Antidepressant medication prescribing patterns in Irish general practice from 2016 to 2020 to assess for long-term use.
The aim of this study was to identify the trends in antidepressant (AD) medication use in two Irish general practices over a 5-year period, 2016 to 2020. The rationale for this study is attributed to the growing prevalence of depression amongst the Irish general public as well as concerns surrounding long-term AD medication use. The research was undertaken in 2021 examining AD prescription rates from 2016 to 2020. The medications of interest were selective serotonin and norepinephrine reuptake inhibitors (SSRI and SNRIs): sertraline, escitalopram, fluoxetine and venlafaxine. The number of medical card holders (MCH) and prescription dispensing rates were analysed for observable trends. AD medication use is rising amongst the Irish MCH population. The number of MCH prescribed AD grew from 9.42 to 12.3 per 100 MCH between the years 2016 and 2020, respectively. The year 2020 represented the largest proportion of MCH prescriptions, 6.32 AD prescriptions per 1000 MCH prescriptions. The years 2019 to 2020 represented the largest annual increase in prescription dispensing with a growth of 0.45 per 1000 MCH prescriptions. Annual figures show a continual increase in AD dispensing refill rates from 4.14 to 5.67 per 1000 MCH prescriptions in 2016 and 2020, respectively. This study illustrates a steady rise in AD medication within the general practice setting, with an observed rise in prescription dispensing rates. The high proportion of refill prescriptions demonstrates the long-term use of AD medications. This may be indicative of chronic depression or may highlight a lack of appropriate medication cessation strategies.


Pancreatic insulinoma: Diagnosis and treatment of a rare tumour with misleading symptoms - A case report.
Insulinomas are an uncommon occurrence, with an annual incidence of approximately 4 per million. These functional pancreatic neuroendocrine tumours can present with a myriad of nonspecific symptoms leading to frequent misdiagnoses. In this case report is presented a 55-year-old man who was misdiagnosed and managed for a seizure disorder with escalating antiepileptic treatments for 11 months. A thorough history after an attack was the main tool in solving the mystery of his refractory seizures, leading to the discovery of a pancreatic insulinoma. Biochemical tests revealed fasting hypoglycaemia and a relative hyperinsulinemia, and a distal pancreatic lesion measuring approximately 1.8 cm × 1.3 cm was detected on CT, MRI and endoscopic ultrasound. Successful laparoscopic pancreatic left resection led to complete resolution of symptoms and restoration of quality of life to pre-illness levels. Insulinomas have historically been difficult to diagnose because their symptoms mimic neurologic and psychiatric conditions. Patterns of symptom occurrence obtained from a carefully-taken history is the single most important tool in assessing patients with insulinomas, who usually present with unusual and refractory neuropsychiatric conditions.


Key Aspects of Neurovascular Control Mediated by Specific Populations of Inhibitory Cortical Interneurons.
Inhibitory interneurons can evoke vasodilation and vasoconstriction, making them potential cellular drivers of neurovascular coupling. However, the specific regulatory roles played by particular interneuron subpopulations remain unclear. Our purpose was therefore to adopt a cell-specific optogenetic approach to investigate how somatostatin (SST) and neuronal nitric oxide synthase (nNOS)-expressing interneurons might influence the neurovascular relationship. In mice, specific activation of SST- or nNOS-interneurons was sufficient to evoke hemodynamic changes. In the case of nNOS-interneurons, robust hemodynamic changes occurred with minimal changes in neural activity, suggesting that the ability of blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) to reliably reflect changes in neuronal activity may be dependent on type of neuron recruited. Conversely, activation of SST-interneurons produced robust changes in evoked neural activity with shallow cortical excitation and pronounced deep layer cortical inhibition. Prolonged activation of SST-interneurons often resulted in an increase in blood volume in the centrally activated area with an accompanying decrease in blood volume in the surrounding brain regions, analogous to the negative BOLD signal. These results demonstrate the role of specific populations of cortical interneurons in the active control of neurovascular function.


Second allogeneic transplantation for relapse of malignant disease: retrospective analysis of outcome and predictive factors by the EBMT.
In patients treated with allogeneic stem cell transplantation (SCT) for malignant disease who suffer from a relapse after the transplantation, the role of second allogeneic SCT is often uncertain. In a retrospective analysis, 2632 second allogeneic transplantations carried out for a relapse after the first transplantation were analyzed to define indications and identify predictive factors. Fifteen percent of the patients remained relapse-free until 5 years after the second SCT. Patients with CML had a better survival than patients with other diseases. In a multivariate analysis, factors associated with better survival were low disease burden, longer remission duration after the first transplantation, longer interval between the transplantations, younger age, absence of grade II-IV acute GvHD or chronic GvHD after the first transplantation, and later year of transplantation. The European Society for Blood and Marrow Transplantation risk score predicted the outcome. Using the same donor as in the first transplantation vs another donor had no predictive value for survival. Sibling donor was a favorable predictive factor. In conclusion, second allogeneic SCT offers a reasonable option especially for young patients with a long remission after the first transplantation and a low disease burden. The present findings do not support the usefulness of changing the donor for the second transplantation.


[Expression of B cell-specific activator protein in lymphomas].
To investigate the expression of B cell-specific activator protein (BSAP)/Pax-5 in lymphomas. One hundred and two cases of diffuse large B-cell lymphoma (DLBCL), 3 cases of follicular lymphoma (FL), 3 cases of extranodal marginal zone B-cell lymphoma, 1 case of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), 10 cases of anaplastic large cell lymphoma (ALCL) and 10 cases of plasmacytoma were studied immunohistochemically for BSAP and CD20. The tumor cells in the 102 cases of DLBCL all expressed CD20, amongst which 100 cases also expressed BSAP. Three cases of FL, 3 cases of extranodal marginal zone B-cell lymphoma and 1 case of NLPHL also expressed BSAP and CD20. All the ALCLs and plasmacytomas did not express BSAP and CD20. The expression rates of CD20 and BSAP were highly consistent. The intensity of staining showed no statistical significance. BSAP/Pax-5 is a novel B-cell marker expressed in tumor nuclei of B-cell lymphomas. Though less sensitive than CD20, anti-BSAP has diagnostic value in routine surgical pathology practice.


[Use of an unmodified conventional respirator in anesthesia. Experience with the Oxylog respirator].
The use of an unmodified conventional ventilator for an anaesthesia circuit is described, whereby the dilution of the anaesthetic gas by the driving gas is avoided due to the connecting deadspace. The method was investigated in model measurements, standard ventilator settings for normoventilation are suggested, and first clinical results are reported.


Synthesis, in vitro cytotoxicity and radiosensitizing activity of novel 3-[(2,4-dinitrophenylamino)alkyl] derivatives of 5-fluorouracil.
Previously, it was reported that 3[3-(2,4-dinitrophenylamino)-propyl]-5-fluorouracil 8c unlike its components 5-fluorouracil (5-FU) 6 and 2,4-dinitroaniline 2 in HT-29 cells under aerobic conditions had no cytotoxicity but showed radiosensitizing activity. In this study several analogues of 8c differing in the number of linking methylene groups were prepared and tested for in vitro cytotoxicity and radiosensitizing activity under both aerobic and hypoxic conditions. Tethered compound 8a was prepared in one pot by the reaction of 5-FU 6 with paraformaldehyde and 2,4-dinitroaniline 2 in the presence of the concentrated hydrochloric acid, and compounds 8b-f were prepared by the reaction of N-(bromoalkyl)-2,4-dinitrobenzeneamines 5b-f with 1-(t-butoxycarbonyl)-5-fluorouracil 7 followed by hydrolysis of the protecting group. The cytotoxicity of the tested compounds were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), and propidium iodide (PI)-digitonin assays and values of sensitization enhancement ratio (SER) as a measure of the radiosensitizing activity were measured from radiation survival curves in the absence and presence of each sensitizer for 37% survival respectively. Results showed that tethered compounds 8a-f induced time- and concentration-dependent cytotoxicity under hypoxia but had no significant effect under aerobic conditions. These compounds also showed selective and concentration-dependent radiocytotoxicity under hypoxic conditions.


Low-density lipoprotein apheresis is effective in reducing lipoprotein(a) levels and in improving symptoms in a patient with refractory angina secondary to accelerated coronary artery disease.
Coronary artery disease remains a significant cause of morbidity and mortality in the Western world. High plasma Lp(a) concentrations are related to the risk of cardiovascular disease, but Lp(a) is rarely assayed and treated. We present the case of a 50-year-old gentleman with refractory angina, whose coronary disease continued to progress despite optimal medical and surgical therapy. We show that the aggressive reduction of Lp(a) successfully ameliorated the progression of coronary stenosis and provides effective and durable relief of symptoms.


Effects of high-intensity interval training with an eccentric hamstring exercise program in futsal players: A randomized controlled trial.
Physiotherapy protocols based on high-intensity interval training (HIIT) or eccentric hamstring exercises like Nordic Curl (NC) have been scarcely studied in futsal players. The objective of this study was to compare the effectiveness of a HIIT combined with an NC exercise program versus a HIIT-only program in futsal players. Twenty-one futsal players were divided into (1) HIIT + NC group (n = 11, mean age = 21.55 [4.25]); and (2) HIIT group (n = 10, mean age = 20.90 [1.29]). The HIIT + NC group performed a HIIT circuit combined with 3 sets of 10 NC repetitions for 4 weeks, while the HIIT group performed the same protocol without NC exercise. Body mass index, intermittent work performance, vertical jump performance without and with arms, isometric strength of quadriceps and hamstrings, and the isometric hamstrings/quadriceps (H/Q) ratio, were assessed before and after the interventions. The HIIT + NC group and the HIIT group showed a significant improvement in intermittent work performance after the intervention (P = .04 and P = .01, respectively). Also, both groups showed a trend of increasing quadriceps and hamstring isometric strength, although no significant changes were found (P > .05). In addition, neither the HIIT + NC protocol nor the HIIT protocol was sufficient to yield changes in body mass index nor to improve the vertical jump performance (P > .05). Both an isolated HIIT protocol and HIIT in combination with NC exercise improved intermittent work performance in futsal players. The present study's findings may guide futsal players' physical preparation and injury prevention programs.


Application of image processing to assess emulsion stability and emulsification properties of Arabic gum.
This paper focuses on the development of an effective methodology to determine the optimum levels of independent variables leading to maximize stability of O/W emulsions containing Arabic gum, as a natural emulsifier and stabilizer. Response surface methodology (RSM) was employed to determine the effect of Arabic gum content (2%, 5%, and 8% (w/w)), homogenization time (5, 12.5, and 20 min) and storage temperature (4, 22, and 40 °C). Image processing was used to determine emulsion stability based on responses including creaming index, centrifugal stability, viscosity, color parameters, and D32 and D43 indices. For each response, a second-order polynomial model with high coefficient of determination (R(2)) values ranging from 0.95 to 0.989 was developed using multiple linear regression analysis. The optimization results showed that the overall optimum region with the highest stability was found to be at the combined levels of 5.81% (w/w) Arabic gum content, 5 min homogenization time, and 22 °C for storage temperature.


226Ra, 210Po and lead isotopes in a pit lake water profile in Sweden.
A pit lake arises as a consequence of anthropogenic activities in opencast mining areas. These water bodies may be enriched in hazardous stable contaminants and/or in naturally occurring radionuclides depending on the local geological conditions. Mining legacy in Sweden produced hundreds of these pit lakes and most of them are used for recreational purposes in the southern part of the country. In this paper, one pit lake was selected for having enhanced levels of natural radionuclides. Physico-chemical parameters (temperature, pH, oxidation-reduction potential, dissolved oxygen and depth), elemental composition (via Inductive Coupled Plasma Mass Spectrometry) and radiometric characterization (via alpha spectrometry of 226Ra, 210Po and 210Pb) were carried along the depth of a 60 m depth pit lake, with the main aim to describe how natural radionuclides and elements behaves with depth in a non-uraniferous pit lake. Based on observed changes in physico-chemical parameters, a thermocline and a chemocline region were identified at around 10 and 30 m depth respectively. Concerning radionuclides, 226Ra ranged from 75 ± 3 up to 360 ± 12 mBq/kg while 210Po ranged from 11 ± 1 up to 71 ± 3 mBq/kg. 210Pb distribution with depth was also determined via secular equilibrium with 210Po after 2 years and also stable Pb was measured. Disequilibrium 226Ra-210Pb was found and the residence time of 210Pb in the water column was assessed. Additionally, different vertical distributions between 210Pb and Pb were found which points out different sources for different lead isotopes in the water body.


Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia.
The study evaluated the efficacy and safety of long-term coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia (HeFH). Aggressive intervention to achieve lipid goals for adolescents with HeFH is recommended to reduce risk of premature cardiovascular disease. In a multicenter, randomized, double-blind, placebo-controlled study, 248 male and female subjects ages >or=10 and <or=17 years with HeFH were randomized to receive: step 1: simvastatin 10, 20, or 40 mg/day plus ezetimibe 10 mg/day or placebo for 6 weeks, followed by step 2: simvastatin 40 mg/day plus ezetimibe 10 mg/day or placebo for 27 weeks; followed by step 3: all subjects received open-label simvastatin 10 or 20 mg/day (titrated to maximum 40 mg/day) plus ezetimibe 10 mg/day for 20 weeks. Safety was assessed throughout the study. Coadministered ezetimibe and simvastatin for 6 weeks (step 1) resulted in significantly greater mean reduction in low-density lipoprotein cholesterol (LDL-C) from baseline (49.5%) compared with simvastatin monotherapy (34.4%; p < 0.01) in pooled dose groups and in individual dose groups (46.7% vs. 30.4%, 49.5% vs. 34.3%, 52.1% vs. 38.6%, respectively; p < 0.01). At 33 weeks (step 2), ezetimibe-simvastatin subjects had a mean 54.0% reduction in LDL-C compared with a mean 38.1% reduction in simvastatin monotherapy subjects (p < 0.01). At 53 weeks (step 3), the pooled reduction in LDL-C was 49.1%. All treatment regimens were well tolerated throughout 53 weeks. Coadministration of ezetimibe with simvastatin was safe, well tolerated, and provided higher LDL-C reduction compared with simvastatin alone in adolescents with HeFH studied up to 53 weeks. (Effects of Ezetimibe With Simvastatin in the Therapy of Adolescents With Heterozygous Familial Hypercholesterolemia; NCT00129402).


Influence of GaAsBi Matrix on Optical and Structural Properties of InAs Quantum Dots.
InAs/GaAsBi dot-in-well structures were fabricated using gas-source molecular beam epitaxy and investigated for its optical and structural properties. GaAsBi-strained buffer layer and strain reduction layer are both effective to extend the photoluminescence (PL) emission wavelength of InAs quantum dot (QD). In addition, a remarkable PL intensity enhancement is also obtained compared with low-temperature-grown GaAs-capped InAs QD sample. The GaAsBi matrix also preserves the shape of InAs QDs and leads to increase the activation energy for nonradiative recombination process at low temperature. Lower density and larger size of InAs QDs are obtained on the GaAsBi surface compared with the QDs grown on GaAs surface.


Sarcoma of the pulmonary artery trunk: report of a case complicated with hemopericardium and cardiac tamponade.
A 64-year-old woman presented initially with a metastatic spindle-cell sarcoma of the lung of unknown primary. She suddenly died nine months later from hemopericardium with cardiac tamponade caused by partial hemorrhagic necrosis of pulmonary artery trunk sarcoma.


Evaluation of Staining-Dependent Colour Changes in Resin Composites Using Principal Component Analysis.
Colour changes in Gradia Direct™ composite after immersion in tea, coffee, red wine, Coca-Cola, Colgate mouthwash, and distilled water were evaluated using principal component analysis (PCA) and the CIELAB colour coordinates. The reflection spectra of the composites were used as input data for the PCA. The output data (scores and loadings) provided information about the magnitude and origin of the surface reflection changes after exposure to the staining solutions. The reflection spectra of the stained samples generally exhibited lower reflection in the blue spectral range, which was manifested in the lower content of the blue shade for the samples. Both analyses demonstrated the high staining abilities of tea, coffee, and red wine, which produced total colour changes of 4.31, 6.61, and 6.22, respectively, according to the CIELAB analysis. PCA revealed subtle changes in the reflection spectra of composites immersed in Coca-Cola, demonstrating Coca-Cola's ability to stain the composite to a small degree.


Thymosin β4 and cardiac protection: implication in inflammation and fibrosis.
Thymosin beta 4 (Tβ4) is a ubiquitous protein with diverse biological functions. The effecter molecules targeted by Tβ4 in cardiac protection remain unknown. We summarize previously published work showing that treatment with Tβ4 in the myocardial infarction setting improves cardiac function by activating Akt phosphorylation, promoting the ILK-Pinch-Parvin complex, and suppressing NF-κB and collagen synthesis. In the presence of Wortmannin, Tβ4 showed minimal cardiac protection. In vitro findings revealed that pretreatment with Tβ4 resulted in reduction of intracellular ROS in the cardiac fibroblasts and was associated with increased expression of antioxidant enzymes, reduction of Bax/Bcl(2) ratio, and attenuation of profibrotic genes. Silencing of Cu/Zn-SOD, catalase, and Bcl(2) genes abrogated the protective effect of Tβ4. Our findings suggest that Tβ4 improves cardiac function by enhancing Akt and ILK activation and suppressing NF-κB activity and collagen synthesis. Furthermore, Tβ4 selectively upregulates catalase, Cu/Zn-SOD, and Bcl(2), thereby protecting cardiac fibroblasts from H(2)O(2) -induced oxidative damage. Further studies are warranted to elucidate the signaling pathway(s) involved in the cardiac protection afforded by Tβ4.


Development and validation of a ultraperformance liquid chromatography-tandem mass spectrometry method for quantifying free and total dabigatran in human plasma: An application for a bioequivalence study.
Dabigatran etexilate mesylate (DABE), a prodrug, quickly changes into dabigatran (DAB) after its oral administration. Accordingly, detecting DABE in plasma is practically unmanageable. An ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed and validated to compute free DAB in participants. For the first time, the central composite design, a type of response surface methodology, was applied for optimizing variables affecting the cleavage of glucuronide bond. In addition, the pharmacokinetic parameters of generic medication (okanadab) were determined, and the obtained outcomes were compared with those of the branded drug (pradaxa). The sample preparation was done using methanol as a protein precipitant and the separation was achieved using an ACQUITY UPLC BEH C18 column (2.1 × 50 mm, 1.7 μm). The elution was isocratically conducted using 10 mM ammonium formate:methanol (72:28, v/v) as a mobile phase and the flow rate was 0.25 mL/min. Multiple reaction monitoring and positive electrospray ionization were used. The determination was performed within 1 min, and the calibration growth curve was established over a range of 1.19-475 ng/mL using DAB-d3 as a tagged internal standard. Bioequivalence research was validated following the US Food and Drug Administration (US FDA) guidelines for bioanalytical procedures and acceptable outcomes were achieved. The outcomes for okanadab and pradaxa did not differ significantly.


Initial anatomic investigations of the I-gel airway: a novel supraglottic airway without inflatable cuff.
The I-gel airway is a novel supraglottic airway that uses an anatomically designed mask made of a gel-like thermoplastic elastomer. We studied the positioning and mechanics of this new device in 65 non-embalmed cadavers with 73 endoscopies (eight had repeat insertion), 16 neck dissections, and six neck radiographs. A full view of the glottis (percentage of glottic opening score 100%) occurred in 44/73 insertions, whereas only 3/73 insertions had epiglottis-only views. Including the eight repeat insertions with a different size, a glottic opening score of > 50% was obtained in all 65 cadavers. The mean percentage of glottic opening score for the 73 insertions was 82% (95% confidence interval 75-89%). In each of the neck dissections and radiographs the bowl of the device covered the laryngeal inlet. We found that the I-gel effectively conformed to the perilaryngeal anatomy despite the lack of an inflatable cuff and it consistently achieved proper positioning for supraglottic ventilation.


The prevalence of hoarseness among health care professionals: time trends and effect of remediation in working conditions in 2007-2018.
The purpose of this study was to investigate time trends in the prevalence of hoarseness among health care professionals in primary health care units (PHC) and in hospitals from 2007 to 2018. Moreover, purpose was to discover potential indoor environmental quality (IEQ) risk factors as well as to determine the effect of the remediation of the indoor air problems on the prevalence of hoarseness. The health status was collected from all employees in these units/hospitals (N = 1564/1199) with questionnaires and the follow-ups were carried out as an open cohort. Based on building condition inspections, buildings were classified to be an "exposed" or "reference" buildings by third-party experts. The before and after remediation results were compared to reference buildings. During follow-up, hoarseness has not increased in those PHC units with good IEQ. In the pilot study, the prevalence of hoarseness in non-exposed reference building was 5.9%, and it stayed approximately at the same level throughout the follow-up. Whereas in buildings with an IEQ problem the prevalence of hoarseness varied between 16.2 and 36.1% and it decreased to 11.4% after the remediations. In a large hospital with severe IEQ problems, the prevalence of hoarseness was 39.1%, and in hospital buildings with a milder exposure 23.3%. The most important risk factors for hoarseness were asthma, allergic rhinitis and IEQ problems. A good indoor environment and the remediation of damaged buildings seem to promote a better condition of the voice in health care workers.


A gene chip study suggests that miR-17-3p is associated with diabetic foot ulcers.
Background of the Study Diabetic foot ulcers (DFUs) are severe effect of diabetes. This research aimed to discover the role of micro-ribonucleic acid (miRNA) in treating DFUs involved in maggot debridement therapy (MDT) via a miRNA chip study. A miRNA chip approach was adopted. Patients with diabetes (type 1 or 2) who had at least one-foot ulcer (current or previous) were enrolled in the study. The alterations of miRNA expressions in the granulation tissue during treatment with MDT were measured. Following MDT, the increased expression of miR17-92 was verified in vivo. The miR-17-3p expression increased, and Flk-1 (vascular endothelial growth factor) expression was significantly reduced in patients with DFUs who received MDT (P < 0.01). Results from human umbilical vein endothelial cells that excrete or secrete showed consistency with in vitro findings (P < 0.001, P < 0.05). The overexpression of miR-17-3p demonstrated inhibitory activity on tube formation (P < 0.05). When DFUs were treated with MDT, it revealed that miR-17-3p had a negative regulatory effect on Flk-1.


[Oral infections and pregnancy: knowledge of health professionals].
The abundance of recent studies on the relationship between oral diseases and complications of pregnancy leads to questions on knowledge of health professionals. This study aims to establish an inventory of knowledge and practice of health professionals in France on this issue. A questionnaire on knowledge of the relationship between oral diseases and complications of pregnancy was referred to gynaecologists and obstetricians, midwives and dentists. This study was conducted at the University Hospital of Nantes and Le Mans General Hospital. Eighty-seven professionals of pregnancy and 259 dentists responded to the survey. Bleeding gums and pregnancy gingivitis are the oral manifestations most cited by all practitioners. There is however a difference concerning the epulis and caries risk. The most cited Pregnancy complications are risk of premature delivery and chorioamniotitis. Only dentists had received initial training on pregnancy complications. Finally, all health professionals point to the lack of continued education on this topic. There is a good knowledge of the pregnancy complications associated with oral disease despite the lack of training of pregnancy, but the attitudes of care are not still in adequacy. It appears necessary to strengthen the training of all practitioners in this field. The design and implementation of a specific questionnaire on oral health status could allow better identification of the patients at risk by the professionals of pregnancy, and optimize so the care of pregnant women.


Potential forensic use of a 33 X-InDel panel in the Argentinean population.
Polymorphic genetic markers located on the X chromosome might become a complement in particular forensic identification when the biological kinship are deficient. We analyzed forensic statistical parameters of 33 X-chromosome InDel polymorphisms in a sample of 320 individuals from Argentina. The X-chromosome InDel polymorphism (X-InDel) panel was amplified in a single multiplex PCR reaction. Hardy-Weinberg Equilibrium was determined in the female cohort, whereas the male cohort was used to calculate linkage disequilibrium (LD) tested by an extension of Fisher's exact test, D', and Chi-square values. Regarding LD, 15 markers were organized and grouped into six blocks containing two or three linked loci each, namely block I (MID356-MID357), block II (MID448804-MID3703-MID218), block III (MID3705-MID3706-MID304737), block IV (MID197147-MID3754), block V (MID3664-MID284601-MID103547), and block VI (MID3763-MID3728). The haplotype diversity was higher than 0.99 in all cases. Blocks III and VI showed the highest match probability in the studied population, whereas block II showed the lowest. The accumulated power of discrimination was 99.9999991 % in women and 99.9992925 % in men. The mean exclusion chance in trios and duos were 99.9891736 and 99.6099391 %, respectively. Since 15 markers are associated as haplotypic blocks, for a conservative treatment of the data, statistical evaluation should consider their haplotypic frequencies and the remaining 18 markers can be evaluated as independent loci.


Evisceration, enucleation, and exenteration.
The removal of the intraocular contents, the globe itself, or the entire orbital contents are three procedures that each present distinct pre- and postoperative problems. These procedures and the management challenges they present are discussed in this article.


Frailty and mortality among older patients in a tertiary hospital in Nigeria.
This study determined the frailty status and its association with mortality among older patients. A prospective cohort design. Study was conducted at the medical wards of University College Hospital, Ibadan, Nigeria. Four hundred and fifty older patients (>60 years) were followed up from the day of admission to death or discharge. Information obtained includes socio-demographic characteristics and clinical frailty was assessed using the Canadian Study of Health and Aging (CSHA) scale. Bivariate and multivariate analyses were carried out using SPSS version 21 at a p <0.05. Overall, frailty was identified in 285 (63.3%) respondents. Mortality was significantly higher among frail respondents (25.3%) than non-frail respondents (15.4%) p=0.028. Logistic regression analysis showed factors associated with frailty were: male sex (OR=1.946 [1.005-3.774], p=0.048), non-engagement in occupational activities (OR=2.642 [1.394-5.008], p=0.003), multiple morbidities (OR=4.411 [1.944-10.006], p<0.0001), functional disability (OR=2.114 [1.029-4.343), p=0.042], malnutrition (OR=9.258 [1.029-83.301], p=0.047) and being underweight (OR=7.462 [1.499-37.037], p=0.014). The prevalence of frailty among medical in-hospital older patients is very high and calls for its prompt identification and management to improve their survival. The study was self-funded by the authors.


A summer of phobias: media discourses on 'radical' acts of dissent against 'mass tourism' in Barcelona.
In the summer of 2017, the young group Arran coordinated a series of protests in Barcelona and other Spanish cities to denounce the negative effects of global mass tourism. These acts of dissent fueled a heated public debate in both Spanish and international press, mainly due to the 'radical' tactics employed by the demonstrators. Following the narratives about these protest acts across a diversity of media outlets, this article identifies the complex power struggles between the different actors involved in the discussion on the benefits and externalities of global mass tourism, offering an extensive analysis of the political uses of the term 'turismofobia' (tourismphobia) and a revisited interpretation of the notion of the 'protest paradigm'. This qualitative analysis was based on more than 700 media texts (including news articles, op eds and editorials) collected through the database Factiva, from January 2014 to December 2017.


Update on the pharmacologic therapy for chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease is a treatable disease characterized by progressive airflow limitation. Prevention of disease progression; improvement of symptoms, exercise tolerance, and health status; and decrease in exacerbations and mortality are the goals of management. Inhaled short-acting bronchodilators are recommended for symptoms in mild disease, whereas inhaled long-acting bronchodilators are recommended for maintenance therapy of daily symptoms. When symptoms are not controlled using one bronchodilator, combining bronchodilators may be more effective. Combining a long-acting beta-agonist with an inhaled corticosteroid is more effective than either agent alone. Several novel therapies are in different stages of development.


Secretion of antithrombin is converted from nonpolarized to apical by exchanging its amino terminus for that of apically secreted family members.
The three members of the serpin family, corticosteroid binding globulin, alpha1-antitrypsin, and C1 inhibitor are secreted apically from Madin-Darby canine kidney (MDCK) cells, whereas two homologous family members, antithrombin and plasminogen activator inhibitor-1, are secreted in a nonpolarized fashion. cDNAs coding for chimeras composed of complementary portions of an apically targeted serpin and a nonsorted serpin were generated, expressed in MDCK cells, and the ratio between apical and basolateral secretion was analyzed. These experiments identified an amino-terminal sequence of corticosteroid binding globulin (residues 1-19) that is sufficient to direct a chimera with antithrombin mainly to the apical side. A deletion/mutagenesis analysis showed that no individual amino acid is absolutely required for the apical targeting ability of amino acids 1-30 of corticosteroid binding globulin. The corresponding amino-terminal sequences of alpha1-antitrypsin and C1 inhibitor were also sufficient to confer apical sorting. Based on our results we suggest that the apical targeting ability is encoded in the conformation of the protein.


Biochemical characteristics, phage patterns, and O1 factor analysis of Escherichia coli O1:K1:H7:F11 and O1:K1:H-:F9 strains isolated from patients with urinary tract infections.
Biochemical characteristics, O1 antigen factors and phage patterns were examined in 35 urinary O1:K1 isolates of Escherichia coli different in H and F antigen. Fermentation of dulcitol, decarboxylation of ornithine, requirement for nicotinamide, and determination of O1 factor d allowed maximum differentiation. On the basis of these tests the strains could be divided into two major groups which are obviously of different clonal origin. Members of clone 1 represented by serotypes O1:K1:H7:F11 (12 strains) and O1:K1:H-:F11 (5 strains) were characterized by positive biochemical reactions and absence of O1 antigen factor d. Negative biochemical tests and presence of O1 antigen factor d were shown by strains of clone 2 which were of serotypes O1:K1:H-:F9 (14 strains) and O1:K1:H-:F- (3 strains). Phage patterns are less well correlated with clonal assignment. However, strains of clone 2 were not susceptible to K1-specific phage D and were non-typable with another set of 13 phages.


Personality changes in Alzheimer's disease: a systematic review.
People with Alzheimer's disease (AD) commonly exhibit changes in personality that sometimes precede the other early clinical manifestations of the condition, such as cognitive impairment and mood changes. Although these personality changes reflect the impact of progressive brain damage, there are several possible patterns of personality change with dementia. Early identification of personality change might assist with the timely diagnosis of AD. The objective of this study was to review studies of personality change in AD. Systematic searches of the PubMed, Ovid Medline, EBSCOhost, PsychINFO and CINAHL databases were undertaken from inception to November 2009. Published studies of informant-rated personality traits in AD patients were identified. Studies that mapped changes in traits from the five-factor model of personality which includes factors for Neuroticism, Extraversion, Openness, Agreeableness and Conscientiousness, were selected for analysis. The change in each of these five traits was calculated as the mean difference in score before and after the diagnosis of AD. There was a mean increase in Neuroticism of 10-20 T scores (equivalent to 1-2 SD), a decrease of the same magnitude in Extraversion, consistently reduced Openness and Agreeableness, and a marked decrease in Conscientiousness of about 20-30 T scores (equivalent to 2-3 SD). These changes were systematic and consistent. Particularly striking was the similarity of both the magnitude and direction of change in all studies reviewed. Conscientiousness and Neuroticism are the personality traits that exhibit the most change in dementia. These traits might be useful early markers of dementia.


Tissue distribution of phenoxybenzamine in the rat. Lack of adipose tissue storage.
Rats were given the basic lipophilic drug, phenoxybenzamine, in single i.v. doses of 0.4 and 30 mg/kg. The drug was determined in plasma and 7 tissues by a new HPLC method. Adipose tissue reached peak levels after 30 minutes. At that time levels in heart, kidney, and brain were higher than in subcutaneous, epididymal, and mesenteric adipose tissues. The percentage metabolites in adipose tissue, kidney, and liver was 0, 88, and 96, respectively. Pretreatment with SKF 525-A inhibited metabolism and increased the tissue levels of unchanged drug, however, even under these conditions storage in adipose tissues did not occur, the adipose storage index being still less than unity. These results contradict findings of the 1950s which have been repeatedly reported in textbooks and reviews, but they confirm observations that basic drugs, even when highly lipophilic, are not being stored in adipose tissues.


First total synthesis of (+/-)-3-aza-11-oxa-1,3,5(10)-trieno steroids.
We set out to describe a new and versatile method for preparing 3-aza-11-oxa-1,3,5(10)-trieno steroids via an intramolecular Diels-Alder cycloaddition of o-quinodimethanes as the key step. The characteristic 1H and 13C NMR spectroscopic features of the synthesized compounds are reported.


Glottis motion effects on the particle transport and deposition in a subject-specific mouth-to-trachea model: A CFPD study.
Computational Fluid-Particle Dynamics (CFPD) models have been employed to predict lung aerosol dynamics for decades, estimating the delivery efficiency of inhaled drugs into the tracheobronchial tree. However, existing CFPD models assume the glottis is static during the breathing cycle. Failing to capture the dynamic motion of the glottis may introduce significant errors in drug deposition estimations. A novel CFPD model was developed with the capability of modeling the glottis motion using the dynamic mesh method. To explore the causal relationships between the glottis motion and the inhaled drug particle dynamics, simulations were performed to compare static and different dynamic glottis models in a subject-specific mouth-to-trachea geometry under idealized sinusoidal and realistic breathing waveforms. By defining the movement of each node in the glottis region using a generalized glottis motion function (GGMF) validated with clinical data, the abduction and adduction of the glottis were accurately described. Transient transport characteristics of inhaled particle-laden airflows were investigated and analyzed, including the glottis motion effect on the inhaled particles with the aerodynamic diameters from 0.1 to 10 μm. Numerical results indicate that the static glottis assumption deviates the total deposition fraction predictions by more than 8% in relative differences. Compared with the CFPD models with the static glottis assumption, the dynamic glottis model can more realistically predict the complexity of the secondary flows near the vocal fold and the resultant particle depositions. Inter-subject variabilities of the glottis motion patterns were observed, and their influences on particle transport dynamics are not uniform. Parametric analyses also demonstrate that the maximum deformation ratio of the glottis is a key feature to describe whether the glottis motion can enhance or reduce particle depositions in the mouth-to-trachea region, over the static glottis model. The glottis motion shows a significant influence on the accuracy of predicting inhaled particle dynamics, and it should be integrated into CFPD simulations validated by subject-specific glottis motion data from clinical studies in the future. Furthermore, the proposed dynamic glottis model has been demonstrated to be a computationally effective method to recover the physiologically realistic motions of the glottis, and ready to be added into the next-generation holistic virtual lung modeling approach.


[The pain resource nurse, the guiding light for implanted neurostimulation].
Chronic pain affects a large number of French people, and has a considerable impact on their quality of life. Spinal cord stimulation is a technique for managing and reducing this pain, which is often resistant to (poorly tolerated) medication. Between the consultation with the specialist and the operation, a specific procedure is imperative: the pre-implantation assessment. Numerous appointments and tests are required to verify the patient's eligibility. The pain resource nurse plays a key role in supporting the patient through this process: she is the guiding light in the care process.


Bupivacaine and morphine epidural use for refractory neuropathic pain relief in a Guillain-Barré syndrome patient.
Pain is common in the acute phase of Guillain-Barré Syndrome and can be severe and refractory. Pain in GBS may not always respond to contemporary pain therapy. An epidural can potentially be considered for the treatment of refractory pain after a careful patient-centered discussion with the patient about risks.


Preventive effect of sanguinarine on intestinal injury in mice exposed to whole abdominal irradiation.
Intestinal injury is one of the major side effects that are induced by medical radiation exposure, and has limited effective therapies. In this study, we investigated the beneficial effects of sanguinarine (SAN) on intestinal injury induced by ionizing radiation (IR) both in vitro and in vivo. Mice were exposed to whole abdominal irradiation (WAI) to mimic clinical scenarios. SAN was injected intraperitoneally to mitigate IR-induced injury. Histological examination was performed to assess the tissue injuries of the spleen and small intestine. A small intestinal epithelial cell line-6 (IEC-6) was analyzed for its viability and apoptosis in vitro under different treatments. Inflammation-related pathways and serum inflammatory cytokines were detected via Western blot analysis and ELISA, respectively. High-throughput sequencing was used to characterize the gut microbiota profile. High-performance liquid chromatography was performed to assess short-chain fatty acid contents in the colon. In vitro, SAN pretreatment protected cell viability and reduced apoptosis in IEC-6 cells. In vivo, SAN pretreatment protected immune organs, alleviated intestinal injury, and promoted intestinal recovery. SAN also reduced the levels of inflammatory cytokines, suppressed high mobility group box 1 (HMGB1)/ Toll-like receptor 4 (TLR4) pathway activation, and modulated gut microbiota composition. Our findings demonstrate that the beneficial properties of SAN alleviated intestinal radiation injury. Thus, SAN represents a therapeutic option for protecting against IR-induced intestinal injury in preclinical settings.


Increased risk of stroke in patients with diffuse idiopathic skeletal hyperostosis: a nationwide population-based cohort study.
Diffuse idiopathic skeletal hyperostosis (DISH) is frequently an incidental finding during X-ray examination. Although it has been shown to be associated with several chronic diseases, the hazard of cerebrovascular disease has seldom been explored. Our study aimed at determining the risk of stroke conferred by DISH, which is a retrospective cohort study adopting the largest medical database in Taiwan. Patients with a diagnosis of DISH at least three times from 2005 to 2010 were identified as the study group, and those in the control group were selected by matching age and gender. Patients were followed up until the end of 2015 to trace the incidence of stroke. Cox regression analysis was performed to compute the hazard ratio of stroke. Among the included 5300 patients, 1060 had a diagnosis of DISH. Significantly higher prevalence rates of stroke, hypertension, diabetes, and hyperlipidemia were noted in these patients. Overall, DISH conferred a 1.68 times higher risk of developing stroke. The significantly higher hazard ratio could be identified in both genders whether hypertension existed or not. Even in those without comorbidities, DISH still conferred a significantly higher risk of cerebrovascular disease in the future, which should never be ignored when encountered during clinical practice.


Significant correlation between openness personality in normal subjects and brain myelin mapping with T1/T2-weighted MR imaging.
The objective of this study was to examine the relationship between the myelination and the psychological trait of openness to experience in young cognitively normal volunteers using regional T1-weighted (T1w)/T2w ratios on magnetic resonance imaging (MRI). It was hypothesized that axonal myelination would be related to openness, thus linking trait creativity and mental illness. We recruited 37 healthy subjects and administered the NEO Five-Factor Inventory to assess personality factors. Regional T1w/T2w MRI values were computed as surrogate indicators of myelination status and correlations between T1w/T2w values and various personality factors (e.g., trait of openness) were calculated with a voxel-based analysis using statistical parametric mapping. Significant negative correlations were identified between the trait of openness and T1w/T2w values in the medial frontal cortex, anterior cingulate cortex, posterior cingulate cortex, and posterior insula/adjacent putamen. These relationships remained significant even after adjusting for age, sex, and education as covariates. There were no significant correlations between other personality factors and regional volumes. Individual differences in openness may be associated with variations in intra-cortical myelination, specifically in the imaginative network of the brain including the midline core 'hubs' of the default mode network (anterior cingulate/medial frontal cortex and posterior cingulate cortex) and regions related to motivational state (posterior insula and adjacent putamen). Signal interference related to decreased myelination may facilitate flexible imagination and the trait of openness. Our findings assist in understanding the relationship between myelination and openness, as a link between creativity and mental illness.


Fully "Recombinant Enzyme-Linked Immunosorbent Assays" Using Genetically Engineered Single-Chain Antibody Fusion Proteins for Detection of Citrus tristeza virus.
ABSTRACT Recombinant single-chain variable fragment antibodies (scFv) that bind specifically to Citrus tristeza virus (CTV), which cause the most detrimental viral disease in the citrus industry worldwide, were obtained from the hybridoma cell lines 3DF1 and 3CA5. These scFv were genetically fused with dimerization domains as well as with alkaline phosphatase, respectively, and diagnostic reagents were produced by expressing these fusion proteins in bacterial cultures. The engineered antibodies were successfully used for CTV diagnosis in plants by tissue print enzyme-linked immunosorbent assay (ELISA) and double antibody sandwich-ELISA. The fully recombinant ELISAs were as specific and sensitive as conventional ELISAs performed with the parental monoclonal antibodies, showing the usefulness of recombinant antibodies for routine detection of a virus in woody plants for the first time.


The paradoxical evolution in an unusual case of disseminated tuberculosis: Spontaneous resolution with disease progression.
Mycobacterium tuberculosis can cause a myriad of clinical manifestations. We describe a case of a patient with end-stage renal failure, who presented with disseminated tuberculosis over the course of five months, manifesting with a self-resolving mediastinal mass, progressive lymphadenopathy, genitourinary, and musculoskeletal tuberculosis.


It is unlikely that oxygen supplementation in COPD patients with chronic respiratory failure reduce cardiac troponin level.
Cardiac troponin T (cTnT) is a biomarker of myocardial injury frequently elevated in COPD patients, potentially because of hypoxemia. This non-randomised observational study investigates whether long-term oxygen treatment (LTOT) reduces the cTnT level. We compared cTnT between COPD patients who were candidates for LTOT (n = 20) with two reference groups. Patients from both reference groups were matched with the index group using propensity score.Reference groups consists of institutional pulmonary rehabilitation patients (short-term group) (n = 105 after matching n = 11) and outpatients at a pulmonary rehabilitation clinic (long-term group)(n = 62 after matching n = 10). Comparison was done within 24 h after LTOT initiation in first reference group and within 6 months after inclusion in the second group. The geometric mean of (standard deviation in parentheses) cTnT decreased from 17.8 (2.3) ng/L (between 8 and 9 a.m.) to 15.4 (2.5) ng/L between 1 and 2 p.m. in the LTOT group, and from 18.4 (4.8) ng/L to15.4 (2.5) ng/L in group (1) The corresponding long-term results were 17.0 (2.9) ng/L at inclusion (between 10 and 12 a.m.) to 18.4 (2.4) ng/L after 3 months in the LTOT-group, and from 14.0 (2.4) ng/L to 15.4 (2.5) ng/L after 6 months in group (2) None of the differences in cTnT during the follow-up between the LTOT-group and their matched references were significant. Initiation of LTOT was not associated with an early or sustained reduction in cTnT after treatment with oxygen supplementation.


Urinary proteomics combined with home blood pressure telemonitoring for health care reform trial-First progress report.
High blood pressure (BP) and type-2 diabetes (T2DM) are forerunners of chronic kidney disease and left ventricular dysfunction. Home BP telemonitoring (HTM) and urinary peptidomic profiling (UPP) are technologies enabling risk stratification and personalized prevention. UPRIGHT-HTM (NCT04299529) is an investigator-initiated, multicenter, open-label, randomized trial with blinded endpoint evaluation designed to assess the efficacy of HTM plus UPP (experimental group) over HTM alone (control group) in guiding treatment in asymptomatic patients, aged 55-75 years, with ≥5 cardiovascular risk factors. From screening onwards, HTM data can be freely accessed by all patients and their caregivers; UPP results are communicated early during follow-up to patients and caregivers in the intervention group, but at trial closure in the control group. From May 2021 until January 2023, 235 patients were screened, of whom 53 were still progressing through the run-in period and 144 were randomized. Both groups had similar characteristics, including average age (62.0 years) and the proportions of African Blacks (81.9%), White Europeans (16.7%), women 56.2%, home (31.2%), and office (50.0%) hypertension, T2DM (36.4%), micro-albuminuria (29.4%), and ECG (9.7%) and echocardiographic (11.5%) left ventricular hypertrophy. Home and office BP were 128.8/79.2 mm Hg and 137.1/82.7 mm Hg, respectively, resulting in a prevalence of white-coat, masked and sustained hypertension of 40.3%, 11.1%, and 25.7%. HTM persisted after randomization (48 681 readings up to 15 January 2023). In conclusion, results predominantly from low-resource sub-Saharan centers proved the feasibility of this multi-ethnic trial. The COVID-19 pandemic caused delays and differential recruitment rates across centers.


Morphogenetic lung defects of JSAP1-deficient embryos proceeds via the disruptions of the normal expressions of cytoskeletal and chaperone proteins.
Recent studies have shown that JNK/stress-activated protein kinase-associated protein 1 (JSAP1)-deficient mice die from respiratory failure shortly after birth. To understand the underlying mechanism, we investigated the histological appearances and cell type changes in developing jsap1(-/-) lungs between E12.5 and E18.5. At the light microscopic level, no overt abnormality was detected in jsap1(-/-) until E16.5. However, alveoli and airway formations that normally occur after E16.5 were poorly advanced in jsap1(-/-). Despite these morphological defects, surfactant secreting cells labeled by anti-SP-B or anti-SP-C were present in normal ranges in jsap1(-/-) lungs. Smooth muscle alpha-actin expressing cells were also developed in jsap1(-/-) lungs, although actin expression was decreased. The expressions of transcriptional factors, such as, nuclear factor Ib (Nfib), N-myc, and octamer transcriptional factor 1 (Oct-1), which play a critical role in lung morphogenesis, were found to be down-regulated, whereas signal transducer and activator of transcription 3 (Stat3), sonic hedgehog (Shh), and smoothened (Smo) were up-regulated, in jsap1(-/-) lungs at E17.5-E18.5 compared with those in jsap1(+/+) lungs. Proteomics analysis of E17.5 lung identified 39 proteins with altered expressions, which included actin, tropomyosin, myosin light chain, vimentin, heat shock protein (Hsp27), and Hsp84. These results suggest that JSAP1 is required for the normal expressions of cytoskeletal and chaperone proteins in the developing lung, and that impaired expressions of these proteins might cause morphogenetic defects observed in jsap1(-/-) lungs.


Rapid and selective shutoff of plasma protein production in herpes simplex virus type 2-infected hepatoma cells.
The effect of herpes simplex virus type 2 (HSV-2) infection of hepatoma McA-RH7777 cells on the production of alpha-fetoprotein (AFP) and several other secreted plasma proteins was examined. Cells infected with HSV-2 were labeled with [35S]methionine for various times postinfection (p.i.). Culture media and intracellular extracts were immunoprecipitated with plasma protein antibodies and examined by polyacrylamide gel electrophoresis. The relative levels of AFP and several other plasma proteins decreased substantially in infected cells compared with mock-treated controls; however, the level of at least one secreted plasma protein was unchanged after infection and the level of another increased after infection. Hybridization analyses with AFP cDNA showed that AFP RNA decreased to 43 and 30% of controls at 3.5 and 6.5 hr p.i., respectively. These observations were supported by the results of cell-free translation of isolated poly(A)-containing RNA. HSV-2 proteins were not detectable at times p.i. when AFP synthesis, secretion, and mRNA levels were significantly diminished. No decrease in AFP levels was observed in cells infected with ultraviolet-irradiated virus. We conclude that HSV-2 infection of McA-RH7777 cells leads to a rapid decrease in synthesis and secretion of specific plasma proteins which is apparent, at least for AFP, at the level of mRNA. This shutoff is not common to all McA-RH7777 cell proteins and, although seen early after infection, most likely requires the expression of a virus gene(s).


A novel corporoplasty technique with a urethral plate flap in hypospadias repair.
To report a novel corporoplasty technique with a urethral plate flap in hypospadias repair and evaluate its safety and efficacy for ventral lengthening. Data were retrospectively collected from consecutive patients with hypospadias who underwent urethral plate flap corporoplasty between July 2021 and March 2022. All patients underwent hypospadias repair using the Duckett technique. The corporoplasty procedure involved the following key steps: the half-spongiosum of the urethral plate was harvested as a flap (with a pedicle attached to the corpus cavernosum); a transverse incision of the tunica albuginea was made adjacent to the pedicle; and the flap was patched onto the corporal defect. The study included 10 patients, with a median age of 20 months. The initial meatal location was penile in two patients, penoscrotal in four patients, and scrotal in four patients. The median ventral curvature was 45° after degloving and urethral plate transection. The median ventral lengthening distance proportional to penis length was 0.21. During the median follow-up of 13.8 months, complications occurred in three cases, including two cases of fistula and one case of urethral stricture with secondary diverticulum. No cases of recurrent ventral curvature, meatal stenosis, or urethral dehiscence were noted. Postoperative ultrasonography showed a good continuation of the tunica albuginea and integrity of the stratum spongiosum at the corporoplasty site. Urethral plate flap corporoplasty is a simple and effective ventral lengthening procedure. The novel corporoplasty technique allows for anatomical and architectural repair of corporal disproportion.


Haemolytic anaemia in analpha-lipoproteinaemia (Tangier disease): morphological, biochemical, and biophysical properties of the red blood cell.
A patient with familial analpha-lipoproteinaemia (Tangier disease) was found to have stomatocytosis and haemolytic anaemia. The analysis of the red cell membrane constituents revealed a low cholesterol content (90 nmol/ml red cells, control 130 nmol/ml red cells), a decreased cholesterol/phospholipid ratio (0.54, control 0.78), high phosphatidylcholine (41.5%, control 30.6%) and low sphingomyelin (18.8%, control 27.6%). The electrophoretic membrane protein pattern was normal. Osmotic gradient ektacytometry and osmotic resistance showed a decreased surface/volume ratio, which caused an increased filtration resistance in 3 microns pores. The elasticity of the membrane was unchanged. Functional membrane properties were altered: the anion exchange rate was increased, whereas alkali cation fluxes were normal. The capacity to release vesicles was reduced. This case represented a new type of stomatocytosis. It contributes to the understanding of the role of cholesterol and phospholipids in the red cell membrane and biomembranes in general.


The effect of marijuana use on short-term outcomes with bariatric surgery.
Despite increasing marijuana use nationwide, there are limited data on implications of marijuana use on bariatric surgery outcomes. We investigated associations between marijuana use and bariatric surgery outcomes. Multicenter statewide study utilizing data from the Michigan Bariatric Surgery Collaborative, a payor-funded consortium including over 40 hospitals and 80 surgeons performing bariatric surgery statewide. We analyzed data from the Michigan Bariatric Surgery Collaborative clinical registry on patients who underwent a laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass between June 2019 and June 2020. Patients were surveyed at baseline and annually on medication use, depression symptoms, and substance use. Regression analysis was performed to compare 30-day and 1-year outcomes between marijuana users and nonusers. Of 6879 patients, 574 reported baseline marijuana use and 139 reported use at baseline and 1 year. Marijuana users were more likely to be current smokers (14% versus 8%, P < .0001), screen positive for alcohol use disorder (20.0% versus 8.4%, P < .0001), and score higher on the Patient Health Questionnaire-8 (6.1 versus 3.0, P < .0001). There were no statistically significant differences in 30-day outcomes or co-morbidity remission at 1 year. Marijuana users had higher adjusted total mean weight loss (47.6 versus 38.1 kg, P < .0001) and body mass index reduction (17 versus 14 kg/m2, P < .0001). Marijuana use is not associated with worse 30-day outcomes or 1-year weight loss outcomes and should not be a barrier to bariatric surgery. However, marijuana use is associated with higher rates of smoking, substance use, and depression. These patients may benefit from additional mental health and substance abuse counseling.


Intraoperative effect of low doses of ketamine or dexmedetomidine continuous rate infusions in healthy dogs receiving propofol total intravenous anaesthesia and epidural anaesthesia: A prospective, randomised clinical study.
The present study aimed to determine the effect of either ketamine or dexmedetomidine constant rate infusion (CRI) on intraoperative propofol anaesthetic requirements during total intravenous anaesthesia (TIVA) in healthy dogs undergoing hindlimbs orthopaedic procedures receiving epidural anaesthesia. In this randomised, blinded clinical study, thirty-nine healthy client-owned dogs were premedicated intramuscularly (dexmedetomidine 4 μg/kg and methadone 0.3 mg/kg). General anaesthesia was induced to effect with propofol administered as intravenous bolus, and maintained with propofol TIVA (18 mg/kg/h), adjusted to meet the suitable clinical anaesthetic depth (indicatively±20%) based on clinical judgement. Lumbosacral epidural anaesthesia was performed using bupivacaine (1 mg/kg) and morphine preservative free (0.1 mg/kg). Dogs randomly received either saline (SP; loading dose 1 mL/kg, CRI 1 mL/kg/h), or ketamine (KP; loading dose 1.5 mg/kg, CRI 1.5 mg/kg/h), or dexmedetomidine (DP; loading dose 1 μg/kg/, CRI 1 μg/kg/h). Physiological variables were recorded intraoperatively at 5-min intervals using standard-of-care monitoring. Recovery quality and duration were recorded. Treatment groups were compared with parametric and non-parametric tests as appropriate, p < 0.05. Propofol rates and recovery scores were similar between groups. Overall mean and diastolic blood pressures were higher in group DP compared to group KP (12-14 mmHg, p = 0.016 and p = 0.015, respectively). More dogs required mechanical ventilation in group KP (12 dogs) than in either group SP or DP (7 dogs per group, p = 0.037). Ketamine or dexmedetomidine CRIs, at the studied rates, did not reduce propofol TIVA requirements in dogs undergoing orthopaedic surgery with epidural anaesthesia.


Research progress on classical traditional Chinese medicine formula Liuwei Dihuang pills in the treatment of type 2 diabetes.
In traditional Chinese medicine (TCM), type 2 diabetes mellitus (T2DM) is regarded as Xiao Ke disease. Liuwei Dihuang pills (LWP), a classical TCM formula, with the function of nourishing kidney yin, has been used for treating Xiao Ke disease in clinic. In this review, we systematically highlighted recent evidence on LWP and T2DM data from clinical and animal studies, summarized the clinical application, pharmacological mechanism and the active compounds of LWP for the treatment of T2DM. This systematic review will provide an insightful understanding of TCM formulas, pharmacological mechanisms, medicinal-disease interactions, and will lay a foundation for the development of new drug therapy for T2DM.


Unusual simultaneous multifocal rupture of oesophagus, stomach and diaphragm after blunt trauma.
An unusual case of simultaneous multifocal rupture of the oesophagus, stomach and diaphragm after blunt trauma is described. The characteristic computed tomography scans (with intraluminal contrast application) of the ruptured oesophagus are shown, and successful management is presented.


Topo-optical reactions of the human blood platelet membrane.
The polarization optical analysis of human blood platelets was carried out by means of topo-optical staining reactions. Similar studies have not been performed so far. With this approach we were able to demonstrate the spatially oriented nature of glycoprotein components in the platelet membrane. Using a sialic acid specific topo-optical reaction the sialic acid component of human platelet membrane was selectively demonstrated and the even distribution of sialic acid residues on the membrane surface was also suggested. Polarization optical analysis has shown a membrane-parallel orientation of oligosaccharide chains carrying sialic acids.


Building a panel data set on fuel stations located in the Spanish regional areas of Madrid and Barcelona.
The data described in this article were collected daily over the period June 10, 2010, to November 25, 2012, from the website of the Spanish Ministry of Industry, Energy and Tourism. The database includes information about fuel stations regarding to their prices (both gross and net of taxes), brand, location (latitude and longitude), and postal code in the Spanish provinces of Madrid and Barcelona. Moreover, obtaining the postal codes has allowed us to select those stations that are operating within the metropolitan areas of Madrid and Barcelona. By considering those fuel stations that uninterruptedly provided prices during the entire period, the data can be especially useful to explore the dynamics of prices in fuel markets. This is the case of Balaguer and Ripollés (2016), "Asymmetric fuel price responses under heterogeneity" [1], who, taking into account the presence of the potential heterogeneity of the behaviour of fuel stations, used this statistical information to perform an analysis on asymmetric fuel price responses.


Chlamydia, mycoplasmas, ureaplasmas, and yeasts in the lower genital tract of females. Comparison between a group attending a venereal disease clinic and a control group.
162 women were investigated. Group I consisted of 85 women, who were partners to men with non-gonococcal urethritis (NGU) or presented macroscopic signs of cervicitis; patients who had harbored Neisseria gonorrhoeae were excluded from the study. Group II was a control group of 77 women without any complaints from the urogenital tract and with normal findings at pelvic examination. All the women were tested for infection with Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, and Candida albicans. In group I, chlamydiae and mycoplasmas were recovered in 44% and 36%, respectively, the corresponding figures for the control group (group II) being 5% and 19%. The difference is highly significant. No such difference between the two groups was found for ureaplasmas. Sixteen percent of the patients in group I were positive for C. albicans; 12% were positive in group II. Fifty per cent of asymptomatic NGU-partners were chlamydia-positive, and about one-third of patients with either dysuria or vaginal discharge harbored the organism. No difference in the isolation frequency of mycoplasmas was observed between asymptomatic partners to male NGU carriers and women with increased vaginal discharge, whereas the organism was isolated more frequently from patients with dysuria. Fifty-nine per cent of patients with cervicitis were chlamydia-positive, compared with 30% of patients with normal cervical appearance and normal vaginal discharge. Samples obtained from the cervix were more often positive than samples from the urethra. In conclusion, if samples can be taken from only one of the two sites in patients with lower genital tract infection, the cervix is the optimal sampling site.


The use of additive and subtractive approaches to examine the nuclear localization sequence of the polyomavirus major capsid protein VP1.
A nuclear localization signal (NLS) has been identified in the N-terminal (Ala1-Pro-Lys-Arg-Lys-Ser-Gly-Val-Ser-Lys-Cys11) amino acid sequence of the polyomavirus major capsid protein VP1. The importance of this amino acid sequence for nuclear transport of VP1 protein was demonstrated by a genetic "subtractive" study using the constructs pSG5VP1 (full-length VP1) and pSG5 delta 5'VP1 (truncated VP1, lacking amino acids Ala1-Cys11). These constructs were used to transfect COS-7 cells, and expression and intracellular localization of the VP1 protein was visualized by indirect immunofluorescence. These studies revealed that the full-length VP1 was expressed and localized in the nucleus, while the truncated VP1 protein was localized in the cytoplasm and not transported to the nucleus. These findings were substantiated by an "additive" approach using FITC-labeled conjugates of synthetic peptides homologous to the NLS of VP1 cross-linked to bovine serum albumin or immunoglobulin G. Both conjugates localized in the nucleus after microinjection into the cytoplasm of 3T6 cells. The importance of individual amino acids found in the basic sequence (Lys3-Arg-Lys5) of the NLS was also investigated. This was accomplished by synthesizing three additional peptides in which lysine-3 was substituted with threonine, arginine-4 was substituted with threonine, or lysine-5 was substituted with threonine. It was found that lysine-3 was crucial for nuclear transport, since substitution of this amino acid with threonine prevented nuclear localization of the microinjected, FITC-labeled conjugate.


Intermolecular hydrogen bonding of alcohols with dinitrobenzene radical anion and dianion: A combined electrochemical and DFT study.
Hydrogen bonding is one of the most important inter-molecular interactions in the field of biochemistry and medicinal chemistry. Such non-covalent interactions play a vital role in self-assembly phenomena, chemical structures, material properties and enzymatic catalysis. Herein, we present hydrogen bonding phenomenon in alcohols-dinitrobenzene (DNB) radical anion/dianion systems using electrochemical and computational approaches. First, 1,3-DNB radical anion and dianion were generated through electrochemical method and then hydrogen bonding interactions with aliphatic alcohols in DMSO are studied through cyclic voltammetry (CV). CV results show that the cathodic peak potential of 1,3-Dinitrobenzene in Dimethyl sulfoxide is shifted catholically upon addition of alcohols which represent hydrogen bonding phenomenon. Theoretical investigations are performed to gain deep insight on hydrogen bonding interaction strength in DNB-alcohol systems. H-bonding interaction of all isomers of DNB (1,2-, 1,3-, 1,4-), its corresponding radical anion, and dianion with aliphatic alcohols is studied using density functional calculations. The strength of H-bonding is evaluated both qualitatively and quantitatively using interaction energies, vibrational and electronic spectroscopic analysis. Understanding of these interactions will be helpful in gaining insight into biological systems where these interactions play significant role.


Regional Disparities of Cardiovascular Risk Factors and Major Cardiovascular Events in Non-electively Hospitalized Young Adults.
Cardiovascular diseases contribute to considerable morbidity and mortality in the USA. We sought to establish regional disparities across the nation contributing to cardiovascular disease (CVD) among non-elective young adult hospitalizations. The National Inpatient Sample (2019) was utilized to identify the incidence of non-elective hospitalizations among young adults (18-44 yrs) and analyze the burden of CVD risk factors and outcomes (MACCE; all-cause mortality, AMI, cardiac arrest and stroke) in different US regions. A total of 5,833,930 (median age 32 [26-37] years) non-elective admissions were recorded; plurality from the south (39.6%). Most admissions were white (51.4%) and female (65.5%) amid all regions. The burden of CVD risk factors was significantly higher in the South followed by the Mid-west regions. The South had the highest and the Northeast had the lowest rates of MACE (2.9% vs 2.3%) and stroke (1.0% vs 0.8%). The risk of AMI was high for the south and Midwest regions (1.1%). All-cause mortality was highest in South and West regions (0.7%). Multivariate adjusted odds for these cardiovascular events were higher in the West (aOR 1.22; 95%CI 1.12-1.33) followed by South (aOR 1.16; 95%CI 1.07-1.26) regions. This population-based study assessing non-elective admissions in the young revealed a higher burden of CVD risk factors and rate of MACCE in the South compared to other areas of the USA. Regional policies should be tailored to the local CVD risk burden.


Sulfur-Phenolate Exchange As a Fluorine-Free Approach to S(VI) Exchange Chemistry on Sulfonyl Moieties.
SuFEx chemistry has recently evolved as next-generation click chemistry. However, in most SuFEx syntheses, additional reagents/catalysts and carefully controlled conditions are still needed. Here, we aim to further generalize S(VI) exchange chemistry, using 4-nitrophenyl phenylmethanesulfonate as example, in which the nitrophenolate group is exchanged for a wide range of (substituted) phenols and alkyl alcohols. Quantitative yields were reached within 10 min under ambient conditions and required only filtering through silica as workup.


Role of individual-housing-based socioeconomic status measure in relation to smoking status among late adolescents with asthma.
We aimed to assess whether smoking status among individuals in late adolescence (19-22 years) with asthma was associated with socioeconomic status (SES) defined by HOUSES, an individual-housing-based SES measure. A population-based cross-sectional study was conducted among the 1988-1989 Olmsted County, Minnesota Birth Cohort, with physician-diagnosed asthma and that lived in the community during the study period (November 1, 2008-October 31, 2012). Using a z score for housing value, actual square footage, and numbers of bedrooms and bathrooms, HOUSES was formulated and categorized into quartiles. Smoking status (both current and past smoker) was compared among subjects with different SES as measured by HOUSES using logistic regression, adjusting for age and sex. Among 289 eligible subjects, 287 (99%) were successfully geo-coded to real property data for HOUSES. Of the 257 subjects whose smoke exposure was recorded, 70 (27%) had a history of smoking (either past or current). An inverse association was observed between HOUSES and smoking status after accounting for age, gender, and General Medical Examination status (adjusted OR = 0.39, 95% CI = 0.18-0.87 for comparing highest vs. lowest HOUSES in quartile; overall P = .02). A significant proportion of individuals with asthma in late adolescence was smokers during the study period, disproportionally affecting those with lower SES.


Breathing-induced forces influence lung cell fate.
Respiration exerts a mechanical strain on the lungs, which has an unclear effect on epithelial cell fate. Now in Cell, Shiraishi et al.1 reveal the crucial role of mechanotransduction in maintaining lung epithelial cell fate, representing a significant milestone in understanding how mechanical factors regulate differentiation.


[An update on the most recent mini-invasive surgical and interventional techniques in the management of benign prostatic obstruction].
New surgical techniques for the treatment of benign prostatic obstruction (BPO) have emerged in recent years. We sought to give an overview on each of these technologies. A comprehensive review of the literature between 2013 and 2020 was carried out by a panel of national experts already practicing these interventions. All the data were then discussed among all the co-authors in order to obtain a consensus with regard to the selected articles and their analysis. Finally, an inventory was drawn to provide an overview of these technological advances and their availability in France. The treatment benign prostatic obstruction has diversified greatly over the past 5 years. 5 new technologies have emerged, allowing today a transurethral non-ablative treatment (UROLIFT®, ITIND®), a transurethral ablative treatment (REZUM®), a transurethral ablative treatment with robotic assistance (AQUABEAM®) or an endovascular management by embolization of the prostatic arteries. Only UROLIFT® is considered an established technology in the latest EAU-Guidelines. The other four are under evaluation and recommendations have only been issued for two of them, AQUABEAM® and the embolization of the prostatic arteries. These new minimally invasive techniques aim to increase the therapeutic options for the management of BPO in order to offer a management more suited to the wishes of the patient. Some are positioned as an alternative to surgical or medical treatment, others between medical and surgical treatment. These technologies are not all at the same level of development, evaluation and level of proof, but have in common a limited distribution in France, in particular given their cost. Validated studies will allow them to position their subsequent use more precisely.


Leishmaniasis.
Leishmaniasis caused by Leishmania infantum is an important zoonotic disease transmitted by sand flies with a high prevalence of infection in dogs and cats in regions whereby transmission occurs. Clinical disease is systemic with variable presenting signs and degrees of severity. It affects the skin, lymph nodes, eyes, bone marrow, kidneys, and other organs. The clinical findings in dogs and cats with L. infantum infection are generally similar. Subclinical infection of canines and felines in endemic areas is frequent. Long-term treatment of the disease with allopurinol, or combination of allopurinol with meglumine antimoniate or miltefosine, is needed, and clinical relapse is probable.


Age does not influence the disease course in a mouse model of Streptococcus pneumoniae serotype 3 meningitis.
In order to elucidate the causes for the increased mortality of aged patients with bacterial central nervous system (CNS) infections, we compared the course of Streptococcus pneumoniae (S. pneumoniae) meningitis in aged and young mice. Aged (21.2 ± 3.1 months, n = 40) and young (3.2 ± 0.9 months, n = 42) C57BL/6N and B6/SJL mice were infected by intracerebral injection of 50-70 CFU S. pneumoniae serotype 3 and monitored for 15 days. Aged and young mice did not differ concerning mortality (35% versus 38%), weight loss, development of clinical symptoms, bacterial concentrations in cerebellum and spleen as well as the number of leukocytes infiltrating the CNS. In contrast to results from our geriatric mouse model of Escherichia coli (E. coli) meningitis, where aged mice showed a higher mortality and an impaired elimination of bacteria, we did not find any differences between aged and young mice after intracerebral infection with S. pneumoniae serotype 3. This indicates that the increased susceptibility of aged mice to bacterial CNS infections is pathogen-specific: It appears less prominent in infections caused by hardly phagocytable pathogens with thick capsules like S. pneumoniae serotype 3, where the age-related decline of the phagocytic capacity of microglia and macrophages has a minor influence on the disease course.


CgSTE11 mediates cross tolerance to multiple environmental stressors in Candida glabrata.
Candida glabrata is a human commensal and an opportunistic human fungal pathogen. It is more closely related to the model yeast Saccharomyces cerevisiae than other Candida spp. Compared with S. cerevisiae, C. glabrata exhibits higher innate tolerance to various environmental stressors, including hyperthermal stress. Here we investigate the molecular mechanisms of C. glabrata adaptation to heat stress via adaptive laboratory evolution. We show that all parallel evolved populations readily adapt to hyperthermal challenge (from 47 °C to 50 °C) and exhibit convergence in evolved phenotypes with extensive cross-tolerance to various other environmental stressors such as oxidants, acids, and alcohols. Genome resequencing identified fixation of mutations in CgSTE11 in all parallel evolved populations. The CgSTE11 homolog in S. cerevisiae plays crucial roles in various mitogen-activated protein kinase (MAPK) signaling pathways, but its role is less understood in C. glabrata. Subsequent verification confirmed that CgSTE11 is important in hyperthermal tolerance and the observed extensive cross-tolerance to other environmental stressors. These results support the hypothesis that CgSTE11 mediates cross-talks between MAPK signaling pathways in C. glabrata in response to environmental challenges.


Monitoring the interactions between N-degrons and N-recognins of the Arg/N-degron pathway.
As defined by the N-degron pathway, single N-terminal (Nt) amino acids can function as N-degrons that induce the degradation of proteins and other biological materials. Central to this pathway is the selective recognition of N-degrons by cognate N-recognins that direct the substrates to either the ubiquitin (Ub)-proteasome system (UPS) or autophagy-lysosome pathway (ALP). Eukaryotic cells have developed diverse pathways to utilize all 20 amino acids in the genetic code as pro-N-degrons or N-degrons which can be generated through endoproteolytic cleavage or post-translational modifications. Amongst these, the arginine (Arg) N-degron plays a key role in both cis- and trans-degradation of a large spectrum of cellular materials by the proteasome or lysosome. In mammals, Arg/N-degrons can be generated through endoproteolytic cleavage or post-translational conjugation of the amino acid L-Arg by ATE1-encoded R-transferases (EC 126.96.36.199), which requires Arg-tRNAArg as a cofactor. Arg/N-degrons of short-lived substrates are recognized by a family of N-recognins characterized by the UBR box for polyubiquitination and proteasomal degradation. Under stresses, however, the same degrons can be recognized for autophagic degradation by the ZZ domain of the N-recognin p62/SQSTSM-1/Sequestosome-1 or KCMF1. Biochemical tools were developed to monitor the interaction of Arg/N-degrons with its cognate N-recognins. These assays were employed to identify new N-recognins and to characterize their biochemical properties and physiological functions. The principles of these assays may be applied for other types of N-degron pathways. Below, we describe the methods that analyze the interaction of Arg/N-degrons and their chemical mimics to N-recognins.


[The relationship between expression of fas mRNA and apoptosis after traumatic brain injury in rats and the role of GM-1 in protecting the brain].
To explore the mechanism of apoptosis after traumatic brain injury (TBI) in rats and elucidate the role of GM-1 by detecting the expression of Fas mRNA and apoptosis in hippocampi. After creating the model of Marmarou cranio-cerebral trauma and offering GM-1 therapy, we observed the expression of Fas mRNA and apoptotic cell death using in situ hybridization and terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) technique. Increased expression of Fas mRNA and increased apoptotic cells in hippocampi after TBI were observed. GM-1 could decrease the expression of Fas mRNA and apoptotic cell death. The increased expression of Fas mRNA may be a noteworthy cause of apoptotic cell death after traumatic brain injury. GM-1 may play a protective role by way of decreasing the expression of Fas mRNA and apoptotic cell death.


An integrated omics approach to investigate summer mortality of New Zealand Greenshell™ mussels.
Green-lipped mussels, commercially known as Greenshell™ mussels (Perna canaliculus Gmelin 1791), contribute > $300 million to New Zealand's aquaculture exports. However, mortalities during summer months and potential pathogenic outbreaks threaten the industry. Thermal stress mechanisms and immunological responses to pathogen infections need to be understood to develop health assessment strategies and early warning systems. P. canaliculus were collected during a mortality event at a commercial aquaculture farm in Firth of Thames, New Zealand. Gill tissues from six healthy and six unhealthy mussels were excised and processed for metabolomic (GC-MS) and label-free proteomic (LC-MS) profiling. Univariate analyses were conducted separately on each data layer, with data being integrated via sparse multiple discriminative canonical correlation analysis. Pathway enrichment analysis was used to probe coordinated changes in functionally related metabolite sets. Findings revealed disruptions of the tricarboxylic acid (TCA) cycle and fatty acid metabolism in unhealthy mussels. Metabolomics analyses also indicated oxidative stress in unhealthy mussels. Proteomics analyses identified under-expression of proteins associated with cytoskeleton structure and regulation of cilia/flagellum in gill tissues of unhealthy mussels. Integrated omics revealed a positive correlation between Annexin A4 and CCDC 150 and saturated fatty acids, as well as a negative correlation between 2-aminoadipic acid and multiple cytoskeletal proteins. Our study demonstrates the ability of using integrative omics to reveal metabolic perturbations and protein structural changes in the gill tissues of stressed P. canaliculus and provides new insight into metabolite and protein interactions associated with incidences of summer mortality in this species.


Experience with deep hypothermia and elective circulatory arrest for cardiac surgery in infants.
During hypothermic circulatory arrest (19 C nasal) averaging 55 minutes in 25 infants, the mean increase in base deficit was only --3.95 mEq/liter, when arterial gases before circulatory arrest were compared with samples ten minutes after perfusion had been resumed. Few significant arrhythmias occurred, and all survivors appeared neurologically normal at discharge.


Pivotal factors for successful withdrawal of nonsteroidal anti-inflammatory drugs in rheumatoid arthritis patients in remission or with low-disease activity.
The purpose of this study is to examine the patient-reported outcomes (PRO) after discontinuing nonsteroidal anti-inflammatory drugs (NSAIDs) and clinical factors associated with a favorable outcome in patients with rheumatoid arthritis (RA) in remission or with low-disease activity (LDA). A 16-week prospective open-label trial was conducted at eight rheumatology clinics in Korea. RA patients with 28-joint disease activity score based on erythrocyte sedimentation rate (DAS28-ESR) < 3.2 who were on NSAIDs for more than a month were enrolled, and NSAIDs were discontinued. Acetaminophen (AAP) was used as the rescue medication, and NSAIDs were restarted when joint pain was intolerable with AAP. The endpoint was to analyze the group of patients who continued to withdraw NSAIDs. Among 109 enrolled patients, 105 completed the 16-week follow-up. Eighty-nine (84.8%) patients remained without restarting NSAIDs. In these patients, there was a slight increase in their pain levels compared with baseline (median 14.0 versus 19.0 using the pain-visual analog scale, p = 0.010). However, changes in DAS28-ESR (p = 0.638) and routine assessment of patient index data 3 (RAPID-3) (p = 0.128) were insignificant. Moreover, 66 (62.9%) patients showed sustained effectiveness on PRO without restarting NSAIDs. In the multivariate regression models, joint swelling was the detrimental factor in NSAID withdrawal (odds ratio [OR] 0.149, 95% confidence interval [CI] 0.033-0.680, p = 0.014) and sustained effectiveness (OR 0.284, 95% CI 0.091-0.883, p = 0.030). Joint pain in RA patients in remission or with LDA can be well managed without NSAIDs, especially in those without swollen joints at the time of cessation.


Strategies for the Prevention of Central Nervous System Complications in Patients with Langerhans Cell Histiocytosis: The Problem of Neurodegenerative Syndrome.
Diseases of the central nervous system (CNS) are common in patients with Langerhans cell histiocytosis (LCH). Besides active LCH lesions, neurodegenerative (ND) lesions of the cerebellum and/or basal ganglia may occur as late sequelae of LCH. While the etiology of this ND disease remains unclear, biomarkers in cerebrospinal fluid (CSF) may reflect the activity of CNS disease in these patients. However, no well-planned CSF studies have yet been performed in patients at high risk for ND-CNS-LCH. Potential parallels with other neuroinflammatory/neurodegenerative disease suggest the utility of examining these other disorders in establishing strategies for the prevention and/or treatment of ND-CNS-LCH.


Ischemia as a factor affecting innate immune responses in kidney transplantation.
Ischemic injury inevitably occurs during the procurement of organs for transplantation, and the injury is worsened by inflammation following reperfusion. The purpose of this review is to describe the role of the innate immune system in ischemia-induced renal injury in kidneys procured for transplantation. The key role of pattern recognition receptors in immune responses to ischemia is described. Innate immune receptors are emerging novel targets for the amelioration of ischemic injury of donor kidneys. Several families of pattern recognition receptors are direct mediators of early injurious events during kidney procurement, and also innate and adaptive immune responses after transplantation. The deleterious events associated with the activation of the innate immune system in donor kidneys significantly contribute to short and long-term allograft outcomes. Although a number of therapies have been proposed to decrease ischemic donor kidney injury, targeting the innate immune system is an exciting new area that is gaining significant interest in transplantation. As we learn more about how these important receptors are regulated by ischemia, strategies will likely evolve to allow their modulation in ischemic renal injury.


Resonance Raman imaging as a tool to assess the atmospheric pollution level: carotenoids in Lecanoraceae lichens as bioindicators.
Raman spectroscopy differentiation of carotenoids has traditionally been based on the ν 1 position (C = C stretching vibrations in the polyene chain) in the 1500-1600 cm(-1) range, using a 785 nm excitation laser. However, when the number of conjugated double bonds is similar, as in the cases of zeaxanthin and β-carotene, this distinction is still ambiguous due to the closeness of the Raman bands. This work shows the Raman results, obtained in resonance conditions using a 514 mm laser, on Lecanora campestris and Lecanora atra species, which can be used to differentiate and consequently characterize carotenoids. The presence of the carotenoid found in Lecanoraceae lichens has been demonstrated to depend on the atmospheric pollution level of the environment they inhabit. Astaxanthin, a superb antioxidant, appears as the principal xanthophyll in highly polluted sites, usually together with the UV screening pigment scytonemin; zeaxanthin is the major carotenoid in medium polluted environments, while β-carotene is the major carotenoid in cleaner environments. Based on these observations, an indirect classification of the stress suffered in a given environment can be assessed by simply analysing the carotenoid content in the Lecanoraceae lichens by using resonance Raman imaging.


Multiscale spectroscopy using a monolithic liquid core waveguide with laterally attached fiber ports.
In conventional absorption spectrometers, the range of accessible concentrations of analytes in aqueous solution is significantly limited by the dynamic range of the measurement system. Here we introduce the concept of multiscale spectroscopy allowing extending that range by orders of magnitude within one single device. The concept relies on using multiple light-sample interaction lengths, boosting the accessible concentration range by a particular extension factor. We experimentally implement our concept by a liquid core waveguide having multiple fiber ports side-wise attached to the waveguide, thus probing the light propagating inside the core at predefined distances from the input. This configuration provides three orders of magnitude of interaction length in one device. To verify the concept we exemplarily determine the concentrations of nitrate and of Rhodamine 6G in water, showing one hundred times improved measurement capabilities. The multiscale spectrometer uses the entire sample volume and allows the simultaneous measurement of fluorescence and attenuance. Due to its integrated design and the extended measurements capabilities, we anticipate application of our device in many application-relevant areas such as water quality analysis or environmental science.


Ethical dimensions of non-aggressive fetal management.
This article discusses the clinical ethics concept of the fetus as a patient, and identifies the implications of this for non-aggressive fetal management. The clinical ethical concept of the fetus as a patient is explained by reference to the ethical principles of beneficence and respect for autonomy. We argue that non-aggressive fetal management is ethically justified when there is a very high probability -- but sometimes less than complete certainty -- about the diagnosis, and either (1) a very high probability of death as an outcome of the anomaly diagnosed, or (2) survival with a very high probability of a severe and irreversible deficit of cognitive developmental capacity as a result of the anomaly diagnosed.


Seeking muscle stem cells.
Skeletal muscle development requires the formation of myoblasts that can fuse with each other to form multinucleate myofibers. Distinct primary and secondary, slow and fast, populations of myofibers form by the time of birth. At embryonic, fetal, and perinatal stages of development, temporally distinct lineages of myogenic cells arise and contribute to the formation of these multiple types of myofibers. In addition, spatially distinct lineages of myogenic cells arise and form the anterior head muscles, limb (hypaxial) muscles, and dorsal (epaxial) muscles. There is strong evidence that myoblasts are produced from muscle stem cells, which are self-renewing cells that do not themselves terminally differentiate but produce progeny that are capable of becoming myoblasts and myofibers. Muscle stem cells, which may be multipotent, appear to be distinguishable from myoblasts by a number of indirect and direct criteria. Muscle stem cells arise either in unsegmented paraxial mesoderm (anterior head muscle progenitors) or in segmented mesoderm of the somites (epaxial and hypaxial muscle progenitors). These initial stages of myogenesis are regulated by positive and negative signals, including Wnt, BMP, and Shh family members, from nearby notochord, neural tube, ectoderm, and lateral mesoderm tissues. The formation of skeletal muscles, therefore, depends on the generation of spatially and temporally distinct lineages of myogenic cells. Myogenic cell lineages begin with muscle stem cells which produce the myoblasts that fuse to form myofibers.


General and specific combining ability from partial diallels of radiata pine: implications for utility of SCA in breeding and deployment populations.
Variances for general combining ability (GCA) and specific combining ability (SCA) and the relationship between mid-parental GCA and SCA effects were estimated for tree diameter (DBH) from a series of 20 sets of 6x6 half-diallel mating experiments in radiata pine, planted at ten sites across Australia. Significant SCA variance for DBH was almost equal to GCA variance for the combined analysis of all ten sites. The importance of SCA variance varied among sites, from non-significant to SCA variance accounting for all genetic variation among full-sib families. Significant SCA x site interaction was detected among the ten sites. A significant and positive correlation between mid-parental breeding values and best linear unbiased predictions of the SCA effects was observed. About a quarter of extra genetic gain is achievable through use of SCA variance if selection is based on the best breeding values. To fully exploit genetic gain from SCA variance in a deployment population, positive assortative matings are required for the best parents. It is estimated that the additional deployment gain of 46.0% for ten sites combined, or 52.9% for four sites combined that had significant GCA as well as SCA effects, were achievable relative to gain from GCA only, if all SCA variance within this breeding population was exploited. For a breeding population, selection for breeding values may be sufficient due to positive correlations between breeding values and SCA values. For a deployment population to capture more SCA genetic gain, it is preferable to make more pair-wise mating for parents with higher breeding values.


Erratum to "Surgical Management with Radiation Therapy for Metastatic Spinal Tumors Located on Cervicothoracic Junction : A Single Center Study" by Park HY, et al. (J Korean Neurosurg Soc 57 : 42-49, 2015).
[This corrects the article on p. 42 in vol. 57, PMID: 25674343.].


AURKA facilitates the psoriasis-related inflammation by impeding autophagy-mediated AIM2 inflammasome suppression.
Psoriasis is an immune-mediated genetic disease involving innate and the adaptive immune system. Aurora kinase A (AURKA) belongs to a seine/threonine kinases family and is elevated in lesional psoriatic tissues. This research aimed to investigate the effects of AURKA on psoriasis progression and whether it worked by regulating autophagy or inflammasome activation. The results showed that the expression of AURKA was higher in psoriasis tissue than that in the psoriasis skin. IFN-γ (100 ng/mL) plus poly (dA:dT) (2 mg/mL) induced the increased AURKA, secretion of IL-1β, IL-18 and the active form of caspase-1 (p20). AURKA knockdown inhibited the inflammatory responses of keratinocytes and the activation of AIM2 inflammasome, and enhanced autophagy. 3MA (autophagy inhibitor) attenuated the effects of AURKA on AIM2 inflammasome. In addition, AURKA promoted the activation of the AKT/mTOR pathway. Akt inhibitor (PI-103) attenuated AIM2 inflammasome activation induced by Aurka overexpression. In conclusion, this research demonstrated that AURKA promoted the psoriasis-related inflammation by blocking autophagy-mediated AIM2 inflammasome suppression. AURKA has the potential to be explored as a new promising target for the treatment for psoriasis.