From paradigm to paradox: divergency between intracranial pressure and intracranial pulse pressure during atmospheric pressure fall. A case study.
The main objectives are to determine relation between intracranial pressure (ICP) and its amplitude and to ascertain meteorological variables as possible confounding factors. This is a retrospective observational study of a patient with suspicion of normotensive hydrocephalus. The intracranial pressure, the blood pressure, atmospheric pressure and geomagnetic activity were continuously monitored capturing extraordinary sudden and unexpected atmospheric pressure fall. The physiological changes exceptionally observed during sudden weather changes were described by means of statistical parameters. The data from 73 consecutive hourly measurements was eligible for this analysis. It contained 1022 data points corresponding to all recorded parameters, both climate and physiological ones. After initial stable period, the atmospheric pressure started to decrease from 767 mmHg to 746 mmHg. In parallel, the mean ICP ncreased significantly from 4 mmHg to 14 mmHg. Thus, the mean ICP changed inversely during atmospheric pressure drop. Whereas mean intracranial pressure increased by 10 mmHg during atmospheric pressure fall, the intracranial amplitude decreased by 5 mmHg. On timescale of several dozen hours in this study, the short-term periodic diurnal variations of ICP and blood pressure were displayed. The association between diurnal atmospheric pressure oscillation and geomagnetic activity variation was observed. Both intracranial and blood pressure variations differed significantly between day and night. This study shows that increasing ICP is associated with its paradoxically decreasing amplitude under the influence of sudden and unexpected barometric pressure fall. This study suggests that abrupt changes in atmospheric pressure might impact ICP.


Acute stroke care in France: Survey in the 138 stroke units.
According to the French regulation, stroke units (SU) include both an intensive (I-SU) and a non-intensive (NI-SU) component. Their standard operating procedures have been detailed in governmental directives in 2003 and 2007. To evaluate (i) resources available in French SU, (ii) differences between regions, and between France and the 2 close European countries of similar size, and (iii) to identify avenues for improvement. We performed a survey of all French SU, with an online questionnaire, to evaluate available resources and activity. We compared the 17 French regions, and France, with Germany and Italy. We used 2019 as year of reference. The 138 French SU, shared 911 I-SU beds; 123 SU (89.1%) answered the questionnaire. The number of I-SU beds per million inhabitants was 13.6 for the whole country, with important differences between regions, ranging from 7.0 (Reunion Island) to 20.9 (Occitanie region). Per million inhabitants, France had fewer I-SU beds than Germany and Italy (13.5 vs. 29.9 and 23.2 respectively), and fewer thrombectomy centres (0.6 vs. 1.8 and 1.0). Per million inhabitants, France had also lower thrombolysis (203 vs. 402) and thrombectomy (104 vs. 194) rates than Germany, but, compared with Italy, similar thrombolysis rates (203 vs. 202) and higher thrombectomy rates (104 vs. 81). There are still avenues for improvement in acute stroke care in France, especially concerning the number and regional repartition of I-SU beds, and access to reperfusion therapies.


Mesenchymal stem cell treatment attenuates liver and lung inflammation after ethanol intoxication and burn injury.
Cutaneous burn injury is one of the most devastating injuries one can obtain, with tissue damage extending beyond the skin wound to distal organs, including the gastrointestinal tract, liver, and lungs. Multiple organ failure is a leading cause of death after burn injury, resulting in excessive systemic and localized inflammation directly contributing to end organ damage. We postulated that the gut-liver-lung inflammatory axis underscores multiple organ failure in the context of burn injury and is hyper-activated when ethanol intoxication precedes burn. Mesenchymal stem cells (MSCs) are regenerative and anti-inflammatory, and MSC treatment has been shown to be beneficial in several immune disorders and injury models. Our objective was to determine whether intravenous infusion of exogenous bone marrow-derived MSCs could reduce post-burn and intoxication pulmonary, hepatic, and systemic inflammation. Vehicle- or ethanol- (1.6 g/kg) treated mice were subjected to sham or 15% total body surface area scald burn. One hour post-injury, mice were given 5 × 105 CFSE-labeled MSCs or phosphate-buffered saline intravenously (i.v.) and were euthanized 24 h later. We assessed circulating biomarkers of inflammation and liver damage, measured cytokine and chemokine production, and quantified apoptosis in lung and liver tissue. Compared to intoxicated and burned mice, those treated with MSCs had less cellularity, limited apoptosis, and a slight reduction in the pro-inflammatory cytokine interleukin-6 (IL-6) and the neutrophil chemokine, KC (CXCL1) in lung tissue. Mice with MSCs treatment had more dramatic anti-inflammatory effects on systemic and hepatic inflammation, as serum IL-6 levels were diminished by 43%, and il6 and kc expression in liver tissue were markedly reduced, as were biomarkers of liver damage, aspartate transaminase (AST) and alanine transaminase (AST), compared with intoxicated and burned mice. Taken together, our results suggest intravenous MSCs treatment can diminish systemic inflammation, lessen hepatic damage, and decrease liver and lung apoptosis and inflammation, indicating MSCs as a novel therapy for restoring homeostasis of multiple organ systems in intoxicated burn patients.


In vitro selection of a deoxyribozyme that can utilize multiple substrates.
Deoxyribozymes that could catalyze the formation of an internucleotide phosphorothioester linkage were selected from a random sequence pool. During the course of the selection, the pool was successively challenged with five oligonucleotide substrates, each of which terminated in the same hexanucleotide sequence. Selected deoxyribozyme ligases could use all five substrates, albeit to different degrees, and appeared to form secondary structures that allow differential pairing between the deoxyribozyme and each substrate. These results suggest that early replicases may have been able to bind a variety of oligonucleotide substrates while catalyzing ligation via a common junction.


Phototherapy and Combination Therapies for Vitiligo.
Vitiligo is a disease characterized by disappearance of melanocytes from the skin. It can negatively influence the physical appearance of affected individuals, and may profoundly affect a person's psychosocial function and quality of life. Therefore, vitiligo should not be considered as merely a condition that affects a patient's appearance, but needs to be actively treated in patients who seek medical help. Phototherapy has been used as the main treatment modality for patients with vitiligo. Different forms of phototherapy for vitiligo include broadband UVB, narrowband UVB, excimer light and excimer laser, and psoralen plus UVA.


An In Vitro Hemodynamic Flow System to Study the Effects of Quantified Shear Stresses on Endothelial Cells.
Numerous in vitro systems have previously been developed and employed for studying the effects of hemodynamics on endothelial cell (EC) dysfunction. In the majority of that work, accurate flow quantification (e.g., uniformity of the flow over the ECs) remains elusive and wall shear stress (WSS) quantifications are determined using theoretical relationships (without considering the flow channel aspect ratio effects). In addition, those relationships are not applicable to flows other than steady laminar cases. The present work discusses the development of a novel hemodynamic flow system for studying the effects of various well-quantified flow regimes over ECs. The current work presents a novel hemodynamic flow system applying the concept of a parallel plate flow chamber (PPFC) with live microscopy access for studying the effects of quantified WSS on ECs. A range of steady laminar, pulsatile (carotid wave form) and low-Reynolds number turbulent WSSs were quantified through velocity field measurements by a laser Doppler velocimetry (LDV) system, to validate the functionality of the current hemodynamic flow system. Uniformity of the flow across the channel width can be analyzed with the current system (e.g., the flow was uniform across about 65-75% of the channel width for the steady cases). The WSS obtained from the experiments had higher values in almost all of the cases when compared to the most commonly-used theoretical solution (9% < error < 16%), whereas another relationship, which considers the channel dimensions, had better agreement with the experimental results (1% < error < 8%). Additionally, the latter relationship predicted the uniform flow region in the PPFC with an average difference of <5% when compared to the experimental results. The experimental data also showed that the WSS at various locations (D, E and F) at the test section differed by less than 4% for the laminar cases representing a fully developed flow. WSS was also determined for a low-Re (Re = 2750) turbulent flow using (1) the Reynolds shears stress and (2) the time-averaged velocity profile gradient at the wall, with a good agreement (differences <16%) between the two where the first method returned a higher value than the second. Porcine aortic endothelial cell (PAEC) viability in the system and morphological cell response to laminar WSS of about 11 dyne/cm(2), were observed. These results provide performance validation of this novel in vitro system with many improved features compared to previous similar prototypes for investigation of flow effects on ECs. The integration of the LDV technique in the current study and the comparison of the results with those from theory revealed that great care must be taken when using PPFCs since the commonly used theoretical relation for laminar steady flows is unable to predict the flow uniformity (which may introduce significant statistical bias in biological studies) and the predicted WSS was subjected to greater error when compared to a more comprehensive equation presented in the current work. Moreover, application of the LDV technique in the current system is essential for studies of more complex cases, such as disturbed flows, where the WSS cannot be predicted using theoretical or numerical modelling methods.


Recurrent synovial chondromatosis of the temporomandibular joint: report of two cases.
Synovial chondromatosis is the most common tumour-like lesion that is found in the temporomandibular joint (TMJ). Although it is benign and self-limiting, it can recur. We retrospectively reviewed 274 cases that were treated in our department from 2001-16 and found two recurrences, the radiological, surgical, histopathological, and follow-up results of which we report here. The reasons for their recurrence were analysed and elucidated.


Metabolism and properties of 3-methoxy-4-hydroxyphenyl-pyruvate; a metabolite of dihydroxyphenylalanine.
The pathway of 3,4-dihydroxyphenylalanine undergoing metabolism via transamination and subsequent oxidative rearrangement to 2,4,5-trihydroxy-phenylacetate was investigated. 3-Methoxytyrosine does not pursue an identical course, since its corresponding keto acid is not subject to action of p-hydroxy-phenylpyruvate hydroxylase. The radiochemical synthesis of 3-methoxy-4-hydroxy[carboxy-14C] pyruvate was accomplished. This metabolite was used to demonstrate that this keto acid does not proceed through oxidative rearrangement both in vitro and in vivo. The keto acid was found to be a competitive inhibitor of the hydroxylase and can help account for some of the metabolites observed in the urine of patients treated with 3,4-dihydroxyphenylalanine.


Bispectral Index Monitoring With Density Spectral Array for Delirium Detection.
Delirium in hospitalized patients often goes undetected. Cerebral state monitors, which measure limited-channel electroencephalography, have shown potential for improving delirium detection. The aim of this study was to compare an FDA-approved cerebral state monitor, bispectral index monitoring with density spectral array (DSA), for delirium identification with clinical screening methods. Hospitalized patients receiving psychiatric consultation were assessed for delirium using the 3-minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) and underwent bispectral index monitor + DSA monitoring. Visual inspection of frequency band power of the DSA was performed by 2 trained independent raters. Average hue values were calculated for each frequency band using image analysis software as the device did not allow for extraction of raw electroencephalography data. Delirious versus nondelirious group averages, sensitivity, specificity, and area under the curve were calculated for significant DSA variables and the 3D-CAM. In an initial cohort of 43 patients, visual ratings of the DSA were not associated with delirium (P > 0.1). In a larger cohort of 123 subjects, multiple band hue ratios were associated with delirium, although none survived correction for multiple comparisons. In a subgroup of 74 non-neurological patients, low theta/low delta ratio was significantly associated with delirium (P = 0.001) (sensitivity/specificity/area under the curve: 83%/70%/0.757; 3D-CAM: 67%/77%/0.717; paired-sample area under the curve difference: -0.040, P = 0.68). In 21 patients with dementia, low theta power demonstrated significantly greater sensitivity/specificity/area under the curve of 83%/78%/0.824, whereas 3D-CAM achieved 50%/78%/0.639 (P = 0.04). Bispectral index monitor + DSA was similar to 3D-CAM for detecting delirium in hospitalized patients with and without neurological disorders, and was significantly more accurate in patients with dementia. More studies are needed to validate the use of cerebral state monitors for quantitative delirium detection.


Differential in vivo effects of alpha-naphthoflavone and beta-naphthoflavone on CYP1A1 and CYP2E1 in rat liver, lung, heart, and kidney.
Male Sprague-Dawley rats were treated intraperitoneally with corn oil, the aryl hydrocarbon receptor (AHR) agonist beta-naphthoflavone (betaNF), or the relatively weak AHR agonist alpha-naphthoflavone (alphaNF). Animals treated with betaNF experienced a significant loss (12%) of total body mass over 5 days and a dramatic elevation of CYP1A1 mRNA in all of the organs studied. Treatment with alphaNF had no significant effect on body mass after 5 days and caused only minor increases of liver, kidney, and heart CYP1A1 mRNA. In contrast, lung CYP1A1 mRNA was increased by alphaNF treatment to levels comparable to that seen with betaNF treatment. CYP2E1 mRNA levels were also elevated in liver, lung, kidney, and heart in response to betaNF treatment, whereas alphaNF was without effect. Large increases of CYP1Al-dependent 7-ethoxyresorufin O-deethylation (EROD) activity occurred with microsomes prepared from the tissues of betaNF-treated animals. Comparatively small changes were associated with alphaNF treatment, with the exception of lung, where EROD activity was increased to approximately 60% of that with betaNF treatment. CYP2E1-dependent p-nitrophenol hydroxylase (PNP) activity was also increased by betaNF treatment in microsomes prepared from kidney (3.1-fold), whereas alphaNF was without effect. In contrast, alphaNF or betaNF treatment caused significant decreases of lung microsomal PNP (72% and 27% of corn oil control, respectively) and 7-pentoxyresorufin O-deethylation (48% and 17% of corn oil control, respectively) activities, indicating that PNP activity may be catalyzed by P450 isoforms other than CYP2E1 in rat lung. We conclude that betaNF and alphaNF have differential effects on the expression and catalytic activity of CYP1A1 and CYP2E1, depending upon the organ studied. These changes most likely occur as a result of the direct actions of these compounds as AHR agonists, in addition to secondary effects associated with AHR-mediated toxicity.


Monocyte chemoattractant protein 1 plasma concentration in blood from varicose veins decreases under venoactive drug treatment.
Vein-specific inflammation leads to vascular smooth muscle cells proliferation and extracellular matrix degradation of vein wall. This process is known as remodeling and is promoted by "trapped" leukocytes. Monocyte chemoattractant protein 1 (MCP-1) is a chemokine responsible for trafficking of leukocytes from blood to vein wall. The aim of this study was to measure the MCP-1 concentration in varicose veins blood before and after venoactive drug therapy and to compare it with a concentration of blood from varicose veins of subjects who did not receive drug treatment. Non-randomized comparative study was conducted on 30 patients with primary varicose veins. 20 patients of the study group received diosmin 900 mg/hesperidin 100 mg once daily. 10 controls received no treatment. MCP-1 level was measured (pg/mL) in the blood from varicose veins twice, at the day of inclusion and after 60 days. Legs discomfort related to chronic venous disease (CVD) symptoms was measured with 10-cm Visual Analogue Scale (VAS) at inclusion and at completion of the study. Median (interquartile range, IQR) MCP-1 concentrations in treatment and control groups at inclusion were 171.9 (124.4-216.0) and 157.0 (120.1-163.1), resp., P=0.285. After 60 days of treatment MCP-1 level decreased, but non-significantly to 152.3 (124.1-178.3). In patients who did not receive treatment chemokine level slightly increased to 163.0 (134.0-172.9). Median changes over time were -6.6 (-30.9-7.4) and 10.6 (-3.7-19.2) in the study and control groups, resp. (P=0.048). After 60 days in 12 of 19 and 2 of 9 patients of treatments and control groups MCP-1 decreased (P=0.103). Odds ratio for MCP-1 decreasing was 9.5 (95% CI 1.1-81.5, P=0.043) for those who received venoactive drug. Mean (± standard deviation [SD]) legs discomfort significantly dropped in the study group from 5.7 (±2.5) to 1.9 (±2.2) (P=0.0003), while in controls no changes were registered: 3.4 (±1.3) and 3.5 (± 1.4), resp., P=0.28). Mean difference of VAS at baseline and at follow-up was -3.5 (±2.6) and 0.9 (±2.1), resp. (P<0.0001). Plasma concentration of MCP-1 in varicose veins blood demonstrates a tendency to decrease under two months treatment with a venoactive drug. Future studies are needed to reveal a possible role of MCP-1 as a target considering its role in varicose veins pathogenesis.


Prognosis and surgical management of patients with palpable inguinal lymph node metastases from melanoma.
The appropriate management of melanoma metastatic to inguinal lymph nodes remains controversial. The aim of this study was to identify disease- and treatment-related factors that influence the outcome of patients undergoing therapeutic groin dissection for clinically detectable melanoma lymph node metastases. A retrospective analysis was performed on data collected from the case records of patients who had a therapeutic inguinal lymph node dissection performed between 1984 and 1998. Some 132 patients were suitable for inclusion. Sixty patients had superficial inguinal lymph node dissection (SLND) and 72 had combined superficial inguinal and pelvic lymph node dissection (CLND). There was no difference in postoperative morbidity or major lymphoedema between SLND and CLND. The overall survival rate was 34 per cent at 5 years. On univariate analysis, age (P = 0.003), the number of involved superficial lymph nodes (P = 0.001) and the presence of extracapsular spread (P = 0.003) were found to have a significant impact on survival. The presence or absence of pelvic lymph node metastases in patients who had CLND was a significant prognostic factor for survival (5-year survival 19 versus 47 per cent; P = 0.015). The prognosis of patients with clinically detectable melanoma metastases to the groin is variable and related to the biological characteristics of each case. CLND provided additional prognostic information and optimal regional control with no increased morbidity compared with SLND.


Framing the process in the implementation of care for people with generalized anxiety disorder in primary care: a qualitative evidence synthesis.
Generalized anxiety disorder (GAD) is one of the most common mental disorders in primary care (PC). GAD has low remission and high relapse rates over long follow-up periods. Qualitative evidence was synthesized to understand the implementation of care and treatment options for people with GAD in PC. Research published from 2008 to September 2020 was searched in five databases (MEDLINE, EMBASE, CINAHL, WOS and PsycArticles). Studies that used qualitative methods for data collection and analysis to investigate the implementation of care and treatment options for people with GAD in PC and outpatient settings were included. Non-qualitative studies, mixed methods studies that did not separately report qualitative findings and studies in languages other than English or Spanish were excluded. We used the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) framework to assess the overall confidence in the findings. The results with a moderate level of confidence showed that the trajectory of care for people with GAD in PC and outpatient settings is long and fluctuates over time, involving multiple difficulties in accessing and maintaining initial treatment or successive treatment options. In addition, there are wide variations in the preferences for and acceptability of different treatment options. The results with a high level of confidence indicated that more information on GAD and its treatment options is needed for PC practitioners, GAD patients and their carers. The results with a low level of confidence suggested that patients use antidepressants for longer than recommended and that the interruption of treatment is not usually planned. Initial resistance to new treatments among people with GAD can make access and adherence to treatment difficult. Improving care may require patients to be informed of possible trajectories in stepped care pathways before the initiation of treatment so they are aware that they may need to try a number of options until the most effective treatment for them is found. Increased awareness of and information materials on GAD may facilitate both appropriate diagnosis and long-term care.


Surfactin reduces particulate matter-induced VCAM-1-dependent monocyte adhesion in human gingival fibroblasts by increasing Nrf2-dependent HO-1 expression.
The mechanisms of particulate matter (PM) toxicity involve the generation of ROS and upregulation of proinflammatory molecules. Nrf2 is a multifunctional cytoprotective transcription factor that regulates the expression of various antioxidant, anti-inflammatory, and detoxifying molecules, such as HO-1. As surfactin has potential to induce Nrf2 activation and HO-1 expression, this study aimed to investigate the anti-inflammatory effects of surfactin on PM-exposed human gingival fibroblasts (HGFs) and signaling pathways engaged by surfactin. Human gingival fibroblasts were challenged by PM with or without surfactin pretreatment. The expression of Nrf2, HO-1, VCAM-1, and other molecules was determined by western blot, real-time PCR, or ELISA. Human monocytic THP-1 cells labeled with fluorescent reagent were added to HGFs, and the cell adhesion was assessed. ROS generation and NADPH oxidase activity were also measured. The involvement of Nrf2/HO-1 and ROS signaling pathways was investigated by treating HGFs with specific pathway interventions, genetically or pharmacologically. One dose of surfactin was given to mice before PM treatment to explore its in vivo effect on VCAM-1 expression in gingival tissues. Particulate matter led to VCAM-1-dependent monocyte adhesion in HGFs, which was regulated by PKCα/NADPH oxidase/ROS/STAT1/IL-6 pathway. Surfactin could attenuate monocyte adhesion by disrupting this VCAM-1-dependent pathway. Additionally, surfactin promoted Nrf2-dependent HO-1 expression in HGFs, mitigating VCAM-1 expression. PM-treated mice exhibited the lower expression of IL-6 and VCAM-1 in gingival tissues if they previously received surfactin. Surfactin exerts anti-inflammatory effects against PM-induced inflammatory responses in HGFs by inhibiting VCAM-1-dependent pathway and inducing Nrf2/HO-1 axis.


An alternative protocol for DNA extraction from formalin fixed and paraffin wax embedded tissue.
DNA extraction from paraffin wax embedded tissue requires special protocols, and most described methods report an amplification success rate of 60-80%. To propose a simple and inexpensive protocol consisting of xylene/ethanol dewaxing, followed by a kit based extraction. Xylene/ethanol dewaxing was followed by a long rehydration step and a kit based DNA extraction step. This method produced a 100% amplification success rate for fragments of 121 to 227 bp for tamponated formalin fixed paraffin wax embedded tissue. This cost effective and non-laborious protocol can successfully extract DNA from tamponated formalin fixed paraffin wax embedded tissue and should facilitate the molecular analysis of a large number of archival specimens in retrospective studies.


Effect of 12 months of creatine supplementation and whole-body resistance training on measures of bone, muscle and strength in older males.
The combination of creatine supplementation and resistance training (10-12 weeks) has been shown to increase bone mineral content and reduce a urinary indicator of bone resorption in older males compared with placebo. However, the longer-term effects (12 months) of creatine and resistance training on bone mineral density and bone geometric properties in older males is unknown. To assess the effects of 12 months of creatine supplementation and supervised, whole-body resistance training on bone mineral density, bone geometric properties, muscle accretion, and strength in older males. Participants were randomized to supplement with creatine (n = 18, 49-69 years, 0.1 g·kg-1·d-1) or placebo (n = 20, 49-67 years, 0.1 g·kg-1·d-1) during 12 months of supervised, whole-body resistance training. After 12 months of training, both groups experienced similar changes in bone mineral density and geometry, bone speed of sound, lean tissue and fat mass, muscle thickness, and muscle strength. There was a trend (p = 0.061) for creatine to increase the section modulus of the narrow part of the femoral neck, an indicator of bone bending strength, compared with placebo. Adverse events did not differ between creatine and placebo. Twelve months of creatine supplementation and supervised, whole-body resistance training had no greater effect on measures of bone, muscle, or strength in older males compared with placebo.


Inhibition of bromate formation in plasmon-enhanced catalytic ozonation over silver-doped spinel ferrite.
High energy consumption and formation of harmful byproducts are two challenges faced by advanced oxidation processes (AOPs). While much research efforts have been devoted to improving the treatment efficiency, byproduct formation and control calls for more attention. In this study, the underlying mechanism of bromate formation inhibition during a novel plasmon-enhanced catalytic ozonation process with silver-doped spinel ferrite (0.5wt%Ag/MnFe2O4) as the catalysts was investigated. By scrutinizing the effects of each factor (i.e. irradiation, catalyst, ozone) as well as the combinations of different factors on major Br species involved in bromate formation, examining the distribution of Br species, and probing the reactive oxygen species partaking in the reactions, it was found that accelerated ozone decomposition which inhibited two main bromate formation pathways and surface reduction of Br species (e.g. HOBr/OBr- and BrO3-) contributed to the inhibition of bromate formation, both of which can be enhanced by the plasmonic effects of Ag and the good affinity between Ag and Br. A kinetic model was developed by simultaneously solving 95 reactions to predict the aqueous concentrations of Br species during different ozonation processes. The good agreement between the model prediction and experimental data further corroborated the hypothesized reaction mechanism.


An observational study: associations between nurse-reported hospital characteristics and estimated 30-day survival probabilities.
There is a growing body of evidence for associations between the work environment and patient outcomes. A good work environment may maximise healthcare workers' efforts to avoid failures and to facilitate quality care that is focused on patient safety. Several studies use nurse-reported quality measures, but it is uncertain whether these outcomes are correlated with clinical outcomes. The aim of this study was to determine the correlations between hospital-aggregated, nurse-assessed quality and safety, and estimated probabilities for 30-day survival in and out of hospital. In a multicentre study involving almost all Norwegian hospitals with more than 85 beds (sample size=30, information about nurses' perceptions of organisational characteristics were collected. Subscales from this survey were used to describe properties of the organisations: quality system, patient safety management, nurse-physician relationship, staffing adequacy, quality of nursing and patient safety. The average scores for these organisational characteristics were aggregated to hospital level, and merged with estimated probabilities for 30-day survival in and out of hospital (survival probabilities) from a national database. In this observational, ecological study, the relationships between the organisational characteristics (independent variables) and clinical outcomes (survival probabilities) were examined. Survival probabilities were correlated with nurse-assessed quality of nursing. Furthermore, the subjective perception of staffing adequacy was correlated with overall survival. This study showed that perceived staffing adequacy and nurses' assessments of quality of nursing were correlated with survival probabilities. It is suggested that the way nurses characterise the microsystems they belong to, also reflects the general performance of hospitals.


Safety, efficacy and pharmacokinetics of palivizumab in off-label neonates, infants, and young children at risk for serious respiratory syncytial virus infection: a multicenter phase II clinical trial.
Pediatric patients with certain rare diseases are at increased risk of severe respiratory syncytial virus (RSV) infection. However, the prophylactic use of anti-RSV antibody (palivizumab) in these patients is not indicated at present in Japan. This first-in-the-world multicenter, uncontrolled, open-label, phase II clinical trial was carried out between 28 July 2019 and 24 September 2021 at seven medical institutions in Japan to investigate the efficacy, safety, and pharmacokinetics of palivizumab in 23 subjects recruited from among neonates, infants, or children aged 24 months or younger who had any of the following conditions: pulmonary hypoplasia, airway stenosis, congenital esophageal atresia, inherited metabolic disease, or neuromuscular disease. At least four continuous doses of palivizumab were administered intramuscularly at 15 mg/kg at intervals of 30 days. Twenty-three enrolled subjects completed the study. No subject required hospitalization for RSV. Adverse events (AE) did not notably differ from the event terms described in the latest interview form. Five severe AEs required unplanned hospitalization, but resolved without RSV infection. Therapeutically effective concentrations of palivizumab were maintained throughout the study period. Palivizumab might be well tolerated and effective in preventing serious respiratory symptoms and hospitalization due to severe RSV infection, indicating the prophylactic use in the pediatric patients included in this study. Japan Agency for Medical Research and Development (AMED), grant numbers 19lk0201097h0001 (to MM), 20lk0201097h0002 (to MM), 21lk0201097h0003 (to MM), and 22lk0201097h0004 (to MM). AMED did not have any role in the execution of this study, analysis and interpretation of the data, or the decision to submit the results.


Effect of an anti-tumor platinum complex, Pt(II) diaminotoluene, on mitochondrial membrane properties.
The effects of platinum complexes, selected for their potent anti-tumor activities, have been studied on rat liver mitochondria. Among the mitochondrial properties which have been studied, the most marked effects of platinum complexes were obtained on functions linked to the inner membrane. cis-Pt(II)(3,4-diaminotoluene) dichloride is shown to stimulate state 4 respiration. It inhibits the phosphate transport into mitochondria, decreases the accumulation of Ca2+, and induces a more rapid release of the accumulated Ca2+. A release of Mg2+ from mitochondria incubated in the absence of added divalent cations, and an efflux of divalent cations from mitochondrial membranes are also observed. All these results indicate a profound modification of the of the permeability of mitochondrial membrane.


A non-inferiority study comparing the ultrasound-guided parasacral with a novel greater ischiatic notch plane approach in canine cadavers.
To describe the gross and ultrasound anatomy of the parasacral region and an ultrasound-guided greater ischiatic notch (GIN) plane approach aimed at staining the lumbosacral trunk (LST) in canine cadavers. To evaluate if the ultrasound-guided GIN plane approach is non-inferior to the previously described ultrasound-guided parasacral approach at staining the LST. Prospective, randomized, non-inferiority experimental anatomic study. A total of 17 (23.9 ± 5.2 kg) mesocephalic canine cadavers. Anatomic and echographic landmarks, and the feasibility of performing a GIN plane technique were evaluated using two canine cadavers. The remaining 15 cadavers had each hemipelvis randomly assigned to be administered either parasacral or GIN plane injection of 0.15 mL kg-1 dye solution. The parasacral region was dissected after injections to assess the staining of LST, cranial gluteal nerve, pararectal fossa and pelvic cavity. The stained LST were removed and processed for histological evaluation of intraneural injections. A one-sided z-test for non-inferiority (non-inferiority margin -14%) was used to statistically evaluate the success of the GIN plane versus the parasacral approach. Data were considered statistically significant when p < 0.05. The GIN plane and parasacral approach stained the LST in 100% and 93.3% of the injections, respectively. The success rate difference between treatments was 6.7% [95% confidence interval, -0.6 to 19.0%; p < 0.001 for non-inferiority]. The GIN plane and parasacral injections stained the LST for 32.7 ± 16.8 mm and 43.1 ± 24.3 mm, respectively (p = 0.18). No evidence of intraneural injection was found. The ultrasound-guided GIN plane technique resulted in nerve staining that was non-inferior to the parasacral technique and may be considered an alternative to the parasacral approach to block the LST in dogs.


Ubiquitin proteomics identifies RNA polymerase I as a target of the Smc5/6 complex.
Ubiquitination controls numerous cellular processes, and its deregulation is associated with many pathologies. The Nse1 subunit in the Smc5/6 complex contains a RING domain with ubiquitin E3 ligase activity and essential functions in genome integrity. However, Nse1-dependent ubiquitin targets remain elusive. Here, we use label-free quantitative proteomics to analyze the nuclear ubiquitinome of nse1-C274A RING mutant cells. Our results show that Nse1 impacts the ubiquitination of several proteins involved in ribosome biogenesis and metabolism that, importantly, extend beyond canonical functions of Smc5/6. In addition, our analysis suggests a connection between Nse1 and RNA polymerase I (RNA Pol I) ubiquitination. Specifically, Nse1 and the Smc5/6 complex promote ubiquitination of K408 and K410 in the clamp domain of Rpa190, a modification that induces its degradation in response to blocks in transcriptional elongation. We propose that this mechanism contributes to Smc5/6-dependent segregation of the rDNA array, the locus transcribed by RNA Pol I.


Effects of Ca2+ and EGTA on P680*+ reduction kinetics and O2 evolution of Photosystem II.
We report for the first time significant changes in the P680*+ reduction kinetics of Photosystem II (PS II) in which the 17 and 23 kDa extrinsic polypeptides are intact, in the presence of Ca(2+) or ethylene glycol bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) which were added to vary the Ca(2+) concentration from 5 microM to 30 mM. The decrease in the extent of normal P680*+ reduction decay with lifetimes of 40-370 ns and a corresponding increase in the extent of kinetics with lifetimes of 20-220 micros was interpreted as being due to electron transfer from Y(Z) to P680*+ being replaced by slow forward conduction and by processes including P680*+/Q(A)(-) recombination. The question of whether changes in P680*+ reduction kinetics were caused by loss of Ca(2+) from PS II or by direct interaction of EGTA with PS II was addressed by lowering the free-Ca(2+) concentration of suspensions of PS II core complexes by serial dilution in the absence of EGTA. Despite a significant decrease in the rate of O(2) evolution after this treatment, only small changes in the P680*+ reduction kinetics were observed. Loss of Ca(2+) did not affect P680*+ reduction associated with electron transfer from Y(Z). Since much larger changes in the P680*+ reduction kinetics of intact PS II occurred at comparable free-Ca(2+) concentrations in the presence of EGTA, we conclude that EGTA influenced the P680*+ reduction kinetics by directly interacting with PS II rather than by lowering the free Ca(2+) concentration of the surrounding media. Notwithstanding these effects, we show that useful information about Ca(2+) binding to PS II can be obtained when direct interaction of EGTA is taken into account.


Mate choice on fallow deer leks.
Leks, on which males defend small clustered mating territories, may have evolved because of the unusual opportunities they provide for female choice of mating partners, and several studies of lek-breeding animals have demonstrated correlations between the mating success of males and their phenotype or behaviour. However, these could arise because (1) females select mates on the basis of male phenotypic traits; (2) males interfere with each other's mating attempts; or (3) females show preferences for particular mating territories, and larger or stronger males are more likely to win access to these territories. Here we report that when fallow bucks on a traditional lek were experimentally induced to change their territories, differences in the mating success of bucks persisted, whereas differences in the position of their territories relative to the centre of the lek did not. The observation that bucks rarely interfered with their neighbours' harems and females moved freely between bucks suggests that females choose their mates on the basis of male phenotype rather than territory type or location. In this population, the immediate factor affecting the movements of females between males was the size of a buck's harem.


Characteristics of an Acanthamoeba keratitis outbreak in British Columbia between 2003 and 2007.
Quantify and describe Acanthamoeba keratitis (AK) cases in British Columbia (BC). A comparison of annual incidence rates confirms the presence of an outbreak. A case series describes characteristics of the outbreak. All laboratory-confirmed AK cases (persons) in BC (1988-2011; n = 68) were included in the incidence rate comparison. Of the 42 cases (persons) between 2003 and 2007, 32 were selected to interview (laboratory confirmed, 2005-2007), and the 23 who completed interviews form the case series. A comparison of standardized annual incidence rates in historic to outbreak periods is performed by z-score test. A telephone interview and descriptive analysis detailing demographics, risk factors, and contact lens (CL) wearing habits was completed for 23 cases. We measure number of laboratory confirmed cases in BC. In addition, risk factors and potential exposures of these cases are reported. The annual incidence of AK increased significantly from 0.029 to 0.200 per 100 000 population between historic years (1988-2002) and outbreak years (2003-2007; P = 0.022). The annual incidence of AK has since returned to near historic levels (0.056/100 000 population). The case series identified multiple risk factors, including the use of a specific recalled solution (60.9%), daily soft CL wear (95.7%), all-in-one solutions (95.7%), showering while wearing CL (65.2%), and generally poor CL hygiene. A significant increase in annual AK incidence occurred between 2003 and 2007 in BC. After 2007, the incidence of AK returned to near historic levels. The recalled solution was associated with many cases; however, other risk factors were also identified, including being unaware of the recall and poor CL hygiene practices, highlighting the need for improved education about the severity of AK and consequences of improper CL hygiene. The authors have no proprietary or commercial interest in any of the materials discussed in this article.


Growth hormone response to growth hormone-releasing hormone in early abstinent alcoholic patients.
The alpha-2-adrenoceptor agonist clonidine is able to stimulate GHRH secretion directly or via beta-endorphin and, therefore, induces a GH release in normal subjects. This effect has been shown to be blunted in alcoholism during early abstinence, due to central alterations of adrenergic mechanisms. To evaluate pituitary responsiveness to direct stimulation with GHRH, we have studied the GH and PRL response to GHRH in 10 alcoholics during early abstinence. Our data indicate that the pituitary response to GHRH is intact in abstinent alcoholics, except in obese patients, who displayed a blunted GH response. GHRH did not increase PRL. The dissociation between clonidine and GHRH in GH stimulation could reveal a different neuroendocrine mechanism, in comparison with other psychiatric disorders (anorexia nervosa), in which such a dissociation is accompanied by a PRL response to GHRH.


Detection of Neisseria gonorrhoeae infection by ligase chain reaction testing of urine among adolescent women with and without Chlamydia trachomatis infection.
Culture, the conventional method for detection of Neisseria gonorrhoeae, requires invasive sampling and stringent specimen transport conditions. The recently developed ligase chain reaction test (LCR; Abbott Laboratories; North Chicago, IL) allows noninvasive sampling and stable transport conditions, but has not been evaluated with specimens from adolescent populations. To perform a comparative evaluation of a commercial LCR test and culture for the diagnosis of N. gonorrhoeae in adolescent women. Urine and endocervical swab specimens from 330 teenage women seen in two public health adolescent clinics were tested by LCR and culture. For resolution of discordant results, a polymerase chain reaction (PCR) test was developed that directly amplifies N. gonorrhoeae DNA from urine samples processed for LCR. Thirty-one of 330 (9.4%) cervical specimens were culture-positive for N. gonorrhoeae, and 30 of 330 (9.1%) urine specimens were positive by LCR. After resolution of 13 discordant results, the sensitivity, specificity, and positive and negative predictive values of LCR for urine were 88.2%, 100%, 100%, 98.7%, respectively, and for culture of endocervical specimens were 82.3%, 98.9%, 90.3% and 98%, respectively. Although more expensive than culture, LCR offers a sensitive means for the detection of N. gonorrhoeae in urine samples and may be useful for this purpose in settings where pelvic examinations are difficult to perform and simultaneous detection of N. gonorrhoeae and Chlamydia trachomatis is advantageous.


Future employability, a new approach to cost-effectiveness analysis of antipsychotic therapy.
Schizophrenia patients pose a substantial burden in terms of indirect costs, much of which is attributable to loss of employment. We present a new approach to assess the cost-effectiveness (CE) of risperidone vs. haloperidol using employability as an outcome measure. A decision analytic CE model was developed to compare the two treatments over a 1-year period including all direct medical costs and the number of employable persons as a measure of effectiveness. A measure of executive functioning, the Wisconsin Card Sorting Test Category score (WCST-Cat score), was used as an intermediate endpoint from which employability was modeled. A Monte Carlo procedure, using WCST-Cat score sampling distributions from clinical trials, simulated the WCST-Cat score distribution for a cohort of 10,000 patients. A clinically stable patient, with a Positive and Negative Syndrome Scale (PANSS) score increase of at least 20% and a WCST-Cat score of > or =3.5 was assumed to be employable. Sensitivity analysis was performed for key values. The base case per-patient cost of risperidone and haloperidol was 6,422 US dollars and 4,989 US dollars, respectively, and the number of employable persons was 3,258 (32.58%) and 2,517 (25.17%), respectively, which translates to an incremental CE ratio of 19,609 US dollars per employable person for risperidone. Risperidone remained cost increasing and had higher number of employable persons over all the ranges used in the sensitivity analysis. The incremental CE ratio ranged from a high of 1,000,000 US dollars to a low of 3,000 US dollars per employable persons when the rates of clinical stability for risperidone and haloperidol therapy were varied. Gains from earning rates for employed persons with schizophrenia, savings in informal caregiver costs and other human benefits could justify an incremental cost of 19,609 US dollars for each additional employable person prescribed risperidone.


Cost-effectiveness of doxorubicin-eluting beads versus conventional trans-arterial chemo-embolization for hepatocellular carcinoma.
Doxorubicin-loaded drug-eluting beads TACE (DEB-TACE) has been developed to maximize the therapeutic efficacy of conventional trans-catheter arterial chemo-embolization (cTACE) in patients with hepatocellular carcinoma (HCC); however, its cost-effectiveness (CE) still needs to be assessed. To investigate the CE of DEB-TACE versus cTACE. Results from a meta-analysis of the pertinent literature were used to construct a CE Markov simulation model which followed a hypothetical cohort of HCC patients who underwent DEB-TACE or cTACE, covering the entire post-TACE lifespan until death. Costs were assessed from the health-care provider perspective. Five randomized controlled trials (RCTs) and 11 observational studies, including 1860 patients (883 DEB-TACE and 977 cTACE), were used for the construction of the model. Considering only survival rates from RCTs (heterogeneity: 0%), DEB-TACE returned 4.0 quality-adjusted life-years (QALYs) and TACE returned 3.3 QALYs (effect size=1.288). Total costs of cTACE were €10,389 and those of DEB-TACE were €11,418 (effect size=0.791). DEB-TACE was found more cost-effective than cTACE when a minimum willingness-to-pay of about €2000-3500/QALY was accepted, mainly depending on shorter in-hospital stay and better quality of life. Direct incremental costs of DEB-TACE can be acceptable in respect to cTACE, relying on financial resources available from the payer perspective.


Molecular basis for chirality-regulated Aβ self-assembly and receptor recognition revealed by ion mobility-mass spectrometry.
Despite extensive efforts on probing the mechanism of Alzheimer's disease (AD) and enormous investments into AD drug development, the lack of effective disease-modifying therapeutics and the complexity of the AD pathogenesis process suggest a great need for further insights into alternative AD drug targets. Herein, we focus on the chiral effects of truncated amyloid beta (Aβ) and offer further structural and molecular evidence for epitope region-specific, chirality-regulated Aβ fragment self-assembly and its potential impact on receptor-recognition. A multidimensional ion mobility-mass spectrometry (IM-MS) analytical platform and in-solution kinetics analysis reveal the comprehensive structural and molecular basis for differential Aβ fragment chiral chemistry, including the differential and cooperative roles of chiral Aβ N-terminal and C-terminal fragments in receptor recognition. Our method is applicable to many other systems and the results may shed light on the potential development of novel AD therapeutic strategies based on targeting the D-isomerized Aβ, rather than natural L-Aβ.


Survey of physicians' and patients' understanding, perceptions, and attitudes toward depressive state in atrial fibrillation.
Atrial fibrillation (AF) is the most common sustained arrhythmia among older people and has a significant impact on quality of life. However, it is not always perceived as a serious mental health risk. This study investigated the understanding, perceptions, and attitudes toward the risk of depressive state associated with older patients with AF. We conducted a quantitative survey in April-June 2021 among patients with AF aged ≥65 years (n = 156), and physicians or cardiologists attending at least 10 older patients with AF annually (n = 158). In total, 45% of patients considered AF a cause of a depressive state. In contrast, 16% of physicians reported that they considered AF a cause of a depressive state. Fifty-two percent of the patients had experienced a depressive state. Of these, 98% expressed that a depressive state lowered their quality of life. Two of the three patients reported that they would consult their physicians if they felt depressed. By contrast, 30% of physicians responded that even if they perceived their patients as depressed, they prescribe anti-anxiety medication but do not refer the patient to psychiatrists. Of the physicians, 50% stated that they did not regard the association of AF and depressive state as serious, although both physicians and patients understood that negative anxiety, such as fear of AF attacks, strokes, or heart failure, was the most important contributor to a depressive state. Establishing mental healthcare involving physicians together with psychiatrists is necessary to improve the mental and physical health outcomes for older patients with AF. Geriatr Gerontol Int 2023; 23: 543-548.


Arylsulfonates as sole source of sulfur for Clostridium pasteurianum DSM 12136.
A variety of arylsulfonates were examined for their ability to support growth of Clostridium pasteurianum as sole source of sulfur. Among the eleven different arylsulfonates tested, six of them (benzenesulfonate, 4-toluenesulfonate, 4-xylene-2-sulfonate, 4-aminobenzenesulfonate, 4-sulfobenzoic acid, 1,3-benzenedisulfonate) could serve as sole sulfur source for C. pasteurianum DSM 12136. None of the sulfonates tested could serve as sole sulfur source for C. pasteurianum ATCC 6013. The two C. pasteurianum in this study could not utilize any of these sulfonates as sole carbon and energy source. We demonstrated that desulfonation of arylsulfonates could take place under anoxic conditions and the sulfur atom of these compounds could be utilized as sole source of sulfur by anaerobic bacteria.


Reducing the waiting time to initiation of infertility treatment at a tertiary care centre in India.
In a low-resource and high-volume setting, it is often felt that patient care cannot be improved within the limitations of existing infrastructure and resources. However, the use of a systematic problem-solving method can bring about significant improvement even in these settings. To decrease the mean waiting time from first visit to initiation of infertility treatment by 70% within 4 weeks (1-30 June 2019) for patients coming to the gynaecological outpatient department (OPD). We constructed a multidisciplinary quality improvement team consisting of an academic consultant, a senior resident physician, a junior resident physician and a nurse to address the problem of long waiting times to initiation of fertility treatment. We collected baseline data from 10 consecutive women presenting to gynaecological OPD with complaints of infertility by calculating the time between their first visit to the facility and the day of performance of hysterosalpingography (HSG). The average waiting time was found to be 6 months and 25 days (mean=6.85 months; 3.5-10 months). The team used process flow diagrams and fishbone analysis to identify various causes of these long waiting times. The main reason for the delay in starting infertility treatment was that the date for HSG was given only after seeing the endometrial aspiration report (ie, after ruling out endometrial tuberculosis as there is a risk of dissemination of tuberculosis during HSG). Also, HSG was done only once a week during a short 2-hour slot in the fluoroscopy room. After the implementation of change ideas, there was significant reduction in the waiting period to starting treatment in patients with infertility. After the first change idea, the average waiting period seen in 10 consecutive patients with infertility reduced to 3.25 months, that is, by 51.8% from baseline within a 2-week interval, and there is shift in the run chart diagram. After the second change idea, the waiting time reduced to 2 months, that is, by 70%, seen in the next 10 consecutive patients with infertility within the next 2 weeks' time. The results were sustained to the average waiting time of 2 months for 6 months without any additional resources. With a well-organised and conducted quality improvement project and team efforts, the required changes can be brought about in an established conventional healthcare delivery system and improvements can be sustained over a long period of time.


Trypanosoma cruzi: an in vitro cycle of cell differentiation in axenic culture.
The operation of an in vitro cycle of cell differentiation of Trypanosoma cruzi in axenic culture was obtained. When epimastigote forms, grown in LIT medium, were transferred to a modified LIT medium (E. Chiari, 1981, "Diferenciação do Trypanosoma cruzi em cultura." Ph.D. dissertation, Universidade Federal de Minas Gerais, Brazil), metacyclic trypomastigotes were generated. The latter, upon treatment with fresh human serum, and subsequent incubation in LIT medium gave origin to clusters of spheromastigote cells. The spheromastigotes were resistent to lysis mediated by the complement system and possess a morphology shown by optical and electron microscopy to be very similar to spheromastigotes derived from tissues of infected vertebrates. Blood-like trypomastigotes, or epimastigotes, could be obtained from spheromastigotes depending on the incubation conditions: at high serum concentration (55%) at 37 C, blood-like trypomastigotes were generated; by aging or heating (37 C), at low serum concentration (10%), epimastigotes were formed, closing the whole sequence of cell differentiation of T. cruzi. The molecular characterization of the different cell forms by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of metabolic pulse labeled proteins showed that the in vitro differentiated cells were distinct, not only by morphological criteria, but by differential gene expression as well. All the forms described could be obtained in large amounts (6 x 10(7) to 1 x 10(8)/ml), making it possible to perform preparative biochemical, molecular biological, and immunological experiments.


Patch engineering: a general approach for creating proteins that have new binding activities.
Patch engineering is a technique for creating folded proteins that have new binding activities. Different protein scaffolds are used to present a patch of discontinuous residues on a folded-protein surface. By varying simultaneously the residues in these patches and displaying these mutant proteins on phage, one can select proteins that have new binding activities. Patch engineering is applicable to any protein fold. Novel proteins derived by this approach might replace antibodies in certain applications or provide lead molecules for the design of non-peptide analogues.


Influence of hormone replacement therapy on proteomic pattern in serum of postmenopausal women.
Proteomics approaches to cardiovascular biology and disease hold the promise of identifying specific proteins and peptides or modification thereof to assist in the identification of novel biomarkers. By using surface-enhanced laser desorption and ionization time of flight mass spectroscopy (SELDI-TOF-MS) serum peptide and protein patterns were detected enabling to discriminate between postmenopausal women with and without hormone replacement therapy (HRT). Serum of 13 HRT and 27 control subjects was analyzed and 42 peptides and proteins could be tentatively identified based on their molecular weight and binding characteristics on the chip surface. By using decision tree-based Biomarker Patternstrade mark Software classification and regression analysis a discriminatory function was developed allowing to distinguish between HRT women and controls correctly and, thus, yielding a sensitivity of 100% and a specificity of 100%. The results show that peptide and protein patterns have the potential to deliver novel biomarkers as well as pinpointing targets for improved treatment. The biomarkers obtained represent a promising tool to discriminate between HRT users and non-users. According to a tentative identification of the markers by their molecular weight and binding characteristics, most of them appear to be part of the inflammation induced acute-phase response.


Ethanol, thyroid hormones and acute liver injury: is there a relationship?
Alcoholic liver disease continues to be an important cause of morbidity and mortality, and the hypermetabolic hypothesis continues to be an attractive area for research. However, the current state of knowledge does not allow unequivocal acceptance or rejection of the role of thyroid hormone and antithyroid medication in alcoholic hepatitis. Clinical trials will help to establish or disprove the veracity of this hypothesis. What has been established is that chronic ethanol ingestion enhances EMR (19-22) which probably reflects the degree of hepatocellular necrosis, at least when relatively mild (25). The influence of thyroid hormone or a hyperthyroid-like state on EMR would be established if it could be shown that different antithyroid medications inhibit the enhanced EMR in chronic alcoholics. This effect has been shown in rats (125), but not in man. It is not apparent that events in the rat model can be readily applied to man. Furthermore, proof that antithyroid medications can inhibit enhanced EMR in chronic ethanol-consuming patients may allow this feature to be used to select patients who may best benefit from such treatment. A controlled randomized clinical trial using different anti-thyroid medications in alcoholic hepatitis may shed light on this important question. At the very least, demonstration of inhibition of enhanced EMR by antithyroid medications may provide the rationale for research concerning the role of thyroid hormone (or a similar hypermetabolic factor) in alcohol-mediated hepatocellular injury.


Carotid-subclavian arterial reconstruction: concomitant ipsilateral carotid endarterectomy increases risk of perioperative stroke.
Carotid-subclavian bypass (CSB) and carotid-subclavian transposition (CST) have excellent long-term patency with low perioperative mortality and morbidity. Carotid endarterectomy (CEA) is necessary for severe ipsilateral internal carotid artery stenosis in a small subset of these patients. CEA can be performed as a combined or separate procedure. This study was undertaken to delineate the results of CSB and CST at our institution and to determine if concomitant CEA with CSB or CST is safe. We evaluated the outcome of 36 patients with symptomatic subclavian artery stenosis treated surgically at a single institution during a 22-year period. Outcomes of patients undergoing CSB or CST with concomitant CEA were compared with those of patients undergoing CSB or CST alone. Available literature was reviewed to compare the rate of perioperative stroke following CSB or CST with concomitant CEA versus CSB or CST alone. Twenty-one patients underwent CST and 15 patients underwent CSB. There were 2 (5.6%) deaths and 2 (5.6%) strokes within 30 days of surgery. Concomitant CEA was performed in 6 CST patients and 2 CSB patients. Both perioperative strokes occurred in patients who had concomitant CEA. There were no strokes in the CST or CSB alone group (P = .044). In a collected review of 12 evaluable studies plus our experience, the rate of perioperative stroke was 0.32% in 617 patients who underwent CSB or CST alone versus 4.73% in 148 patients who had concomitant CEA with CSB or CST (P < .001). Both CSB and CST are safe and effective for symptomatic subclavian artery stenosis, with excellent long-term results. In patients also requiring CEA, the rate of perioperative stroke is significantly higher with a combined procedure. Consideration should be given to performing CEA separately from CSB or CST.


Ultrasound-based radiomics in the diagnosis of carpal tunnel syndrome: The influence of regions of interest delineation method on mode.
In the recent years, artificial intelligence (AI) algorithms have been used to accurately diagnose musculoskeletal diseases. However, it is not known whether the particular regions of interest (ROI) delineation method would affect the performance of the AI algorithm. The purpose of this study was to investigate the influence of ROI delineation methods on model performance and observer consistency. In this retrospective analysis, ultrasound (US) measures of median nerves affected with carpal tunnel syndrome (CTS) were compared to median nerves in a control group without CTS. Two methods were used for delineation of the ROI: (1) the ROI along the hyperechoic medial edge of the median nerve but not including the epineurium (MN) (ROI1); and (2) the ROI including the hyperechoic epineurium (ROI2), respectively. The intra group correlation coefficient (ICC) was used to compare the observer consistency of ROI features (i.e. the corresponding radiomics parameters). Parameters α1 and α2 were obtained based on the ICC of ROI1 features and ROI2 features. The ROC analysis was used to determine the area under the curve (AUC) and evaluate the performance of the radiologists and network. In addition, four indices, namely sensitivity, specificity, positive prediction and negative prediction were analyzed too. A total of 136 wrists of 77 CTS group and 136 wrists of 74 control group were included in the study. Control group was matched to CTS group according to the age and sex. The observer consistency of ROI features delineated by the two schemes was different, and the consistency of ROI1 features was higher (α1 ˃ α2). The intra-observer consistency was higher than the inter-observer consistency regardless of the scheme, and the intra-observer consistency was higher when chose scheme one. The performances of models based on the two ROI features were different, although the AUC of each model was greater than 0.8.The model performed better when the MN epineurium was included in the ROI. Among five artificial intelligence algorithms, the Forest models (model1 achieved an AUC of 0.921 in training datasets and 0.830 in testing datasets; model2 achieved an AUC of 0.967 in training datasets and 0.872 in testing datasets.) obtained the highest performance, followed by the support vector machine (SVM) models and the Logistic models. The performances of the models were significantly better than the inexperienced radiologist (Dr. B. Z. achieved an AUC of 0.702). Different ROI delineation methods may affect the performance of the model and the consistency of observers. Model performance was better when the ROI contained the MN epineurium, and observer consistency was higher when the ROI was delineated along the hyperechoic medial border of the MN.


Colleague interactions and new drug prescribing behavior: the case of the initial prescription of antidepressants in Taiwanese medical centers.
This research explores the social factors influencing hospital physicians' initial adoption of duloxetine hydrochloride, with a focus on colleague interactions. The study analyzes archival data compiled by the National Health Insurance Research Database of Taiwan to examine how the prescribing decisions made by psychiatrists' colleagues influence the likelihood of the psychiatrists' initial prescription. The results show that the adoption ratio of a physician's colleagues in a medical center is positively associated with the likelihood of a physician's adoption of the new drug. Specifically, colleague groups with similar and longer tenure as well as similar and older age have significantly positive effects. Colleague groups with the same and different gender also have positive effects. In summary, tenure and age, rather than gender, are vital sources of heterogeneous colleague interactions.


Molecular characterization and antimicrobial resistance of nasal Staphylococcus aureus in the community of Kabul.
This study aimed to investigate the prevalence and molecular characteristics of community methicillin-resistant Staphylococcus aureus (MRSA) nasal carriage among students at Kabul University. Nasal swabs were collected from anterior nares of 150 healthy non-medical students at Kabul University. Antimicrobial susceptibility testing was performed on all S. aureus isolates, and all detected MRSA isolates were then confirmed by mecA/mecC polymerase chain reaction and characterized using DNA microarray. A total of 50 S. aureus strains were isolated from the anterior nares of the 150 participants. The prevalence of S. aureus and MRSA nasal carriage among Kabul students was 33.3% and 12.7%, respectively. Seven (36.8%) MRSA isolates and 8 (25.8%) methicillin-susceptible S. aureus (MSSA) isolates were multidrug-resistant (i.e. resistant to at least three different antimicrobials tested). All MRSA isolates (n = 19) were susceptible to linezolid, rifampicin, and fusidic acid. Seven MRSA clones, belonging to four clonal complexes (CCs), were identified. The most commonly identified clone was CC22-MRSA-IV TSST-1-positive, which accounted for 63.2% (12/19) of MRSA isolates. SCCmec typing showed that most MRSA strains harboured SCCmec type IV (94.7%). Thirteen (68.4%) MRSA isolates carried the TSST-1 and 5 (26.3%) PVL genes. Our findings revealed the relatively high prevalence of MRSA nasal carriers in the community in Kabul, with the predominance of the CC22-MRSA-IV TSST-1-positive clone and frequent multidrug resistance among these isolates.


Advantages of mesenchymal stem cell over the other stem cells.
A stem cell is a particular group of cells that has the extraordinary potential to convert within the body into particular cell types. They are used to regenerate tissues and cells in the body that have been damaged or destroyed by the disease. Stem cells come in three different varieties: adult stem cells, embryonic stem cells and induced pluripotent stem cells (iPSCs). Embryonic stem cells have a high chance of immune rejection and also have ethical dilemmas and iPSCs have genetic instability. Adult stem cells are difficult to analyze and extract for research since they are frequently insufficient in native tissues. However, mesenchymal stem cells (MSC) one of the categories of adult stem cells are stromal cells with a variety of potentials that can differentiate into a wide range of cell types. MSCs can be transplanted into a variety of people without worrying about rejection because they have demonstrated the ability to prevent an adverse reaction from the immune system. These transplants have powerful anti-inflammatory and immunosuppressive effects and greatly enhance the body's inherent healing capacity. While MSCs do not offer treatment for illnesses, the idea behind them is to enable the body to recover sufficiently for a protracted reduction in symptoms. In many cases, this is sufficient to significantly enhance the patient's well-being. Inspite of several advantages some potential long-term concerns connected to MSC therapy are maldifferentiation, immunosuppression and cancerous tumor growth. In this review, we will compare the mesenchymal stem cells with other stem cells with respect to the source of origin, their properties and therapeutic applications, and discuss the MSC's disadvantages.


Influence of polyfunctional interactions between organic zwitter-ion eremomycin and carboxylic cation exchangers on forming concentration front.
The nature of the polyfunctional interactions between the organic zwitter-ions of eremomycin and the carboxylic sorbents was studied. A cation exchange and hydrophobic mechanisms of interactions in the studied sorption system were determined as preponderant over other ones. The typical features of the eremomycin diffusion into the pores of the structurally segregated carboxylic sorbents were studied. The physical-chemical properties of the sorption system which influence the formation of the target product concentration zone with sharp boundary were investigated. The effect of column sizes on the eremomycin unified elution peak formation was shown. The height to diameter ratio leading to the eremomycin concentration front division into two zones was determined.


Localization and modulation of calcitonin gene-related peptide-receptor component protein-immunoreactive cells in the rat central and peripheral nervous systems.
Calcitonin gene-related peptide (CGRP) is widely distributed in the central and peripheral nervous system. Its highly diverse biological activities are mediated via the G protein-coupled receptor that uniquely requires two accessory proteins for optimal function. CGRP receptor component protein (RCP) is a coupling protein necessary for CGRP-receptor signaling. In this study, we established the anatomical distribution of RCP in the rat central and peripheral nervous system and its relationship to CGRP immunoreactivity. RCP-immunoreactive (IR) perikarya are widely and selectively distributed in the cerebral cortex, septal nuclei, hippocampus, various hypothalamic nuclei, amygdala, nucleus colliculus, periaqueductal gray, parabrachial nuclei, locus coeruleus, cochlear nuclei, dorsal raphe nuclei, the solitary tractus nucleus and gracile nucleus, cerebellar cortex, various brainstem motor nuclei, the spinal dorsal and ventral horns. A sub-population of neurons in the dorsal root ganglia (DRG) and trigeminal ganglia were strongly RCP-IR. Overall, the localization of RCP-IR closely matched with that of CGRP-IR. We also determined whether RCP in DRG and dorsal horn neurons can be modulated by CGRP receptor blockade and pain-related pathological stimuli. The intrathecal injection of the antagonist CGRP(8-37) markedly increased RCP expression in the lumbar DRG and spinal dorsal horn. Carrageenan-induced plantar inflammation produced a dramatic bilateral increase in RCP expression in the dorsal horn while a partial sciatic nerve ligation reduced RCP expression in the ipsilateral superficial dorsal horn. Our data suggest that the distribution of RCP immunoreactivity is closely matched with CGRP immunoreactivity in most of central and peripheral nervous systems. The co-localization of RCP and CGRP in motoneurons and primary sensory neurons suggests that CGRP has an autocrine or paracrine effect on these neurons. Moreover, our data also suggest that RCP expression in DRG and spinal cord can be modulated during CGRP receptor blockade, inflammation or neuropathic pain and this CGRP receptor-associated protein is dynamically regulated.


Influence of temperature on PCDD/PCDF desorption from waste incineration flyash under nitrogen.
A municipal solid waste incinerator flyash was heated to between 200 and 400 degrees C under nitrogen in a bench-scale, static bed reactor for 4 days soak time. The influence of temperature on the levels of PCDD and PCDF remaining in and desorbed from the ash were investigated using GC-MS/MS. PCDD and especially PCDF formation was seen on the flyash between 225 and 300 degrees C. Large increases in the I-TEQ of the treated ash relative to the increase in its overall PCDD/PCDF content indicated that the formation of 2378-substituted congeners was favoured over that of other substitution patterns. In the absence of a source of gaseous oxygen, formation was mainly attributed to de novo reactions involving solid phase oxygen. Dechlorination of the PCDD/PCDF in flyash became increasingly important above 275 degrees C. Maximum desorption was seen at 325 degrees C, with the equivalent of 35 wt% of the PCDD/F in the original flyash being recovered from the exhaust traps at this temperature. The desorbed species were mainly M(1)CDD/CDDF-T(3)CDD/CDDF resulting from dechlorination of higher chlorinated PCDD/PCDF, with consequently low I-TEQ values.


A rare and unexpected clinical progress and location on a primary extradural spinal hydatid cyst in a pediatric patient: a case report.
Involvement of spine in patients with hydatid disease (HD) is less than 1% and primary intra-spinal extradural HD is extremely rare. Although this disease is introduced as benign pathology according to its clinical presentation and biological behavior, intraoperative rupture of the cyst may aggravate the patients' outcome in the long-term especially in pediatric patient population. We report a 9-year-old girl who presented a progressive neurological deterioration due to an enlargement of a ventrally located extradural hydatid cyst within the thoracic spinal canal. Total removal of the cyst was achieved by preserving the capsule integrity for preventing potential seeding. Our preoperative initial diagnosis based on the radiological findings was confirmed as cyst hydatid histopathologically. Cyst hydatid should be considered in the differential diagnosis of the presence of homogenous cystic lesions with regular shape inside the spinal canal especially in patients from endemic region. To our knowledge, this pediatric patient is the first case of cyst hydatid located ventral side of the spinal cord extradurally located inside the spinal canal showing no extension.


Roles of telomerase reverse transcriptase N-terminal domain in assembly and activity of Tetrahymena telomerase holoenzyme.
Telomerase extends chromosome ends by the addition of single-stranded telomeric repeats. To support processive repeat synthesis, it has been proposed that coordination occurs between DNA interactions with the telomerase RNA template, the active site in the telomerase reverse transcriptase (TERT) core, a TERT N-terminal (TEN) domain, and additional subunits of the telomerase holoenzyme required for telomere elongation in vivo. The roles of TEN domain surface residues in primer binding and product elongation have been studied largely using assays of minimal recombinant telomerase enzymes, which lack holoenzyme subunits that properly fold and conformationally stabilize the ribonucleoprotein and/or control its association with telomere substrates in vivo. Here, we use Tetrahymena telomerase holoenzyme reconstitution in vitro to assess TEN domain sequence requirements in the physiological enzyme context. We find that TEN domain sequence substitutions in the Tetrahymena telomerase holoenzyme influence synthesis initiation and elongation rate but not processivity. Functional and direct physical interaction assays pinpoint a conserved TEN domain surface required for holoenzyme subunit association and for high repeat addition processivity. Our results add to the understanding of telomerase holoenzyme architecture and TERT domain functions with direct implications for the unique mechanism of single-stranded repeat synthesis.


Poly(2-hydroxyethyl methacrylate) sponges as implant materials: in vivo and in vitro evaluation of cellular invasion.
The pore size and the in vivo behaviour of four poly(2-hydroxyethyl methacrylate) sponges were investigated. The sponges were synthesized by polymerization of monomer in 70, 80 and 90 wt% water, respectively. In one of the formulations, a high amount of initiator was added. The average pore diameter was calculated with Ferry's equation and the results compared to those obtained by examination of samples using environmental scanning electron microscopy. The use of the equation greatly underestimated the size of pores. We also showed that the pores in polymers obtained in 70 wt% water were not interconnected, whilst the pores in polymers obtained in 80 and 90 wt% water, respectively, were larger and interconnected throughout the polymer. When implanted subcutaneously in rabbits, only the latter polymers allowed invasion and proliferation of cells. Penetration and proliferation of cells in these sponges were also assessed by an in vitro method using cultured human fibroblasts. The procedure included the overlaying of a glass plate covered by confluent cultured cells on to the surface of polymer impregnated with collagen. The depth of migration and number of sections needed to be cut to count a fixed number of invading cells were measured after incubation for 2 wk and used as indicators in comparing the ability of various sponges to allow cellular invasion. The assay showed that more cells invaded a hydrogel sponge produced in 80 wt% water than one produced in 90 wt% water. It also showed that the cut polymer surfaces allowed a greater cellular invasion than the moulded ones.


Deconstructing age estimates for angiosperms.
Estimates of the age of angiosperms from molecular phylogenies vary considerably. As in all estimates of evolutionary timescales from phylogenies, generating these estimates requires assumptions about the rate that molecular sequences are evolving (using clock models) and the time duration of the branches in a phylogeny (using fossil calibrations and branching processes). Often, it is difficult to demonstrate that these assumptions reflect current knowledge of molecular evolution or the fossil record. In this study we re-estimate the age of angiosperms using a minimal set of assumptions, therefore avoiding many of the assumptions inherent to other methods. The age estimates we generate are similar for each of the four datasets analysed, ranging from 130 to 400 Ma, but are far less precise than in previous studies. We demonstrate that this reduction in precision results from making less stringent assumptions about both rate and time, and that the analysed molecular dataset has very little effect on age estimates.


Broadband Dynamics of Ubiquitin by Anionic and Cationic Nanoparticle Assisted NMR Spin Relaxation.
The quantitative and comprehensive description of the internal dynamics of proteins is critical for understanding their function. Nanoparticle-assisted 15 N NMR spin relaxation spectroscopy is a new method for the observation of picosecond to microsecond dynamics of proteins when transiently interacting with the surface of the nanoparticles (NPs). The method is applied here to the protein ubiquitin in the presence of anionic and cationic silica NPs (SNPs) of different sizes. The backbone dynamics profiles are reproducible and strikingly similar to each other, indicating that specific protein-SNP interactions are unimportant. The dynamics profiles closely match the sub-nanosecond dynamics S2 values observed by model-free analysis of standard 15 N relaxation of ubiquitin in free solution, indicating that the bulk of the ubiquitin backbone dynamics in solution is confined to sub-nanosecond timescales and, hence, it is dynamically more restrained than previous NMR studies have suggested.


Lymphoplasmacytic sclerosing pancreatitis.
Lymphoplasmacytic sclerosing pancreatitis is a rare entity that has been described under many different names and constitutes a diagnostic challenge as it may simulate a neoplastic process. Herein, we report a case of a 61-year-old woman who presented to our institution complaining of left flank pain and was found to have normal levels of amylase and lipase. An abdominal magnetic resonance image showed thickening of the pancreatic tail and compression of the pancreatic duct. The radiographic differential included both chronic pancreatitis and a neoplastic process. She underwent an exploratory laparotomy, during which a pancreatectomy and splenectomy were performed. Grossly, the pancreas contained a yellowish white, firm homogeneous mass measuring 6.5 x 3.3 x 2.9 cm involving the entire pancreatic tail and hilum of the spleen. Histologically, pancreatic sections showed extensive fibrosis admixed with an inflammatory infiltrate. This infiltrate was composed mainly of lymphocytes with multiple germinal centers, as well as plasma cells and eosinophils that surrounded pancreatic ducts and extended into the peripancreatic adipose tissue. No malignancy was identified, and the process was diagnosed as lymphoplasmacytic sclerosing pancreatitis.


Assessing the readability and patient comprehension of rheumatology medicine information sheets: a cross-sectional Health Literacy Study.
Patients are often provided with medicine information sheets (MIS). However, up to 60% of patients have low health literacy. The recommended readability level for health-related information is ≤grade 8. We sought to assess the readability of MIS given to patients by rheumatologists in Australia, the UK and Canada and to examine Australian patient comprehension of these documents. Cross-sectional study. Community-based regional rheumatology practice. Random sample of patients attending the rheumatology practice. Readability of MIS was assessed using readability formulae (Flesch Reading Ease formula, Simple Measure of Gobbledygook scale, FORCAST (named after the authors FORd, CAylor, STicht) and the Gunning Fog scale). Literal comprehension was assessed by asking patients to read various Australian MIS and immediately answer five simple multiple choice questions about the MIS. The mean (±SD) grade level for the MIS from Australia, the UK and Canada was 11.6±0.1, 11.8±0.1 and 9.7±0.1 respectively. The Flesch Reading Ease score for the Australian (50.8±0.6) and UK (48.5±1.5) MIS classified the documents as 'fairly difficult' to 'difficult'. The Canadian MIS (66.1±1.0) were classified as 'standard'. The five questions assessing comprehension were correctly answered by 9/21 patients for the adalimumab MIS, 7/11 for the methotrexate MIS, 6/28 for the non-steroidal anti-inflammatory MIS, 10/11 for the prednisone MIS and 13/24 for the abatacept MIS. The readability of MIS used by rheumatologists in Australia, the UK and Canada exceeds grade 8 level. This may explain why patient literal comprehension of these documents may be poor. Simpler, shorter MIS with pictures and infographics may improve patient comprehension. This may lead to improved medication adherence and better health outcomes.


Under construction: The dynamic assembly, maintenance, and degradation of the cardiac sarcomere.
The sarcomere is the basic contractile unit of striated muscle and is a highly ordered protein complex with the actin and myosin filaments at its core. Assembling the sarcomere constituents into this organized structure in development, and with muscle growth as new sarcomeres are built, is a complex process coordinated by numerous factors. Once assembled, the sarcomere requires constant maintenance as its continuous contraction is accompanied by elevated mechanical, thermal, and oxidative stress, which predispose proteins to misfolding and toxic aggregation. To prevent protein misfolding and maintain sarcomere integrity, the sarcomere is monitored by an assortment of protein quality control (PQC) mechanisms. The need for effective PQC is heightened in cardiomyocytes which are terminally differentiated and must survive for many years while preserving optimal mechanical output. To prevent toxic protein aggregation, molecular chaperones stabilize denatured sarcomere proteins and promote their refolding. However, when old and misfolded proteins cannot be salvaged by chaperones, they must be recycled via degradation pathways: the calpain and ubiquitin-proteasome systems, which operate under basal conditions, and the stress-responsive autophagy-lysosome pathway. Mutations to and deficiency of the molecular chaperones and associated factors charged with sarcomere maintenance commonly lead to sarcomere structural disarray and the progression of heart disease, highlighting the necessity of effective sarcomere PQC for maintaining cardiac function. This review focuses on the dynamic regulation of assembly and turnover at the sarcomere with an emphasis on the chaperones involved in these processes and describes the alterations to chaperones - through mutations and deficient expression - implicated in disease progression to heart failure.


The KRAS StripAssay for detection of KRAS mutation in Egyptian patients with colorectal cancer (CRC): a pilot study.
Epidermal growth factor receptor (EGFR) and its downstream factors KRAS and BRAF are mutated in several types of cancer, affecting the clinical response to EGFR inhibitors. Mutations in the EGFR kinase domain predict sensitivity to the tyrosine kinase inhibitors gefitinib and erlotinib in lung adenocarcinoma, while activating point mutations in KRAS and BRAF confer resistance to the anti-EGFR monoclonal antibody cetuximab in colorectal cancer. The development of new generation methods for systematic mutation screening of these genes will allow more appropriate therapeutic choices. Detection of KRAS mutation in Egyptian colorectal cancer (CRC) patients by the KRAS StripAssay. Examination of 20 colorectal cancer (CRC) patients is done to detect KRAS mutations by KRAS StripAssay. For the StripAssay, a mutant-enriched PCR was followed by hybridization to KRAS-specific probes bound to a nitrocellulose strip. Among 20 patients, KRAS mutations were identified in 80% of patients by the KRAS StripAssay. Our preliminary results suggest that KRAS StripAssay is an alternative to protocols currently in use for KRAS mutation detection.


Evaluation of the biocompatibility of a Ni-Cr-Mo dental alloy with human gingival explant culture in vitro: morphological study, immunodetection of fibronectin, and collagen production.
This study was undertaken to evaluate the biocompatibility of a Ni-Cr-Mo dental casting alloy by an in vitro explant culture method. Through ultrastructural features, the immunolabelling of fibronectin, and the immunodetection of type I and III collagen production, we investigated the behaviour of gingival cells (both fibroblasts and epithelial cells) in contact with the alloy in comparison with control cultures. Our results indicate that cultured gingival cells present a well preserved ultrastructure and synthesized fibronectin (the main glycoprotein involved in adhesion to substrates). The alteration of collagen production concerned only type III collagen which decreased significantly in the cultures on the dental alloy.


Anti-nucleosome autoantibodies as markers for autoimmune hepatitis and their correlation with disease activity.
To assess the prevalence of autoantibodies against nucleosomes (anti-nucleosome Ab) in patients with autoimmune hepatitis (AIH), examine the correlation between anti-nucleosome Ab and disease activity, and evaluate the effectiveness of anti-nucleosome Ab in predicting relapse. We analyzed serum anti-nucleosome Ab levels in 38 patients with AIH by enzyme-linked immunosorbent assay, and assessed their correlation with clinical characteristics. Anti-nucleosome Ab levels were significantly higher in AIH, but not in patients with chronic hepatitis B (n = 20) or chronic hepatitis C (n = 20), compared to healthy controls (n = 15). The positive prevalence of anti-nucleosome Ab was 71.1% in AIH. Anti-nucleosome Ab levels were significantly lower during remission compared to that during flares within the same patients with AIH. Total bilirubin levels were significantly higher in patients with anti-nucleosome Ab levels of 53.7 U/mL or more compared to those with less than 53.7 U/mL at disease onset. Analysis of the reduction in anti-nucleosome Ab by immunosuppressive therapy in 16 AIH patients revealed that age at disease onset was significantly lower and IgG levels and relapse rates were significantly higher in patients with a reduction rate of less than 35% compared to those with a reduction rate 35% or more. The International Autoimmune Hepatitis Group score and γ-globulin levels were also higher in patients with reduction rates of less than 35% (borderline significance). Anti-nucleosome Ab in AIH patients may be useful markers not only for disease diagnosis, but also for activity assessment and relapse prediction.


Intrathecal substance P depresses spinal motor and sensory responses to stimulation of nociceptive afferents--antagonism by naloxone.
The effect of an injection of substance P into the subarachnoid space was studied on a motor and a sensory response elicited by supramaximal stimulation of the sural nerve in spinal rats. Substance P 10 micrograms depressed the reflex activation in the electromyogram recorded from the ipsilateral tibialis anterior muscle; the depression was significant 5 and 10 min after the injection. Substance P 10 micrograms reduced the activity in ascending axons of the spinal cord evoked by stimulation of afferent C fibres; the effect developed slowly, lasted longer than 60 min and was abolished by an i.v. injection of nalaoxone 0.2 mg/kg. Only half the number of ascending axons tested showed a depression by substance P, and the administration of a higher dose (50 micrograms) did not produce an effect in a greater number of axons. Substance P did not influence the activity evoked in ascending axons by stimulation of afferent A beta and A delta fibres. The depression by substance P of ascending nocieceptive activity was antagonized by an i.v. injection of naloxone 0.2 mg/kg. When naloxone 0.2 mg/ng i.v. was administered alone, it increased the activity in ascending axons activated by afferent C fibre stimulation. It is concluded that (i) substance P depresses spinal nociceptive activity without the intermediation of endorphinergic neurons, and (ii) naloxone antagonizes tonic inhibition of the spinal nociceptive system mediated by endogenous opioid peptides and, by facilitating excitatory transmission through disinhibition, neutralizes the depression produced by substance P.


Screening for tuberculosis among homeless shelter staff.
The prevalence of tuberculosis (TB) among homeless shelter staff was assessed using the tuberculin skin test (TST) and the Quantiferon TB-Gold in tube interferon-γ release assay (QFT-TB). Investigation of 51 participants for whom both QFT-TB and TST results were available showed 47.1% and 43.1% positivity, respectively, with excellent (92%) concordance between the 2 tests. The high risk for acquiring occupational TB necessitates the development of TB surveillance protocols for homeless shelter staff in Italy.


Vitamin D arrests thyroid carcinoma cell growth and induces p27 dephosphorylation and accumulation through PTEN/akt-dependent and -independent pathways.
We investigated the effects of 1,25-dihydroxycholecalciferol vitamin D(3) (VD) and its noncalciomimetic analog EB1089 on thyroid carcinoma cell growth. VD and EB1089 exhibited anti-proliferative effects in a dose-dependent manner as determined by [(3)H]thymidine incorporation and MIB-1 immunolabeling. VD or EB1089 resulted in similar G(1)-phase arrest. Neither apoptosis nor differentiation was affected. VD and EB1089 induced increased nuclear protein expression of the cyclin-dependent kinase inhibitor, p27(kip1) (p27). VD/EB1089 effects paralleled but were not additive to those of the proteasome inhibitor LLnL, consistent with reduced p27 degradation. As p27 phosphorylation and association with Skp2 is a key step in its degradation, we examined the effects of VD/EB1089 on this reaction. Despite increased total p27, the pThr content of p27 remained unaffected, an effect confirmed by diminished association with Skp2 as well as in situ phosphorylation. Moreover, phosphatase inhibition abrogated the effect of VD/EB1089 on p27 accumulation consistent with a role for phosphatase action in mediating this VD effect. Although VD/EB1089 resulted in comparable increases in p27 in WRO and NPA cells, only WRO but not NPA cells demonstrated a change in the phosphatase PTEN and its downstream target pAkt/PKB in response to VD/EB1089. Transfection of PTEN resulted in p27 accumulation and was partially additive to the effect of VD/EB1089. Moreover, treatment with PI-3 kinase inhibitors decreased pAkt/PKB and increased p27 in both WRO and NPA cells highlighting the potential role of this downstream pathway in regulating p27 in the thyroid. These findings point to a novel mechanism of action for VD/EB1089 inhibition of thyroid carcinoma cell growth by p27 hypophosphorylation, diminished association with Skp2, and consequent accumulation. This effect can be mediated but is not essentially dependent on the phosphatase PTEN/Akt/PKB pathway. These properties support the potential utility of VD analogs in the treatment of thyroid carcinomas irrespective of their PTEN/pAkt status.


Neurosurgical Site Infection Prevention: Single Institute Experience.
To estimate the effect of a multimodal prevention program on controlling surgical site infection (SSI) risk among neurosurgical patients. This prospective study was conducted among adult patients who have undergone neurosurgical procedures in a tertiary-care university-affiliated hospital during January 2008 to December 2013 since the implementation of an infection control program. SSI cases among inpatients were identified by daily active searches, whereas post-discharge surveillance was performed for outpatients through telephone contact 30-35 days after surgery, according to the definition proposed by the Center for Disease Control. The variation of SSI rate during the study period was analyzed by Cochran-Armitage trend test. Overall, a total of 3042 patients were enrolled and 112 SSI cases were identified during the studied period. SSI more likely occurred in patients with older age (t=5.16, p < 0.01), undergoing emergency operations (x2=50.5, p < 0.01), having higher American Society of Anesthesiologists (ASA) scores (x2=7.2, p=0.01) and clean contaminated wound or above (x2=53.8, p < 0.01). The annual incidence rate of SSI was 6.21%, 5.01%, 3.89%, 3.06%, 2.38% and 2.28%, respectively, showing a significant decreasing trend (z=3.96, p < 0.01). The results provide evidence of a significant decreasing trend in the SSI rate following the infection prevention program, demonstrating the role of multimodal approach in controlling SSI.


Evaluation of the role of NMDA receptor function in antidepressant-like activity. A new study with citalopram and fluoxetine in the forced swim test in mice.
The NMDA/glutamate receptors are involved in the mechanism of antidepressant activity. The present study was designed to investigate the effect of NMDA receptor ligands (agonists and antagonists of glutamate sites) on the antidepressant-like activity of selective serotonin reuptake inhibitors (SSRIs), citalopram and fluoxetine, in the forced swim test in mice. The antidepressant activity (reduction in immobility time) of citalopram but not of fluoxetine was antagonized by N-methyl-D-aspartate acid and enhanced by CGP37849 (antagonist of the NMDA receptor). The present literature data indicate that the antidepressant-like activity of conventional antidepressants is generally affected by the NMDA receptor, although by modulation from different sites of the complex. Thus, it supports the issue of the ability of NMDA receptor antagonists to enhance the antidepressant action in human depression.


Analysis of Y chromosome haplogroups in Parkinson's disease.
Parkinson's disease is a complex neurodegenerative disorder that is about 1.5 times more prevalent in males than females. Extensive work has been done to identify the genetic risk factors behind Parkinson's disease on autosomes and more recently on Chromosome X, but work remains to be done on the male-specific Y chromosome. In an effort to explore the role of the Y chromosome in Parkinson's disease, we analysed whole-genome sequencing data from the Accelerating Medicines Partnership-Parkinson's disease initiative (1466 cases and 1664 controls), genotype data from NeuroX (3491 cases and 3232 controls) and genotype data from UKBiobank (182 517 controls, 1892 cases and 3783 proxy cases), all consisting of male European ancestry samples. We classified sample Y chromosomes by haplogroup using three different tools for comparison (Snappy, Yhaplo and Y-LineageTracker) and meta-analysed this data to identify haplogroups associated with Parkinson's disease. This was followed up with a Y-chromosome association study to identify specific variants associated with disease. We also analysed blood-based RNASeq data obtained from the Accelerating Medicines Partnership-Parkinson's disease initiative (1020 samples) and RNASeq data obtained from the North American Brain Expression Consortium (171 samples) to identify Y-chromosome genes differentially expressed in cases, controls, specific haplogroups and specific tissues. RNASeq analyses suggest Y-chromosome gene expression differs between brain and blood tissues but does not differ significantly in cases, controls or specific haplogroups. Overall, we did not find any strong associations between Y-chromosome genetics and Parkinson's disease, suggesting the explanation for the increased prevalence in males may lie elsewhere.