The effect of topographical and mechanical stimulation on the structural and functional anisotropy of cardiomyocytes grown on a circular PDMS diaphragm.
Due to their immature morphology and functional immaturity, cardiomyocytes have limited use as an in vitro disease model of the native heart. Mechanical stimulation induces structural growth in cardiomyocytes in vitro by addressing the electrical-mechanical interactions between the tissues. However, current in vitro models are restricted in their capacity to replicate the milieu observed in natural myocardium. Herein, we proposed a Galinstan strain sensor integrated nanogrooved circular PDMS diaphragm to mimic the native cardiac tissues. The impact of combined topographical and mechanical stimulation on cultured cardiomyocytes at various strain areas on a circular PDMS diaphragm is studied in detail. An inverted microscope is used to image live cells and video acquisition to study the contractility of cultured cardiomyocytes. The structural changes of the cultured cardiomyocytes are investigated by its sarcomere length and connexin-43 (Cx43) expression using immunocytochemistry analysis. Cyclic strain is found to promote structural development in cultured cardiomyocytes, and diaphragms with nano-groove patterns displayed increased contractile activity and gene expression (sarcomere length ∼1.97 ± 0.03 μm and normalized Cx43-1.57) as compared to flat diaphragms (sarcomere length ∼1.82 ± 0.02 μm and normalized Cx43-1.32). The nanogrooved circular diaphragm exhibited distinct stretching mechanisms at various places, with the equibi-axial stretching regions providing the optimal structural growth and formation of natural myocardium at the diaphragm's center. Cardiomyocytes that are more mature have the potential to produce a more realistic in vitro cardiac model for disease modeling and medication development.


Changes in composition of envelope proteins in adenylate cyclase- or cyclic AMP receptor protein-deficient mutants of Escherichia coli.
Synthesis of several envelope proteins in Escherichia coli K-12 is regulated by cyclic AMP and cyclic AMP receptor protein.


Factors affecting adherence to behaviours appropriate for the prevention of pressure injuries in people with spinal cord injury from Malaysia: a qualitative study.
Focus group qualitative study. To explore factors affecting adherence to behaviours appropriate for the prevention of pressure injuries (PIs) in people with spinal cord injury (SCI) in Malaysia. University Hospital, Malaysia METHODS: Four sets of focus group interviews were conducted, each with 5-10 participants, totalling 30 people with SCI. A trained interviewer used structured interviews designed to explore participants' experiences of complying with recommended behaviours for the prevention of PIs. All interviews were digitally recorded, transcribed, and analysed utilising thematic analysis. The factors that affected participants' adherence are classified into four main themes: (a) educational aspects, (b) internal drive, (c) social and environmental factors, and (d) post-SCI physiological changes. This qualitative study provides initial exploratory evidence regarding the thoughts, experience, and opinions pertaining to PI preventive behaviours within the Malaysian SCI population. The emerging themes contribute to an in-depth understanding of the competency of the Malaysian healthcare system in PI prevention, personal and societal factors influenced by the socio-demographic backgrounds, and disease-related factors that influence the adherence to such preventive interventions.


Detection of antibody to mycoplasma F38 in goat sera by an enzyme-linked immunosorbent assay.
An indirect enzyme-linked immunosorbent assay (ELISA) was developed to screen goat sera at a single dilution for antibody to mycoplasma F38. Antibody was detected in sera of six convalescent goats following experimental infection. Antibody was also detected in 34 sera three to four weeks after vaccination. No antibody was detected in 164 sera from goats without a history of vaccination or infection with contagious caprine pleuropneumonia. The ELISA was more sensitive than the complement fixation test in detecting antibody in vaccinated goats.


Recombinant Allergens Production in Yeast.
The methylotropic yeast Pichia pastoris has been extensively used in large-scale production of properly folded recombinant proteins. As an eukaryotic organism P. pastoris presents a series of advantages at expression and processing of heterologous proteins such as post-translational modifications, protein processing, and a reasonably sophisticated quality control of protein folding when compared against Escherichia coli. In this chapter, we describe the modified lab procedure for cloning and expression in Pichia pastoris of common food allergens sequences from the raw fruit to the fully folded biotinylated protein product.


Growth of magnetic nanowires on self-organized stripe templates: Fe on Pd-O/W(110).
The structural and magnetic properties of Fe-Pd nanostructures grown on regular alternating Pd and oxygen stripes on the W(110) surface are studied using SPELEEM methods. The self-organized Pd-O stripe template, formed at about 1000 °C and aligned with the [001] direction, has an average period of only few tens nm and is preserved upon quenching the sample temperature to ambient conditions. Fe is shown to preferentially bond to the Pd stripes, forming an Fe-Pd surface alloy within the stripe phase. The magnetic easy axis is found to be aligned perpendicular to the Fe-Pd stripe axis.


Prospective screening in familial nonmedullary thyroid cancer.
Approximately 8% of nonmedullary thyroid cancers are familial. The optimal age for screening in familial nonmedullary thyroid cancer (FNMTC) is unknown. Kindreds with FNMTC (2 or more first-degree relatives affected) were screened prospectively with thyroid ultrasonography. Fifteen kindreds showed an overall prevalence of thyroid nodule(s) ≥5 mm of 44% at screening; 19% in the second generation, and 90% in the generation anterior to the index case. The youngest age of detection was 10 years for thyroid nodules and 18 years for thyroid cancer. Microcalcification of thyroid nodules at screening was associated with a greater risk of cancer (P < .05). Family members diagnosed with thyroid cancer by ultrasonographic screening were diagnosed at a younger age and had a lower rate of extra thyroidal invasion (P < .05). In FNMTC, first-degree relatives 10 years or older, including the generation anterior to the index case, should have thyroid screening by ultrasonography, which may result in earlier diagnosis.


Mother and child hair cortisol during the COVID-19 pandemic: Associations among physiological stress, pandemic-related behaviors, and child emotional-behavioral health.
The current study assessed the associations between pandemic-related stressors and physiological stress, as indexed by hair cortisol concentration (HCC), for mothers and their children (N = 180) aged 5-14-years old (M = 8.91). The associations between maternal HCC and children's HCC and children's behavioral adjustment were also examined. Mothers reported on COVID-19-related behaviors and children's adjustment, and both mother and child participants collected and mailed hair samples between August and November of 2020. Results indicated that higher maternal HCC was correlated with living in a more urban environment, job loss, working from home, exposure to pandemic-related news, and social isolation. Child HCC was correlated with family job loss and social isolation. Mother HCC and child HCC were significantly associated, and this association was moderated by child age; younger children's HCC was more strongly associated with mothers' HCC than older children's HCC. Finally, maternal HCC was associated with greater child internalizing symptoms, but was not associated with children's externalizing symptoms. Child HCC was not associated with child behavior.


Pelvic osteotomy and symphysis reconstruction in bladder exstrophy: Early (2-6 years) results with a new (Double Door) symphysis reconstruction.
To describe the 2-6-years follow up of a combination of oblique pelvic osteotomies and a new method for symphysis reconstruction, with the aim of creating a stable pelvic ring that will not widen during growth. Five children were operated on between 1998 and 2003 at the age of 2 days to 8 months. One child had a cloacal exstrophy. A 'Double Door' plasty was performed from hinged cartilaginous flaps at either side of the symphysis diastasis. This was followed by primary fixation with heavy resorbable sutures and 6 weeks in vertical traction for the younger ones and a pelvic external fixator (for 3 months) for the older (>6 months). One child had a deep infection at 2 weeks postoperatively and healed with gradually increasing diastasis (39 mm at 3 years+2 months). All the others healed uneventfully and the symphysis stabilized after a few weeks. All had a stable symphysis diastasis of only 15-25 mm during the observation period. A stable, narrow symphysis can be created by combining oblique pelvic osteotomies with a Double Door plasty, allowing uro-genital reconstruction without interfering with pelvic growth or hip function.


A model to measure self-assessed proficiency in electronic medical records: Validation using maturity survey data from Canadian community-based physicians.
Adoption of electronic medical records (EMRs) does not necessarily translate to proficiency -referred to here as EMR maturity. To realize the full benefit of wide scale EMR adoption, the focus must shift from adoption to advancing mature use. This calls for validated assessment models so that researchers, health system planners and digital health developers can better understand what contributes to maturity among physicians. This research aims to validate a measurement model for self-assessed EMR maturity among community-based physicians. As part of an Ontario government-funded EMR adoption program, the EMR Maturity Model for community-based practices was adapted from a hospital-based EMR maturity model. A survey instrument was developed on the foundation of the new model and revised by experts and stakeholders. Content validity, face validity and user acceptance were established before survey administration. Internal consistency and construct validity of the model were tested after survey data were collected. Finally, physicians' comments collected via the survey were qualitatively analyzed to provide additional insights that can be applied to refinement of the model and survey. As of August 1, 2019, 1588 physicians completed the survey. Ordinal alpha tests for reliability and content validity yielded an alpha value of 0.86 across all key measures specifically associated with maturity. Among most of these, there was a pattern of weak to moderate significant (p < .0001) positive Spearman inter-correlations. One factor was extracted for items measuring dimensions of maturity and all factor loadings of the key measures were greater than 0.40. The fit of the one-factor model was moderately adequate. This indicates the model is valid and reliable, with consistency across key measures for measuring one factor: maturity. This is the first known validated model published in English that measures EMR maturity among community-based physicians. While the model is shown to be valid and reliable statistically and qualitative analysis supports this, there is room for improvement. Both the statistical analysis and portions of the qualitative analysis suggest areas of exploration to strengthen the model and survey. Future efforts will include refining the survey to improve user interface and accrue further data, as the sample to date is insufficient for generalizability.


A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis development.
Macrophages play a central role in the development of atherosclerosis through the accumulation of oxidized LDL (oxLDL). AIM (Spalpha/Api6) has previously been shown to promote macrophage survival; however, its function in atherogenesis is unknown. Here we identify AIM as a critical factor that protects macrophages from the apoptotic effects of oxidized lipids. AIM protein is induced in response to oxLDL loading and is highly expressed in foam cells within atherosclerotic lesions. Interestingly, both expression of AIM in lesions and its induction by oxidized lipids require the action of LXR/RXR heterodimers. AIM-/- macrophages are highly susceptible to oxLDL-induced apoptosis in vitro and undergo accelerated apoptosis in atherosclerotic lesions in vivo. Moreover, early atherosclerotic lesions in AIM-/-LDLR-/- double knockout mice are dramatically reduced when compared to AIM+/+LDLR-/- controls. We conclude that AIM production facilitates macrophage survival within atherosclerotic lesions and that loss of AIM decreases early lesion development by increasing macrophage apoptosis.


Localization of amylase and mucins in the major salivary glands of the mouse.
Antibodies against murine submandibular and sublingual mucins have been raised in rabbits. Both antisera appeared to be specific. Using these antibodies, the mucins were localized in the acinar cells of the submandibular and sublingual glands respectively. The dyed amylopectin method was used to estimate the activity of amylase in the salivary glands. The enzyme was localized either by a starch-substrate film method or with antibodies against purified parotid amylase. The activity of amylase in parotid homogenates is about 1000-fold higher than that in homogenates of either submandibular or sublingual glands, in which the activity was comparable. Amylase was localized in the acinar cells of the parotid gland with both localization techniques. In the sublingual gland, amylase was found predominantly in the stroma around the acini, and there was some evidence that amylase was present in the demilune cells as well. In the submandibular gland, contradictory results were obtained with both techniques. With the starch-substrate film method, amylase activity was found in the granular convoluted tubular cells, whereas immuno-reactive amylase could only be demonstrated in the acinar cells of this gland. It is concluded that in the submandibular gland amylase and mucin are present in the same cell type.


Implications of sentinel lymph node mapping on nodal staging and prognosis in colorectal cancer.
Sentinel lymph node (SN) mapping for staging in colorectal cancer remains controversial and needs to be validated before it can be implemented in daily practice. We prospectively assessed the effect of SN mapping on nodal staging and its implication on survival in patients with colorectal cancer. Between November 2005 and July 2009, 331 patients underwent a resection for colorectal cancer. In 189 patients (group A) an ex-vivo SN procedure was performed with immunohistochemical analysis of the SN. Tumour cell deposits between 0.2 mm and 2.0 mm were referred to as micrometastases (pN1mi+). The remaining patients (n = 142, group B) had standard nodal staging. Multivariate Cox regression analysis was performed to identify prognostic factors for disease recurrence. The average number of harvested lymph nodes was higher in group A than in group B (15.5 ± 7.3 vs 12.1 ± 5.2, P < 0.0001). After conventional staging, 81 (43%) patients of group A were judged to have nodal metastasis. This increased to 89 (47%) patients when immunohistochemically detected micrometastases were included. In group B, 50 (35%) patients had nodal metastasis. During follow up, a lower recurrence rate was seen in N0 patients after SN mapping compared with the conventional staging group (4%vs 15.2%, P = 0.04). The SN procedure (hazard ratio = 4.1) was an independent predictor of disease recurrence. The SN procedure results in a more accurate staging of patients with colorectal cancer. This is reflected by a better prognosis of N0 patients after SN mapping.


Real-life evaluation of the clinical, functional, and hematological effects of mepolizumab in patients with severe eosinophilic asthma: Results of a single-centre observational study.
Mepolizumab is a humanized monoclonal antibody which targets interleukin-5 (IL-5) and is nowadays available in many countries for add-on biological therapy of severe eosinophilic asthma. Although the approval of mepolizumab use in clinical practice has been made possible by several successful pre-marketing controlled trials, so far only a very few studies have been performed in a real-life setting. Within such a context, our present observational investigation refers to 14 patients with refractory eosinophilic asthma, currently treated with mepolizumab at the Respiratory Unit of "Magna Græcia" University Hospital located in Catanzaro, Italy, whose anti-IL-5 treatment began between June 2017 and January 2018. These patients experienced a significant increase in asthma control test (ACT) score, that was evaluated at baseline (13.64 ± 3.00), as well as after 4 weeks (18.86 ± 3.15; p < 0.0001) and 24 weeks (20.07 ± 1.94; p < 0.0001) of add-on therapy with mepolizumab. This relevant improvement in symptom control was paralleled by a dramatic fall of blood eosinophil numbers, counted at baseline (647.1 ± 274.7 cells/μl), and at the 4th (147.8 ± 66.5 cells/μl; p < 0.0001) and 24th week (98.6 ± 40.3 cells/μl; p < 0.0001) after starting add-on treatment with mepolizumab. These changes were associated with significant and stable increases in FEV1, which was recorded at baseline (1389 ± 454.3 mL), as well as after 4 weeks (1711 ± 482.3 mL; p < 0.001) and 24 weeks (1701 ± 456.0 mL; p < 0.01). Moreover, in comparison to the 6 months preceding the beginning of treatment with mepolizumab, after 24 weeks of anti-IL-5 therapy significant decreases were detected with regard to exacerbation numbers (from 3.64 ± 1.86 to 1.0 ± 0.78; p < 0.001) and oral intake of prednisone (from 24.11 ± 10.36 mg/day to 1.78 ± 3.82 mg/day). Therefore, these preliminary data referring to our single-centre observational study corroborate, in a real-life environment, the efficacy of mepolizumab for treatment of patients with exacerbation-prone, corticosteroid-refractory, severe eosinophilic asthma.


Socioeconomic status and health outcomes: cystic fibrosis as a model.
Socioeconomic status (SES), which indicates one's access to financial, educational, and social resources, is a powerful determinant of health outcomes in multiple chronic diseases. Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in a single gene. Although life expectancy and quality of life for patients with CF have improved exponentially, disease severity varies substantially, even among individuals with identical genotypes. CF disease progression and outcomes are influenced by a number of nongenetic factors, such as material well-being, educational attainment, living and working conditions, physical environment and exposures, family environment, social support, health behaviors, and health care. This review discusses pathways by which financial, educational, and social resources are translated into health advantages in CF. Expert commentary: To achieve equitable CF outcomes, the contribution of nongenetic factors must be emphasized, highlighting the mechanisms through which the social and physical environments influence disease variability.


Calling Out MS Fatigue: Feasibility and Preliminary Effects of a Pilot Randomized Telephone-Delivered Exercise Intervention for Multiple Sclerosis Fatigue.
Fatigue is a common and debilitating symptom of multiple sclerosis (MS). Exercise therapy is effective in reducing MS-related fatigue; however, its feasibility, acceptability, and effectiveness when delivered over the telephone remain unknown. This randomized study aimed to determine the feasibility and acceptability of a telephone-delivered exercise intervention for MS-related fatigue. In addition, pre-/postchange in fatigue and secondary outcomes were compared with an otherwise identical in-person delivered exercise intervention. Twenty participants with MS and clinically significant fatigue were randomized to 8 sessions of either telephone (n = 10) or in-person (n = 10) delivered exercise therapy. Primary outcome measures concerned feasibility (number of sessions attended), acceptability (Client Satisfaction Questionnaire), and fatigue (Fatigue Severity Scale and two 11-point numeric rating scales: fatigue intensity and interference). Data on a range of secondary outcome measures were also collected. There was no difference in average session attendance by group (telephone group: 7.6 ± 1.3 sessions; in-person 7.8 ± 0.42). Acceptability and reductions in fatigue were observed regardless of group, and improvements in a range of secondary outcomes were comparable. A telephone-delivered exercise intervention that targets MS-related fatigue is both feasible and acceptable. Primary and secondary outcome measures signaled that telephone-delivered exercise may be an effective mode of delivery that overcomes barriers to care in persons with MS and warrants testing in larger efficacy trials.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A293).


Invasive mechanical ventilation in patients with fibrosing interstitial pneumonia.
The prognosis of patients with idiopathic pulmonary fibrosis or fibrosing idiopathic nonspecific interstitial pneumonia undergoing invasive mechanical ventilation (MV) for acute respiratory failure is known to be poor. The issue of life support in these patients needs to be reconsidered in light of changes during the past decade in ventilator settings and in the management of acute exacerbation. We therefore aimed to reassess the prognosis of such patients. We retrospectively assessed the outcomes of all medical patients with idiopathic pulmonary fibrosis or fibrosing idiopathic nonspecific interstitial pneumonia who required invasive MV in 3 university hospitals in the Paris area from January 2002 to April 2009. In total, 27 patients (mean age, 66 ± 12.8 years) required invasive MV in the intensive care unit: 8 (30%) were successfully weaned from MV, and 6 and 4 were discharged from the intensive care unit and the hospital, respectively. Survivals for patients who did not undergo lung transplant were 22%, 3.7%, and 3.7%, at 30 days, 6 months, and 12 months, respectively. We confirm that use of invasive MV for acute respiratory failure in patients with idiopathic pulmonary fibrosis or fibrosing idiopathic nonspecific interstitial pneumonia is associated with a high mortality; however, a subset of patients may be discharged alive from the intensive care unit and hospital, providing an opportunity to consider lung transplant in case of eligibility. Our results suggest that invasive MV should not be systematically denied to these patients but discussed on a case-by-case basis.


Effect of Procyanidin-rich Extract from Natural Cocoa Powder on Cellular Viability, Cell Cycle Progression, and Chemoresistance in Human Epithelial Ovarian Carcinoma Cell Lines.
Over the last 400 years, cocoa and chocolate have been described as having potential medicinal value, being consumed as a beverage or eaten as food. Concentration-dependant, antiproliferation, and cytotoxic effects of some of their polyphenolic constituents have been demonstrated against various cancers. Such an effect remains to be demonstrated in ovarian cancer. To investigate the effect of cocoa procyanidins against ovarian cancer in vitro using OAW42 and OVCAR3 cell lines. Cocoa procyanidins were extracted and enriched from non alkalized cocoa powder. The polyphenolic content and antioxidant activity were determined. Effect on cell viability was determined after the treatment with ≤1000 μg/mL cocoa procyanidin-rich extract on OAW42 and OVCAR3 and normal human dermal fibroblasts. Similarly, chemosensitization effect was determined by pretreating cancer cell lines with extract followed by doxorubicin hydrochloride treatment. The effect of treatment on cell cycle and P-glycoprotein (P-gp) expression was determined using flow cytometry. The cocoa extract showed high polyphenolic content and antioxidant activity. Treatment with extract caused cytotoxicity and chemosensitization in OAW42 and OVCAR3 cell lines. Normal dermal fibroblasts showed an increase in cell viability post treatment with extract. Treatment with extract affected the cell cycle and an increasing percentage of cells in hypodiploid sub-G1/G0 phase was observed. Treatment of OVCAR3 with the extract caused reduction of P-gp expression. Cocoa procyanidins were found to be selectively cytotoxic against epithelial ovarian cancer, interfered with the normal cell cycle and sensitized cells to subsequent chemotherapeutic treatment. Chemosensitization was found to be associated with P-gp reduction in OVCAR3 cells. Among the naturally occurring flavonoids, procyanidins have been shown to be effective against cancersNon alkalized cocoa powder is one of the richest sources of procyanidinsCocoa procyanidin-rich extract (CPRE) caused cytotoxicity and chemosensitization in ovarian carcinoma cell lines OAW42 and OVCAR3CPRE affected normal cell cycle progressionCPRE also downregulated P-glycoprotein, which mediates chemoresistance in multidrug-resistant OVCAR3 cell line. Abbreviations used: P-gp: P-glycoprotein, CPRE: Cocoa procyanidin rich extract, DMAC: 4-dimethylaminocinnamaldehyde, DPPH: Diphenylpicrylhydrazyl, ABTS: 2,2';-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid), PI: Propidium iodide, FITC: Fluorescein isothiocyanate, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, TLC: Thin layer chromatography, HPTLC: High-performance thin layer chromatography.


Glycemic exposure is associated with reduced pulmonary function in type 2 diabetes: the Fremantle Diabetes Study.
To examine prospectively the relationship between diabetes, glycemic control, and spirometric measures. From a community-based cohort, 495 Europid (i.e., of European descent) patients with type 2 diabetes who had no history of pulmonary disease underwent baseline spirometry between 1993 and 1994. A subset of 125 patients was restudied a mean of 7.0 years later. The main outcome measures included forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), vital capacity (VC), and peak expiratory flow (PEF) corrected for body temperature, air pressure, and water saturation and were expressed either in absolute terms or as percentage-predicted value for age, sex, and height. Mean percentage-predicted values of each spirometric measure were decreased >10% in the whole cohort at baseline and absolute measures continued to decline at an annual rate of 68, 71, and 84 ml/year and 17 l/min for FVC, FEV1, VC, and PEF, respectively, in the 125 prospectively studied patients. Declining lung function measures were consistently predicted by poor glycemic control in the form of a higher updated mean HbA1c, follow-up HbA1c, or follow-up fasting plasma glucose. In a Cox proportional hazards model, decreased FEV1 percentage-predicted value was an independent predictor of all-cause mortality. Reduced lung volumes and airflow limitation are likely to be chronic complications of type 2 diabetes, the severity of which relates to glycemic exposure. Airflow limitation is a predictor of death in type 2 diabetes after adjusting for other recognized risk factors.


Long-term results of surgical excision of conjunctival retention cyst using trypan blue with methylcellulose.
Conjunctival retention cysts may recur if not completely removed. However, the cyst wall often ruptures during surgical excision, making complete removal difficult. In order to ensure complete cyst excision, we used a method of staining the inner cyst wall using trypan blue augmented by Methyl cellulose. Interventional study. Staining was performed by injecting trypan blue using an insulin needle. Then the needle was kept in place and methyl cellulose was injected to make the cyst content viscous to avoid its collapse after removing the needle. By using this technique, it was possible to excise the lesion as a whole. Three patients were included (unilateral). Two patients had cysts that were secondary to trachoma and were followed for up to 2 years without recurrence. A third patient had a conjunctival cyst following strabismus surgery was not successfully removed. This method is simple and effective for complete excision of conjunctival retention cysts exception for cysts post strabismus surgery.


Commensal Microbiota Modulation of Natural Resistance to Virus Infection.
Interferon (IFN)-Is are crucial mediators of antiviral immunity and homeostatic immune system regulation. However, the source of IFN-I signaling under homeostatic conditions is unclear. We discovered that commensal microbes regulate the IFN-I response through induction of IFN-β by colonic DCs. Moreover, the mechanism by which a specific commensal microbe induces IFN-β was identified. Outer membrane (OM)-associated glycolipids of gut commensal microbes belonging to the Bacteroidetes phylum induce expression of IFN-β. Using Bacteroides fragilis and its OM-associated polysaccharide A, we determined that IFN-β expression was induced via TLR4-TRIF signaling. Antiviral activity of this purified microbial molecule against infection with either vesicular stomatitis virus (VSV) or influenza was demonstrated to be dependent on the induction of IFN-β. In a murine VSV infection model, commensal-induced IFN-β regulated natural resistance to virus infection. Due to the physiological importance of IFN-Is, discovery of an IFN-β-inducing microbial molecule represents a potential approach for the treatment of some human diseases.


Percutaneous Cryoablation of Recurrent Pancreatic Mass for Life-Threatening Pancreatic VIPoma Syndrome: A Case Report.
We present the case of a 73-year-old female who underwent percutaneous cryoablation for recurrent life-threatening pancreatic vasoactive intestinal polypeptide-producing tumor (VIPoma) following a pancreaticoduodenectomy and chemotherapy 5 years earlier. She presented with profuse watery diarrhea causing severe electrolyte and acid-base abnormalities, along with acute kidney injury. Cryoablation was successful in treating her profound symptoms, completely reversing her clinical course. The patient has made a successful recovery for the last 1.5 years since the procedure.


The smallest alpha,gamma-peptide nanotubulet segments: cyclic alpha,gamma-tetrapeptide dimers.
[structure: see text] Cyclic tetrapeptides in which alpha-amino acids alternate with cis-3-aminocycloalkanecarboxylic acids dimerize by forming hydrogen bonds between their alpha-faces but not between their gamma-faces, establishing the minimal structural requirements for the novel alpha,gamma-peptide hybrids SPN.


Inhibitory effects of 2-deoxytetronic acid, a putative endogenous satiety factor, on paraventricular neurons of rats, in vitro.
The endogenous sugar acid, 2-deoxytetronic acid (2-DTA) was investigated for its effects on activity of paraventricular nucleus (PVN) neurons in slice preparations from rats. 2-DTA dose-responsively inhibited the spontaneous activity of 23 of the 53 PVN neurons tested at concentrations of 10(-5) to 10(-2) M, and 2 were excited. The inhibitory responses were not due to osmotic changes by 2-DTA administration. The high concentration of 2-DTA needed to produce responses suggests that it acts as substrate for oxidative metabolism rather than as a neurotransmitter or neuromodulator in the suppression of feeding behavior.


[Update on interstitial brachytherapy].
Minimally invasive treatment procedures, such as image-guided local tumour ablation have gained increasing relevance in oncologic concepts. Limitations of thermal ablation procedures have led to the development of percutaneous, computed tomography (CT) guided brachytherapy. Thermal ablation procedures, such as radiofrequency ablation (RFA) and laser-induced thermotherapy (LITT) show limitations regarding maximum tumour size (<5 cm), cooling effects of adjacent vessels and surrounding risk structures. The image-guided interstitial brachytherapy allows the single application of high-dose rate (HDR) irradiation with an extensive protracted cytotoxic effect. Adjacent risk structures play a minor role due to the steep dose gradient outside the clinical target volume. Studies using CT-guided brachytherapy resulted in a local tumour control rate of approximately 90% after 12 months in the treatment of hepatocellular carcinoma (HCC) and 70-90% in the treatment of colorectal metastases or cholangiocellular carcinoma (CCC). Similar response rates were also seen in the treatment of metastases of renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC) or neuroendocrine tumours. In colorectal liver metastases and HCC the method has proven to have a positive impact on prognosis. In contrast to thermal ablation the method can be used without restriction with respect to tumour location. Cooling effects do not play a role. It has already been applied in more than 5,000 cases and it is used in clinical routine. Image-guided brachytherapy is safe and effective and has found its way into the clinical routine.


The appropriate use of high-cost, high-risk technologies: the case of total parenteral nutrition.
An assessment of total parenteral nutrition (TPN), a high-cost, high-risk technology, is used to illustrate the importance of technology assessment to quality assessment. A review of the literature suggests that TPN is only sometimes effective and that it actually produces measurable harm by increasing complication rates in certain groups of patients. However, there are strong advocates for its use. The economic and ethical implications of TPN for the quality of care are also discussed at the levels both of the individual and of society. Continuous assessment of health care technologies, particularly those that are high-cost and high-risk, is critical to the overall quality of health care.


Investigating the effects of stress on achievement: BIOSTRESS dataset.
The effects of chronic stress on academic and professional achievement can have a substantial impact. This relationship is highlighted through a dataset that includes questionnaires and physiological data from a group of individuals. The questionnaire data of 48 individuals, the physiological data of 20 individuals during sessions with a psychologist, and the exam data of 8 individuals were analyzed. The questionnaire data collected includes demographic information and scores on the TOAD stress scale. Physiological data was captured using the Empatica e4, a wearable device, which measured various signals such as blood volume pulse, electrodermal activity, body temperature, interbeat intervals, heart rate, and 3-axis accelerometer data. These measurements were taken under different stress conditions, both high and low, during therapy sessions and an exam respectively. Overall, this study significantly contributes to our understanding of how stress affects achievement. By providing a large dataset consisting of questionnaires and physiological data, this research helps researchers gain a better understanding of the complex relationship between stress and achievement. It also enables them to develop innovative strategies for managing stress and enhancing academic and professional success.


[Bleomycin-induced pulmonary infiltrations in the treatment of testicular cancer].
Under Cisplatinum/Vinblastine/Bleomycin treatment six of 82 patients with nonseminomatous testicular cancer developed a Bleomycin-induced pulmonary toxicity. After a total Bleomycin dose of 300-360 mg all six patients showed multiple nodular densities near the pleura in the basal lung areas on the computed tomographic scanning (CT). Disseminated interstitial infiltrates, mostly in the lower lung fields were spontaneously observed by means of chest X-rays in only one case. In two other cases only minimal changes were found retrospectively. In five cases the diffusion capacity did not decrease significantly. Diffusion capacity, vital capacity and oxygen fell significantly in only one case. The latter was also the only patient showing clinical symptoms. The lung changes were completely reversible in four patients 4-6 months after cessation of Bleomycin. In two patients there were reversible residual changes after a timespan of 20 and 24 months. Two patients received no further antineoplastic treatment, two were under maintenance therapy, two under further induction chemotherapy because of the assumption of lung metastases. None of the six patients show any evidence at present of testis tumor (observation period 17-34 months). It can be difficult to distinguish between Bleomycin-induced lung damage and tumor metastases by radiological means. We were able to differentiate by observing the clinical course of the six patients. In case of doubt a histological examination is strongly recommended.


Stir-baked Fructus gardeniae (L.) extracts inhibit matrix metalloproteinases and alter cell morphology.
Matrix metalloproteinases (MMPs) play vital roles in many pathological conditions, including cancer, cardiovascular disease, arthritis and inflammation. Modulating MMP activity may therefore be a useful therapeutic approach in treating these diseases. Qing-Kai-Ling is a popular Chinese anti-inflammatory formulation used to treat symptoms such as rheumatoid arthritis, acute hypertensive cerebral hemorrhage, hepatitis and upper respiratory tract infection. In this paper, we report that one of the components of Qing-Kai-Ling, Fructus gardeniae, strongly inhibits MMP activity. The IC50 values for the primary herbal extract and water extract against MMP-16 were 32 and 27 microg/ml, respectively. In addition, we show that the herbal extracts influence HT1080 human fibrosarcoma cell growth and morphology. These data may provide molecular mechanisms for the therapeutic effects of Qing-Kai-Ling and herbal medicinal Fructus gardeniae.


Cystic mucinous hyperplasia in the gallbladder of a ferret.
An 8-year-old male ferret had icterus, hepatomegaly and an enlarged gallbladder. Microscopically, the gallbladder had numerous mucinous cysts and papillary hyperplasia of the mucosa, consistent with a diagnosis of cystic mucinous hyperplasia. No previous published reports of this condition in ferrets were found.


Comparative studies on conventional and microwave synthesis of some benzimidazole, benzothiazole and indole derivatives and testing on inhibition of hyaluronidase.
We have synthesized twelve 2-substituted benzimidazole, benzothiazole and indole derivatives using on both microwave irradiation and conventional heating methods. The microwave method was observed to be more beneficial as it provides an increase of yield from 3% to 113% and a 95 to 98 % reduction in time. All compounds were tested by a stains-all assay at pH 7 and by a Morgan-Elson assay at pH 3.5 for hyaluronidase inhibitory activity at a concentration of 100 microM. The most potent compound was 2-(4-hydroxyphenyl)-3-phenylindole (12) with an IC(50) value of 107 microM at both pH 7 and 3.5.


The effect of group size on health and growth rate of Swedish dairy calves housed in pens with automatic milk-feeders.
Group pens equipped with automatic milk-feeding systems are increasingly being used for young dairy calves in Sweden. The system is, however, associated with an increased risk of clinical respiratory-tract disease and a reduced growth rate. In an experimental study we compared the health and growth rate of two different group sizes of calves (6-9 versus 12-18) kept in pens with automatic milk-feeders. The experiment was performed from September 2002 to February 2004, in nine commercial dairy farms in south-west Sweden. Each farm was equipped with two pens with automatic milk-feeders and no possibility of direct contact between calves from different pens. The calves were housed individually until 3-35 (median, 12) days of age, and then were allocated to one of the two group pens by random-number lists. Altogether 892 calves were studied: 297 in the small- and 595 in the large-sized groups. The calves' heart girths were measured at birth and at 56 days of age. Blood samples for analysis of serum haptoglobin concentration (S-Hp) were collected once for each calf, at four to eight weeks of age. Diseases were recorded by the farmers and by a veterinarian, who visited the farms every third week and physically examined all the calves. The effects of group size on the risks of diarrhoea, clinical respiratory-tract disease and increased respiratory sounds, and on the growth rate and S-Hp were evaluated using multiple logistic- and linear-regression models with herd as fixed effect. Age at transfer to group pen, breed, immunoglobulin concentration of colostrum received, parity of the dam and presence of diarrhoea before transfer to the group pen, season, sex, year, and, in the analysis of growth rate, birth heart girth were extra explanatory variables. Calves in pens for 12-18 calves had a higher incidence of respiratory illness (OR: 1.4) and grew 0.022 cm/day less than calves housed in groups of 6-9 animals (equivalent to approximately 40 g/day). We detected no differences between calves kept in the small-sized versus the large-sized groups in terms of risk of diarrhoea or mean S-Hp. We concluded that housing calves in groups of under 10 calves is preferable from a health and growth perspective.


Quantitative trunk sway analysis under challenging gait conditions in early and untreated Parkinson's disease.
Even experienced clinicians may encounter difficulties in making a definitive diagnosis in the early motor stages of Parkinson's disease (PD). We investigated whether quantitative biomechanical trunk sway analysis could support the diagnosis of PD early on. We quantified trunk sway performance using body-worn sensors during a test battery of six challenging gait conditions in a cohort of 17 early and untreated PD patients (with evidence of reduced tracer uptake in the basal ganglia on dopamine transporter scans) and 17 age- and sex-matched healthy controls (HCs). Compared to HC, the PD group (Hoehn & Yahr ≤ 2, Unified Parkinson's Disease Rating Scale motor score: mean 13.7 ± 3.5 points) showed significant trunk rigidity in five challenging gait tasks (decreased medio-lateral direction and sway angle area). Post hoc receiver operating characteristic analysis of the significant parameters revealed excellent discrimination with high sensitivity and specificity. In the early and untreated motor stages of PD, patients exhibit significant trunk rigidity during challenging gait tasks. Trunk sway motion recorded with body-worn sensors might be a useful tool to disclose a sometimes hard-to-trace cardinal motor sign of PD and support an early clinical diagnosis.


Enantioenriched Boron C,N-Chelates via Chirality Transfer.
Molecules stereogenic only at tetrahedral boron atoms show great promise for applications, for example as chiroptical materials, but are scarcely investigated due to their synthetic challenge. Hence, this study reports a two-step synthesis of enantioenriched boron C,N-chelates. First, the diastereoselective complexation of alkyl/aryl borinates with chiral aminoalcohols furnished boron stereogenic heterocycles in up to 86 % yield and d.r. >98 : 2. Treatment of these O,N-complexes with chelate nucleophiles was surmised to transfer the stereoinformation via the ate-complex into the C,N-products. This chirality transfer succeeded by substitution of the O,N-chelates with lithiated phenyl pyridine to give boron stereogenic C,N-chelates in up to 84 % yield and e.r. up to 97 : 3. The chiral aminoalcohol ligands could be recovered after isolation of the C,N-chelates. The chirality transfer tolerated alkyl, alkynyl and (hetero-)aryl moieties at boron and could be further extended by post-modification: transformations such as catalytic hydrogenations or sequential deprotonation/electrophilic trapping were feasible while maintaining the stereochemical integrity of the C,N-chelates. Structural aspects of the boron chelates were studied by variable temperature NMR and X-ray diffraction.


[The evolution of nursing education in France].
Changes in nursing education are closely linked to changes in the health care system. The nursing profession must indeed continue to occupy a pivotal position within the health system and its representatives must be able to continue their studies to complement their nursing skills with other disciplines. This will require the issuance of a "real" nursing degree by the university and the updating of the students' referential, so that it is consistent with the development of the profession and the work in interprofessionality.


Potentiating role of previously administered agents in the combination chemotherapy of breast cancer.
91 women with metastatic breast cancer, who received prior CTX-5FU or CTX-5FU-PRD, were treated in 3 consecutive clinical trials with either CTX-5FU-PRD-MTX-VCR, MTX-VCR, or MTX-VCR-PRD in order to elucidate whether the effectiveness of 5 drugs was due only to the newly added drugs (MTX-VCR +/- PRD) or whether the previously used drugs (CTX-5FU) were necessary as potentiating agents. There were 17 or 39 responders (43%) in the 5-drug group, 3 of 25 (12%) in the MTX-VCR group and 3 of 27 (11%) in the MTX-VCR-PRD group. The survival in the group treated with 5 drugs was significantly longer. Our results show that CTX-5FU-PRD-MTX-VCR was significantly more effective than MTX-VCR or MTX-VCR-PRD used alone after the patient had already had CTX-5FU +/- PRD. Thus, the previously used drugs (CTX-5FU) seemed to improve the response to the new agents (MTX-VCR +/- PRD) by a potentiating action in the subsequent combination. It is concluded that the exploitation of this enhancing effect represents a significant improvement in the treatment options now available.


Spatiotemporal quantification of gait in common marmosets.
Objective gait evaluation in humans is used as a predictive disability outcome measure as well as an indicator for intervention effectiveness. Parallel methods of gait analysis in nonhuman primate models are essential for clinical translation. The goal of this study was to first assess whether marmosets' gait data could be reliably collected in a Noldus CatWalk XT10.6 and second, establish a testing protocol to assess gait and the intraindividual variability during repeated testing. The CatWalk, originally developed for rodents, was modified and used to assess gait in eight adult common marmoset monkeys across multiple days and trials. Data was first analyzed to identify valid runs. Repeated measures ANOVA was completed for the following gait measures: mean base of support, average stride length, average swing time, and average stance time. Raters had a high level of concurrence of usable data across all trials with successful trials including four consecutive hindfoot footfalls, during a continuous, uninterrupted segment of walking. A significant main effect of time (p < 0.000) but not rater (p = 0.98) was present with significant interactions for time by subject (p < 0.000), but not rater per subject (p = 0.538), time (p = 0.186), or three-way interaction (p = 0.297). Gait has been assessed using force-plate and video data. The CatWalk allowed reproducible, automated and translational locomotor data to be collected at multiple time points with detailed analyses that identified a diagonal gait pattern. The CatWalk system, similar to those used in humans, can be effectively used to quantify spatiotemporal characteristics of gait in the common marmoset.


Developing an Iterative Tracking Algorithm to Guide a Catheter Towards Atrial Fibrillation Rotor Sources in Simulated Fibrotic Tissue.
Locating atrial fibrillation (AF) rotor sources can help target ablation therapy for AF. Our aim was to develop a catheter-tracking algorithm to locate AF rotor sources using a conventional 20-electrode circular catheter. We simulated rotor-driven arrhythmias in homogeneous and fibrotic human atrial tissue and evaluated the algorithm for different initial catheter positions. The algorithm guided and detected a rotor with a success rate of greater than 97.9% independently of the initial position of the catheter with an accuracy of greater than 2.3±1.4 mm.


Autumn stomatal closure in six conifer species of the Central Rocky Mountains.
Environmental and water relations parameters during fall were monitored for six conifer tree species common to the central Rocky Mountains growing naturally at the same location (Pinus contorta, Pinus ponderosa, Pinus flexilus, Pseudotsuga menziesii, Abies lasiocarpa, Picea engelmannii). Subsequent to what appeared to be the beginning of seasonal stomatal closure, leaf conductance to water vapor declined sharply following the onset of freezing air temperatures at night. A coincident rapid decline in morning xylem pressure potentials (ψp) also occurred which resulted in values that were considerably below afternoon ψp. Continuing decreases in maximum leaf conductance during the day were highly correlated with corresponding decreases in minimum nocturnal air temperatures of the preceding night. By mid-December, morning ψp returned to values very near afternoon ψp and were only slightly lower than before the onset of subfreezing nights. A preliminary model is proposed which interprets the qualitative interaction between air and soil temperatures, soil and plant water potentials, and leaf conductance during seasonal stomatal closure in fall.


Lutein/β-carotene ratio in extra virgin olive oil: An easy and rapid quantification method by Raman spectroscopy.
Carotenoids play an important role in the stability, freshness, and nutritional value of extra-virgin olive oil (EVOO). However, the carotenoid content in EVOO changes over time as a function of olive ripening and degrading events. A reliable quality marker is the ratio between the two most abundant carotenoids, namely lutein and β-carotene, since the second degrades more rapidly. Thus, to obtain a fast quantification of the lutein/β-carotene ratio in olive oil could deserve a certain interest. Resonant Raman spectroscopy is a rapid and non-destructive technique, widely applied for food chemical characterization. In this work, using high-performance liquid chromatography and UV-vis absorption spectroscopy as calibration techniques, we present a reliable method to assess the lutein/β-carotene ratio in EVOO using a single Raman spectrum. The novel approach deserves several methodological and applicative interests, since it would allow rapid, on-site screening of EVOO quality and authenticity, especially if implemented as a portable system.


Effect of temperature on long-term storage of codling moth granulovirus formulations.
Codling moth, Cydia pomonella (L.), is the major pest of apple (Malus spp.) in the western United States and many other regions of the world. The codling moth granulovirus (CpGV) provides a selective and safe means of its control. We assessed the long-term stability and storage potential of two commercial formulations of CpGV, Cyd-X, and Virosoft. All assays were performed with individual C. pomonella neonate larvae in 2-ml vials on 1 ml of artificial larval diet that was surface inoculated with 10 microl of the test virus suspension. Baseline quantitative assays for the two formulations revealed that the LC50 and LC95 values (occlusion bodies per vial) did not differ significantly between the formulations. For year-long studies on Cyd-X stability, the product was stored at -20, 2, 25, and 35 degrees C, and quantitative bioassays were conducted after 0, 3, 6, and 12 mo of storage. Cyd-X retained good larvicidal activity from -20 to 25 degrees C, and it was the least negatively affected at the lowest temperature. Storage of Cyd-X at 35 degrees C was detrimental to its larvicidal activity within 3 mo of storage. For longer term storage studies, Cyd-X and Virosoft formulations were stored at 2, 25, and 35 degrees C, and assayed for larvicidal activity over a 3-yr period. For recently produced product, a 10-microl sample of a 10(-5) dilution of both formulations resulted in 95-100% mortality in neonate larvae. Larvicidal activity for the Cyd-X formulation remained essentially unaffected for 156 wk when stored at 2 and 25 degrees C, but it began to decline significantly after 20 wk of storage at 35 degrees C. The Virosoft formulation stored at 2 degrees C also remained active throughout the 3-yr study, but it began to decline in larvicidal activity after 144 wk at 25 degrees C and 40 wk at 35 degrees C. The information reported in this study should be useful to growers and commercial suppliers for avoiding decreases in CpGV potency due to improper storage conditions.


Impaired antiatherogenic function of high-density lipoproteins in the presence of various risk factors for coronary heart disease.
We studied acception of cholesterol from Fu5AH hepatoma cells by blood serum from subjects with normal level of high-density lipoprotein cholesterol and hyperlipidemia (alone or in combination with other risk factors for coronary heart disease). Cholesterol-binding activity of high-density lipoproteins decreased in subjects with hyperlipidemia alone or in combination with excess body weight and/or arterial hypertension. Impairment of high-density lipoprotein activity was associated with changes in their phospholipid composition.


Simulation study of the Lower Cretaceous geothermal reservoir for aquifer thermal energy storage.
The aquifer thermal energy storage (ATES) has gained attention in several countries as an installation for increasing the energy efficiency of geothermal systems and the use of waste heat. The Lower Cretaceous reservoir is known as one of the most prospective for geothermal purposes in Poland. However, in the southern part of the Mogilno-Łódź Trough (Central Poland) is considered to have a lower geothermal potential. The aim of this paper is to study whether the Lower Cretaceous reservoir in this area is suitable for aquifer thermal energy storage. Prior to dynamic simulations in Feflow© software, a regional Petrel© static parametric model which includes a multidisciplinary approach was prepared. A methodology of fitting Petrel's structural and parametrical model to Feflow requirements is provided within this paper. The performance simulation of 4 systems has been conducted for 30 years. Increasing precipitation potential is expected for aragonite and calcite along with a temperature increase, while silica precipitation carries a much smaller risk. The paper presents potential for ATES systems in the Lower Cretaceous reservoir of the study area with the best doublet location having thermal recovery ratio of 0.47 and 0.34 for 30 and 40 K temperature differential scenario. An imbalance in heat injection/production in the storage system can cause the reservoir to cool faster than in conventional geothermal heating installation. ATES can provide a successful geothermal reservoir boosting in the case of applying a balanced injection of waste heat.


An unusual ECG deflection: Fact or artifact?
Peculiar electrocardiographic findings are not unusual and upon careful review can often be clarified. We present a case of an 85year-old woman with no previous cardiac history, incidentally discovered high grade atrioventricular block, and a puzzling electrocardiographic complex of unclear etiology which defies reasonable physiological explanations. The finding resembled a tiny QRS in a perfectly regular R-R interval following only non-conducted P-waves. The patient declined further work-up, so a definite cause could not be determined, but based on history, complex morphology, and inability to reproduce or explain the findings, we were compelled to accept the finding as an artifact.


Three Infants with Pathogenic Variants in the ABCA3 Gene: Presentation, Treatment, and Clinical Course.
ABCA3 deficiency is a rare cause of neonatal respiratory failure. Biallelic complete loss of function variants lead to neonatal demise without lung transplantation, but children with partial function variants have variable outcomes. The favorable clinical course of 3 such infants presenting with respiratory distress at birth is described.


Botulinum toxin treatment of oesophageal achalasia in the old old and oldest old: a 1-year follow-up study.
Intrasphincteric injection of botulinum toxin (BTX) has become one of the most frequent therapeutic approaches for the treatment of oesophageal achalasia. This treatment seems particularly effective in elderly patients who are not candidates for more invasive procedures. There are few or no data on BTX treatment of achalasia in the old old and oldest old. Therefore, we evaluated BTX treatment in a group of patients with achalasia in the extreme age range who were too ill or frail to undergo surgery or pneumatic dilatation. Twelve elderly achalasic patients (age range 81-94 years, average age 86 years) with American Society of Anesthesiologists (ASA) class III-IV status were recruited for the study. After baseline clinical and instrumental evaluations, BTX 100U was injected at time 0 and 1 month later. Clinical follow-up was carried out after 3, 6 and 12 months. A significant improvement in symptom score was documented at each follow-up step. On the basis of improvements in scores, approximately 70% of patients were considered responders at the end of follow-up. BTX treatment is an effective treatment in a substantial proportion of achalasic patients >80 years of age, in whom benefits are still detectable after 12 months. BTX is a therapeutic option in patients unsuitable for surgery or pneumatic dilatation.


The relationship between personality traits of cancer patients and their preferences when receiving bad news.
This study aimed to determine the relationship between the personality traits of cancer patients and their preferences when receiving bad news. In this descriptive correlational study, 200 cancer patients who were selected by the continuous sampling method participated. Patients self-reportedly completed the demographic and medical information questionnaire, the Measure of Patients' Preference (MPP) scale, and the short form of the Eysenck Personality Inventory (EPI). The majority of participants were female (73%), 42.5% had higher education, and 47.5% suffered from breast cancer. In this study, the mean scores of extraversion and neuroticism in patients were 14.59 ± 2.47 and 15.17 ± 3.43, respectively. Regarding patients' preferences for receiving bad news, the score obtained by them in the content category was greater compared to two categories of context and support. This study showed a significant and negative correlation between neuroticism and patients' preferences in the support category (P < 0.001 and r = - 0.265). Regarding the categories of the MPP, there was a significant relationship between gender (P = 0.018) and marital status (P = 0.049) with context category, education (P = 0.011) with content category, and marital status (P = 0.003) and employment (P = 0.009) with support category. Personality traits and demographic characteristics of cancer patients can influence their preferences for receiving bad news. Therefore, the consideration of these traits by health care team members is of particular importance to communicate with and deliver bad news to patients.


El Niño mass coral mortality: a test of resource limitation in a coral reef damselfish population.
The mass mortality of reef corals in the eastern Pacific as a result of the 1982-1983 El Niño oceanographic anomaly permitted the first large scale test of resource limitation for a coral reef fish. Population densities of territorial herbivorous damselfish did not respond to the massive regional increase in space available for the cultivation of algal food following the El Niño event. The proportion of juveniles in the population was low and new recruits were uncommon, indicating that recruitment rates rather than resource supply probably control the abundance of this coral reef damselfish.


Brain Metastasis Recurrence Versus Radiation Necrosis: Evaluation and Treatment.
Radiation necrosis (RN) occurs in 5% to 25% of patients with brain metastases treated with stereotactic radiosurgery. RN must be distinguished from recurrent tumor to determine appropriate treatment. Stereotactic biopsy remains the gold standard for identifying RN. Initial treatment of RN often involves management of edema using corticosteroids, antiangiogenic therapies, and hyperbaric oxygen therapy. For refractory symptoms, surgical resection can be considered. Minimally invasive stereotactic laser ablation has the benefit of providing tissue diagnosis and treating RN or recurrent tumor with similar efficacy. Laser ablation should be considered for lesions in need of intervention where the diagnosis requires tissue confirmation.


Harnessing education and lifestyle change to support transitional health for returning citizens: a feasibility study protocol.
Exercise and healthy eating are known to reduce chronic disease risk; however, formerly incarcerated individuals (i.e., returning citizens) face significant social barriers when attempting to engage with existing community-based physical activity and nutrition programs. Given the high disease burden and unique educational needs of returning citizens, this proposed work fills an important gap in the support services currently offered to this population. This article describes a process for evaluating the feasibility and acceptability of a physical activity and nutrition intervention tailored to the needs of returning citizens via a partnership between an academic research organization and a community-based reentry program for returning citizens. Staff from the community-based reentry program will train four returning citizens as group fitness instructors and work with a nutritionist to design a 16-week nutrition education curriculum. Reentry program staff will enroll up to 15 formerly incarcerated adults (aged 18 +) in the exercise and nutrition program. Participants will take part in weekly nutrition classes led by the nutritionist and weekly group exercise classes led by a peer instructor. Research staff will evaluate program success in four domains: reach, preliminary effectiveness, implementation, and maintenance. This feasibility study will allow us to design and test a program that can eventually be evaluated in a large, randomized trial. It also addresses the multitude of social determinants that impact the health of returning citizens and builds a framework for program sustainability. Individuals recruited as fitness trainers will acquire skills and certifications that may be used to sustain physical fitness activities within the reentry program. This feasibility study will test our ability to address social determinants that impact the health of returning citizens through a peer-led physical activity and nutrition programming. In the long term, study results may inform development and implementation of reentry programming and policy on a wider scale.


Hypertension in the elderly.
Several studies have demonstrated an increased risk of cardiovascular disease (CVD) in relation to high blood pressure in elderly patients aged below 70-75, whereas the risk seemed to decline with age in the older elderly. Early studies on the effect of treatment of mild to moderate hypertension in the elderly indicated (but did not convincingly show) a reduction of CVD. In the 1980s, both the EWPHE trial (European Working Party on High Blood Pressure in the Elderly) and the HEP study (The Randomised Trial of the Treatment of Hypertension in Elderly Patients in Primary Care) provided evidence of the benefit of treating high blood pressure in the elderly, at least up to the age of 70-74. These results have lately been confirmed by three major trials SHEP (Systolic Hypertension in the Elderly Program), STOP (Swedish Trial in Old Patients with Hypertension) and MRC (Medical Research Council), also including older patients (STOP) and those with isolated systolic hypertension (SHEP). This satisfactory effect was not impaired by a low tolerability of the drugs used (beta-blockers and diuretics). In conclusion, drug treatment with beta-blockers and diuretics in hypertensive men and women aged 70 and above confers highly significant and clinically relevant reductions in cardiovascular (especially stroke) morbidity and mortality. The clinical implication of this is that blood pressure lowering therapy should be considered in elderly hypertensives, at least up until they are 80. It should also be remembered that elderly hypertensives often have other diseases as well and that the drug treatment should be adjusted accordingly.


Exhausted-like Group 2 Innate Lymphoid Cells in Chronic Allergic Inflammation.
Mammalian group 2 innate lymphoid cells (ILC2s) are responsible for the early production of type 2 cytokines at mucosal barriers upon exposure to allergen. Inflammatory tissue environmental cues can influence ILC2 activity, and this cellular population can be further categorized into subtypes with additional or alternative functions. Subtypes can include trained (or 'memory-like') ILC2s, which recall previous allergic inflammation, inflammatory ILC2s, which acquire the ability to produce IL-17, and ex-ILC2s, which produce ILC1 cytokines. However, the functional states of ILC2s at sites of chronic or severe inflammation are not well characterized. Here, we discuss the emergence of ILC2s with 'exhausted'-like signatures, and argue that their hyporesponsiveness to stimulation and expression of inhibitory receptors is relevant in mammalian chronic allergic inflammation.


Association of intravascular enhancement sign detected on high-resolution vessel wall imaging with ischaemic events in middle cerebral artery occlusion.
Patients with intracranial artery occlusion have high rates of ischaemic events and recurrence. Early identification of patients with high-risk factors is therefore beneficial for prevention. Here we assessed the association between the intravascular enhancement sign (IVES) on high-resolution vessel wall imaging (HR-VWI) and acute ischaemic stroke (AIS) in a population with middle cerebral artery (MCA) occlusion. We retrospectively analysed the records of 106 patients with 111 MCA occlusions, including 60 with and 51 without AIS, who had undergone HR-VWI and computed tomography angiography (CTA) examinations from November 2016 to February 2023. Numbers of IVES vessels were counted and compared to the CTA findings. Statistical analyses of demographic and medical data were also performed. Occurrence rates and numbers of IVES vessels were significantly higher in the AIS than the non-AIS group (P < 0.05), and most vessels were detected on CTA. Numbers of vessels positively correlated with AIS occurrence (rho = 0.664; P < 0.0001). A multivariable ordinal logistic regression model adjusted for age, degree of wall enhancement, hypertension, and heart status identified the number of IVES vessels as an independent predictor for AIS (odds ratio = 1.6; 95% CI, 1.3-1.9; P < 0.0001). Number of IVES vessels is an independent risk factor for AIS events, and may represent poor cerebral blood flow status and collateral compensation level. It thus provides cerebral haemodynamic information for patients with MCA occlusion for clinical use.


Analysis of F2-isoprostanes as indicators of non-enzymatic lipid peroxidation in vivo by gas chromatography-mass spectrometry: development of a solid-phase extraction procedure.
Recently, it has been reported that a series of prostaglandin F2-like compounds (F2-isoprostanes) are produced in vivo during peroxidation of arachidonic acid by a mechanism independent of the cyclooxygenase pathway. Of these, 8-epi-PGF2 alpha is shown to be a potent vasoconstrictor. We describe an improved method for analysing F2-isoprostanes in biological fluids. The method involves solid-phase extraction on an octadecylsilane (C18) and an aminopropyl (NH2) cartridge. After conversion to pentafluorobenzyl ester and trimethylsilyl ether derivatives, F2-isoprostanes are analysed by negative-ion chemical ionization mass spectrometry using tetradeuterated PGF2 alpha as the internal standard. The limit of detection of the assay was 10 pg/ml, with a coefficient of variation ranging from 9.4 to 15.1%. Analysis of plasma samples from healthy volunteers (n = 7) revealed no quantifiable levels of free (unesterified) 8-epi-PGF 2 alpha. However, the plasma samples contained 58 to 166 pg/ml of 8-epi-PGF2 alpha when analyzed for the total (sum of free and esterified) F2-isoprostanes. The main advantages of the method lie in the improved recovery, gas chromatographic separation and speed compared to existing techniques.


Silver/chiral pyrrolidinopyridine relay catalytic cycloisomerization/(2 + 3) cycloadditions of enynamides to asymmetrically synthesize bispirocyclopentenes as PDE1B inhibitors.
Significant progress has been made in asymmetric synthesis through the use of transition metal catalysts combined with Lewis bases. However, the use of a dual catalytic system involving 4-aminopyridine and transition metal has received little attention. Here we show a metal/Lewis base relay catalytic system featuring silver acetate and a modified chiral pyrrolidinopyridine (PPY). It was successfully applied in the cycloisomerization/(2 + 3) cycloaddition reaction of enynamides. Bispirocyclopentene pyrazolone products could be efficiently synthesized in a stereoselective and economical manner (up to >19:1 dr, 99.5:0.5 er). Transformations of the product could access stereodivergent diastereoisomers and densely functionalized polycyclic derivatives. Mechanistic studies illustrated the relay catalytic model and the origin of the uncommon chemoselectivity. In subsequent bioassays, the products containing a privileged drug-like scaffold exhibited isoform-selective phosphodiesterase 1 (PDE1) inhibitory activity in vitro. The optimal lead compound displayed a good therapeutic effect for ameliorating pulmonary fibrosis via inhibiting PDE1 in vivo.


Mouse skin as a model for cancer chemoprevention by nonsteroidal anti-inflammatory drugs.
The mouse skin model of multistage carcinogenesis has demonstrated that cancer results from a synergism between genotoxic and nongenotoxic factors. The former induce irreversible genetic alterations, whereas the latter promote tumor development by favoring the clonal outgrowth of the genetically altered cells. While therapeutic gene repair is a still unrealized dream, tumor promotion provides an attractive target for cancer prevention. A key event in epithelial tumor development is an aberrant constitutive overexpression of cyclooxygenase-2 (COX-2), being detectable already in premalignant lesions and leading to an overproduction of prostaglandins. In the mouse skin model, prostaglandin F2alpha has been identified as an endogenous tumor promoter. The well-established chemopreventive effect of nonsteroidal anti-inflammatory drugs seems to be mainly due to COX-2 inhibition. Targeted transgenic overexpression of COX-2 in mouse epidermis induces a preneoplastic phenotype and renders the tissue extremely sensitive to genotoxic carcinogens; i.e., for the induction of skin tumor development, tumor promoter treatment can be omitted in those animals. It is concluded that COX-2 acts as an endogenous tumor promoter and that its overexpression represents a first order risk factor for cancer development. Conversely, specific COX-2 inhibitors rank among the most promising agents for cancer chemoprevention.


Effect of age of transfused red blood cells on neurologic outcome following traumatic brain injury (ABLE-tbi Study): a nested study of the Age of Blood Evaluation (ABLE) trial.
Anemia is common in critically ill patients with traumatic brain injury, and often requires red blood cell transfusion. Studies suggest that prolonged storage causes lesions of the red blood cells, including a decreased ability to carry oxygen. Considering the susceptibility of the brain to hypoxemia, victims of traumatic brain injury may thus be more vulnerable to exposure to older red blood cells. Our study aimed to ascertain whether the administration of fresh red blood cells (seven days or less) results in a better neurologic outcome compared with standard red blood cells in critically ill patients with traumatic brain injury requiring transfusion. The Age of Blood Evaluation in traumatic brain injury (ABLE-tbi) study was a nested study within the ABLE study (ISRCTN44878718). Our primary outcome was the extended Glasgow Outcome Scale (GOSe) at six months. In the ABLE study, 217 subjects suffered a traumatic brain injury: 110 in the fresh group, and 107 in the standard group. In the fresh group, 68 (73.1%) of the patients had an unfavourable neurologic outcome (GOSe ≤ 4) compared with 60 (64.5%) in the standard group (P = 0.21). Using a sliding dichotomy approach, we observed no overall effect of fresh red blood cells on neurologic outcome (odds ratio [OR], 1.34; 95% confidence interval [CI], 0.72 to 2.50; P = 0.35) but observed differences across prognostic bands with a decreased odds of unfavourable outcome in patients with the best prognosis at baseline (OR, 0.33; 95% CI, 0.11 to 0.96; P = 0.04) but an increased odds in those with intermediate and worst baseline prognosis (OR, 5.88; 95% CI,1.66 to 20.81; P = 0.006; and OR, 1.67; 95% CI, 0.53 to 5.30; P = 0.38, respectively). Overall, transfusion of fresh red blood cells was not associated with a better neurologic outcome at six months in critically ill patients with traumatic brain injury. Nevertheless, we cannot exclude a differential effect according to the patient baseline prognosis. ABLE study (ISRCTN44878718); registered 22 August, 2008.


Effect of the cavity disinfectant containing chitosan on dentin bonding strength after radiotherapy.
This study aimed to compare the bond strength of teeth treated with radiotherapy with two cavity disinfectants (Chlorhexidine gluconate, a chitosan-containing agent). Eighteen newly extracted, non-carious human third molar teeth were used. The teeth were randomly divided into two main groups, treated and/or non-treated with radiotherapy, then separated into three subgroups for disinfectant agent application (CHX, chitosan, control). A total dose of 70.2 Gy was given over 39 days using a linear radiation accelerator for radiotherapy. After applying the cavity disinfectant, the teeth were restored with composite resin to obtain the stick. All bond strength values from sticks were measured using a universal testing machine. The data were analyzed with ANOVA and Chi-square test at a p < 0.05. Among all groups, Group CH, with no radiotherapy application and containing a chitosan-disinfectant agent, showed the highest bond strength (44.7 ± 8.2). In contrast, Group RC with radiotherapy and disinfectant-free showed the lowest bond strength value (29.1 ± 3.5). The highest bond strength values were obtained after applying the chitosan-containing agent in all groups. Radiotherapy application had a negative effect, while the use of disinfectant agents had a positive effect on the bond strength.


Influence of pore structure and pretreatments of activated carbons and water effects on breakthrough dynamics of tert-butylbenzene.
Several activated carbons differently pretreated (de-ashed, oxidized, reduced, wetted, frozen, and dried) were investigated using static (equilibrium adsorption of nitrogen and benzene) and dynamic (tert-butylbenzene (TBB)) adsorption methods. Treatments of carbons at relatively mild conditions leading to not great changes in their textural characteristics affect the TBB breakthrough concentration because of changes in the chemistry of the surfaces (oxidized or reduced) and the presence of water in airstream or pre-adsorbed on carbon beds. Oxygen-containing functionalities at a carbon surface change condition of competitive adsorption of nonpolar TBB and polar water molecules. Calculations of distribution functions of adsorption potential (A), energy (E), Gibbs free energy (Delta G) of adsorption of benzene and TBB and effective adsorption (first-order) rate pseudoconstant beta e over different ranges of relative exit TBB concentration c(t)/c(0) (from approximately 10(-5) to 0.01-0.4) reveal nonlinear effects caused by the size of carbon granules, the pore size distributions, the presence of water, oxidation or reduction of the surfaces and other treatments resulting in distribution functions f(y) with nonzero intensity in relatively broad ranges of the A, E, Delta G, and beta e values. There are many factors affecting the breakthrough parameters; therefore, simple linear relationships between these parameters and the structural characteristics (S(BET), S(DS), Vp, and V(DS)) are not observed.


Arterial thromboembolic complications in patients with Björk-Shiley and Lillehei-Kaster aortic disc valve prostheses.
Arterial thromboembolic complications were studied in 196 patients who had either a single Björk-Shiley or Lillehei-Kaster aortic disc valve implanted. Eight patients suffered from such complications in the course of the first postoperative month and three of them died, two from myocardial infarction and one from cerebral embolism. Nineteen late thromboembolic complications developed in 18 of the 164 patients who survived the postoperative period, the incidence bein 5.9 episodes per 100 patients per year. The two valve types wer found to be equallly thrombogenic, and the rate was not lower than that in patients with Starr-Edwards aortic ball valves of series 2,300 previously studied. Particularly serious was valve malfunction caused by thrombi that limited the movement of the discs. Early recognition of this condition is essential, because the only effective therapy is removal of the thrombus. Three patients with a Björk-Shiley and one with a Lillehei-Kaster valve suffered this complecation and two died, while cerebral embolism caused a third late death. Two of the three patients who had not received anticoagulants developed thromboembolic complications, while most episodes occurred in spite of well-maintained anti-coagulant treatment. It is concluded that arterial thromboembolic complications remain a considerable problem also after aortic disc valve implantation, and that thrombotic valve malfunction is particularly serious and requires special attention.


Placebo Effect and Its Determinants in Ocular Hypotensive Therapy: Meta-analysis and Multiple Meta-regression Analysis.
The placebo effect and its potential determinants in ocular hypotensive therapy. The placebo effect has been studied and documented within a wide clinical context. It remains unclear whether placebo is effective in glaucoma treatment or, if so, which factors are determinative of effect size (ES). Randomized controlled trials (RCTs) of topical ocular hypotensive therapy for patients with open-angle glaucoma or ocular hypertension, conducted through June 2, 2022, were included. First, a perceived placebo effect was measured as the overall intraocular pressure (IOP) change from the baseline. It was evaluated in terms of the ES (mean difference between the baseline and the end point) and then was compared with the ES, as obtained from the untreated control participant to obtain a true placebo effect. The primary outcome was ES based on 4 weeks of treatment. Meta-analysis-based statistical pooling was performed where appropriate, and 95% confidence intervals (CIs) were used for comparison. Potential placebo effect determinants were scrutinized using a multiple meta-regression model (PROSPERO identifier, CRD42022348098). A total of 40 RCTs (7829 eyes) with 33 placebo groups (2055 eyes) along with 7 untreated groups (1184 eyes) were included. Among placebo-controlled trials, placebo was determined to be effective in lowering IOP (ES, -1.30 mmHg; 95% CI, -1.75 to -0.84 mmHg). Using NMA, the ES for placebo was -2.27 mmHg (95% CI, -3.52 to -1.01 mmHg) greater than ES for untreated control participants.. According to the multiple meta-regression model, the active treatment ES was a significant factor to predict the amount of placebo effect. Placebo additionally lowered IOP by -0.45 mmHg per -1 mmHg of active treatment effect. Add-on study design and larger sample size also were associated with greater amount of placebo effect. No publication bias was evident in either a funnel plot or the Begg and Mazumdar adjusted rank correlation test results (P = 0.24). This meta-analysis indicated that placebo is effective in lowering IOP and is superior to the effect observed for the untreated control participants. However, caution is required in interpreting the results because of the small number of untreated controlled trials and potential bias from the lack of direct comparison between the placebo and untreated arms. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


A review of the toxicity of HIV medications.
Antiretroviral therapy has changed human immunodeficiency virus (HIV) infection from a near-certainly fatal illness to one that can be managed chronically. More patients are taking antiretroviral drugs (ARVs) for longer periods of time, which naturally results in more observed toxicity. Overdose with ARVs is not commonly reported. The most serious overdose outcomes have been reported in neonates who were inadvertently administered supratherapeutic doses of HIV prophylaxis medications. Typical ARV regimens include a "backbone" of two nucleoside reverse transcriptase inhibitors (NRTI) and a "base" of either a protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor. New classes of drugs called entry inhibitors and integrase inhibitors have also emerged. Older NRTIs were associated with mitochondrial toxicity, but this is less common in the newer drugs, emtricitabine, lamivudine, and tenofovir. Mitochondrial toxicity results from NRTI inhibition of a mitochondrial DNA polymerase. Mitochondrial toxicity manifests as myopathy, neuropathy, hepatic failure, and lactic acidosis. Routine lactate assessment in asymptomatic patients is not indicated. Lactate concentration should be obtained in patients taking NRTIs who have fatigue, nausea, vomiting, or vague abdominal pain. Mitochondrial toxicity can be fatal and is treated by supportive care and discontinuing NRTIs. Metabolic cofactors like thiamine, carnitine, and riboflavin may be helpful in managing mitochondrial toxicity. Lipodystrophy describes changes in fat distribution and lipid metabolism that have been attributed to both PIs and NRTIs. Lipodystrophy consists of loss of fat around the face (lipoatrophy), increase in truncal fat, and hypertriglyceridemia. There is no specific treatment of lipodystrophy. Clinicians should be able to recognize effects of chronic toxicity of ARVs, especially mitochondrial toxicity.


Intraoperative floppy iris syndrome associated with risperidone intake.
Intraoperative floppy iris syndrome (IFIS) has been strongly associated with intake of selective a1 adrenergic blockers, particularly tamsulosin. Intraoperative floppy iris syndrome has also been linked to the use of other drugs with some a antagonist activity. We identified patients on long-term treatment with the antipsychotic agent risperidone who showed typical features of IFIS during cataract surgery. We report 3 eyes in 2 patients taking risperidone in which typical features of IFIS were noted during cataract surgery. Risperidone is a widely prescribed drug in psychiatric practice and has a-blocking actions as well as strong affinity for serotonin 2A receptors. Ophthalmologists should be aware of the possible association with IFIS when performing cataract surgery on patients taking risperidone.


The obstetric and gynaecological management of women with inherited bleeding disorders--review with guidelines produced by a taskforce of UK Haemophilia Centre Doctors' Organization.
The gynaecological and obstetric management of women with inherited coagulation disorders requires close collaboration between obstetrician/gynaecologists and haematologists. Ideally these women should be managed in a joint disciplinary clinic where expertise and facilities are available to provide comprehensive assessment of the bleeding disorder and a combined plan of management. The haematologist should arrange and interpret laboratory tests and make provision for appropriate replacement therapy. These guidelines have been provided for healthcare professionals for information and guidance and it is also intended that they are readily available for women with bleeding disorders.


Diabetes and cognitive decline.
Epidemiologic studies have documented an association between diabetes and increased risk of cognitive decline in the elderly. Based on animal model studies, several mechanisms have been proposed to explain such an association, including central insulin signaling, neurodegeneration, brain amyloidosis, and neuroinflammation. Nevertheless, the exact mechanisms in humans remain poorly defined. It is reasonable, however, that many pathways may be involved in these patients leading to cognitive impairment. A major aim of clinicians is identifying early onset of neurologic signs and symptoms in elderly diabetics to improve quality of life of those with cognitive impairment and reduce costs associated with long-term complications. Several biomarkers have been proposed to identify diabetics at higher risk of developing dementia and diagnose early stage dementia. Although biomarkers of brain amyloidosis, neurodegeneration and synaptic plasticity are commonly used to diagnose dementia, especially Alzheimer disease, their role in diabetes remains unclear. The aim of this review is to explore the molecular mechanisms linking diabetes with cognitive decline and present the most important findings on the clinical use of biomarkers for diagnosing and predicting early cognitive decline in diabetics.


Functional mitral regurgitation after a first non-ST segment elevation acute coronary syndrome: very-long-term follow-up, prognosis and contribution to left ventricular enlargement and atrial fibrillation development.
To assess the relationship between functional mitral regurgitation (MR) after a non-ST segment elevation acute coronary syndrome (NSTSEACS) and long-term prognosis, ventricular remodelling and further development of atrial fibrillation (AF), since functional MR is common after myocardial infarction. Prospective cohort study conducted in a tertiary referral centre. We prospectively studied 237 patients consecutively discharged in New York Heart Association class I-II (74% men; mean age 66.1 years) after a first NSTSEACS. All underwent an ECG the first week after admission and were echocardiographically and clinically followed-up (median 6.95 years). MR was detected in 95 cases (40.1%) and became an independent risk factor for the development of heart failure (HF) and major adverse cardiovascular events (MACE) (per MR degree, HRHF 1.71, 95% CI 1.138 to 2.588, p=0.01; HRMACE 1.49, 95% CI 1.158 to 1.921, p=0.002). Left ventricular diastolic (grade I 12.7±40.7; grade II 26.8±12.4; grade III 46.3±50.9 mL, p=0.01) and systolic (grade I 10.4±37.3; grade II 10.12±12.7; grade III 36.8±46.0 mL, p=0.02) mean volumes were higher after follow-up in patients with MR, in proportion to the initial degree of MR. In the rhythm analysis (126 patients; previously excluding those with any history of AF) during follow-up, 11.4% of patients with degree I MR, 14.3% with degree II MR and 75% with degree III MR developed AF, while only 5.1% of those with degree 0 developed AF, p<0.001. MR is common after an NSTSEACS. The presence and greater degree of MR confers a worse long-term prognosis after a first NSTSEACS. This can in part be explained by increased negative ventricular remodelling and increased occurrence of AF.


Direct oral anticoagulants for therapeutic anticoagulation in postoperative pulmonary embolism after meningioma resection.
Acute postoperative pulmonary embolism (PE) is a dreaded complication with severe mortality rates. Brain tumor patients are at the highest risk for postoperative PE. The juxtaposition of low-molecular-weight heparin (LMWH), vitamin K antagonists (VKA) and direct oral anticoagulation (DOAC) in the treatment of postoperative PE in meningioma patients is largely unexplored. This is a single center observational analysis of meningioma patients who underwent neurosurgical resection with a thoracic CT scan confirmation of postoperative PE. The treatment modality, clinical course and outcome were investigated. Of 538 meningioma patients operated, 30 (6%) developed acute postoperative PE. After diagnosis, these patients received different long-term anticoagulation regimes. No significant difference in postoperative hemorrhage (p < 0.56), re-operation rate (p < 0.70) or Karnofsky performance scale (KPS) at 3 (p < 0.34) and 12 months (p = 1) were identified, when compared according to the different anticoagulation regimes. DOACs were not associated with elevated risk for hemorrhage, recurrent thrombosis or poor outcome when compared with traditional anticoagulation regimes. Prospective randomized trials are necessary to verify the non-inferiority of DOACs for long-term anticoagulation in postoperative pulmonary embolism after meningioma resection.


XQ-1H regulates Wnt/GSK3β/β-catenin pathway and ameliorates the integrity of blood brain barrier in mice with acute ischemic stroke.
10-O-(N, N-dimethylaminoethyl) ginkgolide B methanesulfonate (XQ-1H), a novel analog of ginkgolide B, has been preliminarily recognized to show bioactivities against ischemia-induced injury. However, the underlying mechanism still remains to be fully elucidated. The aim of this study was to investigate the effect of XQ-1H against cerebral ischemia/reperfusion injury (CIRI) from the perspective of blood brain barrier (BBB) protection, and explore whether the underlying mechanism is associated with Wnt/GSK3β/β-catenin signaling pathway activation. The therapeutic effects of XQ-1H were evaluated in mice subjected to middle cerebral artery occlusion/reperfusion (MCAO/R) and in immortalized mouse cerebral endothelial cells (bEnd.3) challenged by oxygen and glucose deprivation/reoxygenation (OGD/R). Results showed that treatment with XQ-1H improved neurological behavior, reduced brain infarction volume, diminished edema, and attenuated the disruption of BBB in vivo. In vitro, XQ-1H increased cell viability and maintained the barrier function of bEnd.3 monolayer after OGD/R. Moreover, the protection of XQ-1H was accompanied with activation of Wnt/GSK3β/β-catenin pathway and upregulation of tight junction proteins. Notably, the protection of XQ-1H was abolished by Wnt/GSK3β/β-catenin inhibitor XAV939 or β-catenin siRNA, indicating XQ-1H exerted protection in a Wnt/GSK3β/β-catenin dependent profile. In summary, XQ-1H attenuated brain injury and maintained BBB integrity after CIRI, and the possible underlying mechanism may be related to the activation of Wnt/GSK3β/β-catenin pathway and upregulation of tight junction proteins.


Behavioral effects of acute manganese chloride administration in chickens.
The behavioral effects of manganese chloride at 20 and 40 mg/kg, subcutaneously (sc), were examined in 1-mo-old broiler chickens using the open-field (5 min) and tonic immobility tests. In a separate experiment, chickens were subjected to a pharmacological challenge with the anesthetic combination of xylazine-ketamine following manganese chloride pretreatment at 50 mg/kg, sc. Manganese at 40 mg/kg significantly decreased jumping attempts of the chickens in the open-field test 30 min after the injection when compared with the control (saline) group. Both manganese treatments significantly increased the tonic immobility response of the chickens in a dose-dependent manner in comparison with the control group. Pretreatment with manganese chloride (50 mg/kg, sc) significantly increased the duration of sleep, decreased the latency to onset of analgesia, and increased the duration of analgesia in chickens treated with the anesthetic xylazine-ketamine mixture when compared with the saline control group. The respiratory rate of all anesthetized chickens significantly decreased from respective preanesthetic (time 0) values during the 60-min observation period after injection of the anesthetic. However, 60 min after the anesthetic injection, the respiratory rate of the manganese-treated group was significantly lower than that of the control group. The data suggest a depressant action of acute manganese chloride treatment in chickens.


The InsP3 receptor: its role in neuronal physiology and neurodegeneration.
The InsP3 receptor is a ligand-gated channel that releases Ca2+ from intracellular stores in a variety of cell types, including neurons. Genetic studies from vertebrate and invertebrate model systems suggest that coordinated rhythmic motor functions are most susceptible to changes in Ca2+ release from the InsP3 receptor. In many cases, the InsP3 receptor interacts with other signaling mechanisms that control levels of cytosolic Ca2+, suggesting that the maintenance of Ca2+ homeostasis in normal cells could be controlled by the activity of the InsP3R. In support of this idea, recent studies show that altered InsP3 receptor activity can be partially responsible for Ca2+ dyshomeostasis seen in many neurodegenerative conditions. These observations open new avenues for carrying out genetic and drug screens that target InsP3R function in neurodegenerative conditions.


The erythroblastic island as an emerging paradigm in the anemia of inflammation.
Terminal erythroid differentiation occurs in the bone marrow, within specialized niches termed erythroblastic islands. These functional units consist of a macrophage surrounded by differentiating erythroblasts and have been described more than five decades ago, but their function in the pathophysiology of erythropoiesis has remained unclear until recently. Here we propose that the central macrophage in the erythroblastic island contributes to the pathophysiology of anemia of inflammation. After introducing erythropoiesis and the interactions between the erythroblasts and the central macrophage within the erythroblastic islands, we will discuss the immunophenotypic characterization of this specific subpopulation of macrophages. We will then integrate these concepts into the currently known pathophysiological drivers of anemia of inflammation and address the role of the central macrophage in this disorder. Finally, as a means of furthering our understanding of the various concepts, we will discuss the differences between murine and rat models with regard to developmental and stress erythropoiesis in an attempt to define a model system representative of human pathophysiology.


Time-dependent component-specific regulation of gastric acid secretion-related proteins by roasted coffee constituents.
Consumption of coffee beverages has been reported to cause gastric irritation in some consumers as a result of increased gastric acid secretion. In the complex mechanisms of gastric acid secretion, the activity and expression of the H+,K+-ATPase is regulated by transmitters, such as histamine, acetylcholine, gastrin, somatostatin, and their corresponding receptors. Here, we report the effect of three coffee constituents, chlorogenic acid, caffeine, and N-methyl pyridinium ions, on the expression of the histamine receptor H2, the acetylcholine receptor M3, the gastrin receptor, the somatostatin receptor, and the H+,K+-ATPase. Human gastric cancer cells were exposed to chlorogenic acid, caffeine, or N-methyl pyridinium in their coffee brew-representative concentrations as well as to physiological stimulators of gastric acid secretion. Gene expression levels of receptor proteins and those of the H+,K+-ATPase were measured at different time points by real-time PCR. Expression of prosecretory receptors significantly increased between one and one-half to twofold after treatment with chlorogenic acid or caffeine compared to control cells at the same time point. Chlorogenic acid and caffeine also increased the H+,K+-ATPase gene expression twofold higher compared to control cells. In contrast, N-methyl pyridinium downregulated the expression of the prosecretory gastrin receptor significantly, by -27%. In conclusion, chlorogenic acid, caffeine, and N-methyl pyridinium impair the expression of gastric acid secretion-related proteins in a time-dependent manner. Future work will be aimed at the elucidation of the cooperative interplay of individual components using recombinates of single coffee constituents.


Reduced sodium pump activity in inositol-deficient HL-60 cells: no evidence of control by protein kinase C.
HL-60 cells were cultured in normal and inositol-deficient media. The inositol-deficient cells showed reduced sodium pump activity, as measured by ouabain-sensitive 86Rb+ uptake. The protein kinase C inhibitors staurosporine and H7 did not affect uptake in either normal or inositol-deficient cells. However, U73122, a steroidal inhibitor of phosphoinositidase C, inhibited uptake in both types of cells. Activators of protein kinase C had no effect on Rb+ entry. The inositol deficiency is not considered to affect the sodium pump by a mechanism involving diacylglycerol and protein kinase C.


A comprehensive pediatric bone marrow transplant documentation tool.
To describe the development and use of a tool to document assessment and provision of education to children undergoing bone marrow transplantation (BMT) and their families. A hospital's BMT Clinical Issues Committee, BMT staff, and hospital standards. A comprehensive tool was developed to complement the hospital's admission tool to facilitate assessment and documentation of BMT-specific education of the patient and family. The implementation of the tool was specifically designed to facilitate its use across outpatient and inpatient settings. Based on quality assurance indicators, the tool has succeeded in documenting appropriate education activities. A consistent and organized approach to documentation is beneficial to nursing practice. This tool can be adapted to any clinical situation where educational needs are great.