Home Range and Activity Patterns of Free-Ranging Cats: A Case Study from a Chinese University Campus.
Human activities and the available resources influence the home range and activity patterns of free-ranging cats. Our objective in this study was to determine sex and breeding season vs. non-breeding season home range size, as well as activity patterns for unowned free-ranging cats at a university campus in China. Twenty-nine adult cats (fifteen males and fourteen females) were tracked with attached GPS units from October 2018 to June 2020. We considered the effects of sex and breeding status on the home range size of free-ranging cats. Male cats had larger home ranges (95% KDE: 12.60 ± 2.61 ha) than female cats (95% KDE: 5.02 ± 1.34 ha) in the breeding season. There was a seasonal effect on the home range size of male cats; for example, during the non-breeding season, the home range (95% KDE: 6.68 ± 1.22 ha) was smaller than that during the breeding season (95% KDE: 12.60 ± 2.61 ha), while female cats tended to have larger home ranges in the non-breeding season (95% KDE: 7.73 ± 2.77 ha) than in the breeding season (95% KDE: 5.02 ± 1.34 ha). We used the number of activity steps to measure the activity intensity of cats to explore their activity patterns. The mean (±SE) number of steps a cat takes per day was 19,863.96 ± 1627.21. There were two peak periods of activity in a day, 6:00-10:00 and 17:00-21:00. Our study provided a case study of the home range and activity patterns of free-ranging cats living on a Chinese university campus, and the results show that the home range of free-ranging cats is affected by the breeding status and sex, and free-ranging cats have more intense activities at twilight and relatively lower activity intensity in the afternoon. The results provided theoretical support for the management and conservation implications of free-ranging cats in cities.


Quantification of the progenitors for thymic T cells in various organs.
Partial characterization and frequency determination of the progenitors for thymic T cells in various organs were made by transferring cells directly into the thymus (intrathymically, i.t.). B10. Thy-1.1 (H-2b, Thy-1.1) mice were used as the donor, and C57BL/6 (H-2b, Thy-1.2) mice that had been whole body irradiated with 800 rads and reconstituted with 10(7) syngeneic (B6) bone marrow (BM) cells were used as the recipient. BM cells, spleen cells and thymus cells from young adults and fetal liver cells (day 14 of gestation) were treated with anti-Thy-1.1 antibody plus complement, and transferred i.t. The generation of Thy-1.1+ donor type cells in the recipient's thymus was investigated by using flow cytometry. From the time course of generation, it was shown that the progenitor cells in the thymus were distinct from those in other organs. After the transfer of thymic non-T cells, donor-type cells began to generate on the 4th day, the proportion of donor-type T cells increased quickly thereafter, and the progenitors in this organ ceased to produce T cells by day 21. On the other hand, a latent period of about 10 days was required for progenitor cells in the BM, spleen or fetal liver to generate T cells, and T cell producing-activity of the progenitor cells in these organs lasted as long as 7 weeks. The frequency of progenitor cells was analyzed by transferring serial dilutions of anti-Thy-1.1 plus complement-treated cells i.t. and investigating the generation of donor-type T cells in the recipient's thymus on day 11 in the case transferred with thymic cells and on day 21 in other cases. The proportion of negative recipients which did not contain detectable levels of donor-type cells was plotted on a logarithmic scale against the number of cells transferred on a linear scale. The progenitor cell frequencies in BM, spleen, thymus and fetal liver were estimated to be 12.5 x 10(-5), 6.25 x 10(-5), 0.22 x 10(-5) and 0.14 x 10(-5), respectively. The reliability of the frequency determination was supported by the finding that when a limited number (10(3)) of a 1:1 mixture of BM cells from two mutually identifiable donors was transferred i.t., most of the recipients were negative for donor-type T cells and 3 out of 4 positive recipients were seeded by progenitor cells of a single donor.


Dynamic changes of nasal tight junctions in patients with convalescent COVID-19 with allergic rhinitis.
Nasal tight junction module score correlates negatively to allergy module score in COVID-19. Omicron variant may slow-down tight junction restoration in patients with AR.


Single-cell RNA-seq uncovers novel metabolic functions of Schwann cells beyond myelination.
Schwann cells (SCs) support peripheral nerves under homeostatic conditions, independent of myelination, and contribute to damage in prediabetic peripheral neuropathy (PN). Here, we used single-cell RNA sequencing to characterize the transcriptional profiles and intercellular communication of SCs in the nerve microenvironment using the high-fat diet-fed mouse, which mimics human prediabetes and neuropathy. We identified four major SC clusters, myelinating, nonmyelinating, immature, and repair in healthy and neuropathic nerves, in addition to a distinct cluster of nerve macrophages. Myelinating SCs acquired a unique transcriptional profile, beyond myelination, in response to metabolic stress. Mapping SC intercellular communication identified a shift in communication, centered on immune response and trophic support pathways, which primarily impacted nonmyelinating SCs. Validation analyses revealed that neuropathic SCs become pro-inflammatory and insulin resistant under prediabetic conditions. Overall, our study offers a unique resource for interrogating SC function, communication, and signaling in nerve pathophysiology to help inform SC-specific therapies.


Tumor-associated carbonic anhydrase isoform IX and XII inhibitory properties of certain isatin-bearing sulfonamides endowed with in vitro antitumor activity towards colon cancer.
Three series of indolinone-based sulfonamides (3a-f, 6a-f and 9a-f) were in vitro evaluated as inhibitors of the tumor-associated carbonic anhydrase (CA, EC 22.214.171.124) isoforms hCA IX and XII, using a stopped-flow CO2 hydrase assay. All the investigated sulfonamides displayed single- or double-digit nanomolar inhibitory activities towards both hCA IX (KIs: 6.2-64.8 nM) and XII (KIs: 7.1-55.6 nM) isoforms. All sulfonamides (3a-f, 6a-f and 9a-f) were in vitro examined for their potential anticancer activity against colorectal cancer HCT-116 and breast cancer MCF-7 cell lines. Sulfonamide 9e was found to be the most potent counterpart against HCT-116 (IC50 = 3.67 ± 0.33 µM). Sulfonamide 9e displayed good selectivity profile for inhibition of the tumor-associated isoforms (CAs IX & XII) over the off-target cytosolic CAs I and II. 9e was screened for cell cycle disturbance and apoptosis induction in HCT-116 cells. It was found to persuade cell cycle arrest at G2-M stage as well as alter the Sub-G1 phase. Also, 9e induced the intrinsic apoptotic mitochondrial pathway in HCT-116 cells via down-regulation of the anti-apoptotic protein Bcl-2 level with concurrent boosting the pro-apoptotic Bax, caspase-9, caspase-3, cytochrome C and p53 levels.


Marine Flora of French Polynesia: An Updated List Using DNA Barcoding and Traditional Approaches.
Located in the heart of the South Pacific Ocean, the French Polynesian islands represent a remarkable setting for biological colonization and diversification, because of their isolation. Our knowledge of this region's biodiversity is nevertheless still incomplete for many groups of organisms. In the late 1990s and 2000s, a series of publications provided the first checklists of French Polynesian marine algae, including the Chlorophyta, Rhodophyta, Ochrophyta, and Cyanobacteria, established mostly on traditional morphology-based taxonomy. We initiated a project to systematically DNA barcode the marine flora of French Polynesia. Based on a large collection of ~2452 specimens, made between 2014 and 2023, across the five French Polynesian archipelagos, we re-assessed the marine floral species diversity (Alismatales, Cyanobacteria, Rhodophyta, Ochrophyta, Chlorophyta) using DNA barcoding in concert with morphology-based classification. We provide here a major revision of French Polynesian marine flora, with an updated listing of 702 species including 119 Chlorophyta, 169 Cyanobacteria, 92 Ochrophyta, 320 Rhodophyta, and 2 seagrass species-nearly a two-fold increase from previous estimates. This study significantly improves our knowledge of French Polynesian marine diversity and provides a valuable DNA barcode reference library for identification purposes and future taxonomic and conservation studies. A significant part of the diversity uncovered from French Polynesia corresponds to unidentified lineages, which will require careful future taxonomic investigation.


Altered circulating mitochondrial DNA and increased inflammation in patients with diabetic retinopathy.
We previously showed that circulating mitochondrial DNA (MtDNA) levels are altered in diabetic nephropathy. The aim of the current study was to determine if circulating MtDNA levels are altered in patients with diabetic retinopathy. Patients with diabetes (n=220) were studied in a clinical setting using a cross-sectional study design as the following groups: DR-0 (no retinopathy, n=53), DR-m (mild non-proliferative diabetic retinopathy NPDR, n=98) and DR-s (severe proliferative diabetic retinopathy, n=69). MtDNA content in peripheral blood DNA was measured as the mitochondrial to nuclear genome ratio using real time qPCR. Circulating cytokines were measured using the luminex assay and MtDNA damage was assessed using PCR. Differences were considered significant at P<0.05. Circulating MtDNA values were higher in DR-m compared to DR-0 (P=0.02) and decreased in DR-s compared to DR-m (P=0.001). These changes remained significant after adjusting for associated parameters. In parallel there were increased levels of circulating cytokines IL-4 (P=0.005) and TNF-α (P=0.02) in the DR-s group and increased MtDNA damage in DR-m patients compared to DR-0 (P=0.03). Our data show that circulating MtDNA levels are independently associated with diabetic retinopathy, showing an increase in DR-m and decrease in DR-s with a parallel increase in MtDNA damage and inflammation. Hyperglycemia-induced changes in MtDNA in early diabetes may contribute to inflammation and progression of diabetic retinopathy. Longitudinal studies should be carried out to determine a potential causality of MtDNA in diabetic retinopathy.


Syllable splitting in literate and preliterate Hebrew speakers: onsets and rimes or bodies and codas?
This study examined consonant-vowel-consonant (CVC) syllable splitting among literate (Grade 2) and preliterate (kindergarten) Hebrew speakers. Consideration of both the architecture of Hebrew orthography and phonology led to the prediction that a body-coda rather than an onset-rime subdivision would predominate. Structured and unstructured tasks confirmed the claim that there exists a subsyllabic, supraphonemic level of phonological awareness that is more accessible than individual phonemes. However, as predicted, the syllable body rather than the rime was found to be the more accessible biphonemic unit. Moreover, this preference did not appear to be solely the product of orthographic structure; rather it was also inherent in spoken phonology. Access to single phonemes, in contrast, shifted from an early preliteracy advantage for (monophonemic) onsets to a literacy-based preference for codas.


Normative data for distal line bisection and baking tray task.
Line bisection is one of the tests used to diagnose unilateral spatial neglect (USN). Despite its wide application, no procedure or norms were available for the distal variant when the task was performed at distance with a laser pointer. Furthermore, the baking tray task was an ecological test aimed at diagnosing USN in a more natural context. The aim of this study was to collect normative values for these two tests in an Italian population. We recruited a sample of 191 healthy subjects with ages ranging from 20 to 89 years. They performed line bisection with a laser pointer on three different line lengths (1, 1.5, and 2 m) at a distance of 3 m. After this task, the subjects performed the baking tray task and a second repetition of line bisection to test the reliability of measurement. Multiple regression analysis revealed no significant effects of demographic variables on the performance of both tests. Normative cut-off values for the two tests were developed using non-parametric tolerance intervals. The results formed the basis for clinical use of these two tools for assessing lateralized performance of patients with brain injury and for diagnosing USN.


The impact of whole-body cryotherapy on lipid profile: A systematic review and meta-analysis.
Whole-body cryotherapy (WBC) is an already proven method of supportive therapy in somatic medicine. Emerging evidence suggests that WBC might exert beneficial effects on lipid profile; however, studies in this field have provided mixed findings. We aimed to perform a systematic review and meta-analysis of studies investigating the impact of WBC on lipid profile. Electronic databases (the MEDLINE, the ERIC, the CINAHL Complete, the International Pharmaceutical Abstracts as well as the Academic Search Ultimate and the Health Source: Nursing/Academic Edition) were searched from their inception until 25th April 2020. Meta-analysis was performed using random-effects models and Hedges g' was calculated as the effect size estimate. We identified seven eligible studies. Pooled data analysis revealed significantly lower levels of triglycerides after WBC. Sensitivity analysis also demonstrated significantly lower levels of total cholesterol and low-density lipoproteins (LDL) after removing single studies. Meta-regression analysis showed that lower baseline body mass index (BMI) was significantly associated with greater changes in the levels of total cholesterol and LDL during WBC. Our findings imply that WBC may exert beneficial effects on the lipid profile in terms of lowering the levels of total cholesterol, LDL and triglycerides. Lower BMI may predict a greater improvement of lipid profile during WBC. However, caution should be taken as to the way our results are being interpreted due to low number of studies and considerable methodological heterogeneity of studies included in our meta-analysis.


Recombinant humanized IgG1 maintain liver triglyceride homeostasis through Arylacetamide deacetylase in ApoE-/- mice.
Hyperlipidemia is a lipid metabolism disorder associated with elevated serum triglyceride (TG) and/or cholesterol. Over the years, studies have shown that hyperlipidemia is associated with combordities, incluing diabetes and obesity, gradually becoming a public health concern. Current treatment approaches remain limited due to the lack of effective drugs. Here we investigated the function of recombinant humanized IgG1 in maintaining liver TG homeostasis and the underlying mechanisms. ApoE-/- mice were fed a high-fat diet (HFD) for 20 weeks to induce hyperlipidemia. RNA sequencing (RNA-Seq) was performed to identify differences in gene expression in different groups of ApoE-/- mice liver. In vitro lipid accumulation in primary mouse hepatocytes was induced using a free fatty acid (FFA) mixture. Gene and protein expression were assessed in primary mouse hepatocytes by qPCR and Western blot. Gene reporter assays and ChIP-PCR were used to determine arylacetamide deacetylase (Aadac) promoter activity. Recombinant humanized IgG1 could significantly decrease the serum level of TG and low-density lipoproteins (LDL-C). Moreover, hepatic TG and lipid droplets were also reduced compared to the HFD group. Mouse liver RNA-Seq revealed that administration of recombinant humanized IgG1 significantly elevated the expression of Aadac. In vitro, knock-down of Aadac could nullify the effect of recombinant humanized IgG1 on decreasing the lipid droplets induced by FFA in primary mouse hepatocytes. Gene Reporter assays and ChIP-PCR demonstrated that the foxa1 response element in the Aadac promoter played a key role in Aadac expression induced by recombinant humanized IgG1. Moreover, recombinant humanized IgG1 repressed phosphorylation of PKCδ and resulted in foxa1 elevation. Finally, neonatal Fc receptor (FcRn) knock-down reversed the effect of recombinant humanized IgG1 on the expression of PKCδ phosphorylation, foxa1 and Aadac. Our findings suggest that recombinant humanized IgG1 plays an important role in maintaining liver TG homeostasis via the FcRn/PKCδ/foxa1/Aadac pathway.


PHEPS: web-based pH-dependent Protein Electrostatics Server.
PHEPS (pH-dependent Protein Electrostatics Server) is a web service for fast prediction and experiment planning support, as well as for correlation and analysis of experimentally obtained results, reflecting charge-dependent phenomena in globular proteins. Its implementation is based on long-term experience (PHEI package) and the need to explain measured physicochemical characteristics at the level of protein atomic structure. The approach is semi-empirical and based on a mean field scheme for description and evaluation of global and local pH-dependent electrostatic properties: protein proton binding; ionic sites proton population; free energy electrostatic term; ionic groups proton affinities (pK(a,i)) and their Coulomb interaction with whole charge multipole; electrostatic potential of whole molecule at fixed pH and pH-dependent local electrostatic potentials at user-defined set of points. The speed of calculation is based on fast determination of distance-dependent pair charge-charge interactions as empirical three exponential function that covers charge-charge, charge-dipole and dipole-dipole contributions. After atomic coordinates input, all standard parameters are used as defaults to facilitate non-experienced users. Special attention was given to interactive addition of non-polypeptide charges, extra ionizable groups with intrinsic pK(a)s or fixed ions. The output information is given as plain-text, readable by 'RasMol', 'Origin' and the like. The PHEPS server is accessible at http://pheps.orgchm.bas.bg/home.html.


Deterring the drinking driver: the Stockton experience.
The effectiveness of drunk driving enforcement patrols is generally assumed. However, few adequate evaluations are available in the traffic safety literature. The U.S. Department of Transportation funded a special program in Stockton, a city with a population of 120,000 in the central valley of California, to test the effectiveness of special drunk driving patrols on weekend evenings, applied within a setting in which no other major alcohol safety programs were present. The objective of this effort was to determine the effectiveness of a "traditional" approach to enforcing driving while impaired (DWI) laws; one in which innovative procedures such as sobriety checkpoints were not used. The results indicated that nighttime collisions in Stockton were reduced during the three and a half year period of the special enforcement program.


Lupus education for physicians and patients in a resource-limited setting.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a wide range of manifestations and potential to affect several organ systems. Complications arise from both disease and medications especially glucocorticoids, significantly contributing to overall morbidity and mortality. SLE predominantly affects patients during their prime productive years resulting in substantial economic burden on the patient, caregivers, and society due to direct, indirect, and intangible costs. This illness burden is compounded in developing countries with limited resources due to various disparities in healthcare delivery. Physician education and practical referral and endorsement guidelines adapted to the local setting reinforce continuity and coordinated care. Likewise, patient education, self-help programs, and shared decision-making are essential best practice in the clinics. Both physician education and patient education improve overall outcomes in chronic diseases like SLE. As a developing country with very few rheumatologists and/or lupus specialists, efficient healthcare delivery for most Filipino lupus patients remains elusive. We describe our experience in confronting these challenges through development of strategies which focus on physician and patient education. KEY POINTS: • Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a highly variable course, requiring specialized, individualized, and coordinated care by a healthcare team. • Health disparities and limited resources significantly contribute to illness burden on the patient, family, and society. • Physician education on SLE must commence at undergraduate medical school, be integrated in Internal Medicine and Pediatrics, and reinforced through specialized training in Rheumatology and related specialties. • Patient education and empowerment are integral to improving healthcare outcomes especially in a resource-limited setting.


In-situ food spoilage monitoring using a wireless chemical receptor-conjugated graphene electronic nose.
Monitoring food spoilage is one of the most effective methods for preventing food poisoning caused by biogenic amines or microbes. Therefore, various analytical techniques have been introduced to detect low concentrations of cadaverine (CV) and putrescine (PT), which are representative biogenic polyamines involved in food spoilage (5-8 ppm at the stage of initial decomposition after storage for 5 days at 5 °C and 17-186 ppm at the stage of advanced decomposition after storage for 7 days at 5 °C). Although previous methods showed selective CV and PT detection even at low concentrations, the use of these methods remains challenging in research areas that require in-situ, real-time, on-site monitoring. In this study, we demonstrated for the first time an in-situ high-performance chemical receptor-conjugated graphene electronic nose (CRGE-nose) whose limits of detection (LODs), 27.04 and 7.29 ppb, for CV and PT are up to 102 times more sensitive than those of conventional biogenic amine sensors. Specifically, the novel chemical receptors 2,7-bis(3-morpholinopropyl)benzo[lmn][3,8] phenanthroline-1,3,6,8(2H,7H)-tetraone (NaPhdiMor (NPM)) and 2,7-bis(2-((3-morpholinopropyl)amino)ethyl)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (NaPhdiEtAmMor (NPEAM)) were designed on the basis of density functional theory (DFT) calculations, and their interaction mechanism was characterized by a DFT 3D simulation. Interestingly, the CRGE-nose was connected on a micro sim chip substrate via wire bonding and then integrated into wireless portable devices, resulting in a cost-effective, high-performance prototype CRGE-nose device capable of on-site detection. The portable CRGE-nose can be used for in-situ monitoring of CV and PT concentration changes as low as 27.04 and 7.29 ppb in real meats such as pork, beef, lamb and chicken.


Efficacy and safety of glycopyrrolate/formoterol fumarate metered dose inhaler delivered using co-suspension delivery technology in Japanese patients with moderate-to-very severe chronic obstructive pulmonary disease.
PINNACLE-4 evaluated the efficacy and safety of the long-acting muscarinic antagonist/long-acting β2-agonist fixed-dose combination glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) in patients from Asia, Europe, and the USA with moderate-to-very severe chronic obstructive pulmonary disease (COPD). This pre-specified analysis included Japanese patients in PINNACLE-4. In this double-blind randomized study (NCT02343458), patients received GFF MDI (18/9.6 μg), glycopyrrolate (GP) MDI (18 μg), formoterol fumarate (FF) MDI (9.6 μg), or placebo MDI twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over Weeks 12-24. Secondary lung function endpoints, patient-reported outcomes, and safety were assessed. The Japanese subpopulation (n = 150) analyses were exploratory. GFF MDI improved change from baseline in morning pre-dose trough FEV1 over Weeks 12-24 versus GP MDI, FF MDI, and placebo MDI (least squares mean [LSM] differences [95% confidence interval]: 69 [8-131], 60 [-1 to 121], and 275 [180-370] mL, respectively). GFF MDI numerically improved Transition Dyspnea Index focal score and change from baseline in St George's Respiratory Questionnaire total score versus placebo MDI (LSM differences 0.19 and -3.78, respectively). Treatment-related adverse events occurred in ≤4.5% of patients in any treatment group. GFF MDI improved lung function versus monocomponents and placebo MDI in the Japan subpopulation of PINNACLE-4. The efficacy and safety results were generally consistent with those of the global study population, supporting the use of GFF MDI in Japanese patients with moderate-to-very severe COPD.


RNA interference targeting human FAK and EGFR suppresses human non-small-cell lung cancer xenograft growth in nude mice.
Transfection of plasmid vectors coexpressing short hairpin RNA (shRNA) for focal adhesion kinase (FAK) and epidermal growth factor receptor (EGFR) significantly inhibited protein level of FAK and EGFR. Knockdown of FAK and EGFR expression significantly inhibited cell proliferation and induced cell apoptosis of A549 lung cancer cells in vitro. In A549 subcutaneous xenograft model, mice treated for 3 weeks with plasmid that coexpresses FAK and EGFR shRNA had significantly smaller tumors than those in control mice (P < 0.01). FAK and EGFR dual silencing also significantly decreased microvessel density, tumor cell proliferation and increased the level of apoptosis in tumor cells. Moreover, administration with plasmid that coexpresses FAK and EGFR shRNA significantly inhibited the A549 experimental lung metastases. Collectively, our data suggest that the dual inhibition of FAK and EGFR by using plasmid vector-based RNA interference might be a novel therapeutic approach to the treatment of human NSCLC.


Exploring the benefits of double gloving during surgery.
Breaches in the glove barrier pose a risk for transmission of bloodborne pathogens during surgical procedures. Double gloving or double gloving with an indicator glove system may provide added protection. For this 24-month study, we used a comparative design to examine the effect of double gloving with inner indicator gloves on the durability of inner gloves and the detection of glove tears or perforations during surgery. The frequency of seeing blood on the hand after surgery was greater with single gloving than with double gloving, and the frequency of changing gloves during surgery was significantly higher among those who double gloved with an indicator glove system versus double gloving alone. The majority of health care providers in our study expressed favorable views about double gloving.


The Impact of Integrating Palliative Medicine Into COVID-19 Critical Care.
Ensuring high-quality patient-centered care for critically ill coronavirus disease 2019 (COVID-19) patients presents unprecedented challenges. Many patients become critically ill unexpectedly and have not previously discussed their health-care wishes. Clinicians lack experience with this illness and therefore struggle to predict patient outcomes. Critical care medicine (CCM) providers were surveyed about the effectiveness and efficiency of a pilot intervention. Proactive palliative care rounding with CCM providers on COVID-19 intensive care units. Fifty-four percent of CCM providers responded to the survey (21/39). CCM providers rated the intervention highly across all domains. CCM providers frequently identified that early palliative involvement was critical to providing families with information and support when separated from their loved ones. This pilot study found that proactive rounding improves critical care provider assessments of quality of care for patients and families and allows CCM providers to focus their efforts on managing complex physiology and surges.


Survey for potential soft tick (Acari: Argasidae) vectors of African swine fever on the island of Hispaniola.
A survey of the occurrence of Ornithodoros ticks in animal burrows was conducted in Haiti and the Dominican Republic. Vacuum sampling techniques were used. Four of 8 sample sites in Haiti and 10 of 70 sample sites in the Dominican Republic were positive for O. puertoricensis Fox. Positive sample sites in Haiti were usually near swine. Sites in the Dominican Republic were in drier regions of the country and were not directly associated with previous swine locations. The determination that O. puertoricensis, a potential vector and reservoir of African swine fever (ASF), is present in this region may pose a serious problem for eradication of ASF from the island of Hispaniola.


Apolipoprotein E epsilon 4 allele is associated with increased atrophy in progressive mild cognitive impairment: a voxel-based morphometric study.
The apolipoprotein E (APOE) epsilon4 allele is a risk factor for Alzheimer's disease. Earlier studies have shown differences in brain structure according to the APOE epsilon4 status. To assess possible differences in brain structure according to the APOE epsilon4 status in mild cognitive impairment (MCI) subjects in relation to conversion to dementia. In a follow-up study of 56 MCI subjects, 13 MCI subjects progressed to dementia (PMCI) during a mean follow-up time of 31 months. Brain structure differences in both stable MCI (SMCI) and PMCI epsilon4 carriers and noncarriers in the baseline MRI scan were assessed with voxel-based morphometry. The SMCI epsilon4 carriers had atrophy in the amygdala and hippocampus compared to the SMCI noncarriers. The PMCI epsilon4 carriers revealed atrophy of the left inferior frontal gyrus and parietal cortex compared to the PMCI noncarriers. The rate of brain atrophy in certain brain areas may be increased in epsilon4-positive MCI subjects progressing to dementia.


The human VK locus. Characterization of a duplicated region encoding 28 different immunoglobulin genes.
Two large regions of the human multigene family coding for the variable parts of the immunoglobulin light chains of the K type (VK) have been characterized on cosmid clones. The two germline regions, called Aa and Ab, span together 250,000 base-pairs and comprise 28 different VK gene segments, nine of which have been sequenced. There is a preponderance of VKII genes but genes belonging to subgroups I and III, and genes that cannot be easily assigned to one of the known subgroups, are interspersed within the VKII gene clusters. A number of pseudogenes have been identified. Within the Aa and Ab regions, all gene segments are organized in the same transcriptional orientation. The regions Aa and Ab, whose restriction maps are highly homologous, were shown not to be allelic structures; they must have arisen by a duplication event. Taken together with previous results, one can conclude that the major part of the VK locus exists in duplicated form. One individual has been found who has only one copy of some of the duplicated regions. By chromosomal walking, the A regions could be linked to the O regions, an analysis of which has been reported. The A regions contribute about one-third of the VK genes so far identified.


Degrading products of chondroitin sulfate can induce hypertrophy-like changes and MMP-13/ADAMTS5 production in chondrocytes.
Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in articular cartilage and the loss of CS-GAG occurs early in OA. As a major component of perichondral matrix interacting directly with chondrocytes, the active turnover of CS can affect to break the homeostasis of chondrocytes. Here we employ CS-based 3-dimensional (3D) hydrogel scaffold system to investigate how the degradation products of CS affect the catabolic phenotype of chondrocytes. The breakdown of CS-based ECM by the chondroitinase ABC (ChABC) resulted in a hypertrophy-like morphologic change in chondrocytes, which was accompanied by catabolic phenotypes, including increased MMP-13 and ADAMTS5 expression, nitric oxide (NO) production and oxidative stress. The inhibition of Toll-like receptor 2 (TLR2) or TLR4 with OxPAPC (TLR2 and TLR4 dual inhibitor) and LPS-RS (TLR4-MD2 inhibitor) ameliorated these catabolic phenotypes of chondrocytes by CS-ECM degradation, suggesting a role of CS breakdown products as damage-associated molecular patterns (DAMPs). As downstream signals of TLRs, MAP kinases, NF-kB, NO and STAT3-related signals were responsible for the catabolic phenotypes of chondrocytes associated with ECM degradation. NO in turn reinforced the activation of MAP kinases as well as NFkB signaling pathway. Thus, these results propose that the breakdown product of CS-GAG can recapitulate the catabolic phenotypes of OA.


Dermal γδ T cells--a new player in the pathogenesis of psoriasis.
Psoriasis is considered as a T-cell driven chronic inflammatory skin disease. Both T helper (Th) 1 and Th17 cells have been demonstrated to participate in psoriasis pathogenesis. Recently, a new subset of γδ T cells residing in the dermis has been identified. Dermal γδ T cells are the major source of interleukin (IL)-17 in the skin upon IL-23 stimulation. More importantly, they are also shown to be involved in psoriasis development. In this review, we focus on this newly discovered cell population both in mice and human, particularly discussing its role in the pathogenesis of psoriasis. The biologic therapeutics targeting dermal γδ T cell and its related molecules in the treatment of psoriasis are also included.


A new species of Leposternon Wagler, 1824 (Squamata, Amphisbaenia) from northeastern Argentina.
A new species of Leposternon is described from the Humid Chaco biome in Argentina. The species is known only from its type locality, at El Bagual Ecological Reserve, a conservation unit located in the province of Formosa. The new species can be distinguished from all its congeners by the presence of rostral processes in the maxillae and nasals that contact each other on the facial portion of the skull. Additionally, we present a key for the species of Leposternon.


RNF125 attenuates hepatocellular carcinoma progression by downregulating SRSF1-ERK pathway.
Hepatocellular carcinoma (HCC) is one of the most deadly malignant cancers worldwide. Research into the crucial genes responsible for maintaining the aggressive behaviour of cancer cells is important for the clinical treatment of HCC. The purpose of this study was to determine whether the E3 ubiquitin ligase Ring Finger Protein 125 (RNF125) plays a role in the proliferation and metastasis of HCC. RNF125 expression in human HCC samples and cell lines was investigated using TCGA dataset mining, qRT‒PCR, western blot, and immunohistochemistry assays. In addition, 80 patients with HCC were studied for the clinical value of RNF125. Furthermore, the molecular mechanism by which RNF125 contributes to hepatocellular carcinoma progression was determined with mass spectrometry (MS), coimmunoprecipitation (Co-IP), dual-luciferase reporter assays, and ubiquitin ladder assays. We found that RNF125 was markedly downregulated in HCC tumour tissues, which was associated with a poor prognosis for patients with HCC. Moreover, the overexpression of RNF125 inhibited HCC proliferation and metastasis both in vitro and in vivo, whereas the knockdown of RNF125 exerted antithetical effects. Mechanistically, mass spectrometry analysis revealed a protein interaction between RNF125 and SRSF1, and RNF125 accelerated the proteasome-mediated degradation of SRSF1, which impeded HCC progression by inhibiting the ERK signalling pathway. Furthermore, RNF125 was detected to be the downstream target of miR-103a-3p. In this study, we identified that RNF125 is a tumour suppressor in HCC and inhibits HCC progression by inhibiting the SRSF1/ERK pathway. These findings provide a promising treatment target for HCC.


Philadelphia chromosome positive B-cell type malignant lymphoma expressing an aberrant 190 kDa bcr-abl protein.
The Philadelphia (Ph) chromosome translocation, t(9:22) (q34;q11) is found in some acute lymphoid leukaemias (ALL) and acute myeloid leukaemias (AML). Although cytogenetically all pH chromosomes appear similar, the 22q11 breakpoints found in acute leukaemias are of two kinds, those within the major breakpoint cluster region (Mbcr-1) of the BCR gene as found in chronic myelogenous leukaemia (CML), and those within the first intron of this gene. In the former group the molecular events are the same as those found in CML, p210 bcr-abl, encoded by 8.5 kb mRNA; however, a new aberrant protein, p190 bcr-abl, is found in the latter group. Ph translocation is also found in a few cases with malignant lymphoma, but it has not been characterized at the molecular level. We describe here a non-Hodgkin's lymphoma case with primary splenic presentation, which showed a complex Ph translocation. Neoplastic cells were of a B-cell origin (HLA-DR+, sIgM+, sIg lambda +, CALLA-). Molecular studies revealed the expression of p190 bcr-abl with no Mbcr-1 rearrangement. Our case indicates that the same Ph translocation as seen in acute leukaemias can be found in haematologic disorders other than leukaemias, suggesting that a c-abl gene activating mechanism may be involved in the pathogenesis of wide spectrum of haematologic malignancies.


Genomics of berry fruits antioxidant components.
Reactive oxygen and nitrogen metabolites, which are side products of cell metabolism, can produce a lot of damage in biological macromolecules and tissues, producing a number of chronic illnesses. On the other hand, antioxidant metabolites usually accumulated in fruits and vegetables can provide an effective protection by neutralizing these reactive molecules. Among comestible vegetables, berry fruits are considered one of the richest sources of antioxidant metabolites; hence, they represent a good model for molecular and biochemical investigations about the biosynthesis and the functional role of antioxidants in plants. This review illustrates how recent developments in the fields of genomics and bioinformatics can provide powerful tools to better understand the molecular mechanisms that trigger biosynthesis and accumulation of antioxidant metabolites in berries.


Terahertz Dipole Nanoantenna Arrays: Resonance Characteristics.
Resonant dipole nanoantennas promise to considerably improve the capabilities of terahertz spectroscopy, offering the possibility of increasing its sensitivity through local field enhancement, while in principle allowing unprecedented spatial resolutions, well below the diffraction limit. Here, we investigate the resonance properties of ordered arrays of terahertz dipole nanoantennas, both experimentally and through numerical simulations. We demonstrate the tunability of this type of structures, in a range (∼1-2 THz) that is particularly interesting and accessible by means of standard zinc telluride sources. We additionally study the near-field resonance properties of the arrays, finding that the resonance shift observed between near-field and far-field spectra is predominantly ascribable to ohmic damping.


Microarray Expression Analysis for the Paradoxical Roles of Acanthopanax senticosus Harms in Treating α-Synucleinopathies.
α-Synuclein is a key player in the pathogenesis of neurodegenerative disorders with Lewy bodies. Our previous studies have also showed that Acanthopanax senticosus harms (AS) could significantly suppress α-synuclein overexpression and toxicity. Identifying the RNAs related to α-synucleinopathies may facilitate understanding the pathogenesis of the diseases and the safe application of AS in the clinic. Microarray expression profiling of long non-coding RNAs (lncRNAs) and mRNAs was undertaken in control non-transgenic and human α-synuclein transgenic mice. The effects of AS on central nervous system (CNS) in pathology and physiology were investigated based on the lncRNA/mRNA targets analysis. In total, 341 lncRNAs and 279 mRNAs were differentially expressed by α-synuclein stimulus, among which 29 lncRNAs and 25 mRNAs were involved in the anti-α-synucleinopathies mechanism of AS. However, the levels of 19/29 lncRNAs and 12/25 mRNAs in AS group were similar to those in α-synuclein group, which may cause potential neurotoxicity analogous to α-synuclein. This study demonstrated that some of lncRNAs/mRNAs were involved in α-synuclein related pathophysiology, and AS produced the bidirectional effects on CNS under pathological and physiological conditions.


Ni-citric acid coordination polymer as a practical catalyst for multicomponent reactions.
Coordinative polymers (CP) are a subclass of Metal-organic frameworks (MOFs) with porous microstructures which have been widely synthesized in recent years and applied in various fields especially in catalysis science. In this work Coordinative polymers (CP) of nickel and citric acid (CA) was prepared as a new catalyst (Ni-CP) and applied in organic multicomponent reactions. The obtained catalyst was characterized by SEM, WDX, EDS, AAS, FT-IR, XRD and BET analysis. N2 adsorption-desorption isotherms indicate good BET surface area for Ni-CP; therefore can be employed as an efficient catalyst in multicomponent reactions for the synthesis of polyhydroquinoline and 2,3-dihydroquinazolin-4(1H)-one derivatives. Finally, this catalyst was recovered and reused several consecutive times.


Pd-catalyzed π-chelation assisted ortho-C-H activation and annulation of allylarenes with internal alkynes.
The synthesis of highly substituted naphthalenes from allylarenes and alkynes is described. This reaction proceeds via π-coordination of an allylic carbon-carbon double bond to the Pd(II) center and is followed by ortho selective C-H bond activation.


Inhibitory effect of bromazepam on insulin-stimulated gastric acid secretion in man.
The action of bromazepam on insulin-stimulated gastric acid secretion was examined in 5 healthy volunteers in a randomized study. To measure acid output, the intragastric titration technique and a pH-sensitive telemetering capsule were used. Three series of experiments were performed: (1) insulin (0.2 U/kg body weight), stimulation alone; (2) simultaneous injection of insulin and bromazepam (0.1 mg/kg body weight), subjects kept awake; (3) synchronous injection of insulin and bromazepam but with subjects allowed to fall asleep after drug administration. In all three series after insulin administration a significant initial inhibition of gastric secretion occurred. There were no significant differences between the three series regarding the intensity of hypoglycemia. Blood glucose levels lower than 25 mg/100 ml were reached in all experiments. Bromazepam in subjects kept awake caused drowsiness and a lower gastric acid response to hypoglycemia as compared to insulin alone, but the difference was not significant. In subjects allowed to sleep, this reduction was marked and gastric acid output was significantly lower than in both other series. These findings suggest that sleep and drowsiness, rather than bromazepam itself, cause inhibition of insulin-induced gastric secretion.


Differentiation of human T cells.
This article discusses the ontogeny of human T cells along with the relationship of normal T-cell maturation to the development of various malignant T-cell syndromes. The impact of monoclonal antibody technology, the discovery of the T-cell receptor for antigen, and the discovery of mechanisms of thymocyte-thymic microenvironment interactions on the analysis of human T-cell development are emphasized.


Reprogramming the rapid clearance of thrombolytics by nanoparticle encapsulation and anchoring to circulating red blood cells.
Rapid clearance of thrombolytics from blood following intravenous injection is a major clinical challenge in cardiovascular medicine. To overcome this barrier, nanoparticle (NP) based drug delivery systems have been reported. Although superior than conventional therapy, a large proportion of the injected NP is still cleared by the reticuloendothelial system. Previously, we and others showed that ex vivo attachment of bioscavengers, thrombolytics, and nanoparticles (NPs) to glycophorin A receptors on red blood cells (RBCs) improved the blood half-life. This is promising, but ex-vivo approaches are cumbersome and challenging to translate clinically. Here, we developed a novel Ter119-polymeric NP containing tissue plasminogen activator for on-demand targeting of GPA receptors in vivo. Upon intravenous injection, the Ter119-NPs achieved remarkable RBC labeling efficiencies (>95%), resulting in marked enhancement of blood residence time of tPA from minutes to several days without any morphological, hematological, and histological complications. Our approach of RBC labeling with the NPs also prevented reticuloendothelial detections and the activations of innate and adaptive immune system. Data suggest that real-time targeting of therapeutics to RBC with NPs can potentially improve outcomes and reduce complications against a variety chronic disease.


Sample Errors Call Into Question Conclusions Regarding Same-Sex Married Parents: A Comment on "Family Structure and Child Health: Does the Sex Composition of Parents Matter?"
Because of classification errors reported by the National Center for Health Statistics, an estimated 42 % of the same-sex married partners in the sample for this study are misclassified different-sex married partners, thus calling into question findings regarding same-sex married parents. Including biological parentage as a control variable suppresses same-sex/different-sex differences, thus obscuring the data error. Parentage is not appropriate as a control because it correlates nearly perfectly (+.97, gamma) with the same-sex/different-sex distinction and is invariant for the category of joint biological parents.


The polarity histogram in relation to the average evoked potential.
It is shown analytically that the polarity histogram (PH) and the average evoked potential (AEP) are linearly related under certain conditions. The relative merits of the two approaches are compared both analytically and by statistical simulation. In general, the PH is a biased estimator of the evoked potential and is less efficient than the AEP, which is unbiased. The PH is more robust against artifact, but this advantage vanishes when conventional artifact rejection is used. The detection of an EP using the PH is problematic. The polarity histogram offers little advantage over signal averaging under typical clinical recording conditions.


Cushing's syndrome secondary to adrenal adenoma during pregnancy.
Cushing's syndrome during pregnancy is rare because of the suppressive effect of excessive glucocorticoid on the female reproductive system. Adrenal adenoma is the most common cause of Cushing's syndrome during pregnancy. Surgical treatment by unilateral adrenalectomy was preferred during pregnancy before the advent of laparoscopic adrenalectomy. We describe two patients with Cushing's syndrome secondary to adrenal adenoma diagnosed during the first and second trimester, respectively, and successfully managed by different approaches of laparoscopic adrenalectomy--one patient upon diagnosis and one after pregnancy.


Defective heparan sulfate metabolism in the Sanfilippo syndrome and assay of this defect in the assessment of the mucopolysaccharidoses patient.
The Sanifilippo syndrome is an inherited dementia caused by defective degradation of heparan sulfate. In the course of its catabolism the heparan sulfate polymer must be desulfated. Heparan sulfate sulfatase activity was demonstrated in homogenates of normal tissues and cultured skin fibroblasts, and in normal urine. This activity was found to be grossly depressed or absent in necropsy specimens of liver and spleen from two Sanfilippo patients. The heparan sulfate sulfatase activity was not demonstrable in urine from eleven, or cultured fibroblasts from four Sanfilippo patients. Activities of alpha-N-acetyl-glucosaminidase, the site of the metabolic defect in the Sanfilippo B variant were either normal or slightly elevated in the Sanfilippo tissues and cultured fibroblasts whereas the mean level in the urine of our Sanfilippo patients was about one-third of that encountered in control urines.


Neuroprotective effects of nerolidol against Alzheimer's disease in Wistar rats.
Alzheimer's disease (AD) is the most common type of cognitive disorder in an elderly population associated with the accumulation of amyloid plaques and neurofibrillary tangles. Nerolidol is assumed to have neuroprotection effects. This study aimed to investigate the therapeutic effects of nerolidol on the Aβ-induced model of AD in rats. Hippocampal injection of Aβ was used to induce AD. Animals were randomly divided into control, sham (received PBS as Aβ solvent), AD, DNPZ (AD + donepezil, 4 weeks); NRD-50 (AD + nerolidol, 50 mg/kg, 4 weeks), NRD-100 (AD + nerolidol, 100 mg/kg, 4 weeks; Prot (rats which received 100 mg/kg nerolidol for two weeks before Aβ administration), and Solv (AD + sunflower oil as nerolidol solvent, 4 weeks) groups. All rats were subjected to a memory behavioral passive avoidance test by shuttle box. Thioflavin-S staining was performed to confirm Aβ plaque formation and measured using ImageJ analyzing program. BDNF and CREB-1 expressions were analyzed by immunohistochemistry assay. Aβ induced AD by Aβ plaques formation and increasing step-through latency time. It reduced the expression of BDNF and CREB-1 protein. Administration of nerolidol or donepezil improved these features by decreasing Aβ and increasing BDNF and CREB-1 expression and latency time. Nerolidol is likely to provide protection against AD. It may prevent dementia through the mediation of BDNF-CREB-1 expression and cholinergic nerve cells restoring. It seems that the administration of nerolidol before the onset of the disease will be more effective than after.


Traumatic myiasis from Sarcophaga (Bercaeal cruentata Meigen, 1826 (Diptera, Sarcophagidae) in a hospital environment: reporting of a clinical case following polytrauma.
We present a case of cutaneous myiasis occurring in a hospital environment (nosocomial myiasis) in an patient with serious multiple traumas sustained in a motorcycle accident. The agent responsible for the myiasis was identified as Sarcophaga cruentata (Meigen 1826). The larvae found in the necrotic wound were removed and the necessary environmental measures were taken to avoid further infestation. Although nonocomial myiasis is a form of parasitosis already cited in the in literature, it is a rare event and worthy of attention to aid in identifying parasitosis in hospitalized subjects in order to expedite proper diagnosis and treatment.


Genetic variations in genes of metabolic enzymes predict postoperational prognosis of patients with colorectal cancer.
Genetic alterations in tricarboxylic acid (TCA) cycle metabolic enzymes were recently linked to various cancers. However, the associations of single nucleotide polymorphisms (SNPs) in genes of these enzymes have not been well studied. We genotyped 16 SNPs from 7 genes encoding TCA cycle metabolic enzymes in 697 colorectal carcinoma (CRC) patients receiving surgical resection and analyzed their associations with clinical outcomes by multivariate Cox proportional hazard model. Then, the significant results were validated in another cohort of 256 CRC patients. We identified 4 SNPs in 2 genes had significant associations with CRC death risk and 5 SNPs in 3 genes had significant associations with CRC recurrence risk. Similar significant results were confirmed for rs4131826 in SDHC gene, rs544184 in SDHD gene and rs12071124 in FH gene in a validation cohort. Further analysis indicated that unfavorable genotypes exhibited a significant cumulative effect on overall and recurrence-free survival in a dose-dependent manner. Moreover, survival tree analysis indicated that SNP rs4131826 in SDHC gene and SNP rs12071124 in FH gene were the primary factors contributing to the different overall survival time and recurrence-free survival time of CRC patients, respectively. Immunohistochemical analysis further validated the effect of rs4131826 and rs544184 on expression of SDHC and SDHD in tissue samples. Our study suggests that SNPs in TCA cycle metabolic enzymes might be significantly associated with clinical outcomes in Chinese population diagnosed with CRC. Further functional and validated studies are warranted to expend our results to clinical utility.


Critical role of Nrf2 in oxidative stress-induced retinal ganglion cell death.
NF-E2 related factor 2 (Nrf2) is a key transcription factor that plays a pivotal role in endogenous protection against oxidative stress. However, the role of Nrf2 in visual disorders remains unclear. It has been reported that oxidative stress is thought of as one of the causes of glaucoma. Here, we investigate whether the function of Nrf2 in oxidative stress-induced retinal ganglion cell (RGC) death. This study used adult male Nrf2 deficient mice (Nrf2 KO) and age- and sex-matched wild-type (WT) mice. We dissociated and purified N-4-[4-didecylaminostryryl]-N-methyl-pyridinium iodide-labeled RGCs with fluorescence-activated cell sorting, and tried to detect the Nrf2 and Keap1 genes. In the absence of nerve crush (NC), the number of RGCs in Nrf2 KO mice was almost same as that in WT mice. 1-(2-cyano-3-, 12-dioxooleana-1, 9 (11)-dien-28-oyl) imidazole (CDDO-Im), an Nrf2 activator, prevented NC-induced loss of RGCs in WT mice. Seven days after NC, without treatment, the number of RGCs in Nrf2 KO mice was significantly lower than in WT mice. In addition, after CDDO-Im treatment, quantitative RT-PCR showed increased expression of antioxidant and phase II detoxifying enzymes. These results suggest that up-regulation of Nrf2 signaling after CDDO-Im treatment may be a novel therapeutic strategy for the protection of RGCs, especially in glaucoma. This study suggests that NF-E2 related factor 2 (Nrf2), a transcription factor, plays a pivotal role in counteracting oxidative stress. Most importantly, a neuroprotective effect against oxidative stress-induced retinal ganglion cell (RGC) death was achieved with the pharmacological Nrf2 activator CDDO-Im. This suggests that pharmacological treatment to up-regulate Nrf2 signaling may be a new therapeutic technique to protect RGCs.


Testicular salvage and age-related delay in the presentation of testicular torsion.
Testicular torsion represents a continuing source of morbidity among male patients. Early diagnosis and surgical exploration improve testis salvage but even this approach will result in orchiectomy if there is excessive delay in patient presentation. A 10-year retrospective review of testicular torsion was performed. The interval between onset of scrotal pain and presentation to the emergency department was determined. A specific age-related delay in presentation was identified between patients less than 18 years old (group 1, median delay 20 hours) and those greater than 18 years old (group 2, median delay 4 hours, p less than 0.001). At exploration 44 per cent of the group 1 patients required orchiectomy versus 8 per cent in group 2. Patients less than 18 years old are a high risk group for testicular loss after torsion and represent more than 90 per cent of the orchiectomies performed. We believe that this group should be targeted for improved health education, emphasizing early evaluation of scrotal pain to improve testicular salvage.


Self-expanding intestinal expansion sleeves (IES) for short gut syndrome.
Many disease processes (necrotizing enterocolitis, caustic esophageal injury, malrotation with volvulus), can result in short-gut syndrome (SGS), where remnant intestinal segments may dilate axially, but rarely elongate longitudinally. Here we mechanically characterize a novel model of a self-expanding mesh prototype intestinal expanding sleeve (IES) for use in SGS. Gut lengthening was achieved using a proprietary cylindrical layered polyethylene terephthalate IES device with helicoid trusses with isometric ends. The IES is pre-contracted by diametric expansion, deployed into the gut and anchored with bioabsorbable sutures. IES expansion to its equilibrium dimension maintained longitudinal gut tension, which may permit remodeling, increased absorptive surface area while preserving vascular and nervous supplies. We performed mechanical testing to obtain the effective force-displacement characterization achieved on these prototypes and evaluated minimal numbers of sutures needed for its anchoring. Furthermore, we deployed these devices in small and large intestines of New Zealand White rabbits, measured IES length-tension relationships and measured post-implant gut expansion ex vivo. Histology of the gut before and after implantation was also evaluated. Longitudinal tension using IES did not result in suture failure. Maximum IES suture mechanical loading was tested using 4-6 sutures; we found similar failure loads of 2.95 ± 0.64, 4 ± 1.9 and 3.16 ± 0.24 Newtons for 4, 6 and 8 sutures, respectively (n = 3, n.s). Pre-contracted IES tubes were deployed at 67 ± 4% of initial length (i.l.); in the large bowel these expanded significantly to 81.5 ± 3.7% of i.l. (p = 0.014, n = 4). In the small bowel, pre-contracted IES were 61 ± 3.8% of i.l.; these expanded significantly to 82.7 ± 7.4% of i.l. (p = 0.0009, n = 6). This resulted in an immediate 24 ± 7.8% and 36.2 ± 11% increase in gut length when deployed in large and small bowels, respectively, with maintained longitudinal tension. Maintained IES induced tension produced gut wall thinning; gut histopathological evaluation is currently under evaluation. IES is a versatile platform for gaining length in SGS, which may be simply deployed via feeding tubes. Our results need further validation for biocompatibility and mechanical characterization to optimize use in gut expansion.


Short tryptophan- and arginine-rich peptide shows efficacy against clinical methicillin-resistant Staphylococcus aureus strains isolated from skin and soft tissue infections.
In recent years methicillin-resistant Staphylococcus aureus has posed a challenge in treating skin and soft tissue infections. Finding new antimicrobial agents has therefore become imperative. We evaluated the in vitro antimicrobial activity of a synthetic peptide, P6, against multidrug resistant clinical strains of Staphylococcus aureus isolated from skin and soft tissue infections. The P6 antimicrobial effect was evaluated in vitro by determining MIC/MBC, the ratio of live/dead cells and the effects induced at membrane level. The therapeutic efficiency was determined against human skin cells. P6 inhibited growth for all strains between 8 and 16 mg/L and killed all bacterial strains at 16 mg/L. The therapeutic potential was found to be 30 and 15 in the presence of BSA. We showed that P6 localizes at membrane level, where it acts slowly, by depolarizing it and affecting its integrity. P6 can be considered a good candidate for use as an antimicrobial agent in topical applications.


RNA concentration and protein synthesis in rat brain during development.
As a first approximation of ribosomal concentration we have measured total RNA in some regions of the CNS at different ages and found that the rates of protein synthesis therein are directly proportional to the RNA content. This suggests that the 'RNA activity' remains unchanged during growth and that higher protein synthesis rates in young brain are due to higher content of ribosomal material.


Oral itraconazole for epistaxis in hereditary hemorrhagic telangiectasia: a proof of concept study.
The inhibiting effects of itraconazole, an antifungal drug on vascular endothelial growth factor (VEGF) have recently been discovered. By inhibiting VEGF, itraconazole has shown potential in clinical trials as anti-cancer treatment. In hereditary hemorrhagic telangiectasia (HHT) patients, VEGF levels are elevated and inhibition of VEGF can decrease bleeding. Itraconazole could potentially serve as anti-angiogenic therapy for HHT-related bleeding. We report a proof of concept study with HHT patients and severe epistaxis. Patients were treated with daily 200 mg orally administered itraconazole for sixteen weeks. Twenty-one HHT patients, 8 females (38%), 13 males (62%), median age of 59 years (interquartile range (IQR) 55-69) were enrolled. Of these patients, 13 (62%) were diagnosed with HHT type 1, seven (33%) with HHT type 2 and in one patient (5%), no pathognomonic HHT mutation was found. Four patients (19%) prematurely terminated the study (3 due to mild or moderate side-effects) resulting in 17 patients included in the analyses. The median epistaxis severity score significantly decreased during treatment from 6.0 (IQR 5.1-7.2) to 3.8 (IQR 3.1-5.2) (p = 0.006). The monthly epistaxis frequency decreased from 56 to 38 epistaxis episodes (p = 0.004) and the monthly duration from 407 to 278 minutes (p = 0.005). Hemoglobin levels did not significantly change. The quality of life showed a small but significant improvement. In conclusion, oral itraconazole significantly improved epistaxis in HHT patients. The potential benefit of itraconazole in HHT should be further investigated.


The dysgonic strain of Microsporum canis.
The dysgonic strain of Microsporum canis is described. The colony consists of fascicles of very wide hyphae with short compartments and close branching. Lateral branches often themselves remain short and fail to branch, and many are reflexive, growing in the opposite direction to the parent hypha. Mycelium of three types was noted, dysgonic, apparently normal, and forms intermediate between the two. Change from one form to another occurred in a cyclial manner, the transition from dysgonic to apparently normal being abrupt while that in the reverse direction was gradual. The strain was extremely unstable, both in primary isolations from cats and in subculture. Numerous sectors of other readily recognisable strains were produced, including the typical M. canis and various atypical strains previously obtained from human sources. These strains rapidly submerged their parent colonies and were much more likely to be obtained by subculture from a primary isolation plate than was the dysgonic strain itself. The relationships of the various strains to each other in the saprophytic and parasitic phases are discussed.


Detection of autoantibodies against NMDA-type glutamate receptor in a patient with recurrent optic neuritis and transient cerebral lesions.
We describe the case of a Japanese girl with recurrent optic neuritis and transient cerebral lesions. Antibodies against N-methyl-d-aspartate (NMDA)-type glutamate receptors were detected in both serum and cerebrospinal fluid. Results of this case study suggest that the development of autoantibodies against NMDA-type glutamate receptors may play a role in the pathogenesis of central nervous system demyelinating diseases.


Uncovering the biofumigant capacity of allyl isothiocyanate from several Brassicaceae crops against Fusarium pathogens in maize.
Driven by environmental concerns, chemical fumigants are no longer allowed in many countries. Therefore, other strategies for reducing fungal inoculum in soils and on crop debris are being explored. In the present study, several Brassicaceae crops were screened for their potential to control Fusarium gramineaum and Fusarium poae mycelial growth in an in vitro inverted Petri dish experiment. Volatile production was measured using gas chromatography-mass spectrometry headspace analysis. A selection of cultivars from each crop species was further investigated using a pot experiment with maize. Ethiopian mustard (Brassica carinata) and brown mustard (Brassica juncea) released volatile allyl isothiocyanate (AITC) and a higher concentration of AITC was correlated with a better fungal growth reduction in the in vitro screening. Brown mustard cultivar Etamine completely inhibited growth of both Fusarium spp. Pure AITC in a solution with methanol resulted in a sigmoid dose-response curve for both Fusarium spp. tested. Fusarium poae appeared to be more tolerant to AITC than F. graminearum. A pot experiment revealed that the incorporation of brown mustard plant material could alleviate the clear negative effect of F. graminearum infection on maize growth. The present study demonstrated the correlation between the fungistatic effect of biofumigation crops on Fusarium spp. and their production of volatile AITC in vitro, without the addition of exogenous enzymes, and confirmed the biofumigation potential of brown mustard in a pot experiment with maize. These results may help farmers when selecting a green manure crop suitable for biofumigation. © 2020 Society of Chemical Industry.


A novel induced-fit reaction mechanism of asymmetric hot dog thioesterase PAAI.
Hot dog fold proteins sharing the characteristic "hot dog" fold are known to involve certain coenzyme A binding enzymes with various oligomeric states. In order to elucidate the oligomerization-function relationship of the hot dog fold proteins, crystal structures of the phenylacetate degradation protein PaaI from Thermus thermophilus HB8 (TtPaaI), a tetrameric acyl-CoA thioesterase with the hot dog fold, have been determined and compared with those of other family members. In the liganded crystal forms with coenzyme A derivatives, only two of four intersubunit catalytic pockets of the TtPaaI tetramer are occupied by the ligands. A detailed structural comparison between several liganded and unliganded forms reveals that a subtle rigid-body rearrangement of subunits within 2 degrees upon binding of the first two ligand molecules can induce a strict negative cooperativity to prevent further binding at the remaining two pockets, indicating that the so-called "half-of-the-sites reactivity" of oligomeric enzymes is visualized for the first time. Considering kinetic and mutational analyses together, a possible reaction mechanism of TtPaaI is proposed; one tetramer binds only two acyl-CoA molecules with a novel asymmetric induced-fit mechanism and carries out the hydrolysis according to a base-catalyzed reaction through activation of a water molecule by Asp48. From a structural comparison with other family members, it is concluded that a subgroup of the hot dog fold protein family, referred to as "asymmetric hot dog thioesterases" including medium chain acyl-CoA thioesterase II from Escherichia coli and human thioesterase III, might share the same oligomerization mode and the asymmetric induced-fit mechanism as observed in TtPaaI.


Perceived tutor benefits of teaching near peers: insights from two near peer teaching programmes in South East Scotland.
There is little evidence about the benefits to junior doctors of participating in teaching, or how to train doctors as teachers. We explore (through South East Scotland based teaching programmes): (a) How prepared do junior doctors feel to teach? (b) What junior doctors consider to be the main challenges of teaching? (c) What motivates the junior doctors to continue teaching, and what is the perceived impact of teaching on their professional development? 'Questionnaire 1', distributed at 'tutor training days', explored (i) attitudes towards teaching and (ii) tutors' preparedness to teach. 'Questionnaire 2', distributed after completion of a teaching programme, evaluated the tutor experience of teaching. Seventy-six per cent of tutors reported no previous teacher training; 10% were able to teach during allocated work hours. The strongest motivation for teaching was to help students with their learning and to develop teaching skills. Ninety one per cent of tutors felt more prepared to teach by the end of the programme. Tutors also improved their clinical skills from teaching. There is a body of junior doctors, who see teaching as an important part of their career, developing both teaching and clinical skills in the tutor. If teaching is expected of foundation doctors, rotas ought to be more flexible to facilitate both teaching and teacher training.


Aortic runoff as a sign of intracranial arteriovenous malformation: report of two cases.
Intracranial arteriovenous malformation rarely causes pulmonary hypertension and congestive heart failure in the newborn. Its diagnosis is challenging because cardiomegaly may suggest an intra-cardiac structural lesion. We present two newborns, one 2-day-old male and the other 11-day-old female, with intracranial arteriovenous malformation and misdiagnosis of congenital heart disease. Precise echocardiography revealed the secondary signs of cranial arteriovenous malformation and had the major role in early diagnosis.


A Qualitative Study on the Barriers to Learning in a Primary Care-Behavioral Health Integration Program in an Academic Hospital: the Family Medicine Perspective.
Integrating behavioral health services into the primary care setting is a recognized approach to improving timely access and building capacity for primary care providers. The aim of this study was to examine barriers to family medicine resident learning in a co-located primary care-behavioral health integration program with psychiatrists in an academic hospital. The authors used a descriptive qualitative study design to collect data on participants' learning experiences from focus groups and semi-structured interviews with 5 family medicine residents, 3 psychiatry residents, 5 family physicians, 3 psychiatrists, 2 office coordinators, and 2 educational coordinators. Thematic analysis of transcripts was performed. Three themes were identified with respect to barriers to learning in the program from the family medicine perspective. Organizational barriers encompassed lack of clear vision, goals, roles, and responsibilities. Administrative barriers involved complex appointment bookings and scheduling. Communication and engagement barriers included insufficient communication between team members and lack of patient engagement in the program. The study findings highlight the importance of several factors for the successful implementation of a co-located academic primary care-behavioral health integrated model. This includes the formalization of program structure that encompasses shared vision, goals, roles, and responsibilities; coordinated processes for appointment bookings; team communication and patient engagement; and diverse educational and longitudinal care opportunities. With the growing number of integrated care programs, these results provide guidance for health care leaders involved in the design and management of primary care-behavioral health integration programs.


Nature and nurture in Foxp3(+) regulatory T cell development, stability, and function.
Foxp3(+) regulatory T lymphocytes (Treg) are critical homeostatic regulators of immune and inflammatory responses. Their absence leads to fulminant multiorgan autoimmunity. This review explores recent studies that have altered our emerging view of the development, stability, and plasticity of these cells. Treg appear not to be a single entity, but a family of immunomodulatory cell types with shared capabilities. On a first level, Treg may alternatively form in response to developmental cues in the thymus as a distinct lineage of CD4(+) T cells or adaptively, in response to environmental cues received by mature conventional CD4(+) T lymphocytes. These 2 populations bear distinct specificity, stability, and genetic profiles and are differentially used in immune responses. Secondarily, in a manner analogous to the generation of T helper (Th)-1, Th2, and other T cell subsets, Treg may further specialize, adapting to the needs of their immunologic surroundings. Treg therefore comprise developmentally distinct, functionally overlapping cell populations that are uniquely designed to preserve immunologic homeostasis. They combine an impressive degree of both stability and adaptability.


Generation of Pmel-dependent conditional and inducible Cre-driver mouse line for melanocytic-targeted gene manipulation.
Conditional and inducible gene targeting using Cre/loxP-mediated recombination is a powerful reverse genetics approach used to study spatiotemporal gene functions in specified cell types. To enable temporal gene manipulation in the melanocyte lineage, we established a novel inducible Cre-driver mouse line by targeting an all-in-one tetracycline/doxycycline (Dox)-inducible Cre expression cassette into the Pmel locus (PmelP2A-TetON3G-TRE3G-iCre ), a gene locus preferentially expressed in pigment cells. By crossing these Cre-driver mice with a strong Cre-reporter mouse line, Gt(ROSA)26Sortm9(CAG-tdTomato)Hze , we show the effectiveness of the PmelP2A-TetON3G-TRE3G-iCre mouse line in facilitating Dox-inducible Cre/loxP recombination in a wide variety of pigment cell lineages including hair follicle melanocytes and their stem cells. Furthermore, to demonstrate proof of concept, we ablated Notch signaling postnatally in the PmelP2A-TetON3G-TRE3G-iCre mice. In agreement with the previously reported phenotype, induced ablation of Notch signaling in the melanocyte lineage resulted in premature hair graying, demonstrating the utility of the PmelP2A-TetON3G-TRE3G-iCre allele. Therefore, the PmelP2A-TetON3G-TRE3G-iCre mouse line is suitable for assessing gene functions in melanocytes using an in vivo inducible reverse genetics approach. Furthermore, we unexpectedly identified previously unrecognized PMEL-expressing cells in non-pigmentary organs in the mice, suggesting unanticipated functions of PMEL other than melanosome formation.


Adequate magnesium level as an associated factor of pre-diabetes and diabetes mellitus remission in patients with obesity submitted to bariatric surgery.
Bariatric surgery (BS) can lead to remission of type 2 diabetes mellitus (T2DM), however, the evidence on the influence of preoperative serum magnesium levels on this reversal is scarce. To study the influence of preoperative serum magnesium levels on the pre-T2DM and T2DM remission one year after BS. Retrospective study carried out among 1656 patients with obesity who underwent BS in the Centro Hospitalar Universitário São João. T2DM and pre-T2DM remission were defined as being normal glycaemic measures of at least one year's after BS and without pharmacological therapy. To assess the association between preoperative serum magnesium levels and pre- and T2DM remission, logistic regression models, crude and adjusted for sex, age and body mass index were computed. Patients with normoglycaemia presented hypomagnesaemia less often than those patients with pre-T2DM and T2DM (17.0% vs. 21.3% vs. 39.9%) (p < 0.001). One year after BS, 62.9% of patients with pre-T2DM or T2DM before BS showed remission. Adequate magnesium levels were positively associated with T2DM and pre-T2DM remission, one year after BS (OR 1.79; 95% CI 1.34-2.38), independently of sex, age, and body mass index. Adequate preoperative serum magnesium levels showed to be an important clinical parameter for pre-T2DM and T2DM remission.


Muscular co-contraction during walking and landing from a jump: comparison between genders and influence of activity level.
Women have higher rates of knee ligament injury than men. Co-contraction of knee muscles is proposed to be an important mechanism to protect the joint from injuries. Females have lower co-contraction levels when compared to males. Exploratory, cross-sectional design. Thirty-six men and women equally divided into four groups according to gender and activity level (sedentary and athletic) were compared in relation to vastus lateralis and biceps femoris co-contraction before heel strike during level walking and before floor contact during landing from a jump. Muscular co-contraction was assessed by surface electromyography. Correlations between co-contraction and ligament laxity, extensor and flexor work, and flexion/extension torque ratio were also analyzed. No differences between genders were found in the studied situations (p0.381). During walking, co-contraction was greater in sedentary women compared to athletic women (p=0.002). A moderate inverse correlation was found between co-contraction during walking and women extensor (r=-0.613; p=0.007) and flexor (r=-0.575; p=0.012) work. During landing from a jump, no variables correlated to co-contraction in any of the groups tested (r0.477; p0.061). Co-contraction levels were not different between genders. Results suggest that women compensate strength deficits by means of increasing activation levels, possibly to generate adequate joint stiffness to meet stabilization demands. However, this is not evident in a more stressful activity like landing from a jump. This study contributes to a better understanding of the factors related to joint protection in females, who are at a greater risk of ligament injuries.


Periodontal and microbiologic evaluation of 2 methods of archwire ligation: ligature wires and elastomeric rings.
Prophylactic programs to prevent dental biofilm accumulation must be implemented to minimize the risk for periodontal diseases in orthodontic patients. Therefore, we assessed the possible periodontal and microbiologic changes resulting from the use of 2 methods of orthodontic archwire ligation: elastomeric rings and steel ligatures. The following parameters were measured: plaque index, gingival bleeding index, probing depth, and biofilm samples from the maxillary second premolars and the mandibular lateral incisors were evaluated in 14 subjects without clinical signs of gingival inflammation before orthodontic appliance placement and after 6 months of treatment. Each orthodontic arch was fixed with elastomeric rings on 1 side of the midline, and steel ligatures were used on the opposite side. Polymerase chain reaction analysis was used to detect Porphyromonas gingivalis, Tannerella forsythia, Actinobacillus actinomycetemcomitans, Prevotella intermedia, and P nigrescens. The elastomeric rings were associated with a higher score for plaque index and bleeding than steel ligatures, as well as many positive sites of T forsythia and P nigrescens (P <0.05). Elastomeric rings favored these 2 periodontopathogens and harmed gingival conditions.


Synthesis of cobalt ferrite core/metallic shell nanoparticles for the development of a specific PNA/DNA biosensor.
Controlled synthesis of cobalt ferrite superparamagnetic nanoparticles covered with a gold shell has been achieved by an affinity and trap strategy. Magnetic nanoparticles are functionalized with a mixture of amino and thiol groups that facilitate the electrostatic attraction and further chemisorption of gold nanoparticles, respectively. Using these nanoparticles as seeds, a complete coating shell is achieved by gold salt-iterative reduction leading to monodisperse water-soluble gold-covered magnetic nanoparticles, with an average diameter ranging from 21 to 29 nm. These constitute a versatile platform for immobilization of biomolecules via thiol chemistry, which is exemplified by the immobilization of peptide nucleic acid (PNA) oligomers that specifically hybridize with complementary DNA molecules in solution. Hybridation with DNA probes has been measured using Rhodamine 6G fluorescence marker and the detection of a single nucleotide mutation has been achieved. These results suggest the PNA-nanoparticles application as a biosensor for DNA genotyping avoiding commonly time-consuming procedures employed.


International correlations between indicators of prevalence, hospital admissions and mortality for asthma in children.
There are extensive data on the prevalence of childhood asthma world-wide but the relationships between asthma symptom prevalence, mortality and hospital admissions have not been investigated. The International Study of Asthma and Allergies in Childhood (ISAAC) used a standard questionnaire to measure the 12-month period prevalence of asthma symptoms by parental report in 6-7 year olds in 40 countries, and by self-report in 13-14 year olds in 60 countries. The initial survey was in the mid 1990s (Phase One) and this was repeated in the early 2000s (Phase Three). We correlated the prevalence values of any wheeze and severe wheeze with national data on mortality and hospital admissions for asthma in 5-14 year olds. All correlations with prevalence were positive. In 13-14 year olds, the correlations between severe wheeze in Phase One and contemporaneous mortality and hospital admission rates were r = 0.32 (P = 0.047) and r = 0.73 (P = 0.003), respectively. In 6-7 year olds in Phase One, the correlation with severe wheeze and mortality was r = 0.42 (P = 0.024). In 14 countries the correlation between admission and mortality rates in the 5-14 year age group was r = 0.53 (P = 0.054). There are consistently positive associations between asthma symptom prevalence, admissions and mortality. The prevalence of asthma symptoms in children obtained from local questionnaire studies may provide a guide to estimate the incidence of severe episodes of asthma in countries with incomplete data on hospital admissions or mortality, or vice versa.


Tetrahymenidae infection in mosquito populations in a malaria-endemic region of the Amazon.
In a field survey performed in a malaria-endemic region of Northern Amazon, Brazil, we encountered ciliate protozoa of the family Tetrahymenidae infecting adults and larvae of the following mosquito species: Culex sp., Anopheles albitarsis l.s., Anopheles strodei, Anopheles mattogrossensis, Anopheles darlingi, and Anopheles oswaldoi l.s. Based on morphological features and life style, we have tentatively identified the parasite as Lambornella sp. The association appears pathogenic for the mosquito. Prevalence of infection in both larvae and adults was higher in the dry season.


A service evaluation of the management of patients with suspected cauda equina syndrome from an outpatient physiotherapy service in the United Kingdom.
The expanding scope of physiotherapists worldwide has come with an increased responsibility to identify serious pathologies such as fracture, infection, tumour and cauda equina syndrome (CES). Guidelines recommend a low threshold for emergency MRI to avoid the potentially devastating consequences of CES, but a balanced approach is required to prevent excessive strain on emergency resources. To evaluate the management of patients presenting to an outpatient physiotherapy service with suspected cauda equina syndrome. Service evaluation with an embedded case series of patients with radiological CES. The records of patients who were identified by their outpatient physiotherapists as having suspected CES (n-231) over a 27-month period were included. Data was extracted from patients' medical records by a team of Advanced Clinical Practitioners (ACPs). The lead author further analysed the records of patients with clinical and radiological CES, in order to present the embedded case series. In 79% of cases, it was decided that emergency referral was not required. The remaining 21% of patients were referred to the emergency department and 49% of these had an emergency MRI. In the case series of seven patients with cauda equina compression on MRI, four patients had a disc bulge and underwent emergency surgery. One patient had non-emergency surgery for a disc bulge combined with anterolisthesis and scoliosis. Two patients had stenosis and decided against surgical intervention. Findings from this service evaluation suggest support for the use of safety netting and an effective communication chain to facilitate effective management of patients with suspected CES.


Barriers and facilitators to use of non-pharmacological treatments in chronic pain.
Consensus guidelines recommend multi-modal chronic pain treatment with increased uptake of non-pharmacological pain treatment modalities (NPMs). We aimed to identify the barriers and facilitators to uptake of evidence-based NPMs from the perspectives of patients, nurses and primary care providers (PCPs). We convened eight separate groups and engaged each in a Nominal Group Technique (NGT) in which participants: (1) created an individual list of barriers (and, in a subsequent round, facilitators) to uptake of NPMs; (2) compiled a group list from the individual lists; and (3) anonymously voted on the top three most important barriers and facilitators. In a separate process, research staff reviewed each group's responses and categorized them based on staff consensus. Overall, 26 patients (14 women) with chronic pain participated; their mean age was 55. Overall, 14 nurses and 12 PCPs participated. Seven healthcare professionals were men and 19 were women; the mean age was 45. We categorized barriers and facilitators as related to access, patient-provider interaction, treatment beliefs and support. Top-ranked patient-reported barriers included high cost, transportation problems and low motivation, while top-ranked facilitators included availability of a wider array of NPMs and a team-based approach that included follow-up. Top-ranked provider-reported barriers included inability to promote NPMs once opioid therapy was started and patient skepticism about efficacy of NPMs, while top-ranked facilitators included promotion of a facility-wide treatment philosophy and increased patient knowledge about risks and benefits of NPMs. In a multi-stakeholder qualitative study using NGT, we found a diverse array of potentially modifiable barriers and facilitators to NPM uptake that may serve as important targets for program development.


Arginine vasotocin as a pineal hormone.
The pineal nonapeptide hormone arginine vasotocin (AVT) is synthesized by the ependymal cells of the pineal recess and subcommissural organ and stored in so far undefined cells of the pineal gland proper. AVT is first released into the cerebrospinal fluid (CSF) and reaches the blood only secondarily after its absorption from CSF. It displays a diurnal rhythm in the pineal and CSF, suggesting its release into the CSF during the night in the dark. Melatonin represents its releasing hormone. AVT exerts both its endocrine and non-endocrine effects by a unique mechanism involving the activation of serotonin neurotransmission in the brain with resultant inhibition of release of hypothalamic releasing and inhibiting hormones and induction of sleep. It produces both its endocrine effects and sleep at concentrations equivalent to only several hundreds of molecules, being thus by far the most active hormone so far known. Midbrain raphe nuclei or some structures intimately correlated with these cell bodies, most contain the extremely sensitive and specific AVT receptors in the mammalian brain. In contrast with its natural analogues arginine vasopressin and oxytocin which are mainly blood hormones, AVT is a CSF hormone whose major if not the sole site of action is the brain itself.


Impact of mental disorders on work performance in a community sample of workers in Japan: the World Mental Health Japan Survey 2002-2005.
Most studies that investigate the impact of mental disorders on work performance have been conducted in Western countries, but this study examines the impact of common mental disorders on sick leave and on-the-job work performance in a community sample of Japanese workers. Data from the World Mental Health Japan survey were analyzed. A subsample of 530 workers aged 20-60years were interviewed using the WHO Composite International Diagnostic Interview 3.0. The WHO Health and Work Performance Questionnaire, was used to assess sick days and on-the-job work performance for the previous 30days. Linear regression was used to estimate the impact of mental disorders on these indicators of work performance over 12months. Mood disorders, including major depressive disorder, and alcohol abuse/dependence were significantly associated with decreased on-the-job performance. There were no significant associations between mental disorders and sick/absent days. Consistent with previous studies, major depression has a great impact on on-the-job work performance in Japan. The lost productivity was estimated at approximately 28-30 lost days per year. A similar decrease in on-the-job work performance was found for alcohol abuse/dependence, which is stronger than that in other countries, probably attributable to greater tolerance of problematic drinking at Japanese worksites.


Transient gut retention and persistence of Salmonella through metamorphosis in the lesser mealworm, Alphitobius diaperinus (Coleoptera: Tenebrionidae).
This study was undertaken to determine the retention of Salmonella through Alphitobius diaperinus metamorphosis and its contribution, through defecation, to external contamination. Insects were exposed to a tagged Salmonella enterica and evaluated for external elimination. (i) Each day for 3 weeks, a filter collected frass from a restrained insect for analysis. (ii) Exposed larvae in a closed container were followed through pupation, and newly emerged adults were examined for their retention of marker bacteria. Exposed adults and larvae produced Salmonella-positive frass for an average of 8 days, ranging from 6 to 11 days and 6 to 12 days, respectively. Nineteen per cent of the larvae carried Salmonella through metamorphosis and eclosion, with 5% of the pupal exuviae being positive as well. Many sources of foodborne pathogens within the poultry production facilities, including reservoir populations, currently go unrecognized. This diminishes the ability of producers to mitigate the transfer of pathogens between animals, humans and the environment. Poultry management standards accept the reutilization of litter. Alphitobius diaperinus survive between flock rotations on the reutilized litter, and it was demonstrated in this study that the Salmonella they carry can survive with them.


Does fetal growth restriction lead to increased brain injury as detected by neonatal cranial ultrasound in premature infants?
Intra-uterine growth restriction (IUGR) is an important cause for prematurity as well as a significant risk factor for neurodevelopmental deficits. In this study, we aimed to examine the association between IUGR and early brain injury on neonatal cranial ultrasound in preterm infants. This retrospective cohort study examined the relationship between IUGR and neonatal cranial ultrasound findings in preterm infants <32 weeks gestation with IUGR, compared with gestation and year of birth-matched appropriately grown infants, in a tertiary level neonatal unit. Primary outcome was incidence and severity of intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL) and hydrocephalus detected by cranial ultrasound in the neonatal period. A total of 153 IUGR and 306 non-IUGR preterm infants <32 weeks were included. The rates of IVH (21.6% vs. 23.9%), severe IVH (3.9% vs. 4.6%), PVL (8.4% vs. 9.4%), cystic PVL (2.6% vs. 0%) and hydrocephalus (0.7% vs. 0.3%) were similar in the two groups. Composite outcome of death and severe brain injury (severe IVH, cystic PVL and hydrocephalus) was greater (20.2% vs. 9.1%, P = 0.001) in IUGR infants. IUGR did not lead to increased neonatal brain injury on cranial ultrasound but was associated with increased mortality. Advanced neonatal neuroimaging techniques may be necessary to estimate risk and to provide prognostic information of adverse neurological outcomes in this vulnerable population.


A role for Myc in facilitating transcription activation by E2F1.
Previous work has demonstrated that E2F proteins regulate the expression of various genes encoding proteins essential for DNA replication and cell-cycle progression. E2F1 in particular is required for the initial entry to the cell cycle from a quiescent state and is required for the activation of other E2F genes. Other work has demonstrated a role for the Myc transcription factor in the activation of a large number of genes associated with cell growth, including E2F genes. We now show that Myc is required to allow the interaction of the E2F1 protein with the E2F gene promoters. As such, Myc thus provides a link between the development of a growth-competent state during the initial stage of G(1) and the activation of genes essential for DNA replication at G(1)/S.


[Concentration of potassium and sodium in the white and red muscles of the rat during adaptation to cold].
The K+ and Na+ contents changes considerably in cold adaptation only in the rat white neck muscles, remaining the same in the red muscles of hind-limbs. The ratio of K+/Na+ intracellular concentration gradually reduced from 19.8 +/- 1.7 prior to the adaptation to 12.6 +/- 1.4 within 9 weeks of the cold adaptation.


Effectiveness of an acellular pertussis vaccine in Japanese children during a non-epidemic period: a matched case-control study.
The number of pertussis cases in Japan has decreased dramatically following the nationwide use of an acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccines) which began in 1981. However, the effectiveness of the DTaP vaccine has not been systematically evaluated using appropriate epidemiological methods during a non-epidemic period in Japan. We evaluated the vaccine effectiveness (VE) of the Kaketsuken DTaP vaccine which contains two-component pertussis antigens in Japanese children from 1999 to 2001 using a matched case-control design and data from the Basic Resident Registration and Maternal and Child Health Handbooks. The DTaP vaccination history of 15 children with pertussis and 59 controls was obtained. The VE of 3 or 4 pertussis vaccinations compared with non-vaccination (baseline) was 96.9% for coughing attacks that lasted 7 days, 96.4% for those lasting 14 days, and 95.9% for those lasting 21 days. These findings suggest that DTaP vaccination effectively prevented pertussis during a non-epidemic period in Japan.


Belief, hope and help from others: a qualitative study on what facilitates physical activity in people with depression.
Worldwide, there are more than 264 million people with depression, which is the second-leading cause of years lived with disability. Physical activity can be useful in both preventing and treating mild to moderate depression, but few studies have explored patients' experience of physical activity. To explore experiences of facilitators to initiate and maintain regular physical activity in people with depression. Adults of working age with mild to moderate depression participated in semi-structured interviews. Two researchers analyzed the data using qualitative content analysis. Four categories were identified: 1) Getting over the threshold; 2) Hoping for improvement; 3) A wish to be independent but needing help; and 4) Feeling safe on one's own terms. The results indicate that knowledge and personal experience of how physical activity affects well-being, and an environment including social support, increase the possibilities for people with depression to initiate and maintain physical activity. To promote physical activity, it is important to be receptive to the person's experiences, desires, and needs and to involve them in the planning and adjustment of physical activity. Follow-up appointments, a stepwise approach, and encouragement are important to increase motivation.


A method of in-vitro measurement of the cross-sectional area of soft tissues, using ultrasonography.
Accurate measurement of the cross-sectional area of tendons and ligaments is essential in determining the mechanical properties of biological specimens. We measured these cross-sectional areas in rabbit specimens in vitro, using ultrasonography, in order to evaluate the usefulness of this method as a noncontact measurement technique. The cross-sectional areas of a rabbit's Achilles tendon, medial collateral ligament (MCL), and anterior cruciate ligament (ACL) were measured by means of ultrasonography, digital calipers, and computerized image analysis. For each of these three soft tissues, there was a high correlation between the values yielded by digital calipers and ultrasonography, and there was no significant difference in the values obtained by these three methods. Ultrasonography can detect the concavities on the surface of a specimen such as the ACL, because the shape of the specimen's transverse sonogram resembles its cross-sectional shape on a photograph. We concluded that the values yielded by ultrasonography were acceptable, and that ultrasonography is a useful noncontact measurement technique.


Crossing the line of pain: FMRI correlates of crossed-hands analgesia.
Crossing the hands over the body midline reduces the perceived intensity of nociceptive stimuli applied to the hands by impairing the ability to localize somatosensory stimuli. The neural basis of this "crossed-hands analgesia" has not been investigated previously, although it has been proposed that the effect may be modulated by multimodal areas. We used functional magnetic resonance imaging to test the hypothesis that crossed-hands analgesia is mediated by higher-order multimodal areas rather than by specific somatosensory ones. Participants lay in the scanner while mechanical painful stimuli were applied to their hands held in either a crossed or uncrossed position. They reported significantly lower perceived intensity of pain when their hands were crossed. Although activations elicited by stimuli applied to the crossed hands revealed significantly greater blood oxygen level-dependent responses in the anterior cingulate cortex, the insula, and the medial frontal gyrus, the blood oxygen level-dependent responses in the superior parietal lobe were greater with the hands uncrossed. Our results provide evidence that crossed-hands analgesia is mediated by higher-order frontoparietal multimodal areas involved in sustaining and updating body and spatial representations. We found crossed-hands analgesia to be mediated by multimodal areas, such as the posterior parietal, cingulate, and insular cortices, implicated in space and body representation. Our findings highlight how the perceived intensity of painful stimuli is shaped by how we represent our body and the space surrounding it.