.91-65.58%, and 13.84-52.73%, respectively. Considering that all samples showed low AI and TI indices and that all processed fish products proved to be a good source of beneficial PUFAs, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), their consumption is recommended for humans.


Socio-demographic and clinical characteristics of clients seeking assisted conception at Lagos State University Teaching Hospital, Ikeja, Nigeria.
The socio-demographic and clinical characteristics of 246 consecutive couples seeking assisted conception in a university teaching hospital in Nigeria from inception in 2011 till 2014 were reviewed restrospectively. Eighty-five (34.5%) were in the 35-40 years age group. The body mass index of the women showed that 111 (45.1%) were overweight. One hundred and ninety five (88%) were referred on account of secondary infertility. The mean duration of infertility was 9.6 ± 4.8 years. Major factors identified were male factor 128 (52%), ovarian/age-related decline in fertility 107 (43.5%), tubal 83 (33.7%) and combined male/female factor 71 (28.9%). One hundred and ninety (77.2%) clients seeking assisted conception were Christians at advanced age (greater than 35 years) with a longstanding duration of infertility of more than 10 years. Government, private and religious organisations need to raise public awareness about the availability of in-vitro fertilisation services as well as encourage early resort to assisted reproductive technologies. Impact statement What we already know: Secondary infertility due mainly to tubal factor is reported to be the commonest cause of infertility in developing countries like Nigeria and clients affected seek assisted reproductive techniques late. What the results of this study add: Male factor infertility is more common amongst infertile couples seeking in vitro fertilisation in LASUTH. The implications of the findings for practice and/or further research: A thorough examination of the male partner followed by investigation is vital at the initial visit so that they can be referred early for assisted conception.


Loss of LR11/SORLA enhances early pathology in a mouse model of amyloidosis: evidence for a proximal role in Alzheimer's disease.
Alzheimer's disease (AD) is the most prevalent form of dementia, resulting in progressive neuronal death and debilitating damage to brain loci that mediate memory and higher cognitive function. While pathogenic genetic mutations have been implicated in approximately 2% of AD cases, the proximal events that underlie the common, sporadic form of the disease are incompletely understood. Converging lines of evidence from human neuropathology, basic biology, and genetics have implicated loss of the multifunctional receptor LR11 (also known as SORLA and SORL1) in AD pathogenesis. Cell-based studies suggest that LR11 reduces the formation of beta-amyloid (Abeta), the molecule believed to be a primary toxic species in AD. Recently, mutant mice deficient in LR11 were shown to upregulate murine Abeta in mouse brain. In the current study, LR11-deficient mice were crossed with transgenic mice expressing autosomal-dominant human AD genes, presenilin-1 (PS1DeltaE9) and amyloid precursor protein (APPswe). Here, we show that LR11 deficiency in this AD mouse model significantly increases Abeta levels and exacerbates early amyloid pathology in brain, causing a forward shift in disease onset that is LR11 gene dose-dependent. Loss of LR11 increases the processing of the APP holo-molecule into alpha-, beta-, and gamma-secretase derived metabolites. We propose that LR11 regulates APP processing and Abeta accumulation in vivo and is of proximal importance to the cascade of pathological amyloidosis. The results of the current study support the hypothesis that control of LR11 expression may exert critical effects on Alzheimer's disease susceptibility in humans.


Two eisosome proteins play opposite roles in autophagic control and sustain cell integrity, function and pathogenicity in Beauveria bassiana.
Pil1A and Pil1B are two core eisosome proteins that are homologous to yeast Pil1/Lsp1 or filamentous fungal Pil1A/Pil1B but have been unexplored in entomopathogenic fungi. Here we examined subcellular localization and functions of Pil1A and Pil1B in Beauveria bassiana, a fungal insect pathogen. Either localization or co-localization experiments of the two proteins demonstrated that Pil1A and Pil1B were simultaneously localized at the periphery of hyphal cells for formation of stable, punctuate spots in B. bassiana. This is different from a reliance of proper Lsp1/Pil1B localization upon Pil1/Pil1A in other fungi. Deletions of pil1A and pil1B caused opposite changes in expression of many autophagy-related genes and formation of intravacuolar autophagosomes. Such opposite changes were restored to nearly normal status by exogenous rapamycin, implicating a link of Pil1A/B to the target of rapamycin signalling pathway. All single/double deletion mutants of pil1A and pil1B lost almost all pathogenicity due to reduced ability to secrete Pr1 proteases for cuticle degradation. They also showed differential changes in cell wall integrity and multiple stress responses. These findings unveil opposite roles for Pil1A and Pil1B in autophagic regulation and an essentiality of both for cell integrity, function and pathogenicity of the fungal entomopathogen.


A Case Report of Stuttering Induced by Risperidone and Chlorpromazine.
Stuttering, a disturbance in the normal fluency and time patterning of speech is usually developmental. In some cases, it is acquired, and causes include stroke, brain tumor, and trauma. Implicated in the causation of stuttering are overactive presynaptic dopamine systems in the region of the brain that modulate verbalization. It is a rare side effect of antipsychotic medications and has been reported with phenothiazines, clozapine, and risperidone. This is a report of a patient who developed stuttering when treated first with chlorpromazine and later with risperidone. Patient had a diagnosis of schizoaffective disorder and had been treated with antipsychotic medications including haloperidol, olanzapine, and paliperidone. He developed stuttering for the first time upon receiving intramuscular injections of chlorpromazine for treatment of agitation. The stutter improved and eventually resolved. He subsequently presented with a severe stutter when he was treated with risperidone. The stutter improved after risperidone was discontinued. It is speculated that drug-induced stuttering may be a manifestation of akathisia leading to noradrenergic and serotonergic mechanisms being implicated. It could be that either the cholinergic, dopaminergic or serotonergic systems are involved or that there is an imbalance of these systems that may be relevant.


Organ Location Determination and Contour Sparse Representation for Multiorgan Segmentation.
Organ segmentation on computed tomography (CT) images is of great importance in medical diagnoses and treatment. This paper proposes organ location determination and contour sparse representation methods (OLD-CSR) for multiorgan segmentation (liver, kidney, and spleen) on abdomen CT images using an extreme learning machine classifier. First, a location determination method is designed to obtain location information of each organ, which is used for coarse segmentation. Second, for coarse-to-fine segmentation, a contour gradient and rate change based feature point extraction method is proposed. A sparse optimization model is developed for refining the contour feature points. Experimentations with 153 CT images demonstrate the performance advantages of OLD-CSR as compared with related work.


TIBIAL TUBERCLE AVULSION FRACTURE IN A MALE ADOLESCENT.
Tibial tuberosity fractures are rare in childhood, most frequently due to excessive quadriceps muscle contraction. On performing long jump, a 15-year-old boy sustained tibial tuberosity avulsion fracture type II according to Watson-Jones. The patient was treated operatively with fragment repositioning and screw fixation. Ten months after the injury and rehabilitation, he resumed his sports activities with full range knee motion.


Atypical autoimmune polyglandular syndrome type 3 overlapped by chronic HCV infection resulting in carcinogenesis and fatal infection.
The case of a woman with insulin-dependent diabetes mellitus, autoimmune thyroiditis, atrophic gastritis, pernicious anemia, and immunologic thrombocytopenic purpura consisting of autoimmune polyglandular syndrome type 3 associated with a history of gonadal failure is reported. Hepatitis C viral infection added xerophthalmia, lymphocytic sialadenitis, and exacerbation of idiopathic thrombocytopenic purpura. This unique disease constellation was complicated with splenic marginal zone lymphoma and gastric carcinoids. A lung infection, initially treated on an outpatient basis, proved fatal to the patient.


Structural basis for amino acid export by DMT superfamily transporter YddG.
The drug/metabolite transporter (DMT) superfamily is a large group of membrane transporters ubiquitously found in eukaryotes, bacteria and archaea, and includes exporters for a remarkably wide range of substrates, such as toxic compounds and metabolites. YddG is a bacterial DMT protein that expels aromatic amino acids and exogenous toxic compounds, thereby contributing to cellular homeostasis. Here we present structural and functional analyses of YddG. Using liposome-based analyses, we show that Escherichia coli and Starkeya novella YddG export various amino acids. The crystal structure of S. novella YddG at 2.4 Å resolution reveals a new membrane transporter topology, with ten transmembrane segments in an outward-facing state. The overall structure is basket-shaped, with a large substrate-binding cavity at the centre of the molecule, and is composed of inverted structural repeats related by two-fold pseudo-symmetry. On the basis of this intramolecular symmetry, we propose a structural model for the inward-facing state and a mechanism of the conformational change for substrate transport, which we confirmed by biochemical analyses. These findings provide a structural basis for the mechanism of transport of DMT superfamily proteins.


Human leukocyte interferon for the treatment of varicella in children with cancer.
Human leukocyte interferon was evaluated as a treatment for varicella in a randomized double-blind, placebo-controlled study carried out in two phases. A total of 44 children being treated for cancer were enrolled within 72 hours of the appearance of the exanthem. The mean number of days of new lesion formation was 3.8 +/- 1.89 (+/- S.D.) in the interferon recipients and 5.3 +/- 2.56 in the placebo recipients (P less than 0.05). Eighty-one per cent of the interferon recipients had had no new lesions for 24 hours by Day 7, as compared with 56 per cent of the placebo recipients (P less than 0.025). In the second, higher-dose phase of the study 92 per cent of the interferon recipients had had no new lesions for 24 hours by Day 6, as compared with 45 per cent of the placebo recipients (P less than 0.025). Three of 21 placebo recipients died of progressive varicella. Two of the 23 interferon recipients died two to three weeks after the onset of varicella; viral cultures were negative in one of these patients, and the second had recurrent viremia at the end of the treatment period. Among the survivors, treatment with interferon reduced the number of patients who had life-threatening dissemination (none of 21 vs. three of 18; P = 0.053). We conclude that interferon had an antiviral effect against varicella virus in immunocompromised patients.


Compromised gastrointestinal integrity in pigtail macaques is associated with increased microbial translocation, immune activation, and IL-17 production in the absence of SIV infection.
Pigtail macaques (PTMs) rapidly progress to AIDS after simian immunodeficiency virus (SIV) infection. Given the strong association between human immunodeficiency virus (HIV) and SIV disease progression and microbial translocation and immune activation, we assessed whether high basal levels of immune activation and microbial translocation exist in PTMs. We found that before SIV infection, PTMs had high levels of microbial translocation that correlated with significant damage to the structural barrier of the gastrointestinal tract. Moreover, this increased microbial translocation correlated with high levels of immune activation and was associated with high frequencies of interleukin-17-producing T cells. These data highlight the relationship among mucosal damage, microbial translocation and systemic immune activation in the absence of SIV replication, and underscore the importance of microbial translocation in the rapid course of disease progression in SIV-infected PTMs. Furthermore, these data suggest that PTM may be an ideal model to study therapeutic interventions aimed at decreasing microbial translocation-induced immune activation.


Simultaneous assessment of glomerular filtration and barrier function in live zebrafish.
The zebrafish pronephros is a well-established model to study glomerular development, structure, and function. A few methods have been described to evaluate glomerular barrier function in zebrafish larvae so far. However, there is a need to assess glomerular filtration as well. In the present study, we extended the available methods by simultaneously measuring the intravascular clearances of Alexa fluor 647-conjugated 10-kDa dextran and FITC-conjugated 500-kDa dextran as indicators of glomerular filtration and barrier function, respectively. After intravascular injection of the dextrans, mean fluorescence intensities of both dextrans were measured in the cardinal vein of living zebrafish (4 days postfertilization) by confocal microscopy over time. We demonstrated that injected 10-kDa dextran was rapidly cleared from the circulation, became visible in the lumen of the pronephric tubule, quickly accumulated in tubular cells, and was detectably excreted at the cloaca. In contrast, 500-kDa dextran could not be visualized in the tubule at any time point. To check whether alterations in glomerular function can be quantified by our method, we injected morpholino oligonucleotides (MOs) against zebrafish nonmuscle myosin heavy chain IIA (zMyh9) or apolipoprotein L1 (zApol1). While glomerular filtration was reduced in zebrafish nonmuscle myosin heavy chain IIA MO-injected larvae, glomerular barrier function remained intact. In contrast, in zebrafish apolipoprotein L1 MO-injected larvae, glomerular barrier function was compromised as 500-kDa dextran disappeared from the circulation and became visible in tubular cells. In summary, we present a novel method that allows to simultaneously assess glomerular filtration and barrier function in live zebrafish.


Digital reconstruction of the mandible of an adult Lesothosaurus diagnosticus with insight into the tooth replacement process and diet.
Fragmentary caudal ends of the left and right mandible assigned to Lesothosaurus diagnosticus, an early ornithischian, was recently discovered in the continental red bed succession of the upper Elliot Formation (Lower Jurassic) at Likhoele Mountain (Mafeteng District) in Lesotho. Using micro-CT scanning, this mandible could be digitally reconstructed in 3D. The replacement teeth within the better preserved (left) dentary were visualised. The computed tomography dataset suggests asynchronous tooth replacement in an individual identified as an adult on the basis of bone histology. Clear evidence for systematic wear facets created by attrition is lacking. The two most heavily worn teeth are only apically truncated. Our observations of this specimen as well as others do not support the high level of dental wear expected from the semi-arid palaeoenvironment in which Lesothosaurus diagnosticus lived. Accordingly, a facultative omnivorous lifestyle, where seasonality determined the availability, quality, and abundance of food is suggested. This would have allowed for adaptability to episodes of increased environmental stress.


Cardiac Arrest during Total Hip Arthroplasty in a Patient on an Angiotensin Receptor Antagonist.
Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor antagonists (ARA) are effective and well-tolerated first-line drugs in the therapy of hypertension and, therefore, are frequently encountered in the perioperative setting. Hemodynamic compensation for volume depletion seen in the perioperative period is normally mediated by the renin-angiotensin system, which is blocked by ACEI/ARA. These drugs may contribute to severe hypotension during anesthesia induction and may have contributed to the cardiac arrest seen in this patient. Additional factors such as increased intra-abdominal pressures and respiratory obstructive episodes leading to diminished venous return, as well diuretic use and the fasting state, common in the perioperative orthopedic patient, are likely to have contributed as well. Medication use may be an easily modifiable risk factor for severe hypotension and possible cardiac arrest in the perioperative setting.


[Nurses' participation in heart rehabilitation].
The goal of cardiac rehabilitation is to incorporate patients with heart disease into their physical and social activities in such conditions that will allow them to lead a normal life "as good as possible". Their psychological needs have to be addressed, since these patients on leaving the hospital are anxious and afraid of the their future. The rehabilitation team must train the patients until they reach with success phase II of the heart rehabilitation program. The nurse plays and important role since she/he is the main mentor during phase II. At the cardiac rehabilitation service of the Instituto Nacional de Cardiología "Ignacio Chávez", we worked during May, June, July of last year with 45 patients in phase II; of these, 84% were men, most between 60 and 79 years of age (60%). The most frequent diagnoses were ischemic cardiopathy (71%) and arterial hypertension (64%). The most frequent medical-surgical treatments were: thrombolytic therapy, angioplasty, and placement of stents and aortic-coronary ducts in 48%. Stratification was of high risk in 62.2%.


Mycorrhiza helper bacterium Streptomyces AcH 505 induces differential gene expression in the ectomycorrhizal fungus Amanita muscaria.
The interaction between the mycorrhiza helper bacteria Streptomyces nov. sp. 505 (AcH 505) and Streptomyces annulatus 1003 (AcH 1003) with fly agaric (Amanita muscaria) and spruce (Picea abies) was investigated. The effects of both bacteria on the mycelial growth of different ectomycorrhizal fungi, on ectomycorrhiza formation, and on fungal gene expression in dual culture with AcH 505 were determined. The fungus specificities of the streptomycetes were similar. Both bacterial species showed the strongest effect on the growth of mycelia at 9 wk of dual culture. The effect of AcH 505 on gene expression of A. muscaria was examined using the suppressive subtractive hybridization approach. The responsive fungal genes included those involved in signalling pathways, metabolism, cell structure, and the cell growth response. These results suggest that AcH 505 and AcH 1003 enhance mycorrhiza formation mainly as a result of promotion of fungal growth, leading to changes in fungal gene expression. Differential A. muscaria transcript accumulation in dual culture may result from a direct response to bacterial substances.


Sclerosing perineurioma: Tumor of the hand with a short T2.
We present two cases of sclerosing perineurioma, a rare soft tissue tumor, in the palm and the ring finger respectively, presenting as a small, painless and subcutaneous mass. This tumor has a predilection for the digits and palms of young, predominantly male adults. In the present cases the tumors showed very low signal intensity on T2-weighted magnetic resonance (MR) images. Histologically they contained abundant collagen and hyalinized stroma, which would account for areas of low signal intensity on T2-weighted MR images. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen and human erythrocyte glucose transporter 1 and negative for S-100 protein. To the best of our knowledge, the appearance of sclerosing perineurioma on MR imaging has not been previously reported in the English-language literature. Sclerosing perineurioma should be considered in the differential diagnosis of hand tumors when the tumor shows low signal intensity on T2-weighted MR images.


Bovine nasal granuloma: a review.
The literature on granulomatous nasal diseases of cattle is reviewed, with emphasis on nasal granuloma, a disease of unknown cause which is enzootic in Australian dairy cattle. It is concluded that on available evidence the disease is most probably a form of allergic rhinitis.


Public Perceptions of Advance Care Planning, Palliative Care, and Hospice: A Scoping Review.
Background: Although access to advance care planning (ACP), palliative care, and hospice has increased, public attitudes may still be barriers to their optimal use. Purpose: To synthesize empirical research from disparate sources that describes public perceptions of ACP, palliative care, and hospice in ways that could inform public messaging. Data Sources: Searches of PubMed and other databases were made from January 2011 to January 2020. Study Selection: Studies reporting survey or interview data with the public that asked specifically about awareness and attitudes toward ACP, palliative care, or hospice were included. Data Extraction and Synthesis: Two reviewers independently screened citations, read full texts, and performed data abstraction. Twelve studies met inclusion criteria and included >9800 participants. For ACP, 80% to 90% of participants reported awareness, and a similar proportion considered it important, but only 10% to 41% reported having named a proxy or completed a written document. For palliative care, 66% to 71% of participants reported no awareness of palliative care, and those who reported awareness often conflated it with end-of-life care. However, after being prompted with a tested definition, 95% rated palliative care favorably. For hospice, 86% of participants reported awareness and 70% to 91% rated it favorably, although 37% held significant misconceptions. Limitations: A limited number of studies met inclusion criteria, and some were published in nonpeer reviewed sources. The studies reflect public perceptions pre-COVID-19. Conclusion: Consumer perceptions of ACP, palliative care, and hospice each have a distinct profile of awareness, perceptions of importance, and reports of action taking, and these profiles represent three different challenges for public messaging.


Effects of long-acting thyroid stimulator on thyrotropin stimulation of adenyl cyclase activity in thyroid plasma membranes.
Both thyroid-stimulating hormone (TSH) and long-acting thyroid stimulator (LATS) stimulated adenyl cyclase activity in plasma membranes obtained from bovine thyroid glands. The stimulation induced by LATS was much less than that obtained with maximal amounts of TSH. LATS inhibited TSH stimulation of adenyl cyclase activity while an equivalent amount of normal human gamma-globulin did not influence basal or TSH-stimulated activity. The inhibition by LATS appeared to be noncompetitive and was greatest when the plasma membranes were initially exposed to LATS for 30 min at 0 degrees C before being incubated with TSH for 10 min at 37 degrees C. Inhibition could still be demonstrated when the plasma membranes were incubated for 30 min at 0 degrees C with TSH before the addition of LATS. Prolonging the period of incubation of plasma membranes with LATS from 30 to 60 min did not augment the stimulation of adenyl cyclase or increase the inhibition of the effect of TSH. Papain digests of LATS also increased adenyl cyclase activity of thyroid plasma membrane and inhibited the stimulation induced by TSH. The inhibitory effect of LATS was not completely specific for TSH and thyroid plasma membranes since glucagon stimulation of adenyl cyclase in hepatic plasma membranes was also inhibited, but to a lesser extent. In contrast to the results obtained with thyroid plasma membranes, LATS did not influence basal adenyl cyclase activity in hepatic plasma membranes. Furthermore equivalent amounts of normal human gamma-globulin also decreased glucagon stimulation of adenyl cyclase activity in plasma membranes obtained from liver. The present data suggest that LATS stimulation of adenyl cyclase in thyroid plasma membranes might be due to a change in the membrane configuration rather than binding to a specific receptor site. Such modification of the membrane structure could interfere with the binding of TSH to specific receptors or to the subsequent stimulation of adenyl cyclase. However, the results do not exclude the possibility that some component in the preparation other than LATS might be responsible for the inhibition of the stimulation by TSH.


Thiazolidine derivatives as potent inhibitors specific for prolyl endopeptidase.
A series of N-blocked L-proline-containing compounds and their derivatives were synthesized. Their inhibitory activities for prolyl endopeptidase from bovine brain were examined and compared with that of N-benzyloxycarbonyl-L-prolyl-L-prolinal, which is the most effective enzyme inhibitor hitherto reported. Introduction of a sulfur atom into pyrrolidine ring quite effectively increased the inhibitory activity: replacement of pyrrolidine with thiazolidine or thiazolidine aldehyde (thioprolinal) and conversion of L-proline to L-thioproline residue resulted in increase in the inhibitory activity. Thus, N-benzyloxycarbonyl-L-thioprolyl-thiazolidine (Z-Thiopro-thiazolidine) and Z-L-Thiopro-L-thioprolinal showed Ki values of 0.36 and 0.01 nM, respectively, for prolyl endopeptidase from bovine brain; both values were significantly lower than that of Z-Pro-prolinal (Ki, 3.7 nM).


Enhancement of continuous-flow separation of viable/nonviable yeast cells using a nonuniform alternating current electric field with complex spatial distribution.
The variability in cell response to AC electric fields is selective enough to separate not only the cell types but also the activation states of similar cells. In this work, we use dielectrophoresis (DEP), which exploits the differences in the dielectric properties of cells, to separate nonviable and viable cells. A parallel-plate DEP device consisting of a bottom face with an array of micro-fabricated interdigitated electrodes and a top face with a plane electrode was proposed to facilitate the separation of cells by creating a nonuniform electric field throughout the flow channel. The operation and performance of the device were evaluated using live and dead yeast cells as model biological particles. Further, numerical simulations were conducted for the cell suspensions flowing in a channel with a nonuniform AC electric field, modeled on the basis of the equation of motion of particles, to characterize the separation efficiency by changing the frequency of applied AC voltage. Results demonstrated that dead cells traveling through the channel were focused onto a site around the minimum electric field gradient in the middle of the flow stream, while live cells were trapped on the bottom face. Cells were thus successfully separated under the appropriately tuned frequency of 1 MHz. Predictions showed good agreement with the observation. The proposed DEP device provides a new approach to, for instance, hematological analysis or the separation of different cancer cells for application in circulating tumor cell identification.


Experimental models for the autoimmune and inflammatory blistering disease, Bullous pemphigoid.
Bullous pemphigoid (BP) is a subepidermal skin blistering disease characterized immunohistologically by dermal-epidermal junction (DEJ) separation, an inflammatory cell infiltrate in the upper dermis, and autoantibodies targeted toward the hemidesmosomal proteins BP230 and BP180. Development of an IgG passive transfer mouse model of BP that reproduces these key features of human BP has demonstrated that subepidermal blistering is initiated by anti-BP180 antibodies and mediated by complement activation, mast cell degranulation, neutrophil infiltration, and proteinase secretion. This model is not compatible with study of human pathogenic antibodies, as the human and murine antigenic epitopes are not cross-reactive. The development of two novel humanized mouse models for the first time has enabled study of disease mechanisms caused by BP autoantibodies, and presents an ideal in vivo system to test novel therapeutic strategies for disease management.


[Effects of scopolamine on morphine-dependence in mice and the relationship between the effect and hippocampus intracellular calcium].
To observe the effect and mechanism of scopolamine on morphine(Mor)-induced mice dependence. The Mor-dependent mice model was established by intraperitoneal (ip) administered Mor for seven days. Pain threshold, times of jump and hippocampus intracellular free calcium ion concentration ([Ca2+]i) were determined by the heat plate test, naloxone (Nal)-precipitated jumping response and flow cytometry, respectively. The pain threshold of Mor-dependent mice decreased significantly while there was a marked increase in times of jump, the rate of jumping animals and hippocampus [Ca2+]i. Co-administered scopolamine, the pain threshold of Mor-dependent mice increased significantly; the number of jump, the rate of jumping animals and hippocampus [Ca2+]i all decreased significantly. Scopolamine could antagonize the Mor-induced mice dependence, which could be related to decreasing the levels of brain intracellular free calcium.


Resident nestin+ neural-like cells and fibers are detected in normal and damaged rat myocardium.
The present study examined whether nestin+ neural-like stem cells detected in the scar tissue of rats 1 week after myocardial infarction (MI) were derived from bone marrow and/or were resident cells of the normal myocardium. Irradiated male Wistar rats transplanted with beta-actin promoter-driven, green fluorescent protein (GFP)-labeled, unfractionated bone marrow cells were subjected to coronary artery ligation. Three weeks after MI, GFP-labeled bone marrow cells were detected in the infarct region, and a modest number were associated with nestin immunoreactivity. The paucity of GFP+/nestin+ cells in the scar tissue provided the impetus to explore whether neural-like stem cells were derived from cardiac tissue. Nestin mRNA and immunoreactivity were detected in normal rat myocardium, and transcript levels were increased in the damaged heart after MI. In primary-passage, cardiac tissue-derived neural cells, filamentous nestin staining was associated with a diffuse, cytoplasmic glial fibrillary acidic protein signal. Unexpectedly, in viable myocardium, numerous nestin+/glial fibrillary acidic protein+ fiberlike structures of varying length were detected and observed in close proximity to neurofilament-M+ fibers. The infarct region was likewise innervated, and the preponderance of neurofilament-M+ fibers appeared to be physically associated with nestin+ fiberlike structures. These data highlight the novel observation that the normal rat heart contained resident nestin+/glial fibrillary acidic protein+ neural-like stem cells, fiberlike structures, and nestin mRNA levels that were increased in response to myocardial ischemia. Cardiac tissue-derived neural stem cell migration to the infarct region and concomitant nestin+ fiberlike innervation represent obligatory events of reparative fibrosis in the damaged rat myocardium.


Ultralow quantum-defect eye-safe Er:Sc2O3 laser.
Resonantly pumped Er(3+):Sc(2)O(3) laser operation is achieved with a quantum defect (QD) of 1.5% at liquid nitrogen temperature. The laser, in-line pumped at 1535 nm, operated at 1558 nm with a slope efficiency of over 45%. This is believed to be the lowest QD eye-safe laser ever reported. CW output of over 3.3 W was obtained in this first experiment.


Protein N-glycosylation in the bronchoalveolar space differs between never-smokers and long-term smokers with and without COPD.
Chronic obstructive pulmonary disease (COPD) kills millions of people annually and patients suffering from exacerbations of this disorder display high morbidity and mortality. The clinical course of COPD is associated with dysbiosis and infections, but the underlying mechanisms are poorly understood. Glycosylation of proteins play roles in regulating interactions between microbes and immune cells, and knowledge on airway glycans therefore contribute to the understanding of infections. Furthermore, glycans have biomarker potential for identifying smokers with enhanced risk for developing COPD as well as COPD subgroups. Here, we characterized the N-glycosylation in the lower airways of healthy never-smokers (HNS, n = 5) and long-term smokers (LTS) with (LTS+, n = 4) and without COPD (LTS-, n = 8). Using mass spectrometry, we identified 57 highly confident N-glycan structures whereof 38 oligomannose, complex, and paucimannose type glycans were common to BAL samples from HNS, LTS-, and LTS+ groups. Hybrid type N-glycans were identified only in the LTS+ group. Qualitatively and quantitatively, HNS had lower inter-individual variation between samples compared to LTS- or LTS+. Cluster analysis of BAL N-glycosylation distinguished LTS from HNS. Correlation analysis with clinical parameters revealed that complex N-glycans were associated with health and absence of smoking whereas oligomannose N-glycans were associated with smoking and disease. The N-glycan profile from monocyte-derived macrophages differed from the BAL N-glycan profiles. In conclusion, long-term smokers display substantial alterations of N-glycosylation in the bronchoalveolar space, and the hybrid N-glycans identified only in long-term smokers with COPD deserve to be further studied as potential biomarkers.


Chlamydia--inside out.
The aim was to inform other health care professionals within the field of sexual health about the expanding role of the health adviser in genitourinary medicine. It also highlights the complementary role of a community health adviser that may develop if the chlamydia pilot study became a national screening programme. An audit of time management and workload created by partner notification for the positive patients generated by the chlamydia pilot was undertaken. This was done prospectively over a two-month period and the data were collected by the health advisers in the genitourinary medicine department. The results showed that 164 people generated by the pilot study were treated for chlamydia (80 cases and 84 partners): 25 letters and 8 phone calls were required to achieve this. The national sexual health strategy now addresses the issue of integration of sexual health services. It may be suggested that the role of the health adviser could be fundamental to this strategy and development of a community health adviser may then evolve.


Serial echocardiographic evaluation of the Perimount Magna Ease prosthesis.
The Carpentier-Edwards Perimount Magna Ease prosthesis (PME) represents the latest generation of stented bioprostheses used for surgical aortic valve replacement (SAVR). The aim of our study was to evaluate the long-term clinical outcome and hemodynamic performance of the prosthesis with a focus on the incidence and course of structural valve deterioration (SVD) by serial echocardiographic examinations. SAVR with the PME was performed in 58 consecutive patients between 2007 and 2008. Transthoracic echocardiography was performed preoperatively, at discharge and annually during a 10-year follow-up at the German Heart Center Munich. Mean age at surgery was 62±14 years. At discharge (n=57), the overall mean pressure gradient (MPG) and effective orifice area (EOA) were 15.8±4.1 mmHg and 1.8±0.4 cm2, respectively. Moderate patient-prosthesis mismatch (PPM) was present in 18 patients (32%) and severe PPM in 6 patients (11%) at discharge. Ten years following SAVR (n=33), the overall MPG was 16.6±7.3 mmHg and EOA was 1.3±0.4 cm2.Thirty-day and late mortality was 2% (n=1) and 21% (n=12), respectively. Survival at 1, 5, and 10 years was 94.7%±3.3%, 91.1%±4.1%, and 77.3%±5.9%, respectively. Freedom from reoperation at 10 years was 88.8%±4.7%. Ten years after PME implantation the cumulative incidence of any SVD, severe SVD, and bioprosthetic valve failure (BVF) was 25%±6%, 14%±5%, and 16%±5%, respectively. The PME shows an excellent hemodynamic performance over the course of 10 years with development of clinically relevant SVD as late as 6 years post implant, and a 10-year incidence of severe SVD of 14%.


Free viewing perceptual asymmetries for judgment of brightness and quantity: dependence on stimulus orientation.
Previous research has indicated that normals exhibit strong leftward biases during free-viewing perceptual judgments of brightness and quantity. When participants view two symmetrical objects and they are forced to choose which object appears darker or more numerous, participants usually select the stimulus with the relevant feature on the left side. The present study investigated the possibility that these perceptual asymmetries are dependent on scanning a stimulus horizontally across the midline by administering a task with two rectangular reversed stimuli presented either horizontally or vertically. When the stimuli were presented horizontally (crossing the midline), participants exhibited leftward biases, but these biases disappeared when the stimuli were presented vertically. This result supports the position that free-viewing perceptual asymmetries are dependent on scanning the stimuli across the midline.


Effectiveness of high-intensity interval training on glycemic control and cardiorespiratory fitness in patients with type 2 diabetes: a systematic review and meta-analysis.
The aim of this systematic review and meta-analysis was to quantify the effect of high-intensity interval training (HIIT) on glycemic control and cardiorespiratory fitness compared with moderate-intensity training (MICT) and no training at all in patients with type 2 diabetes (T2D). Relevant articles were sourced from PubMed, Embase, the Web of Science, EBSCO, and the Cochrane Library. Randomized-controlled trials were included based upon the following criteria: participants were clinically diagnosed with T2D, outcomes that included glycemic control (e.g., hemoglobin A1c); body composition (e.g., body weight); cardiorespiratory fitness (e.g., VO2peak) are measured at baseline and post-intervention and compared with either a MICT or control group. Thirteen trials involving 345 patients were finally identified. HIIT elicited a significant reduction in BMI, body fat, HbA1c, fasting insulin, and VO2peak in patients with type 2 diabetes. Regarding changes in the body composition of patients, HIIT showed a great improvement in body weight (mean difference: - 1.22 kg, 95% confidence interval [CI] - 2.23 to - 0.18, P = 0.02) and body mass index (mean difference: - 0.40 kg/m2, 95% CI - 0.78 to - 0.02, P = 0.04) than MICT did. Similar results were also found with respect to HbA1c (mean difference: - 0.37, 95% CI - 0.55 to - 0.19, P < 0.0001); relative VO2peak (mean difference: 3.37 ml/kg/min, 95% CI 1.88 to 4.87, P < 0.0001); absolute VO2peak (mean difference: 0.37 L/min, 95% CI 0.28 to 0.45, P < 0.00001). HIIT may induce more positive effects in cardiopulmonary fitness than MICT in T2D patients.


Ultrastiff Hydrogels Prepared by Schiff's Base Reaction of Bis(p-Formylphenyl) Sebacate and Pillar[5]arene Appended with Multiple Hydrazides.
Herein a facile method is reported to prepare polymer gels based on the formation of acylhydrazone bond under mild conditions. A pillar[5]arene derivative appended with ten hydrazide groups provides multiple sites for the reaction with the aldehyde groups of bis(p-formylphenyl) sebacate in the presence of a small amount of HCl as the catalyst in dimethyl sulfoxide (DMSO), producing transparent polymer organogels. The mechanical properties of gels can be easily tuned by the molar ratio of the reactant compounds. After solvent exchange from DMSO to water, translucent polymer hydrogels with dramatically enhanced strength and stiffness are obtained. The tensile breaking stress and Young's modulus of hydrogels are 20-60 and 1.2-2.7 MPa, respectively, 100 and 20 times those of the corresponding organogels. These robust hydrogels with ultrahigh stiffness should find applications such as in load-bearing artificial organs. This work should merit designing functional materials using other macrocycles.


Coordination of Single-cell and Bulk RNA Sequencing to Construct a Cuproptosis-related Gene Prognostic Index for Endometrial Cancer Prognosis, Immune Microenvironment Infiltration, and Immunotherapy Treatment Options.
Background: This study aims to identify molecular subtypes and develop a cuproptosis-related gene prognostic index (CRGPI) for endometrial cancer (EC), in addition to outlining the immune features and the efficacy of immune checkpoint inhibitor (ICI) therapy in CRGPI-defined groups of EC. Methods: Between malignant and normal cells distinguished from single-cell RNA sequencing data GSE154763 dataset, the difference in KEGG pathways and cuproptosis-related gene (CRG) scores was intensively investigated. On the basis of TCGA dataset (n=492), CRGs were used to identify two distinct molecular subtypes. Using the Cox regression method, a CRGPI was constructed and externally validated with the IMvigor210 dataset (n=348) and GSE78220. Then, the molecular and immune characteristics and the efficacy of ICI therapy in subgroups defined by CRGPI were investigated. Results: Compared to normal cells, the expression of the TCA cycle and CRGs genes was significantly higher in malignant cells. The CRGPI was established on the premise of ATF5, FBXO46, P2RX4, SMARCD3, DAPK3, and C1orf53. Comprehensive results demonstrated a correlation between a low CRGPI score and better overall survival, younger age, early stage, immune cells and functions activation, high tumor mutation burden and high microsatellite instability, as well as better benefit from ICI therapy, and its significance for forecasting immunotherapeutic effects was verified as well (IMvigor210 cohort: HR, 1.358; 95% CI, 1.047, 1.761; p=0.02; GSE78220 cohort: HR, HR = 3.857, 95% CI, 1.009, 14.74; p=0.034). CRGPI anticipated the immunotherapy medication. Conclusions: CRGPI is a prospective biomarker to estimate the prognosis, immune and molecular characteristics, and treatment benefit of immunotherapy in EC.


How important is onset of action in ulcerative colitis therapy?
Pharmacotherapy is the cornerstone of management in ulcerative colitis. However, controversy remains over optimal medical strategies. Specifically, differences in the onset of action of various drug therapies are thought to influence the achievement and maintenance of remission of disease, yet this is poorly characterised. There is a wide range of recent data concerning aminosalicylates, with much debate as to the relative merits of the various formulations and delivery systems. Meta-analyses confirm the efficacy of aminosalicylates for the induction and maintenance of remission and suggest that the newer agents are comparable in efficacy to sulfasalazine. Among aminosalicylates, data from clinical trials reveal that the onset of action is earlier with balsalazide than mesalazine. Although the efficacy of the newer 5-aminosalicylate agents is no greater than that of sulfasalazine, they have better adverse effect profiles. Factors such as tolerability and adherence appear more important than onset of action in long-term maintenance. Corticosteroids have long been used in the treatment of ulcerative colitis, yet there is a paucity of data regarding this. They have a rapid onset of action but considerable systemic adverse effects. Therefore, corticosteroids are reserved for disease that fails to respond to other agents or for primary therapy in patients with severe disease, although there is no universal acceptance of a threshold at which to initiate corticosteroid treatment.Rectal preparations of both aminosalicylates and corticosteroids have been developed in an attempt to exert a more rapid and direct onset of action while minimising adverse systemic effects. In clinical trials, topical preparations of both aminosalicylates and corticosteroids are effective in inducing remission. However, patient acceptability and proximal extent of disease dictate selection of a topical agent more than concern with rate of onset.A wide range of immunomodulators have been investigated in patients with steroid-refractory ulcerative colitis. The thioguanine derivatives are the most widely used but have a limited evidence base to support this use with controlled trials providing equivocal results regarding efficacy in severe ulcerative colitis. In addition, the thioguanine derivatives have a protracted onset of action and a considerable serious adverse effect profile. Calcineurin inhibitors and methotrexate have a more rapid onset of action than the thiopurines but have even less data to support their widespread use. They are widely regarded as salvage therapy and further data are required. Regarding biological agents, infliximab revolutionised the treatment of Crohn's disease, yet results in ulcerative colitis have been disappointing. Further trials are ongoing with great anticipation for more favourable data. The practical clinical implications of any differences between the agents depend on patient satisfaction with various therapies. Noncompliance is a major concern in maintenance therapy and is probably associated with relapse. Dose administration schedules and acceptability of therapy appear to be important factors in adherence. Overall, it is not clear that onset of action has a major influence on patient adherence and addressing issues of compliance may have more direct clinical impact.


Stimuli-Induced Reversible Transformation between Decanuclear and Pentanuclear Gold(I) Sulfido Complexes.
Decanuclear and pentanuclear gold(I) sulfido complexes of phenanthrene- and dibenzothiophene-based diphosphine ligands were synthesized and characterized. Unprecedented stimuli-induced reversible transformation between decanuclear and pentanuclear gold(I) sulfido complexes was observed, which could be readily monitored by NMR and UV-vis absorption spectroscopy in solution. Remarkably, the decanuclear gold(I) sulfido complex (Au10-LPh) was found to show a highly reversible transformation process, which is stable for over 10 successive cycles in solution. The stimuli-induced reversible transformation behavior of the gold(I) sulfido complexes was found to depend on the P-P bite distance of the bidentate phosphine ligands.


Why aren't they happy? An analysis of end-user satisfaction with Electronic health records.
Introduction. Implementations of electronic health records (EHR) have been met with mixed outcome reviews. Complaints about these systems have led to many attempts to have useful measures of end-user satisfaction. However, most user satisfaction assessments do not focus on high-level reasoning, despite the complaints of many physicians. Our study attempts to identify some of these determinants. Method. We developed a user satisfaction survey instrument, based on pre-identified and important clinical and non-clinical clinician tasks. We surveyed a sample of in-patient physicians and focused on using exploratory factor analyses to identify underlying high-level cognitive tasks. We used the results to create unique, orthogonal variables representative of latent structure predictive of user satisfaction. Results. Our findings identified 3 latent high-level tasks that were associated with end-user satisfaction: a) High- level clinical reasoning b) Communicate/coordinate care and c) Follow the rules/compliance. Conclusion: We were able to successfully identify latent variables associated with satisfaction. Identification of communicability and high-level clinical reasoning as important factors determining user satisfaction can lead to development and design of more usable electronic health records with higher user satisfaction.


Ambiguity resolution while mapping free text to the UMLS Metathesaurus.
We propose a method for resolving ambiguities encountered when mapping free text to the UMLS Metathesaurus. Much of the research in medical informatics involves the manipulation of free text. The Metathesaurus contains extensive information which supports solutions to problems encountered while processing such text. After discussing the process of mapping free text to the Metathesaurus and describing the ambiguities which are often the result of such mapping, we provide examples of rules designed to eliminate mapping ambiguities. These rules refer to the context in which the ambiguity occurs and crucially depend on semantic types obtained from the Metathesaurus. We have conducted a preliminary test of the methodology and the results obtained indicate that the rules successfully resolve ambiguity around 80% of the time.


Neural Stem Cell Regulation by Adhesion Molecules Within the Subependymal Niche.
In the mammalian adult brain, neural stem cells persist in neurogenic niches. The subependymal zone is the most prolific neurogenic niche in adult rodents, where residing stem cells generate large numbers of immature neurons that migrate into the olfactory bulb, where they differentiate into different types of interneurons. Subependymal neural stem cells derive from embryonic radial glia and retain some of their features like apico-basal polarity, with apical processes piercing the ependymal layer, and a basal process contacting blood vessels, constituting an epithelial niche. Conservation of the cytoarchitecture of the niche is of crucial importance for the maintenance of stem cells and for their neurogenic potential. In this minireview we will focus on extracellular matrix and adhesion molecules in the adult subependymal zone, showing their involvement not only as structural elements sustaining the niche architecture and topology, but also in the maintenance of stemness and regulation of the quiescence-proliferation balance.


Biotin-conjugated fusogenic liposomes for high-quality cell purification.
Purification of defined cell populations from mixed primary cell sources is essential for many biomedical and biotechnological applications but often very difficult to accomplish due to missing specific surface markers. In this study, we developed a new approach for efficient cell population separation based on the specific membrane fusion characteristics of distinct cell types upon treatment with fusogenic liposomes. When such liposomes are conjugated with biotin, specific cell populations can be efficiently surface functionalized by biotin after liposomal treatment while other populations remain unlabeled. Due to the high affinity of biotin for avidin-like proteins, biotin functionalized cells are ideal targets for conjugation of e.g. avidin tagged magnetic beads, fluorophores or antibodies with bioanalytical relevance. Here, based on the differential biotinylation of distinct cell populations high quality separation of cardiac fibroblasts from myocytes, and cerebromicrovascular endothelial cells from fibroblasts was successfully established.


Polymorphism rs42524 of COL1A2 and sporadic intracranial aneurysms in the Chinese population.
The COL1A2 gene at 7q22.1 has been shown to be associated with familial intracranial aneurysms (IAs) in the Japanese population. In the present study, the authors investigated the correlation between the presence of the rs42524 polymorphism in COL1A2 and the occurrence of sporadic IAs in Chinese patients. The polymorphism rs42524 of the COL1A2 gene was identified by polymerase chain reaction-based restriction analysis in genomic DNA from 226 patients with sporadic IAs (mean age 51.49 +/- 11.47 years) and 326 control participants (mean age 52.33 +/- 10.50 years). Neurological assessments were performed using the Hunt and Hess grading system, and differences in allelic and genotypic frequencies between the patient and control groups were evaluated with the chi-square test. There was a significant difference in either the genotype distribution (chi(2) = 11.99, p = 0.002) or allelic frequencies (chi(2) = 11.96, p = 0.001, odds ratio 2.579, 95% confidence interval 1.486-4.476) between patients with IAs and patients in the control group. The rs42524 polymorphism of COL1A2 could be a genetic risk factor for sporadic IAs among individuals of Chinese Han ethnicity. This study is the first to confirm the association between COL1A2 and IAs.


Perforated corneal ulcer with subsequent endophthalmitis in a patient with graft-versus-host disease.
To describe a case of a perforated corneal ulcer leading to a bacterial endophthalmitis in a patient with graft-versus-host disease (GVHD). Clinical history and examination; slit-lamp photography; surgical intervention; laboratory evaluation including microbiology, polymerase chain reaction (PCR), flow cytometry, and cytopathology. A diagnostic and therapeutic pars plana vitrectomy was performed. The vitreous aspirate was evaluated with microbiology; PCR for herpes simplex, herpes zoster, and cytomegalovirus; flow cytometry; and cytopathology. The patient received intravitreal antibiotics and antifungal and antiviral medication. The vitreous culture grew Staphylococcus epidermidis. Patients with GVHD are at risk for corneal ulcers with subsequent perforation. Commensal ocular flora may seed the vitreous and cause an endophthalmitis. Patients with GVHD may develop a vitritis from many causes including viral, fungal, and bacterial etiologies or a relapse of their original disease. When patients with GVHD present with vitritis, consideration should be given to obtaining a large vitreous aspirate to establish the etiology.


Modern methods in managing urachal adenocarcinoma.
We sought to evaluate modern diagnostic and treatment options for urachal adenocarcinoma (UAC) and to provide clarity regarding the available options and their outcomes for this poorly understood yet damaging disease. We conducted a systematic literature search in PubMed and Medline focusing on updated management of UAC. Surgical intervention continues to be the mainstay of treatment for localized UAC. However, with the increased availability of molecular and genetic profiling, chemotherapy has consistently demonstrated promising response rates and survival outcomes, especially for a disease that commonly presents in a metastatic stage. The role of checkpoint inhibitors remains under investigation. Cross-sectional imaging is vital during postoperative surveillance. However, there may also be a role for the adoption of cystoscopy to detect bladder recurrence. Although the importance of surgical resection remains unchanged, improved survival outcomes with chemotherapy have been found in small retrospective studies. Randomized trial data are required to further assess the influence of systemic treatment as a primary or adjuvant therapy. Moreover, a stringent follow-up regimen incorporating evaluation for distant and local recurrence of UAC must be evaluated and adopted.


Philosophy of science: how to identify the potential research for the day after tomorrow?
We were asked to participate in a workshop to assist the European Commission on how to choose financial support for high-potential, basic research projects that can give new scientific breakthroughs and thus contribute significantly to the positive development of society, industry, and economy for the day after tomorrow. At this workshop, we analyzed the problem in some detail using experience from our own research on the global quality of life. We would suggest that the most promising projects have the following characteristics: (1) they are led by a brilliant researcher who considers his/her research to be "sweet science", who wants to explain the anomalies of his/her field of science, and who lives in a nonmainstream scientific paradigm; (2) they are deeply engaged in the philosophical problems of their research field, they are searching eagerly for a new understanding and a new theory, giving new tools for measurement and creating change, and results are taken as feedback on all levels from tool to theory and philosophy; (3) they are focused on the key point(s), which is an essential feature of the universe that creates global change if intervened upon. At the NEST Pathfinder 2005 Topic Identification Workshop, Brussels 28 May 2004 entitled "Measuring the Impossible", we advised the European Commission Research Directorate to allocate funds for projects focusing on the state of consciousness--how to understand it, how to map it, and how to develop it.


An epigenetic switch governing daughter cell separation in Bacillus subtilis.
Growing cells of Bacillus subtilis are a bistable mixture of individual motile cells in which genes for daughter cell separation and motility are ON, and chains of sessile cells in which these genes are OFF. How this ON/OFF switch is controlled has been mysterious. Here we report that a complex of the SinR and SlrR proteins binds to and represses genes involved in cell separation and motility. We also report that SinR and SlrR constitute a double-negative feedback loop in which SinR represses the gene for SlrR (slrR), and, by binding to (titrating) SinR, SlrR prevents SinR from repressing slrR. Thus, SlrR indirectly derepresses its own gene, creating a self-reinforcing loop. Finally, we show that, once activated, the loop remains locked in a high SlrR state in which cell separation and motility genes are OFF for extended periods of time. SinR and SlrR constitute an epigenetic switch for controlling genes involved in cell separation and motility.


Lower likelihood of falling at age 90+ is associated with daily exercise a quarter of a century earlier: The 90+ Study.
to explore the relationship between risk of falling at age 90+ and prior physical activity at age 60-70s. population-based cohort study (The 90+ Study). California retirement community. of 1596 cohort members, 1536 had both falls and prior activity data. Mean age = 94 years; 78% female; 99% Caucasian. time spent in active physical activity was self-reported in 1980s; medical history, medication, assistive devices, residence type, and falls (outcome) was collected in 2000s. Activity/fall relationships were assessed using logistic regression. falls were reported by 52% of participants, recurrent falls by 32%, and severe injury by 21% of fallers. In univariate analyses risk of falling at age 90+ was significantly related to medical history (heart disease, TIA/stroke, arthritis, vision disease, depression, dementia), medication use (hypnotics, anti-psychotics, anti-depressants), use of assistive devices (cane, walker, wheelchair), residence type (living with relatives, sheltered living), and source of information (self-report vs informant). Risks of falling and recurrent falls at age 90+ were 35-45% lower in those reporting 30+ minutes/day of active physical activity at age 60-70s compared with no activity. The odds ratio of falling was 0.65 (95% CI = 0.44-0.97) for 30-45 minutes/day and 0.64 (0.44-0.94) for 1+ hour/day adjusting for age, sex, medical history (stroke/TIA, vision disease, depression), use of assistive devices, and source of information. falls are extremely common among the oldest-old and a significant proportion lead to severe injury. This work is the first to show an association between exercise at age 60-70s and lower risk of falling at age 90+.


Symptomatic brainstem cavernomas.
The goal of this study was to analyze the natural history of symptomatic brainstem cavernomas (medulla, pons, or midbrain) and outcome after surgical resection. We retrospectively analyzed clinical data of all patients who presented to our institution with symptomatic brainstem cavernomas between 1995 and 2007 (n = 44). After a first neurological event, the median event-free interval was 2 years, with an annual event rate of 42%. After a second neurological event (new neurological deficit or significant worsening of the previous deficit), the median event-free interval was only 5 months, with a monthly event rate of 8%. After an observation period of up to 8 years, all patients ultimately underwent surgery. In 95% of the patients, surgery successfully prevented further events during a median follow-up period of 11 months (1 month-7 years; P < 0.001). The postoperative event rate was 5% per year in the first 2 years and 0% thereafter. In the multivariate analysis, only the preoperative modified Rankin scale score was predictive of the surgical outcome (odds ratio, 36.7; P = 0.015). The conditions of 2 patients (5%) were clinically worse compared with their preoperative conditions during the 1-year follow-up period; in one of these patients, this was caused by recurrent events. There was no mortality. The event rate of symptomatic lesions seems to be high, particularly after recurrent events. Surgical morbidity can be low. Timely and complete surgical resection is recommended for symptomatic brainstem cavernomas to prevent patients' functional decline owing to recurrent events.


[Fear of falling: Validation of a measurement tool in Chilean elderly living in the community].
INTRODUCCIóN: Fear of falling, with or without previous falls history, is a risk factor for decreased mobility, disability, as well as a decreased quality of life, and can trigger the self-restriction of activities with loss of independence and functionality. Validated tools for measuring the fear of falling in the Chilean population is a needed to detect those at risk. There are currently no validated instruments to measure this phenomenon in Chile. The aim of this study is to validate the Spanish version of the short «Falls Efficacy Scale-International» (FES-I) in an elderly population living in the community in Chile. A cross-sectional study was performed using applications at baseline and 4 weeks. The short FES-I was translated using the back-translation method, evaluated by a panel of experts, and piloted in 10 older adults. After the pilot study, the final version was applied to a sample of 113 elderly persons. Data analysis used measures of central tendency, and reliability and confirmatory factor analysis was used. The Spanish version of the short FES-I showed good reliability and validity in an elderly Chilean population. This falls risks measurement tool can be used by clinicians and researchers in order to determine the magnitude of the problem and the impact of fear of falling on falls, functionality, and quality of life of the elderly who live in the community.


Aripiprazole-induced seizure: a second case report.
Aripiprazole has been recognised as a third generation antipsychotic and is considered to be distinguished from typical and atypical antipsychotics. In clinical trials, researchers did not mention the risk of aripiprazole-induced seizure, but during a literature review a case report was found that discussed this potential side effect. The present report concerns a 54-year-old man with chronic schizophrenia who developed a witnessed grand mal seizure after he had abruptly discontinued clozapine and benzodiazepam (BZD) treatment and concurrently reinitiated aripiprazole treatment as the result of an involuntary clinical error. The possible causes were explored, including clozapine-induced or withdrawal seizure, BZD withdrawal syndrome, psychogenic non-epileptic seizure, hyponatraemia, brain tumour and major physical illness, but none of the hypotheses can explain the seizure observed in this case. This second case is presented to corroborate a previous finding and emphasise the possibility of aripiprazole-induced seizure.


Hoarding in the home: a toolkit for the home healthcare provider.
Hoarding is a mental health disorder characterized by difficulties with discarding possessions, yielding cluttered and chaotic home environments that can pose significant safety concerns, impairment to functioning, and distress for those who live in and encounter these situations. Understanding the condition and the strategies available to support individuals who hoard are important skills for the home care provider and are described here in the context of one community organization's response via the development of a Community Clutter and Hoarding Toolkit.


Fluctuating insect diversity, abundance and biomass across agricultural landscapes.
Habitat destruction and deterioration of habitat quality caused a severe decline of biodiversity, such as insect diversity. In this study, we analyze insect diversity and biomass across agro-environments. We collected flying insects with 20 malaise traps across a landscape mosaic consisting of organic (eight traps) and conventional (four traps) farmland, as well as across agricultural land that has been recently converted from conventional to organic farming (eight traps). Sampling was conducted over 2 years, in 2019 and 2020, with in total 340 sampling events. We measured the dry weight of the captured organisms and identified species diversity by analyzing Operational Taxonomic Units (OTUs) and Barcode Index Numbers (BINs) via metabarcoding. The results obtained show temporal dynamics. The number of OTUs were always higher than the number of BINs. OTUs and BINs were moderately to highly correlated, while the number of OTUs and BINs were only moderately positively correlated with dry biomass. OTUs and BINs as well as biomass were highest in the recently transformed farmland if compared with pure organic and conventional farmland sites, which showed no significant differences in respect of insect diversity. OTU and BIN numbers but not the OTU/BIN ratio significantly decreased with increasing distance from the nearest forest fringe. The numbers of OTUs, BINs and the OTU/BIN proportion, as well as OTU and BIN/biomass proportions varied strongly over seasons, irrespective of agricultural practice. Based on our findings, we suggest to combine data on insect species richness and biomass measured over a period of time, to derive a largely complete and meaningful assessment of biodiversity for a specific region.


Facile formation of β-hydroxyboronate esters by a Cu-catalyzed diboration/Matteson homologation sequence.
The copper-catalyzed diboration of aldehydes was used in conjunction with the Matteson homologation, providing the efficient synthesis of β-hydroxyboronate esters. The oxygen-bound boronate ester was found to play a key role in mediating the homologation reaction, which was compared to the α-hydroxyboronate ester (isolated hydrolysis product). The synthetic utility of the diboration/homologation sequence was demonstrated through the oxidation of one product to provide a 1,2-diol.


The Role of Information and Nudges on Advance Directives and End-of-Life Planning: Evidence From a Randomized Trial.
Despite the substantial personal and economic implications of end-of-life decisions, many individuals fail to document their wishes, which often leads to patient dissatisfaction and unnecessary medical spending. We conducted a randomized trial of 1,200 patients aged 55 years and older to facilitate advance directive (AD) completion and better understand why patients fail to engage in high-value planning. We found that including a physical AD form with paper letters as a nudge to decrease hassle costs increased AD completion by 9.0 percentage points (95% confidence interval [CI] = [4.2, 13.9] percentage points). The intervention was especially effective for individuals aged 70 years and older, as AD completion increased by 17.5 percentage points (95% CI = [5.7, 9.4] percentage points). When compared with the impact of costless electronic reminders, each additional AD completion from the letter interventions costs as little as US$37. Our findings suggest that simple, inexpensive interventions with paper communication as behavioral nudges can be effective, especially in older populations.


Overcoming resistance to EGFR tyrosine kinase inhibitors in lung cancer, focusing on non-T790M mechanisms.
despite initial dramatic efficacy of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutant lung cancer patients, emergence of acquired resistance is almost inevitable. The EGFR T790M secondary mutation that accounts for ~50% of resistance is now treatable with osimertinib. However, for the remaining 50% of patients who develop resistance mechanisms other than T790M mutation, cytotoxic chemotherapies are still the standard of care and novel treatment strategies are urgently needed. Areas covered: In this review, we discuss current experimental and clinical evidence to develop better treatment strategies to overcome or prevent acquired resistance to EGFR-TKIs in lung cancers, focusing on non-T790M mechanisms. Expert commentary: There are numerous non-T790M resistant mechanisms to EGFR-TKIs, and therefore, strategies that can be applied to many of these resistance mechanisms may be reasonable and useful in clinical practice. Although the combination of cytotoxic chemotherapy plus an EGFR-TKI has proved to be detrimental following front-line EGFR-TKI treatment failure, promising experimental and/or early clinical data have been reported for the combination of bevacizumab or anti-EGFR monoclonal antibody plus EGFR-TKIs. Upfront polytherapy, which co-targets potential resistance mechanisms or other important signaling for EGFR-mutant lung cancer cells, is also a promising strategy.


A Critique of the Short Test of Functional Health Literacy in Adults.
Effective healthcare relies on the ability to communicate with patients. Ninety-eight million Americans are estimated to have limited health literacy that can impair their ability to read and interpret health-related education and information. Low health literacy is associated with higher mortality and 30-day hospital readmissions. Clinical nurse specialists and other advanced practice nurses must be able to evaluate and select a health literacy assessment instrument that is both reliable and produces valid data for the populations they serve. To assist with this important decision-making process, the psychometric properties of the Short Test of Functional Health Literacy in Adults are critiqued in the following article.