Neutrophils: Novel key players in Rheumatoid Arthritis. Current and future therapeutic targets.
Rheumatoid Arthritis (RA) is a complex systemic autoimmune disease in which various cell types are involved. Among them, neutrophils have been recognized as important players in the onset and the progression of RA. The pathogenic role of neutrophils in RA lies in the alteration of several processes, including increased cell survival and migratory capacity, abnormal inflammatory activity, elevated oxidative stress and an exacerbated release of neutrophil extracellular traps. Through these mechanisms, neutrophils can activate other immune cells, thus perpetuating inflammation and leading to the destruction of the cartilage and bone of the affected joint. Given the considerable contribution of neutrophils to the pathophysiology of RA, several studies have attempted to clarify the effects of various therapeutic agents on this subtype of leukocyte. To date, recent studies have envisaged the role of new molecules on the pathogenic profile of neutrophils in RA, which could represent novel targets in future therapies. In this review, we aim to review the pathogenic role of neutrophils in RA, the effect of conventional treatments and biologic therapies, and the new, potential targets of neutrophil-derived molecules for the treatment of RA.


Biochemical and cellular effects of radiofrequency induced interstitial hyperthermia on normal canine liver.
Interstitial hyperthermia (44.0 +/- 0.5 degrees C for 40 minutes) was delivered to the livers of 16 dogs to determine acute effects of treatment on blood chemistry, histology, and cellular appearance of normal liver. SGOT in treated animals peaked immediately at 300 +/- 21 U/L (within 2 hrs) and returned to control value within 7 days. LDH levels peaked at 1 day post-treatment and again at 2 weeks (300 +/- 16 U/L and 340 +/- 25 U/L respectively) and returned to pre-treatment values by week 4. SGPT remained elevated for 6 to 7 days following hyperthermia, but returned to control value at 2 weeks. There was also a rise in alkaline phosphatase (200 +/- 14 U/L 1 day post-treatment), which returned to a pre-treatment level by week 3. Changes in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, lactate dehydrogenase, and alkaline phosphatase were attributed to both liver parenchymal damage induced by hyperthermia and to surgery. Other deviations in the blood chemistries and hematological parameters measured were ascribed to the stress response from surgical intervention, or to the resultant hemodilution from fluids during surgery. Microscopic examination upon necropsy, performed 4 weeks post-operatively, displayed limited fibrosis with some alteration of liver architecture, generalized sinusoidal dilation and red blood cells in the space of Disse. Cellular ultrastructure changes showed an increase of myelin figures, but mitochondria and other cellular organelles remained essentially normal. Localized tissue inflammation and some loss of function occurred in response to localized hyperthermia for this volume of tissue at therapeutic temperatures. This study showed that the technique was feasible and confirmed that the parenchymal damage caused by interstitial hyperthermia did not produce the severe loss of function that might have been expected.


Immune Response Evaluation in Commercial Turkeys Affected with Clostridial Dermatitis.
Clostridial dermatitis (CD), caused by Clostridium septicum and Clostridium perfringens, is an economically important emerging disease of turkeys characterized by sudden deaths and necrotic dermatitis. Immune responses in CD-affected commercial turkeys are poorly understood. In the present study, C. septicum was isolated from CD-affected commercial turkeys during a recent outbreak, and the tissues (skin, muscle, and spleen) were collected and analyzed for immune gene expression, along with samples from clinically healthy birds. The results showed that CD-affected turkeys had significantly higher levels of IL-1β, IL-6, IFNγ, and iNOS transcripts in the skin, muscle, and spleen tissues compared to healthy birds. Affected turkeys also had a significantly elevated transcription of toll-like receptor (TLR21) gene in the skin and spleen tissues, suggesting a role for this receptor in the immune recognition. The expression of IL-4 and IL-13 genes in the spleen and muscle was also significantly higher in the affected birds. Additional birds from the same affected and healthy farms examined for serology revealed that the CD-affected turkeys had significantly higher levels of serum IgM and IgY antibodies. Furthermore, in vitro stimulation of MQ-NCSU macrophages with C. septicum led to a significant transcriptional upregulation of IL-1β and IFNγ genes, while the IL-10 gene expression was downregulated. The surface expression of MHC-II protein and cellular production of nitric oxide were also significantly increased in the C. septicum-stimulated macrophages, indicating cellular activation. Collectively, our findings suggest that the host responses in CD-affected turkeys involve a robust inflammatory response as well as a response mediated by IL4/IL-13 cytokines that may aid in antibody-mediated immunity.


Learning collaboration at the primary-secondary care interface: a dual-method study to define design principles for interventions in postgraduate training programmes.
Collaboration between primary and secondary care (PSCC) is important to provide patient-centered care. Postgraduate training programmes should provide training to learn PSCC. With a design based research (DBR) approach design principles can be formulated for designing effective interventions in specific contexts. The aim of this study is to determine design principles for interventions aimed to learn PSCC in postgraduate training programmes. DBR is characterised by multi-method studies. We started with a literature review on learning collaboration between healthcare professionals from different disciplines within the same profession (intraprofessional) to extract preliminary design principles. These were used to inform and feed group discussions among stakeholders: trainees, supervisors and educationalists in primary and secondary care. Discussions were audiotaped, transcribed and analysed using thematic analysis to formulate design principles. Eight articles were included in the review. We identified four preliminary principles to consider in the design of interventions: participatory design, work process involvement, personalised education and role models. We conducted three group discussions with in total eighteen participants. We formulated three design principles specific for learning PSCC in postgraduate training programmes: (1) The importance of interaction, being able to engage in a learning dialogue. (2) Facilitate that the learning dialogue concerns collaboration. (3) Create a workplace that facilitates engagement in a learning dialogue. In the last design principle we distinguished five subcategories: intervention emphasises the urge for PSCC and is based on daily practice, the presence of role models, the work context creates time for learning PSCC, learning PSCC is formalised in curricula and the presence of a safe learning environment. This article describes design principles for interventions in postgraduate training programmes with the aim to learn PSCC. Interaction is key in learning PSCC. This interaction should concern collaborative issues. Furthermore, it is essential to include the workplace in the intervention and make adjacent changes in the workplace when implementing interventions. The knowledge gathered in this study can be used to design interventions for learning PSCC. Evaluation of these interventions is needed to acquire more knowledge and adjust design principles when necessary.


Studying Virus-Host Interactions with CRISPR Technology.
The mosquito-borne West Nile virus (WNV) poses a great threat to public health as no vaccine or specific antiviral treatment is available. Exploring virus-host interactions, specifically host factors that are required for virus infection, is important for better understanding the biology, pathogenesis, and transmission of WNV. Such essential host factors may also represent antiviral targets. The development of CRISPR technology has provided a powerful and convenient tool to perturbate host gene expression, allowing for unbiased, genome-wide screens of host factors for virus infection. Here we describe the necessary steps for performing a CRISPR knockout screen, which can also be applied to other viruses, to identify host factors critical for WNV infection.


The in vitro skin irritation of chemicals: optimisation of the EPISKIN prediction model within the framework of the ECVAM validation process.
In view of the increasing need to identify non-animal tests able to predict acute skin irritation of chemicals, the European Centre for the Validation of Alternative Methods (ECVAM) focused on the evaluation of appropriate in vitro models. In vitro tests should be capable of discriminating between irritant (I) chemicals (EU risk: R38) and non-irritant (NI) chemicals (EU risk: "no classification"). Since major in vivo skin irritation assays rely on visual scoring, it is still a challenge to correlate in vivo clinical signs with in vitro biochemical measurements. Being particularly suited to test raw materials or chemicals with a wide variety of physical properties, in vitro skin models resembling in vivo human skin were involved in prevalidation processes. Among many other factors, cytotoxicity is known to trigger irritation processes, and can therefore be a first common event for irritants. A refined protocol (protocol 15min-18hours) for the EPISKIN model had been proposed for inclusion in the ECVAM formal validation study. A further improvement on this protocol, mainly based on a post-treatment incubation period of 42 hours (protocol 15min-42hours), the optimised protocol, was applied to a set of 48 chemicals. The sensitivity, specificity and accuracy with the MTT assay-based prediction model (PM) were 85%, 78.6% and 81.3% respectively, with a low rate of false negatives (12%). The improved performance of this optimised protocol was confirmed by a higher robustness (homogeneity of individual responses) and a better discrimination between the I and NI classes. To improve the MTT viability-based PM, the release of a membrane damage marker, adenylate kinase (AK), and of cytokines IL-1alpha and IL-8 were also investigated. Combining these endpoints, a simple two-tiered strategy (TTS) was developed, with the MTT assay as the first, sort-out, stage. This resulted in a clear increase in sensitivity to 95%, and a fall in the false-positive rate (to 4.3%), thus demonstrating its usefulness as a "decision-making" tool. The optimised protocol proved, both by its higher performances and by its robustness, to be a good candidate for the validation process, as well as a potential alternative method for assessing acute skin irritation.


Derivation of Schwann cell precursors from neural crest cells resident in bone marrow for cell therapy to improve peripheral nerve regeneration.
We have previously successfully enriched post-migratory neural crest cells (NCCs) from postnatal rat bone marrow (BM). These BM-NCCs possess glial and neuronal differentiating potential. Based on the neural crest origin of Schwann cells (SCs), in this study, we aimed at using a straightforward protocol to derive Schwann cell precursors (SCPs) from BM-NCCs. Several clonal subpopulations were isolated from BM-NCCs, displaying long-term proliferative capacity and maintaining the NCC identity. The BM-NCC clones could be induced to differentiate into SCs. In particular, clone N1 gave rise to a large and pure population of SCs. Clone N1-derived SCs demonstrated the myelinating capacity in their co-culture with primary dorsal root ganglion (DRG) neurons. The decreased expression of NCC-markers and increased expression of SC-markers were related to the differentiation state of clone N1-derived SCs. To investigate the repair-promoting effects of clone N1 on injured peripheral neurons in vitro and in vivo, on one hand, the oxygen glucose deprivation-injured DRG neurons were treated with clone N1-conditioned medium, improving the cell survival and axon growth of neurons; on the other hand, clone N1 or clone N1-derived SCs were respectively implanted to the crush sciatic nerve of rats, and clone N1 yielded the better outcome of nerve regeneration and function restoration than clone N1-derived SCs. Taken together, all the results collectively showed that clone N1 could be identified as SCPs, which might hold promise for cell therapy to improve peripheral nerve regeneration.


Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production.
Although gonadotropin-releasing hormone (GnRH) is believed to mediate the hypothalamic control of pituitary gonadotropin secretion, continuous or repeated administration of GnRH or its agonist analogues has been shown to cause paradoxical antifertility effects in several species, including primates. GnRH-induced interruption of reproductive cycles and pregnancy is associated with diminished progesterone production, implying defective function of the corpus luteum. These luteolytic effects have been attributed to the well recognized desensitising actions of elevated luteinising hormone (LH) levels on ovarian LH receptors and steroidogenesis, subsequent to GnRH-induced gonadotropin release from the anterior pituitary. However, treatment with high doses of exogenous LH did not cause suppression of serum progesterone levels during early pregnancy in rats, whereas a highly active GnRH analogue was effective in this regard. These observations suggested that GnRH and its agonist analogues, given in high or sustained doses, can exert a direct action on the ovary that is independent of the pituitary. This hypothesis was further supported by the ability of GnRH and its agonists to inhibit human chorionic gonadotropin (HCG)-induced ovarian and uterine weight gain in hypophysectomised rats and to delay the onset of puberty in intact female rats. Also, GnRH and its agonist analogues have recently been shown to inhibit steroidogenesis induced by follicle-stimulating hormone (FSH) in cultured granulosa cells, confirming the direct action of such peptides on the ovarian follicle. The marked inhibitory effects of GnRH and its agonists on corpus luteum function suggest that these compounds could exert direct actions by binding to specific receptors on luteal cells. The present experiments, which examine the effects of GnRH agonists on luteal steroidogenesis, demonstrate the existence of such actions and their mediation by specific high-affinity receptor sites present in luteal cell membranes.


Pharmacogenomics: a tool for improving cancer chemotherapy.
When an anticancer drug is captured and transported to the interior of a cell, many biochemical processes intervene in the metabolism of the drug. First, the Phase I and Phase II enzymes produce metabolites, which are then excreted via the ABC-transporter enzymes. Finally, the remaining drug binds to its molecular target. Genetic alterations known as polymorphisms in any of the proteins that intervene in these processes can affect the efficacy of treatment. Interestingly, these polymorphisms can be detected in both normal and tumour cells. In this article, we will review the most effective method of detecting single-nucleotide polymorphisms (SNPs) and describe the principal SNPs in enzymes involved in drug metabolism and in DNA repair. Finally, we will briefly describe promising lines of future research in this field.


Combination treatment of acupoint therapy and conventional medication for motor function of Parkinson's disease: A systematic review and meta-analysis.
Combination treatment with acupoint therapy and conventional medication (CM) has been proposed as a strategy that could improve motor dysfunction in Parkinson's disease (PD). We performed this systematic review and meta-analysis to assess the effects of this combination treatment on motor function in patients with PD. We searched randomized controlled trials (RCTs) from eight databases, comparing combined acupoint therapy and CM and CM (alone or with sham interventions). The quality of the trials was evaluated according to the Cochrane risk of bias. Subgroup and sensitivity analyses were performed on different types of acupoint interventions. Forty-seven trials of 2929 participants were included, with 45 studies used for the meta-analyses. Combination treatment yielded an improved reduction in United Parkinson's disease rating scale (UPDRS) III of -3.85 [95% CI, -4.83 to -2.86] and Webster scale score of -3.17 [95% CI, -4.07 to -2.27]. Further analyses demonstrated that real (compared with sham) intervention was linked to a decreased UPDRS III of -2.02 ([95% CI, -3.60 to -0.44], I2 = 40%), and beneficial effects were observed when combination intervention was used for patients with Hoehn-Yahr (H-Y) stages >3 with mild to moderate stimulation for 4-12-week treatment. Acupoint therapy and CM treatment may improve motor function of patients with PD. Patients with H-Y stage >3 could tolerate real acupoint intervention with mild to moderate stimulation for 4-12-week treatment and showed improvement. However, this was demonstrated with low to moderate levels of evidence in statistical description.


Herpes simplex infection of the larynx requiring laryngectomy.
Herpes simplex virus infection of the larynx is an exceedingly rare clinical entity, most frequently reported in the pediatric population or in immunocompromised adults. We present a 62-year-old woman presented with neck pain, hoarseness, crepitus over the larynx, and what appeared to be a necrotic mass of the right true vocal cord on laryngoscopy. Due to near-complete destruction of the cartilaginous framework of the larynx, a total laryngectomy was performed. The final pathology report showed squamous mucosal changes consistent with herpes simplex infection, confirmed by immunohistochemical staining. Though herpes simplex laryngitis is uncommon, this case shows the potential for herpes simplex to cause extensive damage and compromise airway patency when left untreated.


KMI-358 and KMI-370, highly potent and small-sized BACE1 inhibitors containing phenylnorstatine.
Recently, we reported a novel substrate-based octapeptide BACE1 inhibitor KMI-008 containing hydroxymethylcarbonyl (HMC) isostere as a transition-state mimic. Using KMI-008 as a lead compound, a small-sized and highly potent BACE1 inhibitor KMI-370 (IC(50)=3.4 nM) was designed and synthesized.


Cytogenetic evidence of clonal evolution in a case of hemopoietic dysplasia with a 5q- chromosome.
A 70-year-old Japanese male with hemopoietic dysplasia is described. Cytogenetic investigation revealed an abnormal karyotype, 46,XY,del(5)(q13q33), in all metaphases examined at the time of diagnosis. Eight months later, a newly appearing abnormal hyperdiploid karyotype, 47,XY,5q-, +21, was observed in 74% of the cells analyzed, which was associated with evolution of the disease when a pathologic diagnosis of a myeloproliferative disorder was made.


The intracranial B-waves' amplitude as prognostication criterion of neurological complications in neuroendovascular interventions.
The purpose of this study was to evaluate dynamics of B-waves' amplitudes (BWA) of blood flow velocity (BFV) in patients with cerebrovascular diseases during endovascular operations. We examined 12 patients with neurovascular pathology during neuroendovascular interventions. Patients were divided into two groups: 1st group (6 cases)--without intraoperative neurological complications, 2nd group (6 cases)--with complications. Bilateral monitoring of BFV in middle cerebral arteries was carried out applying Multi Dop X. To estimate BWA Fourier analysis was used. In the 1st group preoperative BWA on the affected side was 3.9 +/- 0.6 cm/s. Intraoperative (during an access to pathologic formation and its embolisation) BWA increased up to 7.7 +/- 1.1 cm/s (p < 0.05). Postoperative BWA decreased to 4.2 +/- 0.8 cm/s. In the 2nd group the preoperative BWA on the affected side was 9.6 +/- 1.1 cm/s (p < 0.05), thus higher than in the 1st group. Intraoperatively we observed further increase of BWA up to 12.1 +/- 2.6 cm/s, accompanied by occurrence or increase of neurological symptoms. Postoperative BWA decreased to 10.4 +/- 2.9 cm/s, whereas we didn't observe regression of neurological symptoms.


1,2-Bis(dibromo-meth-yl)benzene.
In the title compound, C(8)H(6)Br(4), intra-molecular C-H⋯Br hydrogen bonds generate two S(6) rings. The two geminal bromine-atom substituents point to opposite sides of the aromatic ring system. In the crystal, mol-ecules are linked by inter-molecular π-π inter-actions with centroid-centroid distances of 3.727 (9) and 3.858 (9) Å.


Regulation of gene expression of hepatic drug metabolizing enzymes and transporters by the Toll-like receptor 2 ligand, lipoteichoic acid.
Expression of hepatic drug metabolizing enzymes (DMEs) is altered in infection and inflammation. However, the role of Gram+ve bacterial components and their receptor, Toll-like receptor (TLR) 2 in regulation of hepatic DMEs is unknown. Gene expression of DMEs is regulated by members of the nuclear receptor superfamily (PXR, CAR and RXRalpha). The TLR2 ligand, lipoteichoic acid (LTA) reduced RNA levels of CAR and its target genes, Cyp2b10, Cyp2a4 and Sultn in mouse liver ( approximately 60-80% reduction). Hepatic genes regulated by PXR and CAR, Cyp3a11 and Mrp2 were moderately reduced by LTA, along with approximately 50% reduction of PXR RNA and nuclear protein levels of RXRalpha. The effects of LTA were significantly attenuated by pre-treatment with the Kupffer cell inhibitor, gadolinium chloride, indicating that Kupffer cells contribute to LTA-mediated down-regulation of hepatic genes. These results indicate that treatment with Gram+ve bacterial components preferentially down-regulate CAR and its target genes in the liver.


Trends in Pap Testing Over Time for Women With and Without Chronic Disability.
Data from 20 years ago--shortly after passage of the Americans with Disabilities Act--showed that women with significant mobility disability had 40% lower Pap test rates than other women. To examine whether disability disparities in Pap test rates have diminished over time, this study analyzed National Health Interview Survey responses from selected years between 1998 and 2010 from women aged 21-65 years without histories of cervical cancer or hysterectomy. Seven chronic disability types were identified using self-reported functional impairments or participation limitations. Self-reported Pap testing within the previous 3 years was studied. Bivariable analyses and multivariable logistic regression analyses controlling for sociodemographic variables were conducted in 2014. Rates of all chronic disability types increased over time. Pap test rates remained relatively constant over time for all women, holding around 84%-87%. Bivariable analyses found statistically significantly lower rates of Pap testing for women with disability compared with nondisabled women. Multivariable analyses failed to find consistent evidence of lower Pap test rates among women across disability types compared with nondisabled women. In 2010, the AOR for reporting Pap testing for women noting the most severe movement difficulty compared with nondisabled women was 0.35 (95% CI=0.15, 0.79). However, the AOR for this disability type varied over time. Little has changed over time in Pap test rates for all women. Women with certain disabilities continue to experience disparities compared with nondisabled women in receipt of this important screening test.


Student-written single-best answer questions predict performance in finals.
Single-best answer (SBA) questions are widely used for assessment in medical schools; however, often clinical staff have neither the time nor the incentive to develop high-quality material for revision purposes. A student-led approach to producing formative SBA questions offers a potential solution. Cardiff University School of Medicine students created a bank of SBA questions through a previously described staged approach, involving student question-writing, peer-review and targeted senior clinician input. We arranged questions into discrete tests and posted these online. Student volunteer performance on these tests from the 2012/13 cohort of final-year medical students was recorded and compared with the performance of these students in medical school finals (knowledge and objective structured clinical examinations, OSCEs). In addition, we compared the performance of students that participated in question-writing groups with the performance of the rest of the cohort on the summative SBA assessment. Often clinical staff have neither the time nor the incentive to develop high-quality material for revision purposes Performance in the end-of-year summative clinical knowledge SBA paper correlated strongly with performance in the formative student-written SBA test (r = ~0.60, p <0.01). There was no significant correlation between summative OSCE scores and formative student-written SBA test scores. Students who wrote and reviewed questions scored higher than average in the end-of-year summative clinical knowledge SBA paper. Student-written SBAs predict performance in end-of-year SBA examinations, and therefore can provide a potentially valuable revision resource. There is potential for student-written questions to be incorporated into summative examinations.


Population-based cancer incidence in Sikkim, India: report on ethnic variation.
A Population-Based Cancer Registry (PBCR) was set up in Sikkim (a state in the North Eastern India) in 2003. We examined incidence rates by ethnic groups from 2003-2008. Age-adjusted incidence rates (AARs) per 100,000 person-years were calculated by direct method using the world standard population, and analysed by ethnic group (Bhutia, Rai and other). There were a total of 1148 male and 1063 female cases of cancer between 2003 and 2008 on the Sikkim PBCR. The overall AARs were 89.4 and 99.4 per 100,000 person-years in males and females, respectively. Incidence rates were highest amongst the Bhutia group (AAR=172.4 and 147.4 per 100,000 person-years in males and females, respectively), and the largest difference in rates were observed for stomach cancers with AARs being 12.6 and 4.7 times higher in the Bhutia group compared with other ethnic groups in males and females, respectively. These observations call for further epidemiological investigations and the introduction of screening programmes.


Lipopolysaccharide-induced inhibition of gastric acid and pepsin secretion in rats.
We used male Wistar rats to determine the effects of lipopolysaccharide (LPS) on gastric secretion. After pylorus ligation, 24-h fasted rats received i.p. injections of different doses of LPS dissolved in sterile saline. The amounts of gastric acid and pepsin secreted were determined 2, 4 or 8 h after injection. Small doses of LPS (10-1000 ng/rat) significantly inhibited the release of both gastric secretants as compared with control animals, and this inhibitory effect of LPS on gastric secretion was dose-related. The gastric antisecretory effect of LPS was still evident 8 h after injection, indicating that this action of LPS was long-lasting. These results suggest that LPS might be involved in the regulation of gastric secretion under certain pathophysiological conditions such as acute bacterial infections.


Serum S100B level may be correlated with carbon monoxide poisoning.
To investigate the correlation between serum S100B level and carbon monoxide (CO) poisoning by meta-analysis. By searching both English and Chinese language-based electronic databases (PubMed, EBSCO, Ovid, Springerlink, Wiley, Web of Science, Wanfang databases, China national knowledge infrastructure (CNKI), VIP database, etc.) thoroughly, we tabulated and analyzed the collected data with the use of Comprehensive Meta-analysis 2.0 (CMA 2.0). Totally 108 studies have been searched initially (92 studies in Chinese, 16 studies in English). Nine case-control studies (4 studies in English, 5 in Chinese) were chosen for an updated meta-analysis including 542 patients with CO poising and 236 healthy controls. Results identified that the serum S100B level were obviously higher than that in healthy controls (SMD=1.600, 95% CI=1.055-2.145, P<0.001). A subgroup based on the ethnicities revealed that the serum S100B level in Caucasian and Asian subgroups was clearly higher than serum S100B level in healthy controls (Asians: SMD=2.0624, 95% CI=1.736-3.511, P<0.001; Caucasians: SMD=0.447, 95% CI=0.197-0.697, P<0.001). Serum S100B level may be correlated with the CO poisoning and could be effective biomarker for early diagnosis and treatment monitoring in CO poisoning.


Epidermal growth factor (EGF)-induced morphological changes in the basement membrane of chick embryonic skin. An electron-microscopic study.
The effect of epidermal growth factor (EGF) on the basement membrane structure of chick embryonic skin cultured in a chemically defined medium (BGJb) containing 20 mM hydrocortisone, and EGF at 10, 50, or 100 ng/ml supplemented with 5% delipidized fetal calf serum, was examined by electron microscopy. During development of the epidermis in vitro, EGF (100 ng/ml) caused striking changes to occur in the basement membrane structure and in the keratinization process. The basement membrane frequently became discontinuous with many gaps apparent in section, and occasionally became folded following detachment from the basal surface of the epidermis and protruded into the underlying dermis. In the basal and intermediate cells of EGF-treated epidermis, tonofilament bundles were decreased in number, while desmosomes and hemidesmosomes revealed no significant changes in morphology.


Comparative analysis of production and purification of homo- and hetero-polysaccharides produced by lactic acid bacteria.
Lactic acid bacteria (LAB) produce homopolysaccharides (HoPS) and heteropolysaccharides (HePS) with potential functional properties. In this work, we have performed a comparative analysis of production and purification trials of these biopolymers from bacterial culture supernatants. LAB strains belonging to four different genera, both natural as well as recombinant, were used as model systems for the production of HoPS and HePS. Two well characterized strains carrying the gft gene were used for β-glucan production, Pediococcus parvulus 2.6 (P. parvulus 2.6) isolated from cider, and the recombinant strain Lactococcus lactis NZ9000[pGTF] (L. lactis NZ9000[pGTF]). In addition, another cider isolate, Lactobacillus suebicus CUPV225 (L. suebicus CUPV225), and Leuconostoc mesenteroides RTF10 (L. mesenteroides RTF10), isolated from meat products were included in the study. Chemical analysis of the EPS revealed that L. mesenteroides produces a dextran, L. suebicus a complex heteropolysaccharide, and the β-glucan producing-strains the expected 2-substituted (1,3)-β-glucan.


The synthesis and biological evaluation of a novel series of indole PDE4 inhibitors I.
This communication describes the synthesis and in vitro evaluation of a novel potent series of phosphodiesterase type (IV) (PDE4) inhibitors. The compounds described contain an indole moiety which replaces the 'rolipram-like' 3-methoxy-4-cyclopentoxy motif. Several of the compounds presented possess low nanomolar IC50's for PDEIV inhibition. In vivo activities determined from measurement of serum TNF-alpha levels in LPS challenged mice (mouse endotoxemia model) are also reported.


[Amyotrophic lateral sclerosis with degeneration of thalamus and substantia nigra (author's transl)].
A 40-year-old man suffering from amyotrophic lateral sclerosis with symmetrical degeneration of the thalamus and the substantia nigra is reported. The distribution pattern of the thalamic degeneration in the present case was characteristic in that the Nucleus centralis was the severest affected of the thalamic nuclei. As far as we know, there is no such case of amyotrophic lateral sclerosis in the literature. Nosologically, this case may represent a form of combined heredosystemic degeneration.


Determination of iodide in serum and urine by ion-pair reversed-phase high-performance liquid chromatography with coulometric detection.
An HPLC method is described for the determination of iodide in serum and urine using ion-pair chromatography with coulometric detection. After adding hexadecyltrimethylammonium chloride, the ions pairs formed with the iodide in the sample are extracted using an organic solvent. The solvent is then evaporated and the dry residue obtained is mixed with an appropriate volume of mobile phase so as to concentrate the sample prior to injection into the chromatograph. For a sample of 0.5 ml of serum, the method features a limit of detection (signal-to-noise ratio of 3) of 0.2 microgram l-1, sufficient to be applied in paediatric assays for the diagnosis of both iodide deficiency and excess.


Relationship between the EMG ratio of muscle activation and bony structure in osteoarthritic knee patients with and without patellar malalignment.
The aim of this study was to compare muscle activation patterns and patellofemoral joint morphologies between patients with knee osteoarthritis with and without patellar malalignment. The subjects were divided into 3 groups. Group A comprised 11 patients with symptomatic knee osteoarthritis without patellar malalignment. Group B comprised 14 patients with symptomatic knee osteoarthritis with patellar malalignment. Group C comprised 10 age-matched subjects with non-knee osteoarthritis as controls. Isokinetic dynamometry with surface electromyography was used to measure maximal muscle activity in terms of vastus medialis oblique/vastus lateralis ratios. Merchant's view was taken to analyse the bony anatomy of the patellofemoral joint. Recordings were made at angular velocities of 80, 120 and 240 masculine/sec. The electromyographic ratios of group B were lower than groups A and C for all testing velocities (p<0.05). Group B also had larger sulcus angles, lateral patellar tilt and displacement. The electromyographic ratios correlated negatively with sulcus angles. Subjects with knee osteoarthritis with patellar malalignment exhibited an imbalance in quadriceps contraction, as confirmed by altered vastus medialis oblique/vastus lateralis ratios associated with larger sulcus angles of the patellofemoral joints. The sulcus angle may be an important contributing factor in causing abnormal patellar tracking in knee osteoarthritis.


The myometrial response to intra-uterine administration of PGF2alpha and PGE2 in dysmenorrheic women.
Serial recordings of uterine contractility during different phases of the menstrual cycle were carried out in five dysmenorrheic women, and in two subjects during the acute stage of severe dysmenorrheic pain. The sensitivity and reactivity of the uterus to intrauterine administration of small doses of PGF2alpha and PGE2 were studied. A relative insensitivity of the uterus was found in the proliferative phase and around ovulation. The uterus was highly sensitive to the stimulatory effect of PGF2alpha in the secretory phase and at menstruation but probably not more sensitive than in normal women. The corresponding results with PGE2 were rather variable in that small doses did not induce any response or slight stimulation whereas high doses occasionally caused an inhibition in the secretory phase and during menstruation. The results indicate that PGF2alpha may be a significant factor in eliciting uterine hypercontractility and dysmenorrheic pain. Whether the occasional inhibitory effect of PGE2 is of any significant importance in the pathogenesis of dysmenorrhea cannot be stated.


Risk factors for hepatitis C on the Texas-Mexico border.
Our clinical experience suggested that hepatitis C virus (HCV) infection in this Texas-Mexico border area might have features, especially risk factors, that differ from some other areas of the United States. Therefore, we conducted a prospective analysis to investigate the epidemiology, risk factors, and certain other characteristics of HCV infection in the El Paso region. During a 2-yr period, individuals with a positive HCV serology were considered as "patients" and those with a negative hepatitis serology panel were "controls." A questionnaire survey was conducted in person or by telephone with individuals (patients and controls) who agreed to participate in the interview process. We identified and interviewed 320 patients and 307 controls. All of the contacted patients and controls agreed to be interviewed. Many established and potential risk factors for HCV transmission were documented in the patients. Furthermore, multiple potential risk factors were often present in individual patients. However, on multivariate analysis only injection drug use, blood transfusion, and tattooing were found to be significant independent risk factors for HCV infection. In the great majority of patients, tattoos were applied by friends (including gang members), inmates in jail/prison, or self, rather than commercial parlors. Tattooing is an independent risk factor for HCV infection in this United States-Mexico border area. The role of nonsterile tattooing practices in HCV transmission merits additional examination in regard to precise risk settings, frequency, and mechanisms of infection.


The 2015 ESPEN Sir David Cuthbertson lecture: Inflammation as the driving force of muscle wasting in cancer.
Alterations in amino acid protein metabolism are a key feature of the cancer cachexia syndrome. These changes -induced by both hormonal changes (that affect insulin sensitivity) and inflammatory mediators- are present in skeletal muscle influencing both, amino acid uptake and protein synthesis. In addition, skeletal muscle protein turnover is characterized by an exacerbated rate of protein degradation, promoted by an activation of different proteolytic systems that include the ubiquitin-proteasome and the autophagic-lysosomal pathways. Changes in the rate of myogenesis/apoptosis also determine skeletal muscle mass during cancer cachexia. Indeed, a decreased skeletal muscle regeneration capacity is observed together with an increased rate of cell death, resulting in muscle wasting. Mitochondrial dysfunction also results in changes in skeletal muscle metabolism and further contributes to the exacerbation of the cancer-wasting syndrome. Different inflammatory mediators -either released by the tumor or by healthy cells of the cancer patient- are responsible for the activation of these catabolic processes that take place in skeletal muscle.


NK cells are intrinsically functional in pigs with Severe Combined Immunodeficiency (SCID) caused by spontaneous mutations in the Artemis gene.
We have identified Severe Combined Immunodeficiency (SCID) in a line of Yorkshire pigs at Iowa State University. These SCID pigs lack B-cells and T-cells, but possess Natural Killer (NK) cells. This SCID phenotype is caused by recessive mutations in the Artemis gene. Interestingly, two human tumor cell lines, PANC-1 and A375-SM, survived after injection into these SCID pigs, but, as we demonstrate here, these cells, as well as K562 tumor cells, can be lysed in vitro by NK cells from SCID and non-SCID pigs. NK cells from both SCID and non-SCID pigs required activation in vitro with either recombinant human IL-2 or the combination of recombinant porcine IL-12 and IL-18 to kill tumor targets. We also showed that SCID NK cells could be activated to produce perforin, and perforin production was greatly enhanced in NK cells from both SCID and non-SCID pigs after IL-2 cytokine treatment. While CD16+, CD172- NK cells constituted an average of only 4% in non-SCID pigs, NK cells averaged 27% of the peripheral blood mononuclear cell population in SCID pigs. We found no significant differences in killing activity per NK cell between SCID and non-SCID pigs. We conclude that survival of human cancer cells in these SCID pigs is not due to an intrinsic defect in NK cell killing ability.


A miR image of stem cells and their lineages.
MicroRNAs (miRs) comprise a class of tiny (∼19-24 nucleotide), noncoding RNAs that regulate gene expression posttranscriptionally. Since the discovery of the founding members lin-4 and let-7 as key regulators in the developing nematode, miRs have been found throughout the eukaryotic kingdom. Functions for miRs are wide-ranging and encompass embryogenesis, stem cell biology, tissue differentiation, and human diseases including cancers. In this chapter, we begin by acquainting our readers with miRs and introducing them to their biogenesis. Then, we focus on the roles of miRs in stem cells during tissue development and homeostasis. We use mammalian skin as our main paradigm, but we also consider miR functions in several different types of adult stem cells. We conclude by discussing future challenges that will lead to a comprehensive understanding of miR functions in stem cells and their lineages.


Hypertension detection and compliance: permanent site hypertensive evaluation--a new method of increasing patient compliance.
A new method--permanent site hypertensive evaluation with patient revisits--is suggested as a unique way to increase patient compliance. This method reduced mild hypertension for 50% and increased normotension. The easy availability of permanent sites may induce the patient to return regularly, or the patient may be testing the medication or his physician. But whatever the means, normotension is the aim of compliance. Thanks to Mark Cohen and his pharmacy staff, Dot, Ruth, Jim, and George for their many long hours of detection work; to my nurse monitor, Pauline Platt; and to my secretary, Gene Koswoski. This study was done in cooperation with the Montgomery County Branch of the Southeastern Pennsylvania Chapter of the American Heart Association, Philadelphia, Pennsylvania.


Socio-Behavioral Factors Associated with Overweight and Central Obesity in Tehranian Adults: a Structural Equation Model.
This study aimed to test a conceptual model of associations between socio-demographic and behavioral factors and obesity in the Tehran Lipid and Glucose Study (TLGS). Data from 2747 TLGS adult participants (58.3 % female) were analyzed. Socio-demographic and behavioral factors in the conceptual model were tested for their direct and indirect associations with overweight and central obesity, using structural equation modeling (SEM), conducted by IBM SPSS AMOS software. Overweight and central obesity were found in 61.6 and 48.1 % of respondents, respectively. Fit indices were acceptable for the conceptual model. Daily energy intake had a direct association with overweight and central obesity in both genders; however, poor dietary pattern had direct associations with overweight and central obesity only in men. In women, age, marital status, and level of education had direct associations with overweight and central obesity. In men, only age and marital status had direct associations with overweight and central obesity. Age and marital status in both genders and level of education only in women were among the socio-demographic factors which were directly associated with both overweight and central obesity. Among behavioral factors, daily energy intake was the most important factor that was directly associated with both overweight and central obesity in both genders. Adherence to poor diet directly was associated with overweight and central obesity only in men. The current findings provide beneficial information for designing culturally relevant and effective interventions/strategies for prevention of overweight among Tehranian adults.


Activated Caspase 3 Expression in Remnant Disease After Neoadjuvant Chemotherapy May Predict Outcomes of Breast Cancer Patients.
A number of studies have indicated that patients obtaining a pathological complete response (pCR) from neoadjuvant chemotherapy (NAC) have a good prognosis; however, prognostic factors for non-pCR patients are not yet well-established. By examining remnant cancer in non-pCR patients, the expression of cleaved Caspase 3 (Casp3), an activated apoptotic marker, was immunohistochemically investigated to determine whether this protein has the potential to serve as a novel marker for predicting patient outcomes. We investigated 218 patients with invasive breast cancer who received NAC and underwent surgery during the 2006 through 2008 period at our institution. Following surgery, standard adjuvant endocrine therapy was administered if a tumor was hormone receptor-positive. Casp3 was evaluated in remnant cancer based on the number of positive cells in five high-power fields. pCR was obtained in 49 patients, and 50 of the 169 non-pCR patients developed recurrences during the median 82-month observation period. We found large tumor size, lymph node involvement, lymph vessel invasion, estrogen receptor-negative, progesterone receptor-negative, high Ki67 and high Casp3 expression to be factors related to tumor recurrence. A logistic regression model revealed that lymph node involvement, as well as high Ki67 and Casp3, to be factors independently predicting recurrence, while lymph vessel invasion and high Ki67 expression were found to be related to breast cancer mortality. Patients with remnant cancer showing high Casp3 expression had poor outcomes. Our results showed that Casp3 is a potential prognostic marker for non-pCR patients.


Evaluation study of the exploratory visit: an innovative outreach activity of the ILGWU's friendly visiting program.
The exploratory visit to recent retirees, an outreach component of the International Ladies Garment Workers Union Friendly Visiting Program, was evaluated during a ten month period beginning in September 1973. An operations analysis found that need identifying activities of Friendly Vistors by type of service need. A post-test only control group effect study revealed exploratory visits were effective in establishing a link between the program and the retiree although they had no significant impact on the retirees' service needs.


Therapeutic IGF-I receptor inhibition alters fibrocyte immune phenotype in thyroid-associated ophthalmopathy.
Thyroid-associated ophthalmopathy (TAO) represents a disfiguring and potentially blinding autoimmune component of Graves' disease. It appears to be driven, at least in part, by autoantibodies targeting the thyrotropin receptor (TSHR)/insulin-like growth factor I receptor (IGF-IR) complex. Actions mediated through either TSHR or IGF-IR are dependent on IGF-IR activity. CD34+ fibrocytes, monocyte lineage cells, reside uniquely in the TAO orbit, where they masquerade as CD34+ orbital fibroblasts. Fibrocytes present antigens to T cells through their display of the major histocompatibility complex class II (MHC II) while providing costimulation through B7 proteins (CD80, CD86, and programmed death-ligand 1 [PD-L1]). Here, we demonstrate that teprotumumab, an anti-IGF-IR inhibitor, attenuates constitutive expression and induction by the thyroid-stimulating hormone of MHC II and these B7 members in CD34+ fibrocytes. These actions are mediated through reduction of respective gene transcriptional activity. Other IGF-IR inhibitors (1H7 and linsitinib) and knocking down IGF-IR gene expression had similar effects. Interrogation of circulating fibrocytes collected from patients with TAO, prior to and following teprotumumab treatment in vivo during a phase 2 clinical trial, demonstrated reductions in cell-surface MHC II and B7 proteins similar to those found following IGF-IR inhibitor treatment in vitro. Teprotumumab therapy reduces levels of interferon-γ and IL-17A expression in circulating CD4+ T cells, effects that may be indirect and mediated through actions of the drug on fibrocytes. Teprotumumab was approved by the US Food and Drug Administration for TAO. Our current findings identify potential mechanisms through which teprotumumab might be eliciting its clinical response systemically in patients with TAO, potentially by restoring immune tolerance.


Detection of messenger RNA transcribed from genes encoding enzymes of amino acid biosynthesis in Buchnera aphidicola (endosymbiont of aphids).
The aphid Schizaphis graminum is dependent on Buchnera aphidicola, a prokaryotic endosymbiont. One of the functions of the endosymbiont is the synthesis of essential amino acids for the aphid host. Previously we have found that B. aphidicola has many of the genes that encode enzymes of amino acid biosynthesis. Using reverse transcriptase and the polymerase chain reaction, we have detected messenger RNA corresponding to genes involved in the synthesis of tryptophan, isoleucine, valine, leucine, and histidine.


Diffusion abnormality maps in demyelinating disease: correlations with clinical scores.
Magnetic resonance imaging (MRI) has been explored as a noninvasive tool to assess pathology in multiple sclerosis (MS) patients. However, the correlation between classical MRI measures and physical disability is modest in MS. The diffusion tensor imaging (DTI) MRI technique holds particular promise in this regard. The present study shows brain regions where FA and individual diffusivities abnormalities are present and check their correlations with physical disability clinical scores. Eight patients and 12 matched healthy controls were recruited. The Multiple Sclerosis Functional Composite was administered. For MR-DTI acquisitions, a Genesis Signa 1.5 T MR system, an EP/SE scanning sequence, 25 gradient directions were used. Tract Based Spatial Statistics (TBSS) group comparisons showed reduced FA and increased individual diffusivities in several brain regions in patients. Significant correlations were found between FA and: EDSS, 9-HPT(NON)DOM and 25 FW score; between λ2 and: P100 (r&l), 9-HPT(NON)DOM and 25 FW; between λ3 and: 9-HPT(NON)DOM and 25 FW score. Fractional anisotropy and individual radial diffusivities proved to be important markers of motor disabilities in MS patients when the disease duration mean and the disability scores values range are relatively high.


What Kind of Community Development System Can Effectively Support Citywide Philanthropic Efforts to Promote Community Well-Being?
How can the efforts of philanthropic agencies be better supported to promote citywide community well-being? To address this question, this article uses a citywide, engagement-driven initiative led by local practitioners that took place in Detroit between 2016 and 2019. This article is based on the initiative's two main outcomes, namely the identification of seven elements of an effective community development system and a vitality framework designed to measure community progress and success. The author of this article conducted participant observation, interviews, and a literature review, as well as site visits to, and case studies on, four best-practice cities, and then used the outcomes to validate the results of the initiative. Informed by the outcomes of the initiative and the research, the article suggests how best to utilize the seven community development system elements and the vitality success framework effectively to support philanthropy that promotes community well-being. This article focuses on theory-building in Detroit and calls for empirical research to further validate the findings. The article provides useful insights into the benefits of community-based research and citywide engagement as essential components of an effective community development system that can coordinate philanthropic practice more effectively to promote community well-being.


Temperature-compensated cuts for length-extensional and flexural vibrating modes in GaPO4 beam resonators.
Flexural modes are the basic vibrating mode of tuning forks used in quartz wrist watches; they also can be used as the basis for sensors. Very little work, if any, has been done for vibrating beam resonators in GaPO4. In this paper, the possibility of temperature-compensated cuts in GaPO4 is investigated for length-extensional and flexural vibrating modes. A theoretical investigation of rectangular cross-section GaPO4 vibrating beam resonators is accomplished by analytical methods. Modeling temperature effect is achieved by the approximate but classical method in which the effective elastic constants, beam dimensions, and crystal mass density are varied as a function of temperature. Temperature-compensated cuts are given in GaPO4 for length-extensional and flexural modes. Some temperature-compensated cuts of GaPO4 exhibit inversion points at high temperatures.


Dietary patterns and cognitive achievement among school children in socio-cultural context, a case of Montevideo, Uruguay.
The benefits of a healthy diet on children´s cognition have been described in several studies. However, many previous studies have analyzed the effect on general cognitive domains (e.g. intelligence), used measures based almost exclusively on local examinations, and rarely consider social context. The objective of the present study was to examine the relationship between two diet patterns and contextualized cognitive performance measures of children aged 6-8 years from low-average income neighborhoods in Montevideo, Uruguay. 270 first-grade children with complete data participated in the study. Consumption of foods was determined via two averaged 24-h dietary recalls with the mother. Two dietary patterns were identified via principal component analysis: "processed (high calorie) foods" and "nutrient dense". Children´s cognitive performance, including general cognitive abilities, achievement in mathematics and reading, and discrepancy scores between predicted and actual achievement was assessed with the Woodcock-Muñoz Cognitive and Achievement scales. The association of dietary patterns and cognitive endpoints was analyzed in multilevel models, clustered by children´s school. Sociodemographic and biological variables were used as covariates. The nutrient dense foods pattern, characterized by higher consumption of dark leafy and red-orange vegetables, eggs, beans & peas, potatoes, was associated with better performance in reading, with beta coefficient 3.28 (95% CI 0.02, 6.54). There was also an association between the nutrient dense foods factor and the Discrepancy in reading, 2.52 (0.17, 4.87). Processed (high calorie) foods pattern, characterized by higher consumption of breads, processed meats, fats and oils, sweetened beverages, and sweetened yogurt/dairy products; reduced intake of milk, pastries and pizza dinners was not associated with cognitive performance. Nutrient dense food pattern was positively associated with children's reading achievement. A nutrient-rich diet may benefit written language acquisition at the beginning of schooling.


In vitro progesterone modulation on bacterial endotoxin-induced production of IL-1β, TNFα, IL-6, IL-8, IL-10, MIP-1α, and MMP-9 in pre-labor human term placenta.
During human pregnancy, infection/inflammation represents an important factor that increases the risk of developing preterm labor. The purpose of this study was to determine if pre-treatment with progesterone has an immunomodulatory effect on human placenta production of endotoxin-induced inflammation and degradation of extracellular matrix markers. Placentas were obtained under sterile conditions from pregnancies delivered at term before the onset of labor by cesarean section. Explants from central cotyledons of 10 human placentas were pre-treated with different concentrations of progesterone (0.01, 01, 1.0 μM) and then stimulated with 1000 ng/mL of LPS of Escherichia coli. Cytokines TNFα, IL-1β, IL-6, IL-8, MIP-1α, IL-10 concentrations in the culture medium were then measured by specific ELISA. Secretion profile of MMP-9 was evaluated by ELISA and zymogram. Statistical differences were determined by one-way ANOVA followed by the appropriate ad hoc test; P < 0.05 was considered statistically significant. In comparison to the explants incubated with vehicle, the LPS treatment led to a significant increase in the level of all cytokines. In comparison to the explants treated only with LPS, pre-treatment with 0.01-1.0 μM progesterone significantly blunted (73, 56, 56, 75, 25, 48 %) the secretion of TNF-α, IL-1β, IL-6, IL-8, MIP-1α, IL-10, respectively. The MMP-9 induced by LPS treatment was inhibited only with the highest concentration of progesterone. Mifepristone (RU486) blocked the immunosuppressive effect of progesterone. The present results support the concept that progesterone could be part of the compensatory mechanism that limits the inflammation-induced cytotoxic effects associated with an infection process during gestation.


Direct projections from the entorhinal cortical layers to the dentate gyrus, hippocampus, and subicular complex in the cat.
Projections from each layer of the entorhinal cortex (EC) of the cat were traced to the dentate gyrus (DG), Ammon's horn (CA), prosubiculum (ProSb), subiculum (Sb), presubiculum (PreSb) and parasubiculum (ParaSb); the anterograde or retrograde labeling method was used after stereotaxic injection of wheat germ agglutinin-horseradish peroxidase, cholera toxin B subunit, or Phaseolus vulgaris leucoagglutinin. On the side ipsilateral to the tracer-injection, layer II of the EC projected most abundantly to the outer half of the molecular layer (ML) of the DG, less abundantly to the almost entire thickness of the stratum lacunosum-moleculare (SLM) of CA2-3, moderately to the almost entire thickness of the SLM of CA1, and less to the outer part of the ML of the ProSb and Sb. Layer III projected abundantly to the almost entire thickness of the SLM of CA1 and outer part of the ML of the ProSb and Sb, and sparsely to the SLM of CA2-3. Layer IV projected sparsely to the pyramidal cell layer of the ProSb and Sb; Layer IV of the medial part (toward the ParaSb) of the EC projected further to the ML of the DG. Layer VI projected sparsely to the outer part of the ML of the DG, almost entire thickness of the SLM of CA1-3, and outer part of the ML of the ProSb and Sb. More temporal parts of the hippocampal region received the projections from progressively more medial and more rostral parts of layers II and III, and from progressively more rostral parts of layers IV and VI. The ML of the PreSb and ParaSb received projections from all layers of the medial part of the ipsilateral EC. The SLM of CA1 and ML of the ProSb, Sb and ParaSb received projections from layer II and/or III of the contralateral medial entorhinal area.


Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node.
The aim was to study the ionic basis of the chronotropic effects of bath applied acetylcholine and vagal stimulation on the rabbit sinoatrial node. The chronotropic effect of bath applied acetylcholine was measured in single cells and small multicellular preparations from the rabbit sinoatrial node and the chronotropic effect of postganglionic vagal stimulation was measured in the intact sinoatrial node. The roles of the hyperpolarisation activated current, i(f), the acetylcholine activated potassium current, iK,ACh, and the L-type calcium current, iCa, were investigated by blocking the currents with 1-2 mM Cs+ or 10(-6) M UL-FS49, 0.2-1.0 mM Ba2+, and 6 x 10(-6) M nifedipine, respectively. Under control conditions, small multicellular preparations were approximately two orders of magnitude less sensitive to bath applied acetylcholine than single cells. However, after block of acetylcholinesterase by eserine in small multicellular preparations the sensitivities of the two types of preparation were approximately the same. Block of i(f) either had no discernible effect or increased the chronotropic effect of bath applied acetylcholine on single cells or small multicellular preparations, whereas partial block of iK,ACh reduced it substantially. Similarly, block of i(f) did not suppress the initial slowing of spontaneous action potentials by vagal stimulation, whereas partial block of iK,ACh reduced it. The hyperpolarisation of the arrested sinoatrial node in response to vagal stimulation was also substantially reduced by block of iK,ACh. Partial block of iCa caused large decreases in the action potential amplitude and maximum diastolic potential, but little decrease in the rate of spontaneous action potentials, and therefore did not mimic the effect of acetylcholine. The chronotropic effects of bath applied acetylcholine and vagal stimulation are not principally the result of a suppression of i(f) or iCa, whereas the activation of iK,ACh may play an important role.


Highly efficient peroxymonosulfate activation on Fe-N-C catalyst via the collaboration of low-coordinated Fe-N structure and Fe nanoparticles for enhanced organic pollutant degradation.
Supporting Fe catalysts on N doped carbon (Fe-N-C) renders a promising way towards peroxymonosulfate (PMS) activation for water decontamination, but constructing high-efficiency Fe-N-C remains challenging due to the insufficient understanding of the structure-performance relationship. Herein, the N doped carbon nanotube supported Fe catalysts (Fe-NCNT) were prepared towards PMS activation for organic pollutants removal, in which the Fe-N coordination number and Fe species were tuned through changing the pyrolysis temperature to study their roles in PMS activation. Results showed increasing the pyrolysis temperature converted the Fe-N4 structure in Fe-NCNT to low-coordinated Fe-N3 structure and produced Fe nanoparticles (FeNP, encapsulated in carbon). The Fe-NCNT with Fe-N3 and FeNP exhibited a remarkably high specific activity (0.119 L min-1 m-2), which was 1.8 times higher than that of Fe-NCNT with only Fe-N4 and obviously outperformed those of the state-of-the-art PMS activators. The low-coordinated structure and FeNP promoted the PMS reduction on Fe2+ of Fe-Nx for •OH and SO4•- production, which served as major oxidants for pollutants degradation. The experimental results and theoretical calculation corroborated the low-coordinated structure and FeNP jointly enhanced the PMS adsorption and electron density on Fe center, which accelerated electron transfer from Fe center to PMS for radical production.


Mortality trends and risk of dying from colorectal cancer in the seven socioeconomic regions of Mexico, 2000-2012.
In Mexico, there has been an upward trend in mortality rates from colorectal cancer (CRC) over the past three decades. This tumor is ranked among the ten most prevalent causes of morbidity from malignancies in Mexico. To determine the mortality trends by socioeconomic region and by state, and to establish the relative risk between both educational level and socioeconomic region with mortality from CRC within the time frame of 2000-2012. Records of mortality associated with colorectal cancer were obtained. Rates of mortality by state and by socioeconomic region were calculated, along with the strength of association (obtained through the Poisson regression) between both socioeconomic region and educational level and the mortality from CRC. A total of 45,487 individuals died from CRC in Mexico from 2000 to 2012. Age-adjusted mortality rates per 100,000 inhabitants increased from 3.9 to 4.8. Baja California, Baja California Sur, and Sonora had the highest mortality from CRC. Individuals with no school or incomplete elementary school had a higher risk of dying from this cancer (RR of 3.57, 95% CI: 3.46-3.68). Region 7 had the strongest association with mortality from CRC (Mexico City: RR was 2.84, 95% CI: 2.39-3.37 [2000] and 3.32, 95% CI: 2.89-3.82 [2012]). In Mexico, the age-adjusted mortality rates per 100,000 inhabitants that died from CRC increased from 3.9 to 4.8 in the study period, using the world population age distribution as the standard. Baja California, Baja California Sur, and Sonora had the highest mortality from CRC. Mexico City, which was socioeconomic region 7, had the strongest association with mortality from CRC.


A prophenoloxidase from Artemia sinica: cDNA cloning, expression and activity analysis during early development.
To understand the defense mechanisms of Crustacean animals, brine shrimp Artemia sinica prophenoloxidase (AsproPO) cDNA was cloned and its expression at early developmental stages was examined by reverse-transcription PCR (RT-PCR) and semi-quantitative RT-PCR, and activity of phenoloxidase (PO) at different developmental stages was further detected by using l-3,4-dihydroxyphenylalanine (l-DOPA) as a specific substrate in this study. It was found that the full-length of AsproPO cDNA is 2125 bp and it contains an open reading frame of 2100 bp encoding a protein of 699 amino acids. The deduced amino acid sequence of AsproPO has two putative copper binding sites highly conserved in Arthropods. Semi-quantitative RT-PCR analyses showed that the gene of AsproPO expressed at Emergence, Instar I and Instar II stages but did not at 0 h and 6 h stages. Activity measurement showed that PO activity could only be detected at Instar II stage but the other measured stages. All these implied that Artemia proPO immune system was complexly modulated during early development.


Novel antireflux covered metal stent for recurrent occlusion of biliary metal stents: a pilot study.
Feasibility of antireflux metal stent (ARMS), designed to prevent duodenobiliary reflux, was reported in patients with distal malignant biliary obstruction. In this prospective pilot study, we aimed to evaluate a newly designed ARMS as a reintervention for self-expandable metallic stent (SEMS) occlusion believed to be caused by duodenobiliary reflux. Patients with non-resectable distal malignant biliary obstruction were included in whom a prior SEMS was occluded as a result of sludge or food impaction between March 2010 and January 2012 at two Japanese tertiary referral centers. The occluded SEMS were endoscopically removed, if possible, and subsequently replaced by a newly designed ARMS. We evaluated the technical success rate and complications of ARMS and compared the time to occlusion of ARMS with that of prior SEMS. A total of 13 patients were included. ARMS was successfully placed in all patients in a single procedure. No procedure-related complications were identified. ARMS occlusion occurred in two patients (15%), the causes of which were sludge in one patient and unknown in the other. ARMS migration occurred in four patients (31%). ARMS patency time was significantly longer than that of prior SEMS (median, not available vs 58 days; P = 0.039). This newly designed ARMS is a technically feasible, safe, and effective reintervention for SEMS occlusion as a result of sludge or food impaction. An anti-migration mechanism to improve the outcomes of ARMS should be considered.


Phytoremediation of urban wastewater by model wetlands with ornamental hydrophytes.
Phytoremediation offers a cost-effective, non-intrusive, and safe alternative to conventional cleanup techniques. In this study, we used ornamental hydrophytes plants as constructed wetlands to treat urban or rural domestic wastewater. Most ornamental hydrophytes adapted to the wastewater well, and were fairly efficient in scavenging BOD5 (biological oxygen demand 5 d), COD (chemical oxygen demand), TN (total nitrogen), TP (total phosphorus) and heavy metals (Cr, Pb, Cd) in the wastewater. However, the efficiency varied a lot for various species to different contaminants, Iris pseudacorus L. and Acorus gramineus Soland were good choices for treatment of composite-polluted urban wastewater. Some variation in the change of membrane peroxidation and endogenous protective system in responses to wastewater was found among six hydrophytes, which have a correlation with the efficiency of wastewater treatment. It may demonstrate that the developed antioxidative systems of I. pseudacorus and A. gramineus contributed much to their superiority. On the other hand, interaction of different components in the wastewater might have certain effects on phytoremediation.


Sulfotanone, a new alkyl sulfonic acid derivative from Streptomyces sp. IFM 11694 with TRAIL resistance-overcoming activity.
One new alkyl sulfonic acid derivative, sulfotanone (1), and the known panosialin wA (2) were isolated from the methanolic extract of mycelium of Streptomyces sp. 11694. The structure of the new compound (1) was established by a combination of spectroscopic techniques, including HRESIMS, IR, 1D and 2D NMR measurements. Compound 1 (40 µM) in combination with TRAIL showed synergistic activity in sensitizing TRAIL-resistance in human gastric adenocarcinoma cell lines.


A national program director survey of the shift to competency-based education in ophthalmology.
To assess the resources, progress, and barriers for program director (PD) compliance with the Accreditation Council for Graduate Medical Education (ACGME) mandate. Survey. Ophthalmology PDs in the United States. A survey instrument was sent to all ophthalmology PDs in the United States. The survey instrument assessed PD tenure, funding, current efforts, evaluation modalities, barriers, and desired resources to meet the ACGME competency mandate. The survey was completed by 88 of 104 (85%) PDs. Significant disparities exist between PD financial compensation and actual time spent performing PD duties. This disparity and lack of understanding by faculty of the ACGME competencies were the most frequently cited barriers to success in complying with the ACGME mandate. The most commonly utilized assessment tools are the global or 360 degrees evaluations and clinical evaluation exercises. Program directors surveyed believe they are not receiving adequate resources to allow them to comply with the ACGME mandate. Although some tools have been implemented by PDs for assessing the competencies, additional national and centralized resources would be helpful.


Functional traits of poplar leaves and fine roots responses to ozone pollution under soil nitrogen addition.
Concurrent ground-level ozone (O3) pollution and anthropogenic nitrogen (N) deposition can markedly influence dynamics and productivity in forests. Most studies evaluating the functional traits responses of rapid-turnover organs to O3 have specifically examined leaves, despite fine roots are another major source of soil carbon and nutrient input in forest ecosystems. How elevated O3 levels impact fine root biomass and biochemistry remains to be resolved. This study was to assess poplar leaf and fine root biomass and biochemistry responses to five different levels of O3 pollution, while additionally examining whether four levels of soil N supplementation were sufficient to alter the impact of O3 on these two organs. Elevated O3 resulted in a more substantial reduction in fine root biomass than leaf biomass; relative to leaves, more biochemically-resistant components were present within fine root litter, which contained high concentrations of lignin, condensed tannins, and elevated C:N and lignin: N ratios that were associated with slower rates of litter decomposition. In contrast, leaves contained more labile components, including nonstructural carbohydrates and N, as well as a higher N:P ratio. Elevated O3 significantly reduced labile components and increased biochemically-resistant components in leaves, whereas they had minimal impact on fine root biochemistry. This suggests that O3 pollution has the potential to delay leaf litter decomposition and associated nutrient cycling. N addition largely failed to affect the impact of elevated O3 levels on leaves or fine root chemistry, suggesting that soil N supplementation is not a suitable approach to combating the impact of O3 pollution on key functional traits of poplars. These results indicate that the significant differences in the responses of leaves and fine roots to O3 pollution will result in marked changes in the relative belowground roles of these two litter sources within forest ecosystems, and such changes will independently of nitrogen load.


A biometric study of the fetal orbit and lens in normal pregnancies.
To construct nomograms of the size of the fetal orbit and lens and to evaluate the relationships between the gestational age and the biometry of the fetal orbit and lens. Six hundred two normal pregnant women were evaluated from 15 to 40 weeks of gestation. Fetal orbital and lens measurements were added to routine biometric measurements for normal fetuses. A total of 595 measurements were used for analyses. A strong linear correlation was observed between gestational age and orbital diameter, orbital circumference, and orbital surface. A linear correlation was also found between gestational age and lens diameter, lens circumference, and lens surface. A linear growth function was observed between biparietal diameter and both the orbital diameter and the lens diameter. Orbital and lens measurements provide data that correlate with fetal growth and development. These data may also help detect fetal ocular abnormalities.


ABC transporters and the accumulation of imatinib and its active metabolite CGP74588 in rat C6 glioma cells.
Imatinib (Glivec, Gleevec, STI571) is a small tyrosine kinase inhibitor that is currently in phase II clinical trials in patients with recurrent glioblastoma. Its therapeutic benefit is minimal, although it is greater in some patients when combined with hydroxyurea. Imatinib is transported by human and rodent ATP-binding cassette (ABC) transporters like P-glycoprotein (Pgp) and the breast cancer resistance protein (BCRP). We have investigated whether ABC transporters determine the pharmacokinetics of imatinib and its pharmacological active metabolite CGP74588 in rat C6 glioma cells. ABC transporter expressions were measured by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). C6 cells express high concentrations of the Pgp-encoding gene Mdr1b and a 10-fold smaller amount of the Pgp-encoding gene Mdr1a. The relative expression of ABC transporter genes are: Mdr1b>Mrp4>Mrp1>Mrp5>Mdr1a>Mrp3>Mrp2>Bcrp. The accumulation of imatinib into C6 cells increased linearly with the extracellular concentration of imatinib (0.5-50microM) and was not increased by zosuquidar (selective Pgp inhibitor) or elacridar (inhibitor of both Pgp and Bcrp). In contrast, there was less CGP74588 than imatinib in C6 cells and its concentration increased with the extracellular concentration in a sigmoid fashion. Lastly, 10microM valspodar (selective Pgp inhibitor), elacridar and zosuquidar all increased the accumulation of CGP74588 by 2.5-fold. Thus CGP74588 is readily transported by the Pgp in rat C6 gliomas cells, which raises the question of the role of Pgp in the resistance of recurrent glioblastomas to imatinib.


Adrenal insufficiency in an adult on inhaled corticosteroids; recovery of adrenal function with inhaled nedocromil sodium.
Whereas oral corticosteroids and high-dose inhaled corticosteroids may be associated with suppression of the hypothalamic-pituitary-adrenal axis, medium-dose inhaled corticosteroids have not been reported to be associated with clinically significant adrenal insufficiency in the adult. A case study of adrenal responsiveness after prolonged medium-dose inhaled corticosteroids and after replacement of steroid therapy by inhaled nedocromil sodium is described. Standard 250-microg dose ACTH (cosyntropin) stimulation tests were followed after replacement of inhaled triamcinolone acetonide therapy by nedocromil sodium. A 55-year-old woman who had been on inhaled triamcinolone acetonide, 1600 microg/day for 12 years, presented with symptoms of adrenal hypofunction upon inhaled corticosteroid taper. An ACTH stimulation test confirmed adrenal insufficiency. She was switched to inhaled nedocromil sodium with improvement in her clinical syndrome and normalization of her ACTH stimulation test. Withdrawal from prolonged use of inhaled medium-dose corticosteroids may be associated with clinically significant adrenal insufficiency in adults. Steroid sparing agents may be considered for those on long-term inhaled corticosteroid therapy.


Rapid and sensitive detection of dextran sulfate sodium based on supramolecular self-assembly of a perylene diimide derivative in aqueous solution.
Dextran sulfate sodium (DSS) is a heparin polysaccharide, whose overuse would cause many adverse effects, such as stiff and painful joints and loss of hair. It is crucial to search after a rapid and accurate approach for the determination of DSS in the clinical treatment and diagnosis. Regrettably, there are few literatures about analytical methods for detecting DSS at present. In this research, a sensitive and selective method for detecting DSS based on the hydrosoluble perylene diimide (PDI) derivative was established in pure aqueous solution. The sensing mechanism and performance of PDI-PdEC were systematically investigated by ultraviolet and fluorescence spectroscopy. Non-covalent interactions between DSS and PDI-PdEC, like π-π stacking, electrostatic and hydrophobic interaction, promote the aggregation of PDI-PdEC and form supramolecular aggregates, which realize the sensitive and rapid detection of DSS in aqueous system. The detection limit for DSS is as low as 5.51 ng/mL and the linear range is 20-500 ng/mL. Furthermore, this probe was triumphantly applied in the detecting of DSS in serum. To the best of our knowledge, this is the first fluorescent probe for detecting DSS in aqueous media. We consider that our study will not only broaden the range of applications of perylene diimide fluorescent sensors, but also provide valuable reference for the design of new sensors for the rapid determination method of DSS.


Mechanisms of posttransplant hypertension.
Posttransplant hypertension is an important risk factor for cardiovascular mortality and graft function. We performed metabolic studies in 35 hypertensive patients with well-maintained graft function on maintenance immunosuppressive drugs and in 17 normotensive control transplant recipients. The group of hypertensive recipients were characterized by increased peripheral plasma renin activity, lack of change in blood pressure in response to salt loading and restriction, and by increased peripheral and renal resistance. In contrast, on the same protocol in a group of patients with essential hypertension, blood pressure fell significantly on a low-salt intake. Peripheral resistance in hypertensive transplant recipients fell in response to saline loading, in contrast to the effects in normotensive transplant recipients. Hypertensive patients with retained native kidneys as compared to those who had these removed prior to transplant, but were still hypertensive, differed only with regard to reduced renal plasma flow in the former group. These data are consistent with a predominantly renin-dependent hypertension in these renal transplant recipients. When bilateral nephrectomy or repair of graft renal artery stenosis is being considered, response to captopril may offer a means of selection; acute renal failure on captopril suggests functionally significant renal artery stenosis.


Causes of donor rejection in a sperm banking program.
During a 2-year period, 93 men between the ages of 18 and 46 years were screened for sperm donation using a three-stage protocol. Thirty (32%) applicants became active donors. Eighty-five percent of the semen specimens from these men were successfully frozen, quarantined, and released for insemination. The three-stage protocol successfully eliminated most uncommitted or unqualified applicants in an efficient, cost-effective manner. Sperm cryopreservation increased the rejection of otherwise acceptable donors by 27%.


Teaching Forensic Entomology, Forensic Anthropology, and Haematology & Serology during the COVID-19 pandemic: Practical activities for distance learning.
As the COVID-19 pandemic upended college and university instruction throughout the world, instructors were hard-pressed to find suitable alternatives for practical activities typically carried out outside of classrooms-in laboratories, workshops, clinics, and in the field. In response to this unanticipated challenge, they relied on their ingenuity to achieve pre-pandemic goals under pandemic conditions that necessitated the shift to online teaching. The Forensic Science Undergraduate Program housed in the School of Medicine of the National Autonomous University of Mexico was not exempt from this educational upheaval but, due to its interdisciplinary nature, required creating and/or adopting a wide range of activities capable of training students to perform practical tasks associated with subject areas that span the natural and social sciences, the humanities, and the law. This report aims to describe the approaches undertaken in three subjects (Forensic Entomology, Forensic Anthropology, and Hematology & Serology) by interviewing instructors and examining their teaching materials. Also, through online surveys, students' reactions to these approaches were elicited to learn about their suitability and teaching potential. Instructor's experiences during the pandemic have proven to be a rich source of ingenious solutions, with implications well-beyond the current crisis, such as creating blended or fully online courses aimed at larger numbers of students, forensic and legal professionals, and even other instructors. The wide variety of forensic sciences offers the opportunity to innovate and improve the teaching and learning of science, particularly to the benefit of students that must combine their school tasks with professional and/or family duties.


Intensive physical training in geriatric patients after severe falls and hip surgery.
Intensive exercise training can lead to improvement in strength and functional performance in older people living at home and nursing home residents. There is little information whether intensive physical exercise may be applicable and effective in elderly patients suffering from the acute sequelae of injurious falls or hip surgery. To assess the feasibility, safety and efficacy of intensive, progressive physical training in rehabilitation after hip surgery. Prospective, randomised, placebo-controlled intervention study of a 3-months training intervention and a 3-months' follow-up. Physical training 6-8 weeks after hip surgery. Twenty-eight (15 intervention, 13 control) elderly patients with a history of injurious falls admitted to acute care or inpatient rehabilitation because of acute fall-related hip fracture or elective hip replacement. Progressive resistance and functional training to improve strength and functional performance. No training-related medical problems occurred in the study group. Twenty-four patients (86%) completed all assessments during the intervention and follow-up period. Adherence was excellent in both groups (intervention: 93, 0+/-13, 5% versus control: 96, 7+/-6, 2%). Training significantly increased strength, functional motor performance and balance and reduced fall-related behavioural and emotional problems. Some improvements in strength persisted during 3-months follow-up while other strength variables and functional performances were lost after cessation of training. Patients in the control group showed no change in strength, functional performance and emotional state during intervention and follow-up. Progressive resistance training and progressive functional training are safe and effective methods to increase strength and functional performance during rehabilitation in patients after hip surgery and a history of injurious falls. Because part of the training improvements were lost after stopping the training, a continuing training regime should be established.


Peri-aortic fluid after surgery on the ascending aorta: Worrisome indicator of complications or innocent postoperative finding?
The Bentall procedure is associated with several complications often accompanied by accumulation of fluid around the aortic graft. CT is the imaging modality of choice to detect these complications. Since these early complications are, however, not easily distinguished from physiological postoperative changes, our aim was to compare the appearance and amount of peri-aortic fluid on early CT scans following Bentall procedures with either an uncomplicated or a complicated course and follow-up. Ninety-four scans performed within 3 months of a Bentall procedure were retrospectively included. Patients were divided into either the uncomplicated or the complicated group based on occurrence of Bentall-related complications or death up until 1-year after surgery. Diffuse fluid ("stranding") was distinguished from organized, more clearly delineated fluid collections such as haematomas, and was graded both subjectively and quantitatively. Forty-seven patients were assigned to each group. Stranding was found on most of the scans, both in the uncomplicated (7.7±3.9mm, range 0-17mm) and complicated (6.9±5.5mm, range 0-19mm) groups (p=0.32). There were, however, significantly more fluid collections (6 vs. 28; p <0.001), particularly haematomas (1 vs. 17; p<0.001), in the complicated group. When looking at isolated stranding, there was still no significant difference between the two groups (7.8±3.6mm vs. 9.2±3.7mm; p=0.22). Isolated stranding of up to 17mm is a common finding on postoperative CT within three months of a Bentall procedure, regardless of the occurrence of complications during the procedure or within a 1-year follow-up. Fluid collections are more worrisome indicators of complications that may require closer monitoring.


Discrimination of consonance and dissonance in Java sparrows.
Six adult Java sparrows were trained to discriminate between consonant and dissonant sounds consisting of three tones. In the consonance group, the perching response was reinforced when consonance was presented, but not when dissonance was presented. Both groups were given an inversion test, in which the first inversion of the chord was used as a stimulus. Four of six birds learned the discrimination and were given two tests. In the first test, novel consonances and novel dissonances were presented. All birds maintained the discrimination. When inverted consonances and dissonances were presented in the second test, the discriminative behavior was not well demonstrated. When novel dissonances consisting of tones with different intervals were presented in the third test, birds trained to perch for dissonance performed well, whereas those trained to perch for consonance did not. In summary, Java sparrows were able to discriminate between consonances and dissonances and demonstrated generalization to new combinations, they do not discriminate the same consonances and dissonances.


Identification and classification of papain-like cysteine proteinases.
Papain-like cysteine peptidases form a big and highly diverse superfamily of proteins involved in many important biological functions, such as protein turnover, deubiquitination, tissue remodeling, blood clotting, virulence, defense, and cell wall remodeling. High sequence and structure diversity observed within these proteins hinders their comprehensive classification as well as the identification of new representatives. Moreover, in general protein databases, many families already classified as papain like lack details regarding their mechanism of action or biological function. Here, we use transitive remote homology searches and 3D modeling to newly classify 21 families to the papain-like cysteine peptidase superfamily. We attempt to predict their biological function and provide structural characterization of 89 protein clusters defined based on sequence similarity altogether spanning 106 papain-like families. Moreover, we systematically discuss observed diversity in sequences, structures, and catalytic sites. Eventually, we expand the list of human papain-related proteins by seven representatives, including dopamine receptor-interacting protein 1 as potential deubiquitinase, and centriole duplication regulating CEP76 as retaining catalytically active peptidase-like domain. The presented results not only provide structure-based rationales to already existing peptidase databases but also may inspire further experimental research focused on peptidase-related biological processes.


Communicating the risk of contracting Zika virus to low income underserved pregnant Latinas: A clinic-based study.
Frequent travel between the Southern border states in the USA, Mexico, and Latin American countries increases the risk of the Zika virus (ZIKV) spread. Patient education on virus transmission is fundamental in decreasing the number of imported cases, particularly among pregnant women. The study used cross-sectional methodology to investigate information sources and knowledge concerning the ZIKV virus among 300 under-served pregnant Latinas recruited from prenatal care clinics in the North Texas region. Bivariate and multiple logistic regression models were used to investigate associations between the primary outcomes and patient characteristics. Physicians, nurses, and families are the major sources for pregnancy information, while media/internet (65%) and physician/nurse (33%) are the main sources for ZIKV information. Less than one-half of the mothers reported that their physician/nurse did not discuss safe sexual practices or inquired about their sexual practices. A considerable proportion of women from the community clinic were neither warned nor queried about travel to ZIKV risk countries. There is an overall understanding of Zika virus transmission, symptoms, complications, and recommended guidelines. Younger age and single mother status are risk factors for lack of ZIKV knowledge. Foreign-born mothers are 2.5-3.0 times more likely to have knowledge on disease transmission, symptoms, and microcephaly condition. While, younger mothers (18-24) are less likely to have knowledge of ZIKV infection symptoms (fever, rash and pink eye) and transmission of infection via unprotected sexual (vaginal, anal, or oral) behavior, compared to older mothers. Interventions are needed to heighten the knowledge of ZIKV, particularly among women of reproductive age and their male partners in the community health care setting. Our study underscores the need for health care providers to be trained in delivering messages to enhance risk perception during health emergencies to vulnerable and underserved families (lower economic background, language ability, and culture). During health emergencies, clinics must disseminate crucial information via multi modalities to ensure messages reach the targeted patients.


Analysis of clinical case records from dairy co-operatives in Bangladesh.
Records of 28,266 clinical cases collected over a period of three years from a veterinary clinical service to small dairy farms in Bangladesh were analysed. The major clinical conditions encountered were those which adversely affect the performance of draught animals and those causing infertility. Gastrointestinal disorders and general debility were also of major significance. It was concluded that the most pressing constraint on cattle productivity in Bangladesh is inadequate nutrition. Although infectious diseases were of minor importance overall, annual epidemics of foot-and-mouth disease were associated with seasonal movement of cattle. Difficulties involved in the analysis of clinical case records are discussed.


Predicting spring migration of two European amphibian species with plant phenology using citizen science data.
Habitat fragmentation is one of the drivers for amphibian population declines globally. Especially in industrialized countries roads disrupt the seasonal migration of amphibians between hibernation and reproduction sites, often ending in roadkills. Thus, a timely installing of temporary mitigation measures is important for amphibian conservation. We wanted to find out if plant phenology can be a proxy in advance to determine the start of amphibian migration, since both phenomena are triggered by temperature. We analysed data of 3751 amphibian and 7818 plant phenology observations from citizen science projects in Austria between 2000 and 2018. Using robust regression modelling we compared the migration of common toads (Bufo bufo) and common frogs (Rana temporaria) with the phenology of five tree, one shrub, and one herb species. Results showed close associations between the migration of common frogs and phenological phases of European larch, goat willow and apricot. Models based on goat willow predict migration of common frog to occur 21 days after flowering, when flowering was observed on 60th day of year; apricot based models predict migration to occur 1 day after flowering, observed on the 75th day of year. Common toads showed weaker associations with plant phenology than common frogs. Our findings suggest that plant phenology can be used to determine the onset of temporary mitigation measures for certain amphibian species to prevent roadkills.


National character, suicide and homicide.
In a sample of 18 industrialized nations with available data, mean scores on the "big five factors" were not significantly associated with national suicide or homicide rates.


Location of rat liver iodothyronine deiodinating enzymes in the endoplasmic reticulum.
The iodothyronine-deiodinating enzymes (iodothyronine-5- and 5'-deiodinase) of rat liver were found to be located in the parenchymal cells. Differential centrifugation of rat liver homogenate revealed that the deiodinases resided mainly in the microsomal fraction. The subcellular distribution pattern of these enzymes correlated best with glucose-6-phosphatase, a marker enzyme of the endoplasmic reticulum. Plasma membranes, prepared by discontinuous sucrose gradient centrifugation, were found to contain very little deiodinating activity. Analysis of fractions obtained during the course of plasma membrane isolation showed that the deiodinases correlated positively with glucose-6-phosphatase (r larger than or equal to 0.98) and negatively with the plasma membrane marker 5'-nucleotidase (r ranging between -0.88 and -0.97). It is concluded that the iodothyronine-deiodinating enzymes of rat liver are associated with the endoplasmic reticulum.


Utility of linear mixed effects models for event-related potential research with infants and children.
Event-related potentials (ERPs) are advantageous for investigating cognitive development. However, their application in infants/children is challenging given children's difficulty in sitting through the multiple trials required in an ERP task. Thus, a large problem in developmental ERP research is high subject exclusion due to too few analyzable trials. Common analytic approaches (that involve averaging trials within subjects and excluding subjects with too few trials, as in ANOVA and linear regression) work around this problem, but do not mitigate it. Moreover, these practices can lead to inaccuracies in measuring neural signals. The greater the subject exclusion, the more problematic inaccuracies can be. We review recent developmental ERP studies to illustrate the prevalence of these issues. Critically, we demonstrate an alternative approach to ERP analysis-linear mixed effects (LME) modeling-which offers unique utility in developmental ERP research. We demonstrate with simulated and real ERP data from preschool children that commonly employed ANOVAs yield biased results that become more biased as subject exclusion increases. In contrast, LME models yield accurate, unbiased results even when subjects have low trial-counts, and are better able to detect real condition differences. We include tutorials and example code to facilitate LME analyses in future ERP research.


Correlation between vestibular neuritis and cerebrovascular risk factors.
To investigate the relationship between cerebrovascular risk factors, including carotid plaques, and vestibular neuritis (VN). According to the inclusion and exclusion criteria, this retrospective study included 90 VN patients and 74 age- and sex-matched healthy controls from January 2016 to December 2017. All subjects' records of cerebrovascular risk factors, such as age, sex, height, weight, history of hypertension and diabetes mellitus, living habits, serum levels of glucose, lipids, glycosylated haemoglobin (HbA1c), creatinine (CR), albumin (ALB), haemoglobin (HGB); and results of carotid colour Doppler ultrasound, were obtained and compared. No significant differences in age; sex ratio; body mass index; history of hypertension or diabetes mellitus; or mean serum lipids, glucose, creatinine, haemoglobin or HbA1c were found between patients with VN and healthy controls (all P > 0.05). The mean serum ALB level was significantly lower in VN patients than in healthy controls (40.65 ± 3.77 vs 42.84 ± 4.32, P = 0.001).The prevalence of carotid plaques was significantly higher in VN patients than in healthy controls (36.67% vs. 16.22%, P = 0.003). Regression analyses demonstrated that a high frequency of carotid plaques was associated with VN with an odds ratio of 2.252 (95% CI 1.165-5.458, P = 0.019). A high frequency of carotid plaques may be a risk factor for VN.


Previsit Multidomain Psychosocial Screening Tools for Adolescents and Young Adults: A Systematic Review.
Adolescence and young adulthood constitute a period when exploratory behaviors can evolve into risky behaviors. Most causes of adolescent ill health are preventable; therefore, it is a priority to detect them early before they turn into health problems. Previsit multidomain psychosocial screening tools are used by professionals to detect and prioritize potentially problematic issues. In conjunction with appropriate clinician training, these tools have improved clinician screening rates in several areas of adolescent health. This article reviews existing multidomain previsit psychosocial screening tools developed in the 21st century and describes their characteristics using a systematic methodology. We reviewed 10,623 records to identify 15 different tools in use since 2000 and described their characteristics. Results show that all tools were developed in high-income countries. The tools provide sufficient coverage of many psychosocial domains relevant to young people's health. However, some psychosocial domains such as screen use and strengths are seldomly addressed. Furthermore, the tools rarely focus on young adults as a target population. Future research should assess the effectiveness, acceptability, and psychometric properties of validated psychosocial screening tools and examine how to expand their use in low- and middle-income countries.