Modeling the lag phase of Listeria monocytogenes.
An estimate of the lag phase duration is an important component for predicting the growth of a bacterium and for creating process models and risk assessments. Most current research and data for predictive modeling programs initiated growth studies with cells grown to the stationary phase in a favorable pH, nutrient and temperature environment. In this work, Listeria monocytogenes Scott A cells were grown in brain heart infusion (BHI) broth at different temperatures from 4 to 37 degrees C to the exponential growth or stationary phases. Additional cells were suspended in a dilute broth, desiccated or frozen. These cells were then transferred to BHI broth at various temperatures from 4 to 37 degrees C and the lag phase durations were determined by enumerating cells at appropriate time intervals. Long lag phases were observed for cells initially grown at high temperatures and transferred to low temperatures. In general, exponential growth cells had the shortest lag phases, stationary phase and starved cells had longer, frozen cells had slightly longer and desiccated cells had the longest lag phases. These data were from immediate temperature transitions. When a computer-controlled water bath linearly changed the temperature from 37 to 5 degrees C over a 3.0- or 6.0-h period, the cells had short lags and grew continuously with declining growth rates. Transitions of 0.75 or 1.0 h had 20-h lag phases, essentially that of immediate transitions. When the transition was 1.5 h, an intermediate pattern of less than 1 log of growth followed by no additional growth for 20 h occurred.


Benchmarking inappropriate empirical antibiotic treatment.
Inappropriate empirical antibiotic treatment for severe infections is associated with increased mortality. Superfluous treatment is associated with resistance induction. We aimed to define acceptable rates of inappropriate empirical antibiotic treatment. We included all prospective cohort studies published between 1975 and 2009 reporting the proportion of appropriate and inappropriate empirical antibiotic treatment of microbiologically documented infections. Studies were identified in PubMed and in reference lists of included studies. Funnel plots were drawn using the proportion of inappropriate empirical treatment as the effect size. A pooled estimate of inappropriate empirical antibiotic treatment was calculated using a β-binomial model. Control limits were calculated with the overdispersion factor technique and 20% winsorized data. Heterogeneity was assessed through subgroup analysis for categorical moderators and meta-regression for continuous variables. Eighty-seven studies, comprising 92 study groups, with 27 628 patients met inclusion criteria. The pooled rate of inappropriate empirical antibiotic treatment was 28.6% (95% CI 25.4-31.8). Funnel plot analysis yielded a dispersed graph with only 37 (40%) studies falling within the control limits. Using the overdispersion factor technique with 20% winsorizing, 79 (86%) studies fell within the control limits. None of the clinical or methodological factors could explain the large heterogeneity observed. The funnel plot presented can be used to benchmark rates of inappropriate empirical antibiotic treatment. Based on the control limits found, at least 500 patients should be evaluated before establishing a local rate. Lower and higher than expected rates might indicate overly aggressive treatment or poor performance, respectively.


Effect of testosterone and season on proenkephalin messenger RNA expression in the preoptic area of the hypothalamus in the ram.
Enkephalin appears to exert an inhibitory action on LH secretion, but whether testosterone regulates enkephalin gene expression is unknown. This study tested the hypothesis that testosterone and/or season modulate preproenkephalin mRNA expression in specific areas of the hypothalamus. Romney Marsh rams were castrated (wethers) either during the breeding season or nonbreeding season and received intramuscular injections of either oil or testosterone propionate (five/group). Blood samples were taken for the assay of plasma LH and testosterone. Preproenkephalin mRNA expression was quantified in hypothalamic sections by in situ hybridization. Mean plasma LH concentrations were reduced and the interpulse interval for LH pulses was greater in testosterone propionate-treated wethers compared with oil-treated wethers, with no change in LH pulse amplitude. Testosterone propionate treatment reduced proenkephalin expression in the diagonal band of Broca, the caudal preoptic area, and the bed nucleus of the stria terminalis. Seasonal differences in proenkephalin expression were observed in the bed nucleus of the stria terminalis, lateral septum, periventricular nucleus, and paraventricular nucleus. No differences were observed between treatments in seven other regions examined. We conclude that testosterone and season regulate proenkephalin mRNA levels in the preoptic area/hypothalamus in the ram in a region-specific manner.


Fibroblast growth factor-2 increases the renal recruitment and attachment of HIV-infected mononuclear cells to renal tubular epithelial cells.
The role of circulating growth factors in the pathogenesis of childhood HIV-1-associated nephropathy (HIVAN) is not clearly understood. In previous studies, we found a significant accumulation of fibroblast growth factor-2 (FGF-2) in the circulation and kidneys of children with HIVAN. The purpose of this study was to determine whether circulating FGF-2 may play a role in the pathogenesis of HIVAN by increasing the renal recruitment and attachment of HIV-infected mononuclear cells to renal epithelial cells. Using in vitro cell adhesion assays, we showed that FGF-2 increased the attachment of peripheral blood mononuclear cells (PBMCs) to fibronectin-coated tissue culture dishes by approximately threefold through a mechanism that involved the alpha5 integrin subunit. In addition, we found that FGF-2 induces a similar increase in the attachment of HIV-infected PBMCs and monocytes/macrophages to plastic tissue culture dishes and to monolayers of primary renal tubular epithelial cells harvested from the urine of HIV-infected children with renal disease. Finally, we injected 16 adult C57Bl6/J male mice with recombinant adenoviral vectors carrying either the LacZ gene or a secreted form of human FGF-2 (5 x 10(8)pfu/mouse) and demonstrated that high levels of circulating FGF-2 can increase the renal recruitment of circulating inflammatory cells and induce transient tubulointerstitial injury in vivo. These data suggest that FGF-2 may have an immunomodulatory role in the pathogenesis of HIVAN by recruiting HIV-infected cells in the kidney.


Transcriptomic and Metabolic Analyses Provide New Insights into the Apple Fruit Quality Decline during Long-Term Cold Storage.
Long-term low-temperature conditioning (LT-LTC) decreases apple fruit quality, but the underlying physiological and molecular basis is relatively uncharacterized. We identified 12 clusters of differentially expressed genes (DEGs) involved in multiple biological processes (i.e., sugar, malic acid, fatty acid, lipid, complex phytohormone, and stress-response pathways). The expression levels of genes in sugar pathways were correlated with decreasing starch levels during LT-LTC. Specifically, starch-synthesis-related genes (e.g., BE, SBE, and GBSS genes) exhibited downregulated expression, whereas sucrose-metabolism-related gene expression levels were up- or downregulated. The expression levels of genes in the malic acid pathway (ALMT9, AATP1, and AHA2) were upregulated, as well as the content of malic acid in apple fruit during LT-LTC. A total of 151 metabolites, mainly related to amino acids and their isoforms, amines, organic acids, fatty acids, sugars, and polyols, were identified during LT-LTC. Additionally, 35 organic-acid-related metabolites grouped into three clusters, I (3), II (22), and III (10), increased in abundance during LT-LTC. Multiple phytohormones regulated the apple fruit chilling injury response. The ethylene (ET) and abscisic acid (ABA) levels increased at CS2 and CS3, and jasmonate (JA) levels also increased during LT-LTC. Furthermore, the expression levels of genes involved in ET, ABA, and JA synthesis and response pathways were upregulated. Finally, some key transcription factor genes (MYB, bHLH, ERF, NAC, and bZIP genes) related to the apple fruit cold acclimation response were differentially expressed. Our results suggest that the multilayered mechanism underlying apple fruit deterioration during LT-LTC is a complex, transcriptionally regulated process involving cell structures, sugars, lipids, hormones, and transcription factors.


The role of the microbiome and the NLRP3 inflammasome in the gut and lung.
The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family, pyrin domain-containing protein 3 (NLRP3) inflammasome, is one of the most well-characterized inflammasomes, activated by pathogen-associated molecular patterns and damage-associated molecular patterns, including from commensal or pathogenic bacterial and viral infections. The NLRP3 inflammasome promotes inflammatory cell recruitment and regulates immune responses in tissues such as the gastrointestinal tract and the lung, and is involved in many diseases that affect the gut and lung. Recently, the microbiome in the gut and the lung, and the crosstalk between these organs (gut-lung axis), has been identified as a potential mechanism that may influence disease in a bidirectional manner. In this review, we focus on themes presented in this area at the 2019 World Congress on Inflammation. We discuss recent evidence on how the microbiome can affect NLRP3 inflammasome responses in the gut and lung, the role of this inflammasome in regulating gut and lung inflammation in disease, and its potential role in the gut-lung axis. We highlight the exponential increase in our understanding of the NLRP3 inflammasome due to the synthesis of the NLRP3 inflammasome inhibitor, MCC950, and propose future studies that may further elucidate the roles of the NLRP3 inflammasome in gut and lung diseases.


Schisandrin B protects against menadione-induced hepatotoxicity by enhancing DT-diaphorase activity.
Pretreating mice with schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, at a daily dose of 1 mmol/kg for 3 days protected against menadione-induced hepatic oxidative damage in mice, as evidenced by decreases in plasma alanine aminotransferase activity (78%) and hepatic malondialdehyde level (70%), when compared with the menadione intoxicated control. In order to define the biochemical mechanism involved in the hepatoprotection afforded by Sch B pretreatment, we examined the activity of DT-diaphorase (DTD) in hepatocytes isolated from Sch B pretreated rats. Hepatocytes isolated from Sch B pretreated (a daily dose of 1 mmol/kg for 3 days) rats showed a significant increase (25%) in DTD activity. The increase in DTD activity was associated with the enhanced rate of menadione elimination in the hepatocyte culture. The ensemble of results suggests that the ability of Sch B pretreatment to enhance hepatocellular DTD activity may at least in part be attributed to the protection against menadione hepatotoxicity.


[Goat smallpox in Chad: study of the pathogeny of the virus in sheep and goats].
A local strain of goat pox virus was tested in goats and sheep. The results showed that 65% of goats and 20% of sheep reacted positively. Only goats died few days after the inoculation (55%) and no mortality was recorded in the sheep. The strict species specificity of this strain was not observed. The difference of sensitivity between sheep and goats was statistically significant.


Short-term effects of erythropoietin on neurodevelopment in infants with cerebral palsy: a pilot study.
Cerebral palsy (CP) is a disabling condition characterized by the motor impairment, which is difficult to be ameliorated. In the brain of infants with CP, there are persistent pathomechanisms including accentuated neuroinflammation. Since erythropoietin was demonstrated to have neuroprotective effect via anti-inflammatory and anti-apoptotic properties, we hypothesized that the administration of recombinant human EPO (rhEPO) could help children with CP, especially young infants. We investigated the therapeutic efficacy of rhEPO for infants with CP, who had been undergoing active rehabilitation in hospitalized setting to eliminate treatment bias. Twenty infants with CP were randomly divided into EPO or control group equally. We compared the changes in the Gross Motor Function Measure (GMFM) and the Bayley Scales of Infant Development-II (BSID-II) scores during one month of hospitalization between two groups. The improvements after 1 month on the GMFM A and GMFM total scores differed significantly between the groups (p = 0.003, p = 0.04, respectively). However, the changes after 6 months were not different between the two groups. The scores of BSID-II did not show any differences at 1-month and 6-months post-treatment. These results indicated that rhEPO could have therapeutic efficacy for infants with CP during the active rehabilitation and anti-inflammation was suggested to be one of its therapeutic mechanisms.


Dye sensitivity correlated with envelope protein changes in dye (sfrA) mutants of Escherichia coli K12 defective in the expression of the sex factor F.
Mutations of the dye gene on the E. coli chromosome result in sensitivity to the dye toluidine blue and, in male cells, cause loss of F pili, producing sterility in conjugation. Compared with its dye+ parent, a strain deleted for dye (delta dye) showed an altered sensitivity to a wide range of dyes and antibiotics which affect different intracellular processes, and hence it appeared likely that the barrier properties of the cell envelope were impaired. Unlike mutants known to be defective in LPS structure, there appeared to be no correlation between the hydrophobicity of the compounds and the sensitivity of the delta dye strain. Moreover there was no difference between dye+ and delta dye strains in their sensitivity to LPS-specific phages, and chemical and GLC analysis of LPS components revealed no difference between the two strains. Examination of outer and inner membrane proteins from isogenic strains having the delta dye deletion and the dye+ gene cloned into the plasmid pACYC184, with or without insertional inactivation of dye by the transposon gamma delta, was performed by SDS-PAGE. This revealed a number of differences in the profile of proteins from both inner and outer membranes, correlated with mutation in the dye gene. The dye gene appears to be identical to the sfrA gene, which has been shown to be required for efficient transcription of the sex factor F. It is therefore proposed that the dye (sfrA) gene product may also control the expression of chromosomal genes coding for envelope proteins.


Menorraghia's impact on quality of life: A case control study from a teaching Hospital in Lahore.
Menorrhagia is one of the common complaints presenting in gynaecology outdoor and clinics. Menorrhagia is defined as excessive uterine bleeding occurring at regular intervals or prolonged uterine bleeding lasting for more than seven days. This is a very distressing condition effecting almost all ages, and has multiple causes. The objective of this study was to determine effect of menorrhagia on quality of life of a woman. It was a case control study, conducted at Arif Memorial Teaching Hospital Lahore from January 2017 to December 2017. It included 230 women. Out of these, 150 women who had menorrhagia were included in Group A (cases). Group B included 80 women accompanying them and have normal menstrual cycles (controls). The mean age of the participants was 35.56±8.85 years. Duration of menorrhagia was more than 4 years in 11% of the patients, 22% had menorrhagia for 1-2 years and 1.2% for three months. Among all age groups, quality of life was better in female without menorrhagia as compared to female with menorrhagia (p-value <0.001). Health care providers should have knowledge to treat patients with menorrhagia, also future qualitative studies should be done to determine perception of patients regarding treatment and management of menorrhagia.


Lay persons' perception of the requirements for research in emergency obstetric and newborn care.
Factors that could potentially act as facilitators and barriers to successful recruitment strategies in perinatal clinical trials are not well documented. The objective was to assess lay persons' understanding of the informed consent for randomized clinical trial in emergency obstetric and newborn care. This was a qualitative study conducted among survivors of severe obstetric complications who were attending the post-natal clinic of Kawempe National Referral Hospital, Uganda, 6-8 weeks after surviving severe obstetric complications during pregnancy or childbirth. The study that involved 18 in-depth interviews was conducted from June 1, 2019 to July 6, 2019. The issues explored included perceptions of the purpose and necessity to conduct such research how research-related information would be disclosed, and what could be the potential benefits and risks of participation. The data was analyzed by thematic analysis. Respondents felt that research was necessary to investigate the cause, prevention or complications of an illness, especially as much was known about some pregnancy and newborn complications. Most believed that the emergency contexts affects whether and what prospective participants may understand if information about research was disclosed. Whereas they did not see the value of procedures like randomization, they felt that if these and any other procedures necessary should be done transparently and fairly. The decisions to participate would significantly be influenced by possibility of risk to the unborn baby or the newborn. Solidarity was an important influence on decision-making. Respondents valued participation in RCTs in emergency obstetric and newborn care. However, they expressed concerns and valued openness, transparency and accountability with regard to how clinical trials information is disclosed and the decision-making process for clinical trial participation. While autonomy and solidarity are contradictory values, they complement each other during decision-making for informed consent.


Triple intrathecal chemotherapy for leptomeningeal carcinomatosis in solid tumors: Treatment outcomes, response and their determinants.
Leptomeningeal carcinomatosis (LC) is the metastatic infiltration of leptomeninges by malignant cells originating from an extrameningeal primary tumor site, either extraneural or intraneural. In the absence of treatment, survival is usually measured in weeks, however with treatment this may be extended to a few months. Our institutional protocol has been to offer intrathecal chemotherapy (ITC) to patients having solid tumors with cerebrospinal fluid (CSF) cytology positive leptomeningeal carcinomatosis. This study was performed to describe the oncological outcomes in this cohort and their determinants. A retrospective review of data of patients treated at Amrita Institute of Medical Sciences, Kochi, India was performed. Patients with CSF cytology positive solid tumors treated with triple ITC (methotrexate, cytosine arabinoside and hydrocortisone) were assessed for patient characteristics, treatment response, survival and the factors affecting them. Twenty patients of LC treated with triple ITC were included in the study. The median age of the study group was 49 years with a slight female preponderance (55%). All patients had positive CSF cytology with mean CSF glucose of 60 mg/dL, mean CSF protein of 92 mg/dL and mean cell count of 5. Breast cancer was the most common primary tumor (45%), followed by lung (35%) and stomach (5%). Symptomatic improvement was reported in 70% of patients after initiating ITC. Median overall survival (OS) at 6 and 12 months was 38% and 14%, respectively. Median progression-free survival (PFS) was 2 months. Patients with brain parenchymal metastasis had poor 6 month OS (25% vs 50%, P = 0.013) and 6 month PFS (0% vs 20%, P = 0.023). A triple drug combination of methotrexate, cytosine arabinoside and hydrocortisone when given intrathecally for patients with LC showed good control of symptoms and reasonable survival. It may be beneficial in patients with no brain parenchymal involvement.


Intrauterine growth restriction: a perspective for Pakistan.
Intrauterine growth restriction (IUGR) is the second leading contributor to the prevailing perinatal mortality and morbidity. It affects 23.8% of newborns around the world and 75% of these affected infants are born in Asia. In Pakistan the incidence of IUGR is around 25%, more than the WHO criteria for triggering a public health action. IUGR is implicated with profound long-term impacts in adult life; like coronary heart disease, NIDDM and abnormal cortisol levels. The effects of the short and long term sequelae are reviewed. IUGR is associated with a wide variety of etiological factors. But the factor unique in its importance to Pakistan is maternal malnutrition. The fetal gene expression is under the influence of nutrition. Growth projection curves showing the interaction between the genetic and environmental factors are discussed. Identification of IUGR baby in a primary care setting and the options in diagnosis in secondary and tertiary care settings are overviewed. The roots of this problem, with multi factorial causes are in the socioeconomic infrastructure. This calls for a synergistic approach of reducing this public health issue. Women empowerment can help us to get out of this intergenerational cycle of growth failure. Availability of resources aside, it is also a matter of political will to change things for the better.


[Clinical implications and prognostic significance of the study on the circadian variation of heart rate variability in patients with severe pulmonary hypertension].
A reduction of heart rate variability (HRV) is currently considered an independent risk factor for morbidity, mortality and severity of severalcardiac disease, however, the dynamic sympathovagal modulation on HRV during 24 hr in primary pulmonary hypertension (PPH) had not been described. 24 hr Holter monitoring (HA) were recorded in 32 patients (mean age 34, +/-12, 90% female) with severe primary pulmonary hypertension (mean pulmonary pressure, 90:t:12 mm Hg), and in 34 patients (mean age 36 +/-14, 60% female) with Eisenmenger syndrome (ES) secondary to septal ventricular defect or atent ductus arteriosus. A control group (n=44) paired for age, gender and arterial pulmonary pressure was included. HRV time and spectral parameters (mean, SDNN, SDANN, rMSSD, PNN50, LF, HF and LF/HF ratio) were analyzed during three periods: 24 hr; day (8-22:00), night (23-07:00) and also every hour of recording at 5 min-intervals). After detection of sympatho-vagal balance 15 patients were randomized, Treprostinil (prostaglandin) was administered to 6 patients and subcutaneous placebo to 9. HRV frequency parameters during 24 hr HM were significantly different among groups. LF/HF (day) 5.9:1:12.5:1:1P.001 and LF/HF night) 2.8:tlvs.1.5:l:.8.034. Sympathovagal modulation on 24 hr HRV showed that heart rate circadian rhythm is clearly altered in both PPH and ES, but the sympathetic tone in PPH is higher at l 24 hr. (p < .05), after administering treprostinil a recovery of sympathovagal balance was observed Autonomic cardiac disturbance is clearly present in PPH and ES. The circadian rhythm of HRV is first lost due to an increase of sympathetic tone. These changes may be markers of autonomic disbalance that favor the development of arrhythmias and sudden death. The sympathovagal balance in PPH could be considered an important risk marker.


Phenolic ablation of the nail matrix.
Therapeutic ablation of nail is necessary in a variety of settings. The challenge is to achieve destruction of nail matrix with minimal pain and to ensure that there is no re-growth of nail. There are many different methods of nail ablation, with excisional surgery and phenolic ablation of matrix representing the most common. The balance of published data favours phenolic ablation as a simple procedure with low morbidity and the least chance of recurrence.


Comfort Among Older Lesbian and Gay People in Disclosing Their Sexual Orientation to Health and Aged Care Services.
Being comfortable in disclosing one's sexual orientation to health and aged care providers is important for older lesbian and gay adults, given that nondisclosure is associated with poorer health and well-being outcomes. In a sample of 752 lesbian and gay adults aged 60 years and older living in Australia, we found only 51% of lesbian women and 64% of gay men felt fully comfortable to disclose their sexual orientation to health and aged care service providers. For both the women and the men, those who felt fully comfortable to disclose reported significantly less internalized homophobia; had fewer experiences of discrimination in the past year; and reported greater lesbian, gay, bisexual, transgender, and intersex (LGBTI) community connectedness. Feeling fully comfortable was also predicted by fewer experiences of lifetime discrimination among the men. These findings may help those seeking to assist older lesbian and gay people in feeling comfortable and being open with health and aged care service providers.


The subendothelium of the HMEC-1 cell line supports thrombus formation in the absence of von Willebrand factor and collagen types I, III and VI.
The macromolecular composition of the extracellular matrix (ECM) produced by the human microvascular endothelial cell line (HMEC-1) was determined by ELISA and its thrombogenicity was studied in blood perfusion assays. Results were compared with those obtained with the ECM produced by human umbilical vein endothelial cells (HUVEC). The HMEC-1's ECM contains collagen type IV, fibronectin, laminin and thrombospondin, but no detectable levels of collagen types I, III and VI, or von Willebrand factor (vWF), whereas all these components were found in the ECM synthesized by HUVEC. HMEC-1's ECM was perfused with low-molecular-weight heparin-anticoagulated blood at two wall shear rates (650/s and 2,600/s), representative of moderate and high arterial wall shear rates, in parallel plate flow chambers for 5 min. This resulted in the formation of large platelet aggregates, compared to essentially a monolayer of adherent platelets on HUVEC's ECM. Interestingly, large thrombi were formed at 2,600/s when HMEC-1's ECM was perfused with the blood of a patient with severe type III von Willebrand disease lacking both plasma and platelet vWF, indicating that vWF was not absolutely required for thrombus formation on this matrix. Thrombin generated on the HMEC-1's ECM contributed importantly to the large platelet thrombi formed, shown by performing blood perfusion experiments in the presence of thrombin inhibitors. Our results indicate that 1) platelet adhesion and aggregate formation on a subendothelium may occur at a high shear rate (2600/s) without the participation of collagen types I, III and VI, and vWF; and 2) the HMEC-1 cell line may prove useful for in vitro studies of the thrombogenic properties of microvascular subendothelium which in most cases does not contain fibrillar collagens and vWF.


Clinical efficacy of lopinavir/ritonavir in the treatment of Coronavirus disease 2019.
The Coronavirus disease 2019 (COVID-19) which outbroke in December 2019 is highly contagious with a low cure rate. In view of this, there is an urgent need to find a more appropriate therapeutic scheme against COVID-19. The study aimed to investigate whether lopinavir/ritonavir (LPV/r) in combination with other pneumonia-associated adjuvant drugs has a better therapeutic effect on COVID-19. Totally 47 patients with COVID-19 infection who were admitted to Rui'an People's Hospital between January 22 and January 29, 2020 were collected. The patients were divided into the test group and the control group according to whether they had been treated with LPV/r or not during hospitalization. Patients in the test group were treated with LPV/r combined with adjuvant medicine, while those in the control group were just treated with adjuvant medicine. The changes of body temperature, blood routine and blood biochemistry between the two groups were observed and compared. Both groups achieved good therapeutic effect with the body temperature of patients decreased gradually from admission to the 10th day of treatment. But the body temperature of patients in the test group decreased faster than that of the control group. Blood routine indexes showed that compared with the control group, the abnormal proportion of white blood cells, lymphocytes and C-reactive protein of the test group could be reduced to some extent. Blood biochemical indexes exhibited that the proportion of patients with abnormal alanine aminotransferase and aspartate aminotransferase in the test group were lower than the control group. The number of days for nCoV-RNA turning negative after treatment was significantly decreased in the test group than that in the control group. Compared with the treatment of pneumonia-associated adjuvant drugs alone, the combination treatment with LPV/r and adjuvant drugs has a more evident therapeutic effect in lowering the body temperature and restoring normal physiological mechanisms with no evident toxic and side effects. In view of these conclusions, we suggested that the use of LPV/r combined with pneumonia-associated adjuvant drugs in the clinical treatment for patients with COVID-19 should be promoted.


Tuberous sclerosis with cardiogenic cerebral embolism: magnetic resonance imaging.
A girl with tuberous sclerosis and intracardiac masses had at least two episodes of cardiogenic cerebral embolization, the attacks characterized by acute onset of prolonged neurologic dysfunction arising from different vascular distributions in both cerebral hemispheres. Renal embolization was suggested by hematuria. Magnetic resonance imaging (MRI) demonstrated ischemic lesions in cerebral locations predicted by the clinical signs. MRI also demonstrated extensive areas compatible with the dysmyelination of tuberous sclerosis.


[Tuberculous lymphadenopathy. Diagnosis and treatment. Case report].
Tuberculosis is a common cause of morbimortality among children, especially in developing countries, where 95% of cases occur. Child tuberculosis is closely related to tuberculosis in the adult, since the diagnosis is an indicator of poor surveillance, treatment, and effort to eradicate it. Tuberculous lymphadenitis (tuberculosis of the lymph node) is the most common form of extrapulmonary tuberculosis. We describe the case of an infant diagnosed with disseminated tuberculous lymphadenitis, by axillary lymph node excisional biopsy. Medical treatment first line antituberculosis drugs with allowed complete healing of the patient.


Structural basis for plant plasma membrane protein dynamics and organization into functional nanodomains.
Plasma Membrane is the primary structure for adjusting to ever changing conditions. PM sub-compartmentalization in domains is thought to orchestrate signaling. Yet, mechanisms governing membrane organization are mostly uncharacterized. The plant-specific REMORINs are proteins regulating hormonal crosstalk and host invasion. REMs are the best-characterized nanodomain markers via an uncharacterized moiety called REMORIN C-terminal Anchor. By coupling biophysical methods, super-resolution microscopy and physiology, we decipher an original mechanism regulating the dynamic and organization of nanodomains. We showed that targeting of REMORIN is independent of the COP-II-dependent secretory pathway and mediated by PI4P and sterol. REM-CA is an unconventional lipid-binding motif that confers nanodomain organization. Analyses of REM-CA mutants by single particle tracking demonstrate that mobility and supramolecular organization are critical for immunity. This study provides a unique mechanistic insight into how the tight control of spatial segregation is critical in the definition of PM domain necessary to support biological function.


[Lytic activity of aerobic sporulating bacteria].
The paper deals with lytic activity of 226 strains belonging to 13 species of Bacillus genus, isolated from various econiches, in respect of the cells of Staphylococcus aureus, Escherichia coli and Candida albicans as representatives of Gram-positive, Gram-negative and yeast groups of microorganisms. All the studied strains of bacilli displayed lytic activity of various extent and various spectrum of substrate specificity. Possible dependence of the extent of activity and substrate specificity of bacilli strains on their species belonging and isolation sources did not display distinctly. Two different factors of aggression and antagonism of aerobic bacilli--the capacity to lyse as well as to inhibit growth of test-cultures do not correlate and can either coincide or not coincide. The Bacillus genus and its species are characterized, to a certain extent, as a lytically active group and are estimated as the promising source of obtaining highly active producers of lytic enzymes different as to their properties. Highly active producers of lytic enzymes with the primary degree of lysis from 30% to 60% of the cells of test cultures during 1 hour of the reaction have been obtained.


Catalytic Gasification and Reforming of Residual Biomass in a Bench Scale System with Low Cost Catalysts.
This paper demonstrates the effectiveness of using of different catalysts for reforming tars contained in the syngas of biomass gasifiers. The conversion of the tar content allows to obtain high quality syngas and to maximize the gas fraction. A bench scale equipment consisting of an autothermal fluidized bed gasifier and a downstream packed bed reformer was used. Pine sawdust was selected as the feedstock for gasification. TGA analysis showed that the temperature must be above 350 °C to ensure the ignition of the biomass and maintain the process in an autothermal steady-state. Dolomite and pyrolysis char were used to test of the fluidized bed catalysts. In the reformer, dolomite, pyrolysis char, iron doped activated carbon and spent HDS catalyst were used. All catalysts decreased the CO2 concentration in the product gas and increased H2 , CH4 and CO. When iron doped activated carbon is used, tar contents below 60 g/Nm3 in the product gas could be obtained, reaching less than 1 g/Nm3 . The best value of LHV (lower heating value) was obtained with pyrolysis char as a catalyst (4.8 MJ/Nm3 ). The results demonstrate that catalytic biomass gasification with downstream tar reforming with low-cost catalysts is a promising solution for energy applications.


WR-2721 inhibits parathyroid adenylate cyclase.
WR-2721 [S-2-(3-aminopropylamino)ethylphosphorothioic acid] is a chemoprotective and radioprotective agent that has been shown to lower serum calcium in dogs and in humans. This is secondary both to impaired release of Ca2+ from bone and diminished secretion of parathyroid hormone (PTH) from parathyroid glands. Because cAMP plays a role in the regulation of PTH secretion and WR-2721 has been shown to lower cAMP levels in radiated mouse spleen, we investigated the effects of WR-2721 on cAMP production in dispersed bovine parathyroid cells. Additionally, we studied the adenylate cyclase in plasma membranes from normal bovine parathyroid glands after exposure to WR-2721. With parathyroid cells incubated at 0.5 mM Ca2+, addition of WR-2721 in concentrations ranging from 0.02 to 2.0 mM resulted in a progressive decrease in intracellular cAMP (42-50%, respectively). In plasma membranes of bovine parathyroid cells a dose-dependent decrease in adenylate cyclase activity was noted. Inhibition of the cyclase was seen over a wide range of Mg2+ concentrations (2.5-40 mM). WR-2721 inhibited both basal and NaF, Gpp(NH)p, forskolin, and pertussin toxin-stimulated adenylate cyclase. These data suggest that WR-2721 inhibits the activity of parathyroid adenylate cyclase.


Street lighting disturbs commuting bats.
Anthropogenic disturbance is a major cause of worldwide declines in biodiversity. Understanding the implications of this disturbance for species and populations is crucial for conservation biologists wishing to mitigate negative effects. Anthropogenic light pollution is an increasing global problem, affecting ecological interactions across a range of taxa and impacting negatively upon critical animal behaviors including foraging, reproduction, and communication (for review see). Almost all bats are nocturnal, making them ideal subjects for testing the effects of light pollution. Previous studies have shown that bat species adapted to foraging in open environments feed on insects attracted to mercury vapor lamps. Here, we use an experimental approach to provide the first evidence of a negative effect of artificial light pollution on the commuting behavior of a threatened bat species. We installed high-pressure sodium lights that mimic the intensity and light spectra of streetlights along commuting routes of lesser horseshoe bats (Rhinolophus hipposideros). Bat activity was reduced dramatically and the onset of commuting behavior was delayed in the presence of lighting, with no evidence of habituation. These results demonstrate that light pollution may have significant negative impacts upon the selection of flight routes by bats.


Nine-month angiographic and intravascular ultrasound outcomes after resolute zotarolimus-eluting stent implantation for the treatment of in-stent restenosis.
We aimed to evaluate the mid-term outcomes of resolute zotarolimus-eluting stent (R-ZES) implantation for in-stent restenosis (ISR). There has been a paucity of data regarding the effects of new-generation drug-eluting stent to treat ISR. From 2009 to 2010, a total of 98 patients with 98 ISR lesions were prospectively enrolled after R-ZES implantation for the treatment of ISR. Among 98 patients, 73 patients underwent follow-up angiography at 9 months. Serial intravascular ultrasound (IVUS) at both postprocedure and 9 months was evaluated in 55 patients. The overlapped segment of R-ZES was defined as the portion of R-ZES superimposed on previous stent. Late loss and binary restenosis rate were 0.3 ± 0.5 mm and 5.5% at 9 months. On IVUS, the percentage of neointimal volume and maximum percentage of neointimal area were 3.9 ± 6.3% and 17.3 ± 15.5%, respectively. There was no significant change of vessel volume index between postprocedure and 9 months (16.9 ± 4.7 mm³ /mm vs. 17.1 ± 4.6 mm³ /mm, P = 0.251). Late-acquired incomplete stent apposition was observed in 5 (5/55, 9.1%) cases. Compared with nonoverlapped segments of R-ZES, the overlapped did not show larger neointimal volume index (0.3 ± 0.5 mm³ /mm vs. 0.2 ± 0.3 mm³ /mm, P = 0.187) on 9-month IVUS. During follow-up (median, 353 days), repeat target-lesion revascularization was performed in four cases, but there were no death or stent thrombosis. This study suggested that R-ZES implantation for the treatment of ISR was effective up to 9 months and showed favorable vascular responses on serial IVUS assessment.


Efficacy and tolerability of three different doses of oral pimecrolimus in the treatment of moderate to severe atopic dermatitis: a randomized controlled trial.
Adult atopic dermatitis (AD) can seriously affect quality of life of patients and their families, and patients' disease is frequently not satisfactorily controlled with topical therapy. There is a need for alternatives to topical treatment in patients with moderate to severe AD. To investigate the efficacy and safety of oral pimecrolimus, and to determine the response to three different doses in the treatment of AD. In a double-blind, placebo-controlled, parallel-group, dose-finding study, patients with moderate to severe AD were randomized to receive either placebo, or oral pimecrolimus 10, 20 or 30 mg twice daily. The study consisted of a pretreatment phase, a 12-week double-blind treatment phase, and a 12-week post-treatment phase. In total, 103 patients were randomized. A clear, dose-dependent therapeutic effect of pimecrolimus treatment was observed, with a statistically significant onset of efficacy at week 2 and the greatest reduction from baseline of the Eczema Area and Severity Index of 66.6% at week 7 in the 30 mg twice daily dose group. Oral pimecrolimus was well tolerated and there were no signs of nephrotoxicity or the induction of hypertension. These data demonstrate the clinically relevant efficacy and short-term safety of oral pimecrolimus in adults with moderate to severe AD. Longer-term studies in larger cohorts are now required.


Navigating the Potential Energy Surface of CdSe Magic-Sized Clusters: Synthesis and Interconversion of Atomically Precise Nanocrystal Polymorphs.
Magic-sized clusters (MSCs) are kinetically stable, atomically precise intermediates along the quantum dot (QD) reaction potential energy surface. Literature precedent establishes two classes of cadmium selenide MSCs with QD-like inorganic cores: one class is proposed to be cation-rich with a zincblende crystal structure, while the other is proposed to be stoichiometric with a "wurtzite-like" core. However, the wide range of synthetic protocols used to access MSCs has made direct comparisons of their structure and surface chemistry difficult. Furthermore, the physical and chemical relationships between MSC polymorphs are yet to be established. Here, we demonstrate that both cation-rich and stoichiometric CdSe MSCs can be synthesized from identical reagents and can be interconverted through the addition of either excess cadmium or selenium precursor. The structural and compositional differences between these two polymorphs are contrasted using a combination of 1H NMR spectroscopy, X-ray diffraction (XRD), pair distribution function (PDF) analysis, inductively coupled plasma optical emission spectroscopy, and UV-vis transient absorption spectroscopy. The subsequent polymorph interconversion reactions are monitored by UV-vis absorption spectroscopy, with evidence for an altered cluster atomic structure observed by powder XRD and PDF analysis. This work helps to simplify the complex picture of the CdSe nanocrystal landscape and provides a method to explore structure-property relationships in colloidal semiconductors through atomically precise synthesis.


Sepsis and septic shock: Pathogenesis and treatment perspectives.
The majority of bacteremias do not develop to sepsis: bacteria are cleared from the bloodstream. Oxygen released from erythrocytes and humoral immunity kill bacteria in the bloodstream. Sepsis develops if bacteria are resistant to oxidation and proliferate in erythrocytes. Bacteria provoke oxygen release from erythrocytes to arterial blood. Abundant release of oxygen to the plasma triggers a cascade of events that cause: 1. oxygen delivery failure to cells; 2. oxidation of plasma components that impairs humoral regulation and inactivates immune complexes; 3. disseminated intravascular coagulation and multiple organs' failure. Bacterial reservoir inside erythrocytes provides the long-term survival of bacteria and is the cause of ineffectiveness of antibiotics and host immune reactions. Treatment perspectives that include different aspects of sepsis development are discussed.


[Mortality trend in nasopharynx cancer in Chinese resident from 1987 to 2015].
To analyze epidemical features, distribution and time trend for nasopharynx cancer deaths in China from 1987 to 2015. Methods: Negative binomial regression model was used to explore population-level risk factors for nasopharynx cancer deaths and a joinpoint regression model was used to estimate annual changes in nasopharynx cancer mortality in various populations. Results: A falling trend in age-standardized nasopharynx cancer mortality rates was observed among Chinese residents with the average annual percent change (AAPC) at -2.97% among urban female residents and -2.60% among rural female residents (P<0.05), -2.01% among urban male residents, and -1.68% among rural male residents (P<0.05), respectively. It decreased yearly for urban male aged over 85 years with AAPC at -1.54% and the age-specific mortality rates decreased yearly for the urban female aged over 85 years with AAPC at -0.60%, the age-specific mortality rates decreased yearly for rural male residents aged more than 65 years with AAPC at -0.56% and for rural female residents aged more than 85 with AAPC at 1.17%, with no significant difference (P<0.05). The nasopharynx cancer deaths risks were higher in urban residents than those in rural residents (OR=1.11, P<0.01), and they were also higher in male residents than those in female residents (OR=2.34, P<0.01). A 5-year increment in age was associated with a 23% increase in nasopharynx cancer mortality (OR=1.23, P<0.01) and a one year increment in calendar year was related to a 2% decrease in mortality (OR=0.98, P<0.01). Conclusion: There was a significant gender and age difference in a decreased trend of nasopharynx cancer mortality among Chinese residents in a long period; no increased trend was observed in the overall populations over 85 years old.


Crystal structure of an archaeal intein-encoded homing endonuclease PI-PfuI.
Inteins possess two different enzymatic activities, self-catalyzed protein splicing and site-specific DNA cleavage. These endonucleases, which are classified as part of the homing endonuclease family, initiate the mobility of their genetic elements into homologous alleles. They recognize long asymmetric nucleotide sequences and cleave both DNA strands in a monomer form. We present here the 2.1 A crystal structure of the archaeal PI-PfuI intein from Pyroccocus furiosus. The structure reveals a unique domain, designated here as the Stirrup domain, which is inserted between the Hint domain and an endonuclease domain. The horseshoe-shaped Hint domain contains a catalytic center for protein splicing, which involves both N and C-terminal residues. The endonuclease domain, which is inserted into the Hint domain, consists of two copies of substructure related by an internal pseudo 2-fold axis. In contrast with the I-CreI homing endonuclease, PI-PfuI possibly has two asymmetric catalytic sites at the center of a putative DNA-binding cleft formed by a pair of four-stranded beta-sheets. DNase I footprinting experiments showed that PI-PfuI covers more than 30 bp of the substrate asymmetrically across the cleavage site. A docking model of the DNA-enzyme complex suggests that the endonuclease domain covers the 20 bp DNA duplex encompassing the cleavage site, whereas the Stirrup domain could make an additional contact with another upstream 10 bp region. For the double-strand break, the two strands in the DNA duplex were cleaved by PI-PfuI with different efficiencies. We suggest that the cleavage of each strand is catalyzed by each of the two non-equivalent active sites.


Is routine postoperative chest radiography needed after open nephrectomy?
To assess whether routine postoperative chest radiography (CXR) is required after open nephrectomy for the detection and possible management of a pneumothorax. It has become the standard of care by many urologists to obtain routine postoperative CXRs after open nephrectomy to assess for the presence of a pneumothorax. However, at our institution, very few patients have developed a pneumothorax postoperatively, and, furthermore, the CXR findings almost never affected the clinical management. Retrospective data were collected on the last 150 open nephrectomies performed by two urologists at our institution. All laparoscopic nephrectomies and thoracoabdominal nephrectomies were excluded from analysis. A total of 150 patients underwent open nephrectomy between 1998 and 2003. The procedure was performed with an anterior subcostal, 11th rib, 12th rib, midline, and 10th rib incision in 60 (40%), 51 (34%), 18 (12%), 20 (13.3%), and 1 (0.67%) patient, respectively. Of the 150 patients, 92 (61.3%) underwent postoperative CXR and 58 (38.7%) did not. Of the 150 patients, 92 of whom had undergone postoperative CXR, 4 (2.7%) had a postoperative pneumothorax. One of these patients (0.67%) received a chest tube. Of the 4 patients with a pneumothorax, 3 had had a recognized pleural tear that was repaired at nephrectomy and the fourth had had an unrecognized pleural injury. Routine postoperative CXRs are not needed after open nephrectomy. Obtaining a selective CXR when a recognized intraoperative pleural tear has occurred, a central line is placed, the physical examination reveals an abnormality (ie, decreased breath sounds), or the patient experiences respiratory difficulties in the postoperative period is safe, cost-effective, and decreases the radiation exposure to patients.


Clinical assessment of bone quality of human extraction sockets after conversion with growth factors.
The study was conducted to evaluate the effect of mineralized freeze-dried bone allograft (FDBA), alone or in combination with growth factors in extraction sockets, on subjective assessment of bone quality during implant placement. Forty-one patients whose treatment plan involved extraction of anterior or premolar teeth were randomized into four groups: Group 1, collagen plug (control); Group 2, FDBA/β-tricalcium phosphate (β-TCP)/collagen plug; Group 3, FDBA/β-TCP/platelet-rich plasma (PRP)/collagen plug; Group 4, FDBA/β-TCP/recombinant human platelet-derived growth factor BB (rhPDGF-BB)/collagen plug. After 8 weeks of healing, implants were placed. The clinicians assessed bone quality according to the Misch classification. A benchtop calibration exercise test was conducted to evaluate agreement and accuracy of operators in recognizing different bone qualities. Differences were analyzed using one-way analysis of variance (ANOVA) or chi-square tests for continuous and categorical data. Pairwise comparisons were tested using least squares means (LS means). Spearman correlation coefficients were used to evaluate the relationship of bone growth with potential confounders. P < .05 was considered statistically significant. A simple (not weighted) kappa statistic was used to assess the agreement between raters. To assess accuracy in identifying bone quality, a chi-square test was used to compare the percent correct for each rater. The benchtop calibration exercise test demonstrated agreement among clinicians (0.75 and 0.92 between raters 1 and 2 and raters 1 and 3, respectively). Raters were more likely to identify the correct bone quality (P > .05). Inclusion of bone grafting is associated with a shift from D4 quality to D3 quality bone. Inclusion of PRP in bone grafting eliminates the incidence of D4 bone, establishing D3 and D2 quality bone as prevalent (56% vs. 42%, respectively). Inclusion of rhPDGF-BB and β-TCP in combination with the bone grafting has the same effect, although D2 quality is less prevalent. When compared to sockets grafted with FDBA/β-TCP/collagen plug alone, the sockets with growth factors demonstrated fewer residual bone graft particles. (1) Inclusion of bone grafting enhanced bone quality as assessed during implant placement. (2) Overall inclusion of PRP and rhPDGF-BB enhanced subjective bone quality, eliminating incidence of D4 quality in human extraction sockets. (3) The use of PRP or rhPDGF-BB may enhance healing within extraction sockets and decrease the healing time prior to dental implant placement.


Vertical load capacities of roof truss cross members.
Trusses used for roof support in coal mines are constructed of two grouted bolts installed at opposing forty-five degree angles into the roof and a cross member that ties the angled bolts together. The load on the cross member is vertical, which is transverse to the longitudinal axis, and therefore the cross member is loaded in the weakest direction. Laboratory tests were conducted to determine the vertical load capacity and deflection of three different types of cross members. Single-point load tests, with the load applied in the center of the specimen and double-point load tests, with a span of 2.4 m, were conducted. For the single-point load configuration, the yield of the 25 mm solid bar cross member was nominally 98 kN of vertical load, achieved at 42 cm of deflection. For cable cross members, yield was not achieved even after 45 cm of deflection. Peak vertical loads were about 89 kN for 17 mm cables and 67 kN for the 15 mm cables. For the double-point load configurations, the 25 mm solid bar cross members yielded at 150 kN of vertical load and 25 cm of deflection. At 25 cm of deflection individual cable strands started breaking at 133 and 111 kN of vertical load for the 17 and 15 mm cable cross members respectively.


Caregiver Burden and Work Productivity Among Japanese Working Family Caregivers of People with Dementia.
We examined the association between caregiver burden and work productivity (i.e., absenteeism, presenteeism, and overall work impairment) among working family caregivers of people with dementia and whether job characteristics (i.e., job demands, job control, supervisor and coworker support) moderate this association. A cross-sectional correlational study design using a web-based questionnaire survey was conducted among 379 Japanese working family caregivers of people with dementia (105 female, age range 20-77) in May 2016, which measured caregiver burden, work productivity, care situation, job characteristics, and demographics. Caregiver burden was designated as an independent variable and each aspect of work productivity as a dependent variable in a hierarchical multiple regression analysis, adjusting for demographics. Interaction terms between caregiver burden and each job characteristic were also included in the model. Caregiver burden was significantly and positively associated with presenteeism (β = 0.219, p < 0.001) and overall work impairment (β = 0.181, p < 0.001), while the association of caregiver burden with absenteeism was not significant (β = - 0.003, p = 0.953). Interaction effects of caregiver burden × coworker support on presenteeism (β = - 0.189, p = 0.023) and overall work impairment (β = - 0.172, p = 0.034) were significant. According to simple slope analyses, caregiver burden was greater at lower levels of coworker support compared to higher levels of coworker support for both presenteeism and overall work impairment. Our study suggests that higher caregiver burden is associated with a decrease in work productivity. Additionally, coworker support appears to buffer the association of caregiver burden with presenteeism and overall work impairment among working family caregivers of people with dementia.


Effects of 5-HT₃ receptor antagonists on cisplatin-induced kidney injury.
Nausea, vomiting, and renal injury are the common adverse effects associated with cisplatin. Cisplatin is excreted via the multidrug and toxin release (MATE) transporter, and the involvement of the MATE transporter in cisplatin-induced kidney injury has been reported. The MATE transporter is also involved in the excretion of ondansetron, but the effects of 5-HT3 receptor antagonists used clinically for cisplatin-induced renal injury have not been elucidated. Therefore, the aim of this study was to investigate the effects of 5-HT3 receptor antagonists in a mouse model of cisplatin-induced kidney injury and to validate the results using medical big data analysis of more than 1.4 million reports and a survey of 3000 hospital medical records. The concomitant use of a first-generation 5-HT3 receptor antagonist (ondansetron, granisetron, or ramosetron) significantly increased cisplatin accumulation in the kidneys and worsened renal damage. Conversely, the concomitant use of palonosetron had no effect on renal function compared with the use of cisplatin alone. Furthermore, an analysis of data from the US Food and Drug Administration Adverse Event Reporting System and retrospective medical records revealed that the combination treatment of cisplatin and a first-generation 5-HT3 receptor antagonist significantly increased the number of reported renal adverse events compared with the combination treatment of cisplatin and a second-generation 5-HT3 receptor antagonist. These results suggest that compared with the first-generation antagonists, second-generation 5-HT3 receptor antagonists do not worsen cisplatin-induced acute kidney injury. The findings should be validated in a prospective controlled trial before implementation in clinical practice.


Impact of 3D cell culture on bone regeneration potential of mesenchymal stromal cells.
As populations age across the world, osteoporosis and osteoporosis-related fractures are becoming the most prevalent degenerative bone diseases. More than 75 million patients suffer from osteoporosis in the USA, the EU and Japan. Furthermore, it is anticipated that the number of patients affected by osteoporosis will increase by a third by 2050. Although conventional therapies including bisphosphonates, calcitonin and oestrogen-like drugs can be used to treat degenerative diseases of the bone, they are often associated with serious side effects including the development of oesophageal cancer, ocular inflammation, severe musculoskeletal pain and osteonecrosis of the jaw.The use of autologous mesenchymal stromal cells/mesenchymal stem cells (MSCs) is a possible alternative therapeutic approach to tackle osteoporosis while overcoming the limitations of traditional treatment options. However, osteoporosis can cause a decrease in the numbers of MSCs, induce their senescence and lower their osteogenic differentiation potential.Three-dimensional (3D) cell culture is an emerging technology that allows a more physiological expansion and differentiation of stem cells compared to cultivation on conventional flat systems.This review will discuss current understanding of the effects of different 3D cell culture systems on proliferation, viability and osteogenic differentiation, as well as on the immunomodulatory and anti-inflammatory potential of MSCs.


Neurotrophins: from pathophysiology to treatment in Alzheimer's disease.
Alzheimer's disease (AD) is the most common diagnosis among dementia. As increasing longevity results in larger numbers of AD patients and thus rising economic costs, there has been intense research about the pathophysiology and treatment strategies during the last years. Since neurotrophic factors are not only responsible for neuronal development but also critical for the maintenance of neurons, they represent mediators of high interest within the research of neurodegeneration. Thereby, NGF has been identified as a dynamic pattern during the time course of neurodegeneration in AD. Post mortem studies point to a lack of NGF action in early stages of AD. In contrast NGF is found in enhanced concentrations in brains with severe AD partly due to a pathologically altered axonal transport of NGF in the neurons. Therefore, pharmacological interventions strategies focus on an neurotrophin substitution in mild to moderate cases of AD. Intensive research mostly in rodents has recently led to first promising clinical trials of intracerebral neurotrophin application pointing to a growing role of neurotrophins in the establishment of new pharmacological strategies concerning AD.


'Young saplings on fire' newly graduated nurses in the COVID-19 pandemic: A qualitative study.
To explore the experiences of newly graduated nurses during the pandemic. Newly graduated nurses were employed during the pandemic by several countries to meet the increasing demand for healthcare services. A descriptive qualitative study with thematic analysis. The study was conducted with 14 newly graduated nurses. Themes were systematized into four variables of the system research organization model, and a total of 12 themes were identified. Nurses, who started to work in the beginning months of the pandemic, faced several difficulties in their transition period, including the difficulties of starting employment and the effects of the pandemic on both society and health systems. During the pandemic, newly graduated nurses faced various difficulties in transition processes, difficulties in starting the employment process and the effects of the pandemic on both society and health systems. In order to reduce these effects, regulations are needed at all stages of the health system. It is the responsibility of health system policymakers, hospital managers, nurse managers and senior nurses to ensure that newly graduated nurses endure these pandemic conditions, which are quite challenging even for senior nurses, without any damage, and continue in the profession.


Cost-effectiveness of Spa treatment for fibromyalgia: general health improvement is not for free.
To estimate the cost-effectiveness of an adjuvant treatment course of spa treatment compared with usual care only in patients with fibromyalgia syndrome (FM). 134 patients with FM, selected from a rheumatology outpatient department and from members of the Dutch FM patient association were randomly assigned to a 2(1/2) week spa treatment course in Tunisia or to usual care only. Results are expressed as quality-adjusted life years (QALYs) for a 6-month as well as a 12-month time horizon. Utilities were derived form the Short Form 6D (SF-6D) scores and the visual analogue scale (VAS) rating general health. Costs were reported from societal perspective. Mean incremental cost per patient and the incremental cost utility ratio (ICER) were calculated; 95% confidence intervals (CIs) were estimated using double-sided bootstrapping. The data of 128 (55 spa and 73 controls) of the 134 patients (96%) could be used for analysis. Improvement in general health was found in the spa group until 6 months of follow-up by both the SF-6D (AUC 0.32 vs 0.30, P < 0.05) and the VAS (AUC 0.23 vs 0.19, P < 0.01). After 1yr no significant between-group differences were found. Mean incremental cost of spa treatment was 1311 Euro per patient (95% CI 369-2439), equalling the cost of the intervention (thalassotherapy including airfare and lodging), or 885 Euro per patient based on a more realistic cost estimate. The temporary improvement in quality of life due to an adjuvant treatment course of spa therapy for patients with FM is associated with limited incremental costs per patient.


When Chronic Pain Is Not "Chronic Pain": Lessons From 3 Decades of Pain.
The current move in physical therapy toward the biopsychosocial management of chronic pain has led some interpreters to call for a less hands-on approach, as awareness of central sensitization leads to specific management trends and a move away from pathoanatomical considerations. The authors of this Viewpoint suggest that no approach, no matter how vocal and evangelistic its followers, would likely be any more certain than what preceded it. This Viewpoint poses the question, why, when we (as a profession) appear (according to the new physical therapy gurus) to have been so wrong before, do we appear to believe that we are right this time? J Orthop Sports Phys Ther 2017;47(8):515-517. doi:10.2519/jospt.2017.0606.


Tadalafil treatment had a modest effect on endothelial cell damage and repair ability markers in men with erectile dysfunction and vascular risk.
The number of the circulating angiogenic cells (CACs) and colony forming units (CFUs) derived from cultured circulating mononuclear cells (MNCs) represents a laboratory surrogate for endothelial cell repair ability. The serum of men with erectile dysfunction (ED) and vascular risk factors (VRFs) showed an increased level of endothelial cell damage/dysfunction markers and reduced the numbers of CACs and CFUs derived from the cells of healthy men. We analyzed whether treating men with ED and VRFs with the selective phosphodiesterase type 5 inhibitor tadalafil improved the endothelial cell repair ability and reduced the levels of the serum markers of endothelial cell damage/dysfunction. MNCs from healthy men were cultured with 20% serum from 36 ED patients to obtain CACs and CFUs. The ED patients were evaluated before and after 4 weeks of treatment with tadalafil (20 mg every other day) or with a placebo. The tadalafil treatment improved erectile function (P = 0.0028), but had no effect on the inhibitory effects of serum from ED patients on the CACs and CFUs derived from healthy men. The levels of endothelin-1 (P = 0.011) and tissue type plasminogen activator (P = 0.005) were reduced after treatment compared to baseline and those of the placebo group, whereas no changes were observed in the E-selectin levels. The tadalafil treatment in the ED patients with VRFs resulted in only a modest effect on the laboratory measures of the endothelial cell damage/dysfunction and repair ability. The proposed beneficial effect of phosphodiesterase type 5 inhibition on vascular homeostasis requires further analysis.


Systematic development of pH-independent controlled release tablets of carvedilol using central composite design and artificial neural networks.
The purpose of this study was to apply the optimization method incorporating artificial neural network (ANN) using pH-independent release of weakly basic drug, carvedilol from HPMC-based matrix formulation. Because of weakly basic nature of carvedilol, drug shows pH-dependent solubility. The enteric polymer EUDRAGIT L100 was added formulations to overcome pH-dependent solubility of carvedilol. Effects of the Hydroxypropylmethyl cellulose (HPMC) K4M and EUDRAGIT L100 amount on drug release were investigated. For this purpose 13 kinds of formulations were prepared at three different levels of each variables. The optimization of the formulation was evaluated by using ANN method. Two formulation parameters, the amounts of HPMC K4M and Eudragit L100 at three levels (-1, 0, 1) were selected as independent/input variables. In-vitro dissolution sampling times at twelve different time points were selected as dependent/output variables. By using experimental dissolution results and amount of HPMC K4M and EUDRAGIT L100, percentage of dissolved carvedilol was predicted by ANN. Similarity factor (f2) between predicted and experimentally observed profile was calculated and f2 value was found 76.33. This value showed that there was no difference between predicted and experimentally observed drug release profile. As a result of these experiments, it was found that ANNs can be successfully used to optimize controlled release drug delivery systems.


Symptoms of depression and psychological distress among Hispanics with rheumatoid arthritis.
To explore the roles played by Hispanic ethnic background and acculturation to the mainstream English language culture of the United States in the depressive symptoms and mental health of rheumatoid arthritis (RA) patients. Members of a consecutive cohort of patients with RA were studied cross-sectionally. All underwent a comprehensive clinical and psychosocial evaluation. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D), and psychological distress was measured with the Medical Outcomes Study Short Form 36 (SF-36) mental health scale. Two hundred thirty-six patients were studied. Women had significantly higher median CES-D scores than men (19 versus 14, P = 0.0004), Hispanics scored higher than non-Hispanics (14 versus 8, P = 0.0002), and foreign-born scored higher than US-born patients (14 versus 10, P = 0.009). Compared with those who were fully acculturated, patients who were partially acculturated were more likely to have a score > or = 16 on the RA-adjusted CES-D (odds ratio [OR] = 1.79, 95% confidence interval [95% CI] 1.37 to 2.35, P < or = 0.001). Among unacculturated patients, the likelihood of a score > or = 16 increased 6-fold (OR = 6.68; 95% CI 3.50 to 12.72; P < or = 0.001). A similar, inverse pattern was observed for the SF-36 mental health scale. In multivariate models accounting for age, sex, education, income, articular pain, deformity, and the level of disability, low acculturation was independently associated with high depressive symptoms, and a Hispanic background was independently associated with lower SF-36 mental health. In this consecutive series of RA patients, Hispanics, particularly those who are not fully acculturated to the mainstream Anglo society, had more depressive symptoms and psychological distress than did non-Hispanics.


Concerted folding of a Candida ribozyme into the catalytically active structure posterior to a rapid RNA compaction.
Folding of the major population of Tetrahymena intron RNA into the catalytically active structure is trapped in a slow pathway. In this report, folding of Candida albicans intron was investigated using the trans-acting Ca.L-11 ribozyme as a model. We demonstrated that both the catalytic activity (k(obs)) and compact folding equilibrium of Ca.L-11 are strongly dependent on Mg(2+) at physiological concentrations, with both showing an Mg(2+) Hill coefficient of 3. Formation of the compact structure of Ca.L-11 is shown to occur very rapidly, on a subsecond time scale similar to that of RNase T1 cleavage. Most of the ribozyme RNA population folds into the catalytically active structure with a rate constant of 2 min(-1) at 10 mM Mg(2+); neither slower kinetics nor obvious Mg(2+) inhibition is observed. These results suggest that folding of the Ca.L-11 ribozyme is initiated by a rapid magnesium-dependent RNA compaction, which is followed by a slower searching for the native contacts to form the catalytically active structure without interference from the long-lived trapped states. This model thus provides an ideal system to address a range of interesting aspects of RNA folding, such as conformational searching, ion binding and the role of productive intermediates.


Atypical form of non-Langerhans histiocytosis with disseminated brain and leptomeningeal lesions.
An 18 year old girl presented with acute visual loss. T2 weighted brain MRI showed areas of hyperintensities in the thalamic nuclei, internal capsule, lentiform nuclei, the subarachnoidal spaces, and a retrobulbar infiltration. Analysis of CSF showed numerous foamy histiocytes without malignant cells, raised protein, and depressed glucose concentration. Biopsy of the right thalamus demonstrated aggregates of histiocytes with immunohistological and ultrastructural characteristics of non-Langerhans cell histiocytosis. The patient improved with chemotherapy and corticosteroids. After 3 months of treatment, CSF analysis showed no more histiocytes. Cytological examination of CSF can be helpful for the management of patients with extensive histiocytic infiltration.


Interventions for Strengthening General Self-Efficacy Beliefs in College Students: An Integrative Review.
To assess the evidence regarding the effectiveness of interventions aimed at strengthening self-efficacy beliefs in college students. Integrative Review conducted on the Lilacs, PubMed, CinahL, Cochrane Collaboration Databases, Scopus, and PsycInfo databases. The methodological quality of the studies was assessed using tools proposed by the Joanna Briggs Institute, and the results were analyzed descriptively. Out of the 10 selected studies, six demonstrated that interventions aimed at strengthening self-efficacy were effective (Levels of Evidence II and III), and four revealed contrary results (Levels of Evidence I and II). Programs aimed at enhancing self-efficacy should include content on positive mental health, psychoeducation strategies, cover a period of eight to twelve weeks, and consider the completion of homework assignments. The synthesis of evidence pointed to pathways for building an effective self-efficacy strengthening program to be implemented in universities.


[Chorionic gonadotropin concentration dependence on the phenotype of the Rhesus system].
The phenotypes of the rhesus system in pregnant females were studied for impact on maternal blood chorionic gonadotropin (CGT) levels in the second trimester. The polymorphism of the rhesus system was determined in the groups of pregnant females (n = 1591) having different blood CGT levels. There was a significant increase in the frequency of the Rh(d) phenotype (p < 0.01) among the pregnant women with lower chorionic gonadotropin levels. There was also an evident bimodality in the distribution among RH(d) pregnant females.


Variability of airborne cat allergen, Fel d1, in a public place.
Allergen exposure is a risk to develop an IgE-mediated sensitization. The amount of allergen inhaled per unit time should be related to the amount present in the air, i.e. airborne allergen. Thus, measuring allergen levels in the air would be more relevant than measuring allergen levels in dust. Allergens are present in the air in very minute quantities and usually become airborne after disturbance. Large variation of allergen levels have been found in dust. In this study, we measured variability of airborne cat allergen, Fel d1, in a public place using a high-volume air-sampler. We also studied the distribution and relationship between dust and airborne cat allergens in homes and schools. Air samples were collected at three different airflow rates, i.e. 55, 40, and 30 m3 of air per hour. The concentration of airborne Fel d1 in the community gymnastic hall varied from 1 to 10 pg/m3 within a period of 3 weeks, at airflow rates 55-30 m3/h. The coefficient of variation for repeated samplings was 14-43% (day-to-day variation) and 27-38% (within-day variation). As expected, higher levels of airborne cat allergens were found in homes with cats than in cat-free environments. There was a significant relationship between cat allergen levels in dust and air (r=0.7, P<0.01). Our study demonstrates that when measuring airborne cat allergen a large variation is observed within a day and between days. The large variability of measurement may be explained by the disturbance in the environments. We suggest, that when exposure assessment is made the environment in question should be analyzed, if possible in several occasions.


Low bending loss characteristics of hybrid plasmonic waveguide for flexible optical interconnect.
The bending loss characteristics of the hybrid plasmonic waveguide are investigated theoretically and experimentally. Simulation results showed that the guided mode is confined mainly into outer high index slab as the bending radius decreases. Thus, the radiation loss due to bending is greatly suppressed. We fabricate flexible hybrid plasmonic waveguide consisted of 5 nm-thick Au stripe and flexible multiple polymer cladding layers. The measured bending loss is lower than 1 dB/180° at a wavelength of 1310 nm for the bending radii down to 2 mm.


Noopept normalizes parameters of the incretin system in rats with experimental diabetes.
Experiments on adult Wistar rats with streptozotocin-induced diabetes showed that antihyperglycemic activity of an original nootropic and neuroprotective drug Noopept (N-phenylacetyl-L-prolylglycine ethyl ester) is more pronounced under conditions of oral application than after intraperitoneal injection. These data provided a basis for studying the effect of Noopept on major indexes of the incretin system. Streptozotocin was shown to decrease the concentrations of incretin GLP-1 and insulin in the blood. Noopept had a normalizing effect on these parameters. This influence of Noopept was not related to the inhibition of a major enzyme metabolizing incretins (dipeptidyl peptidase IV). A reference drug sitagliptin also increased the contents of incretins and insulin, which was associated with the inhibition of dipeptidyl peptidase IV. It is known that GLP-1 increases NGF expression in the insular system. Our results suggest that the increase in incretin activity contributes to the antiapoptotic effect of Noopept on pancreatic β cells. The mechanism for an increase in blood GLP-1 level after oral application of Noopept requires further investigations.


A novel role for adipose ephrin-B1 in inflammatory response.
Ephrin-B1 (EfnB1) was selected among genes of unknown function in adipocytes or adipose tissue and subjected to thorough analysis to understand its role in the development of obesity. EfnB1 mRNA and protein levels were significantly decreased in adipose tissues of obese mice and such reduction was mainly observed in mature adipocytes. Exposure of 3T3-L1 adipocytes to tumor necrosis factor-α (TNF-α) and their culture with RAW264.7 cells reduced EFNB1 levels. Knockdown of adipose EFNB1 increased monocyte chemoattractant protein-1 (Mcp-1) mRNA level and augmented the TNF-α-mediated THP-1 monocyte adhesion to adipocytes. Adenovirus-mediated adipose EFNB1-overexpression significantly reduced the increase in Mcp-1 mRNA level induced by coculture of 3T3-L1 adipocytes with RAW264.7 cells. Monocyte adherent assay showed that adipose EfnB1-overexpression significantly decreased the increase of monocyte adhesion by coculture with RAW264.7 cells. TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was reduced by EFNB1-overexpression. EFNB1 contributes to the suppression of adipose inflammatory response. In obesity, reduction of adipose EFNB1 may accelerate the vicious cycle involved in adipose tissue inflammation.


Development and evaluation of an ELISA using secreted recombinant glycoprotein B for determination of IgG antibody to herpes simplex virus.
An ELISA for the determination of IgG antibody to herpes simplex virus (HSV) was developed using a secreted recombinant HSV-1 glycoprotein B (gB-1s) as a solid phase. The clinical validity of the ELISA was established by testing different groups of sera containing HSV-1, HSV-2, or mixed antibody, in parallel with gB-1s ELISA and conventional HSV-1/HSV-2 ELISA. The new gB-1s ELISA detected HSV-1/HSV-2 antibody in sera from 48 subjects with either HSV-1 or HSV-2 past infection as well as in sera from 20 patients with primary infections by either serotype, in complete agreement with the results obtained using conventional ELISA. In 7 patients with HSV-1 encephalitis the kinetics of the gB-1s serum/cerebrospinal fluid antibody-titre ratio paralleled that of conventional ELISA over a period of time of up to 4 years. Acute and convalescent-phase sera from 28 patients with acute infections by human herpesviruses other than HSV did not show a significant cross-reactivity with gB-1s. In conclusion, gB-1s ELISA is a reliable assay for determination of HSV immune status as well as for diagnosis of both primary HSV-1 and HSV-2 infections and for diagnosis of HSV-1 encephalitis.


Universal fractional noncubic power law for density of metallic glasses.
As a fundamental property of a material, density is controlled by the interatomic distances and the packing of microscopic constituents. The most prominent atomistic feature in a metallic glass (MG) that can be measured is its principal diffraction peak position (q1) observable by x-ray, electron, or neutron diffraction, which is closely associated with the average interatomic distance in the first shell. Density (and volume) would naturally be expected to vary under compression in proportion to the cube of the one-dimensional interatomic distance. However, by using high pressure as a clean tuning parameter and high-resolution in situ techniques developed specifically for probing the density of amorphous materials, we surprisingly found that the density of a MG varies with the 5/2 power of q1, instead of the expected cubic relationship. Further studies of MGs of different compositions repeatedly produced the same fractional power law of 5/2 in all three MGs we investigated, suggesting a universal feature in MG.


High-throughput quantification of emerging "nitazene" benzimidazole opioid analogs by microextraction and UHPLC-MS-MS.
Benzimidazole opioids, often referred to as nitazenes, represent a subgroup of new psychoactive substances with a recent increase in fatal overdoses in the USA and Europe. With a variety of analogs emerging on the illicit drug market, forensic laboratories are challenged to identify these potent drugs. We here present a simple quantitative approach for the determination of nine nitazene analogs, namely, clonitazene, etodesnitazene, etonitazene, etonitazepyne, flunitazene, isotonitazene, metodesnitazene, metonitazene and protonitazene in whole blood using liquid-phase microextraction and electromembrane extraction in a 96-well format and liquid chromatography-tandem mass spectrometry. Green and efficient sample preparation was accomplished by liquid-phase microextraction in a 96-well format and resulted in high extraction yields for all analytes (>81%). Here, blood diluted with buffer (1:1, %v) was extracted from a donor compartment across a thin organic liquid membrane and into an aqueous acceptor solution. The acceptor solution was collected and directly injected into the analysis platform. Chromatographic separation was accomplished with a biphenyl column, allowing for a baseline separation of the structural isomers isotonitazene and protonitazene before detection by multiple reaction monitoring. Validation was performed according to Scientific Working Group of Forensic Toxicology guidelines. The calibration range was from 0.5 to 50 nM (except for protonitazene and clonitazene from 0.1 nM) with good linearity and limits of detection down to 0.01 nM. An AGREEprep assessment was performed to evaluate sample preparation greenness, with a final score of 0.71. Nitazenes represent a current threat to public health, and analytical methods that cover a wide range of these analogs are limited. Here, the described method may assist in the detection of nitazenes in whole blood and prevent these substances from being missed in postmortem investigations.


Mondini dysplasia--late complications.
Mondini's deformity is the second most common malformation seen in congenital genetic deafness. It is characterized by bony and membranous abnormalities of the inner ear, with a wide range of morphological and functional abnormalities. The importance of the Mondini malformation is that the patient is at an increased risk of developing meningitis or bilateral total hearing loss (or both) at an early age. Six cases are presented which illustrate the various sequelae of the Mondini malformation including meningitis, vertigo, and auditory deterioration. Decompression of the endolymphatic sac was undertaken in three patients. Emphasis is placed on the danger of head trauma, even minor, in these patients. The necessity of early diagnosis with adequate patient counseling is stressed.


Species identification key of Korean mammal hair.
The hair microstructures of Korean terrestrial mammals from 23 species (22 wild and one domestic) were analyzed using light and scanning electron microscopy (SEM) to construct a hair identification key. The hairs were examined using the medulla structures and cuticular scales of guard hairs from the dorsal regions of mature adult animals. All cuticular scale structures in the hair of Rodentia, Lagomorpha, Carnivora and Insectivora showed the petal pattern, and those of Artiodactyla and Chiroptera showed the wave pattern and coronal pattern, respectively. Rodentia, Lagomorpha and Carnivora showed multicellular, and Insectivora and Artiodactyla showed unicellular regular, mesh or columnar in the medulla structures, respectively. Chiroptera did not show the medulla structures in their hair. We found that it is possible to distinguish between species and order based on general appearance, medulla structures and cuticular scales. Thus, we constructed a hair identification key with morphological characteristics from each species. This study suggests that hair identification keys could be useful in fields, such as forensic science, food safety and foraging ecology.


Depression: a role for neurosurgery?
After providing an overview of depression this article briefly reviews the development of psychosurgery and outlines the current procedures in use world wide. Stereotactic subcaudate tractotomy (SST) is described in particular detail, and the rationale for its use in the treatment of resistant depression is then discussed by considering the findings of neuropsychological, neurophysiological and neuroimaging studies. The emerging evidence suggests that the prefrontal cortex subserves an essential function in emotion and that disruption of its connections modifies mood.


What do differences between multi-voxel and univariate analysis mean? How subject-, voxel-, and trial-level variance impact fMRI analysis.
Multi-voxel pattern analysis (MVPA) has led to major changes in how fMRI data are analyzed and interpreted. Many studies now report both MVPA results and results from standard univariate voxel-wise analysis, often with the goal of drawing different conclusions from each. Because MVPA results can be sensitive to latent multidimensional representations and processes whereas univariate voxel-wise analysis cannot, one conclusion that is often drawn when MVPA and univariate results differ is that the activation patterns underlying MVPA results contain a multidimensional code. In the current study, we conducted simulations to formally test this assumption. Our findings reveal that MVPA tests are sensitive to the magnitude of voxel-level variability in the effect of a condition within subjects, even when the same linear relationship is coded in all voxels. We also find that MVPA is insensitive to subject-level variability in mean activation across an ROI, which is the primary variance component of interest in many standard univariate tests. Together, these results illustrate that differences between MVPA and univariate tests do not afford conclusions about the nature or dimensionality of the neural code. Instead, targeted tests of the informational content and/or dimensionality of activation patterns are critical for drawing strong conclusions about the representational codes that are indicated by significant MVPA results.


Identification and characterization of two bacteriocin-producing bacteria isolated from garlic and ginger root.
Two bacteriocin-producing bacterial strains were isolated from garlic and ginger root by the agar overlay method. The bacteria were identified by 16S rRNA sequence analyses and fermentation patterns as Leuconostoc mesenteroides (garlic isolate) and Lactococcus lactis (ginger isolate). The bacteriocins were assigned the names leucocin BC2 and lactocin GI3, respectively. Physiochemical properties and antimicrobial spectra of the bacteriocins were determined by the spot-on-lawn method. Both bacteriocins were inhibited by proteolytic enzymes. Leucocin BC2 exhibited a narrow antimicrobial spectrum, inhibiting only Bacillus, Enterococcus, and Listeria species. Lactocin GI3 had a broader spectrum, inhibiting Bacillus, Clostridium, Listeria, Enterococcus, Leuconostoc, Pediococcus, and Staphylococcus species. Both bacteriocins remained active when heated at 90 degrees C for 15 min or 120 degrees C for 20 min. Leucocin BC2 assayed at 37 degrees C showed an inhibitory activity of 1,600 AU/ml, whereas at 8 degrees C the activity was 12,800 AU/ml. Conversely, lactocin GI3 activity was the same at both assay temperatures. Both bacteriocins remained active over a pH range of 2.0 to 9.0 and in various organic solvents. The activity of leucocin BC2 was increased when treated with 0.5% acetic acid and 0.5% lactic acid, whereas lactocin GI3 activity was decreased with either acid. The molecular mass values were 3.7 kDa for leucocin BC2 and 3.9 kDa for lactocin GI3. These results show that the inhibitory substances produced by the bacteria isolated from garlic and ginger are bacteriocins that appear to be different in some characteristics from previously reported bacteriocins.


Oridonin inhibits vascular inflammation by blocking NF-κB and MAPK activation.
Oridonin, an active diterpenoid compound isolated from the plant Rabdosia Rrubescens, has various pharmacological activities, including antioxidant, anti-tumor capacities and anti-inflammation. In the present study, we explore the role of oridonin in regulating endothelial inflammation and its underlying mechanism. Endothelial cell-monocyte interaction was detected by Leukocyte-endothelium Adhesion Assay. The protein expression was measured by Western blot. NF-κB p65 translocation was measured by immunofluorescence. Acute lung inflammation model was used to evaluate leukocyte infiltration in vivo. The endothelial-leukocyte adhesion and the leukocyte transmigration were profoundly reduced by oridonin. Oridonin dramatically inhibited the expression of TNF-α-induced endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1) and E-selectin) and the pro-inflammatory cytokine (IL-6, IL-8 and monocyte chemoattractant protein-1(MCP-1)). Oridonin suppressed the penetration of the leukocyte in the acute lung injury mice model. Furthermore, Oridonin also suppressed the TNF-α-activated MAPK and Nuclear factor kappa B (NF-κB) activation. Our results suggest that oridonin has the anti-inflammatory properties in endothelial cells, at least in part, through the suppression of MAPK and NF-κB activation, which may have a potential therapeutic use for inflammatory vascular diseases.


The role of capitation in quality behavioral healthcare systems of the future.
Capitation is more than just a challenge for the behavioral healthcare industry. It also presents an opportunity to develop comprehensive systems of care--driven by the appropriate use of technology and of quality methods--that will meet the needs of designated populations.


Carcinosarcoma of the stomach. A case report with light microscopic, immunohistochemical, and electron microscopic study.
A carcinosarcoma of the stomach in a 66-year-old man is reported. The tumor which had a diameter of 4 cm was an ulcerofungating mass in the posterior wall of the antrum. Histologically it was composed of well-differentiated adenocarcinoma admixed with sarcomatous elements which showed chondrocytic differentiation on light and electron microscopy. The sarcomatous areas were multifocally scattered in the central portion of the tumor and intimately blended with adenocarcinoma cells. CEA immunoreactivity was found not only in the adenocarcinoma but also in the transitional sarcomatous cells, supporting the hypothesis that this tumor might derive from mesenchymal metaplasia of a primarily epithelial neoplasm.


Depressive Symptoms Moderate the Association Between the Recent History of Alcohol Use Severity and Suicide Attempt History Among Adults in a Pretrial Jail Diversion Program.
Background: Justice-involved individuals are at elevated risk for suicidal behavior; however, research examining risk for suicidal behavior in pretrial jail diversion programs (pretrial diversion) is limited. Aims: We aimed to test (1) associations between depressive symptoms and alcohol and drug use, and suicide attempt history (SAH), and (2) interactions between depressive symptoms and alcohol and drug use in relation to SAH among adults in an urban pretrial jail diversion program. Method: The design was cross-sectional, including self-report assessments and file reviews of historical information. Adults (N = 274; Mage = 33.72; 73.7% men; 52.6% non-Hispanic Black) completed assessments within two weeks of beginning the pretrial program. Results: Depressive symptoms were positively associated with SAH after adjusting for other covariates. The significant depressive symptoms by alcohol use interaction indicated that adults with low to average depressive symptoms evidenced a similar likelihood of SAH to those with high depressive symptoms when they also had elevated alcohol use scores. Limitations: We used cross-sectional self-report data. Conclusion: It may be important to conduct suicide risk assessments for justice-involved people who use alcohol even when depressive symptoms are low.


Increased androgen receptor gene copy number is associated with TMPRSS2-ERG rearrangement in prostatic small cell carcinoma.
Small cell carcinoma of the prostate (PSCC) is a highly aggressive malignancy that often develops in patients previously treated with hormonal therapy for metastatic prostatic acinar adenocarcinoma. The TMPRSS2-ERG gene rearrangement is highly specific for prostate cancer and shared by PSCC; however, the role of androgen receptor (AR) gene alterations and interaction with TMPRSS2-ERG rearrangement are incompletely understood in PSCC. Sixty-one cases of PSCC were examined for AR gene copy number and TMPRSS2-ERG rearrangement by fluorescence in situ hybridization (FISH) and AR protein expression by immunohistochemistry. Of 61 cases of PSCC, 51% (31/61) demonstrated increased AR gene copy number (FISH+), 54% (33/61) were positive for TMPRSS2-ERG gene fusion, and 38% (23/61) showed AR protein expression. Of the 31 AR FISH+ cases, 23 also showed TMPRSS2-ERG gene fusion, and 16 expressed AR protein. Of the 33 cases with TMPRSS2-ERG fusion, 28 were AR FISH+ or expressed AR protein. Statistically significant correlations were observed between AR gene copy number or AR protein expression and TMPRSS2-ERG gene fusion (P = 0.001 and P = 0.03, respectively). In summary, high AR gene copy number emerges during the development of PSCC, often in association with TMPRSS2-ERG rearrangement. This potential mechanism warrants further study. Improvement will come from understanding the biology of the disease and integrating new therapies into the treatment of this rare and aggressive tumor.


Benzene and sulfide removal from groundwater treated in a microbial fuel cell.
Sulfidic benzene-contaminated groundwater was used to fuel a two-chambered microbial fuel cell (MFC) over a period of 770 days. We aimed to understand benzene and sulfide removal processes in the anoxic anode chamber and describe the microbial community enriched over the operational time. Operated in batch feeding-like circular mode, supply of fresh groundwater resulted in a rapid increase in current production, accompanied by decreasing benzene and sulfide concentrations. The total electron recoveries for benzene and sulfide were between 18% and 49%, implying that benzene and sulfide were not completely oxidized at the anode. Pyrosequencing of 16S rRNA genes from the anode-associated bacterial community revealed the dominance of δ-Proteobacteria (31%), followed by β-Proteobacteria, Bacteroidetes, ϵ-Proteobacteria, Chloroflexi, and Firmicutes, most of which are known for anaerobic metabolism. Two-dimensional compound-specific isotope analysis demonstrated that benzene degradation was initiated by monohydroxylation, probably triggered by small amounts of oxygen which had leaked through the cation exchange membrane into the anode chamber. Experiments with [(13)C(6) ]-benzene revealed incorporation of (13)C into fatty acids of mainly Gram-negative bacteria, which are therefore candidates for benzene degradation. Our study demonstrated simultaneous benzene and sulfide removal by groundwater microorganisms which use an anode as artificial electron acceptor, thereby releasing an electrical current.


Arthroscopic Lateral Retinacular Release in Adolescents With Medial Patellofemoral Ligament-centered Knee Pain.
The medial patellofemoral ligament (MPFL) has been implicated as a common pain generator in adolescents with anterior knee pain. The purpose of this study is to report the clinical outcomes of arthroscopic lateral retinacular release (ALRR) for refractory MPFL-centered pain and to identify risk factors for poor outcomes and surgical failures. A single-surgeon database was queried to identify all patients undergoing ALRR. Inclusion criteria included minimum 12-month follow-up and ALRR performed for MPFL pain rather than for generalized anterior knee pain or patellar instability. All patients had persistent MPFL-centered pain despite participating in a nonsurgical protocol before surgery. Primary outcomes included International Knee Documentation Committee (IKDC) subjective score and need for further surgery, typically tibial tubercle osteotomy (TTO). Eighty-eight knees in 71 patients [66 female, 5 male; average age, 15.7 y (range, 8.4 to 20.2 y)] were included. Average follow-up was 59 months (range, 12 to 138 mo). Average preoperative IKDC score was 41.9 (range, 18.4 to 67.8), whereas average postoperative IKDC score was 77.8 (range, 11.5 to 98.9; P<0.01). Postoperative IKDC scores were worse in patients with a preoperative sulcus angle of <134 degrees than those with sulcus angle of ≥134 degrees (69.9±22.1 vs. 82.0±12.5, P=0.04). Lower preoperative IKDC score correlated negatively with improvement of IKDC score postoperatively (r=-0.40, P<0.05). Seventeen knees (19.3%) subsequently underwent TTO for persistent symptoms. Patients who ultimately required TTO were younger than patients who did not (14.8±1.5 vs. 15.9±2.1; P=0.04) and had lower mean preoperative Blackburne-Peel ratio (0.95±0.25 vs. 1.11±0.24; P=0.02). This study demonstrates that patients with refractory MPFL-centered knee pain had significant improvements in clinical outcomes after undergoing ALRR at mean 5 years' follow-up. Poor outcomes and surgical failures were associated with lower preoperative IKDC score, younger age, lower preoperative Blackburne-Peel ratio, and sulcus angle of <134 degrees. Outcomes were not recorded prospectively, but mean IKDC scores <60 months postoperatively were similar to those collected ≥60 months after surgery (80.4 vs. 78.3, P=0.15). Level IV.