Elevated decision uncertainty and reduced avoidance drives in depression, anxiety and substance use disorders during approach-avoidance conflict: a replication study.
Decision-making under approach-avoidance conflict (AAC; e.g., sacrificing quality of life to avoid feared outcomes) may be affected in multiple psychiatric disorders. Recently, we used a computational (active inference) model to characterize information processing differences during AAC in individuals with depression, anxiety and/or substance use disorders. Individuals with psychiatric disorders exhibited increased decision uncertainty (DU) and reduced sensitivity to unpleasant stimuli. This preregistered study aimed to determine the replicability of this processing dysfunction. A new sample of participants completed the AAC task. Individual-level computational parameter estimates, reflecting decision uncertainty and sensitivity to unpleasant stimuli ("emotion conflict"; EC), were obtained and compared between groups. Subsequent analyses combining the prior and current samples allowed assessment of narrower disorder categories. The sample in the present study included 480 participants: 97 healthy controls, 175 individuals with substance use disorders and 208 individuals with depression and/or anxiety disorders. Individuals with substance use disorders showed higher DU and lower EC values than healthy controls. The EC values were lower in females, but not males, with depression and/or anxiety disorders than in healthy controls. However, the previously observed difference in DU between participants with depression and/or anxiety disorders and healthy controls did not replicate. Analyses of specific disorders in the combined samples indicated that effects were common across different substance use disorders and affective disorders. There were differences, although with small effect size, in age and baseline intellectual functioning between the previous and current sample, which may have affected replication of DU differences in participants with depression and/or anxiety disorders. The now robust evidence base for these clinical group differences motivates specific questions that should be addressed in future research: can DU and EC become behavioural treatment targets, and can we identify neural substrates of DU and EC that could be used to measure severity of dysfunction or as neuromodulatory treatment targets?


Genetic amniocentesis in twin pregnancy.
Among 1041 pregnancies 13 twin gestations were detected by routine ultrasonography prior to genetic amniocentesis at the Department of Prenatal Physiopathology of the University of Bologna. Clear amniotic fluid from both sacs was obtained in 12 of 13 sets of twins. All 12 sets were cytogenetically normal with normal levels of alpha-fetoprotein. Only one patient spontaneously aborted liveborn immature twins 30 days after the procedure. The technique used to obtain samples of fluid is described in detail and the need for additional counselling prior to amniocentesis in twins is stressed.


Hydroxychloroquine and COVID-19 story: is the low-dose treatment the missing link? A comprehensive review and meta-analysis.
Hydroxychloroquine (HCQ) has been repurposed and used for the treatment of COVID-19 patients; however, its efficacy remains controversial, maybe partly due to the dosage, ranging from 200 to 800 mg/day, reported in different studies. Indeed, HCQ low dose (≤ 2.4 g/5 days) showed a lower risk of side effects compared to high doses. In this study, we performed a systematic review and meta-analysis to investigate the effect of low-dose HCQ used alone on three outcomes including in-hospital mortality, the need for mechanical ventilation, and ICU admission in COVID-19 patients. A systematic review of English literature was conducted from January 2020 to April 2022, in PubMed, Cochrane Library, and Google Scholar. Studies reporting a dosage of 400 mg twice the first day, followed by 200 mg twice for four days were included. Pooled odds ratios and 95% confidence intervals were calculated using random-effects models. Eleven studies (12,503 patients) were retained in the quantitative analysis, four observational cohort studies, and seven RCTs. When pooling both observational and RCTs, low-dose HCQ was associated with decreased mortality (OR = 0.73, 95% CI: [0.55-0.97], I2 = 58%), but not with mechanical ventilation need (OR = 1.03, 95% CI: [0.56-1.89], I2 = 67%) and ICU admission rate (OR = 0.70, 95% CI: [0.42-1.17], I2 = 47%). However, no effect was observed when pooling only RCTs. Despite RCTs limitations, treatment with low-dose HCQ was not associated with improvement in mortality, mechanical ventilation need and ICU admission rate in COVID-19 patients.


In vitro antifungal activity of fatty acid methyl esters of the seeds of Annona cornifolia A.St.-Hil. (Annonaceae) against pathogenic fungus Paracoccidioides brasiliensis.
Fatty acids are abundant in vegetable oils. They are known to have antibacterial and antifungal properties. Antifungal susceptibility was evaluated by broth microdilution assay following CLSI (formerly the NCCLS) guidelines against 16 fungal strains of clinical interest. In this work, fatty acid methyl esters (FAME) was able to inhibit 12 clinical strains of the pathogenic fungus Paracoccidioides brasiliensis and were also active in the bioautographic assay against Cladosporium sphaerospermum. FAME was a more potent antifungal than trimethoprim-sulfamethoxazole against P. brasiliensis under the experimental conditions tested.


Isoniazid resistance-conferring mutations are associated with highly variable phenotypic resistance.
High-dose isoniazid is recommended in the 9-12 months short-course regimen for multidrug-resistant tuberculosis with inhA mutation. However, there is insufficient evidence to support the assumption of genotypic-phenotypic concordance. This study aimed to identify the genetic mutations associated with high-level phenotypic isoniazid resistance. Clinical isolates from patients with drug-resistant tuberculosis were profiled by whole-genome sequencing and subjected to minimum inhibitory concentration (MIC) testing using MGIT based-method. MICs were performed in concentration ranges based on the mutation present: isolates with no isoniazid resistance-conferring mutations and H37Rv, 0.016-0.256 µg/ml; inhA, 0.256-4.0 µg/ml, katG 1.0-16.0 µg/ml; and inhA + katG, 4.0-64.0 µg/ml. Isolates demonstrating resistance at the upper limit of the concentration range were tested up to the maximum of 64.0 µg/ml. Bootstrap of the mean MICs was performed to increase the robustness of the estimates and an overlap index was used to compare the distributions of the MICs for each mutation profile. A total of 52 clinical isolates were included in this analysis. Bootstrap MIC means for inhA, katG and inhA + katG were 33.64 (95% CI, 9.47, 56.90), 6.79 (4.45, 9.70) and 52.34 (42.750, 61.66) µg/ml, respectively. There was high overlap between inhA and inhA + katG mutations (eta = 0.45) but not with inhA and katG (eta = 0.19). Furthermore, katG showed poor overlap with inhA + katG mutations (eta = 0.09). Unexpectedly, 4/8 (50.0%) of all InhA mutants demonstrated high-level resistance, while 20/24 (83.3%) of katG mutants demonstrated moderate-level resistance. InhA mutations demonstrated unexpectedly high MICs and showed high overlap with inhA + katG. Contrary to the common belief that katG mutants are associated with high-level resistance, this mutation primarily showed moderate-level resistance.


Comparative analysis of the mitochondrial genomes of the family Mactridae (Mollusca: Venerida) and their phylogenetic implications.
Taxonomy and phylogenetic relationships within the family Mactridae have remained debatable because of the plasticity of morphological characteristics and the lack of accurate molecular data, thereby resulting in abundant synonyms and taxa rearrangements. Mitochondrial genomes (mitogenomes) have been widely used as powerful tools to reconstruct phylogenies of various groups of mollusks; however, they have not been used for studying the phylogeny of mactrids specifically. In the present study, mitogenomes of seven Mactridae species, namely Mactra chinensis, Mactra cygnus, Mactra quadrangularis, Mactra cumingii, Mactrinula dolabrata, Raeta pulchella, and Raeta sp., were sequenced by Illumina high-throughput sequencing, and a comparative mitochondrial genomic analysis was conducted. The newly sequenced mitogenomes were double-stranded circular molecules, with all functional genes encoded on the heavy strand. All the new mactrid mitogenomes had two rRNA genes (12S and 16S), 13 protein-coding genes (PCGs) (atp6, cox1, cox2, cox3, cytb, nad1, nad2, nad3, nad4, nad4l, nad5, nad6, and atp8), and 22 tRNAs. The mitogenomes showed considerable variation in AT content, GC skew, and AT skew. The results of the phylogenetic analysis confirmed monophyly of the family Mactridae and suggested that genera Mactrinula, Spisula, Rangia, and Mulinia should not be placed under subfamily Mactrinae. Our results supported that potential cryptic species existed in Mactra antiquata. We also proposed subfamily Kymatoxinae should belong to the family Mactridae rather than Anatinellidae and Mactra alta in China should be Mactra cygnus. Additionally, conservation in functional gene arrangement was found in genera Mactra, Raeta, and Lutraria. But gene orders in S. sachalinensis and S. solida were quite different, questioning their congeneric relationship. Our results further suggested that the taxonomy within the family Mactridae requires an integrative revision.


Induction of apoptosis in Vero cells by Newcastle disease virus requires viral replication, de-novo protein synthesis and caspase activation.
Newcastle disease virus causes (NDV) apoptotic death of infected cells. In the present study, the stimulus that provoked the induction of apoptosis in infected cells was examined. Vero cells infected with NDV developed apoptosis as characterized by DNA fragmentation and decreased DNA content. In presence of ammonium chloride, infected cells did not show reduced DNA content indicating the requirement of virus entry for the induction of apoptosis. UV-inactivated NDV did not induce apoptosis in cells suggesting the need of virus replication. Although cycloheximide blocked NDV-induced apoptosis, actinomycin-D did not, suggesting that de-novo viral protein synthesis was critical for the induction of apoptosis. In addition, activation of caspases was also detected by flowcytometry, indirect fluorescent and colorimetric assays. Based on the results, it was concluded that NDV-induced apoptosis in Vero cells required virus replication, de-novo protein synthesis and caspase activation.


Comparison of Coronary Artery Involvement and Mortality in STEMI Patients With and Without SARS-CoV-2 During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis.
Cardiovascular injury with SARS-CoV-2 infection is well known. Several studies have outlined baseline characteristics in patients presenting with STEMI and SARS-CoV-2. Paucity in data exists in selective coronary involvement in patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic. A systematic search and meta-analysis of studies meeting the inclusion and exclusion criteria obtained from MEDLINE, Scopus, and Cochrane databases was performed utilizing PRISMA criteria. The main outcome was likelihood of coronary artery involvement among patients with STEMI and SARS-CoV-2 versus without SARS-CoV-2. The primary adverse outcome measured was in-hospital mortality. The final analysis included 5 observational studies with a total of 2,266 patients. There was no statistical significance in LM (OR 1.40; 95% CI: 0.68, 2.90), LAD (OR 1.09; 95% CI 0.83, 1.43), LCX (OR 1.17; 95% CI: 0.75, 1.85), or RCA (OR 0.59; 95% CI: 0.30, 1.17) disease among the 2 groups. LAD disease was the most prevalent coronary involvement among patients with STEMI and SARS-CoV-2 (49.6%). Higher in-hospital mortality was observed in the STEMI and SARS-CoV-2 group (OR 5.24; 95% CI: 3.63, 7.56). Our analysis demonstrated no statistical significance in selective coronary involvement in patients with STEMI and SARS-CoV-2 during the COVID-19 pandemic. The higher mortality among patients with SARS-CoV-2 and STEMI has been noted in prior studies with concerns being late presentation due to fear of infection, delayed care time, and poor resource allocation. Focus should be placed on identifying and managing comorbidities to reduce mortality.


Compliance with follow-up in patients with diabetic macular edema: Eye care center vs. diabetes care center.
The study was conducted to compare the compliance to intravitreal injection treatment and follow-up in patients with center-involving diabetic macular edema (CI-DME) and treatment outcomes between a tertiary eye care facility and a tertiary diabetes care center. A retrospective review was conducted on treatment naïve DME patients who had received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in 2019. Participants were people with type 2 diabetes who were under regular care at the eye care center or the diabetes care center in Chennai. The outcome measures were noted at months 1, 2, 3, 6, and 12. A review of 136 patients treated for CI-DME (72 from the eye care center and 64 from a diabetes care center) was carried out. The severity of diabetic retinopathy (DR) was similar in both centers. There was no statistically significant (P > 0.05) difference in the choice of initial intravitreal drug in the two centers. At 12-month follow-up, only 29.16% came for a follow-up in the eye center vs. 76.56% in a diabetes care center (P = 0.000). The multivariate logistic regression showed increasing age was associated with non-compliance in both the groups (eye care center: odds ratio [OR] 0.91; 95% confidence interval [CI] 0.82-1.21; P = 0.044) and diabetes care center (OR 1.15; 95% CI 1.02-1.29; P = 0.020). The follow-up rate between eye care and diabetic care center with DME showed a significant disparity. By providing comprehensive diabetes care for all complications under one roof, compliance with follow-up can be improved in people with DME.


Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder.
Inflammatory processes are implicated in the aetiology of Major Depressive Disorder (MDD); however, the relationship between peripheral inflammation, brain structure and depression remains unclear, partly due to complexities around the use of acute/phasic inflammatory biomarkers. Here, we report the first large-scale study of both serological and methylomic signatures of CRP (considered to represent acute and chronic measures of inflammation respectively) and their associations with depression status/symptoms, and structural neuroimaging phenotypes (T1 and diffusion MRI) in a large community-based sample (Generation Scotland; NMDD cases = 271, Ncontrols = 609). Serum CRP was associated with overall MDD severity, and specifically with current somatic symptoms- general interest (β = 0.145, PFDR = 6 × 10-4) and energy levels (β = 0.101, PFDR = 0.027), along with reduced entorhinal cortex thickness (β = -0.095, PFDR = 0.037). DNAm CRP was significantly associated with reduced global grey matter/cortical volume and widespread reductions in integrity of 16/24 white matter tracts (with greatest regional effects in the external and internal capsules, βFA= -0.12 to -0.14). In general, the methylation-based measures showed stronger associations with imaging metrics than serum-based CRP measures (βaverage = -0.15 versus βaverage = 0.01 respectively). These findings provide evidence for central effects of peripheral inflammation from both serological and epigenetic markers of inflammation, including in brain regions previously implicated in depression. This suggests that these imaging measures may be involved in the relationship between peripheral inflammation and somatic/depressive symptoms. Notably, greater effects on brain morphology were seen for methylation-based rather than serum-based measures of inflammation, indicating the importance of such measures for future studies.


Isolation and characterization of a Bacillus subtilis strain that degrades endosulfan and endosulfan sulfate.
Endosulfan has emerged as a major environmental menace worldwide due to extensive usage and environmental persistence, seeking its remedial by a cheaper and efficient means. Therefore, natural resource (soil) was explored to search a potential candidate for biodegradation of endosulfan. A soil bacterium was enriched and isolated by applying a strong nutritional selection pressure, using a non-sulfur medium supplemented with endosulfan as sole source sulfur. The microbial strain was found to degrade endosulfan as well as its equally toxic metabolite endosulfan sulfate to non-toxic metabolites (endodiol and endosulfan lactone) very efficiently (up to 94.2 %) within 7 days, estimated qualitatively by thin layer chromatography and quantitatively by gas chromatography-electron capture detection methods. The isolate was characterized for its morphological, physiological, biochemical and 16S rRNA sequencing and identified as a new strain of Bacillus subtilis with strain designation AKPJ04, which was deposited with accession number Microbial Type Culture Collection and Gene Bank (MTCC) 8561, at MTCC, Institute of Microbial Technology, Chandigarh, India. The partial 16S rRNA sequence was submitted to Genbank, Maryland, USA, with the accession number EU 258611. The primary investigation for endosulfan degrading gene(s) localization suggested its location on chromosomal DNA.


A note on the characteristics of alcohol abusers with controlled drinking aspirations.
In an outpatient treatment sample, alcohol abusers who chose controlled drinking as a goal had characteristics in common with those who succeed in controlled drinking programs. There was no evidence that denial or other aspects of psychopathology were associated with the selection of controlled drinking as a goal.


Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor.
Although histaminergic neurones have not yet been histochemically visualized, there is little doubt that histamine (HA) has a neurotransmitter role in the invertebrate and mammalian central nervous system. For example, a combination of biochemical, electrophysiological and lesion studies in rats have shown that histamine is synthesized in and released from a discrete set of neurones ascending through the lateral hypothalamic area and widely projecting in the telencephalon. Histamine acts on target cells in mammalian brain via stimulation of two classes of receptor (H1 and H2) previously characterized in peripheral organs and probably uses Ca2+ and cyclic AMP, respectively, as second messengers. It is well established that several neurotransmitters affect neuronal activity in the central nervous system through stimulation not only of postsynaptic receptors, but also of receptors located presynaptically which often display distinct pharmacological specificity and by which they may control their own release. Such 'autoreceptors' have been demonstrated (or postulated) in the case of noradrenaline, dopamine, serotonin, acetylcholine and gamma-aminobutyric acid (GABA) neurones but have never been demonstrated for histamine. We show here that histamine inhibits its own release from depolarized slices of rat cerebral cortex, an action apparently mediated by a class of receptor (H3) pharmacologically distinct from those previously characterized, that is, the H1 and H2 receptors.


Postpartum tubal ligation: A retrospective review of anesthetic management at a single institution and a practice survey of academic institutions.
The primary aim was to evaluate institutional anesthetic techniques utilized for postpartum tubal ligation (PPTL). Secondarily, academic institutions were surveyed on their clinical practice for PPTL. An institutional-specific retrospective review of patients with ICD-9 procedure codes for PPTL over a 2-year period was conducted. Obstetric anesthesia fellowship directors were surveyed on anesthetic management of PPTL. Labor and delivery unit. Internet survey. 202 PPTL procedures were reviewed. 47 institutions were surveyed; 26 responses were received. Timing of PPTL, anesthetic management, postoperative pain and length of stay. There was an epidural catheter reactivation failure rate of 26% (18/69 epidural catheter reactivation attempts). Time from epidural catheter insertion to PPTL was a significant factor associated with failure: median [IQR; range] time for successful versus failed epidural catheter reactivation was 17h [10-25; 3-55] and 28h [14-33; 5-42], respectively (P=0.028). Epidural catheter reactivation failure led to significantly longer times to provide surgical anesthesia than successful epidural catheter reactivation or primary spinal technique: median [IQR] 41min [33-54] versus 15min [12-21] and 19min [15-24], respectively (P<0.0001). Fifty-eight percent (15/26) of respondents routinely leave the labor epidural catheter in-situ if PPTL is planned. Sixty-five percent (17/26) and 7% (2/26) would not attempt to reactivate the epidural catheter for PPTL if >8h and >24h post-delivery, respectively. Epidural catheter reactivation failure increases with longer intervals between catheter placement and PPTL. Failed epidural catheter reactivation increases anesthetic and operating room times. Our results and the significant variability in practice from our survey suggest recommendations on the timing and anesthetic management are needed to reduce unfulfilled PPTL procedures.


Multidetector computed tomography arthrography of the knee: diagnostic accuracy and indications.
To evaluate the diagnostic accuracy and indications of arthrography with multidetector computed tomography (arthro-MDCT) of the knee, in patients with absolute or relative contraindications to MRI and in patients with periarticular metal implants using diagnostic arthroscopy as the gold standard. After intra-articular injection of iodixanol and volumetric acquisition, 68 knees in patients of both sexes (30 females, 38 males, age range 32-60 years) were examined with a 16-detector-row CT scanner. The patients had arthralgia but no radiologically detected fractures. They could not be studied by MRI either because of absolute contraindications (subcutaneous electronic implants), surgical metal implants or claustrophobia. In 37 of 68 patients who had had previous knee surgery, the arthro-CT examination was preceded by an MRI on the same day. All examinations were interpreted by two experienced musculoskeletal radiologists. The findings were compared with arthroscopic findings carried out within 28 days of the CT study. In non-operated patients the comparison between arthro-MDCT and arthroscopy showed sensitivity and specificity ranging between 86% and 100%. In the 37 operated knees, arthro-MDCT had an accuracy of 95% compared with 53% of the MRI. Inter-observer agreement was almost perfect (K=0.97) in the evaluation of all types lesions, both on MDCT and MRI. When arthro-MDCT was compared with MRI in post-operative patients by a McNemar test, a significant difference (p<0.05) was found between these two techniques. Arthro-MDCT of the knee is a safe technique that provides accurate diagnosis in identifying chondral, fibrocartilaginous and intra-articular ligamentous lesions, in patients that cannot be evaluated by MRI, and in patients after surgical.


Complete Spinal Accessory Nerve Palsy From Carrying Climbing Gear.
We report an unusual case of spinal accessory nerve palsy sustained while transporting climbing gear. Spinal accessory nerve injury is commonly a result of iatrogenic surgical trauma during lymph node excision. This particular nerve is less frequently injured by blunt trauma. The case reported here results from compression of the spinal accessory nerve for a sustained period-that is, carrying a load over the shoulder using a single nylon rope for 2.5 hours. This highlights the importance of using proper load-carrying equipment to distribute weight over a greater surface area to avoid nerve compression in the posterior triangle of the neck. The signs and symptoms of spinal accessory nerve palsy and its etiology are discussed. This report is particularly relevant to individuals involved in mountaineering and rock climbing but can be extended to anyone carrying a load with a strap over one shoulder and across the body.


Unidirectional motility occurring in association with the axopodial membrane of Echinosphaerium nucleofilum.
A system of rapid, unidirectional motility associated with surface of Echinosphaerium axopodia is demonstrated using polystyrene micropheres as exogenous markers.


Pilot-scale fermentation, purification, and characterization of recombinant human Oncostatin M in Pichia pastoris.
Oncostatin M (OSM) is a multifunctional cellular regulator that belongs to the IL-6 subfamily and can act on a wide variety of cells, which has potential roles in the regulation of gene activation, cell survival, proliferation and differentiation. In order to achieve the higher level yield of recombinant human Oncostatin M (rhOSM), we determined the optimal pH condition of rhOSM expressed in the methylotrophic yeast Pichia pastoris X-33 and carried out the fermentation culture of rhOSM in 80 L fermentor in a fed-batch mode. SDS-PAGE and Western blotting assays demonstrated that rhOSM was successfully expressed and secreted into the culture medium with an apparent molecular weight of 28 kDa. N-terminals were correctly processed through amino-terminal sequencing. The maximum yield of rhOSM was 280 mg/L. rhOSM was purified by phenyl Sepharose hydrophobic interaction chromatography and SP Sepharose Fast Flow cation exchange chromatography, which resulted in a final yield of purified rhOSM of 6.94 g with a recovery of 62% and a purity of 95%. The purified rhOSM had a specific growth inhibition activity of 6.26 x 10(4)RU/microg, which was commensurate with typical values (6.2 x 10(4)RU/microg) obtained with standard hOSM.


The influence of immigrant background and parental education on overweight and obesity in 8-year-old children in Norway.
Little is known about the prevalence of overweight/obesity and socio-economic position (SEP) in children with immigrant background in Scandinavia. The purpose of this study is to examine the prevalence of overweight/obesity by immigrant background among children in Norway and to explore the role of SEP in explaining differences in weight status. Anthropometric data from 8,858 children (age 8.3 years) from the population-based Norwegian Childhood Growth Study were used. Information about immigrant background, country of origin, and parental education (used as an indicator of SEP) were provided by Statistics Norway. For children with immigrant background, regional background was determined based on country of origin. Prevalence ratios (PR) were estimated for overweight/obesity and weight-to-height-ratio (WHtR) ≥ 0.5 by immigration and regional background, using generalized estimating equation log-binominal models adjusting for sex, age, survey year (model 1), residential area, population density (model 2) and parental education (model 3). Children with immigrant background had a higher prevalence of overweight/obesity and WHtR ≥ 0.5 than non-immigrant background children. Adjusted for parental education, children with an immigrant background from Southern and Eastern Europe, Asia except South-Asia, and Africa had a higher prevalence of overweight/obesity [PR: 1.37 (95% confidence interval (CI): 1.10-1.72), 1.28 (1.05-1.57), 1.47 (1.13-1.91), respectively] than children with a non-immigrant background. Children originating from Asia except South-Asia had a higher prevalence of WHtR ≥ 0.5 (PR: 1.64, CI: 1.25-2.15) compared to non-immigrant background children. The adjustment for parental education did not substantially change the results. Children with immigrant background had higher prevalence of overweight/obesity than non-immigrant background children. The difference varied according to region of origin but not substantially according to parental education. There is a need for culturally acceptable preventative measures targeting the parents of immigrant background children.


Visible light photocrosslinking of sugar beet pectin for 3D bioprinting applications.
Herein, we report the hydrogelation of sugar beet pectin (SBP) via visible light-mediated photocrosslinking and its applications in extrusion-based 3D bioprinting. Rapid hydrogelation (<15 s) was achieved by applying 405 nm visible light to an SBP solution in the presence of tris(bipyridine)ruthenium(II) chloride hexahydrate ([Ru(bpy)3]2+) and sodium persulfate (SPS). The mechanical properties of the hydrogel could be tuned by controlling the visible light irradiation time and concentrations of SBP, [Ru(bpy)3]2+, and SPS. High-fidelity 3D hydrogel constructs were fabricated by extruding inks containing 3.0 wt% SBP, 1.0 mM [Ru(bpy)3]2+, and 1.0 mM SPS. Human hepatoblastoma (HepG2) cells encapsulated in SBP hydrogels remained viable and metabolically active after 14 d of culture. Overall, this study demonstrates the feasibility of applying SBP and a visible light-mediated photocrosslinking system to the 3D bioprinting of cell-laden constructs for tissue engineering applications.


Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial.
The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).


Evaluation of prokaryotic and eukaryotic cells as food source for Balamuthia mandrillaris.
Balamuthia mandrillaris is a recently identified free-living protozoan pathogen that can cause fatal granulomatous encephalitis in humans. Recent studies have shown that B. mandrillaris consumes eukaryotic cells such as mammalian cell cultures as food source. Here, we studied B. mandrillaris interactions with various eukaryotic cells including, monkey kidney fibroblast-like cells (COS-7), human brain microvascular endothelial cells (HBMEC) and Acanthamoeba (an opportunistic protozoan pathogen) as well as prokaryotes, Escherichia coli. B. mandrillaris exhibited optimal growth on HBMEC compared with Cos-7 cells. In contrast, B. mandrillaris did not grow on bacteria but remained in the trophozoite stage. When incubated with Acanthamoeba trophozoites, B. mandrillaris produced partial Acanthamoeba damage and the remaining Acanthamoeba trophozoites underwent encystment. However, B. mandrillaris were unable to consume Acanthamoeba cysts. Next, we observed that B. mandrillaris-mediated Acanthamoeba encystment is a contact-dependent process that requires viable B. mandrillaris. In support, conditioned medium of B. mandrillaris did not stimulate Acanthamoeba encystment nor did lysates of B. mandrillaris. Overall, these studies suggest that B. mandrillaris target Acanthamoeba in the trophozoite stage; however, Acanthamoeba possess the ability to defend themselves by forming cysts, which are resistant to B. mandrillaris. Further studies will examine the mechanisms associated with food selectivity in B. mandrillaris.


Nutritional intake after colorectal surgery: a comparison of a traditional and a new post-operative regimen.
The energy and protein intake was studied for 12 days after colorectal surgery in 36 patients. Eighteen patients followed a traditional management with nasogastric suction until bowel movements occurred after which a liquid diet, protective diet and normal food were successively administered. In a subsequent period a new regimen was introduced. Nasogastric suction was not used. Instead, 18 patients received liquid diet from the first post-operative day and normal food, when the patient wanted to eat it. In addition, the nutritional intake was supplemented by protein-enriched refreshing drinks and milk products between the meals. The new regimen was tolerated without discomfort and resulted in a significant increase in protein intake (43 g/day vs. 26 g/day, p<0.001) and energy intake (78% vs. 71% of the basal metabolic rate, p<0.05). The increase was most pronounced in the first 4 days after the operation. Finally, the weight loss was significantly lower on the new regimen (1.8 kg vs. 3.9 kg, p<0.001).


Chronic β2 -adrenoceptor agonist treatment alters muscle proteome and functional adaptations induced by high intensity training in young men.
While several studies have investigated the effects of exercise training in human skeletal muscle and the chronic effect of β2 -agonist treatment in rodent muscle, their effects on muscle proteome signature with related functional measures in humans are still incompletely understood. Herein we show that daily β2 -agonist treatment attenuates training-induced enhancements in exercise performance and maximal oxygen consumption, and alters muscle proteome signature and phenotype in trained young men. Daily β2 -agonist treatment abolished several of the training-induced enhancements in muscle oxidative capacity and caused a repression of muscle metabolic pathways; furthermore, β2 -agonist treatment induced a slow-to-fast twitch muscle phenotype transition. The present study indicates that chronic β2 -agonist treatment confounds the positive effect of high intensity training on exercise performance and oxidative capacity, which is of interest for the large proportion of persons using inhaled β2 -agonists on a daily basis, including athletes. Although the effects of training have been studied for decades, data on muscle proteome signature remodelling induced by high intensity training in relation to functional changes in humans remains incomplete. Likewise, β2 -agonists are frequently used to counteract exercise-induced bronchoconstriction, but the effects β2 -agonist treatment on muscle remodelling and adaptations to training are unknown. In a placebo-controlled parallel study, we randomly assigned 21 trained men to 4 weeks of high intensity training with (HIT+β2 A) or without (HIT) daily inhalation of β2 -agonist (terbutaline, 4 mg dose-1 ). Of 486 proteins identified by mass-spectrometry proteomics of muscle biopsies sampled before and after the intervention, 32 and 85 were changing (false discovery rate (FDR) ≤5%) with the intervention in HIT and HIT+β2 A, respectively. Proteome signature changes were different in HIT and HIT+β2 A (P = 0.005), wherein β2 -agonist caused a repression of 25 proteins in HIT+β2 A compared to HIT, and an upregulation of 7 proteins compared to HIT. β2 -Agonist repressed or even downregulated training-induced enrichment of pathways related to oxidative phosphorylation and glycogen metabolism, but upregulated pathways related to histone trimethylation and the nucleosome. Muscle contractile phenotype changed differently in HIT and HIT+β2 A (P ≤ 0.001), with a fast-to-slow twitch transition in HIT and a slow-to-fast twitch transition in HIT+β2 A. β2 -Agonist attenuated training-induced enhancements in maximal oxygen consumption (P ≤ 0.01) and exercise performance (6.1 vs. 11.6%, P ≤ 0.05) in HIT+β2 A compared to HIT. These findings indicate that daily β2 -agonist treatment attenuates the beneficial effects of high intensity training on exercise performance and oxidative capacity, and causes remodelling of muscle proteome signature towards a fast-twitch phenotype.


The use of SN-5 to differentiate chronic rhinosinusitis and chronic adenoiditis in children.
Chronic adenoiditis (CA) and chronic rhinosinusitis (CRS) present with similar symptoms, but an accurate diagnosis is critical for optimal treatment. We aim to differentiate CRS and CA based on sinonasal symptoms using the Sinus and Nasal Quality of Life Survey (SN-5) in children. This is a retrospective cohort study. Children (age 12 and younger) presenting with chronic sinonasal symptoms were divided into 2 groups based on CT scan sinus findings: CA group included patients with CT Lund-Mackay (LM) score <5 and CRS group included patients with CT LM score of 5 and more. SN-5 scores for each group were then compared, and both groups were compared to a control group. Other demographic data were also collected and analyzed. There were 27 patients in the CA group, 42 patients in CRS group and 38 patients in the control group. Mean SN-5 scores were 2.03±0.71 for the control group, 3.49±1.00 for the CA group, and 4.53±0.77 for the CRS group (p < 0.0001); Statistical significance persisted when CA and CRS were compared in subset analysis (p < 0.0001). CT LM score was 2.70±2.07 for the CA group and 9.94±3.46 for the CRS group (p < 0.0001). Rates of asthma, allergic rhinitis, and smoke exposure differed between the three groups (p < 0.01), but they were not statistically different when CA and CRS were compared in subset analysis. Children with CRS have higher SN-5 score than children with CA. SN-5 score can be used to help otolaryngologists differentiate between these two clinical entities.


In rat B lymphocyte genesis sixty percent is lost from the bone marrow at the transition of nondividing pre-B cell to sIgM+ B lymphocyte, the stage of Ig light chain gene expression.
The cycling B precursor cells in rat bone marrow (BM) that carry the B220 antigen and no surface Ig daily produce 780 million new cells. The pool of recirculating B lymphocytes in the rat, however, renew at a rate of only about 40 million cells/day. To analyze at which stages in B lymphocyte genesis the cell loss occurs, we identified post-mitotic cells in the rat BM B lineage, and determined their renewal rates. We used 5-bromo-deoxyuridine (BrdUrd) to label DNA-synthesizing cells, identifying incorporated BrdUrd with the mouse monoclonal antibody BU-1. B lineage cell subsets were identified by the markers HIS24 antigen (rat B220), terminal deoxynucleotidyl transferase (TdT), Ig mu heavy chain, and complete Ig. By use of double and triple immunocytology, we determined the extent of BrdUrd incorporation in the various B lineage compartments [HIS24+TdT-Ig-, TdT+, cytoplasmic mu chain (c mu)+ surface (s) IgM- pre-B, sIgM+ B]. Both sIgM+ B lymphocytes and all B precursors with cell diameters less than 11-12 microns were virtually devoid of DNA synthesis, as indicated by S-phase indices below 2%. In contrast, S-phase indices of large B precursors ranged between 43%-66%. We established the renewal rates of nondividing BM B lineage cells by placing osmotic minipumps containing BrdUrd subcutaneously in the flank of rats. The nondividing BM B lineage cells all renewed rapidly at rates between 2.4% and 5.6%/h, representing average half-lives of 29 to 12 h. In absolute numbers, the renewal/day/whole body BM was 165 X 10(6) for sIgM+ B lymphocytes, 422 X 10(6) for small c mu+ sIgM- pre-B cells, 89 X 10(6) for small TdT+ cells and 35 X 10(6) for small HIS24+TdT-Ig- cells. Assuming that recirculating B lymphocytes in the periphery are the descendants of BM sIgM+ B lymphocytes, which in their turn are the progeny of small pre-B cells, the renewal data indicate the following. Of the 165 million potentially available BM B lymphocytes, only 40 million cells become incorporated in the pool of recirculating B lymphocytes, representing a loss of 75%. BM B lymphocytes, in turn, use only (165/422 X 100% = ) 40% of the potential output from their immediate precursors. The 60% loss that occurs here may reflect the extent of aberrant Ig light chain gene rearrangement in normal B lymphocyte genesis.(ABSTRACT TRUNCATED AT 400 WORDS)


New species and records of Phanoperla (Plecoptera: Perlidae) from southwestern China.
A species of Phanoperla, P. wangi sp. nov., is described from Yunnan Province, China as new to science and compared with related species. Phanoperla himalayana Zwick, 1977, P. vietnamensis Zwick, 1986, and P. wieng Sivec Stark, 2010 are reported as new records from China.


[Roles and missions of the reliable person at the hospital: Insufficiently known by the patients].
The law of March 4th, 2002 allows the patient hospitalized to appoint a reliable person who can support him, help him and represent him throughout his disease. This possibility must be necessarily proposed by hospitals. The roles and the missions entrusted to this reliable person do not stop becoming more marked since. A study was realized to know if the hospitalized patients knew that is a reliable person and if yes how had they learnt him? The study tried to know who is or would then be appointed and who are or would be and would be the roles and missions which appear to him important? By one question semi-directive distributed to the patients hospitalized in units of pointed care, following care and the long-term care of Nantes (France), these estimated the roles and the missions awarded to the reliable person by the legal texts. A meadow of a patient on two does not know who is a reliable person. A direct relative (parent children, spouse and not the regular doctor) is or would be indicated. The reliable person is a help considered very important by the patients. More than 8 patients on 10 estimate him very precious audience in the accompaniment during the hospitalization and in the respect for their last wills more than in the direct support. The patients of more than 65 years old and retired know less well this reliable person. The information delivered to the reliable person has to be the object for the patient of a real partnership with the teams of care. The information and the knowledge by the patients and the nursing of the roles and the missions of the reliable person are clearly insufficient. Establishments in other did not take all the measure of this obligation to propose his name. An initial and continuous training nursing on its subject would be necessary. The patients grant a big importance for this reliable person and this study shows that the patients would tune him a lot of importance if hospital departments answered their obligations.


Ionic channels in the plasma membrane of Schizosaccharomyces pombe: evidence from patch-clamp measurements.
Patch-clamp studies of the yeast Schizosaccharomyces pombe reveal that the plasma membrane contains a voltage-gated channel mildly selective for potassium over sodium, lithium, and chloride. The channel exhibits several conductances with a maximum of 153 pS. The channel gates in the region of physiologically relevant voltages, being closed at hyperpolarizing and open at depolarizing voltages. It is not inhibited by tetraethylammonium, quinine, or quinidine applied from the cytoplasmic side of the membrane; similarly, ATP and stretch have no effect. The frequency of its occurrence in patches implies that about 35 channels of this kind are present in the plasma membrane of a single cell.


Influence of approach on outcome in radiofrequency ablation of liver tumors.
In this article some recent data concerning the approach on radiofrequency ablation (RFA) of liver tumors are reviewed. Specifically, several critical statements between surgical and percutaneous approach are raised and discussed: (1) Open approach may lead to a higher complication rate; (2) Temporary occlusion of hepatic inflow during surgical approach may lead to a higher rate of ablation of the liver tumors; (3) Surgical approach may permit better targeting of the tumor to be ablated. (4) Surgical approach may discover additional liver tumors. Finally, several conclusions and recommendations are also addressed.


Sex differences in property crime in a Danish adoption cohort.
Sex differences in genetic and environmental influences on criminal behavior against property were studied in a birth cohort of 6129 male and 7065 female Danish adoptees and their biological and adoptive parents. Both genetic and environmental factors were found to contribute to variation in liability to property criminality, the relative proportions of variance explained being similar in males and females. Important shared- and nonshared-family environmental factors were present. In separate analyses of average liability toward property criminality, however, convicted females appeared to be more genetically predisposed than convicted males, a conclusion based on the finding that female property offenders were more likely than male offenders to have convicted biological (but adopted-away) offspring. On the other hand, property-offending males and females did not appear to differ in their average shared-family environmental liabilities, since conviction rates did not differ for adoptees of convicted adoptive mothers and fathers. Also, social class in the adoptive parents of convicted sons and daughters were comparable, further indicating that average shared-family environmental liabilities do not differ between the sexes.


Fractional calcium currents through recombinant GluR channels of the NMDA, AMPA and kainate receptor subtypes.
1. Simultaneous fluorescence and whole-cell current measurements using the calcium indicator dye fura-2 were made in HEK 293 cells expressing recombinant glutamate receptor (GluR) channels, and fractional Ca2+ currents (the proportion of whole-cell current carried by Ca2+; Pf) were determined. 2. Cells expressing N-methyl-D-aspartate receptor (NMDAR) channels showed glutamate activated Ca2+ inflow in the voltage range -60 to 40 mV in normal extracellular solution. Ca2+ inflow decreased in a voltage-dependent manner at membrane potentials more negative than -30 mV due to Mg2+ block. Voltage dependence of block at negative potentials was stronger in cells expressing the NR1-NR2A as compared with cells expressing NR1-NR2C subunits. 3. Fractional Ca2+ currents through NMDARs were independent of extracellular Mg2+ and varied between 8.2% (NR1-NR2C subunits) and 11% (NR1-NR2A subunits) in normal extracellular solution (1.8 mM Ca2+) at -60 mV membrane potential. Pf values increased with increasing [Ca2+]o in the range of 0.5-10mM [Ca2+]o in a saturating fashion. 4. In cells expressing alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR) subunits which were unedited at the Q/R site of the putative transmembrane segment TM2 (Q-form), or in cells coexpressing unedited and edited subunits (R-form), the glutamate-evoked Ca2+ inflow increased from 20 to -80 mV in an almost linear way. 5. Fractional Ca2+ currents through AMPAR channels depended on subunit composition. Pf values of Q-form homomeric channels at -60 mV and 1.8 mM [Ca2+]o were between 3.2 and 3.9%. They were slightly voltage dependent and increased with [Ca2+]o in the range 1.8-10mM. Pf values in cells co-expressing Q- and R-form subunits were almost one order of magnitude smaller (0.54%). 6. Relative concentrations of Q-form and R-form GluR-B subunit-specific cDNAs used for cell transfection determined the expression of functionally different heteromeric AMPARS. Pf decreased with increasing relative concentration of R-form encoding CDNAs from 3.4 to 1.4%, demonstrating that editing of the Q/R site of GluR-B subunits decreases Ca2+ inflow through heteromeric AMPARs. 7. Cells expressing the GluR-6 subunit of the kainate receptor (KAR) family were characterized by Pf values which depended on the editing in the TM1 and TM2 segments. Pf values were largest for the Q-form (1.55-2.0%) and lowest for R-form channels (< 0.2%), suggesting that Q/R site editing also decreases Ca2+ inflow through KAR channels. Cells co-expressing both subunit forms showed an intermediate value (0.58%).(ABSTRACT TRUNCATED AT 400 WORDS)


Opioid therapy for chronic noncancer back pain. A randomized prospective study.
A randomized, open, long-term, repeated-dose comparison of an anti-inflammatory drug and two opioid regimens in 36 patients with back pain. To examine the long-term safety and efficacy of chronic opioid therapy in a randomized trial of patients with back pain. All participants underwent a 4-week washout period of no opioid medication before being randomly assigned to one of three treatment regimens for 16 weeks: 1) naproxen only, 2) set-dose oxycodone, or 3) titrated-dose oxycodone and sustained-release morphine sulfate. All patients then were assigned to a titrated dose of opioids for 16 weeks and then gradually tapered off their medication for 12 weeks. Finally, all participants were monitored for a 1-month posttreatment washout period. Each patient was called once a week for a report on pain, activity, mood, medication, hours awake, and adverse effects and was monitored carefully for signs of abuse and noncompliance. Weekly reports during the experimental phase showed the titrated-dose group to have less pain (P < 0.001) and less emotional distress (P < 0.001) than the other two groups. Both opioid groups were significantly different from the naproxen-only group. During the titration phase, patients also reported significantly less pain and improved mood. Few differences were found in activity or hours asleep, or between average pretreatment and posttreatment phone-interview and questionnaire variables. No adverse events occurred, and only one participant showed signs of abuse behavior. The results suggest that opioid therapy has a positive effect on pain and mood but little effect on activity and sleep. Opioid therapy for chronic back pain was used without significant risk of abuse. However, tapered-off opioid treatment is palliative and without long-term benefit.


Comparative study of quantitative ultrasonography and dual-energy X-ray absorptiometry for evaluating renal osteodystrophy in children with chronic kidney disease.
Our aim was to assess bone parameters in children with chronic kidney disease (CKD) with both dual-energy X-ray absorptiometry (DXA) and quantitative ultrasonography (QUS) and additionally with biochemical markers of bone turnover. Twenty children (12 boys and 8 girls) with CKD and a mean decimal age of 9.47 ± 4.44 years were included in the study where anthropometric parameters (height and weight), pubertal status, bone mineral density (BMD) at lumbar spine, speed of sound (SOS) measured by QUS at radius and at tibia, and biochemical markers of bone metabolism were measured. Six patients (30%) had tibial SOS Z score <-1, and 52.7% had radial SOS Z score <-1, whereas only 16.67% had BMD Z score <-1. Patients had significantly increased levels of serum intact parathormone (p < 0.001), serum bone alkaline phosphatase (BAP) (p < 0.001) and serum N-terminal-mid fragment (aminoacids 1-43) of osteocalcin (p < 0.001) compared to controls, whereas serum osteoprotegerin was significantly decreased in patients compared to controls (p = 0.001). SOS was significantly correlated to BAP (r = -0.586, p = 0.013 and r = -0.709, p = 0.001, respectively, for radius and tibia). In conclusion no association between DXA and QUS measurements was documented in our study, whereas QUS was better correlated to biochemical indices of ROD.


Reliability of diurnal salivary cortisol metrics: A meta-analysis and investigation in two independent samples.
Stress-induced dysregulation of diurnal cortisol is a cornerstone of stress-disease theories; however, observed associations between cortisol, stress, and health have been inconsistent. The reliability of diurnal cortisol features may contribute to these equivocal findings. Our meta-analysis (5 diurnal features from 11 studies; total participant n = 3307) and investigation (15 diurnal cortisol features) in 2 independent studies (St. Louis Personality and Aging Network [SPAN] Study, n = 147, ages 61-73; Minnesota Longitudinal Study of Risk and Adaptation [MLSRA] Study, n = 90, age 37) revealed large variability in the day-to-day test-retest reliability of diurnal features derived from salivary cortisol data (i.e., ICC = 0.00-0.75). Collectively, these data indicate that some commonly used diurnal cortisol features have poor reliability that is insufficient for individual differences research (e.g., cortisol awakening response) while others (e.g., area under the curve with respect to ground) have fair-to-good reliability that could support reliable identification of associations in well-powered studies.


Subepicardial aneurysm after anticoagulant therapy for a mural thrombus following anterior myocardial infarction.
A subepicardial aneurysm became evident in a male patient after anticoagulant therapy. On admission, it appeared to be an old anterior infarction accompanied by a mural thrombus. After warfarin administration, the thrombus disappeared and an echo-free space emerged outside the apical myocardial wall. The echo-free space communicated with the left ventricular cavity through the apical myocardial wall. Emergency surgery was undertaken and the patient survived. The aneurysm was covered with epicardium and there was an endomyocardial rupture of the muscle in the apical wall, which was the entrance of the aneurysm. This case suggests that cautious follow-up with echocardiography is necessary when anticoagulant therapy is selected for thrombi following myocardial infarction.


The potential for induction peptide receptor chemoradionuclide therapy to render inoperable pancreatic and duodenal neuroendocrine tumours resectable.
To assess the clinical utility of peptide receptor chemoradionuclide therapy (PRCRT) using (177)Lu-octreotate (LuTate) with concurrent 5FU chemotherapy in patients with inoperable primary pancreatic and duodenal neuroendocrine tumours (NETs). Between December 2006 and October 2009, five patients with progressive inoperable pancreatic and duodenal NETs without distant metastatic disease or with a potentially resectable solitary distant metastasis were treated with PRCRT; in combination with external beam radiotherapy in one case. Patients were followed up three months post-treatment with somatostatin receptor scintigraphy, radiology, biochemical markers and clinical assessment. Radiological response classification was defined by Response Evaluation Criteria in Solid Tumours (RECIST) with the addition of a minor response (MR; 10-30% size reduction) classification. Long-term follow up was performed until July 2011. At three months post-treatment, all five patients had a scintigraphic response, four had a radiological response and three of the four symptomatic patients responded clinically. All five patients had an ongoing treatment response beyond three months including one where further tumour shrinkage facilitated curative surgery. All five patients are alive with 12-42 months of follow-up post-treatment. PRCRT can be effective in inoperable pancreatic and duodenal neuroendocrine tumours and may play a role as neoadjuvant therapy in this patient group.


Spontaneous and evoked release of met-enkephalin-like material from the spinal cord of arthritic rats in vivo.
Perfusion of the intrathecal space with artificial CSF was achieved in control and arthritic rats under halothane anaesthesia in order to collect the met-enkephalin-like material (MELM) released from the whole spinal cord. On the fourth week following the intradermal injection of Freund's adjuvant to induce arthritis, a marked reduction (-56%) in the spontaneous outflow of MELM was noted in arthritic rats. This effect did not involve changes in the degradation process of MELM, since it persisted when kelatorphan was added to the perfusing fluid in order to inhibit completely the peptidases acting on met-enkephalin. Raising the K+ concentration in the perfusing fluid from 2.4 to 40 mM, as well as moving the hind paws, produced a significant enhancement of MELM release which was (at least) as pronounced in arthritic as in control rats. These results suggest that the basal activity of spinal enkephalinergic neurones, but not that triggered by various stimuli, is reduced in arthritic rats.


Species differences in the hepatic response to mirex: ultrastructural and histochemical studies.
Mirex was fed at levels of 1, 5, 15, and 30 ppm to mice, 5 and 30 ppm to rats, while monkeys received the chemical by stomach tube at levels of 0.25 and 1 mg/kg (equal to 5 and 20 ppm). Mice were killed and their livers obtained at 2, 4, 6, 9, 10, 15 and 18 months, whereas rats were killed and surgical biopsies were taken at 16, 19, 26, and 36 months. Cytochemical techniques were employed to detect activities of lysosomal beta-glycerol phosphatase (ACpase) and glucose 6-phosphatase (G-6-pase). ACpase and G-6-pase remained unchanged and comparable to controls in livers of mice receiving 1 ppm. G-6-pase decreased in centrilobular areas while ACpase increased with time in the higher groups. At 12 months, liver cells that lost their G-6-pase activity surrounded by Kupffer cells that contained strong ACpase. In contrast, rat livers had no increase in ACpase and little loss in G-6-pase. Surprisingly, and in spite of the high levels of mirex ingested, monkey livers showed no loss of G-6-pase or activation of ACpase. Ultrastructurally, the underlying feature in all livers was proliferation of smooth endoplasmic reticulum (SER) displaying species variation. Thus, in mice, intense proliferation of SER that was both time- and dose-dependent was localized in specific regions of the cytosol. Hepatic cells, damaged and necrotic in mice fed 5, 15, and 30 ppm, were phagocytosed by activated Kupffer cells. SER proliferation in rat and monkey liver cells was less conspicuous than in mice. Except for this change, rat and monkey liver cells were normal. There studies emphasize species and enzyme variations in response to mirex. An interesting aspect observed was the lack of lysosomal catabolism during liver enlargement.


Pharmacotherapy for posttraumatic stress disorder: empirical review and clinical recommendations.
Growing awareness of the psychological effects of trauma has emphasized the need for clinicians across a range of practice settings to be aware of evidence-based treatment options for posttraumatic stress disorder (PTSD). The purpose of this article is to review the available empirical data on pharmacological approaches to PTSD and to provide recommendations for clinical practice. Although a comprehensive search of PsychInfo and Medline databases revealed a multitude of case reports and open-label trials, this paper focuses primarily on evidence obtained from randomized controlled trials to determine the most effective pharmacological treatments for PTSD. The research data overwhelmingly supports antidepressant medication as the first-line pharmacotherapy for PTSD, with selective serotonin re-uptake inhibitors having the strongest body of empirical support. Other medications, and with care, combination pharmacotherapy, may also have a role in the management of certain presentations. Cautions for clinicians in treating this complex disorder are provided. Despite a substantial increase in the amount and quality of research into pharmacological treatments for PTSD in recent years, there is still a pressing need for more data to guide routine clinical practice. In particular, future research regarding the psychobiological basis of PTSD may guide the development of a PTSD-specific drug, designed to treat the unique characteristics of this disorder.


Attitudes and perceptions of influenza vaccination among Hong Kong doctors and medical students before the 2009 pandemic.
Vaccination is an important preventive measure for preparing against the influenza pandemics. This study investigated the attitudes and perceptions of influenza vaccination among doctors and medical students in Hong Kong. A cross-sectional survey was conducted among 204 doctors and 242 medical students in a teaching hospital in 2009. Participants' demographic and job characteristics, and influenza experience and vaccination in the previous year were assessed in the questionnaire. Logistic regression models were used to examine the associations between uptake of influenza vaccination and the perceived benefits. Medical students were more likely to have receive an influenza vaccination in the previous year (66.9 vs. 39.7%) and acknowledged the related benefits than doctors. Moreover, uptake of influenza vaccine was associated with perceived benefits of vaccination in both doctors and medical students. The perceived benefits of influenza vaccination are an important factor in vaccine uptake for both doctors and medical students in Hong Kong, and should be reinforced in the professional training.


Comparison of Symbicort® versus Pulmicort® on steroid pharmacodynamic markers in asthma patients.
Combination therapy with inhaled corticosteroids (ICS) and long-acting β(2)-adrenergic agonists (LABA) is reported to have superior effects on controlling asthma symptoms to ICS alone; however, there is no molecular-based evidence to explain the clinical effects. Here, the effect of the ICS/LABA combination was compared with ICS on glucocorticoid receptor (GR) activation in sputum macrophages. In a randomised, double-blind cross-over placebo-controlled 6-visit study, 10 patients with mild asthma were given placebo, formoterol (Oxis(®) 12 μg), budesonide (Pulmicort(®) 200 μg :BUD200, or 800 μg :BUD800), or budesonide/formoterol combination (Symbicort(®)) as a single 100/6 μg (SYM100) or double 200/12 μg (SYM200) dose. Sputum macrophages were separated by plate adhesion from induced sputum. GR binding to the glucocorticoid-response elements on oligonucleotides (GR-GRE binding) was evaluated by ELISA. mRNA expression of MAP-kinase phosphatase (MKP)-1 and IL-8 were measured by quantitative RT-PCR. GR-GRE binding was significantly increased after treatment with SYM100 (3.5 OD/10 μg protein, median, p < 0.05) versus placebo (1.3) and BUD200 (1.6), and the induction was higher than that of BUD800 (2.4). MKP-1 mRNA was increased and IL-8 mRNA was significantly inhibited by BUD800, SYM100 and SYM200 versus placebo. The effects of SYM100 and SYM200 on GR activation were not different from that of BUD800 and superior to BUD200. Thus, it has been confirmed at a molecular level that inhaled combination therapy with a lower dose of budesonide has an equivalent effect to a high dose of budesonide alone. In addition, GR-GRE binding is found to be a valuable pharmacodynamic marker for steroid efficacy in clinical studies.


Improvement of the sagittal alignment of the spine in patients with achondroplasia after subtrochanteric femoral lengthening.
Limb-lengthening surgery to treat short stature has undergone great development in recent years with the use of intramedullary telescopic nails (TIMNs). A limited number of studies have explored the impact of lower limb lengthening on the spine, though their conclusions are not consistent. The aim of this research is to analyze changes in spinopelvic sagittal alignment and balance after lower limb lengthening in achondroplastic patients. Prospective study of patients with achondroplasia treated with bilateral femoral lengthening using an TIMN. Different sagittal spinal and pelvic plane parameters were measured on pre- and 2 year postoperative lateral spine radiographs: cervical lordosis, thoracic kyphosis, TL junction, lumbar lordosis (LL), pelvic incidence, pelvic tilt (PT), sacral slope (SS), and sagittal vertebral axis (SVA). Similarly, information regarding the elongation procedure was recorded. A total of 10 patients were included (60% male), with a median age of 13.39 (2.32) years at first surgery and a median height of 120.3 (5.75) cm. A 10 cm elongation was performed in all patients through femoral subtrochanteric osteotomy. Statistically significant changes were found in LL -15.2 (7.4-17.9)º (p = 0.028), PT 11.7 (10.3-13.4)º (p = 0.018), SS - 11.6 (- 13.4 to - 10.4)º (p = 0.018) and |SVA| - 34.3 (- 39.10 to - 1.7) mm (p = 0.043). Bilateral lower limb lengthening in patients with achondroplasia not only increases their size, but also improves sagittal spinopelvic alignment and balance. This may be due to retroversion of the pelvis and subsequent decrease in SS and LL as a result of the increased tightness of the gluteus maximus and hamstring muscles after femoral lengthening through subtrochanteric osteotomy. II, prospective comparative cohort study, before and after intervention.


Effects of surgery and propofol-remifentanil total intravenous anesthesia on cerebrospinal fluid biomarkers of inflammation, Alzheimer's disease, and neuronal injury in humans: a cohort study.
Surgery and anesthesia have been linked to postoperative cognitive disturbance and increased risk of Alzheimer's disease. It is not clear by which mechanisms this increased risk for cognitive disease is mediated. Further, amyloid β production has been suggested to depend on the sleep-wake cycle and neuronal activity. The aim of the present study was to examine if cerebrospinal fluid (CSF) concentrations of a number of biomarkers for Alzheimer's disease-related processes, including amyloid β, neuronal injury, and inflammation, changed over time during intravenous anesthesia in surgical patients. We included patients scheduled for hysterectomy via laparotomy during general anesthesia with intravenous propofol and remifentanil. CSF samples were obtained before, during, and after surgery (5 h after induction) and tested for 27 biomarkers. Changes over time were tested with linear mixed effects models. A total of 22 patients, all females, were included. The mean age was 50 years (± 9 SD). The mean duration of the anesthesia was 145 min (± 40 SD). Interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, and vascular endothelial growth factor A increased over time. IL-15 and IL-7 decreased slightly over time. Macrophage inflammatory protein 1β and placental growth factor also changed significantly. There were no significant effects on amyloid β (Aβ) or tau biomarkers. Surgery and general anesthesia with intravenous propofol and remifentanil induce, during and in the short term after the procedure, a neuroinflammatory response which is dominated by monocyte attractants, without biomarker signs of the effects on Alzheimer's disease pathology or neuronal injury.


Association of identification of facility and transportation for childbirth with institutional delivery in high priority districts of Uttar Pradesh, India.
Timely and skilled care is key to reducing maternal and neonatal mortality. Birth preparedness involves preparation for safe childbirth during the antenatal period to reach the appropriate health facility for ensuring safe delivery. Hence, understanding the factors associated with birth preparedness and its significance for safe delivery is essential. This paper aims to assess the levels of birth preparedness, its determinants and association with institutional deliveries in High Priority Districts of Uttar Pradesh, India. A community-based cross-sectional survey was conducted between June-October 2018 in the rural areas of 25 high priority districts of Uttar Pradesh, India. Simple random sampling was used to select 40 blocks among 294 blocks in 25 districts and 2646 primary sampling units within the selected blocks. The survey interviewed 9458 women who had a delivery 2 months prior to the survey. Descriptive statistics were included to characterize the study population. Multivariable logistic regression analyses were performed to identify the determinants of birth preparedness and to examine the association of birth preparedness with institutional delivery. Among the 9458 respondents, 61.8% had birth preparedness (both facility and transportation identified) and 79.1% delivered in a health facility. Women in other caste category (aOR = 1.24, CI 1.06-1.45) and those with 10 or more years of education (aOR = 1.68, CI 1.46-1.92) were more likely to have birth preparedness. Antenatal care (ANC) service uptake related factors like early registration for ANC (aOR = 1.14, CI 1.04-1.25) and three or more front line worker contacts (aOR = 1.61, CI 1.46-1.79) were also found to be significantly associated with birth preparedness. The adjusted multivariate model showed that those who identified both facility and transport were seven times more likely to undergo delivery in a health facility (aOR = 7.00, CI 6.07-8.08). The results indicate the need for focussing on marginalized groups for improving birth preparedness. Increasing ANC registration in the first trimester of pregnancy, improving frontline worker contact, and optimum utilization of antenatal care check-ups for effective counselling on birth preparedness along with system level improvements could improve birth preparedness and consequently institutional delivery rates in Uttar Pradesh, India.


Polychlorinated and polybrominated biphenyl congeners and retinoid levels in rat tissues: structure-activity relationships.
The purpose of this study was to examine the structural requirements of polychlorinated and polybrominated biphenyls (PCBs and PBBs) for altering tissue levels of retinoids. Seven congeneric PCBs and PBBs were studied: 3,3',4,4'-tetrachlorobiphenyl (TCB), 2',3,3',4,5- and 3,3',4,4',5-pentachlorobiphenyls (-PeCBs), 3,3',4,4'- and 3,3',5,5'-tetrabromobiphenyls (-TBBs), 2,2',3,3',5,5'-hexachlorobiphenyl (-HCB), and 3,3',4,4',5,5'-hexabromobiphenyl (-HBB). Male Sprague-Dawley rats were fed a vitamin A-adequate diet (1.3 mg/kg) for 30 days before being given a single IP injection of one of seven polyhalogenated biphenyls (150 mumol/kg) in corn oil (10 ml/kg) or vehicle alone. Rats were killed 1 week later. Except for 3,3',4,4',5,5'-HBB, all PCBs and PBBs studied significantly decreased serum retinol levels and, except for 3,3',4,4',5,5'-HBB and 2,2',3,3',5,5'-HCB, all PCBs and PBBs also lowered the serum retinol-binding-protein (RBP) content. The activity of hepatic retinyl ester hydrolase (REH) was reduced by the treatment of 3,3',4,4',5-PeCB, 3,3',4,4'-TBB, and 3,3',4,4',5,5'-HBB. The levels of hepatic retinol were decreased by 2,2',3,3',5,5'-HCB, 2',3,3',4,5-PeCB, and 3,3',4,4',5-PeCB, while levels of hepatic retinyl palmitate were decreased by 2',3,3',4,5-PeCB, 3,3',4,4',5-PeCB, 3,3',4,4'-TCB, 3,3',4,4'-TBB, and 3,3',4,4',5,5'-HBB. The substantial decreases in hepatic retinyl palmitate levels could not be explained solely on the basis of hepatomegaly caused by acutely toxic PCBs and PBBs. All halogenated biphenyls which caused a decrease in hepatic retinyl palmitate also caused an increase in renal retinyl palmitate except 3,3',4,4',5-PeCB. In summary, the acutely toxic (nonortho substituted) congeners had pronounced effects on hepatic, renal, and serum retinoids whereas other biphenyls only decreased serum retinol levels. The effects of these seven compounds on REH activity were not correlated with the effects on serum retinol or RBP levels. Therefore, this study shows that the structure-activity relationships for altering hepatic retinoids differ from those for serum retinol, implying the involvement of multiple mechanisms.


Occupational exposure to pesticides: DNA damage in horticulturist from Nativitas, Tlaxcala in Mexico.
Mexico is a country where agricultural activity is of great importance, but biomonitoring data are still scarce. With more intensive pesticides use per unit area/surface in horticultural productivity, there is a higher impact on environmental contamination and workers' health. Considering that exposure to various pesticide and pesticide mixtures represents an additional genotoxic risk, the appropriate characterization of exposure, confounding factors and the risk itself are very much needed. We compared genetic damage in 42 horticulturists and 46 unexposed controls (Nativitas, Tlaxcala) using alkaline comet (whole blood) and micronucleus (MN) test with nuclear abnormalities (NA) (buccal epithelial cells). Workers demonstrated significantly higher levels of damage (TI%=14.02 ± 2.49 vs. 5.37 ± 0.46; MN=10.14 ± 5.15 vs. 2.40 ± 0.20), with more than 90% of them not using protective clothing nor gloves during application. Combined DNA damage techniques and periodic monitoring together with educational programs for safe pesticide application is the best strategy to assess and prevent workers' health risks.


Adsorption of fibrinogen and fragment D of fibrinogen onto the insolubilized alpha-chain of fibrin.
After thrombin treatment insolubilized fibrinmonomer, which is obtained from insolubilized fibrinogen covalently bound to agarose, adsorbs soluble fibrin and its derivatives from solutions. The immobilized proteins are attached to the agarose by the 'A' alpha-chain. After reduction of the disulfide bridges the beta- and gamma-chains can be removed from the agarose. After thrombin treatment the immobilized alpha-chain adsorbs fibrinogen and fragment D. To some extent the beta- and gamma-chain do not seem necessary for the adsorption. The amount adsorbed increases, when thrombin treatment of the insolubilized protein follows the reduction process. This may indicate that the fibrinopeptides 'A' of the insolubilized alpha-chain are better accessible after the removal of the beta- and gamma-chains.


Radiographic manifestations of transfusion-related acute lung injury.
The purpose of this article is to describe the clinical symptoms and illustrate the radiological manifestations of transfusion-related acute lung injury (TRALI) as the condition develops. We mention those findings that aid the discrimination from transfusion-associated cardiac overload. We will also point some of the characteristics that increase the risk of TRALI. TRALI generally occurs within 1 to 2 h of the start of a blood transfusion. Though the radiographic features of TRALI are nonspecific, the diagnosis is established using clinical and radiological parameters. The diagnosis warrants a high index of suspicion as well as knowledge of its risk factors. There are no specific treatments; the best chance of survival in TRALI is with early diagnosis and prevention.


Studies of connective tissue mast cell-mediated cytotoxicity.
Although mast cells have been implicated in mediating antitumor activity, the kinetics, mechanism(s), and suspectibility of different tumors to mast cell-mediated cytotoxicity have not been defined. Rat connective tissue mast cells (CTMC) of greater than or equal to 99% purity were investigated in vitro and found to express maximal spontaneous cytotoxicity against the mouse fibrosarcoma cell line WEHI-164 (56.0% +/- 2.1 SEM), the ultraviolet B (UVB)-induced, cutaneous fibrosarcoma 5C25 (34.7% +/- 3.4 SEM), and the human renal cell tumor Currie (26.8% +/- 2.0 SEM) at an effector to target (E:T) ratio of 80:1. Kinetic studies of CTMC-mediated cytotoxicity demonstrated significant detectable lysis against these tumors within 8 h, which was maximal by 16 h. Binding experiments showed that CTMC formed conjugates with all three lytic-sensitive targets; however, CTMC also attached to the lytic-resistant target YAC-1, indicating that conjugate formation alone is not sufficient for mast cell-mediated cytotoxicity. At two different concentrations, mast cell granules (MCG) lysed WEHI-164 (36.5% +/- 6.8 SEM) and 5C25 (34.4% +/- 6.9 SEM), but were only slightly cytotoxic (5.7% +/- 2.9 SEM) against Currie. A potential role for tumor necrosis factor-alpha (TNF-alpha) in CTMC-mediated cytotoxicity also was investigated. Polyclonal antibodies to TNF-alpha greatly reduced CTMC and TNF-mediated lysis of WEHI-164, but only partially inhibited CTMC killing of the slightly TNF-sensitive 5C25 tumors, and had no effect on CTMC cytolysis of Currie. Thus, this study demonstrates that CTMC mediate cytotoxicity in vitro by both TNF-associated and TNF-independent mechanisms. We conclude that CTMC are capable of mediating antitumor activity and that this effect may be important for tumor surveillance in the skin and other sites.


Dopamine receptors mediate drug-induced but not Pavlovian conditioned contralateral rotation in the unilateral 6-OHDA animal model.
Following Pavlovian conditioning treatment sessions with apomorphine, animals receiving the paired treatment showed substantial contralateral rotation when placed without drug into the test environment previously paired to the apomorphine (0.5 mg/kg) injection while animals in the unpaired control treatment showed only ipsilateral rotation. Subsequent tests with the D1 antagonist (SCH 23390), or the D2 antagonist (haloperidol) partially suppressed and the combined D1-D2 antagonists completely suppressed the apomorphine-induced response of contralateral rotation. The identical contralateral rotation response occurring as a Pavlovian conditioned response in the paired apomorphine treatment group was not attenuated by dopamine receptor blockade. In both paired and unpaired groups, the spontaneous ipsilateral rotation response was completely blocked. Thus, non-dopaminergic mechanisms mediate conditioned rotation whereas the drug-induced as well as the spontaneous rotation responses require stimulation of striatal dopamine receptors.


Isolated tumefactive demyelinating lesions: diagnosis and long-term evolution of 16 patients in a multicentric study.
Isolated tumefactive demyelinating lesion (TDL) is a rare disease and a challenging entity especially for the differential diagnosis, biopsy indications, and therapeutic decisions. Long-term evolution is not well known. The objective of the study is to describe clinical and MRI characteristics and long-term follow-up of patients with isolated TDL. We performed a retrospective study including patients (1) with one TDL radiologically defined by a ≥20 mm FLAIR hyperintensity involving the white matter associated with T1 hypointensity that enhanced after gadolinium injection and (2) without any other MS lesion on the first MRI. Tumor, abscess, or other inflammatory diseases (ADEM, Baló's concentric sclerosis, systemic disease) were excluded. Sixteen patients (11 females/5 males) were included. The mean age of onset was 35.7 years (range 20-65). MRI disclosed supratentorial lesions with a mean size of 39.4 mm and usually mild edema/mass effect. Peripheral (mainly open-ring pattern) and central (mainly heterogeneous) enhancement were respectively seen in 9/16 and 11/16 patients. CSF study (n = 15) found oligoclonal bands (OCB) in seven. A cerebral biopsy was performed in 11 cases showing acute inflammatory demyelination. Thirteen patients were treated by pulse steroids with marked improvement in ten. At last clinical follow-up (mean 65.8 months, range 6-181), diagnosis was MS in 5 (31 %), isolated TDL in 10 (63 %) and one patient had a second TDL (6 %). Isolated tumefactive demyelinating lesions are a rare diagnostic entity. After a mean follow-up of 5 years, almost one-third became MS whereas most of the patients had no further event.


Toward Augmented Intelligence: The First Prospective, Randomized Clinical Trial Assessing Clinician and Artificial Intelligence Collaboration in Dermatology.
Han et al. (2022) report the first randomized, prospective clinical trial in dermatology evaluating the performance of clinicians working in collaboration with artificial intelligence (AI). This foundational work shows the limitations of AI in a real-world clinical setting and shows its potential for improving the performance of nonspecialists diagnosing skin diseases.


Nurse teacher candidates learned to use social media during the international teacher training course.
The purpose of this study was to describe the nurse teacher candidates' learning outcomes and experiences in social media during the international nurse teacher training course, Empowering learning environments in nursing education, Intensive Program (EleneIP). The pre-post research design was used. The data was collected before and after the course, with the questionnaire consisting of structured and open questions. Altogether, 24 nurse teacher candidates from four different European countries participated in the course and this study. The results showed that the knowledge of using social media applications increased during the course from 5.2 (range 1-9) to 8.1 (range 4-10), and their skills increased from 4.5 (range 1-8) to 7.6 (range 4-10).The main topics learnt during the course were divided in two categories: subjects of the course and teaching and learning methods. The students' experiences concerning the EleneIP course were positive in both categories. The international group created during EleneIP course also allowed the students to achieve another important aim, learning from a collaborative group the importance and possibilities of different learning environments, considering the cultural and social characteristics of each country participating in it.


The impact of advanced age on hepatic resection of colorectal liver metastases.
The aim of this study was to evaluate the impact of patient age on surgical therapy for colorectal liver metastases. Between 1992 and 2004, 212 consecutive patients underwent potentially curative hepatic resection. Sixty-two patients were 70 years or older at the time of resection (older group) and 150 patients were less than 70 years at the time of resection (younger group). A proportion of older patients had a history of severe cardiopulmonary disease (32.3%) and respiratory insufficiency (6.5%). Intraoperative variables, such as resected liver volume, operation time, estimated blood loss, and blood transfusion, were not notably different between older and younger patients. Postoperative complications after resection occurred in 19.7% of older patients and at a similar rate (23.3%) in the younger group. Resection mortality was 0% in older patients and 0.49% in younger patients. The 5-year survival rates of older and younger patients were 34.1% and 53.1%, respectively. Compared with younger patients, the overall survival rate of older patients was markedly lower (p<0.01). Advanced chronologic age cannot be regarded as a medical contraindication for hepatic resection of colorectal liver metastases in patients who are more than 70 years of age.


Polarization singularities in a stress-engineered optic: erratum.
This erratum gives corrections for the errors in a previously published paper [J. Opt. Soc. Am. A36, 312 (2019)JOAOD60740-323210.1364/JOSAA.36.000312].


Fibrinogen, cigarette smoking, and risk of cardiovascular disease: insights from the Framingham Study.
During the tenth biennial examination, 1315 Framingham study participants free of cardiovascular disease had fibrinogen measured along with other major cardiovascular risk factors including cigarette smoking. The fibrinogen values were significantly higher in smokers than in nonsmokers, increased with the amount smoked in each sex, and exsmokers had values as low as those of nonsmokers. Over 10 years of follow-up, 165 men and 147 women developed cardiovascular disease, the risk in both sexes increasing progressively in relation to antecedent fibrinogen values over the 180 to 450 mg/dl range. Risk gradients for cardiovascular disease in men diminished with advancing age. In men, risk of cardiovascular disease was related to cigarette smoking. This was true in the multivariate case taking all standard risk factors into account. As for fibrinogen, the impact diminished with advancing age. Regression coefficients were actually larger in the multivariate than in the univariate case because of a negative correlation between smoking and blood pressure. Fibrinogen contributed to cardiovascular disease, risk taking into account both cigarette smoking and other risk factors. When fibrinogen is added to the multivariate model for prediction of cardiovascular disease the coefficient for smoking becomes much reduced and is no longer statistically significant. However, each independently contributed to risk in cross-sectional analysis. These data provide another mechanism whereby cigarette smoking influences the occurrence of atherocardiovascular disease and also another reason for prohibiting cigarette use.


Trichomonas vaginalis induces IL-1β production in a human prostate epithelial cell line by activating the NLRP3 inflammasome via reactive oxygen species and potassium ion efflux.
Trichomonas vaginalis is a sexually transmitted protozoan parasite that causes vaginitis in women, and urethritis and prostatitis in men. IL-1β is synthesized as immature pro-IL-1β, which is cleaved by activated caspase-1. Caspase-1 is, in turn, activated by a multi-protein complex known as an inflammasome. In this study, we investigated the inflammatory response of a prostate epithelial cell line (RWPE-1) to T. vaginalis and, specifically, the capacity of T. vaginalis to activate the NLRP3 inflammasome. RWPE-1 cells were stimulated by live T. vaginalis, and subsequent expression of pro-IL-1β, IL-1β, NLRP3, ASC and caspase-1 was determined by real-time PCR and Western blotting. IL-1β and caspase-1 production was also measured by ELISA. To evaluate the effects of NLRP3 and caspase-1 on IL-1β production, the activated RWPE-1 cells were transfected with small interfering RNAs to silence the NLRP3 and caspase-1 genes. Activation of the NLRP3 inflammasome was observed by fluorescence microscopy. Intracellular reactive oxygen species (ROS) were evaluated by spectrofluorometry. When RWPE-1 cells were stimulated with live T. vaginalis, the mRNA and protein expression of IL-1β, NLRP3, ASC, and caspase-1 increased. Moreover, silencing of NLRP3 and caspase-1 attenuated T. vaginalis-induced IL-1β secretion. The NADPH oxidase inhibitor DPI and high extracellular potassium ion suppressed the production of IL-1β, caspase-1, and the expression of NLRP3 and ASC proteins. The specific NF-κB inhibitor, Bay 11-7082, inhibited IL-1β production, and also inhibited the production of caspase-1, ASC and NLRP3 proteins. T. vaginalis induces the formation of the NLRP3 inflammasome in human prostate epithelial cells via ROS and potassium ion efflux, and this results in IL-1β production. This is the first evidence for activation of the NLRP3 inflammasome in the inflammatory response by prostate epithelial cells infected with T. vaginalis. Prostate 76:885-896, 2016. © 2016 Wiley Periodicals, Inc.


Caspase-dependent apoptotic pathways in CNS injury.
Recent studies have suggested a role for neuronal apoptosis in cell loss following acute CNS injury as well as in chronic neurodegeneration. Caspases are a family of cysteine requiring aspartate proteases with sequence similarity to Ced-3 protein of Caenorhabditis elegans. These proteases have been found to contribute significantly to the morphological and biochemical manifestations of apoptotic cell death. Caspases are translated as inactive zymogens and become active after specific cleavage. Of the 14 identified caspases, caspase-3 appears to be the major effector of neuronal apoptosis induced by a variety of stimuli. A role for caspase-3 in injury-induced neuronal cell death has been established using semispecific peptide caspase inhibitors. This article reviews the current literature relating to pathways regulating caspase activation in apoptosis associated with acute and chronic neurodegeneration, and suggests that identification of critical upstream caspase regulatory mechanisms may permit more effective treatment of such disorders.


Inhibition of lipogenesis and sebum secretion for Lotus corniculatus seed extract in vitro and in vivo.
Botanical ingredients are widely used in hair- and skin-care products. However, few studies have investigated the effectiveness of botanical products on counteracting sebum synthesis and secretion. To investigate the composition of Lotus corniculatus seed extract (LC) and its potential inhibition of lipogenesis in SZ95 sebocytes and oily human skin. The active components of LC solutions were identified by high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). The in vitro effects of LC were evaluated using SZ95 cells treated with linoleic acid (LA) and dihydrotestosterone (DHT) and incubated with LCs for 24 h and 72 h. Lipogenesis was assessed by Oil Red O and Nile Red staining of the cells. In vivo effects were assessed on 30 subjects with oily skin who were enrolled in a randomized, blank-controlled trial and were treated with LC solution for 6 h and 4 weeks. The skin sebum contents and area on the forehead and cheeks were evaluated using a Sebumeter SM815 and Sebfix sebutape with Visioscan VC98. In addition, VISIA was used to collect half-face photos for analysis. A novel active molecule, 5'-o-rhamnosyl uridine, was identified in LC. LC exhibited a dose-dependent inhibitory effect on LA and DHT-induced lipid synthesis. When 5% LC was applied for 3 h, the skin sebum contents and area were significantly reduced compared with the vehicle control, with an obvious reduction after 6 h. Continued use of the serum containing 5% LC for 4 weeks resulted in a significant reduction in the skin sebum contents and area. No adverse reactions were reported during the study. Topical application of LC resulted in an immediate and long-lasting reduction of the sebum contents and area of oily human skin by reducing sebaceous lipogenesis through the LA and DHT pathways. This indicates the potential of LC as a new biological treatment for oily skin.


Superficial Fungal Infections.
Superficial fungal infections grow in dark and moist areas and invade various parts of the body. These infections are easily treatable in immunocompetent individuals. In immunosuppressed individuals, the presentation can be quite severe, requiring use of more potent antifungal agents. The treatment for these conditions consists of topical antifungal agents, creams, and oral systemic medications. The use of prednisone can alter the appearance of superficial fungal infections, making them difficult to diagnose. It is important for primary care providers to become adept at understanding the epidemiology, transmission, clinical presentation, diagnosis techniques, and treatment options available.


Establishing aversive, but not safe, taste memories requires lateralized pontine-cortical connections.
Aversive and safe taste memory processing is dramatically disrupted by bilateral lesions of the pontine parabrachial nucleus (PBN). To determine how such lesions affect patterns of neuronal activation in forebrain, lesions were combined with assessment of cFos-like immunoreactivity (FLI) in insular cortex (IC) and amygdala after conditioned taste aversion (CTA) training. Increases in FLI in amygdala and IC, which are normally seen following novel (versus familiar) CS-US pairing, were eliminated after PBN lesions. This suggests that PBN lesions prevent transmission of critical CS and US information to forebrain regions for the processing of both aversive and safe taste memories. Unilateral asymmetrical lesions of PBN and IC blocked CTA acquisition as well as normal patterns of FLI in amygdala after novel CS-US pairing, an effect not seen when unilateral lesions were confined to a single hemisphere. The crossed-disconnection experiments provide compelling evidence that functional interactions between PBN and IC are required for CTA acquisition, but not for safe taste memory formation and retrieval. The dissociation between effects of the different types of lesions on safe and aversive taste memories supports emerging evidence that the neural underpinnings of the two types of taste learning differ.


N-alkylation of highly quaternized chitosan derivatives affects the paracellular permeation enhancement in bronchial epithelia in vitro.
This study describes the structure-activity relationship for carefully characterized N-alkyl-N-quaternary chitosan derivatives as permeation enhancers for drugs that are mainly absorbed through the paracellular pathway, such as macromolecular drugs and hydrophilic drugs, in a well defined bronchial epithelial cell line. The O-methyl free derivatives used in the study were fully trimethylated (100%) N,N,N-trimethyl chitosan (TMC) and N-propyl-(QuatPropyl), N-butyl-(QuatButyl) and N-hexyl (QuatHexyl)-N,N-dimethyl chitosan, with 85-91% degree of quaternization. The fully trimethylated TMC, from 0.25mg/ml, decreased transepithelial electrical resistance (TER) in a reversible manner and enhanced the permeation of the macromolecule FITC-dextran 4kDa (FD4) 2-5 fold. TMC did not cause any alterations in the tight junction (TJ) protein claudin-4 or in F-actin architecture. QuatHexyl was the most effective polymer to produce enhanced permeation and decreased TER from 0.016mg/ml. Nevertheless, this enhanced permeation was accompanied by reduced viability and dissociation of F-actin and claudin-4 proteins. The structure-activity relationship suggests that more lipophilic derivatives show more permeation enhancement, TJ disassembly, and less viability in the order of hexyl≈butyl>propyl>methyl and demonstrates that the permeation effect is not only mediated by permanent positive charge but also by the extent of N-alkylation. These results are relevant to elucidate the structural factors contributing to the permeation enhancement of chitosan derivatives and for potential use in pulmonary applications.


Ginkgo biloba extracts EGb 761 and bilobalide increase NADH dehydrogenase mRNA level and mitochondrial respiratory control ratio in PC12 cells.
In the present study, we investigated the effect of Ginkgo biloba extract, EGb 761, and one of its components, bilobalide, on gene expression of subunit 1 of mitochondrial NADH dehydrogenase (ND1) in PC12 cells. By Northern blot analysis we found a approximately 2-fold significant increase in NDI mRNA level, after 48 and 72 h exposure to 100 microg/ml EGb 761 and to 10 microg/ml bilobalide. We also evaluated, by oxygraphy measurements, mitochondrial respiration during state 3 and state 4. In cells treated with EGb 761 and bilobalide for 48 and 72 h, state 4 respiration was significantly decreased, and the respiratory control ratio was increased. These results provide evidence that EGb 761 and bilobalide exert their protective effects by up-regulating mitochondrial ND1 gene expression and by decreasing state 4 respiration, whose increase is thought to be responsible for oxidative damage.


Sleep deprivation increases thalamocortical excitability in the somatomotor pathway, especially during seizure-prone sleep or awakening states in feline seizure models.
Pathological somatomotor system excitability and generalized seizures occur throughout the sleep-awake cycle but peak at different times in the amygdala kindling and systemic penicillin epilepsy models. Sleep loss increases seizure activity in both models during all waking and sleep states but does not alter the timing of seizure susceptibility in the sleep-wake cycle. Although the mechanism for sleep-deprivation seizures is unknown, we propose that sleep loss magnifies somatomotor system hyperexcitability patterns in all states, thereby increasing seizure vulnerability at all times but preferentially during seizure-prone intervals. To evaluate this hypothesis, the timing of ventral lateral thalamic and motor cortex excitability, indexed by amplitudes of primary evoked responses, was studied throughout the sleep-wake cycle in eight cats before and after nearly total sleep deprivation. Sleep loss was induced by 24-h exposure to a modified "flower pot" procedure; the control procedure consisted of 24-h exposure to a larger pedestal which did not affect sleep time. Findings confirmed the hypothesis, as follows: (i) Sleep deprivation increased ventral lateral thalamic and motor cortical excitability nonspecifically. (ii) Motor cortex hyperexcitability correlated best with penicillin seizure activity; both were elevated in slow-wave sleep and drowsiness after awakening from slow-wave sleep before sleep loss and were further increased by sleep loss. (iii) Ventral lateral thalamic hyperexcitability patterns correlated best with the timing of kindled seizure susceptibility; both peaked during transitions from slow-wave to REM sleep before and after sleep loss but were maximal after sleep loss. (iv) Sleep loss increased thalamocortical excitability and seizure susceptibility during stable REM sleep in both models, but values were lower than in other states. These results suggest a chronic neuropathology at different levels of the neuraxis for dissimilar epilepsy models and upon which the sleep-waking state modulation of seizures is superimposed. Sleep deprivation may aggravate seizures in both models by nonspecific enhancement of thalamic and cortical excitability.


Classification of hypertensive intracerebral hemorrhage by means of computed tomography.
This classification concerns the size and site of the intracerebral hematoma and the existence and degree of the intraventricular hemorrhage examined in 144 cases, with regard to the prognosis quod vitam et functionem.