Co-regulation of histone-modifying enzymes in cancer.
Cancer is characterized by aberrant patterns of expression of multiple genes. These major shifts in gene expression are believed to be due to not only genetic but also epigenetic changes. The epigenetic changes are communicated through chemical modifications, including histone modifications. However, it is unclear whether the binding of histone-modifying proteins to genomic regions and the placing of histone modifications efficiently discriminates corresponding genes from the rest of the genes in the human genome. We performed gene expression analysis of histone demethylases (HDMs) and histone methyltransferases (HMTs), their target genes and genes with relevant histone modifications in normal and tumor tissues. Surprisingly, this analysis revealed the existence of correlations in the expression levels of different HDMs and HMTs. The observed HDM/HMT gene expression signature was specific to particular normal and cancer cell types and highly correlated with target gene expression and the expression of genes with histone modifications. Notably, we observed that trimethylation at lysine 4 and lysine 27 separated preferentially expressed and underexpressed genes, which was strikingly different in cancer cells compared to normal cells. We conclude that changes in coordinated regulation of enzymes executing histone modifications may underlie global epigenetic changes occurring in cancer.


Study on genetic coadaptability of wild quail populations in China.
Genetic coadaptability of wild Japanese quail, wild Common quail and Domestic quail populations in China was studied using 7 microsatellite DNA markers and Monte Carlo method to test genetic disequilibrium. The molecular effects of genetic coadaptability were analyzed through a new statistical model of neutral site. The results showed that genetic coadaptability dominated the genetic disequilibrium of the three quail populations, and totally 16.67%, 9.66% and 10.05% of non-allelic combinations were in the genetic disequilibrium in wild Japanese quail, wild Common quail and Domestic quail populations, respectively. Genetic coadaptability existed at almost all the tested sites. In the molecular point of view, genetic coadaptability plays an important role of keeping lots of polymorphisms in natural populations. Therefore, it is another key factor to the genetic disequilibrium in the population except for linkage. The results enrich the conceptions and connotations of genetic disequilibrium, and help us know more about genetic coadaptability and its effects, and lay a foundation of evaluation and protection of wild quail genetic resources in China.


The Effect of Serious Games for Nursing Students in Clinical Decision-Making Process: A Pilot Randomized Controlled Trial.
Background: Serious games (SGs) have been proposed as a type of technology-enhanced simulation that may provide nursing students with an opportunity to practice their clinical reasoning and decision-making skills in a realistic and safe environment. Materials and Methods: The aim of this study is to determine the effect of serious play on nursing students' self-confidence (SC) and anxiety in clinical decision making. The randomized controlled trial evaluated the efficacy of SGs for undergraduate nursing students using pre- and posttests. The study was conducted during nursing students' clinical practice and teaching. All undergraduate nursing students (n = 120) attending internal medicine nursing lesson were approached. Sixty students out of 120 answered the questionnaires at both baseline and follow-up (30 in the experimental group [EG] and 30 in the control group). The students answered the questionnaire after taking the first clinical practice, taking the endocrine course. In the 1 week, the EG played the game and both groups returned to clinical practice. Questionnaire data were collected after clinical application. Results: SC and two subdimensions, using the information in hand to determine the problem, and knowing and taking action, were improved in the intervention group and a significant interaction effect was found for changes over time between the two groups. Anxiety scores between groups were not statistically significant differences. Conclusions: Nursing professional educators can adopt SGs to improve cognitive and attention skills, strengthen judgment, require making time efficient, practice making safe decisions, and encourage the exploration of decision.


Peptide YY inhibits cholecystokinin-stimulated sphincter of Oddi activity in the prairie dog.
Peptide YY (PYY), a recently discovered gut peptide, has been shown to have a number of actions that are antagonistic to the effects of cholecystokinin. This study was designed to determine whether PYY would inhibit cholecystokinin-stimulated sphincter of Oddi activity in the prairie dog. In 12 prairie dogs PYY was infused intravenously at 1, 10, and 100 ng/kg/min, and arterial blood samples were obtained. A dose-response curve was obtained, with the 10 ng/kg/min dose producing serum levels of 725 pg/ml. In seven additional prairie dogs a side-hole, pressure-monitored perfusion catheter was passed into the duodenum through a choledochotomy and positioned in the sphincter of Oddi. A perfusion catheter was also placed in the gallbladder fundus. Sphincter of Oddi and gallbladder pressures were recorded before and during 20-minute infusions of cholecystokinin and then cholecystokinin plus PYY at 10 ng/kg/min. PYY significantly inhibited cholecystokinin-stimulated sphincter of Oddi phasic wave frequency (3.8 +/- 0.2 vs 3.3 +/- 0.4; p less than 0.05) and sphincter of Oddi motility index (26.2 +/- 4.3 vs 18.7 +/- 4.8; p less than 0.025) but did not affect the increase in gallbladder pressure induced by cholecystokinin. These findings are consistent with other known anticholecystokinin effects of PYY. We conclude that PYY may also inhibit sphincter of Oddi activity in the prairie dog by an anticholecystokinin effect, thus reducing flow through the sphincter.


A case of non-insulin dependent diabetes mellitus with antiinsulin antibody: effect of subcutaneous injection of human recombinant insulin-like growth factor-I.
We saw a 57-yr-old female non-insulin dependent diabetes mellitus (NIDDM) patient with antiinsulin antibody, in whom insulin-like growth factor-I (IGF-I) was shown to be effective as a blood glucose-lowering agent. Due to the presence of the antibody, the patient suffered from postprandial hyperglycemia and frequent hypoglycemia, which were uncontrollable even by multiple insulin injection therapy. In contrast to insulin injection (0.24 IU/kg body wt) which showed a delayed glucose-lowering effect, subcutaneous injection of recombinant human IGF-I (0.05-0.1 mg/kg body wt) caused a quick fall in plasma glucose levels. Prolongation of the glucose-lowering effect of "rapid-acting" insulin frequently caused subsequent hypoglycemia in this patient, but the effect of IGF-I seemed to have disappeared within the first three hours.


[Knowledge and practices of university day care center workers relative to acute respiratory infections in childhood].
Given the increasing frequency of acute respiratory infections in day care centers, the objective of this work was to identify knowledge and practices of day care center workers relative to the prevention, precocious detection and management of these illnesses. Through fourteen structured interviews in two university day care centers of the city of São Paulo, it was verified that the workers: demonstrate familiarity with several respiratory illnesses; indicate fever and noisy breath as danger signals; consider pollution and transmission as main causes; refer to environment care as the best form of control; keep continuous observation of the child and interventions of hygiene and comfort, and greater emotional care; consider education and care complementary in child attendance, revealing the need for better preparation for caring; have in daily activities the source of their knowledge.


IgMAT: immunoglobulin sequence multi-species annotation tool for any species including those with incomplete antibody annotation or unusual characteristics.
The advent and continual improvement of high-throughput sequencing technologies has made immunoglobulin repertoire sequencing accessible and informative regardless of study species. However, to fully map dynamic changes in polyclonal responses precise framework and complementarity determining region annotation of rearranging genes is pivotal. Most sequence annotation tools are designed primarily for use with human and mouse antibody sequences which use databases with fixed species lists, applying very specific assumptions which select against unique structural characteristics. For this reason, data agnostic tools able to learn from presented data can be very useful with new species or with novel datasets. We have developed IgMAT, which utilises a reduced amino acid alphabet, that incorporates multiple HMM alignments into a single consensus to automatically annotate immunoglobulin sequences from most organisms. Additionally, the software allows the incorporation of user defined databases to better represent the species and/or antibody class of interest. To demonstrate the accuracy and utility of IgMAT, we present analysis of sequences extracted from structural data and immunoglobulin sequence datasets from several different species. IgMAT is fully open-sourced and freely available on GitHub ( https://github.com/TPI-Immunogenetics/igmat ) for download under GPLv3 license. It can be used as a CLI application or as a python module to be integrated in custom scripts.


Production and purification of Streptococcus pneumoniae hemolysin (pneumolysin).
Pneumolysin was found to be produced by 112 of 113 clinical isolates of Streptococcus pneumoniae and to be an intracellular hemolysin. A 10-liter-scale fermentor production and purification procedure was developed for this hemolysin. The culture was concentrated by filtration 10 times before centrifugation. The cellular content was purified by ion-exchange chromatography, covalent thiopropyl gel chromatography, and gel filtration. One batch operation resulted in 6 mg of highly purified pneumolysin, with a yield of 66% and a specific activity of 1,400,000 hemolytic units per mg. The pneumolysin had a molecular weight of 53,000 and an isoelectric point of 5.2. The purification method developed will be of value in future studies on this hemolysin.


Epidemiologic, experimental, and clinical links between respiratory syncytial virus infection and asthma.
Virtually all children experience respiratory syncytial virus (RSV) infection at least once during the first 2 years of life, but only a few develop bronchiolitis and more severe disease requiring hospitalization, usually in the first 6 months of life. Children who recover from RSV-induced bronchiolitis are at increased risk for the development of recurrent wheeze and asthma in later childhood. Recent studies suggest that there is an association between RSV-induced bronchiolitis and asthma within the first decade of life but that this association is not significant after age 13. Despite the considerable progress made in our understanding of several aspects of respiratory viral infections, further work needs to be done to clarify the molecular mechanisms of early interactions between virus and host cell and the role of host gene products in the infection process. This review provides a critical appraisal of the literature in epidemiology and experimental research which links RSV infection to asthma. Studies to date demonstrate that there is a significant association between RSV infection and childhood asthma and that preventing severe primary RSV infections can decrease the risk of childhood asthma.


A simple procedure to facilitate chin implants placement via submental approach.
In order to facilitate chin implants placement by submental incision, the use of two threads is described. They are separately passed through the extremities of the implant and inserted into the previously created subperiosteal pocket using a grooved guide. Once the landmarks of dissection have been reached, the tip of the needle exits through the skin just a few centimetres laterally to the augmentation area and, only by pulling the free ends of the threads, the implant can easily be inserted into the pocket and the sutures cut and removed. This procedure was successfully performed in 79 patients of both sexes presenting with deficiencies in the sagittal dimension at the pogonion and in width, laterally to the symphysis. Therefore, in the authors' opinion, the before-described technique could be a useful tool that facial plastic surgeons can employ to facilitate alloplastic chin implants placement, by minimising the invasiveness of the procedure, reducing the operative time, and greatly improving the aesthetic result, without sacrificing the safety of the operation.


Adrenaline but not noradrenaline is a determinant of exercise-induced lipid mobilization in human subcutaneous adipose tissue.
The relative contribution of noradrenaline (norepinephrine) and adrenaline (epinephrine) in the control of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise was evaluated in men treated with a somatostatin analogue, octreotide. Eight lean and eight obese young men matched for age and physical fitness performed 60 min exercise bouts at 50% of their maximal oxygen consumption on two occasions: (1) during i.v. infusion of octreotide, and (2) during placebo infusion. Lipolysis and local blood flow changes in SCAT were evaluated using in situ microdialysis. Infusion of octreotide suppressed plasma insulin and growth hormone levels at rest and during exercise. It blocked the exercise-induced increase in plasma adrenaline while that of noradrenaline was unchanged. Plasma natriuretic peptides (NPs) level was higher at rest and during exercise under octreotide infusion in lean men. Under placebo, no difference was found in the exercise-induced increase in glycerol between the probe perfused with Ringer solution alone and that with phentolamine (an alpha-adrenergic receptor antagonist) in lean subjects while a greater increase in glycerol was observed in the obese subjects. Under placebo, propranolol infusion in the probe containing phentolamine reduced by about 45% exercise-induced glycerol release; this effect was fully suppressed under octreotide infusion while noradrenaline was still elevated and exercise-induced lipid mobilization maintained in both lean and obese individuals. In conclusion, blockade of beta-adrenergic receptors during exercise performed during infusion of octreotide (blocking the exercise-induced rise in adrenaline but not that of noradrenaline) does not alter the exercise-induced lipolysis. This suggests that adrenaline is the main adrenergic agent contributing to exercise-induced lipolysis in SCAT. Moreover, it is the combined action of insulin suppression and NPs release which explains the lipolytic response which remains under octreotide after full local blockade of fat cell adrenergic receptors. For the moment, it is unknown if results apply specifically to SCAT and exercise only or if conclusions could be extended to all forms of lipolysis in humans.


Plasma thyroid hormone and glucocorticosteroid concentrations in the male rat following prolonged exposure to stress.
Exposure of male CSF rats to a signalled unpredictable 60-day stress regimen induced a significant elevation in circulating triiodothyronine (T3) concentration above the control for the first 20 days of stress before the rate of secretion returned to normal. On the other hand, circulating thyroxine (T4) concentration fell significantly below the control value for the first 5 days of stress before the normal rate of secretion was reached in 10 days. A histological study of the thyroid gland revealed no change in activity among any of the control and stressed groups. At the same time this regimen also induced an initial extreme corticosterone elevation which was maintained for the first 5 days of stress and thereafter gradually fell to re-establish a new level by 40 days with no further change up to 60 days of stress. The possible physiological significance of the marked elevation in T3/T4 ratio as a result of stress is discussed, in particular with relation to higher glucocorticoid secretion.


Early teenage obstetrics at Waikato Hospital.
New Zealand has the second highest published teenage pregnancy rate in the world. Different papers have shown adverse obstetric outcome for teenage mothers. The aim of this study was to compare the obstetric parameters, such as birth weight, gestation at birth, Apgar scores, breech delivery, caesarean sections, instrumental deliveries, incidences of birth defects, twins, and gestational hypertension/pre-eclampsia of early teenage mothers with the rest of the population. The data were obtained from the perinatal information management system (PIMS) at Waikato Hospital for the period 1994 to 1996. The data were statistically analysed. There were 306 women in the early teenage group (17 years and younger) and 206 randomly selected women in the control group who were 18 years or older. In the early teen group more than 92% of women were primiparous, whereas in the control group most women were multiparous. The analyses detected no differences in the two groups in the parameters studied except increased incidence of ventouse delivery in the early teenage group (P = 0.004). This was surprising because, older and parous women are supposed to have better outcomes. Hence there was no evidence from this study of any of obstetric risk factors associated with early teenage pregnancy. Also, race did not affect the means of birth weights, gestational age at birth and Apgar scores. Adjustment for race and parity differences did not change the conclusions apart from making the difference in incidence of ventouse delivery less significant (P = 0.067 when adjusted for parity differences).


Developmental lead exposure alters the distribution of protein kinase C activity in the rat hippocampus.
Chronic low-level lead (Pb) exposure in children is known to cause a deficit in learning and memory. In vitro studies have demonstrated that Pb altered protein kinase C (PKC) activity. Especially, hippocampal PKC has been correlated with performance in several learning tasks. The effects of Pb exposure on hippocampal PKC were investigated during development at various postnatal ages: postnatal day (PN) 7, 14, 28, and 56. Two-tenth % Pb acetate was administered to pregnant and lactating dams and then administered to weanling rats in drinking water. PKC activity was measured in both membrane and cytosolic fractions from the hippocampi of the controls and Pb-exposed animals. Pb-induced increase in PKC activity in the cytosolic fraction was observed in the PN56 rats. In contrast, PKC activity was decreased by Pb at PN7 in the membrane fraction. Furthermore, a significant decrease in the ratio of membrane to cytosolic PKC activity which is representative of PKC distribution was observed in the PN28 and PN56 Pb-exposed rats relative to the same-age controls. This study indicates that chronic Pb exposure during development influences hippocampal PKC activity and distribution. These changes may be involved in the subclinical neurotoxicity of chronic Pb exposure in young children.


4-Year Trajectory of Visceral Adiposity Index in the Development of Type 2 Diabetes: A Prospective Cohort Study.
Our aim was to evaluate whether visceral adiposity index (VAI) could predict the risk of type 2 diabetes (T2D) in different genders and to compare the predictive ability between VAI and other fatness indices. Four thousand seventy-eight participants including 1,817 men and 2,261 women, aged 18 and older and free of T2D at baseline were enrolled in 2010 and followed up for 4 years. New cases of T2D were identified via the annual medical examination. Cox regression analysis was used to assess the association between VAI and incidence of T2D. Receiver operating characteristic curve and area under the curves (AUC) were applied to compare the prediction ability of T2D between VAI and other fatness indices. During the 4-year follow-up, 153 (8.42%) of 1,817 men and 88 (3.89%) of 2,261 women developed T2D. The multivariable-adjusted hazards ratios for developing T2D in the highest tertile of VAI scores were 2.854 (95% CI 1.815-4.487) in men and 3.551 (95% CI 1.586-7.955) in women. The AUC of VAI was not higher than that of other fatness indices. VAI could predict the risk of T2D among Chinese adults, especially in women. However, the prediction ability of T2D risk for VAI was not higher than that of the other fatness indices.


Prevalence and antimicrobial susceptibility of Listeria monocytogenes on chicken carcasses in Bandung, Indonesia.
This study was conducted to determine the prevalence and quantify the number of Listeria monocytogenes in fresh chicken carcasses sold in traditional markets and supermarkets in Bandung, West Java, Indonesia, and to determine the antimicrobial resistance patterns of the isolated L. monocytogenes strains. The overall prevalence of L. monocytogenes in chicken carcasses was 15.8% (29/184). When comparing samples from traditional markets and supermarkets, no significant difference in the L. monocytogenes prevalence was detectable (15.2 versus 16.3%). Of the samples, 97.3% had L. monocytogenes counts <100 CFU/g, 2.2% had L. monocytogenes counts between 101 and 1,000 CFU/g, and 0.5% had L. monocytogenes counts of 1,001 to 10,000 CFU/g. Of the isolates, 27.6% were resistant to at least one of the 10 antimicrobials tested, with the major resistant phenotypes to penicillin (17.2%), ampicillin (6.9%), and erythromycin (6.9%). All 29 isolates recovered in this study were grouped into the molecular serogroup IIb, comprising the serovars 1/2b, 3b, and 7.


Epidemiology of biological-exposure incidents among Spanish healthcare workers.
To determine the frequency and the epidemiological characteristics of biological-exposure incidents occurring among healthcare personnel. Prospective surveillance study. Participating Spanish primary-care and specialty centers from January 1994 to December 1997. 70 centers in 1994, 87 in 1995, 97 in 1996, and 104 in 1997. Absolute and relative frequencies were calculated for several variables (position held, area of care, type of injuring object, activity, etc) and for the different categories of each variable. There were 20,235 registered incidents. Annual incidence rates were as follows: 1994, 51 per 1,000; 1995, 58 per 1,000, 1996, 54 per 1,000; and 1997, 59 per 1,000. Mean age of accident victims was as follows: 1994, 35.68 (standard deviation [SD], 16.26); 1995, 33.6 (SD, 11.9); 1996,38.2 (SD, 17.27); and 1997, 36.7 (SD, 16.33) years. Of the 20,235 incidents, 15,860 (80.7%) occurred to women; 50% (9,833) accidents were among nursing staff. The type of incident most frequently reported was percutaneous injury (81.1%). The highest frequency of accidents was seen in medical and surgical areas (28% and 25.6%, respectively). Blood and blood products were the most commonly involved material (87.6%). Administration of intramuscular or intravenous medication was the activity associated with the highest accident rate (20.3%). The most frequent immediate action in response was rinsing and disinfecting (65.6%). The incident registry was highly stable in terms of incidence rates over the observation period and served to highlight the large number of incidents recorded each year. The potential implications of the results are the need to explore reasons for increased exposures in certain areas, with the aim of focusing prevention efforts, and, similarly, to establish the factors associated with diminished incidence rates to model successful measures.


3D-visualization of amyloid-β oligomer interactions with lipid membranes by cryo-electron tomography.
Amyloid-β (Aβ) assemblies have been shown to bind to lipid bilayers. This can disrupt membrane integrity and cause a loss of cellular homeostasis, that triggers a cascade of events leading to Alzheimer's disease. However, molecular mechanisms of Aβ cytotoxicity and how the different assembly forms interact with the membrane remain enigmatic. Here we use cryo-electron tomography (cryoET) to obtain three-dimensional nano-scale images of various Aβ assembly types and their interaction with liposomes. Aβ oligomers and curvilinear protofibrils bind extensively to the lipid vesicles, inserting and carpeting the upper-leaflet of the bilayer. Aβ oligomers concentrate at the interface of vesicles and form a network of Aβ-linked liposomes, while crucially, monomeric and fibrillar Aβ have relatively little impact on the membrane. Changes to lipid membrane composition highlight a significant role for GM1-ganglioside in promoting Aβ-membrane interactions. The different effects of Aβ assembly forms observed align with the highlighted cytotoxicity reported for Aβ oligomers. The wide-scale incorporation of Aβ oligomers and curvilinear protofibrils into the lipid bilayer suggests a mechanism by which membrane integrity is lost.


How Can Jewish and Non-Jewish People Collaborate to Improve Healthcare in the US? Considering Community, Autonomy, and Solidarity.
The coronavirus 2019 (COVID) pandemic has highlighted the ways in which municipal, state, and Federal agencies in the USA have failed to address the inequities of present-day health systems. As alternative organizing centers outside these agencies, local communities are potentially situated to redress the inequities of present-day health systems in a collaborative manner that demonstrates solidarity by supplementing a purely scientific model of medicine and healthcare. In the mid-twentieth century, the Black Panthers, a revolutionary African American nationalist organization that focused on socialism and self-defense, introduced highly influential free clinics, which sought to bring expertise to the Black community on their own terms. This required bringing the benefits of biomedicine to those who customarily had not seen them. By extension, their approach raises questions regarding community- and expertise-centered approaches for the Jewish community: how is it engaged in healthcare for itself (in its diverse subcategories) and for others? Moreover, understanding how the Jewish community has been ill-served by present-day health-care systems might spur Jewish institutions to reimagine how healthcare should work.


Rapid molecular microbiologic diagnosis of prosthetic joint infection.
We previously showed that culture of samples obtained by prosthesis vortexing and sonication was more sensitive than tissue culture for prosthetic joint infection (PJI) diagnosis. Despite improved sensitivity, culture-negative cases remained; furthermore, culture has a long turnaround time. We designed a genus-/group-specific rapid PCR assay panel targeting PJI bacteria and applied it to samples obtained by vortexing and sonicating explanted hip and knee prostheses, and we compared the results to those with sonicate fluid and periprosthetic tissue culture obtained at revision or resection arthroplasty. We studied 434 subjects with knee (n = 272) or hip (n = 162) prostheses; using a standardized definition, 144 had PJI. Sensitivities of tissue culture, of sonicate fluid culture, and of PCR were 70.1, 72.9, and 77.1%, respectively. Specificities were 97.9, 98.3, and 97.9%, respectively. Sonicate fluid PCR was more sensitive than tissue culture (P = 0.04). PCR of prosthesis sonication samples is more sensitive than tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection and provides same-day PJI diagnosis with definition of microbiology. The high assay specificity suggests that typical PJI bacteria may not cause aseptic implant failure.


Investigating xylem embolism formation, refilling and water storage in tree trunks using frequency domain reflectometry.
Trunks of large trees play an important role in whole-plant water balance but technical difficulties have limited most hydraulic research to small stems, leaves, and roots. To investigate the dynamics of water-related processes in tree trunks, such as winter embolism refilling, xylem hydraulic vulnerability, and water storage, volumetric water content (VWC) in the main stem was monitored continuously using frequency domain moisture sensors in adult Betula papyrifera trees from early spring through the beginning of winter. An air injection technique was developed to estimate hydraulic vulnerability of the trunk xylem. Trunk VWC increased in early spring and again in autumn, concurrently with root pressure during both seasons. Diurnal fluctuations and a gradual decrease in trunk VWC through the growing season were observed, which, in combination with VWC increase after significant rainfall events and depletion during periods of high water demand, indicate the importance of stem water storage in both short- and long-term water balance. Comparisons between the trunk air injection results and conventional branch hydraulic vulnerability curves showed no evidence of 'vulnerability segmentation' between the main stem and small branches in B. papyrifera. Measurements of VWC following air injection, together with evidence from air injection and xylem dye perfusion, indicate that embolized vessels can be refilled by active root pressure but not in the absence of root pressure. The precise, continuous, and non-destructive measurement of wood water content using frequency domain sensors provides an ideal way to probe many hydraulic processes in large tree trunks that are otherwise difficult to investigate.


Pharmacokinetics of the antiprogesterone RU 486: no correlation to clinical performance of RU 486.
The pharmacokinetics and metabolism of RU 486 were characterized in 17 women who received a single dose of 600 mg of RU 486 for termination of an early unwanted pregnancy. Based on the clinical outcome and serum chorionic gonadotropin values, the subjects were divided into two groups: those who aborted completely (i.e. responders: N = 13) and those who did not respond to RU 486 treatment (i.e. non-responders: N = 4). The serum levels of RU 486, the monodemethylated, didemethylated and hydroxylated metabolites of RU 486 were measured by HPLC preceded by column chromatography. There were no significant differences in the serum levels of RU 486 or its metabolites between the two groups. The serum concentrations of alpha 1-acid glycoprotein, the binding protein for RU 486, were quantitated by immunoturbidimetry. The alpha 1-acid glycoprotein concentrations were similar in responders and non-responders. The metabolism of RU 486 was also studied by fractionating extracts of serum pools of responders and non-responders on thin-layer chromatography, and subsequent RIA analysis of the eluates of the sliced thin-layer chromatography. Spots with similar distribution and percentages of cross-reactivity were found in both groups on the chromatography; the results were also similar to those from a serum pool to which synthetic RU 486 and its three metabolites had been added. Hence it is concluded that failure to abort in response to RU 486 therapy is not associated with altered pharmacokinetics or metabolism of RU 486.


The field of clinical psychology: a response to Thorne.
This article begins with a retrospective review of the editorial written in 1945 by Frederick C. Thorne at the inauguration of his new publication, the Journal of Clinical Psychology. It first considers the predictions made by Thorne about the future of clinical psychology and which of these turned out to be accurate, partially accurate, or inaccurate. At the time, the editorial caused its author to be accused of anti-Semitism and thus got the journal off to a rather bad start, from which it may have recovered only recently. The article then moves on to consider the past, present, and future of the field of clinical psychology from a contemporary vantage-point.


Patient Case Report Daptomycin Holiday-A Daptomycin Dosing Strategy for Asymptomatic Increases in Creatine Phosphokinase Levels.
Daptomycin possesses excellent activity against many multidrug-resistant gram positive organisms. However, a side effect of concern with daptomycin is skeletal muscle injury, which is manifested in the form of elevated creatine phosphokinase (CPK). Management of such CPK elevations has traditionally been discontinuation of the offending agent, with many studies showing a resolution of a normal CPK level within 1 week of discontinuation and no long term adverse effects. Nevertheless, the question remains if daptomycin can be successfully restarted in such patients. Here, we present a case of a "daptomycin holiday" in which daptomycin was withheld upon CPK elevation and successfully reintroduced to the patient's regimen again after several days without further elevation of the CPK. The patient had a peak CPK of 2,557 U/L, and had no associated symptoms. A hypothesis for this holiday could be the adaptability of the skeletal muscle myocytes, in which the extra period between doses may allow for additional recovery of the membrane structure to further daptomycin exposure. Giving an asymptomatic patient with elevated CPK level, a short daptomycin holiday to allow for the CPK level to trend downward before resuming daptomycin therapy could be a potential strategy in patients for whom continuing daptomycin is still preferred.


Biomarkers and the Development of a Personalized Medicine Approach in Spinal Muscular Atrophy.
Recent unprecedented advances in treatment for spinal muscular atrophy (SMA) enabled patients to access the first approved disease modifying therapy for the condition. There are however many uncertainties, regarding timing of treatment initiation, response to intervention, treatment effects and long-term outcomes, which are complicated by the evolving phenotypes seen in the post-treatment era for patients with SMA. Biomarkers of disease, with diagnostic, prognostic, predictive, and pharmacodynamic value are thus urgently required, to facilitate a wider understanding in this dynamic landscape. A spectrum of these candidate biomarkers, will be evaluated in this review, including genetic, epigenetic, proteomic, electrophysiological, and imaging measures. Of these, SMN2 appears to be the most significant modifier of phenotype to date, and its use in prognostication shows considerable clinical utility. Longitudinal studies in patients with SMA highlight an emerging role of circulatory markers such as neurofilament, in tracking disease progression and response to treatment. Furthermore, neurophysiological biomarkers such as CMAP and MUNE values show considerable promise in the real word setting, in following the dynamic response and output of the motor unit to therapeutic intervention. The specific value for these possible biomarkers across diagnosis, prognosis, prediction of treatment response, efficacy, and safety will be central to guide future patient-targeted treatments, the design of clinical trials, and understanding of the pathophysiological mechanisms of disease and intervention.


Osteopathy may decrease obstructive apnea in infants: a pilot study.
Obstructive apnea is a sleep disorder characterized by pauses in breathing during sleep: breathing is interrupted by a physical block to airflow despite effort. The purpose of this study was to test if osteopathy could influence the incidence of obstructive apnea during sleep in infants. Thirty-four healthy infants (age: 1.5-4.0 months) were recruited and randomized in two groups; six infants dropped out. The osteopathy treatment group (n = 15 infants) received 2 osteopathic treatments in a period of 2 weeks and a control group (n = 13 infants) received 2 non-specific treatments in the same period of time. The main outcome measure was the change in the number of obstructive apneas measured during an 8-hour polysomnographic recording before and after the two treatment sessions. The results of the second polysomnographic recordings showed a significant decrease in the number of obstructive apneas in the osteopathy group (p = 0.01, Wilcoxon test), in comparison to the control group showing only a trend suggesting a gradual physiologic decrease of obstructive apneas. However, the difference in the decline of obstructive apneas between the groups after treatment was not significant (p = 0.43). Osteopathy may have a positive influence on the incidence of obstructive apneas during sleep in infants with a previous history of obstructive apneas as measured by polysomnography. Additional research in this area appears warranted.


More severe initial manifestations and worse short-term functional outcome of intracerebral hemorrhage in the plateau than in the plain.
Intracerebral hemorrhage (ICH) is one of the most devastating forms of stroke. However, studies on ICH at high altitude are insufficient. We aimed to compare the initial manifestations, imaging features and short-term functional outcomes of ICH at different altitudes, and further explore the effect of altitude on the severity and prognosis of ICH. We retrospectively recruited ICH patients from January 2018 to July 2021 from two centers at different altitudes in China. Information regarding to clinical manifestations, neuroimages, and functional outcomes at discharge were collected and analyzed. Association between altitude and initial severity, neuroimages, and short-term prognosis of ICH were also investigated. A total of 724 patients with 400 lowlanders and 324 highlanders were enrolled. Compared with patients from the plain, those at high altitude were characterized by more severe preliminary manifestations (P < 0.0001), larger hematoma volume (P < 0.001) and poorer short-term functional outcome (P < 0.0001). High altitude was independently associated with dependency at discharge (adjusted P = 0.024), in-hospital mortality (adjusted P = 0.049) and gastrointestinal hemorrhage incidence (adjusted P = 0.017). ICH patients from high altitude suffered from more serious initial manifestations and worse short-term functional outcome than lowlanders. Control of blood pressure, oxygen supplementation and inhibition of inflammation may be critical for ICH at high altitude.


The structural characteristics of the lifestyle among older adults and its impact on the health in China.
Enhancing overall health remains a primary global objective, with lifestyle being a crucial factor impacting the health status among older adults. This study focuses on the lifestyle of Chinese older adults, systematically exploring the evolution and characteristics of their lifestyle and investigating its impact on their health. Utilizing panel data from the Chinese Longitudinal Health Longevity Survey (CLHLS) from 2008, 2011, 2014, and 2018, we adopted 15 indicators reflecting older adults' lifestyle. Latent class analysis and ordinary least square regression were used to uncover the structural nuances of the Chinese older adults' lifestyle and its effects on health. The study identifies three distinct lifestyle categories for the older adults: relatively positive, mixed, and relatively negative. It reveals that the Chinese older adults do not predominantly adopt a positive lifestyle, and this trend persisted from 2008 to 2018. Each improvement in lifestyle category significantly boosts the older adults' physical health, mental health, and self-assessed health by 11.2%, 3.6%, and 17.1%, respectively. To attain the strategic aim of healthy aging, efforts should prioritize encouraging the older adults to adopt a positive lifestyle, enhance the geriatric health service system, and promote an intelligent lifestyle management model.


Experimental ovarian transplantation on stomach for bone repair in ovariohysterectomized rabbits.
To evaluate the bone repair process in ovariohysterectomized rabbit submitted to an ovarian transplant to stomach that may supplying some quantity of estrogen occurs to improve bone healing. In 20 female rabbits three holes of 1, 2 and 3mm diameter in tibial shaft were made and after that all animals received OHE through a ventral incision and they were randomly divided into two groups of ten rabbits each. In group one, animals received one of their self-ovaries that transplanted on serosal layer of stomach and group two did not receive treatment. Animals were kept during bone healing for a period of 45 days and radiological, biochemical, biomechanical and histopathological evaluation. The tibial defects in group one healed completely after 45 days and had more callous than second group. There is significant difference between two groups after operation in 21, 28 and 35 days about estrogen, progesterone and phosphatase Alkaline. The maximum forces in group one, were significantly higher than that for the group two. Ovarian transplantation prevents the effects of ovariohysterectomized on bone healing of rabbit tibia, suggesting that unilateral transplanted ovaries can substitute for the action of ovaries on the skeleton in ovariohysterectomized animals.


Temperature sensitivity of soil respiration rates enhanced by microbial community response.
Soils store about four times as much carbon as plant biomass, and soil microbial respiration releases about 60 petagrams of carbon per year to the atmosphere as carbon dioxide. Short-term experiments have shown that soil microbial respiration increases exponentially with temperature. This information has been incorporated into soil carbon and Earth-system models, which suggest that warming-induced increases in carbon dioxide release from soils represent an important positive feedback loop that could influence twenty-first-century climate change. The magnitude of this feedback remains uncertain, however, not least because the response of soil microbial communities to changing temperatures has the potential to either decrease or increase warming-induced carbon losses substantially. Here we collect soils from different ecosystems along a climate gradient from the Arctic to the Amazon and investigate how microbial community-level responses control the temperature sensitivity of soil respiration. We find that the microbial community-level response more often enhances than reduces the mid- to long-term (90 days) temperature sensitivity of respiration. Furthermore, the strongest enhancing responses were observed in soils with high carbon-to-nitrogen ratios and in soils from cold climatic regions. After 90 days, microbial community responses increased the temperature sensitivity of respiration in high-latitude soils by a factor of 1.4 compared to the instantaneous temperature response. This suggests that the substantial carbon stores in Arctic and boreal soils could be more vulnerable to climate warming than currently predicted.


Health-related Quality of Life in Patients on Hemodialysis and Peritoneal Dialysis: a Meta-Analysis of Iranian Studies.
Health-related quality of life (HRQOL) is an index to calculate wellbeing of patients and is an important concept in patients with end-stage renal disease. There are many studies calculating HRQOL for patients on different treatment modalities of end-stage renal disease. Pooling reports from Iran, this systematic review aimed to measure the HRQOL in patients on hemodialysis and peritoneal dialysis using meta-analysis techniques. Four databases including PubMed and Scopus in English and the SID and IranMedex in Persian were searched. Based on the inclusion criteria, 26 English and Persian-language articles reporting HRQOL in the scales between zero and 100 (or scales convertible to this range) for hemodialysis or PD were included in the meta-analysis. The mean HRQOL scores ranged between 34.40 and 69.16 for hemodialysis reports and between 38.00 and 65.70 for PD reports. The pooled quality of life scores for hemodialysis and PD were 52.257 and 52.722, respectively (t = 0.928, P = .36). The results showed that HRQOL in patients using hemodialysis and peritoneal dialysis were not significantly different. Similar studies in other countries had found similar results.


Ethanol Production from Oil Palm Trunk: A Combined Strategy Using an Effective Pretreatment and Simultaneous Saccharification and Cofermentation.
Oil palm trunk (OPT) with highly cellulose content is a valuable bioresource for bioethanol production. To produce ethanol from biomass, pretreatment is an essential step in the conversion of lignocellulosic biomass to fermentable sugars such as glucose and xylose. Several pretreatment methods have been developed to overcome biomass recalcitrance. In this study, the effects of different pretreatment methods such as alkali pretreatment, microwave-alkali, and alkaline peroxide combined with autoclave on the lignocellulosic biomass structure were investigated. Moreover, ethanol production from the treated biomass was performed by simultaneous saccharification and cofermentation (SSCF) under different temperatures, fermentation times, and cell ratios of Saccharomyces cerevisiae NCYC 479 and pentose-utilizing yeast, Pichia stipitis NCYC 1541. Pretreatment resulted in a significant lignin removal up to 83.26% and cellulose released up to 80.74% in treated OPT by alkaline peroxide combined with autoclave method. Enzymatic hydrolysis of treated OPT resulted in an increase in fermentable sugar up to 93.22%. Optimization of SSCF by response surface method showed that the coculture could work together to produce maximum ethanol (1.89%) and fermentation efficiency (66.14%) under the optimized condition. Pretreatment by alkaline peroxide combined with autoclave method and SSCF process could be expected as a promising system for ethanol production from oil palm trunk and various lignocellulosic biomass.


The transition from abortion to miscarriage to describe early pregnancy loss in British medical journals: a prescribed or natural lexical change?
In British medical research, the transition from abortion to miscarriage, to describe early pregnancy loss, occurred in the late twentieth century. A 1985 letter to The Lancet by a group of eminent obstetricians was long considered unilaterally to have prompted this shift. More recently, however, this conclusion was challenged, and it was suggested instead that the transition constituted natural language change, as medical professionals responded to their changing social and professional milieu. This paper, however, uses a pioneering statistical modelling technique to demonstrate decisively that the 1985 Lancet letter was indeed pivotal in promoting miscarriage as an acceptable variant for use in medical journals. The abrupt nature of the vocabulary shift in question is made clear through the pioneering application of the statistical modelling technique change point analysis. This methodological innovation demonstrates clearly the decisive impact of the 1985 letter, while also showcasing the remarkable suitability of change point analysis to the study of such sudden linguistic changes. With an increasing emphasis on patient-centred models of care, it is likely that further prescriptive interventions relating to medical language will be made in coming years. Indeed, beyond the medical profession, there are already increasing calls for further reform to the language of pregnancy loss. To understand how such language reforms might successfully be enacted, and to ensure that linguistic prescriptivism is employed only where change is appropriate, proportionate, and evidence-based, it is necessary to understand fully this historical precedent. Against the backdrop of recent 'lay' demands for reforms, this paper affirms the decisive impact of the 1985 intervention, and considers the ramifications of this finding for the study of linguistic prescriptivism and future medical language reform.


Analgesic and Sedative-Hypnotic Potentiality of Crude Methanolic Extract of Gomphandra tetrandra (Wall.) Sleumer Leaves.
Gomphandra tetrandra (Wall.) Sleumer (leaves) belonging to the family Stemonuraceae was investigated for preliminary phytochemical screening and evaluating their pharmacological activities in various pharmacological models. The crude methanolic extract was screened with different chemical reagents for the qualitative detection of different phytochemical groups. The peripheral analgesic function was determined using the acetic acid-induced writhing procedure and sedative-hypnotic behaviors were assessed using hole-board, open field, and hole-cross tests using different doses of the extract (200 mg/kg and 400 mg/kg body weight). Phytochemical screening revealed that methanolic extract of G. tetranda leaves contains steroids, gums, mucilages, phytosterols, carbohydrates, and flavonoids. The crude methanolic extract at 200 mg/kg and 400 mg/kg doses showed statistically significant activity in acetic acid-induced writhing inhibition test with 60% (p<0.01) and 76.47% (p<0.01) inhibition, respectively, compared to control. The extract also had dose-dependent substantial (p<0.01) sedative-hypnotic activities compared with diazepam in the hole-board, open field, and hole-cross tests. It may be assumed that the methanolic leaf extract of G. tetrandra possesses a strong possibility of having analgesic and sedative-hypnotic activity due to the presence of bioactive compounds in its leaves. Moreover, observed results have opened a new era of in-depth research to discover the possible mechanism of analgesic and sedative-hypnotic activity.


Improvement of vascular endothelial function using the oral endothelin receptor antagonist bosentan in patients with systemic sclerosis.
Increased endothelin activity may play a role in the pathogenesis of vascular injury, a primary feature of systemic sclerosis (SSc; scleroderma). Our goal was to test the hypothesis that treatment with the oral endothelin receptor antagonist bosentan might improve vascular endothelial function in SSc patients. A 4-week, prospective, parallel-group study compared 12 SSc patients who did not receive bosentan treatment with 12 patients who did receive treatment (125 mg/day) for pulmonary hypertension and/or digital ulcers. There were no differences in demographic and clinical characteristics or medications between the 2 groups. Baseline endothelial dysfunction was documented by decreased brachial artery ultrasound-derived flow-mediated dilation (FMD%; <5.5). Pulse wave analysis, venous occlusion plethysmography, and measurement of serum vascular markers were performed in parallel. FMD%, the main end point, increased significantly from a mean +/- SD of 3.1 +/- 1.3% to 8.4 +/- 2.6% after 4 weeks of bosentan treatment (P < 0.001, compared with a change from 2.4 +/- 1.6% to 2.4 +/- 2.2% in control patients). Arterial blood pressure, endothelium-independent vascular function, augmentation index, peripheral flow reserve, as well as circulating intercellular adhesion molecule 1, E-selectin, vascular endothelial growth factor, and endothelin 1 were not significantly affected by bosentan treatment. In patients continuously treated for 4 months, during which the dosage of bosentan remained at 125 mg/day (n = 5) or increased to 250 mg/day (n = 5), the 4-week results remained unchanged. Small doses of bosentan improve endothelial function without affecting hemodynamic parameters or endothelial activation-related processes, thus supporting a direct, reversible effect of endothelin in SSc-associated vascular injury. A long-term, controlled trial to examine the potentially global clinical benefit of endothelin receptor blockade in patients with early SSc may be warranted.


Neoliberal precarity and primalization: A biosocial perspective on the age of insecurity, injustice, and unreason.
In light of the observed rise in social instability and populist politics that has emerged recently even in some of the world's oldest and presumed stable democracies, this paper reappraises the role of the neoliberal political and economic consensus in fermenting popular discontent. While this is very well trodden ground the paper approaches the issues from a wholly new direction, specifically addressing how exposure to the destabilizing conditions of the present can be seen to have negatively impacted on the neurological functioning of many of the disenchanted and distressed of the current era, generating chronic negative emotional arousal and an associated impact on the capacity for rational thought and conduct. This condition of mental and emotional fugue, it is argued, has also rendered growing numbers more susceptible to marginal and radicalizing discourses, largely extended and amplified via social media, and not least the emotionally charged overtures of populist politicians. Against a backdrop of increasing insecurity, transformative changes to work and living conditions precipitated by neoliberal policy and the digital revolution, together with the epochal crisis presented by the global pandemic, it is argued that the task of understanding the deep and fundamental causes of social and political fracture have rarely been more urgent.


On the bioherbicide potential of Ulex europaeus and Cytisus scoparius: Profiles of volatile organic compounds and their phytotoxic effects.
The phytotoxic potential of the legume shrubs Ulex europaeus L. (gorse) and Cytisus scoparius (L.) Link. (Scotch broom) is studied in this work for the first time. On the basis of their richness in active principles, the previous evidence of biological activity, and the abundance of biomass in their native range and invaded areas, a question arose: can U. europaeus and C. scoparius be considered as potential sources of natural herbicides for sustainable agriculture? By means of volatile bioassays, the flowering fresh plant material of both shrub species was shown to produce and emit volatile organic compounds (VOCs) able to inhibit the germination and/or early growth of two agricultural weeds: Amaranthus retroflexus and Digitaria sanguinalis. Novel complete VOCs profiles from the volatile extracts of the shrub species were obtained by GC and GC/MS. A total of 20 compounds were identified from U. europaeus flowering biomass, theaspirane and eugenol, among others, being described in gorse for the first instance. The chemical profile of C. scoparius yielded 28 compounds and was rich in oxygenated monoterpenes such as terpinen-4-ol, verbenol, α-terpineol, and verbenone, which were also identified in this species for the first time. Using dose-response bioassays with pure compounds, these VOCs were argued to be involved in the phytotoxicity observed for the plant materials, even at very low concentrations. The phytotoxic effects were predominantly irreversible, particularly for D. sanguinalis, since the seeds exposed to the VOCs produced damaged seedlings, were unable to recover germination capacity after removing the phytotoxin or, when recovered, produced unviable seedlings. Our results extend the interest of the abundant U. europaeus and C. scoparius for the obtention of natural products with bioherbicide potential, or to be used as allelopathic biomass in the development of new sustainable agricultural practices.


Ocular flora and their antibiotic resistance patterns in the midwest: a prospective study of patients undergoing cataract surgery.
To determine the spectrum of conjunctival flora and the antibiotic susceptibility profiles of patients undergoing cataract surgery at a Midwestern university. Prospective in vitro laboratory investigation of a patient cohort. Conjunctival cultures were obtained from patients undergoing cataract surgery at a single ambulatory center on the day of surgery before the instillation of any ophthalmic medications. Isolates and antibiotic susceptibility profiles were identified using standard microbiological techniques. A total of 183 eyes were cultured, yielding 225 isolates. Twenty-seven eyes (14.8%) showed no growth. Coagulase-negative staphylococci (CNS) were the most commonly isolated organisms (74.8%). Overall susceptibility was highest for gentamicin (94%), which was also true of the CNS isolates (95.0%). A total of 64.5% of CNS isolates were sensitive to ciprofloxacin; 30.1% of CNS isolates were resistant to ≥3 classes of antibiotics; 46.6% of CNS isolates were oxacillin-resistant, and they were more resistant to antibiotics than their oxacillin-sensitive counterparts (P < .001), including fluoroquinolones (P < .001). Among eyes with multiple CNS strains, 41.4% had different antibiotic susceptibility profiles even though they were the same species. Our cohort harbored organisms with similar rates of antibiotic resistance as elsewhere in the country, including oxacillin resistance; however, the rate of fluoroquinolone resistance was less than in other reports. A surprisingly large proportion of different CNS strains from the same eye harbored different antibiotic susceptibility profiles. Our in vitro results, along with those of other investigators, should prompt further dialogue regarding antibiotic of choice for perioperative surgical prophylaxis in ophthalmic surgery.


Compounds inhibiting the bioconversion of hydrothermally pretreated lignocellulose.
Hydrothermal pretreatment using liquid hot water, steam explosion, or dilute acids enhances the enzymatic digestibility of cellulose by altering the chemical and/or physical structures of lignocellulosic biomass. However, compounds that inhibit both enzymes and microbial activity, including lignin-derived phenolics, soluble sugars, furan aldehydes, and weak acids, are also generated during pretreatment. Insoluble lignin, which predominantly remains within the pretreated solids, also acts as a significant inhibitor of cellulases during hydrolysis of cellulose. Exposed lignin, which is modified to be more recalcitrant to enzymes during pretreatment, adsorbs cellulase nonproductively and reduces the availability of active cellulase for hydrolysis of cellulose. Similarly, lignin-derived phenolics inhibit or deactivate cellulase and β-glucosidase via irreversible binding or precipitation. Meanwhile, the performance of fermenting microorganisms is negatively affected by phenolics, sugar degradation products, and weak acids. This review describes the current knowledge regarding the contributions of inhibitors present in whole pretreatment slurries to the enzymatic hydrolysis of cellulose and fermentation. Furthermore, we discuss various biological strategies to mitigate the effects of these inhibitors on enzymatic and microbial activity to improve the lignocellulose-to-biofuel process robustness. While the inhibitory effect of lignin on enzymes can be relieved through the use of lignin blockers and by genetically engineering the structure of lignin or of cellulase itself, soluble inhibitors, including phenolics, furan aldehydes, and weak acids, can be detoxified by microorganisms or laccase.


Student voices on an interprofessional course.
Investigations of outcomes of interprofessional education as a component of the basic preparation of health and human service professionals have lacked a strong focus on student perceptions, the student voice. This qualitative study examined students' insights regarding the interprofessional component of an elective course offered to 23 students; five from medicine and six from each of pharmaceutical sciences, nursing and social work. Fourteen students participated in focus group interviews at the conclusion of the course and 12 participated in telephone interviews six months later. The interviews explored perceptions regarding learning, including insights about the effectiveness of teaching-learning strategies, and improvements required. Experiential components of the course were more meaningful to students than theoretical components. Students perceived the use of practice-based learning, student interprofessional teams, and interprofessional collaboration in the classroom as particularly effective. The course contributed to students' development of their own professional voices and their understanding of those of other professions. Additional interpretive studies of students' experiences and those of faculty and professionals in practice are needed, particularly regarding strategies for increasing the effectiveness of experiential learning.


Acid-etching technique of non-decalcified bone samples for visualizing osteocyte-lacuno-canalicular network using scanning electron microscope.
The aim of this study was to define the acid-etching technique for bone samples embedded in polymethyl metacrylate (PMMA) in order to visualize the osteocyte lacuno-canalicular network (LCN) for scanning electron microscopy (SEM). Human jaw bone tissue samples (N = 18) were collected from the study population consisting of patients having received dental implant surgery. After collection, the bone samples were fixed in 70% ethanol and non-decalcified samples embedded routinely into polymethyl metacrylate (PMMA). The PMMA embedded specimens were acid-etched in either 9 or 37% phosphoric acid (PA) and prepared for SEM for further analysis. PMMA embedded bone specimens acid-etched by 9% PA concentration accomplishes the most informative and favorable visualization of the LCN to be observed by SEM. Etching of PMMA embedded specimens is recommendable to start with 30 s or 40 s etching duration in order to find the proper etching duration for the samples examined. Visualizing osteocytes and LCN provides a tool to study bone structure that reflects changes in bone metabolism and diseases related to bone tissue. By proper etching protocol of non-decalcified and using scanning electron microscope it is possible to visualize the morphology of osteocytes and the network supporting vitality of bone tissue.


[Long-term results of surgical treatment of the extracranial arteries aneurysm].
Aneurysms of extracranial arteries are sufficiently rare pathology in the extracranial arteries surgery. The authors aimed to research the frequency of occurrence of the extracranial arteries aneurysm, reasons of the onset, the localization, clinical manifestations and surgical treatment strategy. A retrospective study presents 10 cases of the extracranial arteries aneurysm for the last 5 years. A presence of aneurysmatic dilatation of extra-cranial arteries was detected according to the data of ultrasonic duplex scanning (UDS) and patients were directed to the hospital. The UDS was carried out as a routine procedure because of the presence of earlier acute stroke or the transitory ischemic attack. All the patients were carefully examined. A computed tomography and the recurring UDS were performed and the neurologic status of patients was estimated. An indication to surgical treatment was an increase of the internal carotid artery diameter and the common carotid artery more than 50% or equal to it. The presence of the local saccular aneurysm was one of the reasons. Surgical treatment strategy was determined by the anatomic position and possibilities for the reconstruction. The results of given operations showed, that the surgical treatment strategy should be recommended and could be fully justified in this pathology.


[Vasoactive factors in patients with a severe combined trauma].
46 patients with craniocerebral trauma combined with chest, abdominal, locomotor injuries were hospitalized to the critical care unit. At admission, blood pressure was low, blood loss reached 28% of circulating blood volume. Serum levels of hydrocortisone, nitrite, the activity of angiotensin-converting enzyme (ACE) were measured at admission, on admission hour 4, 24, day 3 and 7. Vasopressor to vasodepressor ratio (hydrocortisone x ACE/nitrite) was also estimated. It was found that severe combined trauma induces an intensive and long-term rise of blood hydrocortisone (a 3-fold rise at admission). ACE activity was low at all the measurements, nitrite levels were reduced only on day 1 and went up to normal on posttrauma day 3-7. The ratio hydrocortisone x ACE/nitrite was significantly elevated in all tests. It is concluded that in severe combined trauma low blood pressure was unrelated to nitric oxide.


Long-term prognosis for atypical and malignant meningiomas: a study of 71 surgical cases.
To contribute to a better understanding of the prognostic differences between atypical and malignant meningiomas as defined by the World Health Organization (WHO) and the influence of the grade of initial surgical excision on postoperative course, 42 cases of atypical and 29 of malignant meningioma were studied, along with long-term follow up. The two groups were compared with respect to long-term survival, recurrence-free survival, and median time to recurrence. The prognostic significance of the Simpson grade of surgical resection and tumor location was also considered. Survival at 5 and 10 years was recorded in 95% and 79%, respectively, of patients with atypical meningioma and in 64.3% and 34.5% of patients with malignant meningioma (p = 0.001). Recurrence-free survival and median time to recurrence were also significantly longer in patients with atypical than in those with malignant meningiomas: 11.9 versus 2 years (p = 0.001) and 5 versus 2 years (p < 0.0041), respectively. Six (26%) of the 23 recurring atypical meningiomas became malignant. Simpson Grade I resection and location in the cerebral convexity, which were closely related, were found to be associated with a significantly better clinical course in the entire series (p < or = 0.0016). Patients with atypical meningiomas fared better than those with malignant meningiomas after incomplete surgical excision (Simpson Grades II-III), but the difference was not statistically significant. Multivariate analysis using the Cox model indicated that radical extirpation (Simpson Grade I vs. II-III) and histological findings (atypical meningioma vs. malignant meningioma) were significantly related to prolonged survival (p < 0.0003 and p < 0.0388, respectively). In conclusion, the current study shows that for most patients with atypical meningioma the prognosis was less severe than for those with malignant meningioma, but the risk of a downhill course resulting from malignancy after incomplete resection and recurrence was not negligible (26%). In addition, the WHO classification was found to be inadequate for a minority of the atypical meningioma cases, which currently have the same unfavorable course as cases of malignant meningioma. The results also indicate that objective Simpson Grade I extirpation of convexity meningiomas can be successful despite histological findings of malignancy.


Short-term adaptations in spinal cord circuits evoked by repetitive transcranial magnetic stimulation: possible underlying mechanisms.
Repetitive transcranial magnetic stimulation (rTMS) has been shown to induce adaptations in cortical neuronal circuitries. In the present study we investigated whether rTMS, through its effect on corticospinal pathways, also produces adaptations at the spinal level, and what the neuronal mechanisms involved in such changes are. rTMS (15 trains of 20 pulses at 5 Hz) was applied over the leg motor cortical area in ten healthy human subjects. At rest motor evoked potentials (MEPs) in the soleus and tibialis anterior muscles were facilitated by rTMS (at 1.2xMEP threshold). In contrast, the soleus H-reflex was depressed for 1 s at stimulus intensities from 0.92 to 1.2xMEP threshold. rTMS increased the size of the long-latency depression of the soleus H-reflex evoked by common peroneal nerve stimulation and decreased the femoral nerve facilitation of the soleus H-reflex. These observations suggest that the depression of the H-reflex by rTMS can be explained, at least partly, by an increased presynaptic inhibition of soleus Ia afferents. In contrast, rTMS had no effect on disynaptic reciprocal Ia inhibition from ankle dorsiflexors to plantarflexors. We conclude that a train of rTMS may modulate transmission in specific spinal circuitries through changes in corticospinal drive. This may be of relevance for future therapeutic strategies in patients with spasticity.


Constitutive and conditional cadherin expression in cultured human ovarian surface epithelium: influence of family history of ovarian cancer.
Epithelial ovarian carcinomas arise in a simple mesothelium (ovarian surface epithelium, OSE) but exhibit properties of oviductal and endometrial epithelia. Thus, during malignant progression, their differentiation proceeds from simple to complex, in contrast to carcinomas in other tissues. Related changes in OSE of women with a history of familial ovarian cancer indicate that this aberrant differentiation is initiated very early in neoplastic progression. The mechanisms underlying this process are not understood. Because cadherins are known regulators of differentiation, we investigated the relationship of the cadherins E, N and P to OSE morphology, growth patterns and differentiation in cultures of normal and metaplastic OSE from women with (FH-OSE) and without (NFH-OSE) a family history of ovarian cancer and in the ovarian carcinoma lines OVCAR-3 and CaOV3. We used immunofluorescence, RT-PCR, in situ hybridization and Western blotting. Our results define N-cadherin as the constitutively expressed cadherin of normal and metaplastic OSE and indicate that P-cadherin is undetectable while E-cadherin expression is conditional and related to genotype, stage of neoplastic progression and growth pattern. The altered expression of E-cadherin in apparently normal OSE of women with hereditary ovarian cancer syndromes in conjunction with the known capacity of E-cadherin to induce epithelial characteristics implicates this adhesion molecule as a possible inducer of the aberrant Mullerian differentiation which characterizes epithelial ovarian carcinomas. Abnormal differentiation in such (pre)-neoplastic tissues may represent an early, irreversible, non-mutational step in ovarian epithelial neoplastic progression.


Albendazole: single or combination therapy with permethrin against pediculosis capitis.
Pediculosis capitis is a worldwide problem and a growing concern because of resistance to pediculicides. In the present study, we investigated whether albendazole could be used in the treatment of pediculosis capitis in combination with 1% permethrin or alone. A total of 150 children were randomly divided to five groups of 30 each. Group 1 got albendazole in a single dose (400 mg), group 2 got albendazole at 400 mg for 3 days, group 3 was given 1% permethrin, group 4 took 1% permethrin and albendazole in a single dose (400 mg), and group 5 got 1% permethrin and albendazole in a dose of 400 mg for 3 days. Groups given albendazole were also given another 400 mg dose of albendazole after 1 week. The success rate of treatment at the 2-week follow-up for all groups was 61.5%, 66.6%, 80.0%, 84.6%, and 82.1%, respectively. No statistically significant difference was found between the groups. The results of this study suggest that albendazole is effective against pediculosis capitis and there is no synergistic effect between albendazole and 1% permethrin.


Acquired immunodeficiency syndrome and the risk of stroke.
Although acquired immunodeficiency syndrome (AIDS) is thought to increase the risk of stroke, few data exist to quantify this risk. This is the first population-based study to quantify the AIDS-associated risk of stroke. We identified all incident ischemic stroke (IS) and intracerebral hemorrhage (ICH) cases among young adults 15 to 44 years of age in central Maryland and Washington, DC, who were discharged from any of the 46 hospitals in the study area in 1988 and 1991. Using data from the medical records, 2 neurologists reviewed each case to confirm the diagnosis. Cases of AIDS among these patients with stroke were defined using Centers for Disease Control and Prevention criteria (1987). The number of cases of AIDS in the central Maryland and Washington population during 1988 and 1991 was determined from regional health departments working with the Centers for Disease Control and Prevention. Poisson regression was used to estimate the age-, race-, and sex-adjusted relative risk of stroke associated with AIDS. There were 385 IS cases (6 with AIDS) and 171 ICH cases (6 with AIDS). The incidences of IS and ICH among persons with AIDS were both 0.2% per year. AIDS conferred an adjusted relative risk of 13.7 (95% confidence interval [CI], 6.1 to 30.8) for IS and 25.5 (95% CI, 11.2 to 58.0) for ICH. After exclusion of 5 cases of stroke in AIDS patients in whom other potential causes were identified, AIDS patients continued to have an increased risk of stroke with an adjusted relative risk of 9.1 (95% CI, 3.4 to 24.6) for IS and 12.7 (95% CI, 4.0 to 40.0) for ICH. This population-based study found that AIDS is strongly associated with both IS and ICH.


Quantitative Analysis of the Transcriptome of Two Commonly Used Human Monocytic Cell Lines-THP-1 and Mono Mac 6-Reveals Their Arrest during Early Monocyte/Neutrophil Differentiation.
Cell lines of monocyte/macrophage origin are often used as model systems to study monocyte/macrophage biology. A relevant question is how similar these cell lines are to their in vivo counterparts? To address this issue, we performed a detailed analysis of the transcriptome of two commonly used human monocyte/macrophage cell lines, Mono Mac 6 and THP-1. Both of these cell lines originate from leukemic cells with myelo-monocytic characteristics. We found that both Mono Mac 6 and THP-1 represent cells of very immature origin. Their transcriptomes show more similarities to immature neutrophils than cells of the monocyte/macrophage lineage. They express significant levels of N-elastase, proteinase 3, cathepsin G, and azurocidin but very low levels of CD14, ficolin, and complement factor P. All major MHC class II genes are also expressed at low levels. They show high levels of lysozyme and low levels of one of the immunoglobulin Fc receptors, FCGRIIA, which is characteristic of both neutrophils and monocytes. THP-1, but not Mono Mac 6, also expresses the high-affinity receptor for IgG, FCGRIA. Both cell lines lack the expression of the connective tissue components fibronectin, proteoglycan 4, and syndecan 3, which are characteristics of tissue macrophages but are absent in blood monocytes, indicating that they originate from bone marrow precursors and not yolk sac-derived hematopoietic cells. Both of these cell lines seem, therefore, to represent cells arrested during early myelo-monocytic development, at a branch point between neutrophil and monocyte differentiation. Their very immature phenotype indicates that great care should be taken when using these cell lines as models for normal monocyte/macrophage biology.


How aging impacts the encoding of binaural cues and the perception of auditory space.
Over the years, the effect of aging on auditory function has been investigated in animal models and humans in an effort to characterize age-related changes in both perception and physiology. Here, we review how aging may impact neural encoding and processing of binaural and spatial cues in human listeners with a focus on recent work by the authors as well as others. Age-related declines in monaural temporal processing, as estimated from measures of gap detection and temporal fine structure discrimination, have been associated with poorer performance on binaural tasks that require precise temporal processing. In lateralization and localization tasks, as well as in the detection of signals in noise, marked age-related changes have been demonstrated in both behavioral and electrophysiological measures and have been attributed to declines in neural synchrony and reduced central inhibition with advancing age. Evidence for such mechanisms, however, are influenced by the task (passive vs. attending) and the stimulus paradigm (e.g., static vs. continuous with dynamic change). That is, cortical auditory evoked potentials (CAEP) measured in response to static interaural time differences (ITDs) are larger in older versus younger listeners, consistent with reduced inhibition, while continuous stimuli with dynamic ITD changes lead to smaller responses in older compared to younger adults, suggestive of poorer neural synchrony. Additionally, the distribution of cortical activity is broader and less asymmetric in older than younger adults, consistent with the hemispheric asymmetry reduction in older adults model of cognitive aging. When older listeners attend to selected target locations in the free field, their CAEP components (N1, P2, P3) are again consistently smaller relative to younger listeners, and the reduced asymmetry in the distribution of cortical activity is maintained. As this research matures, proper neural biomarkers for changes in spatial hearing can provide objective evidence of impairment and targets for remediation. Future research should focus on the development and evaluation of effective approaches for remediating these spatial processing deficits associated with aging and hearing loss.


TRIM28 haploinsufficiency predisposes to Wilms tumor.
Two percent of patients with Wilms tumors have a positive family history. In many of these cases the genetic cause remains unresolved. By applying germline exome sequencing in two families with two affected individuals with Wilms tumors, we identified truncating mutations in TRIM28. Subsequent mutational screening of germline and tumor DNA of 269 children affected by Wilms tumor was performed, and revealed seven additional individuals with germline truncating mutations, and one individual with a somatic truncating mutation in TRIM28. TRIM28 encodes a complex scaffold protein involved in many different processes, including gene silencing, DNA repair and maintenance of genomic integrity. Expression studies on mRNA and protein level showed reduction of TRIM28, confirming a loss-of-function effect of the mutations identified. The tumors showed an epithelial-type histology that stained negative for TRIM28 by immunohistochemistry. The tumors were bilateral in six patients, and 10/11 tumors are accompanied by perilobar nephrogenic rests. Exome sequencing on eight tumor DNA samples from six individuals showed loss-of-heterozygosity (LOH) of the TRIM28-locus by mitotic recombination in seven tumors, suggesting that TRIM28 functions as a tumor suppressor gene in Wilms tumor development. Additionally, the tumors showed very few mutations in known Wilms tumor driver genes, suggesting that loss of TRIM28 is the main driver of tumorigenesis. In conclusion, we identified heterozygous germline truncating mutations in TRIM28 in 11 children with mainly epithelial-type Wilms tumors, which become homozygous in tumor tissue. These data establish TRIM28 as a novel Wilms tumor predisposition gene, acting as a tumor suppressor gene by LOH.


[Techniques to block the sciatic nerve by a lateral approach through the popliteal fossa].
Lateral approaches to the sciatic nerve through the popliteal fossa have recently been described as useful for providing adequate anesthesia and postoperative analgesia for foot and ankle surgery. Numerous publications have appeared on the approach in recent years, proposing new anatomical landmarks to facilitate location of the nerve, reduce the rate of complications, and increase the rate of success. When the lateral popliteal approach has been compared to other approaches to the sciatic nerve, similar success rates have been observed. However, when this technique is used certain factors must be borne in mind because they can influence both latency time and success. This review describes the lateral popliteal approach, its main variations, the factors that can affect latency time or success, and the possibility of providing continuous analgesia. We also sought to compare this approach to other techniques for blocking the sciatic nerve.


Altered expression of wild-type p53 tumor suppressor gene during murine epithelial cell transformation.
An epidermal cell model in which initiated, benign tumor-producing and carcinoma stages were derived from a cloned parental cell strain was used to examine p53 expression during multistage epithelial carcinogenesis. Increased steady-state levels of p53 RNA were detected in squamous cell carcinomas compared to papilloma and normal epidermal cells. Nontumorigenic initiated cell precursors of the carcinomas exhibited normal p53 expression, localizing altered p53 regulation to the malignant conversion stage. Immunoprecipitation and Western immunoblot analyses demonstrated elevated levels of p53 protein in the moderately differentiated carcinoma compared to normal cells, and negligible levels of p53 in the poorly differentiated carcinoma cells. Sequence analysis of p53 complementary DNA from normal and carcinoma cells revealed no mutations in the coding or 5'- and 3'-untranslated regions, suggesting a novel mechanism of p53 inactivation.


Allergen inhalation generates pro-inflammatory oxidised phosphatidylcholine associated with airway dysfunction.
Oxidised phosphatidylcholines (OxPCs) are produced under conditions of elevated oxidative stress and can contribute to human disease pathobiology. However, their role in allergic asthma is unexplored. The aim of this study was to characterise the OxPC profile in the airways after allergen challenge of people with airway hyperresponsiveness (AHR) or mild asthma. The capacity of OxPCs to contribute to pathobiology associated with asthma was also to be determined.Using bronchoalveolar lavage fluid from two human cohorts, OxPC species were quantified using ultra-high performance liquid chromatography-tandem mass spectrometry. Murine thin-cut lung slices were used to measure airway narrowing caused by OxPCs. Human airway smooth muscle (HASM) cells were exposed to OxPCs to assess concentration-associated changes in inflammatory phenotype and activation of signalling networks.OxPC profiles in the airways were different between people with and without AHR and correlated with methacholine responsiveness. Exposing patients with mild asthma to allergens produced unique OxPC signatures that associated with the severity of the late asthma response. OxPCs dose-dependently induced 15% airway narrowing in murine thin-cut lung slices. In HASM cells, OxPCs dose-dependently increased the biosynthesis of cyclooxygenase-2, interleukin (IL)-6, IL-8, granulocyte-macrophage colony-stimulating factor and the production of oxylipins via protein kinase C-dependent pathways.Data from human cohorts and primary HASM cell culture show that OxPCs are present in the airways, increase after allergen challenge and correlate with metrics of airway dysfunction. Furthermore, OxPCs may contribute to asthma pathobiology by promoting airway narrowing and inducing a pro-inflammatory phenotype and contraction of airway smooth muscle. OxPCs represent a potential novel target for treating oxidative stress-associated pathobiology in asthma.


The folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dubé syndrome is required for murine B-cell development.
Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant disorder characterized by cutaneous fibrofolliculomas, pulmonary cysts, and kidney malignancies. Affected individuals carry germ line mutations in folliculin (FLCN), a tumor suppressor gene that becomes biallelically inactivated in kidney tumors by second-hit mutations. Similar to other factors implicated in kidney cancer, FLCN has been shown to modulate activation of mammalian target of rapamycin (mTOR). However, its precise in vivo function is largely unknown because germ line deletion of Flcn results in early embryonic lethality in animal models. Here, we describe mice deficient in the newly characterized folliculin-interacting protein 1 (Fnip1). In contrast to Flcn, Fnip1(-/-) mice develop normally, are not susceptible to kidney neoplasia, but display a striking pro-B cell block that is entirely independent of mTOR activity. We show that this developmental arrest results from rapid caspase-induced pre-B cell death, and that a Bcl2 transgene reconstitutes mature B-cell populations, respectively. We also demonstrate that conditional deletion of Flcn recapitulates the pro-B cell arrest of Fnip1(-/-) mice. Our studies thus demonstrate that the FLCN-FNIP complex deregulated in BHD syndrome is absolutely required for B-cell differentiation, and that it functions through both mTOR-dependent and independent pathways.


[Dactylogyrids (Monogenea: Dactylogyridea) with unusual number of the anchors, their origin and phylogenetic significance. Original data].
The haptors Dactylogyrus spp., Anacanthorus sp., Trianchoratus sp. and Schilbetrematoides pseudodactylogyrus are investigated. On the base of the morphology, transfer of the domus, etc. a homology of the hooks in dactylogyrids (s. s.) and the pin-like structures (4 "A") in the haptor of Anacanthorinae and Dactylogyridae sensu Bychowsky et Nagibina, 1978 is demonstrated. The vestiges of the anchors in the haptor of dactylogyrids (s. l.), according to morphological data, correspond to the point of anchor formed during the ontogenesis. In S. pseudodactylogyrus the pins are redescribed as typical vestiges of the anchors.


Increment Antimicrobial Resistance During the COVID-19 Pandemic: Results from the Invifar Network.
Aim: This study aims to assess the changes in antimicrobial resistance among some critical and high-priority microorganisms collected previously and during the coronavirus disease 2019 (COVID-19) pandemic in Mexico. Methods: We collected antimicrobial susceptibility data for critical and high-priority microorganisms from blood, urine, respiratory samples, and from all specimens, in which the pathogen may be considered a causative agent. Data were stratified and compared for two periods: 2019 versus 2020 and second semester 2019 (prepandemic) versus the second semester 2020 (pandemic). Results: In the analysis of second semester 2019 versus the second semester 2020, in blood samples, increased resistance to oxacillin (15.2% vs. 36.9%), erythromycin (25.7% vs. 42.8%), and clindamycin (24.8% vs. 43.3%) (p ≤ 0.01) was detected for Staphylococcus aureus, to imipenem (13% vs. 23.4%) and meropenem (11.2% vs. 21.4) (p ≤ 0.01), for Klebsiella pneumoniae. In all specimens, increased ampicillin and tetracycline resistance was detected for Enterococcus faecium (p ≤ 0.01). In cefepime, meropenem, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Escherichia coli; and in piperacillin-tazobactam, cefepime, imipenem, meropenem, ciprofloxacin, levofloxacin, and gentamicin (p ≤ 0.01), resistance was detected for Pseudomonas aeruginosa. Conclusion: Antimicrobial resistance increased in Mexico during the COVID-19 pandemic. The increase in oxacillin resistance for S. aureus and carbapenem resistance for K. pneumoniae recovered from blood specimens deserves special attention. In addition, an increase in erythromycin resistance in S. aureus was detected, which may be associated with high azithromycin use. In general, for Acinetobacter baumannii and P. aeruginosa, increasing resistance rates were detected.


Traffic lead pollution of some edible crops in Israel.
Fruit, vegetables and other crops grown in areas of heavy traffic were sampled and analysed for lead. The maximum lead content in washed vegetables was found in lettuce which contained about 0.5 mg/Kg (fresh weight). The low lead contents of the crops are partially due to the low lead contents of the soils on which they are grown. These in turn are a reflection of the lack of organic matter and clays in the soils. There appears to be no undue danger to health from eating crops tested.


Identification of PCB Congeners and their Thresholds associated with Diabetes using Decision Tree Analysis.
Few studies have investigated the potential combined effects of multiple PCB congeners on diabetes. To address this gap, we used data from 1244 adults in the National Health and Nutrition Examination Survey (NHANES) 2003-2004. We used 1) classification trees to identify serum PCB congeners and their thresholds associated with diabetes; and 2) logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of diabetes with combined PCB congeners. Of the 40 PCB congeners examined, PCB 126 has the strongest association with diabetes. The adjusted OR of diabetes comparing PCB 126 > 0.025 to ≤ 0.025 ng/g was 2.14 (95% CI 1.30-3.53). In the subpopulation with PCB 126 > 0.025 ng/g, a lower PCB 101 concentration was associated with an increased risk of diabetes (comparing PCB 101 < 0.72 to ≥ 0.72 ng/g, OR = 3.3, 95% CI: 1.27-8.55). In the subpopulation with PCB 126 > 0.025&PCB 101 < 0.72 ng/g, a higher PCB 49 concentration was associated with an increased risk of diabetes (comparing PCB 49 > 0.65 to ≤ 0.65 ng/g, OR = 2.79, 95% CI: 1.06-7.35). This nationally representative study provided new insights into the combined associations of PCBs with diabetes.


Magnesium Isoglycyrrhizinate Induces an Inhibitory Effect on Progression and Epithelial-Mesenchymal Transition of Laryngeal Cancer via the NF-κB/Twist Signaling.
Magnesium isoglycyrrhizinate (MI) was extracted from roots of the plant Glycyrrhiza glabra, which displays multiple pharmacological activities such as anti-inflammation, anti-apoptosis, and anti-tumor. Here, we aimed to investigate the effect of MI on the progression and epithelial-mesenchymal transition (EMT) of laryngeal cancer. Forty laryngeal cancer clinical samples were used. The role of MI in the proliferation of laryngeal cancer cells was assessed by MTT assay, Edu assay and colony formation assay. The function of MI in the migration and invasion of laryngeal cancer cells was tested by transwell assays. The effect of MI on apoptosis of laryngeal cancer cells was determined by cell apoptosis assay. The impact of MI on tumor growth in vivo was analyzed by tumorigenicity analysis using Balb/c nude mice. qPCR and Western blot analysis were performed to measure the expression levels of gene and protein, respectively. We identified that EMT-related transcription factor Twist was significantly elevated in the laryngeal cancer tissues. The expression of Twist was also enhanced in the human laryngeal carcinoma HEP-2 cells compared with that in the primary laryngeal epithelial cells. The high expression of Twist was remarkably correlated with poor overall survival of patients with laryngeal cancer. Meanwhile, our data revealed that MI reduced cell proliferation, migration and invasion and enhanced apoptosis of laryngeal cancer cells in vitro. Moreover, MI decreased transcriptional activation and the expression levels of NF-κB and Twist, and alleviated EMT in vitro and in vivo. MI remarkably inhibited tumor growth and EMT of laryngeal cancer cells in vivo. MI restrains the progression of laryngeal cancer and induces an inhibitory effect on EMT in laryngeal cancer by modulating the NF-κB/Twist signaling. Our finding provides new insights into the mechanism by which MI inhibits laryngeal carcinoma development, enriching the understanding of the anti-tumor function of MI.


Glutathione supplementation and training increases myocardial resistance to ischemia-reperfusion in vivo.
The present study examined the effects of oral reduced glutathione (GSH) supplementation in conjunction with endurance training on contractile function, antioxidant defense, and oxidative damage in response to ischemia-reperfusion (I/R) in rat hearts. Female Sprague-Dawley rats (age 4 mo, n = 72) were randomly assigned to a treadmill-trained (T; 25 m/min, 15% grade, for 75 min/day, 5 days/wk, for 10 wk) or untrained (U) group. Each group was further divided into rats receiving 5 g GSH/kg diet during the final 17 days of training (GSH-S) and control (C) groups. One-half of each group of rats was subjected to I/R by surgical occlusion of the main coronary artery for 45 min, followed by 30-min reperfusion or sham operation. Left ventriclar (LV) peak systolic pressure (LVSP) and contractility (+dP/dt), measured with a catheter inserted into the LV via the carotid artery, decreased with I/R in all groups (P < 0.05). However, LVSP with I/R in the T/GSH-S group was 9.5%, 17%, and 18% higher (P < 0.05) than that in the U/GSH-S, T/C, and U/C groups, respectively. +dP/dt with I/R was 19%, 27%, and 29% (P < 0.05) greater in the T/GSH-S group versus the T/C, U/GSH-S, and U/C groups, respectively. I/R decreased heart GSH content by 12-17% (P < 0.05) and increased oxidized glutathione (GSSG) by 20-27% (P < 0.05). T/GSH-S hearts showed 15% higher GSH (P < 0.05) and a 32% higher GSH-to-GSSG ratio (P < 0.05) than the U/C group at the end of I/R. Myocardial superoxide dismutase, GSH peroxidase, glutathione reductase, and gamma-glutamyl transpeptidase activities were increased with treadmill training in both GSH-S and C rats. I/R induced myocardial lipid peroxidation and lactate dehydrogenase release were attenuated with T/GSH-S treatment. The present data indicate that training in conjunction with dietary GSH supplementation can increase myocardial GSH content and antioxidant defense capacity, thereby protecting the intact heart against oxidative damage and functional retardation caused by I/R.


Prognostic implication and functional annotations of APOBEC3G expression in patients with Melanoma.
Aim: Skin cutaneous melanoma (SKCM) is one of the most life-threatening malignancies damaging human health. APOBEC3G (A3G) has been found in several cancers; however, the role of A3G in SKCM is rarely studied. This study aimed to investigate the expression of A3G in tumor tissue and its prognostic value in SKCM patients. Method: A total of 512 SKCM patients from the First Affiliated Hospital of Soochow University (FAHSU) and the Cancer Genome Atlas (TCGA) database were consecutively recruited in analyses. Differential transcriptional and proteome expression profiles were obtained from multiple datasets. GEPIA was used to assess the survival analysis between distinguished groups. Both univariate and multivariate Cox regression analysis was performed to address the influence of independent factors on disease-free survival (RFS) and overall survival (OS). In addition, 31 SKCM and 31 nevus tissues were collected for immunohistochemical (IHC) staining and evaluation. STRING, DAVID and Gene Set Enrichment Analysis (GSEA) was utilized to conduct a network of related genes and significant pathways. Furthermore, we investigated the relationship of A3G with tumor-infiltrating immune cells (TIICs) by TIMER and TISIDB. Result: We found both transcriptional and proteomics expressions of A3G were elevated in SKCM. Survival analysis and ROC curves showed significant diagnostic and prognostic ability of A3G. IHC results showed increased expression of A3G in SKCM compared to nevus tissues. Importantly, A3G expression was closely associated with the immune-infiltrating levels of B cells, CD4+ T, CD8+ T, neutrophils, macrophages and dendritic cells. Conclusion: In summary, our study first reveals that elevated A3G expression is significantly correlated with better prognosis in SKCM patients. The role of A3G in SKCM demonstrated that it might be a prognostic and immunotherapeutic biomarker for SKCM.


Anakinra-Induced Acute Liver Failure in an Adolescent Patient with Still's Disease.
The interleukin-1 (IL-1) family consists of 11 cytokines that play key regulatory roles in many immune and inflammatory processes. Anakinra (Kineret, Amgen, Inc.) is an IL-1 receptor antagonist (IL-1ra). Increased levels of IL-1 are found in several disease states suggesting that anakinra may be beneficial in disorders associated with elevated IL-1 levels. Anakinra has been effectively used in the treatment of systemic juvenile idiopathic arthritis and adult-onset Still's disease (AOSD). Despite its therapeutic benefits, anakinra also has potential side effects, including hepatotoxicity. We present a case of AOSD in an adolescent male that was treated with anakinra. During treatment, the patient developed acute liver failure that resolved upon withdrawal of anakinra. Although anakinra-induced liver injury has been reported in adults, including one case of subacute liver failure, we believe our case is the first to show severe acute liver failure in an adolescent treated with anakinra. This case provides significant insight into a potentially serious complication associated with anakinra. It is important to further delineate these complications as the treatment indications for this drug expand.


Thrust and torque force analysis in the drilling of aramid fibre-reinforced composite laminates using RSM and MLPNN-GA.
Aramid Fibre Reinforced Plastic composites are difficult to be drilled due to anisotropic material properties. Currently, soft computing techniques are used as alternatives to conventional mathematical models, which is robust and can deal with inaccuracy and uncertainty. In this paper, drilling of Aramid Fibre Reinforced Plastics (AFRPs) was carried out using Taguchi L54 experimental layout. Drilling tool used in this experiment was solid carbide. The purpose of this study was to find optimum combination of drilling parameters to obtain minimum thrust and torque force to reduce the delamination. Also, this paper proposed a prediction model of Multilayer Perception Neural Network optimized by Genetic Algorithm (MLPNN-GA). Moreover, RSM technique was used to evaluate the influence of process parameters (spindle speed, feed rate, drill point angle and drill diameter on thrust force and torque. The prediction capability of both RSM and MLPNN-GA was compared with Response optimizer for thrust force and torque. The investigation demonstrated that drill point angle is the primary factor affecting thrust force and drill diameter influences the torque force on the drill bit. Overall, this study recommends the use of high speed and low feed combination and drill point angles of 90°-118° to reduce the delamination of the materials in the drilling of AFRP composites.