Transanal Minimally Invasive Surgery: Review of Indications and Outcomes from 75 Consecutive Patients.
Transanal minimally invasive surgery (TAMIS) is an advanced local excision platform that helps overcome technical limitations and morbidity associated with other resection methods. Our goal was to review the indications and outcomes of TAMIS in a large series. A review of a prospective database identified patients who underwent TAMIS from 2010 to 2014. Demographic, perioperative, short-term outcomes, and recurrence data were analyzed. There were 75 patients with 76 lesions analyzed. Mean age was 64.0 years (SD 11.6 years) and mean BMI was 27.4 kg/m(2) (SD 4.7 kg/m(2)). Median American Society of Anesthesiologists (ASA) score was 2 (range 1 to 4). There were 59 benign (77.3%) and 17 malignant (22.7%) lesions: 6 pT0, 6 pT1, 4 pT2, and 1 pT3. Median lesion distance from the anal verge was 10 cm (range 6 to 16 cm). Mean operative time was 76.0 minutes (SD 36.1 minutes). Three patients had intraperitoneal entry; all were closed transanally, but 2 had temporary diverting ileostomies fashioned to ensure healing. Median length of stay was 1 day (range 0 to 6). One patient had a fragmented lesion (1.3%). Five patients had positive margins: 2 in palliative pT2 resections, and 3 in pT1, pT2, and gastrointestinal stromal tumor (GIST) patients. They were managed with radical resection (pT1 and pT2 lesions) and surveillance/medical oncology (GIST). Postoperatively, 3 patients had complications (bleeding, rectal stricture, and recto-vaginal fistula), and all were managed nonoperatively. After median follow-up of 39.5 months (range 10.5 to 65.3 months), 1 pT1 patient with negative margins developed a local recurrence and underwent salvage APR. Transanal minimally invasive surgery is a viable option for excision of benign or early stage rectal masses, with mid-term oncologic outcomes comparable to those of radical resection. Further, TAMIS minimizes the morbidity and can allow more patients to benefit from the minimally invasive approach.


[Serologic and immunologic evaluation in uveitis].
Following a brief discussion of the various general immunologic examinations useful in uveitis, the author goes on to stress the need for a goal of serologic examinations, taking the clinical picture and clinical context into account. In conclusion, a schematic approach is proposed which should be adhered to in paraclinical investigations.


Comparison of the effect of latanoprost 0.005% and timolol 0.5% on the calculated ocular perfusion pressure in patients with normal-tension glaucoma.
To compare the calculated mean ocular perfusion pressure at the end of 3 weeks' treatment with latanoprost 0.005% once daily or timolol 0.5% twice daily in normal-tension glaucoma patients. In a three-center, double-masked, randomized, crossover study, 36 patients were allocated to two treatment groups; one received 3 weeks each of placebo, latanoprost, placebo, and timolol, whereas the other group had placebo, timolol, placebo, and latanoprost. Intraocular pressure and resting systemic blood pressure were measured at 9 AM, 12 noon, and 4 PM. Ocular perfusion pressure was calculated for each time period as well as the mean of three values (daytime average). Systemic blood pressure and heart rate were also recorded at 30-minute intervals during the last 24 hours of each treatment period. The average daytime mean ocular perfusion pressure (mean +/- SEM) following latanoprost treatment was 53.2 +/- 1.4 mm Hg, an increase of 8% from the latanoprost run-in period, compared with 50.9 +/- 1.1 mm Hg following timolol treatment, an increase of 2% from the timolol run-in period (P < .05, ANOVA). Timolol reduced the blood pressure. The difference in mean daytime and nighttime systolic blood pressure measurements as well as nighttime diastolic blood pressure was about 5 mm Hg between the latanoprost and timolol treatments. The daytime and nighttime heart rates were also slower during the timolol treatment. Because ocular perfusion pressure may be important in some glaucomatous patients, latanoprost appears to affect ocular perfusion pressure more favorably than timolol does in patients with normal-tension glaucoma.


Quantification of Lutein + Zeaxanthin Presence in Human Placenta and Correlations with Blood Levels and Maternal Dietary Intake.
Lutein + zeaxanthin (L + Z) are carotenoids recognized in eye health, but less is known about their status during pregnancy. While quantified in maternal and umbilical cord blood, they have never been analyzed in placenta. The purpose of this study is to quantify combined L + Z concentrations in human placenta and correlate with levels in maternal dietary intake, maternal serum, and umbilical cord blood. The proportions of combined L + Z were compared within diet, placenta, maternal serum, and umbilical cord blood among additional carotenoids (lycopene, β-cryptoxanthin, α-carotene, and β-carotene). This Institutional Review Boardapproved cross-sectional study enrolled 82 mother-infant pairs. Placenta, maternal serum, and umbilical cord blood samples were analyzed for carotenoids concentrations. Mothers completed a food frequency questionnaire and demographic/birth outcome data were collected. L + Z were present in placenta, median 0.105 micrograms/gram (mcg/g) and were significantly correlated with maternal serum (r = 0.57; p < 0.001), umbilical cord blood levels (r = 0.49; p = 0.001), but not dietary intake (p = 0.110). L + Z were the most prevalent in placenta (49.1%) umbilical cord blood (37.0%), but not maternal serum (18.6%) or dietary intake (19.4%). Rate of transfer was 16.0%, the highest of all carotenoids. Conclusively, L + Z were identified as the two most prevalent in placenta. Results highlight unique roles L + Z may play during pregnancy.


Modeling and Design Optimization of a Rotational Soft Robotic System Driven by Double Cone Dielectric Elastomer Actuators.
Dielectric elastomers (DEs) consist of highly compliant electrostatic transducers which can be operated as actuators, by converting an applied high voltage into motion, and as sensors, since capacitive changes can be related to displacement information. Due to large achievable deformation (on the order of 100%) and high flexibility, DEs appear as highly suitable for the design of soft robotic systems. An important requirement for robotic systems is the possibility of generating a multi degree-of-freedom (MDOF) actuation. By means of DE technology, a controllable motion along several directions can be made possible by combining different membrane actuators in protagonist-antagonist configurations, as well as by designing electrode patterns which allow independent activation of different sections of a single membrane. However, despite several concepts of DE soft robots have been presented in the recent literature, up to date there is still a lack of systematic studies targeted at optimizing the design of the system. To properly understand how different parameters influence the complex motion of DE soft robots, this paper presents an experimental study on how geometry scaling affects the performance of a specific MDOF actuator configuration. The system under investigation consists of two cone DE membranes rigidly connected along the outer diameter, and pre-compressed out-of-plane against each other via a rigid spacer. The electrodes of both membranes are partitioned in four sections that can be activated separately, thus allowing the desired MDOF actuation feature. Different prototypes are assembled and tested to study the influence of the inner radius as well as the length of the rigid spacer on the achievable motion range. For the first experimental study presented here, we focus our analysis on a single actuation variable, i.e., the rotation of the rigid spacer about a fixed axis. A physics-based model is then developed and validated based on the collected experimental measurements. A model-based investigation is subsequently performed, with the aim of studying the influence of the regarded parameters on the rotation angle. Finally, based on the results of the performed study, a model-based optimization of the prototype geometry is performed.


Ethanol-induced alterations in rat synaptosomal plasma membrane phospholipids. Relationship to changes in the phospholipid methyltransferases.
The effects of ethanol ingestion on the lipids of the synaptic plasma membrane (SPM) have been measured and correlated with the time frame for the development of physical dependence. Alterations were observed in three of the phospholipid fractions: phosphatidylcholine (PC) increased, and the phosphatidylethanolamine (PE) and phosphatidylserine (PS) plus phosphatidylinositol (PI) fractions decreased. These alterations occurred after the animals showed signs of dependence. Because PC can be synthesized from PE by the methyltransferase pathway, synaptosomal methyl group incorporation was measured. Rats were fed ethanol for 6 days before an increase was observed in methyl incorporation, a shorter length of time than was necessary to demonstrate physical dependence or phospholipid alterations (10 to 14 days). After ethanol withdrawal, 7 days of control diet feeding were required for methyl group incorporation to return to control values. In vitro ethanol (10-250 mM) additions to the methyltransferase incubations resulted in a slight increase in methyl incorporation. These data suggest that synaptic membrane lipid alterations may be related to ethanol dependence and that changes in the PC/PE ratio may be the result of an increase in the incorporation of methyl groups into synaptosomal phospholipids.


Phenotypic expressions of CCR5-delta32/delta32 homozygosity.
As blockade of CC-chemokine receptor 5 (CCR5) has been proposed as therapy for HIV-1, we examined whether the CCR5-delta32/delta32 homozygous genotype has phenotypic expressions other than those related to HIV-1. Study subjects were white homosexual men or men with hemophilia who were not infected with HIV-1. In this study, 15 CCR5-delta32/delta32 homozygotes were compared with 201 CCR5 wild-type (+/+) subjects for a wide range of clinical conditions and laboratory assay results ascertained during prospective cohort studies and routine clinical care. CCR5-delta32 genotype was determined by polymerase chain reaction, followed by single-stranded conformational polymorphism analysis. Hypertension and conditions attributable to hemophilia were the only diagnoses frequently found in clinical records of CCR5-delta32/delta32 study subjects. Based on blood pressure measurement and treatment history, CCR5-delta32/delta32 homozygotes had a 2.8-fold higher prevalence of hypertension than age-matched CCR5-+/+ study subjects (95% confidence interval [CI], 1.2-6.4; p = .01); none of the homozygotes had severe hypertension. Hematologic measures were generally similar across the genotypes, but total lymphocyte counts were approximately 20% higher in CCR5-delta32/delta32 study subjects than in CCR5-+/+ study subjects (p < .05). Among patients with hemophilia who were infected with hepatitis C virus (HCV), mean alanine aminotransferase levels were 117% higher among CCR5-delta32/delta32 homozygotes (p < .05), but serum HCV levels did not differ by CCR5-delta32 genotype. CCR5-delta32/delta32 homozygous study subjects had a lower prevalence of antibodies to measles virus than those with other genotypes, but this association was not confirmed in a group of blood donors. The prevalence of antibodies to nine other common viruses, HBV, and HCV was not related to CCR5 genotype. CCR5-delta32/delta32 homozygotes are generally similar to wild-type persons. Confirmatory investigations are required to determine whether hypertension, increased lymphocyte counts, and higher hepatic enzyme levels in the presence of HCV infection represent true phenotypic expressions of this genotype. CCR5-delta32/delta32 homozygosity does not provide broad protection against viral infections.


ViralRecall-A Flexible Command-Line Tool for the Detection of Giant Virus Signatures in 'Omic Data.
Giant viruses are widespread in the biosphere and play important roles in biogeochemical cycling and host genome evolution. Also known as nucleo-cytoplasmic large DNA viruses (NCLDVs), these eukaryotic viruses harbor the largest and most complex viral genomes known. Studies have shown that NCLDVs are frequently abundant in metagenomic datasets, and that sequences derived from these viruses can also be found endogenized in diverse eukaryotic genomes. The accurate detection of sequences derived from NCLDVs is therefore of great importance, but this task is challenging owing to both the high level of sequence divergence between NCLDV families and the extraordinarily high diversity of genes encoded in their genomes, including some encoding for metabolic or translation-related functions that are typically found only in cellular lineages. Here, we present ViralRecall, a bioinformatic tool for the identification of NCLDV signatures in 'omic data. This tool leverages a library of giant virus orthologous groups (GVOGs) to identify sequences that bear signatures of NCLDVs. We demonstrate that this tool can effectively identify NCLDV sequences with high sensitivity and specificity. Moreover, we show that it can be useful both for removing contaminating sequences in metagenome-assembled viral genomes as well as the identification of eukaryotic genomic loci that derived from NCLDV. ViralRecall is written in Python 3.5 and is freely available on GitHub: https://github.com/faylward/viralrecall.


Breast Cancer Risk - Genes, Environment and Clinics.
The information available about breast cancer risk factors has increased dramatically during the last 10 years. In particular, studies of low-penetrance genes and mammographic density have improved our understanding of breast cancer risk. In addition, initial steps have been taken in investigating interactions between genes and environmental factors. This review concerns with actual data on this topic. Several genome-wide association studies (GWASs) with a case-control design, as well as large-scale validation studies, have identified and validated more than a dozen single nucleotide polymorphisms (SNPs) associated with breast cancer risk. They are located not only in or close to genes known to be involved in cancer pathogenesis, but also in genes not previously associated with breast cancer pathogenesis, or may even not be related to any genes. SNPs have also been identified that alter the lifetime risk in BRCA mutation carriers. With regard to nongenetic risk factors, studies of postmenopausal hormone replacement therapy (HRT) have revealed important information on how to weigh up the risks and benefits of HRT. Mammographic density (MD) has become an accepted and important breast cancer risk factor. Lifestyle and nutritional considerations have become an integral part of most studies of breast cancer risk, and some improvements have been made in this field as well. More than 10 years after the publication of the first breast cancer prevention studies with tamoxifen, other substances such as raloxifene and aromatase inhibitors have been investigated and have also been shown to have preventive potential. Finally, mammographic screening systems have been implemented in most Western countries during the last decade. These may be developed further by including more individualized methods of predicting the patient's breast cancer risk.


Behavioural consistency and hippocampal theta rhythm can reflect age-related anxiety during the behaviour test.
It is known that anxiety has a lot of comorbidity such as depression and may cause older subjects to be more prone to anxiety. Animal studies have also observed that older rats have lower movement in different situations, somewhat like anxiety symptoms (avoidance and freezing). The anxiety level of rodents is commonly evaluated using the elevated plus maze test, and videos are often used to record and quantify the activities of animals during the test. Furthermore, aging can reduce the frequency and activity of locomotion-induced hippocampal theta rhythm, and these reductions are also reflected in sensory-motor integration and cognition. Thus, directly analyzing the hippocampal theta rhythm and the quantity and quality of physical activity (PA) during the anxiety test can help elucidate the mechanisms underlying the anxiety-like behaviour. We explored alterations in the hippocampal theta rhythm, PA, and behavioural consistency (cross-correlation with 8-s window length) from triaxial acceleration vectors and subsequently examined the effects of age during the elevated plus maze test. We hypothesized that middle-aged rats would exhibit more anxiety, which is correlated with a reduction in behavioural consistency and hippocampal theta frequency during the elevated plus maze test. The middle-aged rats had a lower open-arm frequency and more low-frequency theta oscillations. The middle-aged rats had a lower mean power frequency (Frq) of the hippocampal theta rhythm, PA, and behavioural consistency. The Frq of the middle-aged rats was positively correlated with behavioural consistency. The results indicated that behavioural consistency could distinguish age-related anxiety-like behaviour. Behavioural consistency can serve as an index for the quality of movement and be used to distinguish age-related anxiety.


Hip Pain in Adolescent Patients.
Hip pain is a common complaint in adolescents. There are several causes for hip pain in this population, with dysplasia and impingement being the most common; however, other conditions such as extra-articular impingement, torsional disorders, labral tears, and osteochondral lesions also require consideration. Many of these conditions are related to underlying anatomic abnormalities and increased activity in this age group. An understanding of the common pathologies of the adolescent hip is integral to the evaluation, diagnosis, and treatment of these patients.


Mutagenicity and cytotoxicity of benzo(a)pyrene benzo-ring epoxides.
Four benzo-ring epoxides of the environmental carcinogen benzo(a)pyrene (BP) were tested for mutagenic and cytotoxic activity in 3 strains of Salmonella typhimurium (TA1538, TA98, and TA100) and in Chinese hamster V79 cells. Although very unstable in aqueous solution, 7beta,8alpha-dihydroxy-0beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol epoxide 1), with the 7-hydroxyl group on the same face of the molecule as the epoxide oxygen, was 1.5 to 4 times as mutagenic in the bacterial strains as was its more stable stereoisomer 7beta,8alpha-dihydroxy-9alpha,10beta-epoxy-7,8,9.10-tetrahydrobenzo(a)pyrene (diol epoxide 2). In V79 cells, diol epoxide 1 had one-third the mutagenic activity of diol epoxide 2 but was at least 10 times more labile than diol epoxide 2 in the tissue culture medium. The half-life of diol epoxide 1 in tissue culture medium was about 30 sec, whereas the half-life of diol epoxide 2 was between 6 and 12 min. 9,10-Epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, which is saturated in the benzo ring, is also very unstable and has mutagenic activity equal to or greater than diol epoxide 1 in the bacterial and mammalian cells. 7,8-Epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene was more stable in aqueous solution than any of the 9,10-epoxides of BP but was much less mutagenic in both the bacterial and mammalian cells. In v79 cells, diol epoxides 1 and 2 and 9,10-opoxy-7,8,9,10-tetrahydrobenzo(a)pyrene were more than 40 times more cytotoxic than 7,8-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene. The mutagenicity of the 2 tetrahydro epoxides toward strain TA98 of S. typhimurium was readily abolished by purified epoxide hydrase, whereas the mutagenic activity of the 2 diol epoxides was relatively unaffected by coincubation with the enzyme.


Monitoring healthcare quality in an obstetrics and gynaecology department using a CUSUM chart.
To use cumulative sum (CUSUM) charts for the early detection of variations in quality of care in a maternity department. Retrospective analysis of prospectively collected data. Maternity department of a teaching hospital in Paris (France). Data from 20 519 women and 21 448 infants were collected between January 2000 and December 2007. CUSUM charts were used to monitor the rate of 19 pre-selected quality indicators over 3 years (2005-2007), against standards developed by department obstetrician gynaecologists. Periods with adverse event rates that did not meet the standards were identified. Quality indicator rates. Indicators fell into three groups based on the number of periods with unacceptable rates: less than one per year [e.g. the rate of intensive care unit (ICU) admission of mothers and rate of third- or fourth-degree perineal tears]; one every 2-12 months on average (e.g. blood transfusion and sulprostone use in the overall population of women); and at least one per month (insufficient availability of epidural analgesia). CUSUM charts for a broad range of quality indicators can be used to monitor the quality of care in an obstetrics department. A prospective study investigating the ability of CUSUM-based monitoring to improve maternal and neonatal outcomes would be of interest.


Biobehavioral pain research: a multi-institute assessment of cross-cutting issues and research needs.
In 1994 ten NIH institutes sponsored an interagency workshop focusing on biobehavioral pain research. The workshop had three major goals: (1) to review the current status of biobehavioral pain research (2) to identify critical research needs, and (3) to enhance interdisciplinary and interagency cooperation in pain research. The purpose of this article is to summarize the presentations at this meeting and to highlight some of the key research recommendations. Research topics addressed include (a) understanding critical interfaces between biology and behavior; (b) pain, suffering, and emotion; (c) pain and behavior; (d) behavior-related interventions; (e) commonalities and differences in pain expression, experience, and treatment; and (f) pain in special populations. The article concludes with a summary of NIH pain research activities that have taken place since the workshop.


Intraocular pressure and refractive changes following orbital decompression with intraconal fat excision.
The purpose of this study was to measure the changes in intraocular pressure (IOP) and refraction following orbital decompression for thyroid orbitopathy. Retrospective review of 18 eyes in 10 consecutive patients who underwent orbital decompression including intraconal fat excision for proptosis secondary to thyroid orbitopathy. IOP using tonopen, exophthalmometry, autorefraction and autokeratometry measurements were performed at 1-week, 1-month and 3-months after surgery. There was no statistically significant difference between the preoperative and postoperative IOP at 3 months. There were no significant differences found between preoperative and post operative keratometry readings or automated refraction following orbital decompression. Our study did not find a significant change in IOP and refraction following orbital decompression with intraconal fat excision. A larger prospective study is required in order to evaluate the role of intraconal fat excision in reducing IOP due to it's potential role in patients with concurrent glaucoma.


First-line erlotinib followed by second-line cisplatin-gemcitabine chemotherapy in advanced non-small-cell lung cancer: the TORCH randomized trial.
Erlotinib prolonged survival of unselected patients with advanced non-small-cell lung cancer (NSCLC) who were not eligible for further chemotherapy, and two phase II studies suggested it might be an alternative to first-line chemotherapy. A randomized phase III trial was designed to test whether first-line erlotinib followed at progression by cisplatin-gemcitabine was not inferior in terms of survival to the standard inverse sequence. Patients with stage IIIB (with pleural effusion or supraclavicular nodes) to IV NSCLC and performance status of 0 to 1 were eligible. With a 95% CI upper limit of 1.25 for the hazard ratio (HR) for death, 80% power, a one-sided α = .025, and two interim analyses, a sample size of 900 patients was planned. At the first planned interim analysis with half the events, the inferiority boundary was crossed, and the Independent Data Monitoring Committee recommended early termination of the study. Seven hundred sixty patients (median age, 62 years; range, 27 to 81 years) had been randomly assigned. Baseline characteristics were balanced between study arms. As of June 1, 2011, median follow-up was 24.3 months, and 536 deaths were recorded (263 in the standard treatment arm and 273 in the experimental arm). Median survival was 11.6 months (95% CI, 10.2 to 13.3 months) in the standard arm and 8.7 months (95% CI, 7.4 to 10.5 months) in the experimental arm. Adjusted HR of death in the experimental arm was 1.24 (95% CI, 1.04 to 1.47). There was no heterogeneity across sex, smoking habit, histotype, and epidermal growth factor receptor (EGFR) mutation. In unselected patients with advanced NSCLC, first-line erlotinib followed at progression by cisplatin-gemcitabine was significantly inferior in terms of overall survival compared with the standard sequence of first-line chemotherapy followed by erlotinib.


Prioritizing COVID-19 Contact Tracing During a Surge Using Chatbot Technology.
When COVID-19 cases surge, identifying ways to improve the efficiency of contact tracing and prioritize vulnerable communities for isolation and quarantine support services is critical. During a fall 2020 COVID-19 resurgence in San Francisco, California, prioritization of telephone-based case investigation by zip code and using a chatbot to screen for case participants who needed isolation support reduced the number of case participants who would have been assigned for a telephone interview by 31.5% and likely contributed to 87.5% of Latinx case participants being successfully interviewed. (Am J Public Health. 2022;112(1):43-47. https://doi.org/10.2105/AJPH.2021.306563).


[The participation of the epiphysis in the anti-stress protection of the brain].
Modern data on the functional features of epiphysis classify it as a cerebral stress-limiting structure. The anti-stress effect produced, first and foremost by melatonine, the main epiphysis hormone, is achieved through modification of the central neural mediation processes, synchronization of the circadian rhythmicity, optimization of the endocrine and immune status of an organism. Control of the stress-limiting activity is promising for alleviation of neuroses and psychic depressions.


Effect of starting material particle size on its agglomeration behavior in high shear wet granulation.
The effect of anhydrous lactose particle size distribution on its performance in the wet granulation process was evaluated. Three grades of anhydrous lactose were used in the study: "as is" manufacturer grade and 2 particle size fractions obtained by screening of the 60M lactose. Particle growth behavior of the 3 lactose grades was evaluated in a high shear mixer. Compactibility and porosity of the resulting granules were also evaluated. A uniaxial compression test on moist agglomerates of the 3 lactose grades was performed in an attempt to explain the mechanism of particle size effect observed in the high shear mixer. Particle growth of anhydrous lactose in the high shear mixer was inversely related to the particle size of the starting material. In addition, granulation manufactured using the grade with the smallest particle size was more porous and demonstrated enhanced compactibility compared with the other grades. Compacts with similar porosity and low liquid saturation demonstrated brittle behavior and their breakage strength was inversely related to lactose particle size in the uniaxial compression test, suggesting that material with smaller particle size may exhibit more pronounced nucleation behavior during wet granulation. On the other hand, compacts prepared at higher liquid saturation and similar compression force exhibited more plastic behavior and showed lower yield stress for the grade with smallest particle size. The lower yield stress of compacts prepared with this grade may indicate a higher coalescence tendency for its granules during wet granulation.


Lack of IL-1R8 in neurons causes hyperactivation of IL-1 receptor pathway and induces MECP2-dependent synaptic defects.
Inflammation modifies risk and/or severity of a variety of brain diseases through still elusive molecular mechanisms. Here we show that hyperactivation of the interleukin 1 pathway, through either ablation of the interleukin 1 receptor 8 (IL-1R8, also known as SIGIRR or Tir8) or activation of IL-1R, leads to up-regulation of the mTOR pathway and increased levels of the epigenetic regulator MeCP2, bringing to disruption of dendritic spine morphology, synaptic plasticity and plasticity-related gene expression. Genetic correction of MeCP2 levels in IL-1R8 KO neurons rescues the synaptic defects. Pharmacological inhibition of IL-1R activation by Anakinra corrects transcriptional changes, restores MeCP2 levels and spine plasticity and ameliorates cognitive defects in IL-1R8 KO mice. By linking for the first time neuronal MeCP2, a key player in brain development, to immune activation and demonstrating that synaptic defects can be pharmacologically reversed, these data open the possibility for novel treatments of neurological diseases through the immune system modulation.


Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission.
Although D amino acids are prominent in bacteria, they generally are thought not to occur in mammals. Recently, high levels of D-serine have been found in mammalian brain where it activates glutamate/N-methyl-D-aspartate receptors by interacting with the "glycine site" of the receptor. Because amino acid racemases are thought to be restricted to bacteria and insects, the origin of D-serine in mammals has been puzzling. We now report cloning and expression of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine. Serine racemase is a protein representing an additional family of pyridoxal-5' phosphate-dependent enzymes in eukaryotes. The enzyme is enriched in rat brain where it occurs in glial cells that possess high levels of D-serine in vivo. Occurrence of serine racemase in the brain demonstrates the conservation of D-amino acid metabolism in mammals with implications for the regulation of N-methyl-D-aspartate neurotransmission through glia-neuronal interactions.


[Chronic inflammatory demyelinating polyneuropathies].
A chronic inflammatory demyelinating polyneuropathy (CIDP) is described both on the basis of authors' own observations and literary data. The disease is characterised by delayed onset with progredient, progredient-remittent and stable course of flaccid paresis of extremity together with mild distal sensitive disturbances, albumino-cytologic dissociation and dysimmunoglobulinemia. Cranial nerves damages and vestibulo-cerebellar disturbances were observed in a number of patients. This confirms the involvement of CNS in CIDP. The common character of clinical, immunological, laboratory and electrophysiological findings permits to consider CIDP and Guillain-Barré syndrome as autoimmune diseases. Meanwhile some recent findings on the formation of antibodies to peripheral nerves structures as well as high titers of antisulfamide and antigangliosides antibodies permit to suggest CIDP as separate nosological unit. Additional clinical data and the evaluation of the role of etiological and pathogenetic mechanisms are necessary for the final conclusion.


The Effect of Geometry, Spin, and Orbital Optimization in Achieving Accurate, Correlated Results for Iron-Sulfur Cubanes.
Iron-sulfur clusters comprise an important functional motif in the catalytic centers of biological systems, capable of enabling important chemical transformations at ambient conditions. This remarkable capability derives from a notoriously complex electronic structure that is characterized by a high density of states that is sensitive to geometric changes. The spectral sensitivity to subtle geometric changes has received little attention from correlated, large active space calculations, owing partly to the exceptional computational complexity for treating these large and correlated systems accurately. To provide insight into this aspect, we report the first Complete Active Space Self Consistent Field (CASSCF) calculations for different geometries of the [Fe(II/III)4S4(SMe)4]-2 clusters using two complementary, correlated solvers: spin-pure Adaptive Sampling Configuration Interaction (ASCI) and Density Matrix Renormalization Group (DMRG). We find that the previously established picture of a double-exchange driven magnetic structure, with minute energy gaps (<1 mHa) between consecutive spin states, has a weak dependence on the underlying geometry. However, the spin gap between the singlet and the spin state 2S + 1 = 19, corresponding to a maximal number of Fe-d electrons being unpaired and of parallel spin, is strongly geometry dependent, changing by a factor of 3 upon slight deformations that are still within biologically relevant parameters. The CASSCF orbital optimization procedure, using active spaces as large as 86 electrons in 52 orbitals, was found to reduce this gap compared to typical mean-field orbital approaches. Our results show the need for performing large active space calculations to unveil the challenging electronic structure of these complex catalytic centers and should serve as accurate starting points for fully correlated treatments upon inclusion of dynamical correlation outside the active space.


The left ventral premotor cortex is involved in hand shaping for intransitive gestures: evidence from a two-person imitation experiment.
The ventral premotor cortex (PMv) is involved in grasping and object manipulation, while the dorsal premotor cortex (PMd) has been suggested to play a role in reaching and action selection. These areas have also been associated with action imitation, but their relative roles in different types of action imitation are unclear. We examined the role of the left PMv and PMd in meaningful and meaningless action imitation by using repetitive transcranial magnetic stimulation (rTMS). Participants imitated meaningful and meaningless actions performed by a confederate actor while both individuals were motion-tracked. rTMS was applied over the left PMv, left PMd or a vertex control site during action observation or imitation. Digit velocity was significantly greater following stimulation over the PMv during imitation compared with stimulation over the PMv during observation, regardless of action meaning. Similar effects were not observed over the PMd or vertex. In addition, stimulation over the PMv increased finger movement speed in a (non-imitative) finger-thumb opposition task. We suggest that claims regarding the role of the PMv in object-directed hand shaping may stem from the prevalence of object-directed designs in motor control research. Our results indicate that the PMv may have a broader role in 'target-directed' hand shaping, whereby different areas of the hand are considered targets to act upon during intransitive gesturing.


Assessing fear of hypoglycemia in children with Type 1 diabetes and their parents.
This article summarizes the literature on fear of hypoglycemia in pediatric Type 1 diabetes and the assessment of this fear in both children with Type 1 diabetes and their parents. The most common instrument for assessing fear of hypoglycemia in this population is the children's and parent's versions of the Hypoglycemia Fear Survey (HFS), although studies using other assessment measures are also reviewed. Studies using this survey have identified variables contributing to fear of hypoglycemia in children with Type 1 diabetes and their parents, such as history of frequent or traumatic hypoglycemia, as well as trait anxiety. In addition to this summary of the literature, new data are presented supporting the reliability of hypoglycemic fear assessment in younger children and comparing fear of hypoglycemia in children in different age groups (6-18 years old) and their parents. Also reviewed are studies investigating the relationship between fear of hypoglycemia and diabetes control, which have yielded inconsistent results. Given the potential importance of fear of hypoglycemia in pediatric diabetes, there has been limited research in this area.


Didymin reverses phthalate ester-associated breast cancer aggravation in the breast cancer tumor microenvironment.
The present study demonstrated two novel findings. To the best of our knowledge, it is the first study to demonstrate that regulated upon activation, normal T-cell expressed and secreted (RANTES), produced by breast tumor-associated monocyte-derived dendritic cells (TADCs) following breast cancer cell exposure to phthalate esters, may contribute to the progression of cancer via enhancement of cancer cell proliferation, migration and invasion. Furthermore, the present study revealed that didymin, a dietary flavonoid glycoside present in citrus fruits, was able to reverse phthalate ester-mediated breast cancer aggravation. MDA-MB-231 cells were treated with butyl benzyl phthalate (BBP), di-n-butyl phthalate (DBP) or di-2-ethylhexyl phthalate (DEHP). Subsequently, the conditioned medium (CM) was harvested and cultured with monocyte-derived dendritic cells (mdDCs). Cultures of MDA-MB-231 cells with the conditioned medium of BBP-, DBP- or DEHP-MDA-MB-231 tumor-associated mdDCs (BBP-, DBP- or DEHP-MDA-TADC-CM) demonstrated enhanced proliferation, migration and invasion. Exposure of the MDA-MB-231 cells to DBP induced the MDA-TADCs to produce the inflammatory cytokine RANTES, which subsequently induced MDA-MB-231 cell proliferation, migration and invasion. Depleting RANTES reversed the effects of DBP-MDA-TADC-mediated MDA-MB-231 cell proliferation, migration and invasion. In addition, didymin was observed to suppress phthalate-mediated breast cancer cell proliferation, migration and invasion. The present study suggested that didymin was capable of preventing phthalate ester-associated cancer aggravation.


Anatomic localization of immature and mature dendritic cells in an ectopic lymphoid organ: correlation with selective chemokine expression in rheumatoid synovium.
It remains to be clarified whether dendritic cells (DC) reach the rheumatoid arthritis (RA) synovium, considered an ectopic lymphoid organ, as mature cells or undergo local maturation. We characterized by immunohistochemistry the DC subsets and used tonsils as a control. Immature and mature DC were defined by CD1a and DC-lysosome-associated membrane protein/CD83 expression, respectively. Immature DC were mainly detected in the lining layer in RA synovium. Mature DC were exclusively detected in the lymphocytic infiltrates. The DC-lysosome-associated membrane protein/CD1a ratio was 1.1 in RA synovium and 5.3 in tonsils, suggesting the relative accumulation of immature DC in RA synovium. We then focused on the expression of CCL20/CCR6 and CCL19/CCR7, CCL21/CCR7 chemokine/receptor complex, which control immature and mature DC migration respectively. A close association was observed between CCL20-producing cells and CD1a(+) cells, suggesting the contribution of CCL20 to CCR6(+) cell homing. Conversely, CCL21 and CCL19 expression was only detected in perivascular infiltrates. The association among CCL19/21-producing cells, CCR7 expression, and mature DC accumulation is in line with the roles of these chemokines in mature CCR7(+) DC homing to lymphocytic infiltrates. The role of DC in disease initiation and perpetuation makes chemokines involved in DC migration a potential therapeutic target.


Changes in neuronal activities in the two ventral posterior medial thalamic nuclei in an experimental model of trigeminal pain in the rat by constriction of one infraorbital nerve.
The present study analyzes the activity of 120 neurons recorded in the two ventro-postero-medial (VPM) nuclei of the thalamus in a rat model of trigeminal neuropathic pain. Twenty-eight rats were tested 2 weeks after a chronic constriction injury (CCI) of the infraorbital nerve (IoN). These animals exhibited violent pain-related reactions to extremely weak mechanical stimuli applied to the lesioned and, to a lesser extent, unlesioned IoN territories. The activities of neurons recorded in the VPMc (n = 80) and VPMi (n = 40), contralateral and ipsilateral to the injured nerve, respectively, were compared with those of 62 neurons recorded in the VPM of ten normal rats (VPMn). The neuronal background activity was higher in the VPM of CCI-IoN rats than in normal rats (about 4 vs 1 spike/s). The proportion of neurons which were driven by mechanical stimulations applied contralaterally to their recording site, was comparable in the three VPM (63-70%), but the effective stimulus modality differed significantly between the normal and the lesioned rats. In particular, the number of neurons driven by vibrissa or guard hair movements dramatically decreased in the VPM of CCI-IoN rats, mainly in the VPMc (67% of neurons with a receptive field (RF) in the VPMn vs 12% in the VPMc). Inversely, a consistent number of neurons in both the VPMc and VPMi were driven by other stimulus modalities applied to the IoN territory (moderate pressure for VPMc neurons, pinch or pinprick for both VPMc and VPMi neurons). The responses so induced were especially intense and included afterdischarges. In contrast to the VPMn neurons, the RFs of both the VPMc and VPMi neurons included two vibrissae at least, and were occasionally discontinuous and multimodal, including both vibrissae and cutaneous areas for VPMc units. The bilateral changes in VPM responsiveness and in behavior suggest the involvement of central processing of sensory information, which are set off by the CCI-IoN. The putative mechanisms and functional implication of the changes in the VPM neuronal activities are discussed.


Exploring Transthyretin Amyloid Cardiomyopathy: A Comprehensive Review of the Disease and Upcoming Treatments.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is a mutation-based genetic disorder due to the accumulation of unstable transthyretin protein and presents with symptoms of congestive heart failure (CHF) and numerous extracardiac symptoms like carpal tunnel syndrome and neuropathy. Two subtypes of ATTR-CM are hereditary and wild-type, both of which have different risk factors, gender prevalence and major clinical symptoms. Timely usage of imaging modalities like echocardiography, cardiac magnetic imaging resonance, and cardiac scintigraphy has made it possible to suspect ATTR-CM in patients presenting with CHF. Management of ATTR-CM includes appropriate treatment for heart failure for symptomatic relief, prevention of arrhythmias and heart transplantation for nonresponders. With the recent approval of tafamidis in the successful management of ATTR-CM, numerous potential therapeutic points have been identified to stop or delay the progression of ATTR-CM. This article aims to provide a comprehensive review of ATTR-CM and insights into its novel therapeutics and upcoming treatments.


Initiation of ventricular fibrillation by supraventricular beats in patients with acute myocardial infarction.
The role of supraventricular extrasystoles in the initiation of ventricular arrhythmia was studied in 72 consecutive patients who developed primary ventricular fibrillation during the acute phase of myocardial infarction. In six patients (8%), a total of 12 episodes of ventricular fibrillation and 16 episodes of ventricular tachycardia were initiated by supraventricular extrasystoles. Ventricular fibrillation and tachycardia were initiated by single supraventricular extrasystoles in 16 and by salvos greater than or equal to two beats in 12 episodes. The RR coupling interval of the supraventricular impulse immediately preceding ventricular tachycardia ranged from 240 to 420 ms (mean 356 (62)) and was characteristic of R-on-T (prematurity index less than 1) in 63% of episodes. Average peak serum creatine kinase activity in the six patients in whom ventricular tachycardia was initiated by a supraventricular extrasystole was 1275 units compared with 720 units in the remaining 66 patients. Five of these six patients later showed evidence of pump failure. Lignocaine or procainamide or both suppressed the ventricular arrhythmia in five of the six patients. The initiation of ventricular fibrillation or tachycardia by supraventricular extrasystoles in acute myocardial infarction is not uncommon and may reflect the increased vulnerability of the heart after a large infarct. These arrhythmias may respond to drugs that suppress ventricular irritability.


MicroRNA markers for the diagnosis of pancreatic and biliary-tract cancers.
It is difficult to detect pancreatic cancer or biliary-tract cancer at an early stage using current diagnostic technology. Utilizing microRNA (miRNA) markers that are stably present in peripheral blood, we aimed to identify pancreatic and biliary-tract cancers in patients. With "3D-Gene", a highly sensitive microarray, we examined comprehensive miRNA expression profiles in 571 serum samples obtained from healthy patients, patients with pancreatic, biliary-tract, or other digestive cancers, and patients with non-malignant abnormalities in the pancreas or biliary tract. The samples were randomly divided into training and test cohorts, and candidate miRNA markers were independently evaluated. We found 81 miRNAs for pancreatic cancer and 66 miRNAs for biliary-tract cancer that showed statistically different expression compared with healthy controls. Among those markers, 55 miRNAs were common in both the pancreatic and biliary-tract cancer samples. The previously reported miR-125a-3p was one of the common markers; however, it was also expressed in other types of digestive-tract cancers, suggesting that it is not specific to cancer types. In order to discriminate the pancreato-biliary cancers from all other clinical conditions including the healthy controls, non-malignant abnormalities, and other types of cancers, we developed a diagnostic index using expression profiles of the 10 most significant miRNAs. A combination of eight miRNAs (miR-6075, miR-4294, miR-6880-5p, miR-6799-5p, miR-125a-3p, miR-4530, miR-6836-3p, and miR-4476) achieved a sensitivity, specificity, accuracy and AUC of 80.3%, 97.6%, 91.6% and 0.953, respectively. In contrast, CA19-9 and CEA gave sensitivities of 65.6% and 40.0%, specificities of 92.9% and 88.6%, and accuracies of 82.1% and 71.8%, respectively, in the same test cohort. This diagnostic index identified 18/21 operable pancreatic cancers and 38/48 operable biliary-tract cancers in the entire cohort. Our results suggest that the assessment of these miRNA markers is clinically valuable to identify patients with pancreato-biliary cancers who could benefit from surgical intervention.


Oral health and dental care of older persons-A systematic map of systematic reviews.
To examine the current knowledge on oral health status and dental care of older persons through a systematic mapping of systematic reviews of low or moderate risk of bias. Geriatric dentistry covers all aspects of oral health and oral care of older persons. Oral health is part of general health and contributes to a person's physical, psychological and social wellbeing. A literature search was performed in three different databases (PubMed, The Cochrane Library and Cinahl) within 12 domains: Dental caries, periodontitis, Orofacial pain and temporomandibular joint (TMJ) pain, mucosal lesions, oral motor function, dry mouth, halitosis, interaction between oral status and other medical conditions, ability to interrelate and communicate, quality of life, ethics and organisation of dental care for older persons. Systematic reviews were identified and scrutinised, highlighting scientific knowledge and knowledge gaps. We included 32 systematic reviews of which 14 were judged to be of low/moderate risk of bias. Most of the domains lack systematic reviews with low or moderate risk of bias. In two of the domains evidence was identified; in institutionalised people aged 65 or older, effective oral hygiene can prevent pneumonia. Furthermore, there is an evidence of a relationship between malnutrition (protein energy-related malnutrition, PEM) and poor appetite and edentulousness. There is an urgent need for further research and evidence-based knowledge within most domains in geriatric dentistry and in other fields related to oral health and dental care for older persons striving for multi-disciplinary research programmes.


[Antiphospholipid antibodies in Behcet's disease].
35 patients with Behcet's disease (BD) were examined for antiphospholipid antibodies (aPL). Elevated levels of antibodies to cardiolipin (aCL) were registered in 20% of the patients (aCL IgG and IgM in 11.4 and 8.6%, respectively). Low positivity of these antibodies prevailed (33.2 GPL and 41.2 MPL). Lupus anticoagulant was present in 6 patients. No distinct correlation was found between positivity by aPL and vascular disorders. It is inferred that aPL do not seem to play a leading role in thrombotic diathesis in BD. This diathesis is brought by a much more complicated and multifactor process.


Acceptability of Postpartum Contraception Counseling at the Well Baby Visit.
Objectives The postpartum period is a high-risk time for unintended pregnancy, and additional opportunities to provide contraception are needed. Our objective was to evaluate the acceptability of providing postpartum contraceptive counseling at a pediatric well baby visit, and compare it to counseling at the routine postpartum visit. Methods Postpartum women (100 per group) were recruited for this cohort study at pediatric well baby visits and obstetric postpartum visits at an academic medical center. Well baby participants completed a baseline survey followed by contraceptive counseling by an obstetrician or midwife and a post-counseling survey. Postpartum participants were surveyed after their visit only. Results All well baby visit participants completed the intervention and were enrolled earlier in the postpartum period than postpartum visit participants (mean = 4.1 vs. 6.6 weeks, respectively, p < 0.01). Following counseling, 95% of well baby participants reported being very comfortable discussing contraception, compared to 83% before counseling (RR 1.14, 95% CI 1.06, 1.25) and a higher proportion reported being very likely to use a contraception prescription obtained at the well baby visit (79% after counseling vs. 65% before; RR 1.23, 95% CI 1.08, 1.39). Similar proportions of postpartum and well baby participants were very comfortable discussing contraception at their visits (91 vs. 95%, respectively). Conclusions for practice Contraceptive counseling paired with well baby visits is acceptable among postpartum women. Acceptability increased further after the counseling intervention at the well baby visit. Obstetricians and Pediatricians can partner to offer contraceptive counseling at the well baby visit to increase opportunities for contraception education at an earlier time postpartum.


Looking Into Recent Suicide Rates and Trends in Malaysia: A Comparative Analysis.
Background: Suicide is a preventable cause of death. Examining suicide rates and trends are important in shaping national suicide prevention strategies. Therefore, the objectives of this study were to analyze age-standardized suicide trends of Malaysia between 2000 and 2019 using the WHO Global Health Estimates data, and to compare the 2019 rate with countries from the Association of South-East Asian Nations (ASEAN), Muslim majority countries, and the Group of Seven (G7). Methods: The age-standardized suicide rates data were extracted from the WHO Global Health Estimates. We calculated the average age-standardized suicide rates of the last 3 years from 2017 to 2019. Joinpoint regression analysis was conducted to calculate the average annual percentage change (APC) of the age-standardized suicide rates in Malaysia from 2000 to 2019. Results: Between 2000 and 2019, the minimum and maximum suicide rates for both sexes in Malaysia were 4.9 and 6.1 per 100,000 population respectively, whilst the past 3-year (2017-2019) average rates were 5.6, 8.8, and 2.4 for both sexes, males, and females, respectively. The suicide rates decreased significantly for both sexes between 2000 and 2013. Between 2014 and 2019, the suicide rates increased significantly for males. In 2019, Malaysia recorded the rate of 5.8 per 100,000 population, with an estimated 1,841 suicide deaths, i.e., ~5 deaths per day. The Malaysian suicide rate was the second highest amongst selected Muslim majority countries, in the middle range amongst ASEAN countries, and lower than all G7 countries except Italy. Conclusions: There is a need to further explore factors contributing to the higher suicide rates among Malaysian males. In light of the rising suicide rates in Malaysia, national mental health and suicide prevention initiatives are discussed and the importance of high-quality suicide surveillance data is emphasized.


Cucumber mosaic virus is restricted from entering minor veins in transgenic tobacco exhibiting replicase-mediated resistance.
Transgenic tobacco plants expressing an altered form of the 2a replicase gene from cucumber mosaic virus (CMV) strain Fny exhibited a suppression of viral replication and restricted viral movement when inoculated mechanically or by insect vectors. Resistant plants could be infected, however, through a graft-union with an infected nontransformed plant. The infectious entity moved quickly through intergrafts of resistant tissue, indicating that it could move without replicating in the vascular system. Viral replication continued to be suppressed in systemically infected transgenic portions of grafted plants, as demonstrated by the synthesis of lower levels of viral RNA than in systemically infected nontransformed portions of the same grafted plants. Cell-to-cell spread within this tissue also occurred much more slowly than in nontransformed tobacco. Young inoculated levels of transgenic-resistant plants exhibited limited cell-to-cell virus movement, revealed as chlorotic lesions, but no long-distance virus movement occurred. The results of in situ hybridization studies on these lesions indicated that CMV RNA does not traffic from bundle-sheath cells to vascular parenchyma or companion cells in chlorotic lesions on the inoculated leaves of transgenic-resistant tobacco plants. The inhibition of long-distance movement was a consequence of restricted entry of the infectious entity into the vascular system.


Primary tumor sidedness has an impact on prognosis and treatment outcome in metastatic colorectal cancer: results from two randomized first-line panitumumab studies.
Previous studies have reported the prognostic impact of primary tumor sidedness in metastatic colorectal cancer (mCRC) and its influence on cetuximab efficacy. The present retrospective analysis of two panitumumab trials investigated a possible association between tumor sidedness and treatment efficacy in first-line mCRC patients with RAS wild-type (WT) primary tumors. Data from two randomized first-line panitumumab trials were analyzed for treatment outcomes by primary tumor sidedness for RAS WT patients. PRIME (phase 3; NCT00364013) compared panitumumab plus FOLFOX versus FOLFOX alone; PEAK (phase 2; NCT00819780) compared panitumumab plus FOLFOX versus bevacizumab plus FOLFOX. Primary tumors located in the cecum to transverse colon were coded as right-sided, while tumors located from the splenic flexure to rectum were considered left-sided. Tumor sidedness ascertainment (RAS WT population) was 83% (n = 559/675); 78% of patients (n = 435) had left-sided and 22% (n = 124) had right-sided tumors. Patients with right-sided tumors did worse for all efficacy parameters compared with patients with left-sided disease in the RAS WT population and also in the RAS/BRAF WT subgroup. In patients with left-sided tumors, panitumumab provided better outcomes than the comparator treatment, including on median overall survival (PRIME: 30.3 versus 23.6 months, adjusted hazard ratio = 0.73, P = 0.0112; PEAK: 43.4 versus 32.0 months, adjusted hazard ratio = 0.77, P = 0.3125). The results of these retrospective analyses confirm that in RAS WT patients, right-sided primary tumors are associated with worse prognosis than left-sided tumors, regardless of first-line treatment received. RAS WT patients with left-sided tumors derive greater benefit from panitumumab-containing treatment than chemotherapy alone or combined with bevacizumab, including an overall survival advantage (treatment difference: PRIME 6.7 months; PEAK 11.4 months). No final conclusions regarding optimal treatment could be drawn for RAS WT patients with right-sided mCRC due to the relatively low number of paxtients. Further research in this field is warranted. PRIME (NCT00364013), PEAK (NCT00819780).


Early Neurological Assessment in Infants with Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia.
Early neurological assessment in infants with hypoxic ischemic encephalopathy (HIE) treated with hypothermia has not been systematically explored. The aims of the present study were to assess whether the Hammersmith Infant Neurological Examination (HINE) is a good tool to predict later neurodevelopmental outcomes at 2 year from birth in this population of infants. A total of 41 term born infants with HIE treated with hypothermia performed the HINE at 12 months and a neurodevelopmental assessment at 24 months. All the infants who had a global HINE score between 67 and 78 were able to walk independently at 2 years and reported a normal developmental quotient; language disorders were observed in a limited number of infants. HINE scores <67 were always associated with motor impairment. In conclusion, the HINE confirms its role as one of the early neurological examination tools for the diagnosis of high risk infants, even in infants with HIE treated with hypothermia. These results can be useful for clinicians involved in the follow up of these infants for early identification of motor disabilities and in planning appropriate intervention.


[Serological survey for arboviruses in Juruti, Pará State, Brazil].
This study aimed to measure the prevalence of antibodies to arboviruses in the area affected by the Juruti Project before local mining operations. A total of 1,597 human and 85 wild animal sera were examined, using the hemagglutination inhibition test against 19 antigens from the most prevalent arboviruses in the Brazilian Amazon and IgM-ELISA for dengue and yellow fever. Positive sera for Mayaro and Oropouche viruses were also tested by IgM-ELISA. Prevalence of hemagglutination inhibition antibodies to alphaviruses, flaviviruses, and orthobunyaviruses in humans was 28.7%, while for wild animals it was 8.2% for flaviviruses. Recent infections based on presence of IgM was confirmed for Mayaro (n = 5), Oropouche (n = 23), and dengue (n = 20). The results showed active circulation of the dengue, Mayaro, and Oropouche viruses in Juruti, as well as flaviviruses in wild animals, suggesting the circulation of these viruses in the Municipality of Juruti.


CSF Venous Fistulas in Spontaneous Intracranial Hypotension: Imaging Characteristics on Dynamic and CT Myelography.
The objective of this study is to describe the anatomic and imaging features of CSF venous fistulas, which are a recently reported cause of spontaneous intracranial hypotension (SIH). We retrospectively reviewed the records of patients with SIH caused by CSF venous fistulas who received treatment at our institution. The anatomic details of each fistula were recorded. Attenuation of the veins involved by the fistula was compared with that of adjacent control veins on CT myelography (CTM). Visibility of the CSF venous fistula on CTM and a modified conventional myelography technique we refer to as dynamic myelography was also compared. Twenty-two cases of CSF venous fistula were identified. The fistulas were located between T4 and L1. Ninety percent occurred without a concurrent epidural CSF leak. In most cases (82%), the CSF venous fistula originated from a nerve root sleeve diverticulum. On CTM, the abnormal veins associated with the CSF venous fistula were seen in a paravertebral location in 45% of cases, centrally within the epidural venous plexus in 32%, and lateral to the spine in 23%. Differences in attenuation between the fistula veins and the control veins was highly statistically significant (p < 0.0001), with a threshold of 70 HU perfectly discriminating fistulas from normal veins in our series. When both CTM and dynamic myelography were performed, the fistula was identified on both modalities in 88% of cases. CSF venous fistulas are an important cause of SIH that can be detected on both CTM and dynamic myelograph y and may occur without an epidural CSF leak. Familiarity with the imaging characteristics of these lesions is critical to providing appropriate treatment to patients with SIH.


Enhancement of induced disease resistance by simultaneous activation of salicylate- and jasmonate-dependent defense pathways in Arabidopsis thaliana.
The plant-signaling molecules salicylic acid (SA) and jasmonic acid (JA) play an important role in induced disease resistance pathways. Cross-talk between SA- and JA-dependent pathways can result in inhibition of JA-mediated defense responses. We investigated possible antagonistic interactions between the SA-dependent systemic acquired resistance (SAR) pathway, which is induced upon pathogen infection, and the JA-dependent induced systemic resistance (ISR) pathway, which is triggered by nonpathogenic Pseudomonas rhizobacteria. In Arabidopsis thaliana, SAR and ISR are effective against a broad spectrum of pathogens, including the foliar pathogen Pseudomonas syringae pv. tomato (Pst). Simultaneous activation of SAR and ISR resulted in an additive effect on the level of induced protection against Pst. In Arabidopsis genotypes that are blocked in either SAR or ISR, this additive effect was not evident. Moreover, induction of ISR did not affect the expression of the SAR marker gene PR-1 in plants expressing SAR. Together, these observations demonstrate that the SAR and the ISR pathway are compatible and that there is no significant cross-talk between these pathways. SAR and ISR both require the key regulatory protein NPR1. Plants expressing both types of induced resistance did not show elevated Npr1 transcript levels, indicating that the constitutive level of NPR1 is sufficient to facilitate simultaneous expression of SAR and ISR. These results suggest that the enhanced level of protection is established through parallel activation of complementary, NPR1-dependent defense responses that are both active against Pst. Therefore, combining SAR and ISR provides an attractive tool for the improvement of disease control.


Charcot-Marie-Tooth Disease Type 2.
No unique genes have yet been found for CMT2, but both Cx32 and P0 appear to contribute to the phenotype. Not surprisingly, CMT2 is likely to display much more genetic heterogeneity than CMT1. However, it is also likely continue to challenge previous concepts on classification and relationship of traditional inherited phenotypes in neurology. Future work on CMT2 should produce insight not only into the cellular interactions of the peripheral nerve especially Schwann cell and axon relationships, but also into idiopathic neuropathy.


Smoking and nicotine exposure delay development of collagen-induced arthritis in mice.
Recent epidemiologic studies have implicated smoking as an environmental risk factor for the development of rheumatoid arthritis (RA). The aim of the present study is the evaluation of the role of cigarette smoke (CS) in the pathogenesis of collagen-induced arthritis in mice. DBA/1 mice exposed to CS for 16 weeks (n = 25) and mice exposed to nicotine in drinking water (n = 10) were immunized with collagen type II (CII). Severity of arthritis was evaluated clinically and morphologically and compared with control mice (n = 35). Intensity of inflammation was evaluated by serum IL-6 and TNF-alpha levels. Additionally, antibody response to CII (anti-CII) and citrullinated peptides (aCCP) was measured. Clinical evaluation of arthritis showed a delayed onset of arthritis in CS-exposed mice compared with non-smoking controls (P < 0.05). Histologic index and weight changes were comparable between the groups; however, smoking mice presented less weight loss during the acute phase of the disease and gained weight significantly faster in the recovery phase (P < 0.05). Similar results were obtained in the mice exposed to nicotine. Nicotine also showed a direct anti-inflammatory effect diminishing IL-6 production by stimulated splenocytes in vitro (P < 0.001). Additionally, smoking mice had lower levels of aCCP and anti-CII antibodies compared with non-smoking (P < 0.05). Neither smoking nor nicotine exposure aggravates development of CII-induced arthritis in mouse model. Moreover, CS exposure was associated with a lower level of anti-CII antibodies, providing a possible explanation for a delay of arthritis onset in this group.


Flood basalt volcanism during the past 250 million years.
A chronology of the initiation dates of major continental flood basalt volcanism is established from published potassium-argon (K-Ar) and argon-argon (Ar-Ar) ages of basaltic rocks and related basic intrusions. The dating is therefore independent of the biostratigraphic and paleomagnetic time scales. Estimated errors of the initation dates of the volcanic episodes determined from the distributions of the radiometric ages are, approximately, plus or minus 4 percent. There were 11 distinct episodes during the past 250 million years. Sometimes appearing in pairs, the episodes have occurred quasi-periodically with a mean cycle time of 32 +/- 1 (estimated, error of the mean) million years. The initiation dates of the episodes are close to the estimated dates of mass extinctions of marine organisms. Showers of impacting comets may be the cause.


Pediatric Complex Metacarpophalangeal Joint Dislocation of the Index Finger.
Metacarpophalangeal (MCP) joint dislocations are the result of a hyperextension injury. Complex MCP joint dislocations-those that are irreducible to closed maneuvers and require surgical intervention-are considered uncommon, even in the pediatric population. Although several structures have been identified that contribute to irreducible dislocations, the volar plate is the most significant barrier to reduction through interposition into the MCP joint. Key differences that require consideration for MCP joint dislocations in pediatric patients include ligamentous laxity, the absence of sesamoid bones, the possibility for cartilage fractures, and the possibility of growth arrest. Open surgical intervention for a complex MCP joint dislocation is performed through either the volar or dorsal approach. Controversy exists about which approach is superior. We present the case of a 7-year-old female who sustained a complex MCP joint dislocation of the index finger. After numerous unsuccessful attempts at closed reduction, the patient underwent open reduction through the dorsal approach. The phalangeal head had buttonholed through the volar plate and was reduced by using a Freer elevator as a lever and applying gentle traction and flexion. At 4-week follow-up, the patient was pain-free and had regained nearly full range of motion of the index finger MCP joint. In addition to the classic volar and dorsal approaches, different techniques have been used to reduce complex dislocations in pediatric patients, including arthroscopic surgery, a percutaneous technique with manipulation of a skin hook, and a percutaneous technique with a dorsal incision. As demonstrated in this case, open reduction through the dorsal approach remains a viable treatment option for complex MCP joint dislocations in the pediatric population.


Synthesis and structure of [An(RO)PS2]- complexes.
Reaction of An(S)PS(2)P(S)An with NaOR [R = Me, Et, (i)Pr] gives the non-symmetric phosphonodithioato anions [An(RO)PS(2)](-) which can be complexed to a range of metals. The group 10 metals (Ni, Pd and Pt) adopt square planar ML(2) complexes. The zinc and cadmium complexes adopt isostructural dimeric M(2)L(4) structures whilst mercury complexes adopt a subtly different dimeric motif. Two distinctly different lead complexes are reported, one consisting of PbL(2) units joined by Pb...S interactions to form distinct dimeric pairs, the other being a completely new structural motif for complexes of this type, PbL(2) units held together by covalently bonded bridging ligands to form an infinite polymeric chain structure. All new compounds have been characterised spectroscopically and nine demonstrative X-ray structures are reported.


Promoting Colorectal Cancer Screening in South Asian Muslims Living in the USA.
Colorectal cancer is one of the more common forms of cancer in South Asian men and women. Despite the rates of colorectal cancer (CRC) in South Asians, the CRC screening rates remain low in South Asians and Muslims compared with those in Whites and other ethnic minorities in the USA. Religious and cultural barriers have been examined in relation to other types of cancer such as breast and cervical cancers. However, few data are available about CRC screening among Muslims, particularly South Asian American Muslims. A community-based participatory research approach was used to assess attitudes toward CRC screening and various cultural, religious, and gender barriers that prevent CRC screening expressed by Muslim South Asian men and women in the larger San Francisco Bay Area. Six focus groups were conducted (three males and three females) with South Asian American Muslims. The focus groups consisted of a total sample size of n = 32, with 15 men and 17 women, with the average age of participants being 57 years old. This study highlighted key religious, cultural, and gender barriers to CRC screening including lack of awareness of CRC, the notion of fatalism as it relates to screening, lack of emphasis on preventive health, the need to preserve modesty, and stigma around certain CRC screening practices. Religiously tailored interventions and culturally sensitive healthcare providers are needed to better promote CRC screening in South Asian Muslim communities and to help inform the design of health interventions and outreach strategies.


Public health system partnerships: role for local boards of health in preparing the future public health workforce.
The Institute of Medicine's report, Who Will Keep the Public Healthy? Educating Public Health Professionals for the 21st Century, recommended that public health education be accessible to undergraduate students. Promoting access to public health education will ideally contribute to a well-educated public health workforce, thus assuring the fulfillment of the public health mission. In response to this call to action, the authors examined the current practice, feasibility, and value in developing a functional partnership between academic institutions and local boards of health in preparing future public health professionals. Local boards of health in New England were surveyed to: (1) establish a baseline of existing working relationships between them and nearby academic institutions; (2) examine the barriers that inhibit the development of their collaborations with academic partners; and (3) assess how they jointly advance public health workforce development. Despite the main barriers of a lack of time, staff, and funding that are often cited for the absence of collaborations between institutions, one New England state, in particular, reported that their academic institution and local board of health partnerships were important and effective. The authors discuss how academic-practice collaborations hold the potential to combine basic public health principles with leadership and governance experience offered by local boards of health. Such partnerships are underutilized and have the potential to integrate core public health concepts while facilitating applied experiential learning opportunities in a professional public health setting, thus contributing to the development of the future public health workforce.


Olfactory ensheathing cells are attracted to, and can endocytose, bacteria.
Olfactory ensheathing cells (OECs) have been shown previously to express Toll-like receptors and to respond to bacteria by translocating nuclear factor-kappaB from the cytoplasm to the nucleus. In this study, we show that OECs extended significantly more pseudopodia when they were exposed to Escherichia coli than in the absence of bacteria (p=0.019). Co-immunoprecipitation showed that E. coli binding to OECs was mediated by Toll-like receptor 4. Lyso-Tracker, a fluorescent probe that accumulates selectively in lysosomes, and staining for type 1 lysosome-associated membrane proteins demonstrated that endocytosed FITC-conjugated E. coli were translocated to lysosomes. They appeared to be subsequently broken down, as shown by transmission electron microscopy. No obvious adherence to the membrane and less phagocytosis was observed when OECs were incubated with inert fluorescent microspheres. The ability of OECs to endocytose bacteria supports the notion that OECs play an innate immune function by protecting olfactory tissues from bacterial infection.


EGR1 as a potential marker of prognosis in extranodal NK/T-cell lymphoma.
Extranodal natural killer T-cell lymphoma (ENKTL) is an aggressive malignancy with a dismal prognosis. In the present study, gene expression profiling was performed to provide more information on ENKTL molecular signature and offer a rationale for further investigation of prognostic markers in ENKTL. NanoString nCounter Analysis encompassing 133 target genes was used to compare gene expression levels of 43 ENKTL tumor samples. The majority of the patients were under 60 years of age (79.1%); 32 (74.4%) patients had nasal type ENKTL and 23 patients (53.5%) had intermediate/high risk ENKTL based on the prognostic index for natural killer cell lymphoma (PINK). The median follow-up was 15.9 months and the median overall survival (OS) was 16.1 months (95% CI 13.0-69.8). EGR1 upregulation was consistently identified in the localized stage with a low risk of prognostic index based on the PINK. Among the six significantly relevant genes for EGR1 expression, high expression levels of genes, including CD59, GAS1, CXCR7, and RAMP3, were associated with a good survival prognosis. The in vitro test showed EGR1 modulated the transcriptional activity of the target genes including CD59, GAS1, CXCR7, and RAMP3. Downregulation of EGR1 and its target genes significantly inhibited apoptosis and decreased chemosensitivity and attenuated radiation-induced apoptosis. The findings showed EGR1 may be a candidate for prognostic markers in ENKTL. Considerable additional characterization may be necessary to fully understand EGR1.


1918 Influenza Pandemic: In Utero Exposure in the United States and Long-Term Impact on Hospitalizations.
To explore associations between in utero exposure to the 1918 influenza pandemic and hospitalization rates in old age (≥ 70 years) in the United States. We identified individuals exposed (mild and deadly waves) and unexposed in utero to the 1918 influenza pandemic (a natural experiment) by using birth dates from the Asset and Health Dynamics Among the Oldest Old survey. We analyzed differences in hospitalization rates by exposure status with multivariate linear regression. In utero exposure to the deadly wave of the 1918 influenza pandemic increased the number of hospital visits by 10.0 per 100 persons. For those exposed in utero to the deadliest wave of the influenza pandemic, high rates of functional limitations are shown to drive the higher rates of hospitalizations in old age. In utero exposure to the influenza pandemic increased functional limitations and hospitalization rates in old age. Public Health Implications. To determine investments in influenza pandemic prevention programs that protect fetal health, policymakers should include long-term reductions in hospitalizations in their cost-benefit evaluations.


State-of-the-art analytical methods of viral infections in human lung organoids.
Human-based organ models can provide strong predictive value to investigate the tropism, virulence, and replication kinetics of viral pathogens. Currently, such models have received widespread attention in the study of SARS-CoV-2 causing the COVID-19 pandemic. Applicable to a large set of organoid models and viruses, we provide a step-by-step work instruction for the infection of human alveolar-like organoids with SARS-CoV-2 in this protocol collection. We also prepared a detailed description on state-of-the-art methodologies to assess the infection impact and the analysis of relevant host factors in organoids. This protocol collection consists of five different sets of protocols. Set 1 describes the protein extraction from human alveolar-like organoids and the determination of protein expression of angiotensin-converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2) and FURIN as exemplary host factors of SARS-CoV-2. Set 2 provides detailed guidance on the extraction of RNA from human alveolar-like organoids and the subsequent qPCR to quantify the expression level of ACE2, TMPRSS2, and FURIN as host factors of SARS-CoV-2 on the mRNA level. Protocol set 3 contains an in-depth explanation on how to infect human alveolar-like organoids with SARS-CoV-2 and how to quantify the viral replication by plaque assay and viral E gene-based RT-qPCR. Set 4 provides a step-by-step protocol for the isolation of single cells from infected human alveolar-like organoids for further processing in single-cell RNA sequencing or flow cytometry. Set 5 presents a detailed protocol on how to perform the fixation of human alveolar-like organoids and guides through all steps of immunohistochemistry and in situ hybridization to visualize SARS-CoV-2 and its host factors. The infection and all subsequent analytical methods have been successfully validated by biological replications with human alveolar-like organoids based on material from different donors.


An Energy-Efficient MAC Protocol for Medical Emergency Monitoring Body Sensor Networks.
Medical emergency monitoring body sensor networks (BSNs) monitor the occurrence of medical emergencies and are helpful for the daily care of the elderly and chronically ill people. Such BSNs are characterized by rare traffic when there is no emergency occurring, high real-time and reliable requirements of emergency data and demand for a fast wake-up mechanism for waking up all nodes when an emergency happens. A beacon-enabled MAC protocol is specially designed to meet the demands of medical emergency monitoring BSNs. The rarity of traffic is exploited to improve energy efficiency. By adopting a long superframe structure to avoid unnecessary beacons and allocating most of the superframe to be inactive periods, the duty cycle is reduced to an extremely low level to save energy. Short active time slots are interposed into the superframe and shared by all of the nodes to deliver the emergency data in a low-delay and reliable way to meet the real-time and reliable requirements. The interposition slots can also be used by the coordinator to broadcast network demands to wake-up all nodes in a low-delay and energy-efficient way. Experiments display that the proposed MAC protocol works well in BSNs with low emergency data traffic.


Clinical evaluation of axillar lymph nodes compared to surgical and pathological findings.
Reviewing the axillar lymph node status in 196 consecutive breast cancer patients and comparing clinical assessment to pathological findings, the author found an overall erroneous appraisal of 39% with 45% false negative and 29% false positive cases. In more than 15% of the cases there were skip metastases. In the T1 group, stratification to the greatest diameter of the tumor gave a significant difference (P less than 0.01) between axillar LNI in tumours smaller or equal to 1 cm and those with a diameter between 1 and 2 cm. Lymph node metastases in the interpectoral space is extremely rare (less than 0.5%) and always macroscopic. Axillar lymph nodes were always invaded in T4 tumours. The author warns against clinical studies based upon clinical assessment of the axillar lymph node status. He advocates a complete axillar lymph node dissection in all cases. He suggests that the T1 classification should be restricted to tumours with a diameter smaller or equal to 1 cm.


Facilitating a therapeutic milieu in the families of schizophrenia.
For many years, mental health professionals and the families of schizophrenics have coexisted in an atmosphere of mutual distrust and hostility. In this paper, we would like to present some of our experiences in creating a more productive relationship with the families of long-term schizophrenic clients in an aftercare setting. We have found that it is possible to engage these families as allies in the long and difficult process of psychodynamically oriented psychotherapy and resocialization. In many instances, these families actually provide several of the major functions of a vital therapeutic milieu, including containment, support, and structure (Gunderson, 1978).


Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome.
Nonalcoholic fatty liver disease (NAFLD) has been associated with the insulin-resistance syndrome, at present defined as the metabolic syndrome, whose limits were recently set. We assessed the prevalence of the metabolic syndrome in 304 consecutive NAFLD patients without overt diabetes, on the basis of 3 or more criteria out of 5 defined by the U.S. National Institutes of Health (waist circumference, glucose, high-density lipoprotein [HDL]-cholesterol, triglycerides, and arterial pressure). The prevalence of the metabolic syndrome increased with increasing body mass index, from 18% in normal-weight subjects to 67% in obesity. Insulin resistance (Homeostasis Model Assessment method) was significantly associated with the metabolic syndrome (odds ratio [OR], 2.5; 95% CI, 1.5-4.2; P <.001). Liver biopsy was available in 163 cases (54%). A total of 120 patients (73.6%) were classified as having nonalcoholic steatohepatitis (NASH); 88% of them had a metabolic syndrome (vs. 53% of patients with pure fatty liver; P <.0001). Logistic regression analysis confirmed that the presence of metabolic syndrome carried a high risk of NASH among NAFLD subjects (OR, 3.2; 95% CI, 1.2-8.9; P =.026) after correction for sex, age, and body mass. In particular, the syndrome was associated with a high risk of severe fibrosis (OR, 3.5; 95% CI, 1.1-11.2; P =.032). In conclusion, the presence of multiple metabolic disorders is associated with a potentially progressive, severe liver disease. The increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension, and ultimately the metabolic syndrome puts a very large population at risk of forthcoming liver failure in the next decades.


Leukemia inhibitory factor (LIF), cardiotrophin-1, and oncostatin M share structural binding determinants in the immunoglobulin-like domain of LIF receptor.
Leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), and oncostatin M (OSM) are four helix bundle cytokines acting through a common heterodimeric receptor composed of gp130 and LIF receptor (LIFR). Binding to LIFR occurs through a binding site characterized by an FXXK motif located at the N terminus of helix D (site III). The immunoglobulin (Ig)-like domain of LIFR was modeled, and the physico-chemical properties of its Connolly surface were analyzed. This analysis revealed an area displaying properties complementary to those of the LIF site III. Two residues of the Ig-like domain of LIFR, Asp214 and Phe284, formed a mirror image of the FXXK motif. Engineered LIFR mutants in which either or both of these two residues were mutated to alanine were transfected in Ba/F3 cells already containing gp130. The F284A mutation impaired the biological response induced by LIF and CT-1, whereas the response to OSM remained unchanged. The Asp214 mutation did not alter the functional responses. The D214A/F284A double mutation, however, totally impaired cellular proliferation to LIF and CT-1 and partially impaired OSM-induced proliferation with a 20-fold increase in EC50. These results were corroborated by the analysis of STAT3 phosphorylation and Scatchard analysis of cytokine binding to Ba/F3 cells. Molecular modeling of the complex of LIF with the Ig-like domain of LIFR provides a clue for the superadditivity of the D214A/F284A double mutation. Our results indicate that LIF, CT-1, and OSM share an overlapping binding site located in the Ig-like domain of LIFR. The different behaviors of LIF and CT-1, on one side, and of OSM, on the other side, can be related to the different affinity of their site III for LIFR.


Adrenal contribution to cardiac responses elicited by acute hypoxia in piglets.
The adrenal contribution to cardiac responses elicited by acute hypoxia was assessed in 16 piglets, 1-12 wks old, anesthetized with pentobarbital (30 mg/kg). External cardiac work was held constant and parasympathetic blockade was produced in each animal with atropine (1 mg). Hypoxia was produced by addition of N2 to the respirator. In a sham-adrenalectomy group (n = 6) left ventricular (LV) dP/dtmax increased significantly during hypoxia (PaO2 approximately 30 mmHg) to 3,680 +/- 414 mmHg/s from control values of 2,686 +/- 317 mmHg/s (P < 0.01). Heart rate rose from 171 +/- 6 to 186 +/- 7 beats/min (P < 0.02). These responses were not significantly altered by ganglionic blockade with trimethaphan camsylate (0.5 mg x kg-1 x min-1). Equally large increases of LV dP/dtmax appeared when heart rate was held constant by pacing. beta-Adrenoreceptor blockade with practolol (4 mg/kg) sharply reduced but did not eliminate the response. In contrast, no changes in LV dP/dtmax or heart rate were observed during hypoxia in adrenalectomized piglets (n = 6). These findings indicate that the increased cardiac contractility during acute hypoxia in piglets is dependent on the integrity of the adrenal glands and that there is minimal contribution from cardiac sympathetic nerves.


Cross-ethnic measurement invariance of the SCARED and CES-D in a youth sample.
This study evaluated the cross-ethnic measurement invariance of 2 common screening measures of anxiety and depressive symptoms in youth. The measurement invariance of the Screen for Childhood Anxiety and Related Emotional Disorders (SCARED) and the Center for Epidemiologic Studies Depression Scale (CES-D) was tested across 881 African American (Black; n = 396), Hispanic (n = 185), non-Hispanic White (White; n = 166), and Asian/Indian (n = 134) youth in the 7th grade. The measures were administered as part of a grade-wide screening to identify youth with elevated anxiety and depressive symptoms. The 5-factor model of the SCARED and the 4-factor model of the CES-D best represented the data for all ethnic groups. Results provided support for strong invariance of the SCARED across all 4 ethnic groups. Results provided support for strong invariance of the CES-D across Black, White, and Asian/Indian youth, and partial strong invariance for Hispanic youth. Overall, results suggest that factor means and total scores can be compared across groups. Factor mean differences across groups were identified for both measures. In particular, Hispanic youth reported greater levels of anxiety and depression in certain domains than White, Black, and Asian youth. Our findings support the use of the SCARED and CES-D as tools for measuring anxiety and depressive symptoms in ethnically diverse youth in the United States. Results are discussed with respect to the importance of establishing measurement invariance for screening measures of anxiety and depressive symptoms prior to comparing symptom levels across ethnic groups.


Haemolymph parasite of the shore crab Carcinus maenas: pathology, ultrastructure and observations on crustacean haplosporidians.
A protozoan parasite with some features of haplosporidians is described from the European shore crab Carcinus maenas. The parasite establishes a systemic infection through the haemal sinuses and connective tissues. Intracellular stages of the parasite were found within reserve inclusion, connective tissue, and muscle cells, while free forms were present in all haemal spaces. A uninucleate stage appeared to develop to a multinucleate plasmodial stage following multiple mitotic divisions of the nucleus. Histopathology also indicated that nuclear division may occur to form multinucleate plasmodia, in connective tissue, reserve inclusion and muscle cells, the multinucleate plasmodium being enclosed in the host-cell plasma membrane. It appears that the multinucleate plasmodium may then undergo internal cleavages which result in plasmodial fragmentation to form many uninucleate stages. Both stages, but particularly the uninucleate stage, contained cytoplasmic, large, ovoid, dense vesicles (DVs), some of which contained an internal membrane separating the medulla from the cortex, as in haplosporosomes. Golgi-like cisternae, closely associated with the nuclear membrane, formed DVs and haplosporosome-like bodies (HLBs), superficially resembling viruses. Infrequently, HLBs may condense to form haplosporosomes. The DVs, as in spores of some Haplosporidium spp. and paramyxeans, may give rise to, and are homologous with, haplosporosomes. Other features, such as the presence of an intranuclear mitotic spindle, lipid droplets, and attachment of DVs and haplosporosomes to the nuclear membrane, indicate that the C. maenas parasite is a haplosporidian. A similar organism reported from the haemolymph of spot prawns Pandalus spp., and haplosporidians reported from prawns Penaeus vannamei and crabs Callinectes sapidus may belong to this group. It is concluded that the well-characterised haplosporidians of molluscs and some other invertebrates may not be characteristic of the whole phylum, and that morphologically and developmentally similar organisms may also be haplosporidians, whether they have haplosporosomes or not.


The therapeutic effect of the aqueous extract of boswellia serrata on the learning deficit in kindled rats.
It has been reported that epilepsy is a disorder of the central nervous system that causes memory impairment. This study examines the role of the aqueous extract of Boswellia on the learning disability of the pentylenetetrazol (PTZ)-induced kindled rats. In this experimental study, 64 male rats were used. Kindling seizures were induced by three injections of 25 mg/kg of PTZ every 15 min. Control animals received normal saline instead. To evaluate the therapeutic effect of Boswellia extract on the PTZ-induced cognitive deficits, the aqueous extract (0, 0.1, 0.5 or 1 g/kg, i.p.) were administrated to all animals for three consecutive days. At 24 h later, passive avoidance learning of animals was examined using shuttle box apparatus, respectively. The time required for the animal stepping through the dark chamber was determined as step-through latency (STL). Data were subjected to the t-test and analysis of variance and followed by Tukey's test for multiple comparisons. The STL of the kindled rats was significantly reduced compared with control ones (22/375 ± 4/19 for kindled and 295 ± 15/71 for control groups, respectively). Aqueous extract of Boswellia improved passive-avoidance learning ability in both control and PTZ-kindled animals (P < 0.05). The results can be stated that the Boswellia extract is offset by harmful effects of seizures on cognitive function and consumption of Boswellia extract increases the learning ability in epileptic animals.


Master's programs preparing nursing administrators. What are the essential components?
To identify the best educational preparation for nursing administrators the author surveyed recent graduates of nine graduate schools of nursing, one school of public health with a graduate program in nursing, and their employers. She reports that graduates of programs emphasizing management and administrative skills are better prepared for administrative roles than are graduates of clinical specialist programs. She argues for increasing the management, financial, labor relations, and other administrative components of graduate school curricula.


Melatonin suppression and sleepiness in children exposed to blue-enriched white LED lighting at night.
Light-induced melatonin suppression in children is reported to be more sensitive to white light at night than that in adults; however, it is unclear whether it depends on spectral distribution of lighting. In this study, we investigated the effects of different color temperatures of LED lighting on children's melatonin secretion during the night. Twenty-two healthy children (8.9 ± 2.2 years old) and 20 adults (41.7 ± 4.4 years old) participated in this study. A between-subjects design with four combinations, including two age groups (adults and children) and the two color temperature conditions (3000 K and 6200 K), was used. The experiment was conducted for two consecutive nights. On the first night, saliva samples were collected every hour under a dim light condition (<30 lx). On the second night, the participants were exposed to either color temperature condition. Melatonin suppression in children was greater than that in adults at both 3000 K and 6200 K condition. The 6200 K condition resulted in greater melatonin suppression than did the 3000 K condition in children (P < 0.05) but not in adults. Subjective sleepiness in children exposed to 6200 K light was significantly lower than that in children exposed to 3000 K light. In children, blue-enriched LED lighting has a greater impact on melatonin suppression and it inhibits the increase in sleepiness during night. Light with a low color temperature is recommended at night, particularly for children's sleep and circadian rhythm.


Adrenomedullin increases the expression of calcitonin-like receptor and receptor activity modifying protein 2 mRNA in human microvascular endothelial cells.
Adrenomedullin (AM) is a multifunctional peptide hormone, which plays a significant role in vasodilation and angiogenesis, implicating it in hypertension as well as in carcinogenesis. AM exerts its effects via the calcitonin receptor-like receptor (CRLR, now known as CL) complexed with either receptor activity modifying protein (RAMP) 2 or 3. We have investigated the effect of AM on immortalized human microvascular endothelial cells 1, since endothelial cells are a major source as well as a target of AM actions in vivo. Cells treated with AM showed elevated cAMP in a time (5-45 min)-dependent and dose (10(-6)-10(-14) M)-dependent manner. Pre-treatment with the AM receptor antagonist AM(22-52) partially suppressed the AM-induced increase in cAMP levels. An increase in extracellular signal-regulated kinase 1/2 phosphorylation was observed after 5 min of treatment with 10(-8) M AM. This phosphorylation was specific, since we were able to block the AM-induced effect with 1 microM U0126, a specific mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor. Using real-time PCR, we were able to show for the first time that AM upregulates peptide and mRNA expression of vascular endothelial growth factor (VEGF). However, AM treatment of cells did not result in increased cell proliferation. Instead, we observed that AM and VEGF induced cell migration, which could be inhibited by the AM(22-52) and anti-VEGF antibody respectively. AM also significantly elevated mRNA levels of CL (after 2 and 24 h treatment) and RAMP2 (after 1 and 24 h treatment). The upregulation of the AM receptor at two time points reflects possibly different cellular responses to short- and long-term exposure to AM.


Neighborhood resolved fiber orientation distributions (NRFOD) in automatic labeling of white matter fiber pathways.
Accurate digital representation of major white matter bundles in the brain is an important goal in neuroscience image computing since the representations can be used for surgical planning, intra-patient longitudinal analysis and inter-subject population connectivity studies. Reconstructing desired fiber bundles generally involves manual selection of regions of interest by an expert, which is subject to user bias and fatigue, hence an automation is desirable. To that end, we first present a novel anatomical representation based on Neighborhood Resolved Fiber Orientation Distributions (NRFOD) along the fibers. The resolved fiber orientations are obtained by generalized q-sampling imaging (GQI) and a subsequent diffusion decomposition method. A fiber-to-fiber distance measure between the proposed fiber representations is then used in a density-based clustering framework to select the clusters corresponding to the major pathways of interest. In addition, neuroanatomical priors are utilized to constrain the set of candidate fibers before density-based clustering. The proposed fiber clustering approach is exemplified on automation of the reconstruction of the major fiber pathways in the brainstem: corticospinal tract (CST); medial lemniscus (ML); middle cerebellar peduncle (MCP); inferior cerebellar peduncle (ICP); superior cerebellar peduncle (SCP). Experimental results on Human Connectome Project (HCP)'s publicly available "WU-Minn 500 Subjects + MEG2 dataset" and expert evaluations demonstrate the potential of the proposed fiber clustering method in brainstem white matter structure analysis.