RETINAL NONPERFUSION IN THE EARLY TREATMENT DIABETIC RETINOPATHY STUDY SEVEN FIELDS COMPARED WITH WIDEFIELD FLUORESCEIN ANGIOGRAPHY: Correlation and Use of Extrapolation Factor.
In previous landmark studies on central retinal vein occlusion, retinal nonperfusion assessments were obtained using 7-field (7F) angiography. The widespread current use of widefield imaging allows better visualization of the peripheral retina and more comprehensive estimation of the total area of nonperfusion. The relationship between nonperfusion measurement of 7F and widefield angiography (WFA) in central retinal vein occlusion has not been studied. We aim to identify the correlation of retinal nonperfusion measured within the 7F and on WFA in eyes with central retinal vein occlusion. Retinal nonperfusion in participants with central retinal vein occlusion was determined using a 7F Early Treatment Diabetic Retinopathy Study template and the concentric rings method. A total of 153 eyes were included. Pearson correlation test showed a near-perfect positive, linear correlation between the nonperfusion found in the 7F and total retinal nonperfusion on WFA (0.985 95% CI [0.793, 0.999]) The regression line equation for nonperfusion on 7F and WFA was y = 37 + 3.2x. Eyes with 0 disk areas (DA), >0 DA to 10 DA and >10 DA of nonperfusion on 7-fields had on average 23 DA 95% CI (19.20, 27.06), 45 DA 95% CI (35.75, 55.18), and 115 DA 95% CI (88.89, 142.05) on widefield respectively. There is a positive and linear relationship between nonperfusion measured by 7F and WFA in central retinal vein occlusion with more than 3-times the amount of nonperfusion identified on WFA. Despite <10 DA no areas of nonperfusion on 7F, there is typically at least 35 DA of nonperfusion on WFA whereas eyes with >10 DA of nonperfusion on 7F had at least 88 DA on WFA.


Synthesis and antiviral activity of novel isodideoxy nucleosides with exocyclic methylene.
Novel isodideoxy nucleosides with exocyclic methylene were synthesized starting from L-xylose utilizing anomeric demethoxylation, Wittig reaction and Mitsunobu reaction as key steps and evaluated for antiviral activity.


Surgical strategy for patients with pancreatic body/tail carcinoma: who should undergo distal pancreatectomy with en-bloc celiac axis resection?
Indications for distal pancreatectomy with en-bloc celiac axis resection (DP-CAR) in pancreatic carcinoma remain controversial. Fifty-two consecutive patients with pancreatic cancer who underwent distal pancreatectomy, including 36 standard distal pancreatectomies (standard DP) and 16 DP-CAR were reviewed retrospectively. After standard DP, microscopically positive margins were identified at the dissection sites around the transection margins of the splenic arteries and were detected more frequently in the patients with tumors within 10 mm from the root of the splenic artery (14%). After DP-CAR, the estimated overall survival rate in patients who were pathologically negative for portal venous and artery invasion (n = 7) was greater than that of the other patients (n = 9; P = .023, log-rank test). The estimated overall 1- and 2-year survival rates after standard DP/DP-CAR were 81/81% and 52/53%, and the median survival times were 32/25 months, respectively, with no differences noted between the groups. There were no differences in the mortality rates and the incidence of each complication between the 2 groups except for delayed gastric emptying. DP-CAR was a feasible and safe procedure, similar to standard DP. DP-CAR should be reserved for patients without tumor infiltrating either the portal venous or arterial systems.


Development of Ca2+ hotspots between Lymnaea neurons during synaptogenesis.
Calcium (Ca2+) channel clustering at specific presynaptic sites is a hallmark of mature synapses. However, the spatial distribution patterns of Ca2+ channels at newly formed synapses have not yet been demonstrated. Similarly, it is unclear whether Ca2+ 'hotspots' often observed at the presynaptic sites are indeed target cell contact specific and represent a specialized mechanism by which Ca2+ channels are targeted to select synaptic sites. Utilizing both soma-soma paired (synapsed) and single neurons from the mollusk Lymnaea, we have tested the hypothesis that differential gradients of voltage-dependent Ca2+ signals develop in presynaptic neuron at its contact point with the postsynaptic neuron; and that these Ca2+ hotspots are target cell contact specific. Fura-2 imaging, or two-photon laser scanning microscopy of Calcium Green, was coupled with electrophysiological techniques to demonstrate that voltage-induced Ca2+ gradients (hotspots) develop in the presynaptic cell at its contact point with the postsynaptic neuron, but not in unpaired single cells. The incidence of Ca2+ hotspots coincided with the appearance of synaptic transmission between the paired cells, and these gradients were target cell contact specific. In contrast, the voltage-induced Ca2+ signal in unpaired neurons was uniformly distributed throughout the somata; a similar pattern of Ca2+ gradient was observed in the presynaptic neuron when it was soma-soma paired with a non-synaptic partner cell. Moreover, voltage clamp recording techniques, in conjunction with a fast, optical differential perfusion system, were used to demonstrate that the total whole-cell Ca2+ (or Ba2+) current density in single and paired cells was not significantly different. However, the amplitude of Ba2+ current was significantly higher in the presynaptic cell at its contact side with the postsynaptic neurons, compared with non-contacted regions. In summary, this study demonstrates that voltage-induced Ca2+ hotspots develop in the presynaptic cell, concomitant with the appearance of synaptic transmission between the soma-soma paired cells. The appearance of Ca2+ gradients in presynaptic neurons is target cell contact specific and is probably due to a spatial redistribution of existing channels during synaptogenesis.


Steroid hormone regulation of the gene encoding the chicken heat shock protein hsp 108.
We have previously isolated a partial cDNA clone encoding a heat shock protein which has been termed hsp 108 (Zarucki-Schulz, T., Kulomaa, M. S., Headon, D. R., Weigel, N. L., Baez, M., Edwards, D. O., McGuire, W. L., Schrader, W. T., and O'Malley, B. W. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 6358-6362; Sargan, D. R., Tsai, M.-J., and O'Malley, B. W. (1985) Biochemistry 25, 6252-6258). Here we examine the expression of the hsp 108 gene in steroid-stimulated chick oviducts. After 16 h of secondary stimulation with estrogen or progesterone, a 20-50-fold increase in hsp 108 mRNA is detected above unstimulated levels. RNA quantitation by Rot analysis shows that in these oviducts there are 75 molecules of hsp 108 mRNA/oviduct cell. Nuclear "run-off" assays indicate only a 2-4-fold increase in the rate of transcription of the gene in response to either sex steroid, suggesting that the gene is regulated both at the transcriptional level and by mRNA stabilization. On hormone withdrawal, the concentration of hsp 108 mRNA in the oviduct falls to unstimulated control levels within 4 days. Chronic stimulation of the chicks with estrogen (or high acute doses of estrogen) attenuates specifically the inductive response of the hsp 108 gene, but not of ovalbumin, under these conditions. This is not due to a significant reduction of the transcription rate of the gene. We have previously shown that hsp 108 is expressed constitutively in many tissues of the chick (Sargan, D. R., Tsai, M.-J., and O'Malley, B. W. (1985) Biochemistry 25, 6252-6258). In tissues which are not responsive to hormones, no short-term effects of hormone administration on the gene were observed. In the spleen there is a reproducible slow activation of the gene, but the kinetics of this response suggest that it is not a primary response to the hormone. Thus, this hsp 108 gene codes for an interesting new eucaryotic heat shock protein which is regulated also by steroid hormones in a tissue-specific manner.


Understanding the role of glucose regulated protein 170 (GRP170) as a nucleotide exchange factor through molecular simulations.
Glucose Regulated Protein 170 (GRP170), also called Oxygen Regulated Protein 150 (ORP150), is a major molecular chaperone resident in the endoplasmic reticulum (ER). It belongs to the heat shock protein (HSP70) super family and can be induced by conditions such as hypoxia, ischemia and interferences in calcium homeostasis. It was recently reported that GRP170 may act as a nucleotide exchange factor (NEF) for GRP78 or binding immunoglobulin protein (BiP), and the ER canonical HSP70. However, little is known about the mechanism underlying its NEF activity. In this study, two homology models of GRP170 were constructed based on the X-ray crystal structures of ADP and ATP bound HSP110, a cytosolic homolog of GRP170, in order to characterize the differences in the binding modes of both ligands. It was observed that the differences in the binding modes of ADP and ATP led to a conformation change in the substrate binding domain which could potentially influence the binding of its substrates such as BiP. Our findings help understand the effect of nucleotide binding on the function of this chaperone protein as a NEF as well as the structural differences between GRP170 and its family members.


Allergic rhinitis--current approaches to skin and in vitro testing.
This article discusses the currently available techniques used for the diagnosis of IgE-mediated upper respiratory allergy. These methods are necessary to confirm the presence and the intensity of allergy in an effort to select patients for immunotherapy and to dose immunotherapy properly. Specific techniques discussed include epicutaneous and intradermal skin tests and in vitro tests designed to measure antigen-specific IgE antibody.


Adaptation of a Lean Tool Across Surgical Units to Improve Patient Experience.
High reliability organizations (HROs) sustain consistently excellent outcomes over time. Health care systems need to eliminate major quality failures to become reliable. Practice variations, unstructured leader rounds, and unfavorable patient experience outcomes with Responsiveness of Hospital Staff prompted leaders to adopt Kamishibai cards (K-cards). Evidence-based practices (EBPs) such as timeliness of answering call lights, purposeful rounding, communication, and engaging patients were used to develop Responsiveness K-cards. Responsiveness K-cards established standard work for staff responsiveness and audited process compliance. Findings determined what areas needed improvement, and leaders engaged frontline staff in practice changes. Percentile rank for Responsiveness of Hospital Staff had a sustained increase. Four of 6 hospital units using Responsiveness K-cards achieved 80% rank or better in every patient experience domain for the entire fiscal year. K-cards use HRO principles to standardize practice and improve outcomes. They encourage continuous improvement, which supports the sustainability of EBPs.


Are psychological and pharmacologic interventions equally effective in the treatment of adult depressive disorders? A meta-analysis of comparative studies.
A large number of studies suggest that both psychological and pharmacologic therapies are effective in the treatment of mild-to-moderate depressive disorders. Whether both types of intervention are equally effective has not been established definitively. A database was developed through a comprehensive literature search (from 1966 to May 2007) in which 6947 abstracts in PubMed (1244 abstracts), PsycINFO (1736), EMBASE (1911), and the Cochrane Central Register of Controlled Trials (2056) were examined. Abstracts were identified by combining terms indicative of psychological treatment and depression (both MeSH terms and text words). For this database, the primary studies from 22 meta-analyses of psychological treatment for depression were also collected. For the current study, the abstracts of 832 studies were examined. Thirty randomized trials were included in a meta-analysis that compared the effects of a psychological treatment for 3178 adults with a diagnosed depressive disorder (major depressive disorder, dysthymia, minor depressive disorder) with the effects of a pharmacologic treatment. In studies of patients with dysthymia, pharmacotherapy was significantly more effective than psychotherapy (d = -0.28, 95% CI = -0.47 to -0.10). In patients with major depressive disorder, treatments with selective serotonin reuptake inhibitors (SSRIs) were significantly more effective than psychological treatments, while treatment with other antidepressants did not differ significantly. Subgroup and metaregression analyses did not show that pretest severity of depressive symptoms was associated with differential effects of psychological and pharmacologic treatments of major depressive disorder. Dropout rates were smaller in psychological interventions compared with pharmacologic treatments (odds ratio = 0.66, 95% CI = 0.47 to 0.92). Pharmacologic treatments may be more effective than psychological interventions in the treatment of dysthymia. Pharmacologic treatment with SSRIs may also be more effective in the treatment of major depressive disorder, although these differences are small and probably have little meaning from a clinical point of view. We can conclude that both psychological and pharmacologic therapies are effective in the treatment of depressive disorders and that each has its own merits.


Do expressed emotions result in stigma? A potentially modifiable factor in persons with epilepsy in India.
Feeling stigmatized or having comorbid depression in a PWE may significantly influence epilepsy care and treatment. An important contributory factor to this can be the expressed emotions (EEs) from family, friends, or society. The present study aimed at understanding the influence of EEs, as exhibited by close relatives, on the perception of stigma and comorbid depression experienced by PWEs. Eighty PWEs aged 18 years and above, both genders, visiting neurology OPD in AIIMS Hospital, were recruited. Using the PHQ-09, we subdivided them into Group I (PWEs with comorbid depression) and Group II (PWEs without comorbid depression), followed by administration of Levels of Expressed Emotions Scale and Stigma Scale for Epilepsy, respectively. The comparative analysis, using independent t-test (for categorical data), Pearson's correlation (for continuous data), and multivariate regression analysis, reflected significant influence of EEs on depression and stigma, with more than 20% of the participants reporting comorbid depression, out of which more than 50% further expressed feelings of inferiority or disgrace due to the ways in which family or society discriminated them from healthy persons, thereby highlighting a greater associations of high EEs as opposed to low EEs from key individuals on patients' perception of stigma or feeling of depression. The result suggested that EEs from a relative might go unnoticed but may significantly overwhelm the patient, thereby making him succumb to depression or feeling stigmatized. The analysis of such a clinical profile and relationship between EEs and perceived stigma/depression may help us understand the pattern of attribution styles adopted by PWEs, thereby utilizing it further for enhancing the efficacy of cognitive-behavioral therapy for facilitating sustained recovery and improved quality of life for PWEs.


Assessment of methylmercury exposure in Wisconsin.
Between January 2004 and June 2005 the Wisconsin Department of Health and Family Services recruited more than 2000 adults for a methylmercury (MeHg) exposure assessment study. Study participants, including 978 men and 1050 women who ranged in age from 18 to 92 years, completed a fish consumption and advisory awareness survey and provided hair samples for mercury analysis. Fish intake estimates ranged from 0 to 60 meals/month (mean 7.7). Hair mercury levels ranged from 0.012 to 15.2 microg/g and were positively correlated with monthly fish meals. Despite reporting similar fish consumption rates, men tended to have higher hair mercury levels than women. Mercury levels exceeded 1 microg/g in 29% of the men and 13% of the women and increased with age. Approximately, half of the study volunteers were licensed anglers and 77% were familiar with Wisconsin's sportfish consumption advisory. Among consumers of sport-caught fish, 37% of the men and 18% of the women had a hair mercury concentration above 1 microg/g. These findings suggest that exposure to MeHg is widespread and that men may be a previously unrecognized high risk population.


Water and sodium metabolism during intravenous re-feeding in the malnourished rabbit.
Twenty-three New Zealand rabbits were starved until a mean weight loss of 21% was achieved and then re-fed parenterally with two different total parenteral nutrition (TPN) formulae: a standard formula (Group SF, n = 12) containing 100 ml/kg/day of water, 7 mEq/day of sodium and 70% of non-protein calories as glucose; and a modified formula (Group MF, n = 11) containing 70 ml/kg/day of water, no sodium and 70% of non-protein calories as fat. After 6 days of parenteral nutrition, Group SF showed a higher weight gain than Group MF (10 +/- 5.8% vs. 1.4 +/- 5%; p = 0.001) and serum albumin concentration in Group SF was lower than in Group MF (25.9 +/- 4.2 vs. 32 +/- 4.5 g/l; p = 0.004). There was a close correlation between weight gain and water and sodium balances (r(2) = 0.714; p = 0.0001 and r(2) = 0.447; p = 0.0005, respectively). In Group SF, a close correlation was found between the free water clearance and water balance (r(2) = 0.711, p = 0.0006). In conclusion, in Group MF water and sodium restriction led to a better nutritional response in terms of improving serum albumin concentrations and minimising weight gain, probably due to less expansion of the extracellular fluid compartment in this group.


Does work as a nurse increase the risk of adverse pregnancy outcomes?
We conducted a population-based study to assess whether work as a nurse during pregnancy increases the risk of low birth weight, preterm delivery, and small-for-gestational-age. The study population was selected from The Finnish Prenatal Environment and Health Study of 2568 newborns (response 94%) and included 128 (5.0%) newborns of nurses and 559 newborns of office workers (21.8%) as a reference group. The risk of low birth weight (adjusted odds ratio = 1.02; 95% confidence interval = 0.32-3.22) and preterm delivery (0.81; 0.32-2.05) did not differ between newborns of nurses and office workers, but the risk of small-for-gestational-age was substantially higher among newborns of nurses (1.99; 1.10-3.59). This corresponds to a population attributable fraction of 2.5%. The results indicate that working as a nurse during pregnancy could reduce fetal growth.


Radiofrequency ablation of intubation granulomas.
We explored the outcomes and voice parameters of patients undergoing plasma radiofrequency (RF) ablation to treat intubation granulomas. Prospective case series. Patients with intubation granulomas who met the inclusion criteria underwent RF ablation. The complete remission rate and voice function were evaluated preoperatively and at 6 months postoperatively. We enrolled 13 patients with 25 intubation granulomas. The mean time between intubation and initial diagnosis was 38.6 days and that between intubation and surgical diagnosis was 2.7 months. All 25 granulomas were successfully removed and histologically confirmed. No surgical remnant was evident on the vocal folds and complete glottal closure was observed at 2 weeks postoperatively. No recurrence or RF ablation-related complications were observed during the 6-month follow-up. The complete remission rate was 100% (13/13). In addition, the mean hoarseness, roughness, breathiness, asthenia, and strain (GRBAS) scores, and the maximum phonation time (MPT), improved significantly after treatment (all P < 0.05). RF ablation is effective and safe for patients with intubation granulomas who failed medical management or request the procedure. In this study, the complete resolution rate was high and voice restoration outcomes were good.


Rapid inhibition by intragastric triolein of the re-activation of glucose utilization and lipogenesis in the mammary gland during the starved-refed transition in lactating rats. Evidence for a direct effect of oral lipid on mammary tissue.
1. Oral administration of triacylglycerol (triolein) to starved/chow-refed lactating rats suppressed the lipogenic switch-on in the mammary gland in vivo. 2. A time-course study revealed that triolein, administered at 30 min after the onset of refeeding, had no influence on lipogenic rate in the mammary gland between 30 and 60 min, but markedly decreased it between 60 and 90 min. Glucose uptake by the mammary gland (arteriovenous difference) increased by 30 min of refeeding, as did lactate production. Between 30 and 90 min glucose uptake remained high in the control animals, but glucose uptake and net C3-unit uptake were decreased in the triolein-loaded animals by 90 min. 3. Triolein increased [glucose 6-phosphate] in the gland and simultaneously decreased [fructose 1,6-bisphosphate], indicative of a decrease in phosphofructokinase activity. This cross-over occurred at 60 min, i.e. immediately before the inhibition of lipogenesis, and by 90 min had reached 'starved' values. 4. Triolein had no effect on plasma [insulin] nor on whole-blood [glucose], [lactate] or [3-hydroxybutyrate]; a small increase in [acetoacetate] was observed. 5. Infusion of the lipoprotein lipase inhibitor, Triton WR1339, abolished the suppression of mammary-gland lipogenesis by triolein and the increase in the [glucose 6-phosphate]/[fructose 1,6-bisphosphate] ratio, suggesting a direct influence of dietary lipid on mammary-gland glucose utilization and phosphofructokinase activity.


Treatment of acute promyelocytic leukemia and other hematologic malignancies with arsenic trioxide: review of clinical and basic studies.
Acute promyelocytic leukemia (APL) is now the most potentially curable subtype of acute myeloid leukemia in adults because of the introduction of novel approaches in the management of this disease. All-trans-retinoic acid (ATRA)-based therapy is now the first-choice treatment of patients presenting with de novo APL, and clinical studies have shown that nearly all patients who receive ATRA therapy achieve complete remission. However, approximately 20% to 30% of APL patients eventually have relapses with resistance to further ATRA treatment. Arsenic trioxide (As2O3 [ATO]) has been established as highly effective therapy for patients with APL, even for those with disease refractory to ATRA. Furthermore, results of recent studies have suggested a broad therapeutic potential for ATO in the treatment of hematologic malignancies beyond APL. In this review, we discuss the clinical activity and multiple mechanisms of ATO therapy in the management of APL and other hematologic neoplasms.


Health and economic outcomes of a universal early intervention for parents and children from birth to age five: evaluation of the Salut Programme using a natural experiment.
The aim of this study was to investigate the health and economic outcomes of a universal early intervention for parents and children, the Salut Programme, from birth to when the child completed five years of age. This study adopted a retrospective observational design using routinely collected linked register data with respect to both exposures and outcomes from Västerbotten county, in northern Sweden. Making use of a natural experiment, areas that received care-as-usual (non-Salut area) were compared to areas where the Programme was implemented after 2006 (Salut area) in terms of: (i) health outcomes, healthcare resource use and costs around pregnancy, delivery and birth, and (ii) healthcare resource use and related costs, as well as costs of care of sick child. We estimated total cumulative costs related to inpatient and specialised outpatient care for mothers and children, and financial benefits paid to mothers to stay home from work to care for a sick child. Two analyses were conducted: a matched difference-in difference analysis using the total sample and an analysis including a longitudinal subsample. The longitudinal analysis on mothers who gave birth in both pre- and post-measure periods showed that mothers exposed to the Programme had on average 6% (95% CI 3-9%) more full-term pregnancies and 2% (95% CI 0.03-3%) more babies with a birth weight ≥ 2500 g, compared to mothers who had care-as-usual. Savings were incurred in terms of outpatient care costs for children of mothers in the Salut area ($826). The difference-in-difference analysis using the total sample did not result in any significant differences in health outcomes or cumulative resource use over time. The Salut Programme achieved health gains, as a health promotion early intervention for children and parents, in terms of more full-term pregnancies and more babies with a birth weight ≥ 2500 g, at reasonable cost, and may lead to lower usage of outpatient care. Other indicators point towards positive effects, but the small sample size may have led to underestimation of true differences.


Effects of human gamma interferon on cell growth, replication of virus and induction of 2'-5'oligoadenylate synthetase in three human lymphoblastoid cell lines and K562 cells.
Human alpha interferon (IFN-alpha) and beta interferon (IFN-beta) showed antiviral and anticellular effects on human lymphoblastoid Daudi and P3HR-1 cells, but up to 1,000 units/ ml of gamma interferon (IFN-gamma) showed no such effect. Though a fairly high level of dsRNA-dependent 2'-5'-oligoadenylate synthetase (2-5A synthetase) was found in Daudi cells, treatment of these cells with IFN-alpha and beta enhanced the enzyme level in cells at least four-fold, but IFN-gamma did not show any such effect. Lymphoblastoid Raji cells were insensitive to the antiviral and anticellular activities of IFN-alpha, beta and gamma, but 2-5A synthetase was induced in cells by the treatment with IFN-alpha and beta, though the enzyme level was lower than that found in interferon-treated Daudi cells. Human leukemic K562 cells were completely insensitive to IFN-alpha, beta and at the same time to IFN-gamma with regard to the antiviral, anticellular activities and to the induction of 2-5A synthetase.


Editorial for Special Issue "Advances in Soil Microbiome".
The soil microbiome (the community of all soil microorganisms and their surrounding environment) is a critical part of our ecological network [...].


Radiofrequency catheter ablation for the treatment of idiopathic premature ventricular contractions originating from the right ventricular outflow tract: a systematic review and meta-analysis.
Frequent idiopathic premature ventricular contractions (PVCs) have been associated with left ventricular cardiomyopathy. Idiopathic PVCs often originate from the right ventricular outflow tract (RVOT), and radiofrequency catheter ablation (RFCA) is being used as a treatment to alleviate symptoms. A meta-analysis was performed to evaluate RFCA for the treatment of frequent idiopathic PVCs on heart function. A literature search was conducted using Medline and Embase to identify studies evaluating the effects of RFCA as treatment for PVCs originating from the RVOT. Articles were chosen if they reported the effect of RFCA on the quantity of PVCs or ventricular function. Only studies in English were included. Articles were excluded if they did not separate results for PVCs originating from areas other than the RVOT. A total of 450 articles were retrieved from electronic searches, and 14 articles were included in this systematic review. Six of these were meta-analyzed (N = 70) and showed a reduction in the total number of PVCs in 24 hours after RFCA by a mean of -30089.44 confidence interval [CI]: -31658.47, -28520.40, P < 0.00001). Left ventricular ejection fraction (LVEF) was reported in five of the 14 studies, which included 108 patients. RFCA significantly improved LVEF by a mean of 10.36 (CI: 8.75, 11.97, P < 0.00001) in patients with frequent PVCs from the RVOT. The remaining studies reported their results differently and were not included in the meta-analyses but were described separately. RFCA reduces the number of PVCs and improves the cardiac function in patients with idiopathic frequent PVCs originating from the RVOT.


Bone marrow stroma cells promote induction of a chemoresistant and prognostic unfavorable S100A8/A9high AML cell subset.
The bone marrow (BM) stroma represents a protective niche for acute myeloid leukemia (AML) cells. However, the complex underlying mechanisms remain to be fully elucidated. We found 2 small, intracellular, calcium-sensing molecules, S100A8 and S100A9, among the top genes being upregulated in primary AML blasts upon stromal contact. As members of the S100 protein family, they can modulate such cellular processes as proliferation, migration, and differentiation. Dysregulation of S100 proteins is described as a predictor of poor survival in different human cancers, including increased S100A8 expression in de novo AML. Thus, we wanted to decipher the underlying pathways of stroma-mediated S100A8/A9 induction, as well as its functional consequences. Upregulation of S100A8/A9 after stromal cross talk was validated in AML cell lines, was contact independent and reversible and resulted in accumulation of S100A8/A9high cells. Accordingly, frequency of S100A8/A9high AML blasts was higher in the patients' BM than in peripheral blood. The S100A8/A9high AML cell population displayed enhanced utilization of free fatty acids, features of a more mature myeloid phenotype, and increased resilience toward chemotherapeutics and BCL2 inhibition. We identified stromal cell-derived interleukin-6 (IL-6) as the trigger for a Jak/STAT3 signaling-mediated S100A8/A9 induction. Interfering with fatty acid uptake and the IL-6-Jak/STAT3 pathway antagonized formation of S100A8/A9high cells and therapeutic resistance, which could have therapeutic implications as a strategy to interfere with the AML-niche dynamics.


A valid pre-manipulative screening tool is needed.
The Australian Physiotherapy Association's Clinical Guidelines for Pre-Manipulative Procedures for the Cervical Spine represent a positive step towards the goal of reducing the incidence of vertebrobasilar strokes following neck manipulation. Nevertheless, the predictive value of the guidelines is largely contingent upon the validity of the physical screening tests, particularly sustained end-range cervical rotation. The primary issue is the sensitivity of the tests for detecting patients with vertebral artery occlusion and vertebrobasilar insufficiency, and who are at high risk of experiencing significant forces during manipulation which could result in intimal dissection.


Association of body mass index with bladder cancer risk in men depends on abdominal obesity.
The previous epidemiological studies about the associations between obesity and bladder cancer risk have reported inconsistent results. Therefore, we analyzed whether the abdominal obesity effected on the risk of developing bladder cancer according to body mass index (BMI) using nationally representative data from the National Health Insurance System (NHIS). Among people who underwent at least one health examination from 2009 to 2012 in Korea, 11,823,876 men without a previous diagnosis of bladder cancer were followed up until December 2015. Multiple Cox regression analysis was conducted to determine the hazard ratio (HR) and 95% confidence interval (CI) for the association between bladder cancer and BMI or waist circumference (WC). Significant upward trends in the risk of bladder cancer were observed with increasing BMI or WC according to the multivariate-adjusted model. However, the association between BMI and bladder cancer is influenced by the presence of abdominal obesity. In the group with WC < 90 cm, there was no significant change in the HRs for bladder cancer development beyond the reference BMI. In contrast, the HRs for bladder cancer showed statistically significant increase as the BMI increased beyond the reference BMI in the group with WC ≥ 90 cm. This population-based study showed that increasing BMI and increasing WC were risk factors for developing bladder cancer in men, independent of confounding variables. However, there was a discrepancy in the trend of bladder cancer development according to BMI between the groups with abdominal obesity and without abdominal obesity.


Cognitive impairment and edentulism among older adults: an observational study using claims data.
The scientific link between mastication strength and cognitive function has not yet been strongly corroborated in population studies. Utilizing large-scale claims, we aim to investigate the association between edentulism and cognitive impairment in older American adults. Using de-identified claims from a commercial insurer from 2015-2019, we conducted a retrospective cohort study using multilevel regression models to evaluate the association between denture status and clinically diagnosed cognitive impairment. Secondary analysis included symptomatic cognitive impairment in the outcome. Adjusting for individual-level risk factors, denture status was significantly associated with clinical cognitive impairment with odds ratios of 1.13 (95%CI: 1.02-1.25) and 1.26, (95%CI: 1.09-1.45) for complete dentures on one or both jaws, respectively. Including symptomatic cognitive impairment in the analysis did not substantially change our fundamental findings. Prevention and treatment of oral diseases should be considered a key component in preserving the overall wellness of older adults.


Clustering of maternal-fetal clinical conditions and outcomes and placental lesions.
To identify by an inductive statistical analysis mutually similar and clinically relevant clinicoplacental clusters. Twenty-nine maternofetal and 49 placental variables have been retrospectively analyzed in a 3382 case clinicoplacental database using a hierarchical agglomerative Ward dendrogram and multidimensional scaling. The exploratory cluster analysis identified 9 clinicoplacental (macerated stillbirth, fetal growth restriction, placenta creta, acute fetal distress, uterine hypoxia, severe ascending infection, placental abruption, and mixed etiology [2 clusters]), 5 purely placental (regressive placental changes, excessive extravillous trophoblasts, placental hydrops, fetal thrombotic vasculopathy, stem obliterative endarteritis), and 1 purely clinical (fetal congenital malformations) statistically significant clusters/subclusters. The clusters of such variables like clinical umbilical cord compromise, preuterine and postuterine hypoxia, gross umbilical cord or gross chorionic disk abnormalities did not reveal statistically significant stability. Although clinical usefulness of several well-established placental lesions has been confirmed, claims about high predictability of others have not.


Active dry yeast supplementation benefits ruminal fermentation, bacterial community, blood immunoglobulins, and growth performance in young dairy goats, but not for intermittent supplementation.
This study evaluated the effects of active dry yeast (ADY) supplementation and supplementation strategies on ruminal fermentation, bacterial community, blood metabolites, and growth performance in young dairy goats. Sixty young female Guanzhong dairy goats of similar age (4.00 ± 0.50 months) and BW (19.65 ± 0.41 kg) were randomly divided into 3 groups (n = 20): (1) basal diet group (CON); (2) basal diet continuously supplemented with 3.0 g/goat per day commercial ADY (a proprietary strain of Saccharomyces cerevisiae with 5.0 × 109 cfu/g) group (CSY); (3) basal diet with intermittently supplemented ADY group (ISY; 5 d supplementation with ADY at 4.5 g/goat per day following 5 d of no supplementation). The experiment lasted 67 d with the first 7 d as an adaptive period. Rumen fluid and blood samples were collected bi-weekly. Data were analyzed using the MIXED procedure combined with the SLICE option in SAS. Specific orthogonal contrasts of ADY vs. CON and CSY vs. ISY were also analyzed. During the experimental period, ADY supplementation resulted in greater DMI (P = 0.03), ruminal acetate proportion (P < 0.01) and acetylesterase activity (P = 0.01), and blood contents of glucose (P = 0.01) and IgM (P = 0.02) and tended to have greater ADG (P = 0.05) and paunch girth (P = 0.06) than the CON, despite the propionate proportion (P = 0.03) and contents of total protein (P = 0.04) and IgA (P = 0.03) being lower. The lower ruminal NH3-N (P < 0.01) and blood urea nitrogen (P = 0.07) contents indicated greater nitrogen utilization with ADY supplementation. ADY supplementation showed persistent effects after it was stopped because the BW at 12 months of age (P = 0.03) and birth weight of lambs (P = 0.02) were greater than the CON. However, the ISY did not show those benefits and had significantly lower relative abundances of fiber-degrading related bacteria than the CSY. In conclusion, ADY supplementation, especially continuously supplemented, may enhance ADG and ADG:DMI ratio by improving DMI, ruminal cellulolytic bacteria abundance and enzyme activity, nitrogen utilization, and immune status. These findings provide a theoretical basis for the rational application of ADY and have important practical implications for the design of nutritional strategies in growing dairy goats.


The impact of epigenetic landscape on ovarian cells in infertile older women undergoing IVF procedures.
The constant decline in fertility and older reproductive age is the major cause of low clinical pregnancy rates in industrialised countries. Epigenetic mechanisms impact on proper embryonic development in women undergoing in vitro fertilisation (IVF) protocols. Here, we describe the main epigenetic modifications that may influence female reproduction and could affect IVF success.


Prognostic contributions of the underlying inflammatory disease and acute organ dysfunction in critically ill patients with systemic rheumatic diseases.
Knowledge about the clinical features, outcomes and predictors of short-term mortality in critically ill patients with systemic rheumatic disease (SRD) requires further characterization. Single center retrospective observational cohort study of 149 critically ill patients with SRD followed in a French medical intensive care unit over a 20-year period. Multivariate logistic regression was used to identify predictors of day-30 mortality. Most patients (63%) had systemic lupus erythematosus, rheumatoid arthritis, or systemic sclerosis. The critical illness usually developed late after the diagnosis of SRD (median time to ICU admission 82 months, IQR [9-175] in the 127 patients with a previous diagnosis of SRD). Two-thirds of patients were taking immunosuppressive drugs to treat their SRD. Reasons for ICU admission were infection (47%), SRD exacerbation (48%), and iatrogenic complications (11%); the most common organ failure was acute renal failure. Thirty-day mortality was 16%. Predictors of 30-day mortality were the LODS score on day 1 (OR 1.3 (1.06-1.48)), bacterial pneumonia (OR 3.8 (1.03-14.25)), need for vasoactive drugs (OR 7.1 (1.83-27.68)), SRD exacerbation (OR 4.3 (1.15-16.53)), and dermatomyositis (OR 9.2 (1.05-80.78)) as the underlying disease. Year of ICU admission was not significantly associated with 30-day survival. Patients with SRD are mostly admitted in the ICU with infection or SRD exacerbation, and can be treated with immunosuppressive therapy and life-sustaining interventions with acceptable 30-day mortality. Death is associated with both the severity of the acute medical condition and the characteristics of the underlying SRD.


Financial conflicts of interest of OncoAlert: An informal oncology professional network.
Social media platforms have allowed the formation of informal professional healthcare networks. Transparency in funding, membership requirements, financial conflicts of interest (FCOI), and messaging are necessary to ensure best practices for similar networks in the future. To analyze the FCOIs of US-based physician members of the OncoAlert Network and appraise the content of their public Twitter account. This cross-sectional study assessed the FCOIs among US-based physician members of the OncoAlert Network between 2015 and 2020. FCOI data were obtained through the Open Payments Database. Additionally, tweets were examined for content analysis. The number of US-based physician members with FCOIs with the pharmaceutical industry; the amount of general, research, and associated research payments; and the perceived attitude of tweet content from the OncoAlert Network Twitter account. Of 34 US physician members of the OncoAlert Network, 31 (91.2%) received general payments from pharmaceutical companies according to the Open Payments Database. Between 2015 and 2020, US physician members of the OncoAlert Network received a median of $83,600 in general payments (interquartile range [IRQ], $7,200-$221,500). Fourteen members (41.1%) received more than $100,000 in general payments. Additionally, 480 (15.7 %) of 3064 tweets retrieved from the OncoAlert Twitter account mentioned a drug or clinical trial. Of these, 31.6 % (n = 152) had a positive disposition and 3.3 % (n = 16) were negative or critical. Over 90% of US physician members of the OncoAlert Network had FCOIs between 2015 and 2020. Despite the network's non-profit status, FCOIs amongst its members may influence content produced on the network's social media platforms, such as Twitter, where content discussing drugs and clinical trials are often positive and seldom negative or critical. For future informal professional networks, further research is required to establish best practices for issues such as membership requirements, funding, and FCOI disclosure.


Determination of the optimal pore size for improved CO2 adsorption in activated carbon fibers.
Commercially available activated carbon fibers (ACFs) were modified further by a chemical activation method to obtain superior CO(2) adsorption capacity. The relationship between the pore structure of the modified ACF and the CO(2) adsorption behaviors was investigated. Chemical activation (with KOH at a fixed activation temperature of 900°C for 1h and various KOH/ACF weight ratios ranging from 1 to 4) of ACF increased the total pore volume and specific surface area to 1.124 cm(3)g(-1) (KOH/ACF weight ratio of 2) and 2318 m(2)g(-1) (KOH/ACF weight ratio of 4), respectively. Compared to ACF, the total pore volume and specific surface area were improved by factors of 2.5 and 2.3, respectively. Interestingly, the highest CO(2) adsorption capacity of 250 mg g(-1) at 298 K and 1 bar was observed at a KOH/ACF weight ratio of 3. The modified ACF had the narrowest microporosity ranging from 0.5 to 0.7 nm. Therefore, the increase in CO(2) adsorption capacity after chemical activation is closely related to the narrower pore size distribution rather than the total or micropore volume and specific surface area.


Can antepartum computerized cardiotocography predict the evolution of intrapartum acid-base status in normal fetuses?
To study the relationship between antepartum computerized cardiotocography (cCTG) and the evolution of intrapartum fetal acid-base balance in a low-risk population. Forty-nine healthy fetuses were prospectively followed up by antepartum cCTG (Oxford System 8002), fetal scalp blood sampling at the onset of the active phase of dilatation (3 cm) and at the beginning of the second stage of labor (10 cm) and study of acid-base status at birth in the umbilical cord. Correlation studies and linear regression analysis were performed. Normal prelabor cCTG was followed by normal fetal acid-base balance in the different study periods. No relationship was found between cCTG parameters and the absolute values of fetal acid-base status. However, the more favorable the antepartum cCTG parameters were, the more favorable the fetal acid-base evolution during the active phase of dilatation was. In contrast, no significant correlations were found between antepartum cCTG and fetal acid-base changes during the second stage of labor. In normal fetuses, a single antepartum cCTG identified correctly fetal well-being during labor and at birth and was able to predict fetal acid-base evolution during the active phase of dilatation. However, fetal biochemical changes during the second stage could not be predicted by any antepartum cCTG parameter.


Chemically crosslinked nanogels of PEGylated poly ethyleneimine (l-histidine substituted) synthesized via metal ion coordinated self-assembly for delivery of methotrexate: Cytocompatibility, cellular delivery and antitumor activity in resistant cells.
Self-assembled nanogels were engineered by forming Zn(2+)-coordinated micellar templates of PEGylated poly ethyleneimine (PEG-g-PEI), chemical crosslinking and subsequent removal of the metal ion. Creation of stable micellar templates is a crucial step for preparing the nanogels. To this aim, imidazole moieties were introduced to the polymer by Fmoc-l-histidine using carbodiimide chemistry. It was hypothesized the nanogels loaded with methotrexate (MTX), a chemotherapeutic agent, circumvent impaired carrier activity in HepG2 cells (MTX-resistant hepatocellular carcinoma). So, the nanogels were post-loaded with MTX and characterized by (1)H-NMR, FTIR, dynamic light scattering-zeta potential, atomic force microscopy, and drug release experiments. Cellular uptake and the antitumor activity of MTX-loaded nanogels were investigated by flow cytometry and MTT assay. Discrete, spherical and uniform nanogels, with sizes about 77-83 nm and a relatively high drug loading (54 ± 4% w/w), showed a low polydispersity and neutral surface charges. The MTX-loaded nanogels, unlike empty nanogels, lowered viability of HepG2 cells; the nanogels demonstrated cell-cycle arrest and apoptosis comparably higher than MTX as free drug that was shown to be through i) cellular uptake of the nanogels by clathrin-mediated transport and ii) endosomolytic activity of the nanogels in HepG2 cells. These findings indicate the potential antitumor application of this preparation, which has to be investigated in-vivo.


Ischemic optic neuropathy as a model of neurodegenerative disorder: A review of pathogenic mechanism of axonal degeneration and the role of neuroprotection.
Optic neuropathy is a neurodegenerative disease which involves optic nerve injury. It is caused by acute or intermittent insults leading to visual dysfunction. There are number of factors, responsible for optic neuropathy, and the optic nerve axon is affected in all type which causes the loss of retinal ganglion cells. In this review we will highlight various mechanisms involved in the cell loss cascades during axonal degeneration as well as ischemic optic neuropathy. These mechanisms include oxidative stress, excitotoxicity, angiogenesis, neuroinflammation and apoptosis following retinal ischemia. We will also discuss the effect of neuroprotective agents in attenuation of the negative effect of factors involve in the disease occurrence and progression.


Magnetic resonance measurement of blood flow in peripheral vessels after acute exercise.
Velocity-encoded Cine magnetic resonance imaging (MRI) was used to measure blood flow in the anterior tibial artery (AT), posterior tibial artery (PT), and popliteal artery of adult human subjects (mean age 29 yr) before and after 90 s of ankle dorsiflexion exercise. Before exercise, mean flow, peak systolic velocity, and end-diastolic velocity in AT were 8.1 +/- 1.6 (SE, n = 6) ml/min, 26.9 +/- 2.6 cm/s, and -0.6 +/- 0.4 cm/s, respectively. After exercise, mean flow and peak systolic velocity in AT increased by 19-fold and 3-fold, respectively, and end-diastolic velocity increased to 8.7 +/- 1.1 cm/s. Flow in popliteal artery above its bifurcation was similar to the sum of flows in AT and PT, both before and after exercise. Flow in AT declined exponentially after exercise with a mean half-time of 4 min. The results demonstrate the utility of MR phase-encoded flow-velocity measurements for physiological studies of peripheral vascular dynamics after exercise.


Gastroenteritis outbreak at holiday resort, central Italy.
During the summer of 2003, a gastroenteritis outbreak spread throughout a holiday resort in central Italy. Fecally contaminated groundwater and seawater were leaking into the non-drinking-water system, which was found to be connected to the drinking-water system of a large resort. This contamination had a primary role in the onset of the outbreak and spread of the infection.


Lidocaine tripotassium phosphate complex laden microemulsion for prolonged local anaesthesia: In vitro and in vivo studies.
Lidocaine is widely used as a local anaesthetic in the clinical practice to manage pre- and post-operative pain, skin burns, etc. However, the short duration of action (< 2 h) of marketed dosage forms limit their ability to meet clinical needs. Herein, we prepared a lidocaine-tPP(tri potassium phosphate)-complex loaded microemulsion to achieve greater penetration, followed by destabilization of microemulsion in the skin layer to precipitate oil-complex to produce a depot effect in the skin for prolonging the effects of anaesthesia. The lidocaine-tPP-complex-microemulsion was compared with lidocaine base loaded microemulsion, marketed ointment USP and lidocaine HCl. The pseudo ternary phase diagrams at three Smix ratios (1:2, 1:3 and 1:4; Pluronic F127: PEG 400) were constructed using Capmul MCM C8 EP as oil phase. The Smix at 1:4 ratio showed large microemulsion area in comparison to 1:2 and 1:6 ratio. The lidocaine base (LD-1:4-ME10O45SM and LD-1:4-ME20O45SM) and lidocaine-tPP-complex (LDC-1:4-ME10O45SM and LDC-1:4-ME20O45SM) loaded microemulsion batches (1:4 ratio) were thermodynamically stable. The ex vivo diffusion study showed sustained release up to 12 h with microemulsion batches, in comparison to lidocaine HCl (4 h) and ointment base (7 h). The selected LDC-1:4-ME20O45SM batch was non-irritating on the rabbit skin. In drug retention studies, LD-1:4-ME20O45SM and LDC-1:4-ME20O45SM batches showed 2.68- and 3.93-fold greater lidocaine retention in comparison to ointment USP. The radiant heat tail-flick test showed prolong local anaesthesia using LDC-1:4-ME20O45SM in comparison to ointment USP. The findings suggest that lidocaine-tPP-complex loaded microemulsion could be a potential strategy for providing prolong local anaesthesia.


Simplified contaminant source depletion models as analogs of multiphase simulators.
Four simplified dense non-aqueous phase liquid (DNAPL) source depletion models recently introduced in the literature are evaluated for the prediction of long-term effects of source depletion under natural gradient flow. These models are simple in form (a power function equation is an example) but are shown here to serve as mathematical analogs to complex multiphase flow and transport simulators. The spill and subsequent dissolution of DNAPLs was simulated in domains having different hydrologic characteristics (variance of the log conductivity field=0.2, 1 and 3) using the multiphase flow and transport simulator UTCHEM. The dissolution profiles were fitted using four analytical models: the equilibrium streamtube model (ESM), the advection dispersion model (ADM), the power law model (PLM) and the Damkohler number model (DaM). All four models, though very different in their conceptualization, include two basic parameters that describe the mean DNAPL mass and the joint variability in the velocity and DNAPL distributions. The variability parameter was observed to be strongly correlated with the variance of the log conductivity field in the ESM and ADM but weakly correlated in the PLM and DaM. The DaM also includes a third parameter that describes the effect of rate-limited dissolution, but here this parameter was held constant as the numerical simulations were found to be insensitive to local-scale mass transfer. All four models were able to emulate the characteristics of the dissolution profiles generated from the complex numerical simulator, but the one-parameter PLM fits were the poorest, especially for the low heterogeneity case.


New method for measuring bladder pressure.
We measured intramural pressure of the bladder using a pressure transducer embedded between bladder mucosa and muscle layers in female dogs. Intravesical pressure was recorded simultaneously by conventional transurethral catheter method. Results from the former showed slightly lower values than the latter, but both correlated well in all pressure ranges.


Enhanced antifungal activity of fluconazole conjugated with Cu-Ag-ZnO nanocomposite.
Cu-Ag-ZnO nanocomposite (NC) has been successfully synthesized by mechanical alloying the Cu, Zn and Ag powder mixture under Ar atmosphere within 4 h of milling. The nanocomposite is then conjugated with the antifungal drug fluconazole by adding 5 wt% powdered drug to the NC and mechanical alloying the total powder mixture for one more hour. The Rietveld refinement of XRD data and FTIR spectrum analyses reveal the detailed structural and microstructural characterizations of the nanocomposite-drug conjugate (NC-DC). Presence of Cu, Ag, ZnO and drug in the 5 h milled powder are confirmed by analyzing TEM images and FESEM-EDS spectrum. Results obtained from FESEM and TEM images reveal the measure of particle size of the nanocomposite-drug conjugate and it agrees well with the crystallite size obtained from the Rietveld refinement. A significant antifungal activity of NC-DC against Candida sp. fungi has been revealed using disk agar diffusion method. Minimum inhibitory concentration (MIC) test confirms that NC-DC with only 5 wt% fluconazole produces similar antifungal activity of the pure (100 wt%) and conventional fluconazole. Thus, the conjugation of conventional drug to a nanocomposite results in enhancement of drug efficiency by a factor 20 folds. This is very important, particularly, for those antibiotics which are very effective in controlling several epidemic diseases but show intense side effects when used at higher dose and/or for a longer duration.


The p53 codon 249 mutational hotspot in hepatocellular carcinoma is not related to selective formation or persistence of aflatoxin B1 adducts.
Sequence-dependent formation and lack of repair of polycyclic aromatic hydrocarbon-induced DNA adducts correlates well with the positions of p53 mutational hotspots in smoking-related lung cancers (Denissenko et al, 1996, 1998). The mycotoxin aflatoxin B1 (AFB1) is considered to be a major causative agent in hepatocellular carcinoma (HCC) in regions with presumed high food contamination by AFB1. A unique mutational hotspot, a G to T transversion at the third base of codon 249 of the p53 gene is observed in these tumors. To test whether a selectivity of AFB1 adduct formation is related to this peculiar mutational spectrum, we have mapped AFB1-DNA adducts at nucleotide resolution using ligation-mediated PCR and terminal transferase-dependent PCR. Human HepG2 cells were exposed to AFB1 metabolically activated in the presence of rat liver microsomes. Significant adduct formation was seen at the third base of codon 249. However, this was not the major site of AFB1 adducts and strong adduction was also observed at codons 226, 243, 244, 245 and 248 in exon 7 of the p53 gene and at several codons in exon 8. The damage at codon 249 does not consist of a unique abasic site or ring-opened aflatoxin B1 adduct but rather is consistent with the principal N7-guanine adduct of AFB1. Time course experiments indicate that, under the conditions used, AFB1 adducts are not removed in a strand-selective manner and adduct removal from the third base of codon 249 proceeds at a relatively fast rate (50% in 7 h). The incomplete correspondence between sites of persistent AFB1 damage and the specific codon 249 mutation suggests that AFB1 may not be involved in mutation of this site or that additional mechanisms such as parallel infection with hepatitis B virus may be required for selection of codon 249 mutants in HCC.


Alpha-1-antitrypsin and other proteinase inhibitors.
Since the end of the 1980s augmentation therapy with alpha-1 antitrypsin (AAT) from human plasma has been available for specific treatment of emphysema due to AAT deficiency. Intravenous augmentation therapy has demonstrated to be safe and weekly infusions of AAT have demonstrated to result in plasma AAT concentration above those considered protective for the lungs. Randomized, placebo-controlled clinical trials have confirmed a reduction in the decline in lung density in patients receiving augmentation therapy. This is the first example of an antiprotease effective in restoring the protease/antiprotease imbalance in the lungs and changing the natural history of congenital emphysema. On the basis of the results obtained with the long-term infusion of AAT, there is growing interest in the possible use of antiprotease treatment in patients with smokers COPD. However, no drugs are yet available to increase antiprotease protection of the lower airways of smokers.


Intradural tumor recurrence after resection of extradural metastasis: a rare but potential complication of intraoperative durotomy.
Spinal metastases are the most common of spinal neoplasms and occur predominantly in an extradural location. Their appearance in an intradural location is uncommon and is associated with a poor prognosis. Cerebrospinal fluid dissemination accounts for a significant number of intradural spinal metastases mostly manifesting as leptomeningeal carcinomatoses or drop metastases from intracranial tumors. The occurrence of local tumor dissemination intradurally following surgery for an extradural spinal metastasis has not been reported previously. The authors describe 2 cases in which local intradural and intramedullary tumor recurrences occurred following resection of extradural metastases that were complicated by unintended durotomy. To heighten clinical awareness of this unusual form of local tumor recurrence, the authors discuss the possible etiology and clinical consequences of this entity.


An innovative approach for reducing the water and alkali consumption in the lactic acid fermentation via the reuse of pretreated liquid.
This study focuses on enhancing lactic acid (LA) production and declining water and alkali consumption by reusing the pretreated liquid (PL) of spent mushroom substance (SMS) in the co-fermentation of food waste (FW) and SMS. First, the compositions of PL are identified, and the effects of the PL inhibitors on enzymatic hydrolysis and fermentation are explored. The PL phenol concentrations exceeded 2 g/L, which affected LA fermentation. Therefore, PL phenols were removed by adjusting the pH value, and the detoxified PL (DPL) phenol concentrations were 70.3% lower than those of PL. Different PL:DPL ratios were established to reuse in the fermentation process, and the LA concentration in the 50% PL + 50% DPL group was the highest (56.7 g/L). Then, pretreated SMS was not water-washed, and a neutralizer was prepared with the PL, LA production remained unchanged. Water and NaOH consumption decreased by 84.6% and 52.0%, respectively, and no wastewater was produced.


Is befriending a valuable intervention in schizophrenia? A scoping review.
Schizophrenia is a severe, chronic mental disorder that involves disruptions in cognitive processes, emotional responsiveness, and social interactions. Psychotherapeutic and social integration practices have increasingly been added to the pharmacological treatment in an effort to improve the level of functioning and the quality of life of individuals affected by this condition. Befriending, defined as a one-on-one companionship provided by a volunteer who aims to act as an emotionally supportive liaison, is hypothesized to be an effective such intervention, offering support for building and maintaining social relationships in the community. Despite its increase in popularity and acceptance, befriending remains poorly understood and under-researched. We performed a systematic search for studies targeting befriending either as an intervention or a controlled condition in studies on schizophrenia. Searches were performed in four databases: APA PsycInfo, Pubmed, Medline and EBSCO. The keywords "schizophrenia," AND "befriending," were searched for on all databases. The search yielded 93 titles and abstracts, of which 18 met the criteria for inclusion. The studies included in this review have all incorporated befriending as an intervention or a controlled condition, as per our search criteria, and aimed at depicting the value and feasibility of this intervention to address social and clinical deficits in individuals with schizophrenia. The studies selected for this scoping review revealed inconsistent findings regarding the effect of befriending on overall symptoms and the subjective reporting of quality of life in individuals with schizophrenia. This inconsistency may be attributed to differences between the studies and their specific limitations.


Perioperative pain management in veterinary patients.
Pain exists; however, we can prevent it, and we can treat it. The fallacy that pain is protective and must be allowed to avoid risk for damage after surgery needs to be eradicated. Preoperative and postoperative analgesia is directed at aching pain, whereas sharp pain associated with inappropriate movements persists. Analgesia provides much more benefit than concern. This article provides suggestions for development of an analgesic plan from the point of admission to discharge. These guidelines can then be adjusted according to the patient's needs and responses.


Olfactory brain activations in patients with Major Depressive Disorder.
Depression is associated with reduced olfactory function. This relationship is assumed to be based on either a reduced olfactory bulb volume or diminished functioning of higher cortical areas. As previous results are controversial, we aimed to re-evaluate central olfactory processing in depression. We recorded the BOLD signal of 21 patients with Major Depressive Disorder and 21 age and gender matched healthy controls during odor presentation. In addition, we measured the individual olfactory bulb volume, tested odor identification and odor threshold, and asked for hedonic odor perception. In both groups, odor presentation led to a pronounced activation of primary olfactory areas. However, secondary olfactory areas were significantly less activated in depressed individuals. The two groups did not differ in olfactory bulb volume. Our results point towards altered olfactory processing in patients in those regions that relate to sensory integration and attention allocation. Difficulties in cognitive processing could impact olfactory function in depression. We are therefore in favor of a top-down mechanism originating in higher cortical areas explaining parts of the relation between depression and olfaction.


Transcription of the histone loci on lampbrush chromosomes of the newt Notophthalmus viridescens.
We have investigated transcription of the histone gene cluster on lampbrush chromosomes of the newt Notophthalmus viridescens. Clusters of the five histone genes are separated by long tracts of a DNA repeat called satellite 1. Previous in situ hybridization results demonstrated the presence of histone gene coding regions, intergene spacers, and flanking satellite repeats in giant transcription units on lampbrush chromosomes. These results suggested a model in which transcription initiates at histone gene promoters and continues through the rest of the gene cluster into satellite repeats. The readthrough transcription model predicts that spacer regions upstream of the first promoter in the gene cluster should be absent from nascent transcripts on chromosome loops. We have used such upstream spacer probes for in situ hybridization to lampbrush chromosomes. Contrary to our expectation, the results show that upstream spacer regions are transcribed, and indicate that transcription often initiates upstream of the first histone gene promoter. The relationship of giant transcription units in oocyte nuclei to cytoplasmic histone mRNA is discussed.


Comparison of Oral Health-Related Quality of Life scores in children treated for early childhood caries under general and local anesthesia: a quasi-experimental study.
The purpose of this study was to compare the changes in oral health-related quality of life (OHRQoL) scores in children treated for Early Childhood Caries (ECC) under general (GA) and local anesthesia (LA). A quasi-experimental study was carried out on 73 children, with 37 in the GA group and 36 in the LA group. The early childhood oral health impact scale (ECOHIS) was used to measure OHRQoL, with the type of anesthesia (LA or GA) serving as the explanatory variable. A Friedman test was used to assess the difference between the LA and GA groups at baseline, one-week, and one-month follow-up points. The results showed a significant difference in the overall mean ECOHIS scores between the LA and GA groups at 1-week (LAmean ± SD = 6.12 ± 1.11, GAmean ± SD = 5.50 ± 0.88; P = 0.01) and 1-month (LAmean ± SD = 5.87 ± 1.12, GAmean ± SD = 4.96 ± 0.99; P < 0.001) follow-up points. Irrespective of the administered anesthesia, a significant (P < 0.001) reduction in the mean score for dental pain was observed at both 1-week (mean ± SD = 1.30 ± 1.16) and 1-month (mean ± SD = 0.81 ± 0.89) timepoints after the treatment, as compared to the baseline assessment (mean ± SD = 2.02 ± 1.02). Early treatment for ECC reduces pain, restore normal activities, and improves the quality of life of affected children. Specifically, GA was found to be more beneficial for both children and parents. However, further studies using more robust study designs and carefully considering related factors are necessary to confirm these findings.


Nuclear import of Xenopus egg extract components into cultured cells for reprogramming purposes: a case study on goldfish fin cells.
Reprogramming of cultured cells using Xenopus egg extract involves controlling four major steps: plasma membrane permeabilization, egg factors import into the nucleus, membrane resealing, and cell proliferation. Using propidium iodide to assess plasma membrane permeability, we established that 90% of the cultured fin cells were permeabilized by digitonin without any cell losses. We showed that egg extract at metaphase II stage was essential to maintain nuclear import function in the permeabilized cells, as assessed with a fusion GFP protein carrying the nuclear import signal NLS. Moreover, the Xenopus-egg-specific Lamin B3 was detected in 87% of the cell nuclei, suggesting that other egg extract reprogramming factors of similar size could successfully enter the nucleus. Lamin B3 labelling was maintained in most cells recovered 24 h after membrane resealing with calcium, and cells successfully resumed cell cycle in culture. In contrast, permeabilized cells that were not treated with egg extract failed to proliferate in culture and died, implying that egg extract provided factor essential to the survival of those cells. To conclude, fish fin cells were successfully primed for treatment with reprogramming factors, and egg extract was shown to play a major role in their survival and recovery after permeabilization.


Characterization of Chlamydomonas voltage-gated calcium channel and its interaction with photoreceptor support VGCC modulated photobehavioral response in the green alga.
Calcium (Ca2+) signaling plays a major role in regulating multiple processes in living cells. The photoreceptor potential in Chlamydomonas triggers the generation of all or no flagellar Ca2+ currents that cause membrane depolarization across the eyespot and flagella. Modulation in membrane potential causes changes in the flagellar waveform, and hence, alters the beating patterns of Chlamydomonas flagella. The rhodopsin-mediated eyespot membrane potential is generated by the photoreceptor Ca2+ current or P-current however, the flagellar Ca2+ currents are mediated by unidentified voltage-gated calcium (VGCC or CaV) and potassium channels (VGKC). The voltage-gated ion channel that associates with ChRs to generate Ca2+ influx across the flagella and its cellular distribution has not yet been identified. Here, we identified putative VGCCs from algae and predicted their novel properties through insilico analysis. We further present experimental evidence on Chlamydomonas reinhardtii VGCCs to predict their novel physiological roles. Our experimental evidences showed that CrVGCC4 localizes to the eyespot and flagella of Chlamydomonas and associates with channelrhodopsins (ChRs). Further in silico interactome analysis of CrVGCCs suggested that they putatively interact with photoreceptor proteins, calcium signaling, and intraflagellar transport components. Expression analysis indicated that these VGCCs and their putative interactors can be perturbed by light stimuli. Collectively, our data suggest that VGCCs in general, and VGCC4 in particular, might be involved in the regulation of the photobehavioral response of Chlamydomonas.


A semiempirical theory of the optical activity of saccharides.
A semiempirical theory of optical activity of saccharides is developed that (a) goes beyond previous empirical treatments, (b) yields calculated NaD rotations which correlate well with experimental data, and (c) accounts for a characteristic c.d. band observed for polysaccharides in the vacuum u.v. spectrum.


The effect of COVID-19 home quarantine on the psychological state of pharmacy students: a cross-sectional study.
Psychological morbidity has been documented in medical and pharmaceutical undergraduate students in different countries around the world. In this study, we examined the impact of coronavirus disease 2019 (COVID-19) home quarantine on the depressive psychological aspects of last-grade pharmacy students. A cross-sectional study was conducted by the Department of Clinical Pharmacy, Faculty of Pharmacy, Deraya University, Egypt. Two hundred and sixty-eight last-grade pharmacy students were included in this study, and they completed a self-administered, pre-designed, anonymous questionnaire. The main outcome measures were the Hamilton Depression Rating Scale (HRS) and Patient Health Questionnaire-9 (PHQ-9), which were measured to screen for the symptoms of psychological depression and determine the degree of depression severity between the beginning and the end of the COVID-19 home quarantine period. Data entry and analysis were done using the Statistical Package for Social Science (SPSS) software version 26. Descriptive statistics were employed for analyses of the data, and categorical variables were described by frequencies and percentages. Bivariate and multivariable analyses were performed to examine relations between demographic data and psychological scales. The study protocol was approved by the Faculty of Pharmacy, Minia University Ethical Committee. A total of 268 students participated in this study (102 males and 166 females). The mean ± SD score of baseline HRS and HRS at the end of the study was 6.3 ± 4.45, 7.95 ± 5.36, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The mean ± SD score of baseline PHQ-9 and PHQ-9 at the end of the study was 4.35 ± 3.45, 5.37 ± 4.14, respectively, with the presence of a statistically significant difference between the two scores (p < 0.001). The results showed that the COVID-19 home quarantine period led to a depressive psychological effect on the students in this study. Students' psychological depression causes morbidity and, in some cases, mortality. Psychological depressive problems were significantly associated with the COVID-19 home quarantine period, which calls for early intervention to solve it. Student counselling services must be more accessible and affordable to overcome this problem.


Morphological modifications induced by HCV infection in the TOFE human lymphoblastoid cell line.
In this study, we analysed by transmission electron microscopy (TEM), sequential details of morphological modifications that accompanied viral morphogenesis in the lymphoblastoid cell line (LCL) TOFE infected in vitro with hepatitis C virus (HCV). As previously reported, we observed virus-like particles (VLPs) in cytoplasmic vesicles mainly located in the perinuclear region of infected cells. In this area, the Golgi apparatus and the endoplasmic reticulum (ER) appeared hyperplastic, remarkably enriched in vesicles and lysosomal structures. Furthermore, only in this perinuclear region, cytopathic-effect(CPE)-like changes seemed to originate, consisting in enlarged cytoplasmic vacuoles filled with degenerative amorphous material containing VLPs. Finally, the complete filling-up of the cytoplasm with these degenerative vacuoles, in addition to cellular lysis displayed by some cells, appeared as the possible terminal pattern of the infectious process. Our data suggest that in vitro HCV-infected TOFE cells undergo typical CPE-like changes that may be connected with virus replication.


Effects of angle and laminectomy on triangulated pedicle screws.
We aimed to demonstrate the effect of angle and laminectomy on paired pedicle screws to determine whether a 90 degrees screw angle is optimal as has been previously suggested. According to the angle between right and left screws, 28 calf vertebrae were divided into three groups and instrumented as follows: Group I: 60 degrees screw angle; Group II: 90 degrees angle; Group III: 60 degrees angle with laminectomy. The screws were connected using rods and cross-fixators and tested to peak pullout force. Triangulated pedicle screws provided 76.5% more pullout strength than single screws. Most of the specimens failed through loss of convergence angle (toggling of screws on the rods) and subsequent uni- or bilateral screw pullout. Mean+/-SD peak loads were: Group I: 2071+/-622 N; Group II: 1753+/-497 N; Group III: 2186+/-587 N. The differences were not significant (p>0.05). 90 degrees triangulation was not associated with a superior pullout performance versus conventional 60 degrees triangulation, suggesting that achieving additional triangulation angle is not necessary to obtain increased pullout strength. Laminectomy did not alter the effect of triangulation on fixation strength.


Therapeutic use of extracellular mitochondria in CNS injury and disease.
In the central nervous system (CNS), neuronal functionality is highly dependent on mitochondrial integrity and activity. In the context of a damaged or diseased brain, mitochondrial dysfunction leads to reductions in ATP levels, thus impairing ATP-dependent neural firing and neurotransmitter dynamics. Restoring mitochondrial ability to generate ATP may be a basic premise to restore neuronal functionality. Recently, emerging data in rodent and human studies suggest that mitochondria and its components are surprisingly released into extracellular space and potentially transferred between cells. Transferred mitochondria may support oxidative phosphorylation in recipient cells. In this mini-review, we (a) survey recent findings in cell to cell mitochondrial transfer and the presence of cell-free extracellular mitochondria and its components, (b) review experimental details of how to detect extracellular mitochondria and mitochondrial transfer in the CNS, (c) discuss strategies and tissue sources for mitochondria isolation, and (d) explore exogenous mitochondrial transplantation as a novel approach for CNS therapies.


The OPTIMISE study protocol: a multicentre optimisation trial comparing continuous glucose monitoring, snacking habits, sleep extension and values-guided self-care interventions to improve glucose time-in-range in young people (13-20 years) with type 1 diabetes.
The OPTIMISE study uses a Multiphase Optimisation Strategy (MOST) to identify the best combination of four interventions targeting key diabetes self-care behaviours for use in clinical practice to improve short-term glycaemic outcomes. This 4-week intervention trial will recruit 80 young people (aged 13-20 years) with type 1 diabetes ≥ 6 months duration), and pre-enrolment HbA1c ≥ 58 mmol/mol (7.5%) in the prior 6 months. Both main intervention and interaction effects will be estimated using a linear regression model with change in glucose time-in-range (TIR; 3.9-10.0 mmol/L) as the primary outcome. Participants will be randomised to one of 16 conditions in a factorial design using four intervention components: (1) real-time continuous glucose monitoring (CGM), (2) targeted snacking education, (3) individualised sleep extension, and (4) values-guided self-care goal setting. Baseline and post-intervention glucose TIR will be assessed with blinded CGM. Changes in self-care (snacking behaviours, sleep habits and duration, and psychosocial outcomes) will be assessed at baseline and post-intervention to determine if these interventions impacted behaviour change. The study outcomes will enable the selection of effective and efficient intervention components that increase glucose TIR in young people who struggle to achieve targets for glycaemic control. The optimised intervention will be evaluated in a future randomised controlled trial and guide the planning of effective clinical interventions in adolescents and young adults living with type 1 diabetes. This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 7 October 2020 (ACTRN12620001017910) and the World Health Organisation International Clinical Trails Registry Platform on 26 July 2020 (Universal Trial Number WHO U1111-1256-1248).


Green energy security assessment in Morocco: green finance as a step toward sustainable energy transition.
Morocco is an energy-deficient country depending on almost 94% of energy imports to fuel its growing economy. Due to its fast-growing population, Morocco's energy consumption is projected to increase significantly, adding more pressure on the energy system. On the other hand, the rising tension of scarcity of resources, energy price fluctuations, and environmental issues have all made energy security one of its top priorities. Therefore, Morocco launched the National Energy Strategy (NES) in 2009 to reach 42% renewable generation by 2020, which was renewed to up to 52% by 2050. This study analyzes Morocco's energy security under the 4-As framework from 2000 to 2016.The 4-As methodology aims to assess and graphically illustrate the changes in Morocco's energy security by mapping these changes into four key dimensions: the availability of energy resources, the applicability of technology, the acceptability by the environment and society, and the affordability of energy resources. The quantitative analysis shows that Morocco's energy security performance was at its optimum during the first period of study (2000-2004) but then regressed for the remainder of the study period, as energy imports and prices increased, in addition to the low performance in applicability characterized by low energy efficiency. To improve Morocco's energy security status and move toward a sustainable energy transition, this study suggests integrating a higher share of renewable energy into the energy mix and boosting efficient technologies through a large scale of green finance and green investment projects.


In vitro detection of differential and cell-specific hepatobiliary toxicity induced by geldanamycin and 17-allylaminogeldanamycin in rats.
The differential toxicity of two anticancer agents is described using the in vitro rat liver slice culture model. Liver slices from F-344 rats were cultured for 5 days in Waymouth's-based medium with exposure to a range of geldanamycin (GEL) or 17-allylaminogeldanamycin (17-AAG) concentrations. GEL induced concentration-dependent reduction of alkaline phosphatase and of gamma-glutamyl transferase levels, which are indicators of biliary epithelial cell(s) (BEC) viability, and exhibited hepatocellular toxicity at higher concentrations. Histologically, BEC cell injury was evident at the lowest GEL concentration (0.1 microM) and progressed to overt bile duct necrosis at 5 microM, a level at which hepatocellular damage was also more prominent. Slices exposed to the same concentrations were more sensitive to toxic effects of GEL than of 17-AAG. 17-AAG at the lowest concentration had more slice biomarker retention than GEL, and histological analysis revealed minimal toxic effect on BEC. With increasing concentration, BEC were progressively lost, and BEC proliferation was completely inhibited at 5 microM 17-AAG. Hepatocellular injury was evident only at high dose exposures. This is believed to be the first use of an in vitro liver tissue model to accurately predict the differential and concentration-dependent toxicities of these compounds.


Transcutaneous oxygen tension as an index of maturity in hypertrophic scars treated by compression.
Sixteen patients undergoing compression treatment for scar hypertrophy were included in a study to evaluate physical indices of scar maturity. The results show that while thermographic measurements of scar temperature were not clinically valuable, rising levels of transcutaneous oxygen tension in treated scars correlated well with a reduction in scar thickness assessed both clinically and by ultrasound. It is postulated that low levels of tcpO2 in immature scars result from low oxygen diffusibility through scar tissue rather than from rapid metabolic consumption of oxygen by scar tissue.


The effects of aerobic exercise on neuroimmune responses in animals with traumatic peripheral nerve injury: a systematic review with meta-analyses.
Increasing pre-clinical evidence suggests that aerobic exercise positively modulates neuroimmune responses following traumatic nerve injury. However, meta-analyses on neuroimmune outcomes are currently still lacking. This study aimed to synthesize the pre-clinical literature on the effects of aerobic exercise on neuroimmune responses following peripheral nerve injury. MEDLINE (via Pubmed), EMBASE and Web of Science were searched. Controlled experimental studies on the effect of aerobic exercise on neuroimmune responses in animals with a traumatically induced peripheral neuropathy were considered. Study selection, risk of bias assessment and data extraction were performed independently by two reviewers. Results were analyzed using random effects models and reported as standardized mean differences. Outcome measures were reported per anatomical location and per class of neuro-immune substance. The literature search resulted in 14,590 records. Forty studies were included, reporting 139 comparisons of neuroimmune responses at various anatomical locations. All studies had an unclear risk of bias. Compared to non-exercised animals, meta-analyses showed the following main differences in exercised animals: (1) in the affected nerve, tumor necrosis factor-α (TNF-α) levels were lower (p = 0.003), while insulin-like growth factor-1 (IGF-1) (p < 0.001) and Growth Associated Protein 43 (GAP43) (p = 0.01) levels were higher; (2) At the dorsal root ganglia, brain-derived neurotrophic factor (BDNF)/BDNF mRNA levels (p = 0.004) and nerve growth factor (NGF)/NGF mRNA (p < 0.05) levels were lower; (3) in the spinal cord, BDNF levels (p = 0.006) were lower; at the dorsal horn, microglia (p < 0.001) and astrocyte (p = 0.005) marker levels were lower; at the ventral horn, astrocyte marker levels (p < 0.001) were higher, and several outcomes related to synaptic stripping were favorably altered; (4) brainstem 5-HT2A receptor levels were higher (p = 0.001); (5) in muscles, BDNF levels (p < 0.001) were higher and TNF-α levels lower (p < 0.05); (6) no significant differences were found for systemic neuroimmune responses in blood or serum. This review revealed widespread positive modulatory effects of aerobic exercise on neuroimmune responses following traumatic peripheral nerve injury. These changes are in line with a beneficial influence on pro-inflammatory processes and increased anti-inflammatory responses. Given the small sample sizes and the unclear risk of bias of the studies, results should be interpreted with caution.


Coffea arabica extracts and their chemical constituents in a murine model of gouty arthritis: How they modulate pain and inflammation.
Coffea arabica is commonly known for its cardiotonic and neurotonic activities, but in some places' folk medicine, like in Arabia and Africa, C. arabica is used to treat headache, migraine, the flu, anemia, oedema, asthenia, asthma, inflammation and wounds. The aims were to evaluate if the aqueous extracts of Coffea arabica, prepared from beans with different degrees of roasting, and their main chemical constituents could exert an in vivo anti-gouty effect. Coffea extracts were obtained from the beans of not roasted, light, medium and dark roasted coffee and from decaffeinated and traditional coffees and were prepared with water at 25°C and at 98°C. C57BL/6 mice were induced to gout by an injection of monosodium urate crystals and treated with coffee extracts at doses of 25, 75 and 225 mg/kg and their chemical constituents at a dose of 10 mg/kg. The antinociceptive and anti-inflammatory effects were evaluated. Treatments with Coffea extracts prepared with water at 98°C were more effective to exert antinociceptive and anti-inflammatory activities than the ones prepared with water at 25°C. Caffeic and chlorogenic acids reduced hypernociception in animals when compared with negative control group (7.79 and 5.69 vs 18.53; P < 0.05 and P < 0.001, respectively), inhibited neutrophil migration (1.59 × 104 and 0.38 × 104 vs 9.47 × 104; P < 0.0001 both) and decreased pro-inflammatory cytokines concentration (IL-1β, IL-6 and TNF-α). We have demonstrated that our treatments attenuated gout, and this effect could be attributed to a reducement in hypernociception, neutrophil migration and cytokines concentration. These results suggest coffee as a potential candidate for studies in acute gout therapy.


Prophylaxis against infection in Singaporean prostitutes.
One hundred prostitutes were interviewed about the prophylactic measures they took against infection. The use of contraceptive diaphragms and clandestine antibiotics correlated significantly with fewer gonococcal infections.


Functional role for protein kinase Cbeta as a regulator of stress-activated protein kinase activation and monocytic differentiation of myeloid leukemia cells.
Human myeloid leukemia cells respond to 12-O-tetradecanoylphorbol-13-acetate (TPA) and other activators of protein kinase C (PKC) with induction of monocytic differentiation. The present studies demonstrated that treatment of U-937 and HL-60 myeloid leukemia cells with TPA, phorbol-12,13-dibutyrate, or bryostatin 1 was associated with the induction of stress-activated protein kinase (SAPK). In contrast, TPA-resistant TUR and HL-525 cell variants deficient in PKCbeta failed to respond to activators of PKC with the induction of SAPK. A direct role for PKCbeta in TPA-induced SAPK activity in TUR and HL-525 cells that stably express PKCbeta was confirmed. We showed that TPA induced the association of PKCbeta with MEK kinase 1 (MEKK-1), an upstream effector of the SAPK/ERK kinase 1 (SEK1)-->SAPK cascade. The results also demonstrated that PKCbeta phosphorylated and activated MEKK-1 in vitro. The functional role of MEKK-1 in TPA-induced SAPK activity was further supported by the demonstration that the expression of a dominant negative MEKK-1 mutant abrogated this response. These findings indicate that PKCbeta activation is necessary for activation of the MEKK-1-->SEK1-->SAPK cascade in the TPA response of myeloid leukemia cells.


Interactive effect of interleukin-6 and prostaglandin E2 on osteoclastogenesis via the OPG/RANKL/RANK system.
The OPG/RANKL/RANK system regulates osteoclastogenesis. Both cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) and interleukin-6 (IL-6) are reported to induce osteoclast differentiation. The mechanisms underlying these signaling pathways on the OPG/RANKL/RANK system are not fully understood. We herein demonstrate that COX-2 and PGE2 stimulated osteoclastogenesis through inhibition of OPG secretion, stimulation of RANKL production by osteoblasts, and upregulation of RANK expression in osteoclasts. PGE2 also stimulated IL-6 production, and IL-6, in turn, increased PGE2 secretion, COX-2, and EP4/EP2 expression in bone cells. These findings provide evidence of interactive effect of PGE2 and IL-6 signaling pathways in osteoclastogenesis via effect on the OPG/RANKL/RANK system.


Comparison of age-specific mortality from breast cancer in males in the United States and Japan.
Mortality data on breast cancer in males from the United States and Japan were analyzed. The logarithm of the mortality rate increased in a linear fashion with the logarithm of age and had a slope of about 5. Mortality in Japan was about one-fourth that in the United States, but the relationship to age was similar.


Trends and patterns of broadband Internet access speed in a Nigerian university campus: A robust data exploration.
Efficient broadband Internet access is required for optimal productivity in smart campuses. Besides access to broadband Internet, delivery of high speed and good Quality of Service (QoS) are pivotal to achieving a sustainable development in the area of education. In this data article, trends and patterns of the speed of broadband Internet provided in a Nigerian private university campus are largely explored. Data transmission speed and data reception speed were monitored and recorded on daily basis at Covenant University, Nigeria for a period of twelve months (January-December, 2017). The continuous data collection and logging were performed at the Network Operating Center (NOC) of the university using SolarWinds Orion software. Descriptive statistics, correlation and regression analyses, Probability Density Functions (PDFs), Cumulative Distribution Functions (CDFs), Analysis of Variance (ANOVA) test, and multiple comparison post-hoc test are performed using MATLAB 2016a. Extensive statistical visualizations of the results obtained are presented in tables, graphs, and plots. Availability of these data will help network administrators to determine optimal network latency towards efficient deployment of high-speed broadband communication networks in smart campuses.


Rho proteins and cancer.
The Rho family of GTPases has been intensively studied for their roles in signal transduction processes leading to cytoskeletal-dependent responses, including cell migration and phagocytosis. In addition, they are important regulators of cell cycle progression and affect the expression of a number of genes, including those for matrix-degrading proteases implicated in cancer invasion. So far, the expression of some Rho family members has been found to be increased in some human cancers, and some cancer-associated mutations in Rho family regulators have been characterized. This makes Rho protein signalling pathways attractive targets for cancer therapy. However, there is little evidence so far from animal studies to define if and how Rho proteins contribute to cancer cell proliferation, survival, invasion and metastasis.


Raghib's syndrome: a report of two cases.
We treated two patients with a rare developmental complex. The persistent left superior vena cava draining into the left atrium (PLSVC into LA) was associated with an absent coronary sinus and an atrial septal defect. Ligation of PLSVC and patch-repair of the atrial septal defect were successfully performed in one stage. The atrial septal defect was located in the upper and posterior aspect of the interatrial septum and appeared to be an unique type of atrial septal defect. In the other patient, additional multiple cardiac defects were associated with this syndrome, including ventricular septal defect, pulmonary stenosis, tricuspid insufficiency, and complete transposition of the great arteries. Palliative Blalock procedure was used for this patient. The PLSVC into LA was discovered accidentally in both cases during heart catheterization and it was clearly demonstrated by venography. For a preoperative recognition of PLSVC, computed tomograms of the heart are of great assistance. Surgical correction of the persistent superior vena cava was emphasized for treatment of this syndrome.


Term placenta of the southern elephant seal (Mirounga leonina).
The pinnipeds' placenta has been described as zonary, annular, labyrinthic and endotheliochorial, like that of the terrestrial carnivores. This article describes the placenta of Mirounga leonina, a phocid pinniped, focusing on some morphological features related to fetal nutrition. Placental samples from three elephant seals were collected and conditioned after natural delivery at the Antarctic Specially Protected Area 132. Histological and ultrastructural studies were conducted; cytokeratins, vimentin, α-smooth muscle actin, and desmin proteins were detected using immunohistochemistry. The placentas were zonary, lobed, belt-shaped, and showed multiple vivid orange areas, which corresponded to bilirubin crystalline pigment found among chorionic villi and inside trophoblast cells. In the labyrinth, cytotrophoblast cells were isolated and there was a scant syncytium interposed between maternal and fetal vessels. Fetal vessels were small, round, and frequently intratrophoblastic, while maternal vessels were large, irregular, sinuous, and thin-walled. Vimentin and actin were detected in some scattered non-vascular cells throughout the labyrinth. Broad areas of degenerated and necrotic maternal components were also observed. The placentas of pinniped and fissiped carnivores share several traits. However, some remarkable features might maximize respiratory efficiency, collaborating to endure deep-diving hypoxia. Some of them, as the notably large sinuous maternal capillaries and fetal capillary indentation into the syncytium, are shared, e.g., by Phocidae and Mustelidae. Besides hemotropic nutrition taking place through an extremely narrow barrier, the abundant necrotic material and hematic products might allow substantial endocytosis of detritus even in term placentas, in this species giving birth to precocious offspring.


A survey to explore the psychological impact of the COVID-19 pandemic on radiation therapists in Norway and Canada: A tale of two countries.
Several studies have demonstrated the psychological impact of the COVID-19 pandemic on health care providers. However, there is little known about how the COVID-19 pandemic has impacted radiation therapists (RTs) in Norway or Canada. The aim of this investigation was to study the psychological impact of working during the COVID-19 pandemic among RTs in Canada and Norway. Online surveys were administered to a convenience sample of RTs and RT department managers. Approximately 2000 and 300 RTs were invited to participate from Canada and Norway, respectively. The RT survey collected information on demographics, work-related stressors, psychological impact, quality of life, and workplace support programmes. The RT manager survey collected information on departmental changes, patient volumes, staff shortages and redeployment, personal protective equipment, and infection control measures. Descriptive analysis, group comparisons and logistic regression were used to examine the impact of COVID-19 on RTs in the two countries, while open-ended questions were examined through thematic analysis. Work-related stress and anxiety were prevalent among Canadian (n = 155) and Norwegian RTs (n = 124), with Canadian RTs reporting higher levels. Fear of transmission, changes in PPE usage, and changes in staffing were reported as the most frequent work-related stressors. Themes related to working during the pandemic included: generalised anxiety; physical, emotional and cognitive symptoms of stress; and loneliness, as well as negative impact on health and quality of relationships. Survey findings from RT department managers in Canada (n = 12) and Norway (n = 13) suggest that the pandemic had an organisational impact on RT departments due to implemented infection control measures and changes in staffing. The COVID-19 pandemic has led to similar stressors amongst Canadian and Norwegian RTs but relatively higher levels of psychological impact among Canadian RTs. Findings demonstrate the importance of mental health support programmes in the workplace to mitigate the psychological impact of the COVID-19 pandemic on RTs.


Association between cribbing and entrapment of the small intestine in the epiploic foramen in horses: 68 cases (1991-2002).
To determine whether there was an association between a history of cribbing and epiploic foramen entrapment (EFE) of the small intestine in horses. Retrospective study. 68 horses examined at the University of Illinois or the University of Liverpool veterinary teaching hospitals. For horses examined at the University of Illinois that underwent surgery because of strangulating small intestine lesions, information about cribbing was obtained through telephone calls with owners. For horses examined at the University of Liverpool that underwent surgery for colic for any reason, information about cribbing was obtained through a preoperative questionnaire. 13 of 19 (68%) horses with EFE examined at the University of Illinois had a history of cribbing, compared with only 2 of 34 (6%) horses with other strangulating small intestine lesions (odds ratio, 34.7; 95% confidence interval, 6.2 to 194.6). Similarly, 24 of 49 (49%) horses with EFE examined at the University of Liverpool had a history of cribbing, compared with 72 of 687 (10.5%) horses with colic caused by other lesions (odds ratio, 8.2; 95% confidence interval, 4.5 to 15.1). Results suggest that there may be an association between cribbing and EFE in horses, with horses with a history of cribbing more likely to have EFE than horses without such a history.


Platelet-dependent thrombography: a method for diagnostic laboratories.
The thrombin-platelet feedback loop was examined at low concentration tissue factor using calibrated automated thrombography in combination with the elimination of contact factor activation by corn trypsin inhibitor. The results indicated that, when contact factor activation was eliminated, the thrombin-platelet feedback loop was a major determinant of thrombin generating capacity and that platelets had a greater role in regulating the propagation of thrombin generation than its initiation. This method has potential application to the measurement of platelet-dependent thrombin generation in clinical diagnostic laboratories and hence the investigation of patients with apparent hypo- or hypercoagulable phenotypes.