Nucleic acid, protein, and protein-bound lysine and arginine patterns in epidermal nuclei of the mature and senescing onion bulb.
Eight macromolecular indices were determined for nuclei of outer epidermal cells in the equatorial plane from young through old leaf bases (sequential leaf senescence) and for nuclei in basal, equatorial and three apical locations within one leaf base (apical cell senescence). The eight nuclear indices were total nucleic acid. DNA, RNA, histone, non-histone, total protein, and protein-bound lysine and arginine. Cell senescence and death were accompanied by startling decreases in these eight indices. In sequential leaf senescence, nuclei in the second innermost turgid leaf base contained about four to five times the amount of nucleic acids and nuclear proteins in the youngest leaf base. The nuclei in the outermost leaf base contained about 20% less of the nucleic acids and proteins measured than the second outermost leaf base. We infer that this represents a decline in nuclear constituents due to senescence, since less than 30% of the cells in the innermost paperlike leaf base contained nuclei and those present were almost devoid of the nuclear constituents measured. Cell senescence in the apical section of a turgid leaf base showed sequential declines in all nuclear indices studied from areas composed of living cells to areas at the apex composed of dead cells. Possible changes in histone content due to physiological ages were detected in the equatorial but not in the vertical study; the protein-bound lysine to arginine ratios increased from younger to older leaf bases.


[The posteromedial brachioplasty].
Brachial dermo-lipectomy, which has been performed for several decades, became more frequent again with the advent of bariatric surgery. However, brachioplasty still raises the problem of its scars, necessary mostly in the longitudinal axis. Most of the described techniques are with a medial scar. The author's purpose is to show, with a five years follow-up, the reasons of its choice of a postero-medial scar: ease of installation of both arms in the same operative field, the better scar quality than in the medial localization and finally because it is comparatively the least visible under several incidences: not only anterior and posterior in abduction but also posterior in adduction.


Culturally sensitive continence care: a qualitative study among South Asian Indian women in Leicester.
Urinary incontinence is a significant health problem with potentially serious physical, psychological and social consequences. The true prevalence is difficult to ascertain, especially in hard to reach groups such as ethnic minority populations and research in this area is lacking. The UK has an increasingly diverse population, and ascertaining the needs for incontinence care among ethnic minority groups is crucial. This study aimed to explore views and experiences of incontinence and perceptions of care among South Asian Indian women in Leicester, UK. A qualitative focus group study involving four focus groups, each of six women, was undertaken. Focus groups were conducted in the participants' chosen language and facilitated by a bilingual moderator. Groups were tape-recorded, transcribed and analysed in a systematic and iterative way based on the constant comparative method. Women commonly normalized symptoms of urinary incontinence, attributing them to the ageing process or consequences of childbirth. Help-seeking behaviour was hindered not only by feelings of embarrassment in discussing sensitive problems, especially with male health professionals, but also the perceived embarrassment felt by doctors. Women reported a lack of available information in culturally sensitive media. Talk-based media were more highly valued than text-based media. Generational differences in help-seeking behaviour were apparent. This exploratory study provides valuable understanding of the continence needs of South Asian Indian women. Common needs were identified, as were important generational differences. Suggestions offered by women for the existing service improvement seemed relatively modest in terms of resources required.


Diet pattern and prodromal features of Parkinson disease.
To assess the relationship between diet pattern and prodromal Parkinson disease (PD) features. These analyses include 47,679 participants from the Nurses' Health Study and the Health Professionals Follow-up Study. Since 1986, both cohorts have collected dietary information every 4 years and calculated scores for adherence to different diet patterns, including the alternate Mediterranean diet (aMED) and the Alternative Healthy Eating Index (AHEI). In 2012, participants responded to questions regarding constipation and probable REM sleep behavior disorder. For a subset of 17,400 respondents to the 2012 questionnaire, 5 additional prodromal features of PD were assessed in 2014 to 2015. We used multinomial logistic regression to estimate the association between baseline (1986) diet pattern score quintiles and number of prodromal features (0, 1, 2, or ≥3) in 2012 to 2015. Additional analyses investigated the association between long-term adherence to these dietary patterns over 20 years and prodromal features suggestive of PD. In a comparison of extreme aMED diet quintiles, the odds ratio for ≥3 vs 0 features was 0.82 (95% confidence interval [CI] 0.68-1.00, false discovery rate [FDR]-adjusted p trend = 0.03) at baseline and 0.67 (95% CI 0.54-0.83, FDR-p trend < 0.001) for long-term diet; results were equally strong for the association with AHEI scores. Higher adherence to these diets was inversely associated with individual features, including constipation, excessive daytime sleepiness, and depression. The inverse association between these diet patterns and prodromal PD features is consistent with previous findings and suggests that adherence to a healthy diet may reduce the occurrence of nonmotor symptoms that often precede PD diagnosis.


Determining factors associated with inhaled therapy adherence on asthma and COPD: A systematic review and meta-analysis of the global literature.
Adherence to therapy has been reported worldwide as a major problem, and that is particularly relevant on inhaled therapy for Asthma and Chronic Obstructive Pulmonary Disease (COPD), considering its barriers and features. We reviewed the global literature reporting the main determinants for adherence on these patients. Searches were made using the Cochrane Library, MEDLINE, EMBASE and ISI Web of Science databases. Analytical, observational and epidemiological studies (cohort, case-control and cross-sectional studies) were included, reporting association between any type of determinant and the adherence for inhaler therapy on Asthma or COPD. Random-effects meta-analysis were used to summarise the numerical effect estimates. 47 studies were included, including a total of 54.765 participants. In meta-analyses, the significant determinants of adherence to inhaled therapy were: older age [RR = 1.07 (1.03-1.10); I2 = 94; p < 0.0001] good disease knowledge/literacy [RR = 1.37 (1.28-1.47); I2 = 14; p = 0.33]; obesity [RR = 1.30 (1.12-1.50); I2 = 0; p = 0.37]; good cognitive performance [RR = 1.28 (1.17-1.40); I2 = 0; p = 0.62]; higher income [RR = 1.63 (1.05-2.56); I2 = 0; p = 0.52]; being employed [RR = 0.87 (0.83-0.90); I2 = 0; p = 0.76] and using multiple drugs/inhalers [RR = 0.81 (0.79-0.84); I2 = 0; p = 0.80]. Overall, the strength of the underlying evidence was only low to moderate. Many determinants may be associated to patient's adherence, and personalised interventions should be taken in clinical practice to address it by gaining an understanding of their individual features.


Management of type 2 diabetes for prevention of cardiovascular disease. An expert opinion of the Italian Diabetes Society.
Type 2 diabetes mellitus is characterized by an increased risk of developing long-term cardiovascular complications. Several underlying mechanisms have been proposed for the diabetes-related increase in cardiovascular risk, i.e. chronic hyperglycemia, duration of the disease, drug-induced hypoglycemia, coexistence of multiple cardiovascular risk factors, etc. In the last few years, new pharmacological approaches capable of treating chronic hyperglycemia without increasing the risk of hypoglycemia have emerged for the treatment of diabetes. With data mainly obtained from randomized controlled trials recruiting patients with type 2 diabetes in secondary prevention of cardiovascular disease, some of these newer antihyperglycemic drugs have shown to significantly reduce the risk of cardiovascular disease. In addition, the combined control of traditional cardiovascular risk factors, e.g. dyslipidemia, hypertension, etc., has demonstrated to be effective in reducing the burden of cardiovascular diseases in patients with type 2 diabetes. In this document written by some experts of the Italian diabetes society (SID), we will focus our attention on oral antihyperglycemic agents for people with type 2 diabetes in primary or secondary prevention of cardiovascular disease, excluding for brevity the injection therapies for diabetes, such as insulin and glucagon-like peptide-1 receptor agonists.


The crosstalk between M1 macrophage polarization and energy metabolism disorder contributes to polystyrene nanoplastics-triggered testicular inflammation.
Ubiquitous microplastics have become a threat to animal and human health, due to their potential toxicity, persistent nature and consequent bioaccumulation. Supporting evidence elucidates that polystyrene nanoplastics (PS-NPs) can destroy blood-testis barrier integrity, thus causing testicular hypoplasia and impairment of spermatogenesis. Nevertheless, how PS-NPs modulate macrophage polarization-energy metabolism crosstalk has not been fully investigated in testicular tissue. Here, we observed that polystyrene PS-NPs exposure contributes to severe vacuolization in the seminiferous tubules, accompanied by apoptosis of testicular tissue and infiltration of M1 macrophages. Meanwhile, we found that PS-NPs could trigger the M1 polarization phenotype, which activated ROS-macrophage migration inhibitory factor (MIF)/NF-κB signaling that in turn induced apoptosis of GC2 cells in the GC2-macrophage cell coculture model. Simultaneously, we confirmed that PS-NPs exposure increased 3-phospho-D-glycerate, phosphoenolpyruvate and lactate concentrations, accompanied by decreased pyruvate and adenosine triphosphate (ATP) production, likely due to downregulated pyruvate kinase M2 (PKM2) dimer expression. In conclusion, the mechanism of PS-NPs-induced testicular inflammation can be mediated by promoting the infiltration of M1 macrophages, thereby resulting in an ROS burst and subsequent induction of energy metabolism disorders. The current study will provide new insights into PS-NPs-induced male reproductive toxicity and highlight the context-specific roles of testicular macrophages.


Symptomatic xanthogranuloma of the choroid plexus of the third ventricle. A new case with ultrastructural study.
The clinicopathological findings in a new case of a surgically removed, symptomatic xanthogranuloma of the third ventricle are reported. Ultrastructural study showed that the lining epithelium of the tumor was composed of typical leptomeningeal cells, and that transitional forms from leptomeningeal cells into xanthomatous cells were present in the underlying fibrous capsule. These findings support the hypothesis of a leptomeningeal origin of the foamy cells in the present case. The ten cases reported previously of symptomatic xanthogranuloma of the third ventricle are reviewed. We suggest that xanthogranulomas of the choroid plexus might represent a heterogenous entity arising from xanthomatous changes involving various types of cells.


Music and Medicine Come Together Over Pain in the Air Medical Transport Environment.
This study aimed to determine if noise-canceling headphones (NCHs) with music supersedes pain reduction of other hearing protection for patients transported by Guardian Air Transport via rotor or fixed wing aircraft from 2017 to 2019. We designed a randomized pilot study in which patients who received NCHs with or without music were compared with controls who received non-NCH hearing protection alone. Four hundred fifty-four adults 19 to 64 years of age and 36 pediatric patients 4 to 18 years old who received ≥ 1 dose of opioids were included. In the aggregate population, opioid use was reduced by 31% from 14.3 to 10.0 morphine milligram equivalent/h transport (P = .131) with music compared with controls. The mean total pain reduction in the aggregate population from -2.5 (standard deviation [SD] = 3.2) to -4.0 (SD = 2.9) was 1.6-fold more than controls compared with NCH and music (P = .008). This effect was most profound in the pediatric population where the mean total pain reduction with NCHs and music (-5.4, SD = 3.1) was 3.4-fold more than controls (-1.6, SD = 2.7, P = .021). Music may provide greater subjective pain relief when combined with NCHs in the air transport environment; further research is required.


Comparison of alkaline phosphatase isoenzymes determined by an inhibition method and by electrophoresis.
A chemical inhibition procedure suitable for the routine determination of alkaline phosphatase (AP) isoenzymes in serum has been adapted for use with a fast kinetic analyzer, System Olli 3000. The results of this procedure are compared with the electrophoretic separation of alkaline phosphatase isoenzymes. The comparison of the results obtained indicates that the AP-urea/AP ratio can be used to differentiate between patients with bone and liver disease and that it is possible to estimate the relative bone and liver isoenzyme activities from this ratio quickly using two simple equations.


Expression and activity of matrix metalloproteinase-2 and -9 in experimental granulation tissue.
The restoration of functional connective tissue is a major goal of the wound healing process which is probably affected by matrix-modifying enzymes. To evaluate the spatial and temporal expression of matrix metalloproteinases (MMP) MMP-2 and MMP-9 and to study the regulation of MMP-2 in wound healing, subcutaneously implanted viscose cellulose sponges in rats were used to induce granulation tissue formation for up to 3 months. MMP-2 mRNA expression was seen throughout the experiment and it was highest after 2 months. MMP-9 gene expression was low between days 8-21 and increased after 4 weeks of granulation tissue formation. Membrane-type 1 MMP (MT1-MMP) mRNA was upregulated early and tissue inhibitor 2 of MMP (TIMP-2) mRNA later during wound healing. In in situ hybridization the expression of MMP-2 mRNA was seen mostly in fibroblast-like cells and MMP-9 mRNA in macrophage-like cells. MMP-9 immunoreactivity was detected in the polymorphonuclear leukocytes and macrophage-like cells on days 3-8. MMP-9 proteolytic activity was observed only on days 3-8. The active form of the MMP-2 increased up to day 14, whereafter it remained at a constant level, whereas latent MMP-2 did not show any apparent changes during the experimental period. We conclude that MMP-2 is important during the prolonged remodelling phase, whereas the gelatinolytic activity of MMP-9 was demonstrated only in early wound healing, and the MMP-9 gene is upregulated when the granulation tissue matures.


[Intrapulpal temperature change during the setting reactions of various dental cements].
Mixing of certain types of dental materials may produce pulpal injury due to a series of chemical reactions giving way to an exothermic reaction. Three different dental cements; zinc phosphate, polycarboxilate and glass ionomer cements which may increase the intrapulpal temperature were investigated in the present study. The cements were mixed according to the manufacturers' instructions in one group, the liquid and powder ratios were increased by one portion in the other two groups. The intrapulpal temperature changed between 1.32-4.54 degrees C among the three test groups. The intrapulpal temperature rise was markedly influenced when the amount of powder and liquid ratios were changed.


Laparoscopic low anterior resection for rectal carcinoma: complications and management in 132 consecutive patients.
To analyze the clinical manifestations and risk factors of complications in laparoscopic low anterior resection (LAR) for rectal cancer patients. A series of 132 consecutive patients who received laparoscopic LAR for rectal cancer in our center were included. The etiology, diagnosis, treatment and prevention of rectal cancer were studied among the patients with surgery-related complications using both univariate and multivariate regression analysis. No conversion to open surgery was observed and 5 cases converted to hand-assisted laparoscopic operation. The overall morbidity rate was 20.5%. Complications occurred during the operation in 7 patients (5.3%), within 30 postoperative days in 24 patients (18.2%), and within 3 mo in 2 patients (1.5%). The most significant complications were anastomotic leakage (9.1%) and anastomotic hemorrhage (5.3%). Size and location of tumor, pathological staging and preoperative nutrition were significant factors associated with LAR complications, while gender, age and pathological type showed no relevance. Binary logistics regression showed that the size and location of tumor, and pathological staging were independent factors of laparoscopic LAR. All the complications were treated during their onset of clinical manifestations by interventional or conservative therapy. Anastomotic leakage is a major complication in laparoscopic LAR. The complications may be associated with tumor size and site, and pathological stage. Interventional therapies are of value in the management of laparoscopic LAR complications.


Development of metal-chelating inhibitors for the Class II fructose 1,6-bisphosphate (FBP) aldolase.
It has long been suggested that the essential and ubiquitous enzyme fructose 1,6-bisphosphate (FBP) aldolase could be a good drug target against bacteria and fungi, since lower organisms possess a metal-dependant (Class II) FBP aldolase, as opposed to higher organisms which possess a Schiff-base forming (Class I) FBP aldolase. We have tested the capacity of derivatives of the metal-chelating compound dipicolinic acid (DPA), as well a thiol-containing compound, to inhibit purified recombinant Class II FBP aldolases from Mycobacterium tuberculosis, Pseudomonas aeruginosa, Bacillus cereus, Bacillus anthracis, and from the Rice Blast causative agent Magnaporthe grisea. The aldolase from M. tuberculosis was the most sensitive to the metal-chelating inhibitors, with an IC(50) of 5.2 μM with 2,3-dimercaptopropanesulfonate (DMPS) and 28 μM with DPA. DMPS and the synthesized inhibitor 6-(phosphonomethyl)picolinic acid inhibited the enzyme in a time-dependent, competitive fashion, with second order rate constants of 273 and 270 M(-1) s(-1) respectively for the binding of these compounds to the M. tuberculosis aldolase's active site in the presence of the substrate FBP (K(M) 27.9 μM). The most potent first generation inhibitors were modeled into the active site of the M. tuberculosis aldolase structure, with results indicating that the metal chelators tested cannot bind the catalytic zinc in a bidentate fashion while it remains in its catalytic location, and that most enzyme-ligand interactions involve the phosphate binding pocket residues.


Hemoglobin-inulin conjugate as an oxygen carrying blood substitute.
Pyridoxylated hemoglobin was modified with the activated ester of inulin. From the oxygen equilibrium curve, this conjugate was estimated to have about fivefold oxygen carrying capacity compared with a free hemoglobin. The half disappearance time of this conjugate in the circulation of a rat was 21 hours in contrast to 3 hours of a free hemoglobin. The oncotic pressure and the viscosity can be adjusted nearly equal to those of whole blood. This conjugate can be concluded to have sufficient properties for use as a blood substitute.


Seroprevalence of SARS-CoV-2 in Brazil: A systematic review and meta-analysis.
To summarize the data on SARS-CoV-2 seroprevalence surveys conducted in Brazil before the introduction of vaccines METHODS: The authors conducted a systematic review and meta-analysis on the seroprevalence of SARS-CoV-2 infection in Brazil. The present review followed the PRISMA guidelines. The authors searched Medline, Embase, and LILACS databases for serologic surveys conducted in the Brazilian population, in the period from 01/10/2019 to 07/11/2021, without language restrictions. The authors included studies that presented data concerning SARS-CoV-2 antibodies seroprevalence in Brazil and had a sample size ≥50 individuals. Considering the expected heterogeneity between studies, all analyses were performed using the random effects model, and heterogeneity was assessed using the I2 statistic RESULTS: Of 586 publications identified in the initial searches, 54 were included in the review and meta-analysis, which contained the results of 135 surveys, with 336,620 participants. The estimated seroprevalence was 11.0%, ranging from 1.0% to 83.0%, with a substantial heterogeneity (I2 = 99.55%). In subgroup analyses, the authors observed that the prevalence of SARS-CoV-2 antibodies was 13.0% in blood donors, 9.0% in the population-based surveys, 13% in schoolchildren, and 11.0% in healthcare workers. Seroprevalence increases over time. Large differences were observed among the regions of the country. It was higher in the Northern region, decreasing towards the South. The present results may contribute to the analysis of the spread of SARS-CoV-2 infection in the Brazilian population before vaccination, one of the factors that may be influencing the clinical presentation of COVID-19 cases related to the new variants, as well as the effectiveness of the vaccination program.


Learning exceptions to the rule in human and model via hippocampal encoding.
Category learning helps us process the influx of information we experience daily. A common category structure is "rule-plus-exceptions," in which most items follow a general rule, but exceptions violate this rule. People are worse at learning to categorize exceptions than rule-following items, but improved exception categorization has been positively associated with hippocampal function. In light of model-based predictions that the nature of existing memories of related experiences impacts memory formation, here we use behavioural and computational modelling data to explore how learning sequence impacts performance in rule-plus-exception categorization. Our behavioural results indicate that exception categorization accuracy improves when exceptions are introduced later in learning, after exposure to rule-followers. To explore whether hippocampal learning systems also benefit from this manipulation, we simulate our task using a computational model of hippocampus. The model successful replicates our behavioural findings related to exception learning, and representational similarity analysis of the model's hidden layers suggests that model representations are impacted by trial sequence: delaying the introduction of an exception shifts its representation closer to its own category members. Our results provide novel computational evidence of how hippocampal learning systems can be targeted by learning sequence and bolster extant evidence of hippocampus's role in category learning.


Effect of neck extension on ultrasonographic optic nerve sheath diameter as a surrogate for intracranial pressure in patients undergoing palatoplasty: A prospective observational study.
Palatoplasty is performed with neck extension in patients with a cleft palate. The neck extension required for a better surgical view during palatoplasty can affect intracranial pressure. We evaluated the effect of neck extension on intracranial pressure by measuring the optic nerve sheath diameter using ultrasonography during palatoplasty. The optic nerve sheath diameter was measured in 30 patients at 10 min after anesthetic induction in the supine position (T1), at 10 min after neck extension before preparing for a sterile field (T2), at the end of surgery with neck extension (T3), and at 10 min after the supine position (T4). Hemodynamic and respiratory variables such as systolic blood pressure, heart rate, end-tidal carbon dioxide partial pressure, and peak airway pressure were also measured at the same time points. In comparison with the optic nerve sheath diameter measured at 10 min after anesthetic induction in the supine position (T1), the mean optic nerve sheath diameters were significantly increased at 10 min after neck extension before preparing for a sterile field (T2), at the end of surgery with neck extension (T3), and at 10 min after the supine position (T4; 4.19 ± 0.26, 5.20 ± 0.29, 4.38 ± 0.36, and 4.35 ± 0.30 mm, respectively). However, hemodynamic and respiratory variables were not significantly different at all time points. We found that the optic nerve sheath diameter, an indicator of intracranial pressure, was increased during palatoplasty with neck extension, which suggests that the position may affect the intracranial pressure of patients with a cleft palate.


Implant-friendly MRI of deep brain stimulation electrodes at 7 T.
The purpose of this study is to present a strategy to calculate the implant-friendly (IF) excitation modes-which mitigate the RF heating at the contacts of deep brain stimulation (DBS) electrodes-of multichannel RF coils at 7 T. An induced RF current on an implantable electrode generates a scattered magnetic field whose left-handed circularly polarizing component ( B 1 + $$ B{1}^{+} $$ ) is approximated using a B 1 + $$ B{1}^{+} $$ -mapping technique and subsequently used as a gauge for the electrode's induced current. Using this approach, the relative induced currents resulting from each channel of a multichannel RF coil on the DBS electrode were calculated. The IF modes of the corresponding multichannel coil were determined by calculating the null space of the relative induced currents. The proposed strategy was tested and validated for unilateral and bilateral commercial DBS electrodes (directional lead; Infinity DBS system, Abbott Laboratories) placed inside a uniform phantom by performing heating and imaging studies on a 7T MRI scanner using a 16-channel transceive RF coil. Neither individual IF modes nor shim solutions obtained from IF modes induced significant temperature increase when used for a high-power turbo spin-echo sequence. In contrast, shimming with the scanner's toolbox (i.e., based on per-channel B 1 + $$ B{1}^{+} $$ fields) resulted in a more than 2°C temperature increase for the same amount of input power. A strategy for calculating the IF modes of a multichannel RF coil is presented. This strategy was validated using a 16-channel RF coil at 7 T for unilateral and bilateral commercial DBS electrodes inside a uniform phantom.


Genomic profiling of exogenous abscisic acid-responsive microRNAs in tomato (Solanum lycopersicum).
Plant microRNAs (miRNAs) are involved in various biological pathways and stress responses as negative regulators at the posttranscriptional level. Abscisic acid (ABA) is a key signaling molecule that mediates plant stress response by activating many stress-related genes. Although some miRNAs in plants are previously identified to respond to ABA, a comprehensive profile of ABA-responsive miRNAs has not yet been elucidated. Here, we identified miRNAs responding to exogenous application of ABA, and their predicted target genes in the model plant organism tomato (Solanum lycopersicum). Deep sequencing of small RNAs from ABA-treated and untreated tomatoes revealed that miRNAs can be up- or down-regulated upon treatment with ABA. A total of 1067 miRNAs were detected (including 365 known and 702 candidate novel miRNAs), of those, 416 miRNAs which had an abundance over two TPM (transcripts per million) were selected for differential expression analysis. We identified 269 (180 known and 89 novel) miRNAs that respond to exogenous ABA treatment with a change in expression level of |log2FC|≥0.25. 136 of these miRNAs (90 known and 46 novel) were expressed at significantly different levels |log2FC|≥1 between treatments. Furthermore, stem-loop RT-PCR was applied to validate the RNA-seq data. Target prediction and analysis of the corresponding ABA-responsive transcriptome data uncovered that differentially expressed miRNAs are involved in condition stress and pathogen resistance, growth and development. Among them, approximately 90 miRNAs were predicted to target transcription factors and pathogen resistance genes. Some miRNAs had functional overlap in biotic and abiotic stress. Most of these miRNAs were down-regulated following exposure to exogenous ABA, while their related target genes were inversely up-regulated, which is consistent with their negative regulatory role in gene expression. Exogenous ABA application influences the composition and expression level of tomato miRNAs. ABA mainly down-regulates miRNAs that their target genes involve in abiotic stress adaption and disease resistance. ABA might increase expression of stress-related genes via miRNA-mediated posttranscriptional regulation, and our results indicate that ABA treatment has the potential to improve both abiotic stress tolerance and pathogen resistance. This study presents a comprehensive profile of ABA-regulated miRNAs in the tomato, and provides a robust database for further investigation of ABA regulatory mechanisms.


[Lymphocytic infiltrations in normal and pathological thyroid glands (so-called focal lymphocytic thyroiditis) (author's transl)].
A series of 1004 goitres removed surgically before (1959) and after (1970, 1975) the introduction of the iodine prophylaxis reveals an impressive increase in lymphocytic infiltration of the thyroid gland parenchyma. So-called focal lymphocytic thyroiditis is closely associated with the functional state of the organ. Furthermore, there is an increase in focal thyroiditis, especially in younger persons, after the introduction of iodine prophylaxis. Autoantibodies or clinical signs of inflammation were not found in these cases. Focal lymphocytic thyroiditis is seen as the expression of a regulatory function of the immunological system over the thyroid gland.


The Effects of Butyric Acid on the Differentiation, Proliferation, Apoptosis, and Autophagy of IPEC-J2 Cells.
Butyric acid (BT), a short-chain fatty acid, is the preferred colonocyte energy source. The effects of BT on the differentiation, proliferation, and apoptosis of small intestinal epithelial cells of piglets and its underlying mechanisms have not been fully elucidated. In this study, it was found that 0.2-0.4 mM BT promoted the differentiation of procine jejunal epithelial (IPEC-J2) cells. BT at 0.5 mM or higher concentrations significantly impaired cell viability in a dose- and time-dependent manner. In addition, BT at high concentrations inhibited the IPEC-J2 cell proliferation and induced cell cycle arrest in the G2/M phase. Our results demonstrated that BT triggered IPEC-J2 cell apoptosis via the caspase8-caspase3 pathway accompanied by excess reactive oxygen species (ROS) and TNF-α production. BT at high concentrations inhibited cell autophagy associated with increased lysosome formation. It was found that BT-reduced IPEC-J2 cell viability could be attenuated by p38 MAPK inhibitor SB202190. Moreover, SB202190 attenuated BT-increased p38 MAPK target DDIT3 mRNA level and V-ATPase mRNA level that were responsible for normal acidic lysosomes. In conclusion, 1) at 0.2-0.4 mM, BT promotes the differentiation of IPEC-J2 cells; 2) BT at 0.5 mM or higher concentrations induces cell apoptosis via the p38 MAPK pathway; 3) BT inhibits cells autophagy and promotes lysosome formation at high concentrations.


Self-disinfecting surfaces: review of current methodologies and future prospects.
Methods to improve disinfection of environmental surfaces in hospital rooms include improving cleaning/disinfection by environmental service workers through education and feedback on cleaning effectiveness (eg, use of fluorescent dyes), "no-touch" methods (eg, UV-C light), and self-disinfecting surfaces. Self-disinfecting surfaces can be created by impregnating or coating surfaces with heavy metals (eg, silver or copper), germicides (eg, triclosan), or miscellaneous methods (eg, light-activated antimicrobials). These methods are under active investigation but to date have not been assessed for their ability to reduce health care-associated infections.


Usefulness of antidepressants for improving the neuropathic pain-like state and pain-induced anxiety through actions at different brain sites.
Clinically, it is well known that chronic pain induces depression, anxiety, and a reduced quality of life. There have been many reports on the relationship between pain and emotion. We previously reported that chronic pain induced anxiety with changes in opioidergic function in the central nervous system. In this study, we evaluated the anxiolytic-like effects of several types of antidepressants under a chronic neuropathic pain-like state and searched for the brain site of action where antidepressants show anxiolytic or antinociceptive effects. Sciatic nerve-ligated mice exhibited thermal hyperalgesia and tactile allodynia from days 7 to 28 after nerve ligation. At 4 weeks after ligation, these mice showed a significant anxiety-related behavior in the light-dark test and the elevated plus-maze test. Under these conditions, repeated administration of antidepressants, including the tricyclic antidepressant (TCA) imipramine, the serotonin noradrenaline reuptake inhibitor (SNRI) milnacipran, and the selective serotonin reuptake inhibitor (SSRI) paroxetine, significantly prevented the anxiety-related behaviors induced by chronic neuropathic pain. These antidepressants also produced a significant reduction in thermal hyperalgesia and tactile allodynia. Moreover, the microinjection of paroxetine into the basolateral amygdala or cingulate cortex reduced anxiety-related behavior, and microinjection into the primary somatosensory cortex significantly attenuated thermal hyperalgesia. These findings suggest that serotonergic antidepressants are effective for treating anxiety associated with chronic neuropathic pain and may be useful for treating neuropathic pain with emotional dysfunction such as anxiety. Furthermore, SSRIs show anxiolytic and antinociceptive effects by acting on different brain regions.


Impact of endometrial scratching on reproductive outcome in patients: A systematic review and meta-analysis.
Endometrial scratching (ES) has demonstrated initial success in women with recurrent implantation failure, but the effect in women with 1 previous assisted reproductive technology (ART) failure is unknown. This meta-analysis aimed to evaluate the impact of ES as a treatment in clinical outcomes for women with at least 1 failed in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)/Intrauterine Insemination (IUI). PubMed, Medline, Embase, Cochrane Library, Web of Science, CNKI, and EMCC databases were searched for randomized controlled trial studies utilizing endometrial scratching for infertility women with at least 1 failed assisted reproductive technology (ART) to collect pregnancy outcomes, including clinical pregnancy rate (CPR), embryo implantation rate (IR), miscarriage rate (MR), live birth rate (LBR), and multiple pregnancy rate (MPR). Sixteen randomized controlled trial (RCT) studies were included in this meta-analysis, including 1770 women in the intervention group and 1934 women in the control group. Overall, the CPR, IR and LBR were significantly higher in the intervention group than in the control group (for CPR, n = 1430, 16 studies, P = .0002, risk ratio (RR) = 1.59, 95% confidence interval [CI] [1.24, 2.03]; for IR, n = 859, 10 studies, P = .0003, RR = 1.67, 95% CI [1.26, 2.21]; for LBR, n = 156, 6 studies, P = .0005, RR = 1.59, 95% CI [1.22, 2.06]). Nonetheless, there was no significant difference in MR (n = 344, 11 studies, P = .62, risk ratio (RR) = 0.92, 95% confidence interval [CI] [0.66, 1.29]) and MPR (n = 98, 3 studies, P = .39, risk ratio (RR) = 0.81, 95% confidence interval [CI] [0.51, 1.30]) between the intervention group and the control group. Endometrial scratching is considered to enhance the reproductive outcomes of embryo implantation. Additional randomized controlled studies are recommended to identify the appropriate time of invasion and the applicable population to confirm whether it can become a routine operation.


Social recognition in paired but not single male prairie voles.
Social recognition is an integral component of behavior that underlies many much larger behavioral suites. For example, monogamous pair bonding is relatively meaningless if an individual cannot recall with whom the bond was with. Prairie voles (Microtus ochrogaster) are a socially monogamous rodent, well known for their long-term pair bonds between males and females. Although previous work has shown that bonded males reliably spend more time with their pair-mate over an unfamiliar female, recent work has demonstrated that single male prairie voles do not discriminate between females. This discrepancy raises the important question: do paired males distinguish between non-mate females? We asked whether pair bonding alters the expression of social recognition in male voles by comparing social recognition of single and pair bonded males using the habituation/dishabituation paradigm. We found that pair bonded, but not single male prairie voles exhibit social recognition of (non-mate) females, suggesting a shift in cognitive behavior after pair bond formation. This difference is not due to differences in motivation to engage in social exchanges, as males attempted to contact unfamiliar females at similar levels. Based on these data, we speculate that the stage of life (single or bonded) influences the relevance of attending to social information of same- and opposite-sex conspecifics.


EBS7 is a plant-specific component of a highly conserved endoplasmic reticulum-associated degradation system in Arabidopsis.
Endoplasmic reticulum (ER)-associated degradation (ERAD) is an essential part of an ER-localized protein quality-control system for eliminating terminally misfolded proteins. Recent studies have demonstrated that the ERAD machinery is conserved among yeast, animals, and plants; however, it remains unknown if the plant ERAD system involves plant-specific components. Here we report that the Arabidopsis ethyl methanesulfonate-mutagenized brassinosteroid-insensitive 1 suppressor 7 (EBS7) gene encodes an ER membrane-localized ERAD component that is highly conserved in land plants. Loss-of-function ebs7 mutations prevent ERAD of brassinosteroid insensitive 1-9 (bri1-9) and bri1-5, two ER-retained mutant variants of the cell-surface receptor for brassinosteroids (BRs). As a result, the two mutant receptors accumulate in the ER and consequently leak to the plasma membrane, resulting in the restoration of BR sensitivity and phenotypic suppression of the bri1-9 and bri1-5 mutants. EBS7 accumulates under ER stress, and its mutations lead to hypersensitivity to ER and salt stresses. EBS7 interacts with the ER membrane-anchored ubiquitin ligase Arabidopsis thaliana HMG-CoA reductase degradation 1a (AtHrd1a), one of the central components of the Arabidopsis ERAD machinery, and an ebs7 mutation destabilizes AtHrd1a to reduce polyubiquitination of bri1-9. Taken together, our results uncover a plant-specific component of a plant ERAD pathway and also suggest its likely biochemical function.


Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial.
Understanding pharmacokinetics (PK) and pharmacodynamics (PD) of the sustained-release liothyronine (SR-T3) is of paramount importance to design therapeutic regimens that are able to simulate normal thyroid hormone secretion while avoiding excursions in the T3 serum concentration. Here, we designed a parallel randomized clinical trial to characterize the PK and PD of the combined preparations of LT4 + SR-T3 in hypothyroid patients. Radioiodine-treated hypothyroid patients over 20 years of age, who attained euthyroidism with LT4 monotherapy were recruited from the Endocrine Clinic in Tehran. The patients were allocated to two intervention groups of group A: 9 µg SR-T3 plus 68.5 μg LT4 (ratio 1:7.5) and group B: 12 µg SR-T3 plus 60 µg LT4 (ratio 1:5), and a control group with LT4 monotherapy. For PD study, thyroid hormone profile was evaluated at 8 and 12 weeks intervals after intervention. To assess PK properties of SR-T3, T3-Cmax, T3-Tmax and AUC0 - 24 were calculated at the last visit. Serum T4 and FT4 concentrations decreased in the intervention groups after 3 months. No significant difference was observed in serum T3 and FT3 concentrations before and after intervention. Serum T3/T4 ratio increased significantly in the intervention groups after intervention, with the highest increase in group B from 8.6 ± 2.03 at baseline to 12.2 ± 1.6. Comparison of trial groups at follow-up showed no differences in serum TSH, T4, T3 and T3/T4 concentrations among different groups. During 24 h, minimal variation in serum T3 concentration was observed in group B with mean ∆T3 of 15.4 ± 10.5 ng/dl. T3-Tmax, T3-Cmax and AUC0 - 24 in the combined sustained-release preparation were 4.38 ± 1.1 h., 101.0 ± 5.7 ng/dl and 2257 ± 110 ng.h/L, respectively which were significantly different from the control group. Combined treatment with a single dose of SR-T3 plus LT4 is associated with increased serum T3/T4 ratio and minimal excursions in serum T3 concentration during 24 h; however, it was not significantly different from the control group. To incorporate sustained-release T3 in the management of hypothyroidism, a higher ratio of SR-T3 to LT4 than that of the previously recommended by the international organizations is suggested. IRCT20100922004794N13. https://www.irct.ir/search/result?query=IRCT20100922004794N13 . Registration date: 08/12/2021.


Benznidazole biotransformation in rat heart microsomal fraction without observable ultrastructural alterations: comparison to Nifurtimox-induced cardiac effects.
Benznidazole (Bz) and Nifurtimox (Nfx) have been used to treat Chagas disease. As recent studies have de-monstrated cardiotoxic effects of Nfx, we attempted to determine whether Bz behaves similarly. Bz reached the heart tissue of male rats after intragastric administration. No cytosolic Bz nitroreductases were detected, although microsomal NADPH-dependent Bz nitroreductase activity was observed, and appeared to be mediated by P450 reductase. No ultrastructurally observable deleterious effects of Bz were detected, in contrast to the overt cardiac effects previously reported for Nfx. In conclusion, when these drugs are used in chagasic patients, Bz may pose a lesser risk to heart function than Nfx when any cardiopathy is present.


Predictors of complications associated with unerupted maxillary canines: a cone beam computed tomography study.
To detect predictive factors for the occurrence of complications associated with unerupted maxillary canines (C). A total of 83 cone beam computed tomograms (CBCT), made from November 1, 2021 to October 31, 2022, have met the inclusion criteria, whereby 110 unerupted C were detected. Independent variables were: gender, age, and C position. Outcome variables were detected complications: external root resorption (ERR) and dilaceration of adjacent tooth, ERR and dilaceration of C, dentigerous cyst, canine ankylosis, and adjacent teeth malposition. Chi-square test and logistic regression analysis were used to examine the relationship between income variables and detected complications. Vertical position of unerupted C showed as predictor for adjacent tooth dilacerations and malposition. Chance for dilaceration increases 5.5-fold with C position at the middle third of lateral incisor (LI) root, while chance of malposition increases 23.4-fold with its supra-apical position to the LI root, in comparison to the C position occlusal to the LI cemento-enamel junction. Age is a predictive factor for dentigerous cysts, with decreasing the chance of their occurrence 1.5-fold with each additional year of age. Early evaluation of the vertical position and timely treatment of C are decisive steps in preventing complications.


A gathering of minds: expanding understanding of the origins of biological diversity and the evolution of developmental mechanisms.
This paper is a short report on the 2012 Society of Integrative and Comparative Biology Annual Meeting. Charleston, South Carolina, USA. 3-7 January 2012 (abstracts freely available at http://www.sicb.org/meetings/2012/).


Synthesis and antiproliferative activity of a cyclic analog of dolastatin 10.
A cyclic analog of the natural antiproliferative compound dolastatin 10 was synthesized by introducing an ester link between the N- and C-terminal residues which were modified accordingly. The final macrolactonization was performed by using isopropenyl chloroformate and DMAP as reagents. This analog exhibits submicromolar antiproliferative activity against the L1210 and HT29 cell lines and inhibits in vitro tubulin polymerization (IC50, 39 microM).


[Intrathecal synthesis of the anti-Hu antibody in patients with paraneoplastic encephalomyelitis or sensory neuronopathy].
To probe into the pathogenic mechanisms of paraneoplastic encephalomyelitis (PEM) or sensory neuronopathy(PSN). The serum and cerebral spinal fluid(CSF) anti-Hu antibodies and titers in 16 patients with PEM and 14 patients with PSN were detected with indirect immunohistochemistry (ABC) method. Intrathecal IgG synthesis and antibody specific activity (ASA) were calculated with Schuller's formulas according to the titers of the anti-Hu antibodies in the serum and CSF of the patients. Anti-Hu antibodies were identified by detecting the antigens of the nuclear extracts from the human cerebral cortex neurons with Western blot analysis. IgG in the serum and CSF and the albumin in the CSF were tested with electroimmunodiffusion method. The serum and CSF anti-Hu antibody titers in patients with PEM were significantly higher than those in patients with PSN (P < 0.001). A ratio of intrathecal ASA/serum ASA of anti-Hu antibody > 2 in 14 (88%) of the 16 patients with PEM and one (7%) patient with PSN indicated that the patients with PEM had a positive intrathecal anti-Hu antibody synthesis (P < 0.001). The Rankin scores are 4.5 +/- 1.7 in patients with PEM and 3.0 +/- 1.4 in patients with PSN (P < 0.01). Patients with PEM were more disabled than those with PSN. The detection of intrathecal ASA/serum ASA ratio for identifying the anti-Hu antibody intrathecal synthesis is valuable in judging the severity of disease and prognosis in patients with paraneoplastic syndromes of nervous system.


Uranium removal from aqueous solution using macauba endocarp-derived biochar: Effect of physical activation.
The main aim of this study was to evaluate options for addressing two pressing challenges related to environmental quality and circular economy stemming from wastage or underutilization of abundant biomass residue resources and contamination of water by industrial effluents. In this study we focused on residues (endocarp) from Macaúba palm (Acrocomia aculeata) used for oil production, its conversion to activated biochar, and its potential use in uranium (U) removal from aqueous solutions. Batch adsorption experiments showed a much higher uranyl ions (U(VI)) removal efficiency of activated biochar compared to untreated biochar. As a result of activation, an increase in removal efficiency from 80.5% (untreated biochar) to 99.2% (after activation) was observed for a 5 mg L-1 initial U(VI) concentration solution adjusted to pH 3 using a 10 g L-1 adsorbent dosage. The BET surface area increased from 0.83 to 643 m2 g-1 with activation. Surface topography of the activated biochar showed a very characteristic morphology with high porosity. Activation significantly affected chemical surface of the biochar. FTIR analysis indicated that U(VI) was removed by physisorption from the aqueous solution. The adsorbed U(VI) was detected by micro X-ray fluorescence technique. Adsorption isotherms were employed to represent the results of the U adsorption onto the activated biochar. An estimation of the best fit was performed by calculating different deviation equations, also called error functions. The Redlich-Peterson isotherm model was the most appropriate for fitting the experimental data, suggesting heterogeneity of adsorption sites with different affinities for uranium setting up as a hybrid adsorption. These results demonstrated that physical activation significantly increases the adsorption capacity of macauba endocarp-derived biochar for uranium in aqueous solutions, and therefore open up a potential new application for this type of waste-derived biochar.


Telemedicine in Hematopoietic Cell Transplantation and Chimeric Antigen Receptor-T Cell Therapy.
Telemedicine has played an important role in delivering healthcare for primary care, chronic disease patients, and those with solid organ malignancies. However, its application in subspecialties such as hematologic malignancies, hematopoietic cell transplantation (HCT), or chimeric antigen receptor-T cell (CAR-T) therapy is not widespread since physical examination is a vital component in delivering care. During the COVID-19 pandemic, we widely used telemedicine, since protecting our immunocompromised patients became our top priority. The employment of HCT and CAR-T therapies continues to grow for high-risk hematologic malignancies, particularly in older and frail patients who must visit specialty centers for treatment access. Generally, HCT and CAR-T therapy care is highly complex, necessitating commitment from patients, caregivers, and a multidisciplinary team at specialty academic centers. All healthcare systems adapted to the crisis and implemented rapid changes during the COVID-19 public health emergency (PHE). Telemedicine, a vital modality for delivering healthcare in underserved areas, experienced rapid expansion, regardless of the geographic region, during the COVID-19 PHE. The data emerging from practices implemented during the PHE are propelling the field of telemedicine forward, particularly for specialties with complex medical treatments such as HCT and CAR-T therapy. In this review, we examine the current data on telemedicine in HCT and cellular therapy care models for the acute and long-term care of our patients.


Ectopia lentis: management by combined lensectomy and vitrectomy.
A technique is presented for removal of subluxated or dislocated lenses (ectopia lentis), along with performance of vitrectomy. It is believed that this method permits avoidance or reduction of the hazards and complications of techniques used in the past.


Initial experience with transanal proctectomy in children.
The use of transanal proctectomy may have particular advantages for pediatric patients with small pelvic working space. We report short-term outcomes of transanal completion proctectomy (taCP) during surgery for inflammatory bowel disease. All patients (age≤19) underwent taCP from January 1, 2018 to December 31, 2019. Prior total abdominal colectomy (TAC) was performed using a single-incision technique. At operation, patients underwent single-incision laparoscopy with taCP. Patient demographics, pre and perioperative details, and postoperative complications were abstracted. Seven patients (n = 6) with a median age of 18 years [Range: 13-19] were included in this initial series. All patients had a prior TAC with end-ileostomy with taCP occurring a median of 6 [Range: 3-89] months after TAC. Six of 7 had a diagnosis of ulcerative colitis (UC) while 1 patient had Crohn's colitis. For patients with UC, taCP was part of an ileal pouch-anal anastomosis with the majority (n = 4) proceeding as a modified-two stage and the remaining (n = 2) a three-stage approach. Single-incision laparoscopy through the prior ileostomy site was used in all IPAA patients. Median operative time was 226 [Range: 150-264] minutes with no conversions to more invasive technique. Median hospital length of stay (LOS) was 5 [Range: 2-8] days. In-hospital complications occurred in two patients who had watery diarrhea that prolonged LOS but resolved postdischarge. One patient was readmitted for bowel obstruction that resolved with placement of red rubber catheter at the ileostomy site. Of the 4 patients with a functioning ileal pouch, 1 patient reported 6-10 bowel movements per day, while 3 others reported ≤5 bowel movements per day. Half (n = 2) reported 1-2 nocturnal bowel movements at their first postoperative visit. No patients reported soiling or leakage, though one patient had a single episode of incontinence. In this pilot series, transanal proctectomy was effective and safe. Future work should compare traditional MIS completion proctectomy to taCP for applications in pediatric inflammatory bowel disease. Case series. IV.


Approach for ochratoxin A fast screening in spices using clean-up tandem immunoassay columns with confirmation by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS).
An approach for ochratoxin A (OTA) fast cost-effective screening based on clean-up tandem immunoassay columns was developed and optimized for OTA detection with a cut-off level of 10 microg kg(-1) in spices. Two procedures were tested and applied for OTA detection. Column with bottom detection immunolayer was optimized for OTA determination in Capsicum ssp. spices. A modified clean-up tandem immunoassay procedure with top detection immunolayer was successfully applied for all tested spices. Its main advantages were decreasing of the number of analysis steps and quantity of antibody and also minimizing of matrix effects. The total duration of the extraction and analysis was about 40 min for six samples. Chilli, red pepper, pili-pili, cayenne, paprika, nutmeg, ginger, white pepper and black pepper samples were analyzed for OTA contamination by the proposed clean-up tandem immunoassay procedures. Clean-up tandem immunoassay results were confirmed by HPLC-MS/MS with immunoaffinity column clean-up. Among 17 tested Capsicum ssp. spices, 6 samples (35%) contained OTA in a concentration exceeding the 10 microg kg(-1) limit discussed by the European Commission. All tested nutmeg (n=8), ginger (n=5), white pepper (n=7) and black pepper (n=6) samples did not contain OTA above this action level.


Apheresis and COVID-19 in intensive care unit (ICU).
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, and on March 2020 the World Health Organization (WHO) declared it as pandemic, causing a public health crisis. Symptoms of COVID-19 are variable, ranging from mild symptoms like fever, cough, and fatigue to severe illness. Elderly patients and those with comorbidities like cardiovascular disease, diabetes, chronic respiratory disease, or cancer are more likely to develop severe forms of the disease. Asymptomatic infections have been well documented. Accumulating evidence suggests that the severity of COVID-19 is due to high levels of circulating inflammatory mediators including cytokines and chemokines leading to cytokine storm syndrome (CSS). Patients are admitted in ICU with severe respiratory failure, but can also develop acute renal failure and multi organ failure. Advances in science and technology have permitted the development of more sophisticated therapies such as extracorporeal organ support (ECOS) therapies that includes renal replacement therapies (RRTs), venoarterial (VA) or veno-venous (VV) extracorporeal membrane Oxygenation (ECMO), extracorporeal CO2 removal (ECCO2R), liver support systems, hemoperfusion, and various blood purification devices, for the treatment of ARDS and septic shock.


Drug discrimination and generalization in pigeons.
In a three-key operant conditioning situation six pigeons were trained to select the response key which was associated with each of three drug treatment conditions: d-amphetamine (2 mg/kg), pentobarbital (5 mg/kg), and saline. Thus, the drug state served as a discriminative stimulus for food reinforcement. After 20 sessions of discrimination training in each of the three conditions, more than 90% of the responses were correctly emitted in the presence of the appropriate drug or saline stimulus. Acquisition of the discrimination progressed at approximately equal rates for the three treatments. Subsequent to discrimination training, generalization gradients were obtained for several doses of the training drugs and for dose ranges of cocaine, morphine, and methocarbamol. The pigeons responded to morphine by choosing the key paired with pentobarbital during training; further, cocaine administration resulted in choice of the amphetamine key. However, metocarbamol, over the doses used, produced responding more characteristic of saline than of the other training drugs. The data suggest that a three-key operant discrimination procedure using pigeons provides a sensitive method for investigating the stimulus properties of relatively low doses of behaviorally relevant drugs.


Comparative study of the anatomy, CT and MR images of the lateral collateral ligaments of the ankle joint.
Clinical diagnosis of lateral collateral ligamentous injury caused by ankle sprains depends primarily on clinical signs, and X-ray and CT images. None of these, however, provide direct or accurate information about ligamentous injury. MRI has long been testified as a useful tool in the demonstration of ligaments due to its good resolution of soft tissues. We confirmed the appearance of the lateral collateral ligaments of the ankle joints on MR images by comparing MR images with CT images of the ligaments enhanced by coating with contrast medium after dissection of six cadaver feet. Compare study of MR images reveals no difference in the natural position and the dorsal position (P > 0.05), whereas, taken into the consideration the long hour of MRI examination, the natural position is regarded as the optimal position for MRI performance. Measured on transverse MR images, lateral ligaments of acutely injured ankles were significantly thicker than those of normal ankles (P < 0.01). According to the MR images of normal and injured ankles, the lateral collateral ligaments injuries were classified as type I and type II. Osteal contusion, cartilaginous injury, musculotendinous injury, tenosynovitis, and peritenosynovitis were also observed by MRI in type I and type II acute lateral collateral ligament injury. All these complications have higher incidence in type II than in type I injury (P < 0.05). Thus, by comparing with the CT images and the anatomy we confirmed the normal appearance of the lateral collateral ligaments on MR images and figured out that the natural position is the optimal position for MRI performance. The thickness of the ligaments and incidence of the complications could be regarded as useful cue for the assistant in clinical diagnosis of the lateral collateral ligament injury.


Cellular Adaptation Relies on Regulatory Proteins Having Episodic Memory: Proteins Modulate Cell Metabolism and Reproduction by Remembering, Transmitting, and Using Data on the Environment.
The ability to memorize changes in the environment is present at all biological levels, from social groups and individuals, down to single cells. Trans-generational memory is embedded subcellularly through genetic and epigenetic mechanisms. Evidence that cells process and remember features of the immediate environment using protein sensors is reviewed. It is argued that this mnemonic ability is encapsulated within the protein conformational space and lasts throughout its lifetime, which can overlap with the lifespan of the organism. Means to determine diachronic changes in protein activity are presented.


Thermo-mechanical analysis of a compliant poly(carbonate-urea)urethane after exposure to hydrolytic, oxidative, peroxidative and biological solutions.
To date, there is still a great need for a fully viable small diameter (< 6 mm) polymeric vascular graft. Currently in such low flow locations, non-elastic expanded polytetrafluoroethylene (ePTFE) is the best available but it is quite inferior to autologous saphenous vein since it fails due to intimal hyperplasia caused by compliance mismatch between the graft and elastic host artery. Recently, a novel compliant poly(carbonate-urea)urethane vascular graft whose trade name is MyoLink has been developed. In this article, we report the findings of a thermo-mechanical analysis of the polymers chemistry postexposure to in vitro solutions comprised of hydrolytic, oxidative, peroxidative and biological media. The following degradative solutions were used in vitro: plasma fractions I-IV; phospholipase A2 (PLA); cholesterol esterase (CE) and solutions of H2O2/CoCl2, t-butyl peroxide/CoCl2 (t-but/CoCl2) and glutathione/t-butyl peroxide/ CoCl2 (glut/t-but/CoCl2). The MyoLink graft was compared against a conventional poly(ether)urethane (Pulse-Tec). All the graft specimens were 100 mm in length (5.0 mm ID) and were incubated in the latter solutions at 37 degrees C for 70 days in total. The following thermo-mechanical methods were used to analyse both graft types: thermo-mechanical analysis (TMA) and dynamic mechanical thermal analysis (DMTA). Incubation of Pulse-Tec in plasma fractions I-IV, PLA and CE reveals only one observable modification: an increase in the size of the low temperature, melting phase. But incubation in H2O2/CoCl2, and t-but/CoCl2 leads to an increase in the polymeric phase separation coupled with an enlargement in the size of the low temperature melting crystalline phase in Pulse-Tec. The glut/t-but/CoCl2 solution leads to a phase separation between the hard and soft segment domains, coupled with an increase of the internal order within the hard segment domains in Pulse-Tec. The only system in which MyoLink degraded was glut/t-but/CoCl2. In this system, an increase of the phase separation coupled with a simultaneous increase of the crystal size of the low-temperature melting crystalline phase occurred. This study shows dramatic changes in the chemistry of the soft and hard segments occurred in the case of the conventional poly(ether)urethane Pulse-Tec graft material. Such changes were not manifested in the majority of solutions in the case of MyoLink but a hydrolytic-led degradation of the carbonate soft segment was evidenced only in the glut/t-but/CoCl2 system.


Relative contribution of different receptor subtypes in the response of neuroblastoma cells to tumor necrosis factor-alpha.
The effect of tumor necrosis factor-alpha (TNF-alpha) on neuronal viability has been investigated in the SK-N-BE neuroblastoma cell line. These cells undergo differentiation upon chronic treatment with retinoic acid. Exposure of SK-N-BE cells to TNF-alpha produced a proliferative response in undifferentiated cells, whereas a reduced cell number was observed in retinoic acid (RA)-differentiated cultures. This biphasic response may be related to the different expression of TNF-alpha receptors (TNFRs); a significant increase in the density of TNFR1 was in fact observed following RA-induced differentiation. Under these conditions, a pronounced increase in the formation of ceramide-1-phosphate (which was prevented by the selective inhibitor of phosphatidylcholine-specific phospholipase C, D609) and an activation of caspase-3 upon TNF-alpha challenge were evident. Selective blockade of each TNFR subtype allowed a more detailed analysis of the effect observed. Preincubation with an anti-TNFR1 antibody prevented the cytotoxic effect of TNF-alpha in RA-differentiated SK-N-BE cells, whereas the anti-TNFR2 antibody blocked the proliferative activity of the cytokine in undifferentiated cultures.


Pharmaceutical heroin for inhalation: thermal analysis and recovery experiments after volatilisation.
Pharmaceutical heroin for inhalation was developed for a clinical trial on co-prescription of heroin and methadone to chronic treatment-resistant heroin addicts. Diacetylmorphine base was selected as the active pharmaceutical ingredient for this product with caffeine anhydrate added as an excipient. Differential scanning calorimetry and thermogravimetric analysis showed that addition of caffeine resulted in a lower melting temperature and a higher volatilisation rate for the mixture than for diacetylmorphine base alone. Recovery experiments showed that 40.8+/-5.3% of diacetylmorphine base could be found in smoke condensate after volatilisation of diacetylmorphine-caffeine tablets. All of the caffeine from each tablet was recovered unchanged in the fumes, while 85.6% of the diacetylmorphine from each tablet was recovered, either unchanged in the fumes or as non-volatilised residue. Recovery was found to be reproducible and only small differences were found between the tablet types. The experimental set-up was found to efficiently collect the vapours resulting from heating the powder. Under the tested experimental conditions, no evidence was found that degradation products of diacetylmorphine or caffeine, other than 6-acetylmorphine (5.9%) had volatilised, even though a decomposed residue was present after heating diacetylmorphine-caffeine samples. Diacetylmorphine-caffeine was found to be a suitable basis for pharmaceutical heroin to be used by 'chasing the dragon'.


Differentiation therapy of hepatocellular carcinoma by inhibiting the activity of AKT/GSK-3β/β-catenin axis and TGF-β induced EMT with sophocarpine.
Hepatocellular carcinoma progression is thought to be driven by cancer stem cells (CSCs). No clinical trial has, as yet, shown convincing long-term disease free survival results for the majority of patients in HCC. So it is important to discover new anti-cancer agents. In our study, we chose sophocarpine, which is derived from the foxtail-like sophora herb, for its efficacy to inhibit HCC including CSCs and potential mechanism study. Our results show that sophocarpine could not only reduce HCC cell viability, eliminate HCC and reverse hepatoma cells malignant phenotype, but also reduce the ratio of CSCs and inhibit the sphere formation of CSCs in vitro. In vivo, sophocarpine significantly displayed antitumor effects in subcutaneous xenograft HCC models and orthotopic transplantation tumor models. Further studies showed that sophocarpine could exert anti-tumor effects partly via downregulating the activity of the cancer stem cell related pathways and inhibiting EMT induced by TGF-β.


Margin status, local recurrence, and survival: correlation or causation?
The relationship between surgical margin status and outcomes in sarcoma has been an area of controversy for years. Some question whether a positive margin represents inadequate surgery or perhaps is a marker of aggressive cancer biology. This article reviews the literature regarding the natural history of positive margins and its possible influence on sarcoma recurrence and survival.


Clinical presentation and airway management of tracheal atresia: A systematic review.
Tracheal atresia (TA) is a rare congenital condition that typically requires an unexpected and emergent resuscitation in the delivery room. The mortality rate associated is very high, with only a few long-term survival cases reported. We describe the findings of a systematic review on the clinical presentation and airway management of TA. Using the keywords "tracheal atresia", "tracheal agenesis" and "tracheal hypoplasia" a search through Embase and Pubmed databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Articles published from 1950 to 2015 in English, French, Italian, Portuguese and Spanish were included. Exclusion criteria were cases of stillborn, and unclear diagnosis or outcome. 149 cases of TA were identified after reviewing 1125 initial references. There was a male preponderance (65%), and associated malformations were described in 94.2% of patients. Prenatal ultrasound was abnormal in 56.3% of cases, with polyhydramnios being the most common finding. The most frequent type of TA was Faro Type C. 94 (41.3%) patients did not survive beyond the first 24 h of life. Only 13 (8.4%) patients survived more than three months of life, after undergoing a variety of surgical approaches. This review, which to our knowledge is the largest one to date, confirms that TA is a rare malformation, occurs more frequently in males, and has a very high mortality rate. Depending on the presence and type of concomitant malformation, as well of the length of the remaining trachea, different surgical management options are described.


Transcriptional regulation of human corticotropin releasing factor gene expression by cyclic adenosine 3',5'-monophosphate: differential effects at proximal and distal promoter elements.
cAMP participates in the regulation of endogenous hypothalamic and placental CRF by increasing levels of both peptide secretion and mRNA expression. In previous studies we have shown that stimulation of the protein kinase A-dependent pathway by cAMP analogues or forskolin produced a dose-dependent increase in levels of CRF mRNA when the intact hCRF gene was stably transfected and expressed in the mouse corticotroph AtT20 cell line. In the present study, we explored the mechanism of the cAMP-dependent increase in CRF gene expression in the stably transfected AtT20 cell line using pharmacologic, slot-blot, and RNase mapping methodologies. Following incubation with cAMP, there was a rapid increase in CRF mRNA which was completely blocked by pre-treatment with actinomycin D, an inhibitor of transcription. Cycloheximide, an inhibitor of protein synthesis, produced an independent increase in CRF mRNA, but did not change the relative induction of CRF mRNA produced by cAMP. Solution hybridization studies using intron- and exon-specific hCRF probes demonstrated a rapid rise in nuclear CRF hnRNA, which was apparent within 15 min of cAMP incubation and preceded the rise in cytoplasmic CRF mRNA. RNase mapping studies demonstrated that CRF transcription was initiated at discrete promoter sites in CRF-AtT20 cells, and that this pattern of promoter utilization was similar to that observed in mRNA derived from sites of endogenous CRF expression, human placenta and human hepatoma NPLC cell line. Treatment with cAMP selectively increased CRF mRNA transcripts initiated at the proximal promoter site, but had little or no effect on transcripts initiated at the distal promoters. We conclude that cAMP effects on CRF gene expression occur rapidly, do not require new protein synthesis, and are initiated within the nuclear compartment, consistent with a direct effect on CRF gene transcription. This effect is mediated predominantly through the proximal promoter element, while more distal promoters are less sensitive to transcriptional activation by cAMP.


Spectrum of incipient (or precursor) lesions in the mucosa of the seminal vesicles.
The seminal vesicle (SV) mucosa can show epithelial and stromal tumors. The epithelial tumors include both cystadenoma and carcinomas, adenocarcinoma being the most common. Squamous carcinoma may arise in the SV (1). Rarely mixed epithelial and stromal tumors (MESTs) can occur. Incipient lesions, i.e., primary precursor or preinvasive lesions giving rise to such tumors in the mucosa of the SVs, have been observed in anecdotal cases.


Simultaneous spectrophotometric determination of iron, nickel and cobalt in micellar media by using direct orthogonal signal correction-partial least squares method.
A very simple and selective spectrophotometric method for simultaneous determination of iron(II), nickel(II) and cobalt(II) based on formation of their complexes with 1-(2-pyridylazo)-2-naphtol (PAN) in micellar media is described. Although the complexes of Fe(II), Ni(II) and Co(II) with reagent show a spectral overlap, they have been simultaneously determined by partial least squares (PLS) with and without preprocessing step using direct orthogonal signal correction (DOSC). The linear range was 0.30-4.50 microg ml(-1) for Co(II), 0.20-3.00 microg ml(-1) for Ni(II) and 0.30-5.00 microg ml(-1) for Fe(II). The results obtained by the PLS and DOSC-PLS were statistically compared. Interference effects of common anions and cations were studied and the proposed method was also applied satisfactorily to the determination of Fe(II), Ni(II) and Co(II) in synthetic samples.


Dynamic Stabilization of the Lumbar Spine using the Dynesys® System.
To present the clinical results in patients with minor instability with Dynesys® a soft spinal stabilization system. A total of 83 patients were operated upon and the Dynesys® system was applied. Indications for surgery included painful degenerative disc disease, degenerative spondylolisthesis and lumbar canal stenosis. The results for the Dynesys® system were satisfactory, and we have calculated the overall complication rate to be 20.4% (n=17), which is in agreement with the literature. The Dynesys® dynamic stabilization system effectively protects lumbar motion and achieves lumbar stability in patients with lumbar spinal problems. Our clinical result support literature that Dynesys® system is a strong alternative to fusion and instrumentation system in patient with chronic instabilities.


Exogenous ochronosis - successful outcome after treatment with Q-switched Nd:YAG laser.
Exogenous ochronosis (EO), a disfiguring cutaneous complication of topical hydroquinone use, is difficult to treat. There are few reports of successful outcomes following treatment with different modalities. We assessed the results of treatment of EO with the Q-switched Nd:YAG laser. Patients with histologically-confirmed EO were treated with the Q-switched Nd:YAG laser. Q-switched Nd:YAG laser treatment appears to be effective in reducing the dyschromia of EO.


[Closed intestinal decompression in postoperative paralysis: intestinal intubation (author's transl)].
Paralytic distension is a causative or important factor in the pathogenesis of early postoperative intestinal obstruction. The elimination of intestinal distension initiates a decisive change in the course of this disease. The long intestinal tube--comparable to an "intraluminary stoma"--renders the necessary intestinal decompression. The controlled placement of the tube using a gastroscope rules out technical problems. The procedure is highly effective, contributes to the reduction of relaparotomies, and avoids enterotomies with all their inherent risks in the state of ileus.


An ounce of prevention.
The wellness movement is gaining momentum as a way to cut medical costs and improve Americans' health. But skeptics wonder if wellness really works.


Kirschner wire is more effective than the nerve root retractor in treating patients with disc herniation.
To investigate the value of using Kirschner wire in the intraspinal procedures. From May 2011 to October 2013, a total of 46 patients with a single-level lumbar disc herniation with concomitant lumbar instability were randomly assigned to two groups at the time of admission. Group 1 had 23 patients who underwent posterior lumbar fusion using a nerve root retractor to drag nerve root, and Group 2 also had 23 patients who underwent the same operation by fixing Kirschner wires in the vertebral body to drag nerve root. All of these patients were assessed with visual analog scales (VAS) and Japanese Orthopaedic Association (JOA) scores before surgery, and were followed up at the time points of one week (VAS score only), three, six, and twelve months respectively after surgery. The actual retraction time of the nerve root of each patient was also recorded during the operation. The differences in VAS and JOA scores were not significant between Group 1 and 2 before surgery. However, these scores showed significant improvement in Group 2 at one week and three months after surgery compared with those in Group 1. At six and twelve month follow-up time points, no significant difference was observed between these two groups. However, the retraction time of the nerve root of the patients in Group 2 was significantly shorter than in Group 1. Using Kirschner wires instead of the nerve root retractor to pull nerve root in the patients with a single-level lumbar disc herniation accompanied by the lumbar instability is more effective in reducing the dragging damage of the nerve root at early phases after surgery and in shortening retraction time.


Identification of the B subtype of gamma-phospholipase A2 inhibitor from Protobothrops flavoviridis serum and molecular evolution of snake serum phospholipase A2 inhibitors.
A cDNA encoding a novel phospholipase A(2) (PLA(2)) inhibitor (PLI) was isolated from a Protobothrops flavoviridis snake (Tokunoshima island, Japan) liver cDNA library. This cDNA encoded a signal peptide of 19 amino acids followed by a mature protein of 181 amino acids. Its N-terminal amino acid sequence was completely in accord with that of a PLI, named PLI-II, previously found in P. flavoviridis serum. PLI-II showed a high similarity in sequence to the B subtype of gammaPLI, denoted gammaPLI-B, isolated from Agkistrodon blomhoffii siniticus serum. Thus, PLI-II is P. flavoviridis serum gammaPLI-B. Since PLI-I, previously isolated from P. flavoviridis serum, can be assigned as gammaPLI-A, P. flavoviridis serum contains both A and B subtypes of gammaPLI. Phylogenetic analysis of gammaPLIs from the sera of various kinds of snakes, Elapinae, Colubrinae, Laticaudinae, Acanthophiinae, Crotalinae, and Pythonidae, based on the amino acid sequences revealed that A and B subtypes of gammaPLIs are clearly separated from each other. It was also found that phylogenetic topologies of gammaPLIs are in good agreement with speciation processes of snakes. The BLAST search followed by analyses with particular Internet search engines of proteins with Cys/loop frameworks similar to those of PLI-II and PLI-I revealed that gammaPLI-Bs, including PLI-II and PLI-II-like proteins from mammalian sources, form a novel PLI-II family which possesses the common Cys/loop frameworks in the anterior and posterior three-finger motifs in the molecules. Several lines of evidence suggest that PLI-II is evolutionarily ancestral to PLI-I.


Peroxiredoxin-2 nitrosylation facilitates cardiomyogenesis of mouse embryonic stem cells via XBP-1s/PI3K pathway.
Protein nitrosylation is a ubiquitous post-translational modification in almost all biological systems. However, its function on stem cell biology is so far incompletely understood. Here, we demonstrated that peroxiredoxin 2 (Prdx-2) nitrosylation was involved in cardiomyocyte differentiation of mouse embryonic stem (ES) cells induced by S-nitrosoglutathione (GSNO). We found that temporary GSNO exposure could promote ES cell-derived cardiomyogenesis. Using a stable isotope labeling by amino acids in cell culture (SILAC)-based proteomics approach, coupled with biotin switch technique, a total of 104 nitrosylated proteins were identified. Specifically, one of the antioxidant enzymes, Prdx-2, was abundantly nitrosylated and temporarily reduced in antioxidant activity, causing transient endogenous hydrogen peroxide (H2O2) accumulation and subsequent X-box binding protein-1s/phosphatidylinositol 3-kinase pathway activation. The present study reveals the mechanism in which GSNO favors cardiomyocyte differentiation. Prdx-2 nitrosylation could be a potent strategy to affect the pluripotent stem cell-derived cardiomyogenesis.


Sarcolemmal Na+/H+ exchanger activity and expression in human ventricular myocardium.
To determine sarcolemmal Na+/H+ exchanger (NHE) activity and expression in human ventricular myocardium. Although the sarcolemmal NHE has been implicated in various physiological and pathophysiological phenomena in animal studies, its activity and expression in human myocardium have not been studied. Ventricular myocardium was obtained from unused donor hearts with acute myocardial dysfunction (n = 5) and recipient hearts with chronic end stage heart failure (n = 11) through a transplantation program. Intracellular pH (pHi) was monitored in enzymatically isolated single ventricular myocytes by microepifluorescence. As the index of sarcolemmal NHE activity, the rate of H+ efflux at a pHi of 6.90 J(H6.9)) was determined after the induction of intracellular acidosis in bicarbonate-free medium. Na+/H+ exchanger isoform 1 (NHE1) expression in ventricular myocardium was determined by immunoblot analysis. Human ventricular myocytes exhibited readily detectable sarcolemmal NHE activity after the induction of intracellular acidosis, and this activity was suppressed by the NHE1-selective inhibitor HOE-642 (cariporide) at 1 micromol/L. Sarcolemmal NHE activity of myocytes was significantly greater in recipient hearts (JH6.9 = 1.95+/-0.18 mmol/L/min) than it was in unused donor hearts (J(H6.9 = 1.06+/-0.15 mmol/L/min). In contrast, NHE1 protein was expressed in similar abundance in ventricular myocardium from both recipient and unused donor hearts. Sarcolemmal NHE activity of human ventricular myocytes arises from the NHE1 isoform and is inhibited by HOE-642. Sarcolemmal NHE activity is significantly greater in recipient hearts with chronic end-stage heart failure than it is in unused donor hearts, and this difference is likely to arise from altered posttranslational regulation.


Diagnosis and management of cancer metastatic to the uvea: a study of 70 cases.
Although metastatic cancer to the uvea is reported to be the most common intraocular malignancy, most ophthalmologists have had little experience with its diagnosis and treatment. This report describes our experience with the diagnosis and management of 70 patients with metastatic cancer to the uvea. Many patients were evaluated with modern diagnostic modalities such as fluorescein angiography, ultrasonography, and the 32P test when indicated. Thirty-one percent of patients had no history of previous malignancy, and the ocular complaints represented the first symptoms of systemic cancer. The ocular malignancy often simulated better-known ophthalmic entities, and the referring diagnosis was correct in only 38% of cases. This series, therefore, reflects the clinical problem confronting the practicing ophthalmologist. About one-half of the patients were treated with external beam irradiation to the involved eye(s), which often resulted in dramatic resolution of the tumor and visual return. Other patients had either no treatment, chemotherapy, or enucleation in selected instances.


Antiarrhythmic effects of prostaglandins E2 and I2 on ouabain-induced cardiac arrhythmias in cats: effect of vagotomy and adrenergic neuron blockade.
The effects of i.v. prostaglandins (PGs) E2 and I2 on ouabain-induced cardiac arrhythmias were investigated in chloralose-anaesthetized cats. Bilateral vagotomy and guanethidine-pretreatment interventions were employed to elucidate the involvement of vagal and sympathetic neural influences in these effects. PGE2 (1 micrograms/kg/min i.v. infusion for 5 min) and PGI2 (4-16 microgram/kg i.v. bolus injections) effectively suppressed the ouabain-induced arrhythmias in a control group of cats. The bilateral vagotomy or guanethidine-pretreatment interventions did not significantly alter the antiarrhythmic effects of PGE2 and PGI2. It is concluded that the presence of functionally intact sympathetic and vagal nerve supply to the heart is not a prerequisite for the antiarrhythmic effects of i.v. administered PGE2 and PGI2. The possible role of direct action of these PGs on the myocardium is discussed.


UCLMuevete: Increasing the amount of physical activity, work-ability, and cardiorespiratory fitness capacity in university workers through active breaks.
Active breaks programs at the workplace are a promising initiative for increasing workers' physical activity (PA) levels, health, work-ability (WA), and social relationship. To determine the impact of an Active Breaks workplace program based on Bandura's Social Cognitive Theory (SCT) aligned with Behavior Change Techniques (BCT) on PA levels, cardiorespiratory fitness (CRF), WA, and social relationships among university workers. #UCLMuévete is a quasi-experimental, 12-week intervention designed according to the TREND and TIDieR-PHP checklist. Sixtynine university workers were recruited and placed into 17 teams of 3 to 5 people. Participants were instructed to take a 20-min active break every working day (walking, cycling, and functional training). The following variables were measured before and after the 12-week intervention: (1) Amount of PA with accelerometers, (2) CRF through the 6 Min-Walking Test (m), (3) Body composition (fat mass (gr), muscle mass (gr), and bone mineral content (g/cm3) through densitometry, (4) stress with the BodyGuard2 device (5) WA through Work Ability Index (WAI), and (6) social relationships through an ad-hoc questionnaire. Part-time workers, pregnant women, and workers with physical disability were excluded. Significant improvements were observed in the amount of daily moderate-to-vigorous PA (Difference (Dif)., women +8.05 and men +12.31 minutes; p < 0.05; ES = 0.224; 0.379), CRF (Dif., women +52.98 and men +25.53 meters; p < 0.05; ES = 0.578; 0,209), and (Dif., women +2.16 and men +2.39; p < 0.05; ES =;0.150; 0.177). No significant changes were observed in body composition and stress. 20 min/day of aerobic and strength active breaks, based on SCT aligned to BCTs, improves university workers' amount of PA, CRF, WAI, and social relationships.


Susceptibility tests for sulfamethoxazole-trimethoprim by a broth microdilution procedure.
Most media used for susceptibility testing contain sulfonamide inhibitors that make them unacceptable for testing sulfonamides. The major substance that inhibits sulfonamides has been identified as thymidine, and recent efforts to remove it from Mueller-Hinton medium have made it possible to perform susceptibility tests with sulfamethoxazole-trimethoprim by broth microdilution. Some lots of Mueller-Hinton broth are thymidine free, but some contain small amounts of thymidine and require the addition of thymidine phosphorylase or lysed horse blood which contains thymidine phosphorylase. Some lots may contain too much thymidine so that its activity cannot be reversed by adding the recommended amont of thymidine phosphorylase. Therefore the suitability of a medium must be determined by testing with control strains. Some organism, for example enterococci, cannot be tested in thymidine phosphorylase-treated media because thymine works in the same way thymidine does to inhibit the action of sulfamethoxazole-trimethoprim.


Web-based symptom screening in cystic fibrosis patients: A feasibility study.
Cystic fibrosis (CF) causes high illness burden. Screening may identify patients who could potentially benefit from interventions for symptoms or other sources of distress. We evaluated the feasibility of a web-based system for routine monitoring. Adult CF patients enrolled in a study of palliative care service delivery completed web-based assessments every 30 days on global distress, physical and psychological symptom distress, and the perceived benefits of discussing advance care planning (ACP) with CF clinicians. Feasibility was assessed by the rate of survey completion, survey reminders, and missed surveys during a 9-month rolling enrollment period. Of 74 participants (47.3% women, 94.4% white), 36.7% had comorbid diabetes, and 56.9% had an FEV1% predicted score of 40-69. In total, patients completed 456 (80.6%) of 566 surveys every 30 days over the assessment period. Sixty-five (87.8%) completed 405 (79.7%) of 508 surveys online and 9 (12.2%) completed 51 (88.0%) of 58 surveys using a combination of online, telephone, and mail-based methods. Many surveys were completed without reminders (online: 261 [64.4%] of 405; combined methods: 29 [56.9%] of 51), with 166 (36.4%) surveys requiring 1 or more reminders. Further, 23.0% (17) of patients noted elevated global distress; 20.3% (15) endorsed physical symptom distress, 12.2% (9) had psychological distress, and 58.1% (43) reported that discussing ACP would be beneficial. Repeated web-based screening for symptom distress and ACP preferences is feasible in adult CF patients. Future studies should assess the system's generalizability and staff resources when implementing reminders and non-web methods of completion.


[The activity of L-cystine-aminopeptidase (oxytocinase) in the serum of pregnant women during intravenous application of oxytocin (author's transl)].
The oxytocinase levels have been tested prior to, during and after oxytocin challenge tests in 42 pregnant women. There was no relation between labour and the activity of the enzyme. There was no change in the activity during and after oxytocin infusion. Repeated challenge tests did not change these results. The use of the oxytocinase as a parameter of placental function is not influenced by oxytocin infusions.


Disposition of amphotericin B in the isolated perfused rat liver.
The hepatic disposition and biliary excretion of amphotericin B were investigated in the isolated perfused rat liver (IPRL). Bolus dose of 50 microg, 99 microg and 198 microg amphotericin B in lipoprotein-free perfusate and 198 microg amphotericin B in perfusate with 1 microM high-density lipoprotein (HDL) or 1 microM low-density lipoprotein (LDL) were examined in the IPRL. Amphotericin B concentration in perfusate was measured using a validated HPLC assay. Amphotericin B was eliminated from the perfusate in a biexponential manner. The hepatic clearance (CL(H)) increased in proportion to the dose administered (0.27 +/- 0.05 mL min(-1) at low dose, 0.54 +/- 0.23 mL min(-1) at medium dose and 1.06 +/- 0.24 mL min(-1) at high dose), indicating non-linear hepatic disposition of amphotericin B. The hepatic extraction ratio of amphotericin B was very low (0.066 +/- 0.015). Tissue-to-perfusion partition coefficient, calculated at 120 min, increased 1.5 fold from 9.8 +/- 1.7 at low dose to 15.9 +/- 6.4 at high dose, suggesting the significant uptake and extensive retention of amphotericin B in the liver. Biliary excretion made only minor contribution to amphotericin B elimination in the IPRL, representing around 1-3% of the dose administered. No metabolites were detected in perfusate, bile and liver samples. The hepatic disposition of amphotericin B was not affected by the presence of HDL and LDL in the perfusate. In conclusion, the hepatic disposition of amphotericin B demonstrates restrictive elimination and is concentration-dependent, consistent with carrier-mediated uptake, and lipoproteins do not influence amphotericin B hepatobiliary disposition.


Advanced glycation end products induce in vitro cross-linking of alpha-synuclein and accelerate the process of intracellular inclusion body formation.
Cross-linking of alpha-synuclein and Lewy body formation have been implicated in the dopaminergic neuronal cell death observed in Parkinson's disease (PD); the mechanisms responsible, however, are not clear. Reactive oxygen species and advanced glycation end products (AGEs) have been found in the intracellular, alpha-synuclein-positive Lewy bodies in the brains of both PD as well as incidental Lewy body disease patients, suggesting a role for AGEs in alpha-synuclein cross-linking and Lewy body formation. The aims of the present study were to determine 1) whether AGEs can induce cross-linking of alpha-synuclein peptides, 2) the progressive and time-dependent intracellular accumulation of AGEs and inclusion body formation, and 3) the effects of extracellular or exogenous AGEs on intracellular inclusion formation. We first investigated the time-dependent cross-linking of recombinant human alpha-synuclein in the presence of AGEs in vitro, then used a cell culture model based on chronic rotenone treatment of human dopaminergic neuroblastoma cells (SH-SY5Y) over a period of 1-4 weeks, in the presence of different doses of AGEs. Cells (grown on coverslips) and cell lysates, collected at the end of every week, were analyzed for the presence of intracellular reactive oxygen species, AGEs, alpha-synuclein proteins, and intracellular alpha-synuclein- and AGE-positive inclusion bodies by using immunocytochemical, biochemical, and Western blot techniques. Our results show that AGEs promote in vitro cross-linking of alpha-synuclein, that intracellular accumulation of AGEs precedes alpha-synuclein-positive inclusion body formation, and that extracellular AGEs accelerate the process of intracellular alpha-synuclein-positive inclusion body formation.


The impact of the universal infant varicella immunization strategy on Canadian varicella-related hospitalization rates.
Varicella vaccine was introduced to the infant immunization schedule in each province or territory between 2000 and 2007 as a result of the Canadian Immunization Strategy. The impact of vaccinating children against this disease is potentially far reaching, as immunization may also benefit those segments of the population not immunized. The objective of this paper is to examine the effects of varicella vaccine on related hospitalizations across the entire Canadian population. This study is an ecological study using annual hospitalization rates in all ten provinces between 1990 and 2010. There were decreased varicella-related hospitalization rates for all ages across Canada following the introduction of varicella vaccination programs. The majority of changes in hospitalization rates were greater than 70% across all ages less than 40. Statistically significant declines in hospitalization were found for children aged 1-4 (ranges from 65 to 93%), and children less than 1 (ranges from 48 to 100%). Adults aged 20-39 and 40-59 also experienced statistically significant declines (55-100%, and 39-76% respectively). Results suggest that decreased circulation of varicella appears to significantly contribute to declines in varicella-related hospitalizations for infants <1, as well as adults aged 20-39.


Quality control of radiotherapeutic treatment of medulloblastoma in a multicentric study: the contribution of radiotherapy technique to tumour relapse. The French Medulloblastoma Group.
Between 06.86 and 11.89, 88 medulloblastoma or primitive neuroectodermic tumour (PNET) localised in the posterior fossa have been included in the M7 multicentric protocol, 82 received the totality of the radiotherapy treatment and were evaluable for this study. Twenty-two of these 82 patients relapsed: their radiotherapy treatment is analysed in the present study. In 10 cases out of the 22 relapses treatment failure was probably due to a radiotherapeutic imperfection. This study confirms the necessity of a strict radiotherapy control, particularly in multicentric study.


[Pituitary prolactin reserve in acute exacerbation of chronic respiratory insufficiency].
The level of pituitary prolactin reserve (PPR) was studied in 56 patients with chronic respiratory failure (CRF) in the acute stage after injections of metoclopramide and Thyrotropin Releasing Hormone (TRH). PPR was low in 90% of the subjects in both groups so that the pathogenic mechanism is more likely to be hypophyseal than hypothalamic and due to the reduced synthesis of PRL by the pituitary gland as a result of inadequate ATP synthesis and/or functional alterations to the receptors or pituitary cells following hypoxaemia and hypercapnia.


The molecular underpinnings of genetic phenomena.
Epiphenomena are those processes that ostensibly have no precedent at lower levels of scientific organization. In this review, it is argued that many genetic processes, including ploidy, dominance, heritability, pleiotropy, epistasis, mutational load and recombination, all are at least analogous to biochemical events that were requisite features of the RNA world. Most, if not all, of these features of contemporary whole organisms and populations may have their ultimate evolutionary roots in the chemical repertoire of catalytic RNAs. Some of these phenomena will eventually prove to be not only analogous but homologous to ribozyme activities.


Incorporation of benzoyl peroxide nanocrystals into adapalene-loaded solid lipid microparticles: Part II - Solid-in-Oil dispersion of nanoparticulate benzoyl peroxide.
Benzoyl peroxide as a monotherapeutic and in combination with adapalene is a cornerstone of current acne therapy, but its unfavourable side effect profile reduces the therapeutic value of this compound. The incorporation into an adapalene-loaded microparticulate lipid matrix, which - via the principle of targeted erosion - allows the targeted release of active substances in the hair follicles, is a promising approach to reduce side effects such as skin redness, increased scaling and allergic reactions. However, there are challenges to the production of such a vehicle which require a galenic solution. That is in particular the redispersion of nanoparticulate benzoyl peroxide in lipids while maintaining its nanodisperse character. In the present work, the lamellar liquid crystalline phase of a binary water/phospholipid system is used to stabilize a nanosuspension during freeze-drying. Both after redispersing in water and after dispersing in nonpolar fat phases, the initial size of the nanosuspension was recovered with only minor deviations. The found cryoprotective effect of purified phospholipid allows the generation of highly concentrated solid-in-oil systems both in fat phases liquid at room temperature and in lipid melts, which after solidification can serve as starting material for the preparation of lipid microparticles loaded with benzoyl peroxide nanocrystals.