Multidisciplinary team collaboration impact on NGF, BDNF, serum IGF-1, and life quality in patients with hemiplegia after stroke.
This study aimed to study the impact of multidisciplinary team collaboration on NGF, BDNF, serum IGF-1, and life quality in patients with hemiplegia after stroke. For this purpose, 200 post-stroke hemiplegic patients admitted from March 2022 to February 2023 were selected and randomly divided into a control group (100) and an observation group (100). The control group was given routine nursing care, while the observation group was given a multidisciplinary team collaboration model. The neurotroph in [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)] and nutritional status [hemoglobin (HGB), serum albumin (ALB), transferrin (TRF)] of patients were compared before and after the intervention on the second day of admission and on the 30th day of intervention. The FUGL Meyer (FM) motor function assessment scale, NIHSS National Institutes of Health Stroke Scale, and the Specialized Quality of Life Scale (SS-QIL) for stroke patients were used to assess limb motor function, balance function, degree of neurological impairment, and life quality. Results showed that before intervention, there was no statistically significant difference in the levels of NGF, BDNF, IGF-1, HGB, ALB, TRF, limb motor function, balance function, neurological deficits, and quality of life scores between the two (P>0.05); After intervention, the levels of NGF, BDNF, IGF-1, HGB, ALB, and TRF in the observation group were significantly higher (P<0.05); The FM and SS-QOL of patients in the observation group were significantly higher (P<0.05); The NIHSS score of patients in the observation group was significantly lower (P<0.05). In conclusion, multidisciplinary team cooperation can significantly improve the level of neurotrophin, reduce the degree of nerve defect, and promote the recovery of limb function, balance function and life quality for stroke patients with hemiplegia.


A protein corona primer for physical chemists.
Nanoparticles present in any biological environment are exposed to extracellular proteins. These proteins adsorb on the surface of the nanoparticle forming a "protein corona." These proteins control the interaction of nanoparticles with cells. The interaction of proteins with the nanoparticle surface is governed by physical chemistry. Understanding this process requires spectroscopy, microscopy, and computational tools that are familiar to physical chemists. This perspective provides an overview of the protein corona along with two future directions: first, the need for new computational approaches, including machine learning, to predict corona formation and second, the extension of protein corona studies to more complex environments ranging from lung fluids to waste water treatment.


Transfer RNA identity change in anticodon variants of E. coli tRNA(Phe) in vivo.
The anticodon sequence is a major recognition element for most aminoacyl-tRNA synthetases. We investigated the in vivo effects of changing the anticodon on the aminoacylation specificity in the example of E. coli tRNA(Phe). Constructing different anticodon mutants of E. coli tRNA(Phe) by site-directed mutagenesis, we isolated 22 anticodon mutant tRNA(Phe); the anticodons corresponded to 16 amino acids and an opal stop codon. To examine whether the mutant tRNAs had changed their amino acid acceptor specificity in vivo, we tested the viability of E. coli strains containing these tRNA(Phe) genes in a medium which permitted tRNA induction. Fourteen mutant tRNA genes did not affect host viability. However, eight mutant tRNA genes were toxic to the host and prevented growth, presumably because the anticodon mutants led to translational errors. Many mutant tRNAs which did not affect host viability were not aminoacylated in vivo. Three mutant tRNAs containing anticodon sequences corresponding to lysine (UUU), methionine (CAU) and threonine (UGU) were charged with the amino acid corresponding to their anticodon, but not with phenylalanine. These three tRNAs and tRNA(Phe) are located in the same cluster in a sequence similarity dendrogram of total E. coli tRNAs. The results support the idea that such tRNAs arising from in vivo evolution are derived by anticodon change from the same ancestor tRNA.


Charge-driven selective localization of fluorescent nanoparticles in live cells.
Covalent grafting of amino groups onto the carboxylic acid functionalities, naturally covering the surface of fluorescent nanoparticles produced from silicon carbide (SiC NPs), allowed tuning of their surface charge from negative to highly positive. Incubating 3T3-L1 fibroblast cells with differently charged SiC NPs demonstrates the crucial role of the charge in cell fluorescent targeting. Negatively charged SiC NPs concentrate inside the cell nuclei. Close to neutrally charged SiC NPs are present in both cytoplasm and nuclei while positively charged SiC NPs are present only in the cytoplasm and are not able to move inside the nuclei. This effect opens the door for the use of SiC NPs for easy and fast visualization of long-lasting biological processes taking place in the cell cytosol or nucleus as well as providing a new long-term cell imaging tool. Moreover, here we have shown that the interaction between charged NPs and nuclear pore complex plays an essential role in their penetration into the nuclei.


Isolation and Characterization of a Novel Alpha-Hemolytic Streptococcus spp. from the Oral Cavity and Blood of Septicemic Periparturient Immunodeficient Mice.
MISTRG is an immunodeficient mouse strain that expresses multiple human cytokines that support hematopoietic stem cell maintenance and myelopoiesis. While establishing a breeding colony of MISTRG mice in a dedicated barrier room, 6 cases of death or disease occurred in pregnant or postpartum mice. Clinically, this manifested as hunched posture, dyspnea, and 1 case of emaciation with ataxia. Pathologic analysis of 7 mice revealed multisystemic necrosuppurative inflammation variably affecting the uterus and placenta, joints, meninges, inner and middle ears, kidneys, and small intestine. Bacteria cultured from the blood of septic mice were identified with 89% probability by the Vitek 2 identification system as Streptococcus sanguinus with atypical biochemical parameters; the API 20E/NE system fully differentiated the isolates as a novel Streptococcus species. MALDI Biotyper-based mass spectrometry also indicated that the phenotype represented a novel Streptococcus spp. Sequencing revealed that the full-length 16S rRNA gene identity was below 97% with known Streptococcus species, including the 2 closest species Streptococcus acidominimus and Streptococcus azizii. We propose the name Streptococcus murisepticum spp. nov to our novel isolates. All male mice in this colony remained healthy despite their association with diseased female mice. Overall, 19% of the colony carried the novel Streptococcus in their oral cavity, but it could not be detected in feces. The organism was sensitive to amoxicillin, which was administered via drinking water throughout pregnancy and weaning to establish a colony of pathogen-negative future breeders. The colony remained disease-free and culture-negative for Streptococcus murisepticum spp. nov after treatment with amoxicillin. We suspect that oral colonization of MISTRG mice with the novel Streptococcus species and its associated unique pathology in periparturient mice is potentially the principal cause of loss of this strain at several institutions. Therefore, screening the oral cavity for α-hemolytic streptococci followed by targeted antibiotic treatment may be necessary when establishing MISTRG and allied immunodeficient mouse strains.


Toward a Cenozoic history of atmospheric CO2.
The geological record encodes the relationship between climate and atmospheric carbon dioxide (CO2) over long and short timescales, as well as potential drivers of evolutionary transitions. However, reconstructing CO2 beyond direct measurements requires the use of paleoproxies and herein lies the challenge, as proxies differ in their assumptions, degree of understanding, and even reconstructed values. In this study, we critically evaluated, categorized, and integrated available proxies to create a high-fidelity and transparently constructed atmospheric CO2 record spanning the past 66 million years. This newly constructed record provides clearer evidence for higher Earth system sensitivity in the past and for the role of CO2 thresholds in biological and cryosphere evolution.


[Neuropathic pain in the elderly].
Neuropathic pain is characterized by a heavier intensity and a longer duration than in non-neuropathic chronic pain. Its frequency is estimated around 9% of the population aged 65 years and over. Diabetes, shingles, cancer, surgery, radiculopathies or stroke are frequent in elderly and may lead to neuropathic pain. It's treatment is a real challenge in elderly. Beside the difficulties of pain evaluation and choice of a therapeutic strategy, intercurrent diseases associated with aging and polymedication require a complex drug treatment. The leading role of cognition, emotion, physical activity for autonomy preservation, and the dynamic interaction between these domains in the old, oldest old and most fragile persons, imply that any pharmacological treatment must be integrated into a non-pharmacological approach. However, very few studies has been specifically devoted to neuropathic pain in elderly. Epidemiological studies and controlled clinical trials are necessary to optimize pain treatment and could result in polymodal therapeutic strategies, which until now only are evidence-based or intuitively developed.


The binding of metal salts and corrosion products to cells and proteins in vitro.
The binding of metal ions from salts and from corrosion products of 316 LVM stainless steel and MP-35 to blood cells and serum proteins was studied in vitro. In the first series of experiments, metal salts were added to whole blood and then the blood separated into red cells, white cells, and serum. Nickel from nickel chloride or corrosion products of stainless steel bound in very small quantities to blood cells. Cobalt from cobalt chloride bound to both red cells and white cells. Chromium from chromic chloride (Cr3+) bound to cells in very small quantities whereas chromium from potassium dichromate (Cr6+) and corrosion products showed very high to binding to red cells and some binding to white cells. In a second series of experiments the blood was separated into its components and then the metal salts were added and the binding pattern was identical. In a third series of experiments serum which had interacted with the metal salts or corrosion products was separated into its components by isoelectric focusing on polyacrylamide gels. Almost all of the metal, whatever the source, was detected in the albumin region of the gels indicating strong binding to albumin. These studies on the cell and protein binding of the metals help to explain the dissemination of corrosion products from the site of the implant and subsequent systemic responses by some individuals.


Clinical and Radiological Outcomes after Reducing Adult Lytic High-Grade Spondylolisthesis Using a Hybrid Technique: Combination of Percutaneous Pedicle Screws with Midline Microscopic Transforaminal Decompression.
Retrospective study. To analyze the results and effectiveness of percutaneous screws (PS) with midline microscopic transforaminal decompression (MTFD) technique in reducing adult stiff lytic high-grade spondylolisthesis (HGSL) and compare it with the conventional technique. Pedicle screw cannulation and segmental kyphosis negotiation are surgical challenges in HGSL. Open reduction is the preferred approach. PS have the advantage of optimized trajectory and minimized soft tissue exposure. The role of minimally invasive surgery in HGSL remains unknown. We propose a hybrid technique combining PS with MTFD for lytic HGSL. This study included 25 patients with adult lytic HGSL (Meyerding grade III and IV) operated using a hybrid technique from 2012 to 2015. Data were compared with retrospective data on conventional open reduction (n=23) operated from 2000 to 2015. The minimum follow-up was 5 years. Clinical outcomes were assessed using the Visual Analog Scale (VAS) score and modified Oswestry Disability Index (m-ODI). The spinopelvic and peri-operative parameters were recorded. The inter-body fusion and adjacent segment degeneration (ASD) were assessed on radiographs at the final follow-up. The average age in the MTFD and open groups was 45.84±12.70 years (nine males and 16 females) and 49.26±13.33 years (eight males and 15 females), respectively. Further, 22 and three patients in the MTFD group and 19 and four in the open group had grade III and IV listhesis, respectively. The MTFD group demonstrated less operative time, blood loss, and hospital stays than the open group. Significant improvements were observed in VAS and m-ODI in subsequent follow-ups in both groups. The MTFD group fared better at 3 months but outcomes were comparable at the final follow-up. Both techniques were equally effective in restoring spinopelvic parameters. The incidence of ASD is comparable. The technique was proven effective in reducing HGSL. The long-term clinical and radiological outcomes were favorable and comparable with the conventional approach.


Cytokeratin expression in rat mesothelial cells in vitro is controlled by the extracellular matrix.
Rat mesothelial cells co-express vimentin and the simple epithelial cytokeratins. While cytokeratins predominate in situ, under most culture conditions vimentin is the major intermediate filament protein of the cells. This loss of cytokeratin production upon culture can be partly prevented by growing mesothelial cells on a basement membrane matrix. However, the basement membrane-promoted persistence of cytokeratin synthesis is not accompanied by expression of cytokeratin G (no. 19), the major acidic cytokeratin of mesothelium in vivo. While cells grown on plastic establish a prominent juxtanuclear assemblage of tonofilaments, those cultured on basement membrane exhibit cytokeratin filaments which are distributed throughout the cytoplasm and attach to neighboring cells at the plasma membrane. This latter pattern resembles that seen in the intact mesothelium. Intermediate filaments are markers of cellular differentiation, but their roles are obscure. The response of cultured mesothelial cells to different growth substrata supports the hypothesis that intermediate filament synthesis is influenced by cellular contact with the extracellular matrix.


Pain and emotional eating: further investigation of the Yale Emotional Overeating Questionnaire in weight loss seeking patients.
Providers frequently report pain as a barrier to weight loss yet the relationship between the pain experience and eating behavior is poorly understood. The current study examines overeating in response to physical pain (Pain Overeating). Weight-loss seeking Veterans (N = 126) completed the Yale Emotional Overeating Questionnaire, a measure used to assess the frequency of overeating in response to a range of emotions that was adapted to include a Pain Overeating item, and validated measures of pain, eating pathology, and mental health. Fifty-one participants (42.5%) engaged in at least one Pain Overeating episode in the past month, and 14.2% engaged in this behavior daily. Pain Overeating was significantly related to pain intensity and interference, and accounted for statistically significant variance in predicting BMI, eating pathology and depression. Findings suggest eating in response to physical pain is common among weight-loss seeking Veterans and may have important implications for weight management treatment.


Pre-existent vertebral rotation in the human spine is influenced by body position.
Both the humans as well as the quadrupedal spine have been shown to exhibit a pattern of pre-existent rotation that is similar in direction to what is found in the most common types of idiopathic scoliosis. It has been postulated that human bipedalism introduces forces to the spine that increase a tendency of the vertebrae to rotate. The objective of this study was to examine the effect of body position on vertebral rotation in vivo. Thirty asymptomatic volunteers underwent magnetic resonance imaging scanning of the spine (T2-L5) in three different body positions; upright, quadrupedal-like (on hands-and-knees) and supine. Vertebral rotation in the local transverse plane was measured according to a pre-established method and compared at different spinal levels between the three body positions. It was shown that in all three positions the mid- and lower thoracic vertebrae were predominantly rotated to the right. However, vertebral rotation was significantly less in the quadrupedal position than in both the standing upright and supine positions.


Surgical Outcomes in Benign Gynecologic Surgery Patients during the COVID-19 Pandemic (SOCOVID study).
To determine the incidence of perioperative coronavirus disease (COVID-19) in women undergoing benign gynecologic surgery and to evaluate perioperative complication rates in patients with active, previous, or no previous severe acute respiratory syndrome coronavirus 2 infection. A multicenter prospective cohort study. Ten institutions in the United States. Patients aged >18 years who underwent benign gynecologic surgery from July 1, 2020, to December 31, 2020, were included. All patients were followed up from the time of surgery to 10 weeks postoperatively. Those with intrauterine pregnancy or known gynecologic malignancy were excluded. Benign gynecologic surgery. The primary outcome was the incidence of perioperative COVID-19 infections, which was stratified as (1) previous COVID-19 infection, (2) preoperative COVID-19 infection, and (3) postoperative COVID-19 infection. Secondary outcomes included adverse events and mortality after surgery and predictors for postoperative COVID-19 infection. If surgery was delayed because of the COVID-19 pandemic, the reason for postponement and any subsequent adverse event was recorded. Of 3423 patients included for final analysis, 189 (5.5%) postponed their gynecologic surgery during the pandemic. Forty-three patients (1.3% of total cases) had a history of COVID-19. The majority (182, 96.3%) had no sequelae attributed to surgical postponement. After hospital discharge to 10 weeks postoperatively, 39 patients (1.1%) became infected with severe acute respiratory syndrome coronavirus 2. The mean duration of time between hospital discharge and the follow-up positive COVID-19 test was 22.1 ± 12.3 days (range, 4-50 days). Eleven (31.4% of postoperative COVID-19 infections, 0.3% of total cases) of the newly diagnosed COVID-19 infections occurred within 14 days of hospital discharge. On multivariable logistic regression, living in the Southwest (adjusted odds ratio, 6.8) and single-unit increase in age-adjusted Charlson comorbidity index (adjusted odds ratio, 1.2) increased the odds of postoperative COVID-19 infection. Perioperative complications were not significantly higher in patients with a history of positive COVID-19 than those without a history of COVID-19, although the mean duration of time between previous COVID-19 diagnosis and surgery was 97 days (14 weeks). In this large multicenter prospective cohort study of benign gynecologic surgeries, only 1.1% of patients developed a postoperative COVID-19 infection, with 0.3% of infection in the immediate 14 days after surgery. The incidence of postoperative complications was not different in those with and without previous COVID-19 infections.


Addressing Challenges of Distance Learning in the Pandemic with Edge Intelligence Enabled Multicast and Caching Solution.
The COVID-19 pandemic has affected the world socially and economically changing behaviors towards medical facilities, public gatherings, workplaces, and education. Educational institutes have been shutdown sporadically across the globe forcing teachers and students to adopt distance learning techniques. Due to the closure of educational institutes, work and learn from home methods have burdened the network resources and considerably decreased a viewer's Quality of Experience (QoE). The situation calls for innovative techniques to handle the surging load of video traffic on cellular networks. In the scenario of distance learning, there is ample opportunity to realize multi-cast delivery instead of a conventional unicast. However, the existing 5G architecture does not support service-less multi-cast. In this article, we advance the case of Virtual Network Function (VNF) based service-less architecture for video multicast. Multicasting a video session for distance learning significantly lowers the burden on core and Radio Access Networks (RAN) as demonstrated by evaluation over a real-world dataset. We debate the role of Edge Intelligence (EI) for enabling multicast and edge caching for distance learning to complement the performance of the proposed VNF architecture. EI offers the determination of users that are part of a multicast session based on location, session, and cell information. Moreover, user preferences and network's contextual information can differentiate between live and cached access patterns optimizing edge caching decisions. While exploring the opportunities of EI-enabled distance learning, we demonstrate a significant reduction in network operator resource utilization and an increase in user QoE for VNF based multicast transmission.


Antioxidants may protect cancer cells from apoptosis signals and enhance cell viability.
Quercetin is one of the most abundant dietary flavonoids widely present in many fruits and vegetables. Previous in vitro studies has shown that quercetin acts as an antioxidant and anti-inflammatory agent and it has potent anticarcinogenic properties as an apoptosis inducer. In this study we examined apoptotic effects of quercetin on the K562 erythroleukemia cell line. K562 cells were induced to undergo apoptosis by hydrogen peroxide. Cell viability and apoptosis level were assessed by annexin V and PI staining methods using flow cytometry. Viability of K562 cells was increased by low dose of quercetin (5-100 μM) for 3 hours. High doses of quercetin proved toxic (100-500 μM, 24 hours) and resulted in decrease of K562 cell viability as expected (P<0.01). As to results, 100 μM quercetin was defined as a protective dose. Also, K562 cell apoptosis due to hydrogen peroxide was decreased in a dose dependent manner. As indicated in previous studies, reduction of superoxides by free radical scavengers like quercetin could be beneficial for prevention of cancer but consumption of such flavonoids during cancer treatment may weaken effects of chemotherapeutics and radiotherapy. Especially cancer patients should be carefully considered for traditional phytotherapy during cancer treatment, which can lead to controversial results.


Adjuvant Therapies in Nonmetastatic Renal-Cell Carcinoma: A Review of the Literature.
To conduct a review of literature on adjuvant therapy in nonmetastatic renal-cell carcinoma (nmRCC) treated with nephrectomy and to describe the efficacy of adjuvant agents on cancer control outcomes. A review of the literature was performed in January 2018 to identify all studies evaluating adjuvant therapy in patients with nmRCC treated with nephrectomy using PubMed, Embase, Medline, and Cochrane Library databases. The following keywords were used: adjuvant therapy, renal-cell carcinoma, nonmetastatic, targeted molecular therapy, kidney cancer. The ClinicalTrials.gov website was queried to identify ongoing trials. Traditional adjuvant therapy agents consisted of interferon α, interleukin 2, autologous tumor cell vaccines, and monoclonal antibodies. None provided survival benefit. Three contemporary studies (S-TRAC, ASSURE, and PROTECT) using targeted therapy compared sunitinib to placebo (S-TRAC), sunitinib or sorafenib to placebo (ASSURE), and pazopanib to placebo (PROTECT), with controversial results. In contrast to ASSURE and PROTECT, S-TRAC demonstrated improved disease-free survival. Several trials that use checkpoint immunotherapy agents or vascular endothelial growth factor receptor tyrosine kinase inhibitors are ongoing. Many traditional therapies have shown no success as adjuvant therapy for nmRCC after nephrectomy. Targeted adjuvant therapy for nmRCC after nephrectomy showed controversial results, and its routine use is not currently endorsed.


Survival of adult basal forebrain cholinergic neurons after loss of target neurons.
Target cells are thought to regulate the survival of afferent neurons during development by supplying limiting amounts of neurotrophic factors, but the degree to which afferent neurons remain dependent on target-derived support in the adult is uncertain. In this study, uninjured basal forebrain cholinergic neurons did not die after excitotoxic ablation of their target neurons in young adult rats, indicating that they are either not dependent on neurotrophic factors for survival or can obtain trophic support from other sources after target neurons are lost. This finding suggests that cholinergic cell death in neurodegenerative conditions such as Alzheimer's disease is not due solely to a loss of target neurons or factors provided by them.


Steroids, sex hormone-binding globulin, homocysteine, selected hormones and markers of lipid and carbohydrate metabolism in patients with severe hypothyroidism and their changes following thyroid hormone supplementation.
Laboratory markers of thyroid function, selected steroid hormones, sex hormone-binding globulin (SHBG), homocysteine, prolactin, major markers of lipid- and glucose metabolism and of insular-growth hormone axes were investigated in fasting sera from 16 female patients with severe hypothyroidism after thyroidectomy because of thyroid cancer. The results obtained in severe hypothyroidism within 5-6 weeks after withdrawal of thyroid substitution therapy before control scintigraphy were compared with those obtained after correction of thyroid function. Elevated levels of homocysteine and prolactin in hypothyroidism significantly decreased after correction, while SHBG concentration increased. Correction of thyroid function led to significant changes of growth hormone and immunoglobulin F1 (decrease and increase, respectively), while insulin and proinsulin increased only insignificantly. Elevated levels of total cholesterol and triglycerides in hypothyroidism were normalized, along with a significant increase in high density lipoprotein (HDL)-cholesterol. As revealed by correlation and factor analyses, different relationships characterizing both states were found in hypothyroidism and after correction of thyroid function. A strong inverse relationship between homocysteine and free thyroid hormones confirms the effect of thyroid hormones on homocysteine metabolism. No such inverse relation was found in euthyroid state, however. Similarly, in hypothyroidism only, dehydroepiandrosterone sulfate correlated positively with immunoglobulin F1 and homocysteine and negatively with thyroid hormones and SHBG.


Highly Electrophilic Intermediates in the Bypass Mechanism of Glutathione Peroxidase: Synthesis, Reactivity, and Structures of Selenocysteine-Derived Cyclic Selenenyl Amides.
Selenocysteine (Sec)-derived cyclic selenenyl amides, formed by the intramolecular cyclization of Sec selenenic acids (Sec-SeOHs), have been postulated to function as protective forms in the bypass mechanism of glutathione peroxidase (GPx). However, their chemical properties have not been experimentally elucidated in proteins or small-molecule systems. Recently, we reported the first nuclear magnetic resonance observation of Sec-SeOHs and their cyclization to the corresponding cyclic selenenyl amides by using selenopeptide model systems incorporated in a molecular cradle. Herein, we elucidate the structures and reactivities of Sec-derived cyclic selenenyl amides. The crystal structures and reactions toward a cysteine thiol or a 1,3-diketone-type chemical probe indicated the highly electrophilic character of cyclic selenenyl amides. This suggests that they can serve not only as protective forms to suppress the inactivation of Sec-SeOHs in GPx but also as highly electrophilic intermediates in the reactions of selenoproteins.


Self-Identity After Bereavement: Reduced Self-Clarity and Loss-Centrality in Emotional Problems After the Death of a Loved One.
There is evidence that both the centrality of a loss-event as well as reduced self-concept clarity are involved in emotional problems after the death of a loved one. One issue that is still unexplored is the relative importance of these two concepts in predicting bereavement outcome. The current study examined the degree to which both concepts contribute to emotional distress after loss, both concurrently and longitudinally. Data were available from 124 individuals, all bereaved within the previous half year, who completed measures of prolonged grief, posttraumatic stress, and depression at inclusion into the study and again 6 months later. Loss-centrality and self-unclarity were associated with all three outcome measures, in cross-sectional analyses. Longitudinal analyses indicated that loss-centrality predicted symptom levels of prolonged grief, self-unclarity predicted symptom levels of depression, and both loss-centrality and self-unclarity were associated with posttraumatic stress 6 months after baseline. Implications of these findings are discussed.


Cerebellar gray matter lesions are common in pediatric multiple sclerosis at clinical onset.
No data are available on the occurrence of gray matter lesions (GML) in the cerebellum of pediatric multiple sclerosis (pedMS). We analyzed frequency, number and topography of GML, and their correlation with cerebellar-related disability in pedMS at clinical onset. Fifteen adolescents with pedMS (12F/3M; mean age 14.9 ± 2.2, range 11-17) were studied. Neurological and cognitive evaluations were done by means of EDSS, Trail Making Test-Part B (TMT-B) and Symbol Digit Modalities Test-oral version (SDMT). Cerebellar GML were investigated with double inversion recovery (DIR) and phase-sensitive inversion recovery (PSIR) sequences obtained with a 3 T-MRI scan. All patients had white matter lesions (WML) and/or GML in the cerebellum. A significantly higher GML number was observed on PSIR compared to DIR (mean 2.3 ± 2.3 vs 1.1 ± 1.6; median 2.0 (IQR 1.0-2.0) vs 1.0 (IQR 0.0-1.5); p = 0.004). GML were observed in 14/15 (93.3%) patients and were more frequent in the posterior than in the anterior lobe (mean 1.8 ± 2.2 vs 0.47 ± 0.74; median 2.0 (IQR 0.5-2.0) vs 0.0 (IQR 0.0-1.0); p = 0.044). No correlation was found between lesion number or topography and EDSS (r = 0.12, p = 0.69), TMT-B and SDMT. At clinical onset, cerebellar GML are common in pedMS, are very often asymptomatic, do not correlate with physical and cognitive disability, and more frequently affect the posterior lobe.


Reactive 3D Printing of Shape-Programmable Liquid Crystal Elastomer Actuators.
3D printed, stimuli-responsive materials that reversibly actuate between programmed shapes are promising for applications ranging from biomedical implants to soft robotics. However, current 3D printing of reversible actuators significantly limits the range of possible shapes and/or shape responses because they couple the print path to mathematically determined director profiles to elicit a desired shape change. Here, we report a reactive 3D-printing method that decouples printing and shape-programming steps, enabling a broad range of complex architectures and virtually any arbitrary shape changes. This method involves first printing liquid crystal elastomer (LCE) precursor solution into a catalyst bath, producing complex architectures defined by printing. Shape changes are then programmed through mechanical deformation and UV irradiation. Upon heating and cooling, the LCE reversibly shape-shifts between printed and programmed shapes, respectively. The potential of this method was demonstrated by programming a variety of arbitrary shape changes in a single printed material, producing auxetic LCE structures and symmetry-breaking shape changes in LCE sheets.


Graphene nanoribbon-based supramolecular ensembles with dual-receptor targeting function for targeted photothermal tumor therapy.
Triple negative breast cancer (TNBC) is one of the most malignant subtypes of breast cancer. Here, we report the construction of graphene nanoribbon (GNR)-based supramolecular ensembles with dual-receptor (mannose and αvβ3 integrin receptors) targeting function, denoted as GNR-Man/PRGD, for targeted photothermal treatment (PTT) of TNBC. The GNR-Man/PRGD ensembles were constructed through the solution-based self-assembly of mannose-grafted GNRs (GNR-Man) with a pyrene-tagged αvβ3 integrin ligand (PRGD). Enhanced PTT efficacies were achieved both in vitro and in vivo compared to that of the non-targeting equivalents. Tumor-bearing live mice were administered (tail vein) with GNR-Man/PRGD and then each mice group was subjected to PTT. Remarkably, GNR-Man/PRGD induced complete ablation of the solid tumors, and no tumor regrowth was observed over a period of 15 days. This study demonstrates a new and promising platform for the development of photothermal nanomaterials for targeted tumor therapy.


Androgen modulation of adrenal angiotensin receptors.
Several polar androgens increased the binding of angiotensin and its stimulation of aldosteronogenesis in bovine adrenal glomerulosa cells. The effect was seen only if the steroids were applied to the cells and then washed away. This phenomenon and the technique for demonstrating it may have implications for studies of receptor modulation and for clinical states in which responsiveness to angiotensin is increased.


Non-CPAP treatment of obstructive sleep apnoea.
Obstructive sleep apnoea is a frequently occurring disease that can have important consequences including disabling hypersomnolence and sleepiness as well as cardiovascular diseases like hypertension. Treatment modalities are, however, limited. The efficacy of nasal continuous positive airway pressure (CPAP) stands out, but not all patients can tolerate this treatment or be compliant with it. Efficacious alternative therapies are still remarkably few in number. It is demonstrated and concluded that only patients with mild forms of the disease can currently be considered for non-CPAP treatments. Patients with predominantly breathing pattern abnormalities can be cured with medical therapy. Those with predominantly upper airway collapse and with mildly elevated critical closing pressure can be treated with surgical procedures such as uvulopalatopharyngoplasty (UPPP). The exact indications for electrical stimulation of the hypoglossal nerve are still to be determined, although preliminary results seem to be promising for well-selected patients.


[Internal carotid artery stenting with proximal protection systems in patients with concomitant external carotid artery injury].
to evaluate the possibility, efficiency, and safety of using the proximal protection systems in patients with concomitant injury to the ipsilateral external carotid artery (ECA) during internal carotid artery (ICA) stenting. The results of ICA stenting were analyzed in 39 patients. Their mean age was 66.4 +/- 7.8 years; 29 (74.4%) patients were male. All the patients were symptomatic. The time of ICA blood flow arrest averaged 5.4 +/- 2.1 min. Intolerance to blood flow arrest was noted in 3 (7.7%) patients. The intervention time was 27.6 +/- 8.3 min. The results were assessed from progress in positioning a proximal protection system and ensuring adequate cerebral embolic protection and from the presence of new neurological symptoms, acute coronary events, and fatal outcomes during hospitalization. The proximal protection system could be positioned in 100% of cases, which allowed ICA stenting to be successfully accomplished in all the patients with concomitant injury to the ipsilateral ECA. During hospitalization, the patients were found to have no new neurological symptoms. They had no acute coronary events or fatal outcomes either. The proximal protection systems are technically possible, effective, and safe in patients with concomitant ipsilateral ECA during cervical ICA stenting.


A TEM and electron energy loss spectroscopy (EELS) investigation of active and inactive silver particles for surface enhanced resonance Raman spectroscopy (SERRS).
A number of silver particles and aggregates of particles were studied using surface enhanced resonance Raman spectroscopy (SERRS), high resolution transmission electron microscopy (HRTEM) and electron energy-loss spectroscopy (EELS). The SERRS mapping/TEM collage method developed previously in our group allows each SERRS active or inactive species to be reliably identified and analysed by each of the techniques in three different instruments. Our aim is to correlate SERRS activity, particle microstructure, chemical composition and electronic properties of each species to gain an insight into the enhancement mechanism. To date, our findings do not reveal any clear link between particle microstructure and SERRS activity. Additionally, the direction of the polarisation of the incident excitation or the presence of interparticle junctions between aggregated particles was not correlated with SERRS activity. However, spectral variations in the EELS data from structurally similar particles and SERRS active and inactive particles suggest that each species is chemically/electronically distinct. Differences in the spectra of single particles, dimers and clusters were also observed. Further analysis of the data, including extraction of the complex dielectric function from the EELS data, will provide an insight into the relationship between these observations and SERRS activity.


Development of Postpartum Depression Screening Scale (PDSS): a Thai version for screening postpartum depression.
To validate a Postpartum Depression Screening Scale (PDSS) for screening postpartum depressive disorder in Songkhla Thai population, a screening test was conducted. A Thai version of the PDSS was developed using back translation and pre-tested on a prospective cohort of 400 postpartum women at 6-8 weeks from November 2003 to September 2004 in a university hospital, Southern Thailand. The diagnosis of postpartum depression was determined using DSM-IV diagnostic criteria for minor and major depressive disorders. The alpha reliability for the total PDSS was 0.9. The recommended cut-off scores of 51for screening major or minor depressive disorders and of 90 for screening major depressive disorder Area under the receiver operating characteristics (ROC) curve was 0.8 for major and minor depressive disorders and 0.9 for major depressive disorder In conclusion, this is a useful and beneficial instrument as there is no other Thai version validated instrument for postpartum depression.


The immune response and the eye. II. The nature of T suppressor cell induction in anterior chamber-associated immune deviation (ACAID).
We studied the cellular basis for the induction of Ts cells in anterior chamber (AC)-associated immune deviation (ACAID) by using TNP-modified syngeneic spleen cells (TNP-Spl). We demonstrate that the cells responsible for the induction of TNP-ACAID are non adherent, IA- T cells. This is in contrast to the antigen-presenting cells which induce suppression after the i.v. injection of TNP-Spl which are IA+/I-J+ adherent cells. Furthermore, two T cells within the TNP-Spl population are required to initiate suppression in TNP-ACAID: one is Lyt-1+, and I-J+, the other is Lyt-1+ and reactive with a monoclonal antibody, 14-30, which specifically identifies Ts inducer cells. The antigen specificity of ACAID resides in the 14-30+ T cell, and not the I-J+ cell. Although both cells must be viable to induce suppression, neither they (nor their products) must be in direct contact within the eye; one population may be in the right AC, the other in the left. Our results suggest that it is Ts inducer cells placed into the AC of the eye which initiate TNP-ACAID, and that these cells exit (or secrete Ts factors which exit) the eye to induce Ts effector cells in the spleen.


Solar distillation of water from soil and plant materials: a simple desert survival technique.
Water obtained from soil and plant materials by a simple distillation technique can provide a means for survival under desert conditions. A hemispherical hole in soil (in some cases containing cut plant material) is covered with plastic film formed and held in a conical shape by a rock placed in the center. Water collects on the under side of the plastic, runs to the point of the cone, and drops into the container. A yield of 1.5 liters per day of potable water was obtained from a single "survival still."


Childhood sexual abuse and adult psychiatric and substance use disorders in women: an epidemiological and cotwin control analysis.
Women who report childhood sexual abuse (CSA) are at increased risk for developing psychiatric disorders in adulthood. What is the diagnostic specificity and cause of this association? In a population-based sample of 1411 female adult twins, 3 levels of CSA were assessed by self-report and cotwin report: nongenital, genital, and intercourse. Interviews with twins and parents assessed family background and diagnoses of psychiatric and substance dependence disorders. Odds ratios (ORs) were calculated by logistic regression. By self-report, 30.4% reported any CSA and 8.4% reported intercourse. Self-reported CSA was positively associated with all disorders, the highest ORs being seen with bulimia and alcohol and other drug dependence. The ORs were modest and often nonsignificant with nongenital CSA and increased with genital CSA and especially intercourse, where most ORs exceeded 3.0. A similar pattern of findings was seen with CSA as reported by the cotwin, although many ORs were smaller. Controlling for family background factors and parental psychopathology produced a small to modest reduction in ORs. In twin pairs discordant for CSA, the exposed twin was at consistently higher risk of illness. Women with CSA have a substantially increased risk for developing a wide range of psychopathology. Most of this association is due to more severe forms of CSA and cannot be explained by background familial factors. Although other biases cannot be ruled out, these results are consistent with the hypothesis that CSA is causally related to an increased risk for psychiatric and substance abuse disorders.


Getting R-AEDI to save lives in Singapore.
Early cardiopulmonary resuscitation (CPR) and defibrillation prior to the arrival of emergency medical services can improve survival from out-of-hospital cardiac arrest (OHCA) with good neurological outcome. However, the rate of local bystander CPR is only 24.3% and bystander defibrillation 2.1%. In 2015, the R-AEDI (Registry for AED Integration) initiative was started to improve OHCA survival rates. R-AEDI alerts volunteers to nearby OHCA cases via the myResponder mobile application. In 2015-2017, 7,682 AEDs were mapped and made accessible via this app. Comprehensive site inspections also resulted in fewer non-functional AEDs, as AED owners were educated on the importance of the maintenance of pads and batteries. The AED heat map allows us to identify areas that are lacking in or require improved public access AED coverage. The online AED registry found in the myResponder app is useful to locate AEDs rapidly during OHCAs. More community education would improve the rate of bystander defibrillation.


Afibercept treatment for macular edema with and without serous retinal detachment due to branch retinal vein occlusion.
To evaluate the effectiveness of intravitreal aflibercept treatment for macular edema with and without serous retinal detachment due to branch retinal vein occlusion. Thirty-seven eyes with branch retinal vein occlusion treated with intravitreal aflibercept injection for macular edema were evaluated retrospectively. The patients were divided into two groups according to whether they showed serous retinal detachment on spectral domain optical coherence tomography. Pro re nata regimen was applied after 1 dose of intravitreal aflibercept injection. After the initial injection, control treatments were administered at months 1, 2, 3, 6, and 12. The best-corrected visual acuity and central macular thickness were measured. Fifteen patients had serous retinal detachment, and 22 with macular edema only (non-serous retinal detachment). The central macular thickness was significantly greater in the group with than in the group without serous retinal detachment (811.73 ± 220.68 µm and 667.90 ± 220.68 µm, respectively, p=0.04). The difference between the groups disappeared from the third month. The central macular thickness was similar between the two groups at the last control treatment (407.27 ± 99.08 µm and 376.66 ± 74.71 µm, p=0.66). The best-corrected visual acuity increased significantly in both groups. No significant difference was found between the two groups in terms of the best-corrected visual acuities at baseline and the final control. The intravitreal aflibercept treatment was highly effective in improving best-corrected visual acuity and central macular thickness in patients with branch retinal vein occlusion-induced macular edema independent of serous retinal detachment.


Platelet-activating factor primes neutrophil responses to agonists: role in promoting neutrophil-mediated endothelial damage.
During inflammation polymorphonuclear cells (PMNs) are exposed to agonistic stimuli including activated complement, kallikrein, arachidonic acid metabolites, monokines, and platelet-activating factor (PAF). We report that PAF not only directly activates PMNs but in miniscule quantities (10(-12) mol/L) "primes" them as well, that is, permits PMNs to respond to subsequent stimuli that would be otherwise ineffectual. PAF priming of responses including superoxide generation, elastase release, and aggregation is time dependent and is maximal within five minutes. PAF need not be present during the subsequent exhibition of PMN agonists, but priming is inhibited by cold and is also inhibited by the PAF receptor antagonists BN 52021, L-652, and kadsurenone. An intact PAF molecule is required because lyso-PAF and methoxy-PAF do not prime PMN responses. PAF priming is associated with both enhanced expression of the adhesive glycoprotein identified by OKM-1 antibody and an enhanced rise in intracellular calcium levels in response to the subsequent addition of agonists such as FMLP. PMNs primed with PAF and stimulated with either F-Met-Leu-Phe or phorbol esters are more effective in lysing and detaching cultured human endothelial cells--damage that can also be inhibited by the PAF antagonists. Because PAF is synthesized and exhibited on surfaces of endothelial cells perturbed by coagulation, we suggest that this lipid may potentiate otherwise trivial activators of marginated PMNs so that they become damaging to the PAF-synthesizing endothelium itself. If so, our studies suggest a possible therapeutic role for PAF inhibitors in excessive inflammatory states.


Association study of catechol-O-methyltransferase (COMT) gene Val158Met polymorphism with auditory P300 in Chinese Han patients with schizophrenia.
Several studies have reported associations between catechol-O-methyltransferase (COMT) gene Val158Met polymorphism and P300 event-related potentials in schizophrenic patients. But there has been no research to study the association between the P300 component and the Val158Met polymorphism in Chinese Han schizophrenia patients. Therefore, the present article was aimed at investigating the relationship of the Val158Met polymorphism with P300 in Chinese schizophrenic patients. The Val158Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 287 schizophrenia patients and 84 healthy control subjects. P300 recordings were obtained in a subsample. A significant difference was not observed between the patients and control subjects in the genotype distributions and allele frequencies. P300 amplitude in schizophrenia patients was significantly lower than that of controls. The P300 latency in schizophrenia patients was also significantly longer than that of controls. The P300 latency of Met homozygotes was significantly shorter than that of Val/Met and of Val/Val carriers at Cz and Pz. The latency of Val/Met carriers was significantly shorter than that of Val/Val carriers at Pz. The results did not suggest an association between the polymorphism in the COMT gene and susceptibility to schizophrenia in the Chinese Han population. However, the COMT Val158Met polymorphism might be a susceptibility variant for P300 abnormality in Chinese Han schizophrenia.


Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker in Transcatheter Aortic Valve Implantation (TAVI) Patients.
Neutrophil-to-lymphocyte ratio (NLR) is a simple and cost-effective marker of inflammation. This marker has been shown to predict cardiac arrhythmias, progression of valvular heart disease, congestive heart failure decompensation, acute kidney injury, and mortality in cardiovascular patients. The pathologic process of aortic stenosis includes chronic inflammation of the valve and therefore biomarkers of inflammation might offer additive prognostic value. To evaluate NLR and its association with long term mortality in transcatheter aortic valve implantation (TAVI) patients. We evaluated data of 1152 consecutive patient from the Tel Aviv Medical Center TAVI registry who underwent TAVI. Data included baseline clinical, demographic, and echocardiographic findings; procedural complications; and post-procedure mortality. Patients were compared by using the median NLR value (4.1) and evaluated for long-term mortality. Patients with NLR above the median had higher mortality rates (26.4% vs. 16.3%, P < 0.001) at 3 years post-procedure. A multivariable analysis found NLR to be an independent risk factor for mortality (hazard ratio = 1.47, 95% confidence interval 1.09-1.99, P = 0.013). In addition, high NLR was linked to complicationsduring and after the procedure. NLR is an independent prognostic marker among TAVI patients. This marker may represent an increased inflammatory response and should be added to previous known prognostic factors.


Axonal growth regulation of fetal and embryonic stem cell-derived dopaminergic neurons by Netrin-1 and Slits.
The physical restoration of dopamine circuits damaged or lost in Parkinson disease by implanting embryonic stem (ES)-derived cells may become a treatment. It is critical to understand responses of ES-derived dopamine (DA) neurons to guidance signals that determine axonal path and targeting. Using a collagen gel culture system, we examined effects of secreted molecules Netrin-1 and Slits on neurite outgrowth of fetal DA neurons and murine ES-differentiated DA neurons. We have previously shown that fetal DA neurons express DCC and Robo1/2 receptors and that Netrin-1 and Slit2 function as an attractant and a repellent for DA neurite outgrowth. In the present study, we observe that both Slit1 and Slit3 repel and inhibit neurite growth of fetal DA neurons. Here, we also demonstrate that ES-differentiated neurons including DA neurons express the Netrin receptor DCC and Slit receptor Robo proteins. In the gel culture system of ES cells, Netrin-1 promoted neurite outgrowth mediated by DCC receptor, and Slit1 and Slit3 were inhibitory for neurite outgrowth through Robo receptors. Slit2 appeared to exert inhibitory as well as repulsive effects in the coculture assay. However, unlike fetal DA neurites, no directed neurite outgrowth was observed in the cocultures of ES-derived DA neurons with Netrin-1-, Slit1-, and Slit3-producing cells. The findings suggest that ES-derived DA neurons generated by current protocols can respond to guidance cues in vitro in a similar manner to fetal cells but also exhibit distinct responses. This may result from developmental differences generated by present in vitro methods of cell patterning or conditioning during ES cell differentiation.


Analysis and Prediction of Vehicle Kilometers Traveled: A Case Study in Spain.
Knowledge of the kilometers traveled by vehicles is essential in transport and road safety studies as an indicator of exposure and mobility. Its application in the determination of user risk indices in a disaggregated manner is of great interest to the scientific community and the authorities in charge of ensuring road safety on highways. This study used a sample of the data recorded during passenger vehicle inspections at Vehicle Technical Inspection stations and housed in a data warehouse managed by the General Directorate for Traffic of Spain. This study has three notable characteristics: (1) a novel data source is explored, (2) the methodology developed applies to other types of vehicles, with the level of disaggregation the data allows, and (3) pattern extraction and the estimate of mobility contribute to the continuous and necessary improvement of road safety indicators and are aligned with goal 3 (Good Health and Well-Being: Target 3.6) of The United Nations Sustainable Development Goals of the 2030 Agenda. An Operational Data Warehouse was created from the sample received, which helped in obtaining inference values for the kilometers traveled by Spanish fleet vehicles with a level of disaggregation that, to the knowledge of the authors, was unreachable with advanced statistical models. Three machine learning methods, CART, random forest, and gradient boosting, were optimized and compared based on the performance metrics of the models. The three methods identified the age, engine size, and tare weight of passenger vehicles as the factors with greatest influence on their travel patterns.


Sexual assault in the military and its impact on sexual satisfaction in women veterans: a proposed model.
Sexual assault in the military (SAIM) is associated with decreased sexual satisfaction. However, mediators of this association have not been fully described. Using a retrospective analysis of cross-sectional data collected for the national Veterans Affairs (VA) Women's Health Survey, we propose a mediator model to explain the association between SAIM and decreased sexual satisfaction among women veterans. Four mediators of the association between SAIM and decreased sexual satisfaction are tested: (1) emotional health-related quality of life, (2) physical health-related quality of life, (3) lack of a close partner, and (4) gynecological illness. These mediators were chosen to encompass independent domains potentially relevant to sexual satisfaction, including emotional, physical, and relational. Of 3161 women (87%) who answered the sexual satisfaction question, the mean age was 45 (SD 15) years; 85% were white. Twenty-four percent reported a history of SAIM, and 39% reported sexual dissatisfaction. In age-adjusted logistic regression analyses, both SAIM and sexual dissatisfaction were strongly associated with each of the proposed mediators. However, of the four mediators, emotional health-related quality of life most strongly attenuated the association between SAIM and sexual dissatisfaction. After including all mediators, the association between SAIM and decreased sexual satisfaction was markedly attenuated. SAIM's negative impact on sexual satisfaction in women veterans operates both directly and through its physical and mental health sequelae. Of the proposed mediators in this association, the most prominent is mental health-related quality of life; the other proposed mediators were minimally related.


Minimally invasive orthognathic surgery.
Minimally invasive surgery is defined as the discipline in which operative procedures are performed in novel ways to diminish the sequelae of standard surgical dissections. The goals of minimally invasive surgery are to reduce tissue trauma and to minimize bleeding, edema, and injury, thereby improving the rate and quality of healing. In orthognathic surgery, there are two minimally invasive techniques that can be used separately or in combination: (1) endoscopic exposure and (2) distraction osteogenesis. This article describes the historical developments of the fields of orthognathic surgery and minimally invasive surgery, as well as the integration of the two disciplines. Indications, techniques, and the most current outcome data for specific minimally invasive orthognathic surgical procedures are presented.


The impact of ageing simulation education on healthcare professionals to promote person-centred care towards older people: A literature review.
This review aimed to explore the impact of ageing simulation for healthcare professional education to promote person-centred care towards older people. Ageing simulation is an emerging educational approach to facilitate the learning of healthcare professionals on ageing and older people. However, there is limited evidence available exploring its use and impact on the person-centred care of older people. An integrative review approach was used. Four databases were searched from January 2010 to April 2020 including CINAHL, MEDLINE, Web of Science and PsychINFO, 21 papers were identified and analysed. Three interrelating themes were identified to outline the findings across the reviewed studies: ageing simulation use (theme 1), characteristics (theme 2) and impact (theme 3). Results showed literature available on ageing simulation is varied, ranged in study quality and applied several ageing simulation iterations making comparisons across the studies difficult. Despite these challenges it was clear ageing simulation is a promising educational approach currently being used to promote person-centred care for older people in healthcare professionals. Ageing simulation successfully improved the ageing knowledge, empathy levels and attitudes towards older people of healthcare professionals.


Do soil depth and plant community composition interact to modify the resistance and resilience of grassland ecosystem functioning to drought?
While the effect of drought on plant communities and their associated ecosystem functions is well studied, little research has considered how responses are modified by soil depth and depth heterogeneity. We conducted a mesocosm study comprising shallow and deep soils, and variable and uniform soil depths, and two levels of plant community composition, and exposed them to a simulated drought to test for interactive effects of these treatments on the resilience of carbon dioxide fluxes, plant functional traits, and soil chemical properties. We tested the hypotheses that: (a) shallow and variable depth soils lead to increased resistance and resilience of ecosystem functions to drought due to more exploitative plant trait strategies; (b) plant communities associated with intensively managed high fertility soils, will have more exploitative root traits than extensively managed, lower fertility plant communities. These traits will be associated with higher resistance and resilience to drought and may interact with soil depth and depth heterogeneity to amplify the effects on ecosystem functions. Our results showed that while there were strong soil depth/heterogeneity effects on plant-driven carbon fluxes, it did not affect resistance or resilience to drought, and there were no treatment effects on plant-available carbon or nitrogen. We did observe a significant increase in exploitative root traits in shallow and variable soils relative to deep and uniform, which may have resulted in a compensation effect which led to the similar drought responses. Plant community compositions representative of intensive management were more drought resilient than more diverse "extensive" communities irrespective of soil depth or soil depth heterogeneity. In intensively managed plant communities, root traits were more representative of exploitative strategies. Taken together, our results suggest that reorganization of root traits in response to soil depth could buffer drought effects on ecosystem functions.


Frequent Loss of NISCH Promotes Tumor Proliferation and Invasion in Ovarian Cancer via Inhibiting the FAK Signal Pathway.
NISCH encodes the imidazoline receptor Nischarin and is a known tumor suppressor in many human malignancies; however, its roles in ovarian cancer are still largely unknown. Here, we aim to investigate the biologic functions of NISCH in ovarian cancer. We found that NISCH was significantly downregulated, which correlated considerably with advanced tumor stage, poor differentiation, lymph node metastasis, and the serous/mucinous subtypes in a panel of ovarian cancer tissues. Moreover, NISCH gene silencing was mainly the product of promoter hypermethylation, which could be reversed by treatment with 5-aza-dC. In vitro, NISCH overexpression suppressed cell proliferation and colony formation by hindering cell-cycle progression, whereas the opposite was observed in NISCH knockdown counterparts. In vivo, abundant NISCH expression hindered the growth of HO8910 xenografts, whereas NISCH knockdown accelerated the growth of SKOV3 xenografts. In addition, NISCH significantly attenuated cell invasion by inhibiting the phosphorylation of FAK and ERK, which could be neutralized by PF-562271 (a FAK/Pyk2 inhibitor). Accordingly, NISCH knockdown xenografts exhibited increased peritoneal/pelvic metastases that were not present in counterparts treated with PF-562271. Furthermore, NISCH expression in primary ovarian cancer cells predicted a cellular resistance to PF-562271. In conclusion, we showed that NISCH was frequently silenced by promoter hypermethylation in human ovarian cancer. NISCH manipulated cellular proliferation and invasion by arresting cell cycle and inhibiting the FAK signal. Our findings revealed the biologic functions of NISCH in ovarian cancer, and might be useful for treating patients with aberrant expression of NISCH.


Analysis of very elderly (≥80 years) non-hodgkin lymphoma: impact of functional status and co-morbidities on outcome.
Data on outcome, prognostic factors, and treatment for very elderly non-Hodgkin lymphomas (NHL) is sparse. We conducted a multicentre retrospective analysis of NHL patients ≥80 years (at diagnosis) treated between 1999 and 2009. Detailed characteristics were obtained including geriatric syndromes, activities of daily living (ADLs), and co-morbidities using the Cumulative Illness Rating Scale-Geriatrics (CIRS-G). We identified 303 patients: 170 aggressive NHL (84% B cell/16% T cell) and 133 indolent NHL (82% B cell/18% T cell). Median age was 84 years (80-95). A geriatric syndrome was present in 26% of patients, 18% had ≥1 grade 4 CIRS-G, and 14% had loss of ADLs. At 49-month median follow-up, 4-year progression-free (PFS) and overall survival (OS) for aggressive NHLs were 31% and 44% respectively (stage I/II: PFS 53% and OS 66%; stage III/IV: PFS 20% and OS 32%; P < 0·0001 and 0·0002, respectively). Four-year PFS and OS for indolent NHL were 44% and 66% respectively, regardless of stage. Multivariate regression analysis identified two key factors that predicted inferior PFS and OS for both NHL groups: lack of CR and loss of ADLs. Prospective studies for very elderly NHL that incorporate geriatric tools, especially ADLs, are warranted.


Technical note: In silico benchmarking of the linear energy transfer-based functionalities for carbon ion beams in a commercial treatment planning system.
The increasing number of studies dealing with linear energy transfer (LET)-based evaluation and optimization in the field of carbon ion radiotherapy (CIRT) indicates the rising demand for LET implementation in commercial treatment planning systems (TPS). Benchmarking studies could play a key role in detecting (and thus preventing) computation errors prior implementing such functionalities in a TPS. This in silico study was conducted to benchmark the following two LET-related functionalities in a commercial TPS against Monte Carlo simulations: (1) dose averaged LET (LETd ) scoring and (2) physical dose filtration based on LET for future LET-based treatment plan evaluation and optimization studies. The LETd scoring and LET-based dose filtering (in which the deposited dose can be separated into the dose below and above the user specified LET threshold) functionalities for carbon ions in the research version RayStation (RS) 9A-IonPG TPS (RaySearch Laboratories, Sweden) were benchmarked against GATE/Geant4 simulations. Pristine Bragg peaks (BPs) and cuboid targets, positioned at different depths in a homogeneous water phantom and a setup with heterogeneity were used for this study. For all setups (homogeneous and heterogeneous), the mean absolute (and relative) LETd difference was less than 1 keV/ μ $\umu$ m (3.5%) in the plateau and target and less than 2 keV/ μ $\umu$ m (8.3%) in the fragmentation tail. The maximum local differences were 4 and 6 keV/ μ $\umu$ m, respectively. The mean absolute (and relative) physical dose differences for both low- and high-LET doses were less than 1 cGy (1.5%) in the plateau, target and tail with a maximum absolute difference of 2 cGy. No computation error was found in the tested functionalities except for LETd in lateral direction outside the target, showing the limitation of the implemented monochrome model in the tested TPS version.


Research on biogenesis of mitochondria in astrocytes in sepsis-associated encephalopathy models.
To study the structural and functional changes in mitochondria in astrocytes of the cerebral cortex of the rats in the simulated sepsis environment in vitro and the relationship between these changes and the biogenesis of mitochondria in astrocytes by establishing models of sepsis astrocytes. The structural and functional changes in mitochondria in astrocytes of the cerebral cortex of the rats were evaluated. The ultra structural changes in the mitochondria, astrocytes, and ultrathin sections, were observed with a transmission electron microscope. The expression of the regulatory factors related to biogenesis of mitochondria in astrocytes of the cerebral cortex of the rats was evaluated in various experimental groups. RT-PCR and Western blot were used to evaluate the expression of the regulatory factors related to biogenesis of mitochondria in astrocytes of the cerebral cortex of the rats. The "point grid method" was used to evaluate the volume density of the mitochondria in the astrocytes of the cerebral cortex of the rats in various experimental groups. The Western blotting was used to evaluate the role of fusion and fission of mitochondria in the astrocytes of the cerebral cortex of the rats in various experimental groups in regulating the expression of the protein-OPAI and DRPI. In the sepsis astrocyte models established by co-incubation of LPS and IFN-γ and astrocytes of the cerebral cortex of the rats, the mitochondria with a minor injury in the 6 h group (2.97± 0.92) increased significantly when compared with those in the 0 h group (1.08±0.95), 12 h group (1.70±1.01), and 24 h group (1.59±0.55) (p<0.05); the concentration of adenosine triphosphate (ATP) in the astrocytes of the cerebral cortex of the rats in the 6 h, 12 h, and 24 h groups increased significantly when compared with that in the 0 h group (p<0.05). PGC-1α mRNA, NRF-1 mRNA, NRF-2α mRNA, NRF-2β mRNA, and mitochondrial transcription factor A (TFAM) mRNA in the astrocytes of the cerebral cortex of the rats in the 6 h and 12 h groups increased significantly when compared with those in the 0 h group (p<0.05); the concentration of TFAM mRNA (1.20±0.19) increased significantly when compared with that in the 0 h group (p<0.05). The OPAI protein concentration (1.21±0.17:1.34±0.06) and DRPI protein concentration (1.04±0.05; 1.05±0.05) in the astrocytes of the cerebral cortex of the rats in the 12 h group (1.25±0.17), 24 h group (1.33±0.24), and 6 h group increased significantly when compared with that in the 0 h group (p <0.05). The experimental sepsis conditions can cause a minor injury of the ultrastructure of the mitochondria in the astrocytes of the cerebral cortex of the rats. The biogenesis of the mitochondria in the astrocytes of the cerebral cortex of the rats was strengthened to cater for the increased demand for energy of the astrocytes under the sepsis conditions and finally recover the ultrastructure of the mitochondria with a minor injury. In response to the increased mitochondrial biogenesis, the activities of the mitochondrial fusion and fission of the astrocytes of the cerebral cortex of the rats were increased.


Tobacco Quitline toll-free number on tobacco packets in India: An analysis on outcome.
On 1 September 2018, 2 year later the launch of National Tobacco Quitline Services (NTQLS), new health warnings on tobacco products packets consisting of NTQLS toll-free number came into effect in India. The present study aimed to measure the effects of printing tobacco Quitline number on tobacco packets on calls to NTQLS. All calls to the NTQLS were monitored over 1 year, six months before and after the tobacco Quitline number on tobacco packets came to effect. Call details such as tobacco user's demographic profile, tobacco use habit, follow-up and quitting status also extracted through Call Detail Record (CDR) files from the server of NTQLS for the purpose of this study. Calls hit on IVR (Interacted Voice Response) increased by 7.7 times, on an average 6064 calls daily hit on NTQLS's IVR after the new health warning consisting of toll-free number on tobacco packets came into effect. Tobacco user registration increased by 3.3 times (18039 vs 5469). Overall, 264.5% (4790) relative increment in tobacco quitters, as it were only 1314 quitters six months before the new health warning. 100% callers cited tobacco packets as the primary source of tobacco Quitline toll-free number. The helpline number of Quitline on tobacco packet showed a strong potential to aware the public about the tobacco Quitline. This has increased the number of callers calling to National Tobacco Quitline Services and registrations for tobacco cessation. Sharp increase in calls during the first three months of new health warning and latter diminishing rate of calls is the concern for further study.


Bulk Anatomical Density Based Dose Calculation for Patient-Specific Quality Assurance of MRI-Only Prostate Radiotherapy.
Prostate cancer treatment planning can be performed using magnetic resonance imaging (MRI) only with sCT scans. However, sCT scans are computer generated from MRI data and therefore robust, efficient, and accurate patient-specific quality assurance methods for dosimetric verification are required. Bulk anatomical density (BAD) maps can be generated based on anatomical contours derived from the MRI image. This study investigates and optimizes the BAD map approach for sCT quality assurance with a large patient CT and MRI dataset. 3D T2-weighted MRI and full density CT images of 54 patients were used to create BAD maps with different tissue class combinations. Mean Hounsfield units (HU) of Fat (F: below -30 HU), the entire Tissue [T: excluding bone (B)], and Muscle (M: excluding bone and fat) were derived from the CT scans. CT based BAD maps (BADBT,CT and BADBMF,CT) and a conventional bone and water bulk-density method (BADBW,CT) were compared to full CT calculations with bone assignments to 366 HU (measured) and 288 HU (obtained from literature). Optimal bulk densities of Tissue for BADBT,CT and Bone for BADBMF,CT were derived to provide zero mean isocenter dose agreement to the CT plan. Using the optimal densities, the dose agreement of BADBT,CT and BADBMF,CT to CT was redetermined. These maps were then created for the MRI dataset using auto-generated contours and dose calculations compared to CT. The average mean density of Bone, Fat, Muscle, and Tissue were 365.5 ± 62.2, -109.5 ± 12.9, 23.3 ± 9.7, and -46.3 ± 15.2 HU, respectively. Comparing to other bulk-density maps, BADBMF,CT maps provided the closest dose to CT. Calculated optimal mean densities of Tissue and Bone were -32.7 and 323.7 HU, respectively. The isocenter dose agreement of the optimal density assigned BADBT,CT and BADBMF,CT to full density CT were 0.10 ± 0.65% and 0.01 ± 0.45%, respectively. The isocenter dose agreement of MRI generated BADBT,MR and BADBMF,MR to full density CT were -0.15 ± 0.90% and -0.16 ± 0.65%, respectively. The BAD method with optimal bulk densities can provide robust, accurate and efficient patient-specific quality assurance for dose calculations in MRI-only radiotherapy.


Differential isoform expression and interaction with the P32 regulatory protein controls the subcellular localization of the splicing factor U2AF26.
The U2 auxiliary factor (U2AF) is an integral part of the spliceosome that is important for the recognition of the 3' splice site. U2AF consists of a large and a small subunit, the prototypes of which are U2AF65 and U2AF35. Recent evidence suggests that several homologs of both U2AF subunits exist that are able to regulate alternative splicing. Here we have investigated the expression, intracellular localization, and nucleo-cytoplasmic shuttling of one homolog of the small U2AF subunit, U2AF26, and a splice variant lacking exon 7, U2AF26DeltaE7. In contrast to the nuclear U2AF26, which displays active nucleo-cytoplasmic shuttling, U2AF26DeltaE7 is localized in the cytoplasm. Our studies reveal a nuclear localization sequence in the C-terminal exons 7 and 8 of U2AF26 that differs from the known nuclear localization sequence in U2AF35. In addition, we could identify P32 as a protein that is able to interact with U2AF26 through this domain, and we demonstrate that this interaction is required for the nuclear translocation of U2AF26. Our results suggest the existence of two distinct nuclear import pathways for U2AF26 and U2AF35 that could independently control their intracellular distribution and availability to the splicing machinery. Such a mechanism could work in addition to the differential expression of U2AF homologs to contribute to the regulation of alternative splicing.


Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prevention of acute graft-vs.-host disease: effect on chronic graft-vs.-host disease and long-term survival.
Graft-vs.-host disease (GVHD) is a major predictor of outcome following allogeneic bone marrow transplantation (BMT). For patients alive at day 100 after BMT, the presence or absence of chronic GVHD is one of the most important determinants of survival and quality of life. We wished to determine the effects on chronic GVHD of two regimens used for the prophylaxis of acute GVHD: cyclosporine, methotrexate, and prednisone (CSA/MTX/PSE) and cyclosporine and prednisone (CSA/PSE). One hundred forty-nine evaluable patients were entered into the acute GVHD study. As of 31 March 1997, 63 months after the last patient underwent BMT, the median survival time was 4.5 years (range 0.09-9.9). The incidence of chronic GVHD was independent of the prophylactic regimen (55 vs. 54%), and extensive chronic GVHD occurred in 25 and 24% of patients receiving CSA/MTX/PSE and CSA/PSE, respectively. Of note, the median Karnofsky performance status of both groups was 100% (range 70-100%), reflecting the low incidence of extensive chronic GVHD. Survival rates free of chronic GVHD were 52 vs. 42% (p = 0.29) for patients receiving CSA/MTX/PSE vs. CSA/PSE. The incidence of relapse was also similar in both groups of patients. These data suggest that the combinations of CSA/MTX/PSE and CSA/PSE result in comparable chronic GVHD-free survival without an increase in leukemic relapse.


Graft-vs.-host disease in lung and other solid organ transplant recipients.
Graft-vs.-host disease (GVHD) is an uncommon complication of solid organ transplantation. Herein, we report a case of GVHD occurring in a lung transplant recipient and review 29 reported cases of GVHD that complicated thoracic organ, and non-hepatic intra-abdominal organ transplantation. The major presenting clinical symptom of GVHD was skin rash. Less frequent clinical manifestations were cytopenia (16%), diarrhea (11%), and fever (5%). The mainstay of treatment was high-dose corticosteroids. The mortality rate was high (30%). The cause of death was mainly due to infection, suggesting that antimicrobial prophylaxis may improve the outcome of this potentially fatal complication.


Effect of Hemodialysis on Retinal Thickness in Patients with Diabetic Retinopathy, with and without Macular Edema, Using Optical Coherence Tomography.
Background. Effects of hemodialysis (HD) treatment on retinal thickness and macular edema are unclear. Objective. To evaluate changes in retinal thickness using optical coherence tomography (OCT) in end stage renal disease (ESRD) patients with diabetic retinopathy (DR), with and without diabetic macular edema (DME), undergoing HD. Methods. Nonrandomized prospective study. Forty eyes of DR patients with ESRD treated with HD were divided into two groups: patients with macular edema and patients without macular edema. Both eyes were analyzed. Patients underwent an ophthalmic examination including OCT measurements of retinal thickness, blood albumin and hemoglobin A1C levels, blood pressure, and body weight, 30 minutes before and after HD. Results. We found no significant effects of HD on retinal thickness among patients both with and without DME. The former showed a trend towards reduction in retinal thickness in foveal area following HD, while the latter showed an increase. There was no correlation between retinal thickness and mean blood pressure, weight, kinetic model value-Kt/V, glycemic hemoglobin, or albumin levels before and after HD. Conclusions. HD has no significant effect on retinal thickness among patients with or without DME. Further studies on larger cohorts and repeated OCT examinations are needed to confirm the preliminary findings in this study.


Molecular characterization of postoperative adhesions: the adhesion phenotype.
Postoperative adhesion development remains a very frequent occurrence, which is often unrecognized by surgeons because of limited ability to conduct early second-look laparoscopies. The consequences include infertility, pelvic pain, bowel obstruction, and difficult reoperative procedures. To date, approaches to limit adhesions primarily have involved barriers to separate tissue during reepithelization. Future progress in regulating adhesion development and tissue fibrosis likely will require an improved understanding of the molecular processes involved in normal peritoneal repair and its aberrations leading to adhesion development. We hypothesize that tissue hypoxia (in part resulting from tissue incision, fulguration, suture ligation, etc.) is the major inciting event, which leads to a coordinated series of molecular events that promote an inflammatory response leading to enhanced tissue fibrosis. These events are reduced plasminogen activator activity, extracellular matrix deposition, increased cytokine production, increased angiogenesis, and reduced apoptosis (programmed cell death). Improved understanding of these events and their regulation will provide the opportunity to regulate better postoperative adhesion development and tissue fibrosis, thereby reducing the morbidity and mortality they cause.


Do dimensional psychopathology measures relate to creative achievement or divergent thinking?
Previous research provides disparate accounts of the putative association between creativity and psychopathology, including schizotypy, psychoticism, hypomania, bipolar disorder, ADHD, and autism spectrum disorders. To examine these association, healthy, non-clinical participants completed several psychopathology-spectrum measures, often postulated to associate with creativity: the Schizotypal Personality Questionnaire, the Psychoticism scale, the Personality Inventory for DSM-5, the Hypomanic Personality Scale, the Attention Deficit/Hyperactivity Disorder scale, the Beck Depression Inventory, and the Autism-Spectrum Quotient. The goal of Study 1 was to evaluate the factor structure of these dimensional psychopathology measures and, in particular, to evaluate the case for a strong general factor(s). None of the factor solutions between 1 and 10 factors provided a strong fit with the data based on the most commonly used metrics. The goal of Study 2 was to determine whether these psychopathology scales predict, independently, two measures of creativity: 1. a measure of participants' real-world creative achievements, and 2. divergent thinking, a laboratory measure of creative cognition. After controlling for academic achievement, psychoticism and hypomania reliably predicted real-world creative achievement and divergent thinking scored with the consensual assessment technique. None of the psychopathology-spectrum scales reliably predicted divergent thinking scored with the manual scoring method. Implications for the potential links between several putative creative processes and risk factors for psychopathology are discussed.


Claudin-7 expression in human epithelial ovarian cancer.
Claudin-7 (CLDN-7) is a tight junction protein recently found highly differentially expressed in ovarian carcinoma. To evaluate its potential as a novel biomarker, in this study, we quantified and compared claudin-7 expression at messenger RNA and protein level in 110 patients harboring various histologic types of epithelial ovarian carcinomas (EOC). CLDN-7 transcript was found significantly overexpressed in both primary and metastatic EOCs compared to normal human ovarian surface epithelium cell lines (fold change = 111.4, P < 0.001) by reverse transcription-polymerase chain reaction. At the protein level, CLDN-7 expression was found significantly higher in tumors of primary and metastatic origin when compared to normal ovaries (P < 0.001), regardless of the histologic type, the grade of differentiation, and the pathologic stage of the disease (P = 0.12). Moreover, a strong immunoreactivity for CLDN-7 was detected in EOC cells present in ascites fluids, whereas ascites-derived inflammatory cells, histiocytes, and reactive mesothelial cells were negative. Finally, immunohistochemical expression of CLDN-7 was observed in several human normal epithelial control tissues analyzed. CLDN-7 is significantly overexpressed in all main histologic types of EOC and in single neoplastic cells disseminated in peritoneal cavity and pleural effusions, suggesting its potential role as novel diagnostic marker in ovarian cancer. Despite widespread expression of CLDN-7 in several human normal tissues, the high density of CLDN-7 molecules, their membranous localization on EOC cells, and their lack of expression on the celomic epithelium in the peritoneal cavity suggest that this target could be potentially suitable for antibody-mediated localized therapies of ovarian adenocarcinoma.


Preparation and NMR characterization of C70H10: cutting a fullerene pi-system in half
Three isomers of C70H10 were prepared by Zn(Cu) reduction of C70. Three chromatographic bands were identified as C70H10 species by MALDI-FT mass spectrometry, and these compounds were isolated by repeated HPLC treatments. The major isomer (2) was characterized by 1H and 13C NMR, while the minor isomers 3-4 were isolated in such small quantities that only 1H NMR analysis was possible. 1H-coupled and 1H-decoupled 13C NMR of 2 established a 7,8,19,26,33,37,45,49,53,63-substitution pattern. This assignment was confirmed by HMBC and DFQ-COSY experiments. This structure is completely reasonable, as we found that 2 results exclusively from reduction of the 7,19,23,27,33,37,44,53-C70H8 that is formed in the course of the Zn(Cu) reduction of C70.


Additive role of plasma von Willebrand factor levels to clinical factors for risk stratification of patients with atrial fibrillation.
To aid decisions for thromboprophylaxis in atrial fibrillation (AF), several risk stratification schemes that predict stroke risk according to clinical and echocardiographic features have been published. von Willebrand factor (vWf) is a plasma markers of endothelial damage/dysfunction and is associated with the risk of stroke and vascular events in AF patients. This study determined the additive role of plasma vWf levels to clinical factors for risk stratification in patients with AF. We classified 994 AF patients who were enrolled in the SPAF III trial as being at low, moderate, or high risk of stroke and thromboembolism according to the Birmingham and CHADS(2) risk stratification schemes. vWf levels were classified as elevated when >or=158 IU /dL. Rates of ischemic stroke and vascular events within each clinical risk stratum with and without plasma vWf levels were compared. The accuracy of both clinical risk stratification schemes was similar for predicting event rates (Birmingham: ischemic strokes, 0.642; vascular events, 0.670; CHADS(2): ischemic strokes, 0.672; vascular events, 0.672). Subsequent addition of categorized vWf levels to both clinical risk stratification schemes further refined risk stratification for stroke and vascular events. When added to the Birmingham and CHADS(2) clinical risk stratification, high vWf levels were independently associated with a risk of vascular events (hazard ratio, 2.05; 95% confidence interval, 1.30 to 3.22 and 2.01, 1.27 to 3.18 with Birmingham and CHADS(2), respectively) but not ischemic stroke. When added to clinical risk stratification schemes (Birmingham; CHADS(2)), plasma vWf levels refined clinical risk stratification for stroke and vascular events among AF patients. vWf levels may aid decisions about thromboprophylaxis, particularly among AF patients at moderate risk.


Parental influence on systemic sclerosis.
To examine parental influence on the development of systemic sclerosis (SSc; scleroderma). We designed 3 studies: mitochondrial inheritance, birth order (a possible surrogate marker for microchimerism), and paternal age at conception (a possible surrogate for telomere erosion) to examine their association with development of SSc. SSc was defined by International Classification of Diseases, Ninth and Tenth Revision codes (ICD-9 710.1 and ICD 10 M34.0, M34.1, and M34.9) and identified from statewide discharge data, University of Utah Health Science Center Enterprise Data Warehouse (UUHSC), and death certificates that were linked to the Utah Population Database (UPDB) for analysis. Mitochondrial inheritance was evaluated by conditional logistic regression and population attributable risk using familial standardized incidence ratio as the covariate. Chi-square test and logistic regression were used to evaluate birth order and maternal/paternal age at conception of the SSc proband. We found 1,947 unique SSc patients from UUHSC and UPDB. We selected 5 controls per case (n = 9,115), matched by birth year and sex. Mitochondrial inheritance analysis indicated no evidence to suggest SSc was associated with mitochondrial inheritance. Birth order and maternal/paternal age at conception analysis results show that they also do not significantly affect SSc development. Results suggest that although heritable risk of SSc is observed, mitochondrial inheritance, birth order, and parental age are not likely responsible for pathogenesis.


Feline behaviour problems in Brazil: a review of 155 referral cases.
Geographical variations in feline behaviour problems exist. The occurrence of feline behaviour problems in different regions are therefore important to prepare professionals for the emerging needs of cat owners. One-hundred and fifty-five feline behaviour cases that were referred to a veterinary behaviourist in São Paulo (Brazil) during the period 2008-2014 are described. Inter-cat aggression was the main behavioural complaint reported (31%), followed by housesoiling (26.4%). Unlike other international studies, inter-cat aggression was more frequently seen than inappropriate elimination. Oral repetitive behaviours, including problems such as psychogenic alopecia and pica, were also a prevalent problem (ie, 16.8% of the cases). Human-directed aggression accounted for 13.5% of the cases, taking fourth place in the list of the most common feline behavioural problems. Female and male cats were equally likely to be presented (51% and 49% of cases, respectively). This study highlights potentially geographical or temporal variation in the behavioural problems that need to be recognised by veterinary behaviourists in order to meet the emerging needs of owners.


[Infantile visceral leishmaniasis in Morocco. A review of 67 cases managed at the Rabat Hospital for children (1979-1988)].
Sixty-seven cases of visceral leishmaniasis managed at the Rabat Hospital for Children from 1979 through 1988 were studied retrospectively. Mode of onset and outcome were analyzed. Clinical manifestations included enlargement of the spleen (60 cases), fever (45 cases), enlargement of the liver (38 cases), and weight loss (53 cases). Six patients had misleading onset manifestations including one case each of pigmentary lithiasis, severe marasmus without enlargement of the spleen, nephrotic syndrome, evidence of portal hypertension, jaundice, and an abdominal mass. Diagnosis was established by the bone marrow study (positive in 58 of 66 patients) or by indirect immunofluorescence (positive in 21 of 24 patients, including 6 with a negative bone marrow study). In one patient, the parasite was recovered from a jejunal biopsy specimen. Drugs used included N-methyl-glucamine in 86 cases, pentamidine in 26 cases, and sodium gluconate stibio in one case. Complete recovery was achieved in 24 patients. Seven patients failed to respond to therapy. There were 8 deaths, including 4 prior to initiation of therapy; among these four deaths, three were due to acute anemia. Another patient died after leaving the hospital despite the physician's advice to the contrary. The 3 remaining deaths were caused by toxicity of the drugs used. Thirty-one patients were lost to follow-up after initial improvement. The severity of this disease and cost of management make earlier diagnosis and faultless management imperative.


Controlling hospital-acquired infection: focus on the role of the environment and new technologies for decontamination.
There is increasing interest in the role of cleaning for managing hospital-acquired infections (HAI). Pathogens such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus (MRSA), multiresistant Gram-negative bacilli, norovirus, and Clostridium difficile persist in the health care environment for days. Both detergent- and disinfectant-based cleaning can help control these pathogens, although difficulties with measuring cleanliness have compromised the quality of published evidence. Traditional cleaning methods are notoriously inefficient for decontamination, and new approaches have been proposed, including disinfectants, steam, automated dispersal systems, and antimicrobial surfaces. These methods are difficult to evaluate for cost-effectiveness because environmental data are not usually modeled against patient outcome. Recent studies have reported the value of physically removing soil using detergent, compared with more expensive (and toxic) disinfectants. Simple cleaning methods should be evaluated against nonmanual disinfection using standardized sampling and surveillance. Given worldwide concern over escalating antimicrobial resistance, it is clear that more studies on health care decontamination are required. Cleaning schedules should be adapted to reflect clinical risk, location, type of site, and hand touch frequency and should be evaluated for cost versus benefit for both routine and outbreak situations. Forthcoming evidence on the role of antimicrobial surfaces could supplement infection prevention strategies for health care environments, including those targeting multidrug-resistant pathogens.


Microarray-based gene expression profiling and DNA copy number variation analysis of temporal fossa arachnoid cysts.
Intracranial arachnoid cysts (AC) are membranous sacs filled with CSF-like fluid that are commonly found in the temporal fossa. The majority of ACs are congenital. Typical symptoms are headache, dizziness, and dyscognition. Little is known about genes that contribute to the formation of the cyst membranes. In order to identify differences in gene expression between normal arachnoid membrane (AM) and cyst membrane, we have performed a high-resolution mRNA microarray analysis. In addition we have screened DNA from AC samples for chromosomal duplications or deletions using DNA microarray-based copy number variation analysis. The transcriptome consisting of 33096 gene probes showed a near-complete similarity in expression between AC and AM samples. Only nine genes differed in expression between the two tissues: ASGR1, DPEP2, SOX9, SHROOM3, A2BP1, ATP10D, TRIML1, NMU were down regulated, whereas BEND5 was up regulated in the AC samples. Three of the AC samples had unreported human DNA copy number variations, all DNA gains. Extending results of previous anatomical studies, the present study has identified a small subset of differentially expressed genes and DNA alterations in arachnoid cysts compared to normal arachnoid membrane.


"Health in All Policies": taking stock of emerging practices to incorporate health in decision making in the United States.
Policies affecting the determinants of health lie largely outside the control of the health care and public health sectors. Ensuring health considerations in the formation and implementation of policies, programs, projects, and plans from all sectors, though lofty, is the overall aim of Health in All Policies. The purpose of this article was to identify categories of strategies that illustrate how Health in All Policies had been implemented in the United States. We used a 3-phased process: (1) review of the published and gray literature; (2) analysis of case examples to identify a draft framework, which included tactics and strategies for implementing Health in All Policies; and (3) vetting the draft framework through individual and group consultation. We identify 7 interrelated strategies for incorporating health considerations into decisions and systems: (1) developing and structuring cross-sector relationships; (2) incorporating health into decision-making processes; (3) enhancing workforce capacity; (4) coordinating funding and investments; (5) integrating research, evaluation and data systems; (6) synchronizing communications and messaging; and (7) implementing accountability structures. For each strategy, we provide illustrative examples from the United States to help public health leaders identify effective tactics for Health in All Policies implementation. Through our review, we offer a starting point for categorizing and describing the emerging practices used to work across sectors and address the determinants of health. By delineating the different types of strategies and tactics to achieve Health in All Policies, we provide public health practitioners with a "menu" of options for incorporating Health in All Policies into their work.


Cadmium induces caspase-mediated cell death: suppression by Bcl-2.
Apoptosis is a process of active cell death and is characterized by activation of caspases, DNA fragmentation, and biochemical and morphological changes. To better understand apoptosis, we have characterized the dose- and time-dependent toxic effects of cadmium in Rat-1 fibroblasts. Staining of cells with phosphatidylserine (PS)-annexin V, Hoechst 33258 or Rhodamine 123 and Tunel assays showed that incubating cells with 10 microM cadmium induced a form of cell death exhibiting typical characteristics of apoptosis, including cell shrinkage, externalization of PS, loss of mitochondria membrane potential, nuclear condensation and DNA fragmentation. Expression of Bcl-2 or CrmA each suppressed cadmium-induced cell death although Bcl-2 was somewhat more effective than CrmA. In vitro assay of caspase activity carried out using poly(ADP-ribose) polymerase (PARP) as a substrate as well as intracellular caspase assays using a fluorigenic caspase-3 substrate confirmed that caspase-3 is activated in Rat-1 cells undergoing cadmium-induced apoptosis. Both Asp-Glu-Val-Asp-aldehyde (DEVD-cho) and Tyr-Val-Ala-Asp-chloromethylketone (YVAD-cmk), selective inhibitors of caspase-3 and caspase-1, respectively, suppressed significantly cadmium-induced cell death. However, the nonselective caspase inhibitor, z-Val-Ala-Asp-floromethylketone (zVAD-fmk), was the most efficacious agent, almost completely blocking cadmium-induced cell death. Taken together, these results demonstrate that as in other forms of apoptosis, caspases play a central role in cadmium-induced cell death.