Down-regulation of microRNA let-7d inhibits the proliferation and invasion of trophoblast cells in preeclampsia.
Preeclampsia (PE) is a serious pregnancy complication that continues to adverse effects on mother and the fetus. The study investigated the effect of microRNA let-7d (miR-let-7d) on the proliferation and invasion of trophoblast cells (TC) in PE. In situ hybridization techniques were employed to evaluate the miR-let-7d expressions in the placental tissues from 63 PE patients as well as 65 normal placental tissues. Transfection of pre-let-7d, anti-let-7d, and their corresponding control sequences was performed in TCs obtained from PE. The blank group was composed of TCs no transfection and normal group consisted of normal TCs. Expressions of proliferation and invasion markers in TCs were detected by qRT-PCR. Proliferation, apoptosis, and the invasion ability of the TCs were determined using a CCK-8 assay, flow cytometry, and Transwell assay. In comparison to the normal placental tissues, PE placental tissues exhibited increased levels of let-7d expression. Following transfection of anti-let-7d, when compared with the blank group, the anti-let-7d group displayed increased levels of proliferation ability, expression of proliferation labeling proteins PCNA and Ki67, number of TCs as well as expressions of the invasion related proteins MMP-2, MMP-9, and TIMP-1. In contrast declines in cell apoptosis rate were observed. Compared with the blank group, the changes of the indexes were reversed in the pre-let-7d group. The study provided evidence suggesting that low expression levels of miR-let-7d plays a central role in suppressing apoptosis in addition to promoting the proliferation and invasion of PE TCs.


[Etiologic implication of foods in atopic dermatitis: evidence against].
Atopic dermatitis is a typical chronic inflammatory skin disease that usually occurs in individuals with a personal or family history of atopy. Children with atopic dermatitis frequently present IgE-mediated food sensitization, the most commonly involved foods being egg and cow's milk. However, controversy currently surrounds whether food allergy is an etiological factor in atopic dermatitis or whether it is simply an associated factor, accompanying this disease as one more expression of the patient's atopic predisposition. Approximately 40 % of neonates and small children with moderate-to-severe atopic dermatitis present food allergy confirmed by double-blind provocation tests but this allergy does not seem to be the cause of dermatitis since in many cases onset occurs before the food responsible for allergic sensitization is introduced into the newborn's diet.Studies of double-blind provocation tests with food in patients with atopic dermatitis demonstrate mainly immediate reactions compatible with an IgE-mediated allergy. These reactions occur between 5 minutes and 2 hours and present mainly cutaneous symptoms (pruritus, erythema, morbilliform exanthema, wheals) and to a lesser extent, digestive manifestations (nausea, vomiting, abdominal pain, diarrhea), as well as respiratory symptoms (wheezing, nasal congestion, sneezing, coughing). However, these reactions do not indicate the development of dermatitis.Some authors believe that responses to the food in provocation tests may also be delayed, appearing mainly in the following 48 hours, and clinically manifested as exacerbation of dermatitis. However, delayed symptoms are difficult to diagnose and attributing these symptoms to a particular foodstuff may not be possible.Delayed reactions have been attributed to a non-IgE-mediated immunological mechanism and patch tests with food have been proposed for their diagnosis. In our experience and in that of other authors, the results of patch tests with cow's milk do not seem very specific and could be due, at least in part, to the irritant effect of these patches on the reactive skin of children with atopic dermatitis.The involvement of foods in atopic dermatitis will always be difficult to demonstrate given that an exclusion diet is not usually required for its resolution. Food is just one among several possible exacerbating factors and consequently identification of its precise role in the course of the disease is difficult. Further double-blind prospective studies are required to demonstrate the effectiveness of exclusion diets in the treatment of atopic dermatitis.Apart from the controversy surrounding the etiological role of foods, the most important point in atopic dermatitis is to understand that the child is atopic, that is, predisposed to developing sensitivity to environmental allergens; in the first few years of life to foods and subsequently to aeroallergens. Consequently, possible allergic sensitization to foods should be evaluated in children with atopic dermatitis to avoid allergic reactions and to prevent the possible development of allergic respiratory disease later in life.


Leukocyte Ig-like receptor A3 facilitates inflammation, migration and invasion of synovial tissue-derived fibroblasts via ERK/JNK activation.
LILRA3 is a soluble receptor belongs to the immunoglobulin superfamily. Our previous studies demonstrated that LILRA3 is a common genetic risk for multiple autoimmune diseases, including rheumatoid arthritis (RA). Functional LILRA3 conferred increased risk of joint destruction in patients with early RA. We undertook this study to further investigate the pathological role of LILRA3 in joint inflammation of RA. Soluble LILRA3 were measured by ELISA. LILRA3 plasmids were transfected into human fibroblast-like synoviocytes (FLSs) using electroporation. Activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) were determined by Western blots. Cytokine transcripts were quantified by real-time PCR. Migratory and invasive capacities of FLSs were evaluated using transwell migration and matrigel invasion assays. FLS apoptosis was analyzed using flow cytometry. Co-localization of LILRA3, LILRB1, and HLA-G in RA-FLSs were visualized by immunofluorescence staining. Soluble LILRA3 was specifically expressed in synovial fluids and serum LILRA3 was significantly increased and positively correlated with disease activity/severity in RA patients. LILRA3 induced an increased expression of interleukin (IL)-6, IL-8 and matrix metalloproteinase (MMP) 3 in RA-FLSs. In vitro LILRA3 stimulation/overexpression promoted RA-FLS migration and invasion, and enhanced phosphorylation of ERK/JNK. Inhibition of ERK/JNK resulted in suppression of IL-6/IL-8 expression in LILRA3-stimulated RA-FLSs. LILRA3 was co-localized with its homologue LILRB1 and shared ligand HLA-G in RA-FLSs. The present study provides the first evidence that soluble LILRA3 is a novel proinflammatory mediator involved in synovial inflammation by promoting RA-FLS activation, migration and invasion, probably through the ERK/JNK signalling pathways.


Gender Can Influence Student Experiences in MD-PhD Training.
Background: Female physician-scientists have led major advances in medicine broadly and particularly in women's health. Women remain underrepresented in dual MD-PhD degree programs that train many physician-scientists despite gender parity among medical and biomedical research students. Materials and Methods: To explore how the training environment might be experienced differently for male and female students in one MD-PhD program, the authors analyzed gender differences in annual symposium speakers with exact binomial tests, student participation as question-askers at a weekly seminar with logistic regression, and number of publications with quasi-Poisson generalized linear models. They compared male and female students' perceptions of gender-based discrimination using a survey, including qualitative analysis of free text responses. The program consisted of 71 total students in the 2017-2018 and 2018-2019 academic years. Female students comprised 42.0% (81/191) of program matriculants from 1997 to 2019. Results: Male and female students were equally likely to present at the annual program symposium, but faculty (p = 0.001) and keynote (p = 0.012) presenters were more likely to be male. Compared with male counterparts, female students asked fewer seminar questions (p < 0.005) and female speakers received more questions (p = 0.03). Female students perceived less support and differed from men in reasons for asking or not asking seminar questions. Free text responses described repeated small acts of discrimination toward women with cumulative impact. Positive program changes followed presentation of findings to program leaders and students. Conclusions: The authors identified several aspects of one MD-PhD program that could discourage career or training persistence of female students. Increasing awareness of these issues was temporally related to positive programmatic changes.


Regression of primary central nervous system germinoma after dexamethasone administration: a case report.
Childhood central nervous system (CNS) germinoma are highly curable brain tumors characterized pathologically by varying degrees of lymphocytic infiltration. The authors present a case of a CNS germinoma with significant regression in size following surgery and administration of dexamethasone, prior to initiation of chemotherapy or irradiation. The authors speculate the possible mechanism involved in its occurrence. Perioperative corticosteroid administration in patients with CNS germinoma may obfuscate the increase in response demonstrated with various chemotherapy regimens or with irradiation in CNS germinomas.


Impact of positive end-expiratory pressure on cardiac index measured by ultrasound cardiac output monitor*.
To evaluate the impact of different levels of positive end-expiratory pressure on cardiac index in children receiving mechanical ventilation. To explore the effect of lung recruitment on the relationship between positive end-expiratory pressure and cardiac output. Prospective, single center, and interventional. PICU in a tertiary care children's hospital. Fifty mechanically ventilated, hemodynamically stable children between 1 month and 20 years old. Positive end-expiratory pressure was altered to levels of 0, 4, 8, and 12 cm H2O in random order. Cardiac output was measured at different levels of positive end-expiratory pressure by continuous wave Doppler ultrasound (ultrasound cardiac output monitor). Baseline vital signs were recorded, as well as cardiac index and dynamic compliance of the respiratory system at each positive end-expiratory pressure level. Median cardiac index decreased marginally as positive end-expiratory pressure increased, with a median change in cardiac index of 0.4 (< 10%) between positive end-expiratory pressure of 0 and 12 cm H2O (p < 0.001). There was no difference in heart rate or blood pressure as positive end-expiratory pressure increased (p > 0.5). For a subset of 29 patients (58%) in whom the highest dynamic compliance was at a positive end-expiratory pressure of 4 or 8 cm H2O, there was no difference in cardiac index between positive end-expiratory pressure 4 below versus positive end-expiratory pressure at highest dynamic compliance, or cardiac index between positive end-expiratory pressure 4 above versus positive end-expiratory pressure at highest dynamic compliance (p > 0.2). Regardless of optimal dynamic compliance, cardiac index decreased as positive end-expiratory pressure increased (p = 0.02). In hemodynamically stable mechanically ventilated children, although there is a statistically significant decrease in cardiac output as positive end-expiratory pressure is increased between 0 and 12 cm H2O, the mean change is less than 10%, and this is likely not clinically significant. In the presence of lung disease, intensive care physicians should feel less reluctant in their use of positive end-expiratory pressure for hemodynamically stable patients.


Augmented agonist-induced Ca(2+)-sensitization of coronary artery contraction in genetically hypertensive rats. Evidence for altered signal transduction in the coronary smooth muscle cells.
The Ca2+ responsiveness of vascular smooth muscle myofilaments is not unique: it is increased during neuro-humoral activation and decreased during beta-adrenergic stimulation. In this study we tested whether an augmented Ca2+ responsiveness of smooth muscle myofilaments may contribute to the increased coronary tone observed in hypertension using beta-escin-permeabilized coronary arteries from 3-mo-old stroke-prone spontaneously hypertensive rats (SHRSP) and their age matched normotensive reference strain (WKY rats). In intact coronary arteries, the response to 5-hydroxytryptamine (5-HT) but not to KCl was larger in SHRSP than in WKY rats. In beta-escin permeabilized coronary arteries in which the receptor effector coupling is still intact, 5-HT enhanced force at constant submaximal (Ca2+) (pCa 6.38) to a greater extent in SHRSP. The Ca2+ sensitizing effect of 5-HT was mimicked by GTP gamma S (0.01-10 microM); again this effect was larger in SHRSP. In the absence of 5-HT or GTP gamma S the Ca2+ force relation was similar in both groups. Forskolin induced relaxation at constant submaximal (Ca2+). This desensitizing effect was smaller in SHRSP than in WKY rats. In conclusion, this study shows that intracellular signalling pathways involved in modulating the Ca2+ responsiveness of coronary smooth muscle myofilaments are altered in the genetically hypertensive animals favoring a hypercontractile state in the coronary circulation.


Conditionally lethal and recessive UGA-suppressor mutations in the prfB gene encoding peptide chain release factor 2 of Escherichia coli.
Strains carrying mutations in the prfB gene encoding peptide chain release factor 2 of Escherichia coli were isolated. prfB1, prfB2, and prfB3 were selected as suppressor mutations of a lacZ (UGA) mutation at 37 degrees C, one of which, prfB2, is temperature sensitive in growth. A prfB286 strain was selected as a conditionally lethal mutant which grows at 32 but not at 43 degrees C and was shown to have UGA-suppressor activity. All the mutations are recessive UGA-suppressors. These data indicate that release factor 2 is essential to E. coli growth and that all mutants isolated here trigger suppression of the UGA codon.


Characteristics and source apportionment of PM2.5 in Jiaxing, China.
Herein we investigated the morphology, chemical characteristics, and source apportionment of fine particulate matter (PM2.5) samples collected from five sites in Jiaxing. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) showed that soot aggregates and coal-fired fly ash were generally the most abundant components in the samples. All the samples were analyzed gravimetrically for mass concentrations and their various compositions were determined. Our results revealed that the PM2.5 concentrations in the samples were in the following order: winter > spring > autumn > summer. The PM2.5 concentrations in winter and spring were higher than those in autumn and summer, except for inorganic elements. Carbonaceous species and water-soluble inorganic ions were the most abundant components in the samples, accounting for 26.17-50.44% and 34.27-49.6%, respectively. The high secondary organic carbon/organic carbon ratio indicated that secondary organic pollution in Jiaxing was severe. The average ratios of NO3-/SO42-, ranging from 1.01 to 1.25 at the five sites, indicated that mobile pollution sources contributed more to the formation of PM2.5 than stationary sources. The BeP/(BeP + BaP) ratio (0.52-0.71) in samples reflected the influence of transportation from outside of Jiaxing. The positive matrix factorization (PMF) model identified eight main pollution sources: secondary nitrates (26.95%), secondary sulfates (15.49%), secondary organic aerosol (SOA) (19.64%), vehicle exhaust (15.67%), coal combustion (8.6%), fugitive dust (7.7%), ships and heavy oil (5.23%), biomass burning, and other sources (0.91%). Therefore, PM2.5 pollution in Jiaxing during the winter and spring seasons was more severe than that in the summer and autumn. Secondary aerosols were the most important source of PM2.5 pollution; therefore, focus should be placed on controlling gaseous precursors.


Lovastatin induces VSMC differentiation through inhibition of Rheb and mTOR.
It is becoming increasingly clear that cholesterol-independent effects of statins also contribute to the cardioprotective effects, but these mechanisms remain poorly understood. We investigated the effects of lovastatin on vascular smooth muscle phenotype. We have previously shown that mammalian target of rapamycin complex 1 (mTORC1) inhibition with rapamycin induces vascular smooth muscle cell (VSMC) differentiation. We found that lovastatin also inhibits mTORC1 signaling and that this inhibition is required for VSMC differentiation. Lovastatin inhibition of mTORC1 was farnesylation dependent, suggesting the farnesylated G protein Rheb (Ras homologue enriched in brain), a known upstream activator of mTORC1. Rheb overexpression induced mTORC1 activity and repressed contractile protein expression, but a farnesylation-deficient mutant (C18S) elicited the opposite effect. Rheb knockdown with small interfering RNA was also sufficient to inhibit mTORC1 and induce contractile protein expression, and it prevented statin-induced VSMC differentiation. Notably, mTORC1 activity was elevated in VSMC isolated from an intimal hyperplastic patient lesion compared with normal media, and lovastatin treatment inhibited mTORC1 activity in these cultures. Furthermore, lovastatin inhibited mTORC1 activity and prevented the downregulation of contractile protein expression in an ex vivo angioplasty model. In conclusion, these findings illustrate a mechanism for the cardioprotective effects of lovastatin through inhibition of Rheb and mTORC1 and promotion of a differentiated VSMC phenotype.


Innate receptors and cellular defense against pulmonary infections.
In the United States, lung infections consistently rank in the top 10 leading causes of death, accounting for >50,000 deaths annually. Moreover, >140,000 deaths occur annually as a result of chronic lung diseases, some of which may be complicated by an infectious process. The lung is constantly exposed to the environment and is susceptible to infectious complications caused by bacterial, viral, fungal, and parasitic pathogens. Indeed, we are continually faced with the threat of morbidity and mortality associated with annual influenza virus infections, new respiratory viruses (e.g., SARS-CoV), and lung infections caused by antibiotic-resistant "ESKAPE pathogens" (three of which target the lung). This review highlights innate immune receptors and cell types that function to protect against infectious challenges to the respiratory system yet also may be associated with exacerbations in chronic lung diseases.


[Interstitial irradiation of rectal carcinoma with rectal template].
Using Iridium-192 wires through a rectal template after Syed, interstitial brachytherapy was conducted in a patient with inoperable adenocarcinoma of the rectum. 67-year-old man with constipation and change in the stool caliber underwent external radiotherapy (4,000 cGy/4 W) to the whole pelvis including the perineum, followed by interstitial implant using a template, at the Department of Radiology, Osaka University Hospital. Marked tumor regression, marked circumferential fibrosis and a remarkable decline of CEA titers (pre-RT: 35.8 ng/ml, post-RT: 6.2 ng/ml) were observed until 7 months post-RT. The domestic production of Iridium-192 wires has made possible the integrated use of brachytherapy in the perineal region in Japan.


Global survey of escape from X inactivation by RNA-sequencing in mouse.
X inactivation equalizes the dosage of gene expression between the sexes, but some genes escape silencing and are thus expressed from both alleles in females. To survey X inactivation and escape in mouse, we performed RNA sequencing in Mus musculus x Mus spretus cells with complete skewing of X inactivation, relying on expression of single nucleotide polymorphisms to discriminate allelic origin. Thirteen of 393 (3.3%) mouse genes had significant expression from the inactive X, including eight novel escape genes. We estimate that mice have significantly fewer escape genes compared with humans. Furthermore, escape genes did not cluster in mouse, unlike the large escape domains in human, suggesting that expression is controlled at the level of individual genes. Our findings are consistent with the striking differences in phenotypes between female mice and women with a single X chromosome--a near normal phenotype in mice versus Turner syndrome and multiple abnormalities in humans. We found that escape genes are marked by the absence of trimethylation at lysine 27 of histone H3, a chromatin modification associated with genes subject to X inactivation. Furthermore, this epigenetic mark is developmentally regulated for some mouse genes.


Adrenal origin of the increase in plasma dopamine beta-hydroxylase and catecholamines induced by hemorrhagic hypotension in dogs.
Controlled hemorrhagic hypotension in anesthetized dogs causes progressive increases in dopamine beta-hydroxylase (DBH) and catecholamine (CA) plasma levels and in heart rate. The concentration (units per milliliter) and the calculated total plasma content of DBH activity [(units circulating + reservoir + samples] increased 2.6 and 2.3 times, respectively. A significant positive correlation (P less than .001) was found between the plasma levels of DBH and CA; however, the CA plasma levels increased earlier and were of greater magnitude (10-fold) than those of DBH. These results suggest that CAs are more sensitive indicators of acute changes in adrenergic activity than DBH. Surgical bilateral adrenalectomy completely abolished the increases in circulating CA and DBH levels and in heart rate induced by the hemorrhage, independently of the percentage of blood removed. These results indicate that the adrenal glands contribute almost exclusively to the rise in plasma DBH and CA caused by the bleeding stress and that high circulating CA concentrations seem to account for the tachycardia that accompanies the hemorrhagic hypotension. The infusion of the reservoir blood with a lower DBH and CA content than that present in the animal at that time produced a rapid fall in circulating CA levels (59.2 +/- 8.9 to 10.8 +/- 3.3 ng/ml) and no change in the DBH concentration (5.43 +/- 0.42 and 5.40 +/- 0.53 U/ml). A 38% increase in the calculated total plasma content of DBH occurred with the transfusion. Due to the large size of the DBH molecules, trapping in tissues during the hemorrhagic hypotension period might have occurred. The improvement in the hemodynamic conditions caused by the transfusion would facilitate the washout of the enzyme from the tissues into the circulation.


Enhancement of ouabain arrhythmias by fatty acids.
Possible enhancement by free fatty acids (FFA) of the arrhythmogenic actions of ouabain was studied in rabbits. The mean dose of ouabain required for inducing ventricular tachycardia or fibrillation in conscious animals was significantly lowered by intravenous injection of 5 ml of a 20% fat emulsion (Lipofundin), which significantly elevated circulating FFA. Lipofundin alone did not initiate arrhythmias in another group of animals. The transmembrane action potential duration (APD) and the maximum rate of depolarization (Vmax)recorded from rabbit papillary muscles were markedly reduced under the influence of 2 mM octanoate, a short-chain FFA. Ouabain, 10(-7M), reduced significantly only the APD measured at zero level of repolarization. In papillary muscles exposed to both octanoate and ouabain, resting potential, overshoot, APD, and Vmax were all significantly decreased below control values. The synergistic arrhythmogenic actions of FFA and ouabain might be explained by the inhibiting effect of both agents on membrane (Na+ + K+)ATPase.


Social media interventions for autistic individuals: Systematic review.
Research on the use of digital technologies for delivering behavioral interventions has shown mixed evidence on their efficacy for improving both autistic symptoms and co-occurring psychiatric disorders. Little knowledge exists on the specific use or efficacy of using social media in interventions aimed at autistic individuals. To review and describe the current existing evidence-based research on the use of social media in interventions aimed at autistic individuals. A search was conducted across 8 databases (PubMed; EMBASE; Cochrane Library; PsycInfo; ERIC; Education Source; Web of Science; and IEEE Xplore). We included primary studies and reviews that dealt with autism spectrum disorder (ASD); described interventions that use social media; and reported results from the intervention. The quality of the evidence of the included primary studies was graded according to the GRADE criteria, and the risk of bias in systematic reviews was assessed by drawing on the AMSTAR guidelines. Results were synthesized and sorted by quality of evidence. A total of nine articles were included in this review: eight primary studies (five non-randomized interventions and three randomized interventions) and one systematic review. The total number of participants with an ASD-diagnosis in the included studies was 164 (aged 5 to 22 years old). Studies weighted as being of moderate quality of evidence have reported significant positive effects in the groups that received the social media interventions: increased social engagement and participation in life situations; increased physical activity level; increased improvement on occupational performance, specified goals, and behavioral problems; and decreased plaque scores coupled with parent reports of intervention success. None of the studies have reported any negative effects linked to social media interventions. There is very little evidence of good quality on the use of social media in interventions aimed at autistic individuals. While there is a need for more high-quality studies, all the included studies, with one exception found positive results of the interventions. These findings are encouraging, suggesting that social media-based interventions may in fact be useful for supporting behavioral changes in autistic individuals. https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=337185, identifier CRD42022337185.


More effective strategies are required to strengthen public awareness of COVID-19: Evidence from Google Trends.
The outbreak of coronavirus disease 2019 (COVID-19) has posed stress on the health and well-being of both Chinese people and the public worldwide. Global public interest in this new issue largely reflects people's attention to COVID-19 and their willingness to take precautionary actions. This study aimed to examine global public awareness of COVID-19 using Google Trends. Using Google Trends, we retrieved public query data for terms of "2019-nCoV + SARS-CoV-2 + novel coronavirus + new coronavirus + COVID-19 + Corona Virus Disease 2019" between the 31st December 2019 and the 24th February 2020 in six major English-speaking countries, including the USA, the UK, Canada, Ireland, Australia, and New Zealand. Dynamic series analysis demonstrates the overall change trend of relative search volume (RSV) for the topic on COVID-19. We compared the top-ranking related queries and sub-regions distribution of RSV about COVID-19 across different countries. The correlation between daily search volumes on the topic related to COVID-19 and the daily number of people infected with SARS-CoV-2 was analyzed. The overall search trend of RSV regarding COVID-19 increased during the early period of observing time and reached the first apex on 31st January 2020. A shorter response time and a longer duration of public attention to COVID-19 was observed in public from the USA, the UK, Australia, and Canada, than that in Ireland and New Zealand. A slightly positive correlation between daily RSV about COVID-19 and the daily number of confirmed cases was observed (P < 0.05). People across countries presented a various interest to the RSV on COVID-19, and public awareness of COVID-19 was different in various sub-regions within countries. The results suggest that public response time to COVID-19 was different across countries, and the overall duration of public attention was short. The current study reminds us that governments should strengthen the publicity of COVID-19 nationally, strengthen the public's vigilance and sensitivity to COVID-19, inform public the importance of protecting themselves with enough precautionary measures, and finally control the spread of COVID-19 globally.


On the electron correlation effects on electronic and vibrational hyperpolarizability of merocyanine dyes.
Using various ab initio methods (including many-body perturbation theory and coupled cluster method), the full tensor of electronic and vibrational contributions to the first-order hyperpolarizability (beta) for three molecules belonging to the group of merocyanine dyes was computed. Unexpectedly large correlation effects were observed in the electronic counterpart of nonlinear optical response. The analysis of the electronic structure, performed for one of the investigated molecules, reveals that it is the polarity of the low-lying excited state that is affected most upon inclusion of the electron correlation. The vibrational contributions to beta are not significantly influenced by the applied level of theory.


PKCalpha activation downregulates ATM and radio-sensitizes androgen-sensitive human prostate cancer cells in vitro and in vivo.
We previously demonstrated that treatment of human androgen-responsive prostate cancer cell lines LNCaP and CWR22-Rv1 with 12-O-tetradecanoylphorbol 13-acetate (TPA), a known protein kinase C (PKC) activator, decreases ATM protein levels, thus de-repressing the enzyme ceramide synthase (CS) and promoting apoptosis as well as radio-sensitizing these cells.(1) Here we show that PKCalpha mediates the TPA effect on ATM expression, since ATM suppression and apoptosis induced by either TPA or diacylglycerol-lactone (DAG-lactone), both inducing PKCalpha activation,(2) are abrogated in LNCaP cells following transfection of a kinase-dead PKCalpha mutant (KD-PKCalpha). Similarly, KD-PKCalpha blocks the apoptotic response elicited by combination of TPA and radiation, whereas expression of constitutively active PKCalpha is sufficient to sensitize cells to radiation alone, without a need to pre-treat the cells with TPA. These findings identify CS activation as a downstream event of PKCalpha activity in LNCaP cells. Similar results were obtained in CWR22-Rv1 cells with DAG-lactone treatment. Using the LNCaP orthotopic prostate model it is shown that treatment with TPA or DAG-lactone induces significant reduction in tumor ATM levels coupled with tumor growth delay. Furthermore, while fractionated radiation alone produces significant tumor growth delay, pretreatment with TPA or DAG-lactone significantly potentiates tumor cure. These findings support a model in which activation of PKCalpha downregulates ATM, thus relieving CS repression by ATM and enhancing apoptosis via ceramide generation. This model may provide a basis for the design of new therapies in prostate cancer.


[Antiphospholipid syndrome and antiphospholipid antibodies as a risk factors of ischaemic heart disease and myocardial infarction in patients with systemic lupus erythematosus].
Ischemic heart disease and myocardial infarction in patients with SLE--are usually secondary to early coronary atherosclerosis. Estimation if antiphospholipid syndrome and antiphospholipid antibodies are the risk factor for myocardial infarction and ischemic heart disease in patients with TRU. We examined 129 patients with SLE (114 women and 15 men). All the patients underwent comprehensive physical examination. ECG, ultrasound heart examinations were performed. They were followed by heart scintygraphic examination if indicated. Routine biochemical and hematological laboratory tests were performed including fasting glucose level, concentration of homocysteine, uric acid and lipids. Wide range of immunological essays were performed, testing for antinuclear antibodies (ANA), extractable nuclear antigen antibodies (ENA), antiphospholipid antibodies (anticardiolipin antibodies--aCL, lupus anticoagulant--LA, antiprothrombine antibodies aPT, anti-beta2glicoprotein-I antibodies), anti-dsDNA antibodies, anti-nucleosome antibodies, antihistone antibodies, antineutrophil cytoplasmic antibodies (ANCA) and antiendothelial antibodies (AECA). Statistical analysis was performed with chi2 Yates, chi2 Pearson and R rang Spearman tests. Multivariate regression analysis was also done. Ischemic heart disease was found in 20 (15.5%) SLE patients, myocardial infarctions were diagnosed in 9 (6.97%). Ischemic heart disease and myocardial infarction were significantly related to presence of secondary antiphospholipid syndrome (SAPS), OR: 4.21, p = 0.008 and OR: 12.8; p = 0.02 respectively). They were also related to high activity of SLE, OR: 7.18; p = 0.012 and OR: 27.3; p = 0.006 respectively. Ischemic heart disease was significantly more common in older patients (52.75 years versus 42.15 years; p = 0.0008) and in patients with hypertension (p < 0.05). Impaired glucose tolerance (OR: 8.44; p = 0.03), presence of aCL IgG (OR; 2.93; p = 0.05) and p-ANCA anti-MPO (OR: 6.08; p = 0.036) were found to be risk factors of ischemic heart disease. Myocardial infarction was significantly associated with high uric acid level (OR: 5.01; p = 0.052) and impaired glucose tolerance (OR: 7.42; p = 0.047) and with presence of the following antibodies: aCL IgG and/or aCL IgM (OR: 5.61; p = 0.039), ANCA in the indirect immunofluorescence essay (OR: 5.78; p = 0.035), anti-MPO antibodies (OR: 6.58; p = 0.051) and AECA (OR: 11.10; p = 0.026). Presence of antiphospholipid antibodies and SAPS are significant risk factors of ischemic heart disease and myocardial infarction in SLE patients. The risk factors of ischemic heart disease and myocardial infarction in SLE patients significantly differ from the ones in general population.


Relationship between left ventricular diastolic dyssynchrony and systolic dyssynchrony in hypertrophic cardiomyopathy by single-cardiac real-time three-dimensional ultrasonography.
The relationship between left ventricular diastolic and systolic dyssynchrony in hypertrophic cardiomyopathy (HCM) was investigated by single-cardiac real-time three-dimensional ultrasonography. A total of 52 patients with HCM were selected in Jining No. 1 People's Hospital from July 2016 to June 2017. Additionally, a total of 52 healthy people were selected to serve as the control group. All participants received real-time two- and three-dimensional ultrasonography to evaluate left ventricular morphology, function and systolic and diastolic function. The relevant parameters included left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), end-systolic/diastolic sphericity index (ESSI/EDSI), systolic dyssynchrony index (SDI), diastolic dyssynchrony index (DDI), dispersion end systole (DISPES), diastolic dyssynchrony index-late (DDI-late) and dispersion end diastole (DISPED-late). The LVEF of observation group was significantly lower than that of the control group, while LVEDV, LVESV, E/A and E/Ea were significantly higher than those in control group (P<0.05); EDSI, DDI-late and DISPED-late were significantly higher in observation than in control group (P<0.05); ESSI, SDI and DISPES in observation were significantly higher than those in control group (P<0.05); The 16-segment time-volume curve of observation group was disordered without synchronization, while the curve of control group was regular and smooth with synchronization; Pearson's correlation analysis showed that SDI and DDI were positively correlated (P<0.05). In conclusion, three-dimensional ultrasonography can be used to effectively evaluate left ventricular diastolic and systolic dyssynchrony in HCM. The severity of diastolic is positively correlated with systolic dyssynchrony.


MicroRNA and proteome expression profiling in early-symptomatic α-synuclein(A30P)-transgenic mice.
The α-synuclein has been implicated in the pathophysiology of Parkinson's disease (PD), because mutations in the alpha-synuclein gene cause autosomal-dominant hereditary PD and fibrillary aggregates of alpha-synuclein are the major component of Lewy bodies. Since presynaptic accumulation of α-synuclein aggregates may trigger synaptic dysfunction and degeneration, we have analyzed alterations in synaptosomal proteins in early symptomatic α-synuclein(A30P)-transgenic mice by two-dimensional differential gel electrophoresis. Moreover, we carried out microRNA expression profiling using microfluidic chips, as microRNA have recently been shown to regulate synaptic plasticity in rodents and to modulate polyglutamine-induced protein aggregation and neurodegeneration in flies. Differentially expressed proteins in α-synuclein(A30P)-transgenic mice point to alterations in mitochondrial function, actin dynamics, iron transport, and vesicle exocytosis, thus partially resembling findings in PD patients. Oxygen consumption of isolated brain mitochondria, however, was not reduced in mutant mice. Levels of several microRNA (miR-10a, -10b, -212, -132, -495) were significantly altered. One of them (miR-132) has been reported to be highly inducible by growth factors and to be a key regulator of neurite outgrowth. Moreover, miR-132-recognition sequences were detected in the mRNA transcripts of two differentially expressed proteins. MicroRNA may thus represent novel biomarkers for neuronal malfunction and potential therapeutic targets for human neurodegenerative diseases.


Recovered memory of childhood sexual trauma: a documented case from a longitudinal study.
A case of recovered memory of childhood trauma is reported with documented sexual trauma in early childhood, chronicled evidence of the absence of memory for traumatic experience over a period of time, and substantial evidence of 'spontaneous' recovery of memory. This account contains the first available prospective report of memory loss in a case in which there is both documented evidence of trauma and evidence of recovery of memory. The case emerged as part of a broadband, large-scale study of children followed closely from birth to adulthood which was not focused on memory for trauma. Prospective data gathered in a neutral research context, corroborated and supplemented by retrospective information, circumvent many limitations of previous retrospective accounts of recovered memories.


Effect of sumatriptan on cerebral blood flow in the baboon model.
Changes in cerebral blood flow are implicated to be important in the pathophysiology of migraine. Furthermore, serotonin (5-HT) is known to be the most important substance in the etiology of migraine. Sumatriptan (CAS 103628-46-2), a 5-HTID receptor agonist was recently introduced in the treatment of migraine. In the present study a baboon model was used to investigate the changes in cerebral blood flow due to anaesthesia and pharmacological interventions using 99mTc-labelled hexamethylpropylene amine oxime (99mTc-HMPAO) and single photon emission computed tomography (SPECT). The effect of sumatriptan on cerebral blood flow was investigated after 10 min and again after 23 min, with the animal under anaesthesia, i.e. induction with ketamine and maintenance on thiopental. Sumatriptan did not alter the cerebral blood flow during the 10 min procedure. However, sumatriptan reversed the increased cerebral blood flow due to the prolonged anaesthesia (23 min), lowering the cerebral blood flow by more than 20%. No significant changes in the biochemical parameters (blood pressure, heart rate, pO2 and pCO2) were observed. These results also suggest that sumatriptan reverses the increased cerebral blood flow most likely via 5-HTID receptor stimulation.


Subacute staphylococcal pneumonia in a renal transplant recipient.
A patient is reported who developed subacute staphylococcal pneumonia 17 months after renal transplantation. Although the illness was modified by oral antimicrobial drugs, a remarkably benign course was observed, leading to a presumptive diagnosis of opportunistic fungal infection. Thus, staphylococcal pneumonia may complicate the differential diagnosis of pulmonary infection in transplant recipients.


[Administration of diethylstilbestrol during pregnancy, a public health problem].
The analysis of the health risks associated with the administration of diethylstilbestrol (DES) during pregnancy (for the prevention or treatment of threatened abortions) has been largely published. Concerning mothers, a relationship between DES exposure during pregnancy and risk of cancer is unproved. However, existing studies are sufficient cause for serious concern over drug's carcinogenic potential, and further follow-up studies are required. Concerning daughters, a clear association between in utero exposure to DES and clear cell adenocarcinoma of the vagina or cervix is established (incidence between 0.14 and 1.4 per 1000 through age 24). The risk for squamous cell cancer of the vagina and cervix does not seem to be increased. Cervico-vaginal adenosis is frequent (20% to 60% of exposed subjects). This is not a pre-cancerous lesion, its spontaneous evolution is towards regression. No treatment is prescribed. Morphological changes of the genital tract have been described, their consequences on fertility and pregnancy are not clear. Concerning sons, an excess of genital abnormalities (especially of the epididymis and undescended testis) has been reported, but information on the fertility implications of these findings is not available. There is no evidence of an increased risk of testicular cancer. The analysis of all these informations should allow to bring up a policy to take into account these risks in the population.


Chronic idiopathic granulomatous mastitis.
We describe four women with idiopathic granulomatous mastitis, a rare benign disease. Age range was 32-40 years. Disease duration was less than 1 year in three patients and long term in the fourth. The diagnosis was based on histological findings, after extensive workup ruled out malignancy and known causes of granulomatous mastitis. Treatment with prednisone with gradual tapering yielded a good response. Clinicians should consider the possibility of idiopathic granulomatous mastitis in young women with inflammatory breast processes and negative findings on relevant biopsy, laboratory, and imaging studies. Glucocorticoids are the treatment of choice; surgery is not recommended. Some patients require a glucocorticoid-sparing drug.


Licorice consumption and serum testosterone in healthy man.
We have previously found that licorice can reduce serum testosterone in healthy men. These results were not confirmed in another study, where the same amounts of licorice did not decrease salivary testosterone values. In the actual study we treated more cases with the same amount of licorice and reproduced our previous data. The mean testosterone values decreased by 26 % after one week of treatment (p < 0.01). There was also a significant increase in 17-OHP and LH concentrations and a slight, but not significant decrease in free testosterone. Licorice treatment, in addition, did not affect the response of testosterone and 17-OHP to stimulation with beta-HCG.


Malignancies associated with intraductal papillary mucinous neoplasm of the pancreas.
As intraductal papillary mucinous neoplasm (IPMN) has a favorable prognosis, associated malignancies have potential significance in these patients. We examined the incidence and characteristics of pre-existing, coexisting and subsequent malignancies in patients with IPMN. Seventy-nine cases of IPMN were diagnosed by detection of mucous in the pancreatic duct during endoscopic retrograde pancreatography. Histological diagnosis was confirmed in 30 cases (adenoma (n = 19) and adenocarcinoma (n = 11). Other primary malignancies associated with IPMN, occurring in the prediagnostic or postdiagnostic period, were investigated. Postdiagnostic follow-up period was 3.3+/-0.5 years (range, 0.2-20 years). Other 40 malignancies occurred in 28 patients (35%). They were found before (n = 15), at (n = 19) and after (n = 6) the diagnosis of IPMT. Major associated malignancies were gastric cancer (n = 12), colonic cancer (n = 7), esophageal cancer (n = 4), pulmonary cancer (n = 4), and independent pancreatic cancer (n = 3). Pancreatic cancer was synchronous with IPMN in two patients and metachronous in one (3 years after diagnosis of IPMN). Thirty-one lesions were treated surgically or endoscopically. Fourteen patients died of associated cancers. Development of other malignancies was related to age (71.9+/-8.2 vs 66.8+/-9.3, P<0.05), but not to gender or site of the tumor. IPMN is associated with a high incidence of other malignancies, particularly gastric and colonic cancers. Common genetic mechanisms between IPMN and other associated malignancies might be present. Clinicians should pay attention to the possibility of associated malignancies in preoperative screening and follow-up of patients with IPMN.


Paraspinal arteriovenous fistula: Stuttgart classification based on experience and a review of the literature.
The term "paraspinal arteriovenous shunts" (PAVSs) summarizes an inhomogeneous variety of rare vascular disorders. PAVSs have been observed as congenital or acquired lesions. The clinical course of PAVSs may be asymptomatic or present with life-threatening symptoms. Based on a collection of individual cases from three institutions and a literature evaluation, we propose the following classification: PAVSs that are part of a genetic syndrome are separated from "isolated" PAVSs. Isolated PAVSs are subdivided into "acquired", "traumatic" and "congenital" without an identifiable genetic hereditary disorder. The subgroups are differentiated by the route of venous drainage, being exclusively extraspinal or involving intraspinal veins. PAVSs associated to a genetic syndrome may either have a metameric link or occur together with a systemic genetic disorder. Again extra-vs intraspinal venous drainage is differentiated. The indication for treatment is based on individual circumstances (e.g. myelon compression, vascular bruit, high volume output cardiac failure). Most PAVSs can be treated by endovascular means using detachable coils, liquid embolic agents or stents and derivates.


Two distinct microbial communities revealed in the sponge Cinachyrella.
Marine sponges are vital components of benthic and coral reef ecosystems, providing shelter and nutrition for many organisms. In addition, sponges act as an essential carbon and nutrient link between the pelagic and benthic environment by filtering large quantities of seawater. Many sponge species harbor a diverse microbial community (including Archaea, Bacteria and Eukaryotes), which can constitute up to 50% of the sponge biomass. Sponges of the genus Cinachyrella are common in Caribbean and Floridian reefs and their archaeal and bacterial microbiomes were explored here using 16S rRNA gene tag pyrosequencing. Cinachyrella specimens and seawater samples were collected from the same South Florida reef at two different times of year. In total, 639 OTUs (12 archaeal and 627 bacterial) belonging to 2 archaeal and 21 bacterial phyla were detected in the sponges. Based on their microbiomes, the six sponge samples formed two distinct groups, namely sponge group 1 (SG1) with lower diversity (Shannon-Weiner index: 3.73 ± 0.22) and SG2 with higher diversity (Shannon-Weiner index: 5.95 ± 0.25). Hosts' 28S rRNA gene sequences further confirmed that the sponge specimens were composed of two taxa closely related to Cinachyrella kuekenthalli. Both sponge groups were dominated by Proteobacteria, but Alphaproteobacteria were significantly more abundant in SG1. SG2 harbored many bacterial phyla (>1% of sequences) present in low abundance or below detection limits (<0.07%) in SG1 including: Acidobacteria, Chloroflexi, Gemmatimonadetes, Nitrospirae, PAUC34f, Poribacteria, and Verrucomicrobia. Furthermore, SG1 and SG2 only had 95 OTUs in common, representing 30.5 and 22.4% of SG1 and SG2's total OTUs, respectively. These results suggest that the sponge host may exert a pivotal influence on the nature and structure of the microbial community and may only be marginally affected by external environment parameters.


Effect of mesencephalic astrocyte-derived neurotrophic factor on the inflammatory response in human gingival fibroblasts cells.
Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a unique member of the neurotrophic factor family residing in the endoplasmic reticulum, where it functions as a stress response protein maintaining endoplasmic reticulum homeostasis, in addition to being secreted extracellularly as a neurotrophic factor to bind with receptors to initiate intracellular signal transduction pathways. Interestingly, MANF has shown an important protective role in the inflammatory response of many diseases. In neural stem cells, pancreatic β cells, and retinal cells, MANF can inhibit the inflammatory response, modulate the immune response, and promote tissue repair. However, the role of MANF in the periodontal inflammatory response remains unclear. In the present study, we used lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg) to establish a Pg-LPS-stimulated periodontal inflammatory model in human gingival fibroblasts cells (HGF-1) to investigate the role of MANF in vitro. We found that MANF could inhibit pro-inflammatory cytokine secretion, alleviate the endoplasmic reticulum stress response, promote cell survival, and inhibit cell apoptosis. Therefore, MANF might be a novel promising target for the treatment of periodontitis.


Endoscopic ultrasound guided fine-needle aspiration of lymph nodes and solid masses: factors influencing the cellularity and adequacy of the aspirate.
To study the factors that influence the cellularity and adequacy of endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA). An on-site cytopathology service is preferred during EUS-guided FNA. However, this is not always available. Factors that influence the aspirate cellularity and adequacy have not been well defined in the absence of on-site cytopathology. EUS-guided FNA procedures without an on-site cytopathologist from a single center were retrospectively studied. FNA of solid masses and lymph nodes (LN) were included. The FNA cellularity, hemorrhagic content, and endoscopists' assessment of adequacy were analyzed. A total of 166 patients from January 2009 to October 2010 were included. A total of 520 FNA passes were performed. Of the 166 lesions, 70 (42.2%) were solid masses and 96 (57.8%) were LNs. A 22-G needle was used in 72.3% and 25 G in 27.7% of the patients. The median (range) number of FNA passes was 3 (1 to 7) for LNs and 3 (1 to 5) for solid masses. With this, the endoscopists had an accuracy of 92.2% (153/166) for obtaining an adequate aspirate. Of the 166 samples, 4 (2.4%) were acellular, 20 (12.0%) sparsely cellular, 52 (31.4%) moderately cellular, and 90 (54.2%) highly cellular. The 25-G needle had significantly more adequate aspirates than the 22-G needle for solid masses (P=0.011). Also, increasing passes correlated with higher cellularity (P=0.002) and an adequate aspirate (P=0.021). No correlation was found for LN FNA. Lesion size did not influence the cellularity or adequacy (P>0.05). The degree of hemorrhage was not influenced by the needle gauge, number of passes, or lesion size. The diagnostic yield was not affected by hemorrhage in the sample (P>0.05). EUS-guided FNA obtains a high proportion of adequate aspirates for LNs and solid masses, even without an on-site cytopathologist. Small proportions of inadequate samples still occur. For solid masses, a 25-G needle with at least 3 passes is more likely to provide an adequate aspirate than a 22-G needle and fewer passes. Hemorrhage did not affect the cytopathology's ability to make a diagnosis.


Use of rituximab for periocular and intraocular mucosa-associated lymphoid tissue lymphoma.
The clinical efficacy of rituximab therapy in systemic mucosa-associated lymphoid tissue (MALT) lymphoma with both periocular and intraocular involvement is described. Ophthalmic examination and radiologic imaging demonstrated tumor with bilateral periorbital, lacrimal, and subconjunctival infiltration, a pseudohypopyon in one eye, and extensive systemic lymph node involvement. Lymph node biopsy confirmed the pathologic findings of a low-grade MALT lymphoma. The patient had a complete remission within 3 months of starting rituximab therapy. A recurrence 6 months later remitted with a second round of rituximab therapy and the patient remained tumor-free at 1 year.


[Non-invasive tissue oxygen monitoring by near-infrared spectroscopy].
Biological tissues are relatively transparent to light in near infrared region. Brain oxygen metabolism was non-invasively studied by the simultaneous measurement of hemoglobin (Hb) oxygenation and cytochrome oxidase (Cyt. aa3) redox state in the rat brain using near infrared transmission spectrophotometer. Wavelength pairs at 700-805 nm and 830-805 nm were used for the measurements of Hb oxygenation level and of the redox state of cyt. oxidase in situ. Change in the brain blood volume was also monitored by the absorption change at 805 nm. Our estimation of the oxygenation level of brain Hb revealed that present optical measurement picks up mainly that of venous blood. Sharp reduction of the oxidase occurred at the oxygen concentration below 15% in the inspired gas. But above 30% O2, about 85% of the cyt. oxidase was in the oxidized state which was almost constant up to 100% O2. Applications of our techniques for the studies of brain metabolism in acute hemorrhage and in Ca++-antagonist administration were also presented. This non-invasive optical method for the study of human brain metabolism is concluded to be a promissing technique.


Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15.
Indisulam is an aryl sulfonamide drug with selective anticancer activity. Its mechanism of action and the basis for its selectivity have so far been unknown. Here we show that indisulam promotes the recruitment of RBM39 (RNA binding motif protein 39) to the CUL4-DCAF15 E3 ubiquitin ligase, leading to RBM39 polyubiquitination and proteasomal degradation. Mutations in RBM39 that prevent its recruitment to CUL4-DCAF15 increase RBM39 stability and confer resistance to indisulam's cytotoxicity. RBM39 associates with precursor messenger RNA (pre-mRNA) splicing factors, and inactivation of RBM39 by indisulam causes aberrant pre-mRNA splicing. Many cancer cell lines derived from hematopoietic and lymphoid lineages are sensitive to indisulam, and their sensitivity correlates with DCAF15 expression levels. Two other clinically tested sulfonamides, tasisulam and chloroquinoxaline sulfonamide, share the same mechanism of action as indisulam. We propose that DCAF15 expression may be a useful biomarker to guide clinical trials of this class of drugs, which we refer to as SPLAMs (splicing inhibitor sulfonamides).


Effect of Lower Extremity Osteoarthritis on Outcomes of Lumbar Decompression.
The purpose of this study is to evaluate how hip or knee osteoarthritis (OA) and total joint arthroplasty impact the outcomes of patients undergoing lumbar decompression. A retrospective review of 342 patients undergoing lumbar decompression without fusion from January 2019 and June 2021 at a single institution was performed. Univariate and multivariate analyses were used to compare outcomes between patients with and without concomitant hip or knee OA. Forty-six percent of patients had a hip or knee OA diagnosis and were higher risk as they were older, had higher BMIs, were more likely to be former smokers, had higher ASA scores, and were more likely to undergo 3+ level surgery. Postoperatively, after adjusting for differences between groups, hip or knee OA patients were more likely to be readmitted (OR=12.45, p=0.026) or have a complication (OR=13.77, p=0.031). However, patient reported outcomes as measured by Patient Reported Outcomes Measurement Information System-physical function. were similar at 1-3 months and 3-6 months. Higher levels of physical function were observed at 3-6 months postoperatively in hip OA patients with a history of THA. Patients with concomitant hip or knee OA are at higher risk for readmission and postoperative complications but may achieve similar levels of physical function as those without OA.


[Stimulation of gluconeogenesis with 1,3-butanediol in the perfused rat liver].
An intensified synthesis of glucose is observed in gluconeogenesis from endogenous precursor only for the first 30 min of perfusion. Pyruvate introduction into the medium raises phosphoenolpyruvate carboxykinase and fructose-1,6-diphosphatase activities in the liver and determines maintenance of the glucose formation high rate for 90 min of perfusion. 1,3-butanediol is found to have a stimulating effect on gluconeogenesis from pyruvate. Introduction of 1,3 bytanediol into perfusate decreases the redox state of free NAD-pairs, increases the content of phosphoenolpyruvate, malate. ATP and the phosphoenolpyruvate carboxykinase and fructose-1.6-diphosphatase activity in the perfused liver.


Early pathogenesis of transmucosal feline immunodeficiency virus infection.
To identify the early target cells and tissues in transmucosal feline immunodeficiency virus (FIV) infection, cats were exposed to a clade C FIV isolate via the oral-nasal or vaginal mucosa and multiple tissues were examined by virus isolation coculture (VI), DNA PCR, catalyzed tyramide signal-amplified in situ hybridization (TSA-ISH), and immunohistochemistry between days 1 and 12 postinoculation (p.i.). FIV RNA was detected in tonsil and oral or vaginal mucosa as early as 1 day p.i. by TSA-ISH and in retropharyngeal, tracheobronchial, or external iliac lymph nodes and sometimes in spleen or blood mononuclear cells by day 2, indicating that regional and distant spread of virus-infected cells occurred rapidly after mucosal exposure. By day 8, viral RNA, DNA, and culturable virus were uniformly detected in regional and distant tissues, connoting systemic infection. TSA-ISH proved more sensitive than DNA PCR in detecting early FIV-infected cells. In mucosal tissues, the earliest demonstrable FIV-bearing cells were either within or subjacent to the mucosal epithelium or were in germinal centers of regional lymph nodes. The FIV(+) cells were of either of two morphological types, large stellate or small round. Those FIV RNA(+) cells which could be colabeled for a phenotype marker, were labeled for either dendritic-cell-associated protein p55 or T-lymphocyte receptor antigen CD3. These studies indicate that FIV crosses mucous membranes within hours after exposure and rapidly traffics via dendritic and T cells to systemic lymphoid tissues, a pathway similar to that thought to occur in the initial phase of infection by the human and simian immunodeficiency viruses.


Taxonomical classification of 20 newly isolated Listeria bacteriophages by electron microscopy and protein analysis.
A set of 20 newly isolated temperate bacteriophages for phage typing of the pathogen Listeria monocytogenes has been investigated by means of electron microscopy and electrophoretic analysis of phage structural proteins. All phages had isometric capsids (60-64 nm diameter), and long contractile or non-contractile tails of 170-320 nm length. They could be classified into 2 morphotypes (A1 and B1) and were assigned to 3 listeriaphage species (4211, 2671, and 2389). Individual protein profiles were generated by SDS-PAGE of viral polypeptides, as well as isoelectric focusing of solubilized phage proteins in immobilized pH gradient gels. The major structural proteins ranged in size from approximately 15 to 38 kD, and showed isoelectric points from pI 4.3 to 6.2. Protein compositions permitted the differentiation of individual phages as well as the recognition and grouping of similar viruses.


The influence of mandibular ridge anatomy on treatment outcome with conventional complete dentures.
Since prognostic indicators are likely to take on increasing importance as a diagnostic tool for selection of patients for implant provision, this study investigated the influence of the shape and resiliency of the mandibular alveolar ridge on the retention and stability of conventional complete dentures. Ninety- three edentulous patients wearing both maxillary and mandibular conventional complete dentures composed the sample. Data were collected regarding shape and resiliencyof the mandibular residual ridge. Dentures were assessed for retention and stability using an objective and reproducible tool.The associations between the clinical characteristics of the mandibular alveolar ridge and denture retention and stability were analyzed using chi-square and Fisher exact tests (a = 0.05). A significant association between ridge shape and denture stability (p < 0.05) was found, while ridge resiliency was significantly associated to denture retention (p < 0.001). Based on the results, mandibular ridge shape and resiliency influenced the retention and stability of conventional complete dentures.


Extradural hematomas in children.
The authors studied 58 patients, under 12 years of age, admitted to the Emergency Room of the Sao Paulo University Hospital between September 1987 and November 1991 with the diagnosis of traumatic extradural hematoma. Emphasis was given to the etiology of injury, the time interval from head injury to emergency room evaluation, the clinical features and the outcome after surgical and nonsurgical management. The site of hematoma was defined and correlated with the presence of skull fractures. Computerized tomography is the main diagnostic method, although it is not definitive. Fifteen patients were treated nonsurgically according to rigid clinical and radiological parameters. The overall mortality rate was 3.4%.


Suppression of 14-3-3ζ in cholangiocarcinoma cells inhibits proliferation through attenuated Akt activity, enhancing chemosensitivity to gemcitabine.
The protein 14-3-3ζ contributes important regulatory functions in several cellular processes via binding to phosphorylated serine/threonine residues, which promotes cell cycle progression, cell proliferation and anti-apoptosis in multiple types of cancer. The aim of the present study was to investigate the functions of 14-3-3ζ in cholangiocarcinoma (CCA) progression and elucidate the molecular mechanism of 14-3-3ζ expression-mediated protein kinase B (Akt) phosphorylation and chemosensitivity in CCA cells. In the present study, 14-3-3ζ expression was investigated in clinical specimens using immunohistochemistry and compared with the clinicopathological features of patients with CCA. The association between 14-3-3ζ and phosphorylated Akt (pAkt) was determined among the tissues of the same patients using bivariate correlation analysis. The effects of 14-3-3ζ suppression on CCA cell function and gemcitabine sensitivity were investigated using small interfering RNA (siRNA). It was identified that 14-3-3ζ expression was positively correlated with pAkt (P=0.013) and that increased expression of 14-3-3ζ and pAkt were significantly associated with poor overall survival rate and metastasis (P=0.025 and 0.006, respectively). Downregulation of 14-3-3ζ using siRNA in CCA cell lines decreased cell proliferation, resulting in the inhibition of pAkt activity and increasing the protein level of the cell cycle inhibitor p27. The suppression of 14-3-3ζ enhanced the inhibitory effect of gemcitabine on CCA cell proliferation by inducing apoptotic cell death. Taken together, the results of the present study indicated that 14-3-3ζ is a potential target for CCA and may serve as a novel therapeutic approach to enhance chemosensitivity in the treatment of CCA.


CARDIAN: a novel computational approach for real-time end-diastolic frame detection in intravascular ultrasound using bidirectional attention networks.
Changes in coronary artery luminal dimensions during the cardiac cycle can impact the accurate quantification of volumetric analyses in intravascular ultrasound (IVUS) image studies. Accurate ED-frame detection is pivotal for guiding interventional decisions, optimizing therapeutic interventions, and ensuring standardized volumetric analysis in research studies. Images acquired at different phases of the cardiac cycle may also lead to inaccurate quantification of atheroma volume due to the longitudinal motion of the catheter in relation to the vessel. As IVUS images are acquired throughout the cardiac cycle, end-diastolic frames are typically identified retrospectively by human analysts to minimize motion artefacts and enable more accurate and reproducible volumetric analysis. In this paper, a novel neural network-based approach for accurate end-diastolic frame detection in IVUS sequences is proposed, trained using electrocardiogram (ECG) signals acquired synchronously during IVUS acquisition. The framework integrates dedicated motion encoders and a bidirectional attention recurrent network (BARNet) with a temporal difference encoder to extract frame-by-frame motion features corresponding to the phases of the cardiac cycle. In addition, a spatiotemporal rotation encoder is included to capture the IVUS catheter's rotational movement with respect to the coronary artery. With a prediction tolerance range of 66.7 ms, the proposed approach was able to find 71.9%, 67.8%, and 69.9% of end-diastolic frames in the left anterior descending, left circumflex and right coronary arteries, respectively, when tested against ECG estimations. When the result was compared with two expert analysts' estimation, the approach achieved a superior performance. These findings indicate that the developed methodology is accurate and fully reproducible and therefore it should be preferred over experts for end-diastolic frame detection in IVUS sequences.


Competitive consecutive electron transfer in determination of ionization potentials: ketene derivatives.
Kinetics of competitive consecutive electron transfer was used to determine ionization potentials of transient species. Kinetics of two-stage electron transfer reactions in aprotic solvent was studied using 355 nm laser flash photolysis. The concentrations of transients produced by the laser flash photolysis were monitored by their light absorption. Triplet-excited tetrachloro-p-benzo-quinone (p-chloranil) generated by a 355 nm laser flash oxidized diethyl ketene, diphenyl ketene, or phenyl ethyl ketene to form radical cations. The ketene radical cations, in turn, oxidized tertiary amine, forming ground state ketene and ammonium radical cation. The kinetics of the disappearance of ketene radical cations (and/or appearance of ammonium radical cations) due to consecutive, competitive electron transfer to ketene and p-chloranil radical cations was monitored. By monitoring kinetics in the presence of tertiary amines with different oxidation potentials, it was established that in acetonitrile the oxidation potential of diethyl ketene was 5.4 eV; for phenyl ethyl ketene, it was approximately 4.8 eV; and for diphenyl ketene, it was 4.6 eV. The results were in agreement with the oxidation potentials of ketenes computed using published data.


[Effect of hydronephrosis on the contralateral blood flow and glomerular volume].
We designed a following experiment to appraise the effect of unilateral hydronephrosis on the contralateral kidney using weanling rats whose kidneys were in a growing stage. Rats were divided into 4 groups. Complete unilateral (left) ureteral obstruction (CUUO) was made on the experiment rats, and these went through the following procedures on the day 3 after CUUO; 1) Group R: CUUO released, 2) Group N: left nephrectomy performed, 3) Group S: CUUO continued. Sham-operations were performed on the days 0 and 3 to the controls. Renal cortical blood flow and glomerular volume of the contralateral (right) kidneys were determined on the days 5, 7, 9, 14 and 21. Blood flow to the renal cortex per unit volume (ml/min/100 cm3; measured with Laser blood perfusion monitor) in the contralateral kidneys increased gradually in the all groups, but statistical significance was not confirmed in the observed period between any groups. Increases in total renal blood flow (wet kidney weight times renal cortical blood flow per unit volume; g x ml/min/100 cm3) were proportional to the measured wet kidney weight in the all groups. Notably in the group N, a significant increase was noted compared to the group R and the controls. Glomerular volume (GV) of the contralateral kidneys did not show significant changes on the day 3 compared to the controls. GV significantly grew up during the day 5 to the day 14 (2 to 11 days after the relief of CUUO) in the group R and then it settled to the level of the controls on the day 21.(ABSTRACT TRUNCATED AT 250 WORDS)


Reaction properties of hydrophobic enzymes and their immobilization on phospholipid composite membranes.
Reaction rates of hydrophobic enzymes, aminopeptidase, and alkaline phosphatase, in microsomes prepared from the porcine brush border membrane and in vesicles pre pared from microsomes and phospholipids were measured at various temperatures. Interactions between the hydrophobic enzymes and the phospholipid layers are discussed as well as the effects of fluidity change of phospholipid layers on enzyme activity. Further, reaction properties and stabilities of the immobilized vesicles containing microsomal enzymes were studied.


Children and unintentional firearm death.
Children in the United States are at far greater risk of unintentional gun death than children in other developed countries. The relative figures may even be worse since the estimates for US child unintentional gun deaths are derived from the Vital Statistics which have been shown to be underestimates. No study has used a national data system to investigate the circumstances of fatal child gun accidents. We use data from the National Violent Death Reporting System for 16 states from 2005 to 2012. We examine the cases of unintentional gun death involving children in five age groups, 0-1, 2-4, 5-10, 11-12, and 13-14, where the child was either the victim or shooter. We estimate that there were 110 unintentional firearm deaths to children 0-14 annually in the U.S. during this 8 year time period, 80 % higher than reported by the Vital Statistics. The victims were predominantly male (81 %). Approximately two thirds of the shootings were other-inflicted, and in 97 % of those cases the shooter was a male. The typical shooter in other-inflicted shootings is a brother or friend. Indeed, children aged 11-14 are often shot in the home of friends. The large majority of children are shot by other children or by themselves. It is rare for a child accidentally to be shot by or accidentally to shoot an adult who is not a family member. Our study highlights the fact that unintentional firearm death to children is a problem of children shooting children and thus the importance of keeping guns away from children, their siblings, and their friends.


Automated Cognitive Health Assessment Based on Daily Life Functional Activities.
Dementia is increasing day-by-day in older adults. Many of them are spending their life joyfully due to smart home technologies. Smart homes contain several smart devices which can support living at home. Automated assessment of smart home residents is a significant aspect of smart home technology. Detecting dementia in older adults in the early stage is the basic need of this time. Existing technologies can detect dementia timely but lacks performance. In this paper, we proposed an automated cognitive health assessment approach using machines and deep learning based on daily life activities. To validate our approach, we use CASAS publicly available daily life activities dataset for experiments where residents perform their routine activities in a smart home. We use four machine learning algorithms: decision tree (DT), Naive Bayes (NB), support vector machine (SVM), and multilayer perceptron (MLP). Furthermore, we use deep neural network (DNN) for healthy and dementia classification. Experiments reveal the 96% accuracy using the MLP classifier. This study suggests using machine learning classifiers for better dementia detection, specifically for the dataset which contains real-world data.


Physical Nature of Fatty Acid Amide Hydrolase Interactions with Its Inhibitors: Testing a Simple Nonempirical Scoring Model.
Fatty acid amide hydrolase (FAAH) is an enzyme responsible for the deactivating hydrolysis of fatty acid ethanolamide neuromodulators. FAAH inhibitors have gained considerable interest due to their possible application in the treatment of anxiety, inflammation, and pain. In the context of inhibitor design, the availability of reliable computational tools for predicting binding affinity is still a challenging task, and it is now well understood that empirical scoring functions have several limitations that in principle could be overcome by quantum mechanics. Herein, systematic ab initio analyses of FAAH interactions with a series of inhibitors belonging to the class of the N-alkylcarbamic acid aryl esters have been performed. In contrast to our earlier studies of other classes of enzyme-inhibitor complexes, reasonable correlation with experimental results required us to consider correlation effects along with electrostatic term. Therefore, the simplest comprehensive nonempirical model allowing for qualitative predictions of binding affinities for FAAH ligands consists of electrostatic multipole and second-order dispersion terms. Such a model has been validated against the relative stabilities of the benchmark S66 set of biomolecular complexes. As it does not involve parameters fitted to experimentally derived data, this model offers a unique opportunity for generally applicable inhibitor design and virtual screening.


'These nurses have made a terrible situation more bearable'.
I was diagnosed with secondary breast cancer in June last year. Unbelievably, my husband was diagnosed with terminal cancer in July. We had married that March. Now we both have just months to live.


Metastatic plasmacytoid bladder cancer causing malignant priapism.
An 81-year-old man presented to medical services with pelvic pain and evolving urinary retention over 3 months. The patient was found to have a tense glans and penile shaft with surrounding induration consistent with malignant priapism. The extent of the induration included the suprapubic region, scrotum, left iliac region and left flank. A CT scan demonstrated an enhancing, pedunculated lesion arising from the anterior bladder wall measuring 30×31×20 mm. There were multiple enlarged left inguinal lymph nodes. Core biopsies of the subcutaneous tissue on the anterior abdominal wall demonstrated plasmacytoid urothelial carcinoma. The majority of patients with plasmacytoid variant of transitional cell carcinoma will present with >stage 3 bladder disease.


Targeting Pancreatic Cancer Cells with Peptide-Functionalized Polymeric Magnetic Nanoparticles.
Pancreatic cancer is a concealed and highly malignant tumor, and its early diagnosis plays an increasingly weighty role during the course of cancer treatment. In this study, we developed a polymeric magnetic resonance imaging (MRI) nanoplatform for MRI contrast agents. To improve tumor-targeting delivery of MRI contrast agents, we employed a pancreatic cancer targeting CKAAKN peptide to prepare a peptide-functionalized amphiphilic hyaluronic acid-vitamin E succinate polymer (CKAAKN-HA-VES) for delivering ultra-small superparamagnetic iron oxide (USPIO), namely, CKAAKN-HA-VES@USPIO. With the modification of the CKAAKN peptide, CKAAKN-HA-VES@USPIO could specifically internalize into CKAAKN-positive BxPC-3 cells. The CKAAKN-HA-VES@USPIO nanoparticles presented a more specific accumulation into pancreatic cancer cells than normal pancreatic cells, and an obvious decrease in signal intensity was observed in CKAAKN-positive BxPC-3 cells, compared with CKAAKN-negative HPDE6-C7 cells and non-targeting HA-VES@USPIO nanoparticles. The results demonstrated that our polymeric MRI nanoplatform could selectively internalize into CKAAKN-positive pancreatic cancer cells by the specific binding of CKAAKN peptide with pancreatic cancer cell membrane receptors, which provided a novel polymeric MRI contrast agent with high specificity for pancreatic cancer diagnosis, and makes it a very promising candidate for magnetic resonance imaging contrast enhancement.


Evaluation of a dehydrated test strip for the detection of yeasts.
Use of a dehydrated test strip for the detection of yeasts is compared with traditional culture on Sabouraud's agar containing 50 mug/ml chloramphenicol. While the selective medium of the strip is satisfactory for the isolation of species of Candida, Torulopsis glabrata grows only very slowly. The strip has the advantage of a long storage life without deterioration, but a high cost may preclude general usage. The numbers of yeasts collected by a bacteriological swab disadvantages of the selective medium, and the value of direct microscopy in the examination of vaginal swabs are discussed.


Is it worth it to cryopreserve embryos with blastulation delay at day 5?
This is a retrospective study over a 5-year period. In total, 3139 embryos were individually cryopreserved (Cryotop®) and warmed using the Kitazato vitrification/warming kit. They were classified into three categories based on their expansion degree. Transfer, implantation and pregnancy rates were assessed for each embryo category and compared using SPSS (Statistical Package for the Social Sciences) software. In total, 1139 couples enrolled in infertility treatment programme benefitted from embryo vitrification at day 5. After warming, embryos belonging to the three categories showed similar success rates. Although there was a trend towards better outcomes when grade 3 embryos were transferred, the differences did not reach statistical significance: implantation rates (n fetal sac/n embryo transferred) grade 1: 21.9%, grade 2: 22.7% and grade 3: 30.3% (=0.19). Pregnancy rate (n clinical pregnancy/n transfer) (21.9%, 22.7%, 30.3%, respectively; P=0.11). Miscarriage rate was not statistically different in the three categories (14.5%, 20.4%, 20%, respectively, P=0.51). Our overall results show that it is worth vitrifying slow kinetics embryos as they provide a non-negligible chance to give rise to a pregnancy.


Insertion and deletion in a non-essential region of the nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome (PRRS) virus: effects on virulence and immunogenicity.
Developing a vaccine that can differentiate infected and vaccinated animals (DIVA) is a new challenge in the design of a vaccine for porcine reproductive and respiratory syndrome virus (PRRSV). Nonstructural protein 2 (nsp2) is the single largest viral product, and it has multiple roles in polypeptide processing and replication complex formation. Using reverse genetics and an infectious PRRSV cDNA clone, we constructed several deletion mutants in the non-essential region of nsp2. One mutant, which has a 131 amino acid deletion within a relatively conserved region of nsp2, was recovered and found to produce a viable virus. The deleted region was replaced with a peptide tag encoding eight amino acids. A recombinant virus containing the 131 amino acid deletion was found to produce normal virus yields in MARC-145 cells and porcine alveolar macrophages (PAM); however, gross and micro-histopathology showed that the virus was less virulent in pigs. The 131 amino acid peptide was expressed as a recombinant protein and used to coat enzyme-linked immunosorbent assay (ELISA) plates. This peptide was recognized by sera from pigs infected with wild-type virus, but not by sera from pigs infected with the deletion mutant. The results from this study show that nsp2 is an important target for the development of marker vaccines and for virus attenuation.


Insights into Interactions of Human Cytochrome P450 17A1: A Review.
Cytochrome P450s are a widespread and vast superfamily of hemeprotein monooxygenases that metabolize physiologically essential chemicals necessary for most species' survival, ranging from protists to plants to humans. They catalyze the synthesis of steroid hormones, cholesterol, bile acids, and arachidonate metabolites and the degradation of endogenous compounds, such as steroids, fatty acids, and other catabolizing compounds as an energy source and detoxifying xenobiotics, such as drugs, procarcinogens, and carcinogens. The human CYP17A1 is one of the cytochrome P450 genes located at the 10q chromosome. The gene expression occurs in the adrenals and gonads, with minor amounts in the brain, placenta, and heart. This P450c17 cytochrome gene is a critical steroidogenesis regulator which performs two distinct activities: 17 alpha-hydroxylase activity (converting pregnenolone to 17- hydroxypregnenolone and progesterone to 17-hydroxyprogesterone; these precursors are further processed to provide glucocorticoids and sex hormones) and 17, 20-lyase activity (which converts 17-hydroxypregnenolone to DHEA). Dozens of mutations within CYP17A1 are found to cause 17-alpha-hydroxylase and 17, 20-lyase deficiency. This condition affects the function of certain hormone-producing glands, resulting in high blood pressure levels (hypertension), abnormal sexual development, and other deficiency diseases. This review highlights the changes in CYP17A1 associated with gene-gene interaction, drug-gene interaction, chemical-gene interaction, and its biochemical reactions; they have some insights to correlate with the fascinating functional characteristics of this human steroidogenic gene. The findings of our theoretical results will be helpful to further the design of specific inhibitors of CYP17A1.


An Emergency Department Validation of the SEP-3 Sepsis and Septic Shock Definitions and Comparison With 1992 Consensus Definitions.
The Third International Consensus Definitions Task Force (SEP-3) proposed revised criteria defining sepsis and septic shock. We seek to evaluate the performance of the SEP-3 definitions for prediction of inhospital mortality in an emergency department (ED) population and compare the performance of the SEP-3 definitions to that of the previous definitions. This was a secondary analysis of 3 prospectively collected, observational cohorts of infected ED subjects aged 18 years or older. The primary outcome was all-cause inhospital mortality. In accordance with the SEP-3 definitions, we calculated test characteristics of sepsis (quick Sequential Organ Failure Assessment [qSOFA] score ≥2) and septic shock (vasopressor dependence plus lactate level >2.0 mmol/L) for mortality and compared them to the original 1992 consensus definitions. We identified 7,754 ED patients with suspected infection overall; 117 had no documented mental status evaluation, leaving 7,637 patients included in the analysis. The mortality rate for the overall population was 4.4% (95% confidence interval [CI] 3.9% to 4.9%). The mortality rate for patients with qSOFA score greater than or equal to 2 was 14.2% (95% CI 12.2% to 16.2%), with a sensitivity of 52% (95% CI 46% to 57%) and specificity of 86% (95% CI 85% to 87%) to predict mortality. The original systemic inflammatory response syndrome-based 1992 consensus sepsis definition had a 6.8% (95% CI 6.0% to 7.7%) mortality rate, sensitivity of 83% (95% CI 79% to 87%), and specificity of 50% (95% CI 49% to 51%). The SEP-3 septic shock mortality was 23% (95% CI 16% to 30%), with a sensitivity of 12% (95% CI 11% to 13%) and specificity of 98.4% (95% CI 98.1% to 98.7%). The original 1992 septic shock definition had a 22% (95% CI 17% to 27%) mortality rate, sensitivity of 23% (95% CI 18% to 28%), and specificity of 96.6% (95% CI 96.2% to 97.0%). Both the new SEP-3 and original sepsis definitions stratify ED patients at risk for mortality, albeit with differing performances. In terms of mortality prediction, the SEP-3 definitions had improved specificity, but at the cost of sensitivity. Use of either approach requires a clearly intended target: more sensitivity versus specificity.


Onset of alcohol use disorder among alcohol initiates by race/ethnicity.
Prevalence of alcohol use disorders (AUD) varies across racial/ethnic groups. It remains unclear whether rapid transition from first-time alcohol use to developing AUD varies by race and ethnicity. In this study, we investigate racial/ethnic differences in AUD onset among first-time alcohol drinkers and identify specific predictors of AUD onset by racial/ethnic group. The study population was non-institutionalized US residents aged 12 and older. Within four nationally representative probability samples (n ∼70,000/year) drawn from the 2015-2018 National Surveys on Drug Use and Health, we identified 9,381 individuals who initiated alcohol use within 1-12 months prior to the survey. The probability of AUD after initiation was estimated for the entire sample, followed by racial/ethnic group stratification. Bivariate and multivariable logistic regression models were used to identify predictors of AUD onset among alcohol initiates. The overall incidence estimate of AUD among alcohol initiates was 3.7% (95% CI = 3.0%, 4.6%). There was no significant variation in the incidence of AUD between racial/ethnic groups. Drug use, drug use disorders, and major depressive episode were significant predictors of AUD onset among all alcohol initiates. However, these predictors were not significant among non-Hispanic/Latinx Black individuals. Drug use and drug use disorders were strong predictors of AUD onset among alcohol initiates, except among non-Hispanic/Latinx Black individuals. These findings strengthen the importance of focusing on the co-use of alcohol and other drugs and the need to further investigate the risk profile differences between racial/ethnic groups.


Central catheter-associated deep vein thrombosis in cancer: clinical course, prophylaxis, treatment.
The adequate handling of central venous catheters is a key element in the management of patients with cancer. Catheter-associated deep vein thrombosis is frequently observed in patients with malignant diseases; however, despite being a common complication among these patients, objective information concerning its epidemiology, clinical course, prophylaxis and treatment strategies is very limited. The reported incidence of catheter-related thrombosis (CRT) is highly variable, depending on symptomatic events, or if patients are screened for asymptomatic thrombosis. Several factors have been identified as potential predisposing factors for CRT, both technical and pathological aspects. The anticoagulant of choice is still unclear; while low-molecular-weight heparin is most commonly used, recent studies assessing the role of direct oral anticoagulants in the treatment of CRT show promise as an alternative, but the evidence remains insufficient and the decision must be made on a case-by-case basis.


Describing the consequences of disorders: stuttering and the International Classification of Impairments, Disabilities, and Handicaps.
The International Classification of Impairments, Disabilities, and Handicaps (ICIDH) proposed by the World Health Organization (WHO, 1980) can be a useful method for describing the experiences of individuals exhibiting speech and language disorders such as stuttering. Unfortunately, the definitions for the terms impairment, disability, and handicap that were previously presented in the stuttering literature have not accurately represented the true purpose of the ICIDH as a tool for describing the consequences of disorders. This paper reviews the history of these terms in the stuttering literature and proposes alternate definitions that are more consistent with the use of the ICIDH elsewhere in the field of communication disorders, as well as within the health-related professions in general. Based on the ICIDH framework, a model is proposed for discussing the outcomes of various types of stuttering treatments in the context of an individual's experience of the stuttering disorder, and the implications for treatment outcomes research using this framework are discussed.


Induction of opposite response of hindlimb vasculature to adrenergic agents in hypothyroid rats.
In order to investigate whether hypothyroidism induces some functional change in the vascular smooth muscle, the responsiveness of the femoral vascular bed of hypothyroid rats to vasoactive agents was compared with that of euthyroid rats. The vascular beds were perfused by using the constant flow method. Ad libitum feeding of 0.15% 6-propylthiouracil to young male Wistar rats (120 g) over 3 months leads to hypothyroidism. Hypothyroidism did not induce any changes in the Ach- or papaverine-induced vasodilation and 5-HT-induced vasoconstriction. In contrast to euthyroidism, hypothyroidism induces a marked augmentation of the clonidine-induced vasoconstriction, while the phenylephrine-induced vasoconstriction and isoprenaline-induced vasodilation were clearly attenuated. The response to phenylephrine in euthyroidism was predominantly inhibited by prazosin and was slightly modified by yohimbine. While the attenuated response to phenylephrine in hypothyroidism was modified by these blockers in a converse manner, the response to clonidine in each rat group was not modified by prazosin, but markedly inhibited by yohimbine. From these results the following conclusions were obtained: both alpha-1 and alpha-2 adrenoceptors in the femoral vascular beds of eu- and hypothyroid rats responded to phenylephrine; phenylephrine stimulated predominantly alpha-1 adrenoceptors in euthyroidism; hypothyroidism caused an attenuation of the responsiveness mediated through alpha-1 adrenoceptors and an augmentation of that of alpha-2 receptors; hypothyroidism caused an opposite response, mediated through alpha- and beta-receptors, without influencing muscarinic and serotoninergic responses; augmentation of the alpha-2 response and attenuation of alpha-1 and beta-2 responses caused by hypothyroidism may be attributed to functional changes at receptor sites.


Quantitative genetics of secondary hip joint osteoarthritis in a Labrador Retriever-Greyhound pedigree.
To evaluate the quantitative inheritance of secondary hip joint osteoarthritis in a canine pedigree. 137 Labrador Retrievers, Greyhounds, and mixed-breed dogs. Necropsy scores ranging from 0 to 4 were obtained for each hip joint. Seven unaffected Greyhounds with normal hip joint conformation were also used for genetic modeling, but were not euthanized. Sixty-six male and 71 female dogs were allocated to 2 groups (< or = 12 months of age and > 12 months of age). Statistical models were developed to establish the inheritance pattern of hip joint osteoarthritis that developed secondary to hip dysplasia. 62 dogs had evidence of osteoarthritis in a hip joint, and 75 had no evidence of osteoarthritis. After sex was adjusted for, the necropsy score was found to be inherited additively but without dominance. Each Labrador Retriever allele increased the necropsy score by 0.7 to 0.9 points, compared with the Greyhound allele, and male sex increased the necropsy score 0.74 over female sex. Approximately 10% of the variation in necropsy score was attributable to the litter of puppies' origin. Because secondary hip joint osteoarthritis is inherited additively, selection pressure could be applied to reduce its incidence. Similar statistical models can be used in linkage and association mapping to detect the genes in the underlying quantitative trait loci that contribute to hip joint osteoarthritis.


A software framework for real-time multi-modal detection of microsleeps.
A software framework is described which was designed to process EEG, video of one eye, and head movement in real time, towards achieving early detection of microsleeps for prevention of fatal accidents, particularly in transport sectors. The framework is based around a pipeline structure with user-replaceable signal processing modules. This structure can encapsulate a wide variety of feature extraction and classification techniques and can be applied to detecting a variety of aspects of cognitive state. Users of the framework can implement signal processing plugins in C++ or Python. The framework also provides a graphical user interface and the ability to save and load data to and from arbitrary file formats. Two small studies are reported which demonstrate the capabilities of the framework in typical applications: monitoring eye closure and detecting simulated microsleeps. While specifically designed for microsleep detection/prediction, the software framework can be just as appropriately applied to (i) other measures of cognitive state and (ii) development of biomedical instruments for multi-modal real-time physiological monitoring and event detection in intensive care, anaesthesiology, cardiology, neurosurgery, etc. The software framework has been made freely available for researchers to use and modify under an open source licence.


Lasting neuroendocrine-immune effects of traumatic brain injury in rats.
Traumatic brain injury (TBI) is a principal cause of long-term physical, cognitive, behavioral, and social deficits in young adults, which frequently coexist with a high incidence of substance abuse disorders. However, few studies have examined the long-term effects of TBI on the neuroendocrine-immune system. TBI was induced in adult male rats under isoflurane anesthesia by cortical contusion injury with a pneumatic piston positioned stereotaxically over the left parietal cortex. Controls underwent sham surgery without injury. At 4 weeks post-injury, the plasma corticosterone response to 30-min restraint stress was significantly blunted in TBI rats compared to the sham controls. One week later, transmitters were implanted for continuous biotelemetric recording of body temperature and spontaneous locomotor activity. At 6 weeks post-injury, the febrile response to i.p. injection of the bacterial endotoxin, lipopolysaccharide (LPS; 50 microg/kg), was significantly lower in TBI than in sham rats. At 8 weeks, swimming in the forced swim test was significantly less in TBI than sham rats. At 9 weeks, rats were rendered ethanol (EtOH) dependent by feeding an EtOH-containing liquid diet for 14 days. Cosine rhythmometry analysis of circadian body temperature Midline Estimating Statistic of Rhythm (MESOR), amplitudes, and acrophases indicated differential effects of EtOH and withdrawal in the two groups. Light- and dark-phase activity analysis indicated that TBI rats were significantly more active than the sham group, and that EtOH and withdrawal differentially affected their activity. Given the extensive interactions of the neuroendocrine-immune systems, these results demonstrate that TBI produces lasting dysregulation amidst the central substrates for allostasis and circadian rhythmicity.


Communication patterns and conflict in marital dyads.
Responses--pauses, laughter, and interruptions (postulated to be communication techniques of couples with more equal power in decision making) and questions, silence time, and longer decision time (hypothesized to be communication techniques of couples in a dominant-submissive power structure)--of 68 middle-class suburban couples who volunteered to take the Inventory of Marital Conflicts were analyzed. Although study hypotheses were not supported, a high intercorrelation was revealed among communication variables hypothesized to be characteristic of power-sharing couples.


National incidence, prevalence and disability-adjusted life years (DALYs) of common micronutrient deficiencies in Ethiopia from 1990 to 2017: estimates from the global burden of diseases study.
Understanding the national burden and trend of micronutrient deficiencies helps to guide effective intervention strategies under various circumstances. There is, however, a lack of evidence on trends, age- and sex-specific variations in Ethiopia. This study aimed to provide evidence on the trends of common micronutrient deficiencies including, dietary iron, iodine, vitamin A and other nutritional deficiencies in Ethiopia, from 1990 to 2017, using findings from the Global Burden of Disease study. We used estimates from the GBD 2017 study to report the incidence, prevalence and disability-adjusted life years of micronutrient deficiencies in Ethiopia from 1990 to 2017. All estimates, both crude counts, as well as all-age and age-standardized rates per 100,000 population, are accompanied by 95% uncertainty intervals (UIs). We summarized the age- and sex-specific patterns and we compared the burden with the sub-Saharan Africa and global estimate. From 1990 to 2017, the age-standardized prevalence rate of dietary iron, vitamin A and iodine deficiency decreased by 20.1%, 16.7%, and 91.6%, respectively. However, MNDs still account for a large number of DALYs in the country. In 2017, the all-age total DALYs due to dietary iron deficiency were estimated to be 448.4 thousand [95% UI: 298.9-640.7], accounting for 1.18% of the total DALYs. Similarly, the all-age total DALYs due to vitamin A deficiency were 397.8 thousand [256.1-589.2]. The total DALYs due to iodine deficiency were estimated to be 89.6 thousand [48.3-155.4]. Micronutrient deficiencies and associated morbidity and mortality are still high in Ethiopia compared with the sub-Saharan and global estimate. Adolescent and early adult females and children aged under-five are disproportionately affected segments of the population. Therefore, in collaboration with other sectors, the National Nutrition Program needs to place greater emphasis upon improving accessibility and utilization of nutrient-rich foods and supplementation, particularly for vulnerable groups of the population.