Evaluation of Psoriasis Area and Severity Index Thresholds as Proxies for Systemic Inflammation on an Individual Patient Level.
Psoriasis is a chronic and systemic inflammatory disease with a loss of up to 5 life years, which is thought to be reduced by biologic treatment. Disease severity and eligibility for systemic treatment are often based on the cutaneous psoriasis area and severity index (PASI) with a cut-off of 10 in several European countries. However, it is unclear how well this cut-off reflects systemic inflammation and, consequently, the risk for the development of comorbidity. (1) To assess whether specific PASI thresholds, in particular PASI 10, predict elevated biomarkers of systemic inflammation and cardiovascular risk on an individual patient level. (2) To assess the association of PASI and psoriatic arthritis with biomarkers of systemic inflammation and cardiovascular risk. Retrospective cross-sectional study of 72 psoriasis patients without systemic treatment. Overall, 68, 42, and 50% of patients had cardiovascular risk level neutrophil-to-lymphocyte ratio (NLR), C-reactive protein, and elevated platelet-to-lymphocyte ratio (PLR) values, respectively. The respective positive predictive values of PASI 10 were 70, 45, and 70. The performance of the optimal PASI cut-offs according to the Youden index was similarly weak. Subgrouping of patients with a PASI below 10 did not result in a considerably improved reflection of systemic inflammation. PLR was significantly higher in patients with moderate-to-severe compared to mild psoriasis and significantly correlated with PASI in patients with a PASI above 2 (rs = 0.266, n = 64). NLR was significantly higher in patients with psoriatic arthritis. Specific PASI thresholds were not well suited to predict elevated biomarkers of systemic inflammation and cardiovascular risk on an individual patient level. Therefore, PASI, and possibly other purely cutaneous measures, may not be ideal as stand-alone parameters to define disease severity and eligibility for systemic treatment. Our results are relevant for the ongoing discussion on the definition of psoriasis severity and eligibility for systemic treatment. Further research addressing the added value of a set of biomarkers of systemic inflammation in the assessment of psoriasis severity would be desirable.


Endoscopic resection of superficial gastrointestinal tumors.
Therapeutic endoscopy plays a major role in the management of gastrointestinal (GI) neoplasia. Its indications can be generalized into four broad categories; to remove or obliterate neoplastic lesion, to palliate malignant obstruction, or to treat bleeding. Only endoscopic resection allows complete histological staging of the cancer, which is critical as it allows stratification and refinement for further treatment. Although other endoscopic techniques, such as ablation therapy, may also cure early GI cancer, they can not provide a definitive pathological specimen. Early stage lesions reveal low frequency of lymph node metastasis which allows for less invasive treatments and thereby improving the quality of life when compared to surgery. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are now accepted worldwide as treatment modalities for early cancers of the GI tract.


First report of the hibiscus strain of citrus leprosis virus C2 infecting passionfruit (Passiflora edulis).
In Hawaii, passionfruit (Passiflora edulis; Passifloraceae) is grown primarily in residential properties and community gardens (CG). In 2019, passionfruit plants displaying chlorotic spots on young leaves, and green spots in senescing leaves were observed at two CG in Honolulu. Symptoms resembled those of passionfruit green spot virus (PfGSV) infection in Passiflora spp. (Ramos-González et al. 2020) and of the hibiscus strain of citrus leprosis virus C2 (CiLV-C2H) infection in hibiscus in Hawaii (Melzer et al. 2013). Both viruses belong to the genus Cilevirus, family Kitaviridae. Total RNA was extracted from two sample pools comprised of 40 symptomatic leaves collected from both the CG following a CTAB-based procedure (Li et al. 2008). To identify the virus associated with the P. edulis infection, reverse transcription (RT)-polymerase chain reaction (PCR) was performed using CiLV-C2 (Olmedo-Velarde et al. 2021) and PfGSV specific primers (Ramos-González et al. 2020). RT-PCR assay amplified the CiLV-C2 amplicon but failed to produce the PfGSV amplicon from infected leaves. Amplicon sequencing followed by a BLASTn search showed the nucleotide sequence had >99% identity with the CiLV-C2H-RNA1 (KC626783). A ribo-depleted RNA library created using the TruSeq Stranded Total RNA Library Prep kit (Illumina) underwent high throughput sequencing (HTS) on a NextSeq550 Illumina platform (2x75 cycles). The 6.5 million raw reads obtained were trimmed, filtered, and de novo assembled using Metaviral SPAdes v. 3.15.02 (Antipov et al. 2020). The resulting contigs were searched against an in-house database generated from GenBank virus and viroid sequences using BLASTn. This identified 12 and 3 contigs corresponding to CiLV-C2H and watermelon mosaic virus, respectively, with the latter being previously reported in passionfruit (Watanabe et al. 2016). RNA1 contigs covered 80.17% of the CiLV-C2H genome, whereas RNA2 contigs covered 94.5% with an average coverage depth of 31.660 and 57.121, respectively. To obtain the near complete genome of CiLV-C2H, gaps from the assembled HTS data were filled by overlapping RT-PCR followed by Sanger sequencing. RNA1 (8,536 nt, Acc. No. MW413437) and RNA2 (4,878 nt, MW413438) genome sequences shared 99.2% and 97.0% identity with CiLV-C2H-RNA1 (KC626783) and -RNA2 (KC626784). To further confirm the presence of CiLV-C2H in symptomatic P. edulis plants, 40 symptomatic leaf samples were individually tested by RT-PCR, and 30 samples were positive. Brevipalpus mites collected from CiLV-C2H-positive P. edulis leaves were transferred to common bean (Phaseolus vulgaris) seedlings (Garita et al. 2013). At 15-30 days post-transfer, RNA extracted from lesions observed in recipient plants tested positive for CiLV-C2H by RT-PCR. Total RNA from individual Brevipalpus mites was isolated, and cDNA was prepared to tentatively identify the mite species involved in CiLV-C2H transmission in passionfruit (Druciarek et al 2019, Olmedo-Velarde et al. 2021). CiLV-C2H was detected in individual mites, and the 28S ribosomal mite RNA sequence (MZ478051) shared 99-100% nucleotide identity with B. yothersi (MK293678 and MT812697), a vector of CiLV-C2 (Roy et al. 2013). CiLV-C2 currently has a host range limited to the families Malvaceae, Araceae, and Rutaceae (Roy et al. 2015). CiLV-C2H infects hibiscus alone and citrus in mixed infection with CiLV-C2 (Roy et al; 2018) which is responsible for causing citrus leprosis disease. Detection of CiLV-C2H in passionfruit expands the number of host families of CiLV-C2H.


Response modes influence the accuracy of monocular and binocular reaching movements.
The authors manipulated the availability of monocular and binocular vision during the constituent planning and control stages of a goal-directed reaching task. Furthermore, trials were completed with or without online limb vision to determine whether monocular- or binocular-derived ego-motion cues influence the integration of visual feedback for online limb corrections. Results showed that the manipulation of visual cues during movement planning did not influence planning times or overall kinematics. During movement execution, however, binocular reaches--and particularly those completed with online limb vision--demonstrated heightened endpoint accuracy and stability, a finding directly linked to the adoption of a feedback-based mode of reaching control (i.e., online control). In contrast, reaches performed with online monocular vision produced increased endpoint error and instability and demonstrated reduced evidence of feedback-based corrections (i.e., offline control). Based on these results, the authors propose that the combination of static (i.e., target location) and dynamic (i.e., the moving limb) binocular cues serve to specifically optimize online reaching control. Moreover, results provide new evidence that differences in the kinematic and endpoint parameters of binocular and monocular reaches reflect differences in the extent to which the aforementioned engage in online and offline modes of movement control.


Effects of seasons on some semen parameters and bacterial contamination of Awassi ram semen.
The objectives of the present study were to determine the effects of season on some semen parameters and bacterial contamination of Awassi ram semen. Semen samples from six mature Awassi rams were used in this study. Semen collection was performed with artificial vagina every week, from September 2009 to October 2010. Volume, sperm concentration, mass motility, individual motility, percentage live sperm and sperm abnormalities were evaluated. Moreover, determination of viable bacterial count of the rams was also recorded weekly. Higher (p < 0.05) semen volume in the hot summer and spring months was observed of August (1.55 ± 0.08 ml) and March (1.27 ± 0.15 ml). Sperm concentration was highest (p < 0.05) in the breeding season (late summer to early autumn) of September (4.21 ± 0.86 × 10(9) sperm/ml). Sperm individual motility and percent of live sperm observed in August (summer) and May (end of spring) when the environmental temperature started to increase were recorded highest values and differed significantly (p < 0.05) from December and January (winter). The highest value of the mean sperm acrosomal defects (13.33 ± 0.63%) was recorded in December. The highest value of the mean viable bacterial count (138.3 ± 21.6) was recorded in July (summer). A significant decrease (p < 0.01) in the mean viable bacterial count was observed from the middle of winter towards the end of spring. The lowest bacterial count was noted in January (60.5 ± 2.98). It could be concluded from the results of the present study that there is an effect of season on ram semen quality, and summer high temperature in northern Iraq has no effect on Awassi ram semen. There is a significant effect of season on bacterial count on Awassi ram semen.


Disability, participation, and subjective wellbeing among older couples.
This paper investigates the link between disability and subjective wellbeing, using data from the 2009 Disability and Use of Time supplement to the Panel Study of Income Dynamics, the longest running national panel study in the United States. Disability is construed broadly to include both the presence of any physical, cognitive, or sensory impairment or activity limitation and also the severity of underlying impairments. Subjective wellbeing is measured using two distinct approaches: reports of life satisfaction and of moment-to-moment wellbeing-both positive and negative-on the previous day. The latter, collected through 24-h time diaries, also offers for the first time the ability to explore the role of participation in particular kinds of activities linking disability to subjective wellbeing. The analytic sample included married persons ages 60 and older and their spouses (n = 751 married individuals) who completed 1498 diaries. Several new findings emerged: no matter what the measure of wellbeing, older married adults with disability report worse subjective wellbeing than those without, and neither different demographic and socioeconomic profiles nor differences in participation fully account for these disparities. Influences of disability on global life satisfaction and episodic reports of happiness were relatively small and of comparable size. However, notably sizeable differences were identified in the cumulative number of pleasant minutes experienced yesterday by disability status - on the order of 71 fewer minutes on average for those with a disability of average severity. Differences appear to be more strongly linked to somatic symptoms of pain and feeling tired than to differential intensity of experiencing happiness, sadness, frustration, or worry. We also found limited support for the notion that participation partially mediates the relationship between disability and global, but not episodic, subjective wellbeing.


Nasal positive pressure ventilation in patients with acute respiratory failure. Difficult and time-consuming procedure for nurses.
Intubation and mechanical ventilation are well-established techniques in the management of patients with acute respiratory failure; however, there are situations in which these procedures cannot be used safely for various reasons. A recently described noninvasive technique, nasal positive-pressure ventilation (NPPV), has been developed for home ventilation of certain patients with chronic ventilatory insufficiency. We hypothesized that NPPV could be used in selected patients in whom intubation and mechanical ventilation were clearly indicated, but not immediately possible, or even contraindicated. Six patients were treated with NPPV during an episode of acute respiratory failure and enrolled in a prospective study. We found that NPPV was successful in avoiding intubation, but only in the three patients suffering from a restrictive pulmonary disorder, whereas the procedure was unsuccessful in patients with obstructive disorders. Moreover, in every patient, acute NPPV was very time-consuming for the nursing staff: in patients with restrictive disorders, a nurse had to monitor a patient submitted to NPPV during 41 +/- 9 percent of the duration of ventilation and during 91 +/- 9 percent of the NPPV time in patients with obstructive disorders. We conclude that acute NPPV may be attempted in selected patients with acute respiratory failure, predominantly patients with restrictive respiratory disorders, but that this procedure is very time-consuming for nurses.


Determinants of coverage in community-based therapeutic care programmes: towards a joint quantitative and qualitative analysis.
One of the most important elements behind the success of Community-based Therapeutic Care (CTC) programmes for the treatment of severe acute malnutrition has been their ability to achieve high levels of coverage. In CTC, coverage is measured using the Centric System Area Sampling (CSAS) method, which provides accurate and reliable estimates of programme coverage as well as information on the primary reasons for non-attendance. Another important feature of CTC programmes is their use of socio-cultural assessments to determine potential barriers to access and to develop context-specific responses. By analysing data on non-attendance provided by CSAS surveys, in conjunction with data from socio-cultural assessments, it is possible to identify common factors responsible for failures in programme coverage. This paper focuses on an analysis of data from 12 CTC programmes across five African countries. It pinpoints three common factors (distance to sites, community awareness of the programme, and the way in which rejections are handled at the sites) that, together, account for approximately 75 per cent of non-attendance.


The Paradoxical Significance of Headache in Hypertension.
The cardiovascular prognostic value of various types of headache, particularly migraine, in the general population remains controversial. The aim of the present study was to assess their prognostic value for all-cause, cardiovascular and stroke mortalities in hypertensive patients. A total of 1,914 hypertensive individuals were first categorized according to the absence or presence of headache and thereafter according to the 3 subtypes of headache: migraine, daily headache, and other headache. Multiple regression analysis demonstrated that all headache types were predicted by gender (women), diastolic blood pressure, absence of diabetes, secondary hypertension, and a trend for severe retinopathy. After 30 years of follow-up, 1,076 deaths were observed, 580 of whom were from cardiovascular cause and 97 from acute stroke. In a multivariable Cox model adjusted for major confounders, patients having headache had a decreased risk for all-cause mortality (hazard ratio (HR) 0.82; 95% confidence interval (CI) 0.73-0.93) and cardiovascular mortality (HR 0.80; 95% CI 0.68-0.95), but not for stroke mortality (HR 1.00; 95% CI 0.70-1.43). When considering only patients with headache, "daily headache" had a nonsignificant better prognostic value for all-cause and cardiovascular mortality than "other headache" (HR 0.83; 95% CI 0.68-1.01; HR 0.89; 95% CI 0.69-1.16, respectively) and "migraine" (HR 0.85; 95% CI 0.65-1.11; HR 0.78; 95% CI 0.55-1.10, respectively). Presence of nonspecific headache in hypertensive patients has a paradoxical significance in that it is associated with a high-risk profile but does not result in a worse prognosis over the long term.


S100B as a Potential Biomarker and Therapeutic Target in Multiple Sclerosis.
Multiple sclerosis (MS) pathology is characterized by neuroinflammation and demyelination. Recently, the inflammatory molecule S100B was identified in cerebrospinal fluid (CSF) and serum of MS patients. Although seen as an astrogliosis marker, lower/physiological levels of S100B are involved in oligodendrocyte differentiation/maturation. Nevertheless, increased S100B levels released upon injury may induce glial reactivity and oligodendrocyte demise, exacerbating tissue damage during an MS episode or delaying the following remyelination. Here, we aimed to unravel the functional role of S100B in the pathogenesis of MS. Elevated S100B levels were detected in the CSF of relapsing-remitting MS patients at diagnosis. Active demyelinating MS lesions showed increased expression of S100B and its receptor, the receptor for advanced glycation end products (RAGE), in the lesion area, while chronic active lesions displayed increased S100B in demyelinated areas with lower expression of RAGE in the rim. Interestingly, reactive astrocytes were identified as the predominant cellular source of S100B, whereas RAGE was expressed by activated microglia/macrophages. Using an ex vivo demyelinating model, cerebral organotypic slice cultures treated with lysophosphatidylcholine (LPC), we observed a marked elevation of S100B upon demyelination, which co-localized mostly with astrocytes. Inhibition of S100B action using a directed antibody reduced LPC-induced demyelination, prevented astrocyte reactivity and abrogated the expression of inflammatory and inflammasome-related molecules. Overall, high S100B expression in MS patient samples suggests its usefulness as a diagnostic biomarker for MS, while the beneficial outcome of its inhibition in our demyelinating model indicates S100B as an emerging therapeutic target in MS.


Kinetic reconstruction of the free-energy landscape.
We present a new general method to trace back a lot of valuable information from direct simulations and experiments of activated processes. In particular, it allows the reconstruction of the free-energy landscape for an arbitrary reaction coordinate directly from the out-of-equilibrium dynamics of the process. We demonstrate the power of this concept by its application to a molecular dynamics simulation of nucleation of a Lennard-Jones vapor. The same method can be also applied to Brownian dynamics and stochastic simulations.


Differential expression of cytokeratins 8 and 20 distinguishes craniopharyngioma from rathke cleft cyst.
Craniopharyngiomas are epithelial neoplasms usually located in the sellar and suprasellar regions. Distinguishing craniopharyngioma from Rathke cleft cyst is sometimes difficult, and the distinction is clinically significant because Rathke cleft cysts have a better prognosis than craniopharyngiomas. We retrieved 10 cases with a primary diagnosis of craniopharyngioma and 5 cases with a diagnosis of Rathke cleft cyst for analysis. Five cases of normal pars intermedia of pituitary glands from autopsy served as controls. We evaluated the expression patterns of a broad range of low- to intermediate-molecular weight cytokeratins (CK7, CK8, CK10, CK17, CK18, CK19, and CK20) and high-molecular weight cytokeratins (K903: a combination of CK1, CK5, CK10, and CK14; and CK5/6) in these cases. Craniopharyngiomas had a cytokeratin expression pattern distinct from that of Rathke cleft cysts and pituitary gland pars intermedia: craniopharyngiomas did not express cytokeratins 8 and 20, whereas Rathke cleft cysts and pars intermedia of pituitary glands both expressed cytokeratins 8 and 20. The differential expression of cytokeratins distinguishes between craniopharyngioma and Rathke cleft cyst, and this difference could be useful for identifying craniopharyngioma in difficult cases in which only a small biopsy is available. The different cytokeratin profiles of craniopharyngioma and Rathke cleft cyst suggest that these lesions do not come from the same origin, or that they come from a different developmental stage of the pouch epithelium.


Functional evolution on the assembled DNA template.
After more than twenty years of effort, using DNA to fabricate addressable nanostructures is now a well-established technology. In this tutorial review, we attempt to present an overview of the applications of DNA templates, including its biological significance, the directing of chemical reactions at the molecular level, as well as the placing of nanoparticles and proteins in position.


Paclitaxel and mitoxantrone in metastatic breast cancer: a phase II trial of the Italian Oncology Group for Cancer Research.
In a previous dose-finding trial, in previously treated patients with metastatic breast cancer (MBC), we showed that the combination of Mitoxantrone (M) and Paclitaxel (P) may be an interesting (response rate: 69%) and well-tolerated regimen. On the basis of these results, our group started a new trial in chemotherapy-naive patients with MBC. Forty-six women entered in this trial, and all patients were evaluated for response and toxicity. Schedule of treatment was P 175 mg/m2 over 3 hr day 1 and M 12 mg/m2 day 1, every 3 weeks. Patients were reevaluated every 3 months and chemotherapy was continued unless tumor progression or unacceptable toxicity occurred. The intent-to-treat objective response was 61% (95% confidence interval: 49%-78%). Five patients (11%) obtained complete response and 23 (50%) partial response with a median time to failure of 14 months. The median survival was 22 months (range 1-39). The principal toxicity was hematological: 38 (82%) patients had grade 3 to 4 leukopenia; only 2 patients had grade 4 anemia and one grade 4 thrombocytopenia. Nonhematological toxicity (grade 3-4) was mild and cardiotoxicity was infrequent. This trial suggests the combination of M and P is an active palliative regimen for patients with MBC. Toxicity was moderate. The infrequent development of cardiotoxicity suggests this combination may not share the problems reported with P plus doxorubicin combinations.


HIV-2 diagnosis and quantification in high-risk patients.
Current diagnostic assays for HIV-1 do not always test for the presence of HIV-2 in the United States. We present the case of a patient from Cape Verde, who was admitted to our hospital with rapidly deteriorating neurological function and multiple white matter lesions on MRI likely secondary to progressive multifocal leukoencephalopathy (PML). Initially, the patient had a positive EIA for HIV, but a negative HIV-1 Western Blot and no viral load detected on a branched-DNA assay. A repeat viral load by reverse transcriptase methodology (RT-DNA) detected 121,000 copies and an HIV-2 Western Blot was positive. The case highlights an extremely rare presentation of HIV-2 with severe neurological disease. We discuss the different tests available for the diagnosis and monitoring of HIV-2 in the United States.


Responsible prescribing of opioids for the management of chronic pain.
The management of patients with chronic pain is a common clinical challenge. Indeed, chronic pain is often inadequately controlled in patients with cancer and in those with non-cancer chronic pain. Because of the complex nature of chronic pain, successful long-term treatment is more difficult than for acute pain. Most often acute pain is nociceptive, whereas chronic pain can be nociceptive (i.e., in response to noxious stimuli), neuropathic (i.e., initiated by a primary lesion or dysfunction in the nervous system) or mixed in origin. Opioids are the current standard of care for the treatment of moderate or severe nociceptive pain. Opioids mediate their actions by binding and activating receptors both in the peripheral nervous system and those that are found in inhibitory pain circuits that descend from the midbrain to the spinal cord dorsal horn. Opioid agonists exert a number of physiological responses including analgesia, which increases with increasing doses. The use of opioids to manage pain in patients with cancer is well accepted. The WHO step-wise algorithm for analgesic therapy based on pain severity reserves the use of opioid therapy for moderate and severe pain. The WHO algorithm has proven to be highly effective for the management of cancer pain. However, the use of opioids to treat patients with chronic non-cancer pain is controversial because of concerns about efficacy and safety, and the possibility of addiction or abuse. The results of clinical surveys and retrospective case series involving patients with non-cancer chronic pain have been inconsistent in regard to resolving these controversial issues. The oral route of drug administration is most appropriate for patients receiving opioids; although rectal, transdermal and parenteral routes of administration are used in specific situations. For continuous chronic pain, opioids should be administered around-the-clock and several long-acting formulations are available that require administration only once or twice daily. Opioid doses should be titrated according to agent-specific schedules to maximise pain relief and maintain tolerability. Adverse effects include constipation, nausea and vomiting, sedation, cognitive impairment and respiratory depression. Tolerance to the analgesic and adverse effects as well as physical dependence, which causes withdrawal symptoms upon discontinuance, may occur with opioid use. Estimates of addiction rates among patients with chronic non-cancer pain range from 3.2 to 18.9%. Successful pain treatment and symptom management is an attainable goal for the majority of patients with chronic pain. Further controlled clinical trials are needed to define the role of opioid therapy in chronic non-cancer pain, and to establish criteria for patient selection and specific treatment algorithms.


Ab interno trabeculectomy versus trabeculectomy for open-angle glaucoma.
To compare the effect of ab interno trabeculectomy with trabeculectomy. Retrospective, cohort study. A total of 115 patients who underwent ab interno trabeculectomy (study group) compared with 102 patients who underwent trabeculectomy with intraoperative mitomycin as an initial surgical procedure (trabeculectomy group). Inclusion criteria were open-angle glaucoma, age ≥ 40 years, and uncontrolled on maximally tolerated medical therapy. Exclusion criterion was concurrent surgery. Clinical variables were collected from patient medical records. Intraocular pressure (IOP) and Cox proportional hazard ratio (HR) and Kaplan-Meier survival analyses with failure defined as IOP >21 mmHg or less than 20% reduction below baseline on 2 consecutive follow-up visits after 1 month; IOP ≤ 5 mmHg on 2 consecutive follow-up visits after 1 month; additional glaucoma surgery; or loss of light perception vision. Secondary outcome measures include number of glaucoma medications and occurrence of complications. Mean follow-up was 27.3 and 25.5 months for the study and trabeculectomy groups, respectively. Intraocular pressure decreased from 28.1 ± 8.6 mmHg at baseline to 15.9 ± 4.5 mmHg (43.5% reduction) at month 24 in the study group, and from 26.3 ± 10.9 mmHg at baseline to 10.2 ± 4.1 mmHg (61.3% reduction) at month 24 in the trabeculectomy group. The success rates at 2 years were 22.4% and 76.1% in the study and trabeculectomy groups, respectively (P<0.001). Younger age (P = 0.037; adjusted HR, 0.98 per year; 95% confidence interval [CI], 0.97-0.99) and lower baseline IOP (P = 0.016; adjusted HR, 0.96 per 1 mmHg; 95% CI, 0.92-0.99) were significant risk factors for failure in the multivariate analysis of the study group. With the exception of hyphema, the occurrence of postoperative complications was more frequent in the trabeculectomy group (P<0.001). More additional glaucoma procedures were performed after ab interno trabeculectomy (43.5%) than after trabeculectomy (10.8%, P<0.001). Ab interno trabeculectomy has a lower success rate than trabeculectomy. Proprietary or commercial disclosure may be found after the references.


Potential roles of lncRNA-Cox2 and EGR1 in regulating epidural fibrosis following laminectomy.
Epidural fibrosis, one of the common complications after spinal surgery, seriously affects the surgical decompression effect. Effectively inhibiting the fibrous tissue hyperplasia is pivotal to reduce the scar adhesion. Previous studies showed that early growth response 1 (EGR1) is associated with the fibroblast reactivity induced by transforming growth factor-beta (TGF-β) and plays a vital regulatory role in scar formation; however, the upstream targets and mechanisms still remain unclear. In this work, it was found that the level of long non-coding ribonucleic acid (lncRNA)-cyclooxygenase-2 (COX2) was significantly negatively correlated with EGR1 expression and the severity of the scar. Therefore, it was conjectured that lncRNA-COX2 may decrease fibroplasia and scar formation by negatively regulating EGR1. TGF-β was used to activate the embryonic and adult rat fibroblasts. Rats underwent laminectomy to establish the epidural fibrosis model. The changes in the levels of fibroplasia-related genes were measured and analyzed through messenger RNA (mRNA), lncRNA, and micro RNA expression profile chips. Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was applied to determine the levels of EGR1 and lncRNA-COX2, and Western blotting was adopted to detect the content of EGR1, collagen I (Col-1), Col-3, and alpha-smooth muscle actin (α-SMA). The scar formation was reflected by hematoxylin and eosin (HE) staining and Masson staining, and the expression level of α-SMA in the scar tissues was measured via immunohistochemistry. Finally, micro-magnetic resonance imaging (MRI) was utilized to examine the different degrees of epidural fibroplasia. It was found that the reactivity of embryonic rat fibroblasts to the TGF-β stimulation was different from that of adult rat fibroblasts. LncRNA-COX2 was highly expressed in the embryonic rat fibroblasts, but lowly expressed in the adult rat fibroblasts, which had negative correlations with the EGR1 level in embryonic and adult rat fibroblasts. In addition, it was revealed that the expression of EGR1 in the adult rat fibroblasts was remarkably higher than that in the embryonic rat fibroblasts after the activation with TGF-β. Meanwhile, the level of lncRNA-COX2 was lowered after the activation, especially in the adult rat fibroblasts. It was discovered in the in-vivo model that the degree of fibroplasia was positively associated with EGR1 level and negatively correlated with lncRNA-COX2 level. The results of this research elucidated that the down-regulation of lncRNA-COX2 is involved in the epidural scar formation and related to the elevated EGR1 level which regulates the activation of fibroblasts and secretion of massive extracellular matrixes, suggesting that lncRNA-COX2 may modulate the role of fibroblasts in scar formation as an upstream action target of EGR1.


Chemical Composition and Antimicrobial Activity of Selected Essential Oils against Staphylococcus spp. Isolated from Human Semen.
Staphylococcus spp. is not only a commensal bacteria but also a major human pathogen that causes a wide range of clinical infections. Recent evidence suggests that Staphylococcus has the ability to colonize the reproductive system and to affect its structure and functions. The objective of this study was to determine the chemical properties and antibacterial effects of select essential oils (EOs): Amyris balsamifera L., Boswellia carterii Birdw., Canarium luzonicum (Blume) A. Gray, Cinnamomum camphora (L.) J. Presl., Cinnamomum camphora var. linaloolifera Y. Fuita, Citrus x aurantium L., Gaultheria procumbens L., Litsea cubeba (Lour.) Pers., Melaleuca ericifolia Smith., Melaleuca leucadendra L., Pogostemon cablin (Blanco) Benth., Citrus limon (L.) Osbeck, Santalum album L., and Vetiveria zizanoides (L.) Roberty against 50 Staphylococcus spp. cultures isolated from human semen, specifically Staphylococcus aureus, S. capiti, S. epidermidis, S. haemoliticus, and S. hominis. The disc diffusion and broth microdilution methods were used to assess the antimicrobial potential and to determine the minimum inhibitory concentration (MIC) of the selected EOs. The best anti-Staphylococcus activities were found with both methods for the essential oils of C. luzonicum (Blume) A. Gray, A. balsamifera, C. camphora, and P. cabli.


[Supraepitrochlear process and median nerve compression].
The supra-condylar process exists in a small percentage of the population. Infrequently this process may cause compression of the median nerve. The authors such a case associated with compression of the ulnar nerve. Excision of the bony process led to immediate resolution of the symptoms. In the presence of compressive symptoms with neurologic deficit, it is important to always to look for a supracondylar process by palpation.


Assay of acyl-CoA:monoglyceride acyltransferase from rat small intestine using continuous recording spectrophotometry.
Acyl-CoA:monoglyceride acyltransferase in microsomal preparations from the small intestine of the rat has been measured by means of continuous recording spectrophotometry. The reaction of 5,5'-dithiobis(2-nitrobenzoic acid) with CoA has been employed for this assay and optimal conditions for the reaction have been defined. One of the substrates, palmitoyl-CoA, inhibits the reaction even in modest concentrations. This inhibition is largely prevented by the addition of bovine serum albumin to the incubation medium. The reliability of the assay method was confirmed by comparison with the more cumbersome assay method that uses radioactive substrate.


Evaluation of retinal nerve fiber layer thickness in patients with retinitis pigmentosa using spectral-domain optical coherence tomography.
To measure the peripapillary retinal nerve fiber layer (RNFL) thickness using spectral-domain optical coherence tomography in patients with retinitis pigmentosa. Fifty eyes of 30 patients with retinitis pigmentosa underwent a complete ocular examination, including best-corrected visual acuity using a Snellen chart, slit-lamp biomicroscopic examination, and Goldmann applanation intraocular pressure measurement. Dilated fundus examination was performed using both direct and indirect ophthalmoscopy. In addition, all patients underwent peripapillary RNFL thickness measurements using an OPKO spectral-domain optical coherence tomography (OPKO Instrumentations, Miami, FL). The mean (± SD) age of the study cohort was 45.8 (± 16.3) years. Of the 50 eyes, 18 (36%) showed a thinning of the peripapillary RNFL in 1 or more quadrants and 21 (42%) showed a thickening of the peripapillary RNFL in 1 or more quadrants. Four eyes (8%) showed both thinning and thickening of the peripapillary RNFL thickness. The overall circumferential RNFL thickness of the 14 eyes that showed only thinning in at least 1 quadrant was 78.78 μm. For the 17 eyes that showed only thickening in at least 1 quadrant, the RNFL thickness was 119.69 μm. The values of the eyes with thinning and the eyes with thickening were significantly different from normal (t = 6.31 and P < 0.01 for thickening; t = 3.62 and P < 0.01 for thinning). Using spectral-domain optical coherence tomography testing, we demonstrated in the current study that the peripapillary RNFL thickness in patients with RP can be decreased, increased, or maintained within normal limits. Assessment of the RNFL thickness seems prudent in these patients, particularly for identifying notable degrees of RNFL thinning in those being considered for future therapeutic trials.


Early insulin and glucagon responses to different food items.
An early postprandial insulin release has previously been described when high carbohydrate meals are fed. The present investigation on humans shows that this response takes place not only with high carbohydrate (sugar pie) but also with high lipid (whipped cream) and protein (beef steak or fish fillet) meals, suggesting that it is caused by the palatability of the food rather than to its composition. This increment takes place at the very beginning of the meal and even if the period of feeding lasted 10 min, the response has disappeared at that time. Thirty min later due to plasma glucose elevation, a significant increase in insulin was observed with the sugar pie. At that time a similar increase was observed with the fish filet or the beef steak but not with the whipped cream. A cephalic glucagon response was not observed with any of the meals but 30 min after feeding the plasma level of this hormone increased with both beef and fish feeding and decreased significantly with the sugar pie meal. The usefulness of these responses is discussed with relation to the metabolic responses associated with feeding.


On the three-dimensional structure of quick-frozen hepatic Mallory bodies with special reference to the appearance of cytoplasmic vesicles.
Livers containing Mallory bodies (MBs, hyalin degenerative cytoplasmic inclusions) were examined using Heuser's and Van Harreveld's cryo-techniques. The tissues were collected from 1) a patient suffering from alcoholic hepatitis and 2) mice treated with griseofulvin (GF, an anti-mitotic drug). Normal mouse liver and isolated MBs from GF-treated mice were also analyzed by the same methods. Our results suggest that under the toxic influence of alcohol or GF on microtubular elements, MBs are generated by entanglement of elements of 10 nm filaments with microtubule elements. This in turn inhibits cellular transport processes. The reticular net of the ER-element which is usually observable in the normal tissue is changed into numerous small vesicles in the pathological and experimental tissues. The diameters of hepatocytes containing these vesicles were 1.5 to 2 times larger than control diameters. MBs have previously been described in thin sections as filamentous tangles. On replicas we found that they appear to be composed of pairs of filaments twisted in a roughly helical manner, each having a diameter less than 10 nm. The paired helical nature of the MB-filaments is reminiscent of other inclusion bodies, which are also composed of elements of 10 nm filaments, observable in various neurological diseases.


Influence of antidepressants on intracellular levels of cyclic adenosine monophosphate in human peripheral blood mononuclear cells.
This study examines the effects of paroxetine and imipramine on intracellular concentrations of cyclic adenosine monophosphate (cAMP) in human peripheral blood mononuclear cells. It was found that imipramine and paroxetine had no effect on basal cAMP-levels. Stimulation with lipopolysaccharides and phytohaemagglutinin increased intracellular cAMP concentrations. However, pre-incubation with imipramine or paroxetine, did not influence this increase. These data do not support the hypothesis that cAMP may be related to the in vitro anti-inflammatory effects of antidepressants.


[Clinical, experimental and physiopathological aspects of restenosis after coronary angioplasty].
Restenosis is still the main limitation of coronary angioplasty. A comparison of clinical data and experimental observations from animal models showed the early, local and transient features of this phenomenon. Several hypotheses have been advanced to explain the mechanism. Intimal hyperplasia remains an important feature of restenosis in the human but probably does not play the exclusive role as used to be believed. Vascular remodelling which has several mechanisms seems to be a major contribution to reduction of the vessel lumen. The role of thrombosis remains controversial in the clinical setting but is an essential factor in the pig which is a very similar model to the human. Each of these different mechanisms participates in the development of restenosis but in proportion which remain to be defined.


Characterization of the mitochondrial genome in childhood multiple sclerosis. II. Multiple sclerosis without optic neuritis and LHON-associated genes.
The occurrence of mitochondrial mutations with primary pathogenic significance for Leber's hereditary optic neuropathy in patients with a multiple sclerosis-like phenotype and the preferential maternal transmission points to an involvement of the mitochondrial genome in conferring increased susceptibility to MS. To evaluate the link between MS and mtDNA variations we investigated a total of thirteen children with MS as well as twenty controls by sequencing eight mitochondrial encoded genes which are known to be the loci for LHON-associated mutations. Numerous synonymous nucleotide substitutions and common polymorphisms were excluded from comparative analyses. No primary LHON mutations were found. Secondary LHON mutations were identified more frequently in control subjects than in the children with MS. The remaining eight discrete missense mutations were chosen for further characterization. Only two of them were found in more than one patient. Our results suggest that nucleotide substitutions within the ND1, ND2, ND4, ND5, ND6, COI, COIII or cytochrome b genes of mtDNA do not contribute to the etiology of typical MS. However, the association of LHON mutations with visual impairment in MS as well as the relationship between phenotypic diversity in certain subgroups of patients with individual mtDNA genotypes merits further investigations.


Patterns of thromboembolic pulmonary vascular disease in COVID-19.
SARS-CoV-2 (COVID-19) is associated with increased thrombosis. Here, we demonstrate patterns of pulmonary vascular disease in COVID-19 including classical acute pulmonary embolism and subsegmental perfusion defects in the absence of acute pulmonary embolism suggestive of microvascular thrombosis.


Cellular processing and destinies of artificial DNA nanostructures.
Since many bionanotechnologies are targeted at cells, understanding how and where their interactions occur and the subsequent results of these interactions is important. Changing the intrinsic properties of DNA nanostructures and linking them with interactions presents a holistic and powerful strategy for understanding dual nanostructure-biological systems. With the recent advances in DNA nanotechnology, DNA nanostructures present a great opportunity to understand the often convoluted mass of information pertaining to nanoparticle-biological interactions due to the more precise control over their chemistry, sizes, and shapes. Coupling just some of these designs with an understanding of biological processes is both a challenge and a source of opportunities. Despite continuous advances in the field of DNA nanotechnology, the intracellular fate of DNA nanostructures has remained unclear and controversial. Because understanding its cellular processing and destiny is a necessary prelude to any rational design of exciting and innovative bionanotechnology, in this review, we will discuss and provide a comprehensive picture relevant to the intracellular processing and the fate of various DNA nanostructures which have been remained elusive for some time. We will also link the unique capabilities of DNA to some novel ideas for developing next-generation bionanotechnologies.


Hepatic embolization through pancreaticoduodenal arcade: double catheter technique.
Transcatheter arterial embolization through pancreaticoduodenal arcade was performed in a patient with hepatocellular carcinoma using double catheter technique. This method is very useful for hepatic embolization in patients with occlusion and stenosis of the celiac axis or common hepatic artery.


Diagnostic delays in rheumatic diseases with associated arthritis.
The objective of this study was to determine the length of delay in diagnosis of inflammatory rheumatic diseases, and to indicate the main factors responsible for such delays. A retrospective multi-centre questionnaire survey carried out among 197 patients with diagnosed inflammatory rheumatic diseases or undergoing the diagnostic process. The most common early symptoms of inflammatory rheumatic disease included joint pain (94%), joint swelling (78%), morning joint stiffness (77%), fatigue (76%), and sleep disturbed by joint pain (74%). When asked about the reasons for seeking medical help, most patients indicated intensification of the symptoms (89%) and the fact that the symptoms made them unable to perform daily activities or work (86%). Limited access to specialists (70%) and the conviction that the symptoms will resolve spontaneously (57%) had the biggest impact on delaying a visit to a doctor. Before visiting a rheumatologist, the patients consulted their symptoms with their general practitioners (GPs, 95%), orthopaedicians (43%), and neurologists (29%). Almost half of the patients (48%) consulted their symptoms with at least 2 non-rheumatologists, whereas as many as 21% of patients visited 4 or more specialists. After the onset of symptoms of rheumatic disease, 28% of patients delayed seeing any doctor for 4 months or longer. 36% of patients waited 4 months or longer for a referral to a rheumatologist. The great majority of the patients (85%) made an appointment with a rheumatologist within a month of receiving a referral. 25% of patients waited 4 months or longer to see a rheumatologist. Diagnostic delays result from both the level of patients' awareness (ignoring early symptoms) and improper functioning of the health care system. In the case of the health care system, the source of delays is not only "queues to rheumatologists", but also referring patients to non-rheumatologists.


Evaluation of the results of posterior approach in thoracic disc herniation surgery.
The incidence of symptomatic intervertebral disc hernias in the thoracic segment is estimated at 1 case per million people per year, which is about 0.25-0.75% of all symptomatic intervertebral disc hernias and 0.15-1.85% of operative intervertebral disc diseases. The aim of the study was to assess the results of the surgical treatment of symptomatic discopathy in the thoracic spine through the posterior approach. The results of the surgical treatment of 52 patients (35 women, 17 men) with symptomatic thoracic disc herniation in the Department of Neuroorthopedics in the years 2012-2019 were analyzed retrospectively. The neurological and functional status of patients before and after the surgery was assessed, as well as the average duration of the surgery and hospitalization, perioperative complications, intraoperative blood loss and the number of reoperations. Radiculopathy and myelopathy were the main indications for surgery. The largest group included patients operated on in the 5th and 6th decades of life, with women being the majority (67%). Hernia of the distal thoracic spine, i.e. Th10-Th11-Th12-L1, was most often operated on. According to the Frankel scale, the largest number of patients (47 before the surgery and 48 after the surgery) were qualified for groups D and E. As regards the WISCI scale the largest group of patients was classified as level 20. The rate of complications was 7%, the rate of neurological complications was 5.2% and the rate of reoperations was 3.5%. The vast majority of discopathies in the thoracic spine occur at lower levels, i.e. Th10-Th11-Th12-L1. The analysis of the functional status after the surgery of thoracic discopathy based on 2 scales showed a greater usefulness of the WISCI scale than the Frankel scale. A larger number of patients changed the group after surgery in the WISCI scale than in the Frankel scale. Therefore, we can conclude that the WISCI scale is more accurate in assessing the functional state of patients operated on due to thoracic discopathy.


Platelet adhesion onto the wall of a flow chamber with an obstacle.
In the present study, the data of the initial adhesion of platelets onto the wall of a flow chamber with an obstacle in steady human blood flows were obtained. The flowfields and the distribution of stress-related factors were simulated numerically by a finite volume method and the fluid dynamic effect on the platelet adhesion is discussed. In addition to the wall shear effect, the normal stress effect was also taken into account. A parameter Vn/[Vt] was devised to assess the combined effect of both shear and normal forces in platelet adhesion. It was found that the peak adhesion occurred next to, but not on, the impingement point on the obstacle where the value of Vn/[Vt] was negative. In these regions, direct impact played a major role in platelet adhesion. On the other hand, near the separation point before the obstacle where Vn/[Vt] was insignificant, the mechanism was believed to be different from that in the direct impact region. Denser adhesion there might be caused by the accumulation and frequent collision of particles due to flow retardation and/or detour of the flow path. Interestingly, relatively low adhesion was found inside the recirculation regions. These results show that the normal stress effect (impingement) should be considered in platelet adhesion in addition to the shear effect.


In-Vitro Screenings for Biological and Antioxidant Activities of Water Extract from Theobroma cacao L. Pod Husk: Potential Utilization in Foods.
Increasing production of cocoa (Theobroma cacao L.) leads to a higher environmental burden due to its solid waste generation. Cocoa pod husk, one of the major solid wastes of cocoa production, contains rich bioactive compounds unveiling its valorization potential. With that in mind, our research aimed to explore the biological and antioxidant activities of aqueous extracts from cocoa pod husks. In this present work, cocoa pod husk was extracted using water and subsequentially partitioned using n-hexane, ethyl acetate, and methanol. The antimicrobial investigation revealed that the ethyl acetate solubles were active against the Staphylococcus aureus, Escherichia coli, and Candida albicans, where at a 20% w/v concentration, the inhibition diameters were 6.62 ± 0.10, 6.52 ± 0.02, and 11.72 ± 0.36 mm, respectively. The extracts were found non-toxic proven by brine shrimp lethality tests against Artemia salina with LC50 scores ranging from 74.1 to 19,054.6 μg/mL. The total phenolic content and total flavonoid content were obtained in the range of 47.44 to 570.44 mg/g GAE and 1.96 to 4.34 mg/g QE, respectively. Antioxidant activities of the obtained extracts were revealed by 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) assay with EC50 reached as low as 9.61 μg/mL by the ethyl acetate soluble. Phytochemical screening based on gas chromatography-mass spectroscopy analysis on the sample with the highest antioxidant activities revealed the dominant presence of three phytosterols, namely gamma-sitosterol, stigmasterol, and campesterol.


Efficacy of combination of DFMO and diminazene aceturate in the treatment of late stage Trypanosoma brucei brucei infection in rats.
The therapeutic activity of difluoromethylornithine and diminazene aceturate alone and in combination was investigated in albino rats with late stage Trypanosoma brucei brucei infection. The criteria used in the assessment of the trypanocidal effect of the compounds include the degree of parasitaemia, and frequency of relapse and death. DFMO (4 percent administered in drinking water for 6 days) and diminazene aceturate (10 mg per kg intraperitoneal) produced an intermittent aparasitaemia with relapse occurring in the two groups. A combination of the two agents produced a permanent cure. The combination of the two agents appear to act synergistically in the treatment of T.b. brucei C.N.S. infection in rats.


Antiproliferative effects of mistletoe (Viscum album L.) extract in urinary bladder carcinoma cell lines.
The aim of the study was to evaluate the antiproliferative potency of Viscum album extract (VA-E) in human bladder carcinoma cell lines with regard to its possible use for intravesical therapy of superficial bladder cancer. Proliferation (MTT-test or 3H-thymidine incorporation), necrotic disintegration (3H-thymidine release of prelabelled cells) and portions of apoptotic and/or necrotic cells (Annexin-V binding, propidium iodide (PI) labelling and DNA-fluorescence profiles by flow cytometry) were measured in four different human bladder carcinoma cell lines (T24, TCCSUP, J82 and UM-UC3) cultured in vitro. Antiproliferative effects of VA-E were observed in the four bladder carcinoma cell lines tested. Metabolic activity could also be completely abrogated by short-time contact of the cells with VA-E. Apoptosis and necrosis, as underlying mechanisms of action, were differentially expressed by the different cell lines. VA-E and cytotoxic proteins, i.e., mistletoe lectins (ML) and viscotoxins (VT), were able to block the growth of bladder carcinoma cells. Together with the immunomodulating properties of VA-E, the observed antiproliferative potency might give a rationale for the topical intravesical application of VA-E for the treatment of superficial bladder cancer.


Mechanical monolithic horizontal sensor for low frequency seismic noise measurement.
This paper describes a mechanical monolithic horizontal sensor for geophysical applications developed at the University of Salerno. The instrument is basically a monolithic tunable folded pendulum, shaped with precision machining and electric discharge machining, that can be used both as seismometer and, in a force-feedback configuration, as accelerometer. The monolithic mechanical design and the introduction of laser interferometric techniques for the readout implementation makes it a very compact instrument, very sensitive in the low frequency seismic noise band, with a very good immunity to environmental noises. Many changes have been produced since last version (2007), mainly aimed to the improvement of the mechanics and of the optical readout of the instrument. In fact, we have developed and tested a prototype with elliptical hinges and mechanical tuning of the resonance frequency together with a laser optical lever and a new laser interferometer readout system. The theoretical sensitivity curve for both laser optical lever and laser interferometric readouts, evaluated on the basis of suitable theoretical models, shows a very good agreement with the experimental measurements. Very interesting scientific result is the measured natural resonance frequency of the instrument of 70 mHz with a Q=140 in air without thermal stabilization. This result demonstrates the feasibility of a monolithic folded pendulum sensor with a natural resonance frequency of the order of millihertz with a more refined mechanical tuning.


Evaluation of sequence alignments and oligonucleotide probes with respect to three-dimensional structure of ribosomal RNA using ARB software package.
Availability of high-resolution RNA crystal structures for the 30S and 50S ribosomal subunits and the subsequent validation of comparative secondary structure models have prompted the biologists to use three-dimensional structure of ribosomal RNA (rRNA) for evaluating sequence alignments of rRNA genes. Furthermore, the secondary and tertiary structural features of rRNA are highly useful and successfully employed in designing rRNA targeted oligonucleotide probes intended for in situ hybridization experiments. RNA3D, a program to combine sequence alignment information with three-dimensional structure of rRNA was developed. Integration into ARB software package, which is used extensively by the scientific community for phylogenetic analysis and molecular probe designing, has substantially extended the functionality of ARB software suite with 3D environment. Three-dimensional structure of rRNA is visualized in OpenGL 3D environment with the abilities to change the display and overlay information onto the molecule, dynamically. Phylogenetic information derived from the multiple sequence alignments can be overlaid onto the molecule structure in a real time. Superimposition of both statistical and non-statistical sequence associated information onto the rRNA 3D structure can be done using customizable color scheme, which is also applied to a textual sequence alignment for reference. Oligonucleotide probes designed by ARB probe design tools can be mapped onto the 3D structure along with the probe accessibility models for evaluation with respect to secondary and tertiary structural conformations of rRNA. Visualization of three-dimensional structure of rRNA in an intuitive display provides the biologists with the greater possibilities to carry out structure based phylogenetic analysis. Coupled with secondary structure models of rRNA, RNA3D program aids in validating the sequence alignments of rRNA genes and evaluating probe target sites. Superimposition of the information derived from the multiple sequence alignment onto the molecule dynamically allows the researchers to observe any sequence inherited characteristics (phylogenetic information) in real-time environment. The extended ARB software package is made freely available for the scientific community via http://www.arb-home.de.


Delayed posttraumatic Propionibacterium acnes endophthalmitis in a child.
A 7-year-old boy presented with granulomatous anterior uveitis after an unrecognized penetrating injury in the same eye 2 months previously. The uveitis was unresponsive to topical corticosteroid therapy, lensectomy with anterior vitrectomy, and administration of intraocular and subconjunctival injections of vancomycin. Pars plana vitrectomy, capsulectomy, and injection of intravitreal vancomycin were eventually performed, leading to complete resolution of the intraocular inflammation. Culture and histopathologic examination of a capsular specimen confirmed sequestered Propionibacterium acnes infection. This case demonstrates that P. acnes may cause delayed endophthalmitis following penetrating trauma and may persist within capsular remnants in the aphakic eye.


Integration of Internet-based learning and traditional face-to-face learning in an RN-BSN course in Korea.
This article describes the development of and student satisfaction with a distance learning course using both online and face-to-face methods in an RN-BSN program in Korea. Four steps were used for course development: (1) assessment of students' learning needs and determination of objectives of the course, (2) designing of module/assignment instructions, (3) development of the Internet-based learning platform, and (4) evaluation of course and Internet-based learning platform. Student satisfaction was evaluated by using a 4-point Likert-type questionnaire. Forty-eight (92.3%) questionnaires were returned. Overall satisfaction with this course was high (X = 3.29). Appropriateness of learning methods (X = 3.35) was rated the most satisfactory, followed by appropriateness of content (X = 3.31). Most of the students enjoyed the course and they wanted more nursing courses to be offered through the online and on-site format. On the basis of the findings, additional courses using both online and face-to-face methods for RN-BSN students should be developed and implemented for RN-BSN nursing programs in Korea.


The effects of EPA, DHA, and aspirin ingestion on plasma lysophospholipids and autotaxin.
Lysophophatidylcholine (LPC) and lysophosphatidic acid (LPA) are potent lysolipid mediators increasingly linked with atherosclerosis and inflammation. A current model proposing that plasma LPA is produced when LPC is hydrolyzed by the enzyme autotaxin has not been rigorously investigated in human subjects. We conducted a clinical trial of eicosapentaenoic acid/docosahexaenoic acid (EPA/DHA) and aspirin ingestion in normal volunteers. Fasting blood samples were drawn at baseline and after 4-week supplementation with EPA/DHA (3.4 g/d) with and without aspirin (650 mg). Plasma LPC and LPA species and autotaxin activity were measured. EPA-LPC and DHA-LPC concentrations increased significantly with EPA/DHA supplementation whereas EPA- and DHA-LPA did not. Autotaxin activity was unaffected by any treatment, and aspirin had no effect on any endpoint. Taken together, our data demonstrate that plasma LPC, but not LPA, species can be dynamically regulated by dietary supplementation, and argue against a simple model of LPA generation via LPC hydrolysis.


Development of ICF core sets for head and neck cancer.
Based on the International Classification of Functioning (ICF)-Disability and Health, participants from different professional and cultural backgrounds were invited to achieve consensus on a first version of ICF Core Set for head and neck cancer (HNC). It was designed to set standards for the assessment of functioning in HNC. The ICF was adopted by the World Health Organization (WHO) in 2001 and was used as the frame of reference. Preselection of potential ICF categories was based on 4 different preparatory studies: patient interviews, health professional surveys, literature review, and multicenter study applying ICF-nomenclature. After training on the ICF, the results of preparatory studies were presented to 21 invited participants to vote in a formal consensus process on both the Brief and Comprehensive ICF Core Set for HNC. Participants came from all 6 WHO world regions, covering 12 different countries. Professional backgrounds included otorhinolaryngologists, maxillofacial surgeons, medical/radiation oncologists, psychologists, physiotherapists, nurses, and social workers. The Comprehensive ICF Core Set for HNC included 112 categories (8% of entire ICF) and the Brief ICF Core Set for HNC included 19 categories (1% of ICF). A first version of ICF Core Sets for HNC was defined. Further validation is in process.


Landmark Localization for Cephalometric Analysis Using Multiscale Image Patch-Based Graph Convolutional Networks.
Accurate and robust cephalometric image analysis plays an essential role in orthodontic diagnosis, treatment assessment and surgical planning. This paper proposes a novel landmark localization method for cephalometric analysis using multiscale image patch-based graph convolutional networks. In detail, image patches with the same size are hierarchically sampled from the Gaussian pyramid to well preserve multiscale context information. We combine local appearance and shape information into spatialized features with an attention module to enrich node representations in graph. The spatial relationships of landmarks are built with the incorporation of three-layer graph convolutional networks, and multiple landmarks are simultaneously updated and moved toward the targets in a cascaded coarse-to-fine process. Quantitative results obtained on publicly available cephalometric X-ray images have exhibited superior performance compared with other state-of-the-art methods in terms of mean radial error and successful detection rate within various precision ranges. Our approach performs significantly better especially in the clinically accepted range of 2 mm and this makes it suitable in cephalometric analysis and orthognathic surgery.


Effect of monoclonal and polyclonal antibodies against conjugated neurotransmitter on experimental venous thrombosis.
Vasomotoricity in veins is largely controlled by the sympathetic nervous system. Norepinephrine and acetylcholine modulate the vasoconstrictor effect mediated by alpha-adrenergic receptors. Our objective was to study the role of local vasomotoricity in venous thrombosis, and particularly to determine some of the factors regulating it. Although no attempt has been described until now, polyclonal and monoclonal antibodies against L-dihydroxyphenylalanine, acetylcholine, and dopamine were administered in an experimental model of venous thrombosis. In view of the rather high specific antibody recognition for each compound, the presence of endogenous epitopes of L-dopa-like molecules and acetylcholine-like molecules in the circulation can be postulated. The results of this study may open an important new approach in the treatment of vascular diseases.


Folding of beta-sheets in membranes: specificity and promiscuity in peptide model systems.
The interactions that drive the folding of beta-barrel membrane proteins have not been well studied because there have been few available model systems for membrane beta-sheets. In this work, we expand on a recently described model system to explore the contributions of interstrand hydrogen bonds, side-chain/side-chain interactions and side-chain/membrane interactions to beta-sheet formation in membranes. These experiments are based on the observation that the hydrophobic hexapeptide acetyl-Trp-Leu-Leu-Leu-Leu-Leu-OH (AcWLLLLL) folds, cooperatively and reversibly, into oligomeric, antiparallel beta-sheets in phosphatidylcholine membranes. To systematically characterize the important interactions that drive beta-sheet formation in membranes, we have used circular dichroism spectroscopy to determine the membrane secondary structure of each member of a complete host-guest family of related peptides of the form AcWLL-X-LL, where X is one of the natural amino acids. Peptides with hydrophobic X-residues of any size or character (X=Ala, Val, Ile, Leu, Cys, Met, Phe and Trp) form similar beta-sheets in membranes, while peptides with any polar X-residue or Gly or Pro at the X-position are random-coils, even when bound to membranes at high concentrations. The observed membrane sheet preferences correlate poorly with intrinsic sheet propensity scales measured in soluble proteins, but they correlate well with several membrane hydrophobicity scales. These results support the idea that the predominant interactions of the side-chains in membrane-bound beta-sheets are with the membrane lipids, and that backbone hydrogen bonding is the major driving force for the stabilization of beta-sheets in membranes.


Playing-related musculoskeletal problems in children learning instrumental music: the association between problem location and gender, age, and music exposure factors.
Playing-related musculoskeletal problems (PRMP) are common in adult musicians, and risk factors include gender, music exposure, and particularly instrument type. Emerging evidence suggests PRMP are common in children and adolescents and that risk factors may be similar. The aim of this study was to determine the prevalence of PRMP, both symptoms and disorders, and PRMP location in children and adolescents as well as the associations with gender, age, and music exposure factors such as type and number of instruments and playing time. This study surveyed 731 children (460 females), aged 7 to 17 years, studying instrumental music in government schools in Perth, Australia. Lifetime and monthly symptoms, monthly disorders (inability to play an instrument as usual), and PRMP location were examined. Chi-squared analyses were used to evaluate associations between gender, age, music exposure, and PRMP outcomes. Logistic regression evaluated the independent association of these potential risk factors with PRMP prevalence and location. RESULTS) Sixty-seven percent of students reported PRMP symptoms at some point, 56% reported them within the last month, and 30% reported an inability to play as usual within the last month. After adjustment for gender and age, the type of instrument played (upper and lower strings, woodwind, and brass) was significantly associated with all PRMP (p<0.005) and playing three instruments was protective against monthly symptoms (OR 0.43, p=0.05). The right (24%) and left (23%) hand/elbow and neck (16%) were the most commonly reported PRMP locations, with females affected significantly more than males Prevalence of PRMP increased with age for neck (p<0.001), mid-back (p=0.007), low back (p<0.001), right hand/elbow (p=0.008), and mouth (p=0.011). PRMP prevalence for the left hand/elbow and right and left shoulders demonstrated high rates across all childhood ages. Odds ratios for the risk of PRMP in different locations varied by instrument played. The high prevalence and location of PRMP are important issues for child and adolescent instrumentalists. Gender, age, and music exposure are associated with PRMP risk and need to be addressed to ensure musicians' personal well-being and musical longevity.


Act to amend the Unemployment Insurance Act, 1971, 29 March 1988.
This Act amends the Canadian Unemployment Insurance Act, 1971, to do the following, among other things: 1) authorize maternity benefits to be paid to a father who cares for his baby when the mother is dying or is disabled and 2) allow a mother to postpone her postnatal leave until her child leaves the hospital.


Bilateral frontal intracranial xanthoma associated with type II hyperlipidemia in a 42-year-old woman: illustrative case.
Xanthoma is a granulomatous lesion that develops from leakage of circulating serum lipoprotein into the surrounding tissue. An isolated intracranial xanthoma is rarely reported and usually misdiagnosed. Intracranial xanthoma is also rarely found in patients with hyperlipidemia. To the best of the authors' knowledge, no previous studies and literature have reported bilateral involvement of intracranial xanthoma in the frontal lobe. The authors reported an unusual case of bilateral involvement of intracranial xanthoma in the frontal lobe with associated type II hyperlipidemia in a 42-year-old woman. Macroscopically, the tumor had an appearance of greyish-yellow color with a brittle, solid consistency. Histopathological examination revealed numerous lipid-laden macrophages surrounded by a cystic, necrotic, partially hemorrhagic area, with some parts consisting of hemosiderophages and proliferative capillary blood vessels. The histopathological findings indicated the characteristics of xanthoma. Bilateral frontal intracranial xanthoma with associated type II hyperlipidemia is an unusual finding. Despite its rarity and wide variety of radiological presentations, it should be considered one of the differential diagnoses of lesions that develop intracranially and intraaxially. Confirmation with histopathological examination is needed to exclude from other differential diagnoses.


Over-expression of miR-145 enhances the effectiveness of HSVtk gene therapy for malignant glioma.
This study attempts to combine two findings toward developing a rational strategy for improved therapy for glioma. One of the findings, made in this pre-clinical study, is that an hTERT-targeting ribozyme-controlled HSVtk gene (hTERT.Rz.HSVtk) exerts anti-tumor effects. The second observation is that the over-expression of a small noncoding RNA, miR-145, causes down-regulation of metastasis-related genes, such as PLAUR, SPOCK3, ADAM22, SLC7A5 and FASCN1. While blocking in vivo tumor growth only slightly, over-expression of miR-145 significantly inhibits both the migration and invasion of U87MG/U373MG glioma cells. We hypothesized that a simultaneous adenoviral-mediated over-expression of miR-145 might enhance the anti-tumor effects of hTERT.Rz.HSVtk and that a combination therapy with miR-145 and the HSVtk gene would be an effective approach for treating glioma. We tested this by developing adenoviral vectors that over-express miR-145 under the CMV promoter and employing them in combination with hTERT.Rz.HSVtk expression, both in vitro and in vivo in animal studies. We found that the adenovirus Ad5CMV.Rz.HSVtk.miR145 harboring an HSVtk expression cassette plus miR-145 produced prolonged survival benefits compared to administration of Ad5CMV.Rz.HSVtk or Ad5CMV.miR-145 alone. This study demonstrates that combination therapy using the hTERT.Rz.HSVtk gene together with miR-145 over-expression produces enhanced anti-tumor effects compared to that resulting from hTERT.Rz.HSVtk gene therapy alone.


Comparison of central corneal thickness measurements using Pentacam and ultrasonic pachymetry in post-LASIK eyes for myopia.
To compare central corneal thickness (CCT) measurements obtained using the Pentacam Scheimpflug system with those obtained using DGH ultrasound pachymetry (UP) in post-laser in situ keratomileusis (LASIK) eyes for myopia. In a prospective study, measurement agreement was assessed in 143 eyes of 72 post-LASIK patients using both the Pentacam and UP at the Eye Consultants Center in Riyadh, Saudi Arabia. The mean CCT was 522 +/- 42.2 microm with the Oculus Pentacam and 516.2 +/- 40.6 microm with UP. The Bland-Altman plot showed that the mean +/- SD for the differences between the 2 devices was 5.8 +/- 13.6 microm, with 95% confidence interval limits ranging from -20.9 microm to 32.6 microm. A test of statistical significance indicated that the mean differences of 5.8 +/- 13.6 microm differed significantly from zero (p<0.001; Wilcoxon signed-rank test), thus indicating that the Pentacam measurements tended to overestimate CCT compared with UP. Analysis of regression showed a high correlation between the values obtained with both devices (r=0.947, p<0.001). In post-LASIK myopic eyes, although a high correlation has been shown between Pentacam and UP measurements, Pentacam tends to overestimate CCT compared to UP. Pentacam probably cannot be used interchangeably with UP in post-LASIK eyes for myopia.


Screening for Fabry disease among male patients on hemodialysis in Awaji Island.
Fabry disease (FD) manifests decreased α-galactosidase A (α-Gal A) activity and multiorgan damage. There are some undiagnosed cases of the condition among patients on dialysis. The prevalence of FD may also vary with the region. Among 227 male patients undergoing maintenance hemodialysis in Awaji Island, a remote island in Japan, 201 (88.5%) were included in this study. Patients with α-Gal A activity <5.0 pmol/h/disk proceeded to secondary screening. Patients with positive secondary screening underwent further genetic analysis. The number of patients with a family history of cardiac, cerebrovascular, and kidney diseases was 31 (15.4%), 23 (11.4%), and 31 (15.4%) patients, respectively. Although three patients (1.5%) had low α-Gal A activity, none of them was positive in the secondary screening. We could not identify any male hemodialysis patient with FD in Awaji Island, even though some patients had a family history of kidney and cardiovascular diseases.


Targeting smokers with low readiness to change with tailored and nontailored self-help materials.
Few smoking cessation self-help materials are available for smokers who are not planning to quit. However, computer-tailored interventions can be designed specifically for these smokers. In a large randomized field trial (N = 843), two different tailored smoking cessation self-help interventions (multiple tailoring and single tailoring) and one standardized smoking cessation self-help guide were compared with a no-information control group and with each other. The contents of the tailored interventions were adapted to individuals' self-reported stage of change, outcome expectations, self-efficacy levels, and smoking behavior. The primary outcome measure was forward stage transition. The standardized self-help guide had no effect. Among smokers who were not planning to quit within the next 5 years the multiple-tailored intervention was more effective than the single-tailored intervention. This pattern was supported by the cognitive changes caused by the interventions. Among smokers who were planning to quit within the next 5 years but not within the next 6 months, none of the self-help materials had any effect. The present results show that the self-help material currently available in the Netherlands, the standardized self-help guide, was not effective among smokers with low readiness to change. However, computer-generated tailored interventions seem a promising means of communicating information on smoking and smoking cessation to these smokers.


The effect of diazepam on patients' memory.
Ten patients who were prescribed daily doses of diazepam for the treatment of anxiety, insomnia, or psychosomatic symptoms were assessed repeatedly on measures of short-term and long-term memory on and off the drug. Both kinds of memory, especially the latter, appeared detrimentally affected by the drug. However, dosage seemed to be inversely related to the degree of memory impairment. In general, the results are consistent with the hypothesis that diazepam interferes with the memory consolidation process. The negative relationship between drug dosage and degree of memory impairment might be due to habituation toward this particular side effect by heavier drug users. It is suggested that on theoretical grounds, the use of diazepam in conjunction with the behavioral psychotherapies may be contraindicated.


The role of endoscopic ultrasound on the preoperative T staging of gastric cancer: A retrospective study.
Endoscopic ultrasonography (EUS) is used for preoperative assessment of gastric cancer. However, recent studies suggested that EUS staging accuracy is lower than previously thought. We aimed to assess EUS efficacy and image characteristics in preoperative gastric cancer T staging.A retrospective review of clinical and imaging features of 232 gastric carcinoma patients who underwent preoperative EUS assessment of T stage was performed. Only cases with tumor-free resection margin status and no metastases were enrolled. Comparisons of preoperative EUS and postoperative histopathological stagings were also performed to identify vital EUS image features for evaluating gastric carcinoma.EUS accuracy for T staging was 64.2% (149/232) with the highest accuracy for T3 (75.0%). Enlarged lymph nodes, well differentiated histological type and Borrmann IV type were associated with diagnostic accuracy in predicting tumor invasion. Although no factors were associated with overstaging, circumferential lesions ≥1/2, signet ring cell adenocarcinoma, and Borrmann IV type had significantly higher risks of understaging. Gastric wall outer edge irregularity was also an indicator of serosal involvement with a sensitivity of 82.0%. The pancreas and colon were more frequent disease extension sites than previously predicted.Although EUS is likely the best and most accurate option that we have used to stage gastric cancer, the finding that factors including circumferential lesions, signet ring cell adenocarcinoma, and Borrmann IV type carcinoma were more frequently related to incorrect staging warrants attention.


[Ageing and degeneration of human lumbar intervertebral discs].
Intervertebral discs undergo serious age-related changes. It is generally accepted that degeneration of discs begins during the second decade of life, and it is well known that other structures of spine do not change as fast as the intervertebral discs. The most extensive degenerative changes occur in the nucleus pulposus, including degradation of proteoglycans aggregates with its fragmentation, dehydration, and loss of viable cells. Data available in literature, suggests that the most critical factor contributing to the degeneration, is increasing volume of the disc due to its growth, resulting in longer nutritional pathways and insufficient nutrition.


Metabolic responses associated with deer hunting.
Deer hunting is a popular recreational activity with a high rate of cardiovascular events. Previous studies have demonstrated large HR responses during deer hunting. This study compared the HR and metabolic costs of maximal treadmill (TM) exercise with those of hiking while deer hunting and while dragging a deer. Healthy male volunteers (N = 16) performed a maximal TM exercise test, a 0.8-km hiking test, and a 0.4-km dragging test over lightly rolling terrain. VO2 was measured by portable spirometry and HR by radiotelemetry. HR averaged 74.0 +/- 7.0% and 89.1 +/- 4.5% of peak TM HR during the hike and drag, respectively. The peak HR observed during hiking and dragging was 83.2 +/- 6.0% and 94.9 +/- 4.2% of peak TM HR, respectively. VO2 averaged 62.2 +/- 15.8% and achieved a peak of 77.2 +/- 19.0% of TM VO2 while hiking. This corresponded to 86.8 +/- 17.3% and 108.1 +/- 22.3% of ventilatory threshold (VT), respectively. VO2 averaged 72.3 +/- 21.0% and achieved a peak of 91.2 +/- 21.4% of peak TM VO2 while dragging the deer. This corresponded to 101.5 +/- 27.7% and 128.5 +/- 26.8% of VT, respectively. The VO2/HR relationship showed significant (P < 0.05) difference between the dragging test and the TM test with a disproportionately high HR. The VO2/HR relationship between the hiking and TM tests was comparable. In part, the previously described large HR responses and high rate of cardiovascular complications associated with deer hunting may attributable to the elevated metabolic costs of associated activities.


FT-IR Spectral Signature of Sensitive and Multidrug-Resistant Osteosarcoma Cell-Derived Extracellular Nanovesicles.
Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents. Despite aggressive treatment regimens, the outcome is unsatisfactory, and multidrug resistance (MDR) is a pivotal process in OS treatment failure. OS-derived extracellular vesicles (EVs) promote drug resistance to chemotherapy and target therapy through different mechanisms. The aim of this study was to identify subpopulations of osteosarcoma-EVs by Fourier transform infrared spectroscopy (FT-IR) to define a specific spectral signature for sensitive and multidrug-resistant OS-derived EVs. EVs were isolated from sensitive and MDR OS cells as well as from mesenchymal stem cells by differential centrifugation and ultracentrifugation. EVs size, morphology and protein expression were characterized. FT-IR/ATR of EVs spectra were acquired in the region of 400-4000 cm-1 (resolution 4 cm-1, 128 scans). The FT-IR spectra obtained were consistently different in the EVs compared to cells from which they originate. A specific spectral signature, characterized by a shift and a new band (1601 cm-1), permitted to clearly distinguish EVs isolated by sensitive and multidrug-resistant OS cells. Our data suggest that FT-IR spectroscopy allows to characterize and define a specific spectral signature for sensitive and MDR OS-derived EVs.


Lewis Weil v. State of Israel and others, 1987.
The Supreme Court of Israel held that a prisoner has no right to special leave for conjugal relations in order to fulfill the commandment to "be fruitful and multiply." While it stated that the right to matrimonial relations is a basic human right and suggested that such a leave policy would be desirable, it also concluded that existing rules and regulations on prisoner's visits were not unreasonable, and judicial intervention was not warranted.


CT scan findings in mild head trauma: a series of 2,000 patients.
The present study describes the cranial computed tomography (CT) scan findings of 2,000 cases of mild head trauma (HT) in Curitiba, Southern Brazil. The mean age of the entire series was 30.8 +/-19 years. The overall male to female ratio was 2:1. The most common causes of head injury were interpersonal aggression (17.9%), falls (17.4%), automobile accidents (16.2%), falls to the ground (13.1%) and pedestrian injuries (13 %). Alcohol intoxication was associated with HT in 158 cases (7.9%). A normal CT scan was seen in 60.75% (1215) and an abnormal CT scan in 39.25% (785) of patients. Out of 785 abnormal CT scan, 518(65.9%) lesions were related to HT. The most common CT scan HT related findings were: soft tissue swelling (8.9 %), skull fractures (4.3 %), intracranial and subgaleal hematomas (3.4% and 2.4 %), brain swelling (2 %) and brain contusion (1.2%). Out of 785 abnormal CT scans, 267 (34.1%) lesions were not related to head trauma. Incidental CT scan findings included brain atrophy (5.9%), one calcification (5.2%) several calcifications (2.4%) (probably neurocysticercosis in most cases), ischemic infarct (1.9%) and leukoaraiosis (1.3%). These findings showed the importance of CT scan examination in mild head injuries. Further studies to identify mild HT patients at higher risk of significant brain injury are warranted in order to optimize its use.


The Role of Colonoscopy in the Diverticular Disease.
Colonic diverticula are one of the most frequent conditions found during the endoscopic examination of the lower digestive tract, interestingly in >70% of people after 80 years old. Of them, only a few percentage develop complications such as acute diverticulitis or diverticular bleeding. Up to now, colonoscopy represents the most important diagnostic and therapeutic tool on the hands of the clinicians. On the basis of this the need for a standardized and reproducible approach is now emerging. This short review article is tasked to point out some open issues concerning the role of colonoscopy in diverticular disease.


Does a lean prepregnancy body mass index influence outcome in pregnancies complicated by mild preeclampsia remote from term?
To determine the influence of a lean prepregnancy body mass index (BMI) on pregnancy outcome in women with mild preeclampsia. A matched cohort design was used. A total of 99 pregnant women with mild preeclampsia and a nonobese prepregnancy BMI (22-28 kg/m2) were matched 1 : 1 for gestational age at diagnosis, race, and parity to 99 women with mild preeclampsia, but a lean prepregnancy BMI (< or = 20 kg/m2). All patients were enrolled in an outpatient management program between 24 and 36 weeks' gestation for a minimum of 2 days, had singleton pregnancies, and exhibited proteinuria of > or = 1+ at the start of the program. Outpatient monitoring included automated blood pressure measurements and daily assessment of weight, proteinuria, and fetal movement. The mean gestational age at enrollment was 33.4 +/- 2.8 weeks for both groups. By matching, 65% of patients in each group were nulliparous and 79% of patients in each group were of the white race. There were no patients in either group with a history of preterm delivery. The mean gestational age at delivery (36.8 +/- 2.3 versus 36.3 +/- 2.3 weeks, p = 0.047) was greater in the lean prepregnancy BMI group with a lower cesarean section rate (32% versus 52%, p = 0.006) but similar mean birth weights (2728 +/- 698 versus 2679 +/- 802 g, p = 0.635). There were two perinatal deaths in the lean prepregnancy BMI group and one in the nonobese prepregnancy BMI group (p = 1.0). In patients with mild preeclampsia remote from term, a lean prepregnancy BMI was associated with a later gestational age at delivery and a reduced incidence of cesarean delivery. Neonatal outcomes, however, did not differ significantly between the groups.


Nitric oxide amplifies interleukin 1-induced cyclooxygenase-2 expression in rat mesangial cells.
Interleukin 1 and nitric oxide (NO) from infiltrating macrophages and activated mesangial cells may act in concert to sustain and promote glomerular damage. To evaluate if such synergy occurs, we evaluated the effect if IL-1 beta and NO on the formation of prostaglandin (PG)E2 and cyclooxygenase (COX) expression. The NO donors, sodium nitroprusside and S-nitroso-N-acetylpenicillamine, alone did not increase basal PGE2 formation. However, these compounds amplified IL-1 beta-induced PGE2 production. Similarly, sodium nitroprusside and S-nitroso-N-acetylpenicillamine by themselves did not induce mRNA and protein for COX-2, the inducible isoform of COX; however, they both potentiated IL-1 beta-induced mRNA and protein expression of COX-2. The stimulatory effect of NO is likely to be mediated by cGMP since (a) an inhibitor of the soluble guanylate cyclase, methylene blue, reversed the stimulatory effect of NO donors on COX-2 mRNA expression; (b) the membrane-permeable cGMP analogue, 8-Br-cGMP, mimicked the stimulatory effect of NO donors on COX-2-mRNA expression; and (c) atrial natriuretic peptide, which increases cellular cGMP by activating the membrane-bound guanylate cyclase, also amplified IL-1 beta-induced COX-2 mRNA expression. These data indicate a novel interaction between NO and COX pathways.


O-GlcNAc Modification Protects against Protein Misfolding and Aggregation in Neurodegenerative Disease.
Post-translational modifications (PTMs) of proteins are becoming the focus of intense research due to their implications in a broad spectrum of neurodegenerative diseases. Various PTMs have been identified to alter the toxic profiles of proteins which play critical roles in disease etiology. In Alzheimer's disease (AD), dysregulated phosphorylation is reported to promote pathogenic processing of the microtubule-associated tau protein. Among the PTMs, the enzymatic addition of N-acetyl-d-glucosamine (GlcNAc) residues to Ser/Thr residues is reported to deliver protective effects against the pathogenic processing of both amyloid precursor protein (APP) and tau. Modification of tau with as few as one single O-GlcNAc residue inhibits its toxic self-assembly. This modification also has the same effect on the assembly of the Parkinson's disease (PD) associated α-synuclein (ASyn) protein. In fact, O-GlcNAcylation ( O-linked GlcNAc modification) affects the processing of numerous proteins implicated in AD, PD, amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) in a similar manner. As such, manipulation of a protein's O-GlcNAcylation status has been proposed to offer therapeutic routes toward addressing multiple neurodegenerative pathologies. Here we review the various effects that O-GlcNAc modification, and its modulated expression, have on pathogenically significant proteins involved in neurodegenerative disease.


Hog1 mitogen-activated protein kinase plays conserved and distinct roles in the osmotolerant yeast Torulaspora delbrueckii.
Torulaspora delbrueckii has emerged during evolution as one of the most osmotolerant yeasts. However, the molecular mechanisms underlying this unusual stress resistance are poorly understood. In this study, we have characterized the functional role of the high-osmolarity glycerol (HOG) mitogen-activated protein kinase pathway in mediating the osmotic stress response, among others, in T. delbrueckii. We show that the T. delbrueckii Hog1p homologue TdHog1p is phosphorylated after cell transfer to NaCl- or sorbitol-containing medium. However, TdHog1p plays a minor role in tolerance to conditions of moderate osmotic stress, a trait related mainly with the osmotic balance. In consonance with this, the absence of TdHog1p produced only a weak defect in the timing of the osmostress-induced glycerol and GPD1 mRNA overaccumulation. Tdhog1Delta mutants also failed to display aberrant morphology changes in response to osmotic stress. Furthermore, our data indicate that the T. delbrueckii HOG pathway has evolved to respond to specific environmental conditions and to play a pivotal role in the stress cross-protection mechanism.


High correlation of Middle East respiratory syndrome spread with Google search and Twitter trends in Korea.
The Middle East respiratory syndrome coronavirus (MERS-CoV) was exported to Korea in 2015, resulting in a threat to neighboring nations. We evaluated the possibility of using a digital surveillance system based on web searches and social media data to monitor this MERS outbreak. We collected the number of daily laboratory-confirmed MERS cases and quarantined cases from May 11, 2015 to June 26, 2015 using the Korean government MERS portal. The daily trends observed via Google search and Twitter during the same time period were also ascertained using Google Trends and Topsy. Correlations among the data were then examined using Spearman correlation analysis. We found high correlations (>0.7) between Google search and Twitter results and the number of confirmed MERS cases for the previous three days using only four simple keywords: "MERS", "" ("MERS (in Korean)"), "" ("MERS symptoms (in Korean)"), and "" ("MERS hospital (in Korean)"). Additionally, we found high correlations between the Google search and Twitter results and the number of quarantined cases using the above keywords. This study demonstrates the possibility of using a digital surveillance system to monitor the outbreak of MERS.


Effects of competitive and non-competitive NMDA receptor antagonists on behavioral responses induced by 7-OH-DPAT and quinpirole in rats.
The administration of dizocilpine (0.06 mg kg-1), but not of CGP 43487 (0.75 mg kg-1), counteracted the hypolocomotion induced in the rat by low doses (5-80 microg kg-1) of the putative D3 dopamine agonist 7-OH-DPAT. Both NMDA antagonists did not change the reduced locomotion due to the administration of low doses (12.5-50 microg kg-1) of the D2 agonist quinpirole. In spite of the lack of effect of either NMDA receptor antagonist on D2 or D3 recognition sites, as shown by our radioligand binding studies, the behavioural findings suggest that the non-competitive, but not the competitive, NMDA receptor antagonist physiologically antagonizes dopamine D3 receptor mediated mechanisms. Both NMDA receptor antagonists failed to modify the hyperlocomotion induced by high doses (160 and 320 microg kg-1) of 7-OH-DPAT, whereas they inhibited the same behavioural response produced by high doses of quinpirole (150 and 300 microg kg-1). The different effect of the NMDA receptor antagonists on the behavioural responses induced by the dopaminergic agonists could be explained by the different activity of 7-OH-DPAT and quinpirole on D3/D2 receptors. Either dizocilpine or CGP 43487 induced stereotyped responses to high doses of 7-OH-DPAT. This suggests that both NMDA receptor antagonists could potentiate dopaminergic function in the striatum, a region critically involved in the generation of stereotyped behaviour.


[Summary of the multidisciplinary guideline 'Varicella'].
The multidisciplinary guideline 'Varicella' provides guidelines for diagnosis, therapy, and prevention of chickenpox. At the first pregnancy check, patients should be questioned about previous chickenpox; in case of a negative or doubtful history varicella zoster virus (VZV) serology is indicated. VZV antibody determination is also indicated in patients considered for immunosuppressive therapy and for healthcare workers with a negative VZV history who are in contact with immunocompromised patients. Administration of VZV immunoglobulin within 96 hours following VZV contact can mitigate the infection in pregnant women and patients with T-cell deficiency. VZV immunoglobulin treatment should be considered for newborn infants of mothers who developed chickenpox in the period from five days before to two days after delivery. Antivirals can reduce the severity of infection and are safe during pregnancy. Varicella vaccine protects against chickenpox, but is contraindicated in immunocompromised patients and pregnant women.


Case Report: Pediatric Recurrent Acute Liver Failure Caused by Neuroblastoma Amplified Sequence (NBAS) Gene Mutations.
Acute liver failure (ALF) in childhood is a rapidly progressive, potentially life-threatening condition that occurs in previously healthy children of all ages. However, the etiology of ~50% of cases with pediatric ALF remains unknown. We herein report a 4-year-old Chinese girl with recurrent ALF (RALF) due to a mutation in the neuroblastoma amplified sequence (NBAS) gene. The patient had suffered from multiple episodes of fever-related ALF since early childhood. She had also suffered from acute kidney injury, hypertension, mild pulmonary hypertension, pleural effusion, and hypothyroidism. A novel compound heterozygote mutation, c.3596G> A (p.C1199Y)/ex.9del (p.216-248del), in the NBAS gene was identified by whole-exome sequencing (WES). The missense mutation c.3596G> A (p. C1199Y) was inherited from her father, and ex.9del (p.216-248del) was inherited from her mother. The patient was managed with intensive treatments, such as renal replacement therapy (CRRT), intravenous antibiotics, and glucose infusion, and was discharged after full recovery. We identified a novel compound heterozygote mutation in the NBAS gene that caused fever-related RALF in a Chinese child, which further expands the mutational spectrum of NBAS.


Tissue-specific, temporal changes in cell adhesion to echinonectin in the sea urchin embryo.
Echinonectin is a dimeric, glycoprotein found in the hyaline layer of the developing sea urchin embryo. It was found that echinonectin supports adhesion of embryonic cells in vitro. Previous studies have shown that the protein hyalin also supports adhesion. The purpose of this study was to examine the specificity of cell-echinonectin interactions during sea urchin development. Primary mesenchyme cells (PMCs) ingress into the blastocoel during gastrulation. In the process the PMCs lose contact with the hyaline layer. It was found experimentally that differentiating PMCs decreased their adhesion to hyalin at the time of ingression. It was of interest, therefore, to determine whether there was a coordinate loss of adhesion to echinonectin at ingression as well. When cell-echinonectin interactions were quantified using a centrifugal force-based adhesion assay, it was shown that micromeres adhered well to echinonectin. At the time of ingression, PMCs displayed reduced adhesion to echinonectin just as had been found when hyalin was tested as a substrate. There was no change in adhesion of presumptive ectoderm or endoderm to echinonectin over the same time period. Early in gastrulation presumptive ectoderm and endoderm adhered to echinonectin only half as strongly as to equimolar concentrations of hyalin. After gastrulation endoderm cells were observed to retain the same relative affinity to hyalin and echinonectin, while ectoderm cells became equally adhesive for both hyalin and echinonectin. Quantitatively, this represents an overall increase in the affinity of ectodermal cells for echinonectin. Adhesion to combined substrata of echinonectin and hyalin was reduced but not abolished by monoclonal antibodies specific for echinonectin. The antibodies did not cross-react with hyalin. We conclude that both echinonectin and hyalin independently act as adhesive substrata for the developing sea urchin embryo. PMCs lose an affinity for echinonectin and ectodermal cells later increase their affinity for this substrate.