[Emergency Keratoplasty with Porcine Xenografts in Necrotizing Keratitis].
Background The great shortage of donor material in Ukraine makes it necessary to find additional sources of transplant material. A possible suitable material are the porcine corneas, as they are similar in structure and biomechanical parameters to the human cornea. The purpose of our study was to analyze the results of therapeutic keratoplasty (KP) with keratoxenotransplants from cryolyophilized porcine corneas in patients with severe necrotizing keratitis. Methods A retrospective analysis of 32 xenotransplantations patients with severe necrotizing keratitis (17 lamellar, 6 stepped perforating, 4 perforating, 5 "biological coverage" according to Puchkovskaya) was completed. Results All eyes could be preserved, but the graft was rejected in all eyes. A semitransparent xenograft (XG) was achieved in 9 patients (33.3%). The best results were obtained after lamellar XKP with an XT diameter of 3.5 - 6.5 mm. Lamellar XTs with larger diameters (7.0 - 10.0 mm) were opaque. Postoperatively, the intensity of the inflammatory response after stepped XKP was slightly lower than that of the classical perforating XKP. A new KP with human corneas had to be performed in 5 patients, in one case combined with an antiglaucomatous operation and in another case with cataract extraction. Antiglaucomatous surgery had to be performed in 5 patients (15.6%). Conclusion In the absence of human donor corneas, a porcine keratoxenoimplant can be used as temporary therapeutic keratoplasty in case of emergency stop the inflammation process and to save the eye. In cases of keratoxenoimplant, a poor visual outcome is expected.


Describing pain management documentation.
Managing postsurgical pain continues to be one of the nation's top clinical care priorities and concerns. Despite widely publicized national care guidelines, effective pain management for all patients is not a reality. This study explored how nurses in a community hospital documented the process of pain management for a group of postsurgical patients. The results have implications for all adult health nurses.


Lymphangioleiomyomatosis: an unusual cause of dyspnea in young women.
Lymphangioleiomyomatosis is a rare and complicated disorder that affects the young, almost exclusively women. It may be associated with the tuberous sclerosis complex, which includes renal angiolipoma, chylothorax and lymph node myomatosis. Its clinical pulmonary manifestations vary from simple cough to the development of recurrent pneumothoraces, hemoptysis, and even complicated pleural effusions. Progressive dyspnea develops as the disease evolves. Eventually most patients require lung transplantation. This wide array of symptoms and signs makes the differential diagnosis extensive, and the clinician must be familiar with this disorder to arrive promptly to the correct diagnosis. We report a case of a 36-year-old woman with a long history of recurrent pleuritic chest pain with associated dyspnea before being diagnosed with lymphangioleiomyomatosis. A review of the literature pertinent to this case is provided.


Survival of Patients With Multiple Intracranial Metastases Treated With Stereotactic Radiosurgery: Does the Number of Tumors Matter?
Defining prognostic factors is a crucial initial step for determining the management of patients with brain metastases. Randomized trials assessing radiosurgery have commonly limited inclusion criteria to 1 to 4 brain metastases, in part due to multiple retrospective studies reporting on the number of brain metastases as a prognostic indicator. The present study reports on the survival of patients with 1 to 4 versus ≥5 brain metastases treated with radiosurgery. We evaluated a retrospective multi-institutional database of 1523 brain metastases in 507 patients who were treated with radiosurgery (Gamma Knife or Cyberknife) between 2001 and 2014. A total of 243 patients were included in the analysis. Patients with 1 to 4 brain metastases were compared with patients with ≥5 brain metastases using a standard statistical analysis. Cox hazard regression was used to construct a multivariable model of overall survival (OS). To find covariates that best separate the data at each split, a machine learning technique Chi-squared Automated Interaction Detection tree was utilized. On Pearson correlation, systemic disease status, number of intracranial metastases, and overall burden of disease (number of major involved organ systems) were found to be highly correlated (P<0.001). Patients with 1 to 4 metastases had a median OS of 10.8 months (95% confidence interval, 6.1-15.6 mo), compared with a median OS of 8.5 months (95% confidence interval, 4.4-12.6 mo) for patients with ≥5 metastases (P=0.143). The actuarial 6 month local failure rate was 5% for patients with 1 to 4 metastases versus 3.2% for patients with ≥5 metastases (P=0.404). There was a significant difference in systemic disease status between the 2 groups; 30% of patients had controlled systemic disease in the <5 lesions group, versus 8% controlled systemic disease in the ≥5 lesions group (P=0.005). Patients with 1 to 4 metastases did not have significantly improved OS in a multivariable model adjusting for systemic disease status, systemic extracranial metastases, and other key variables. The Chi-squared Automated Interaction Detection tree (machine learning technique) algorithm consistently identified performance status and systemic disease status as key to disease classification, but not intracranial metastases. Although the number of brain metastases has previously been accepted as an independent prognostic indicator, our multicenter analysis demonstrates that the number of intracranial metastases is highly correlated with overall disease burden and clinical status. Proper matching and controlling for these other determinants of survival demonstrates that the number of intracranial metastases alone is not an independent predictive factor, but rather a surrogate for other clinical factors.


Is ultrasonographic enthesitis evaluation helpful for diagnosis of non-radiographic axial spondyloarthritis?
The aim of this study is to evaluate the diagnostic utility of ultrasonographic enthesitis assessment in patients with non-radiographic axial spondyloarthritis (nr-axSpA) and to compare different sonographic scoring methods. Patients with nr-axSpA (n = 30) and mechanical back pain (MBP) (n = 30) were enrolled in the study with standardized clinical criteria. For both of the groups, a total of 18 entheses were evaluated in each patient with B mode ultrasound and power Doppler by a sonographer who is blinded to initial clinical and radiological assessments. Glasgow Ultrasound Enthesitis Scoring System (GUESS), Madrid Sonographic Enthesitis Index (MASEI) and D'Agostino grading system were performed. Intra-rater and inter-rater reliability analyses were evaluated with the intraclass correlation coefficient (ICC). There was at least one enthesitis in 96.7% of patients with nr-axSpA. Median values of the number of enthesitis were 5 in nr-axSpA and 0 in MBP. Mean GUESS total scores were 0.9 in MBP and 4.5 in nr-axSpA. Mean MASEI total scores were 2.3 and 10.5, respectively. The sensitivities were 96.7% and 93.3% for GUESS and MASEI while the detected specificities were 80% for both methods. For Intra-rater reliability analysis, ICC was calculated as 0.981 for GUESS and 0.975 for MASEI, while it was calculated as 0.964 and 0.962 for inter-rater reliability analysis. Thus, evaluation of enthesitis with ultrasound is a reliable, helpful tool for the distinction of patients with nr-axSpA from patients with MBP. We favored the use of MASEI because of assessing upper extremity, using power Doppler and having a correlation with disease activity.


3-Methyladenine inhibits transport from late endosomes to lysosomes in cultured rat and mouse fibroblasts.
The effect of 3-methyladenine on transport from endosomes to lysosomes was studied in rat embryonic and mouse 3T3 fibroblasts. Subcellular fractionation in 27% Percoll gradients showed that the pre-endocytosed (5 min pulse) horseradish peroxidase (HRP) was not transported from endosomes to dense lysosomes in cells chased in the presence of 10 mM 3-methyladenine. However, fractionation in 20% Percoll gradients, which separated early endosomes from late endosomes and lysosomes, as well as light and electron microscopic experiments, showed that HRP was transported from early endosomes to the perinuclear late endosomes. Immunoprecipitation of metabolically labeled cells was used to study the biosynthetic processing of a lysosomal proteinase, cathepsin L. The results showed that the early processing of the precursor to the intermediate form was not affected by 3-methyladenine, while the late processing of the intermediate to the mature form was retarded. In addition, immunofluorescence labeling showed that 3-methyladenine treatment caused accumulation of cathepsin L in the perinuclear area. Another lysosomal enzyme, beta-glucuronidase, was normally distributed in both perinuclear and peripheral vesicles which indicated that the localization of lysosomes was not altered. The results thus suggest that the late processing of cathepsin L was inhibited because transport from perinuclear endosomes to lysosomes was retarded. In conclusion, both endocytic pulse-chase experiments and immunoprecipitation of metabolically labeled cathepsin L indicate that 3-methyladenine inhibits transport from late endosomes to mature lysosomes in both rat and mouse fibroblasts.


Development of bone morphogenetic protein receptors in the nervous system and possible roles in regulating trkC expression.
Characterization of bone morphogenetic protein receptor (BMPR) expression during development is necessary for understanding the role of these factors during neural maturation. In this study, in situ hybridization analyses demonstrate that BMP-specific type I (BMPR-IA and BMPR-IB) and type II (BMPR-II) receptor mRNAs are expressed at significant levels in multiple regions of the CNS, cranial ganglia, and peripheral sensory and autonomic ganglia during the embryonic and neonatal periods. All three BMP receptor subunits are expressed within periventricular generative zones. BMPR-IA is more abundant than the other receptor subtypes, with widespread expression in the brain, cranial ganglia, and peripheral ganglia. By contrast, BMPR-IB mRNA displays significant expression within more restricted regions, including the anterior olfactory nuclei. BMPR-II mRNA exhibits peak expression within the cerebellar Purkinje cell layer and the hippocampus, as well as within cranial ganglia. The distribution of BMP receptors within large neurons in adult dorsal root ganglia suggested a possible role in regulating expression of the neurotrophin receptor trkC. This hypothesis was tested in explant cultures of embryonic day 15 (E15) and postnatal day 1 (P1) sympathetic superior cervical ganglia (SCG). Treatment of the E15 or the P1 SCG with BMP-2 induced expression of trkC mRNA and responsiveness of sympathetic neurons to NT3 as measured by neurite outgrowth. The pattern of expression of BMP receptors in embryonic brain suggests several potentially novel areas for further developmental analysis and supports numerous recent studies that indicate that BMPs have a broad range of cellular functions during neural development and in adult life.


A space for measuring mind and brain: interdisciplinarity and digital tools in the development of brain mapping and functional imaging, 1980-1990.
Brain mapping is said to have opened up the possibility of a new collaboration between the sciences of mind and the sciences of the brain, potentially leading to a new kind of scientist, sometimes called "cognitive neuroscientist." This article traces the recent history of brain mapping and analyzes the processes that have led to a new "close working relationship" between the sciences of mind and brain. A key part of the working relationship is shown to be constituted through the development of the Talairach system, a digital space in which to measure structure and function. The development of meaningful brain mapping data involves the creation of measurement spaces that allow interdisciplinary collaboration and is not the result solely of theoretical developments or of the application of a technology.


The whole-soil carbon flux in response to warming.
Soil organic carbon harbors three times as much carbon as Earth's atmosphere, and its decomposition is a potentially large climate change feedback and major source of uncertainty in climate projections. The response of whole-soil profiles to warming has not been tested in situ. In a deep warming experiment in mineral soil, we found that CO2 production from all soil depths increased with 4°C warming; annual soil respiration increased by 34 to 37%. All depths responded to warming with similar temperature sensitivities, driven by decomposition of decadal-aged carbon. Whole-soil warming reveals a larger soil respiration response than many in situ experiments (most of which only warm the surface soil) and models.


Increased heart rate variability but normal resting metabolic rate in hypocretin/orexin-deficient human narcolepsy.
We investigated autonomic balance and resting metabolic rate to explore their possible involvement in obesity in hypocretin/orexin-deficient narcoleptic subjects. Resting metabolic rate (using indirect calorimetry) and variability in heart rate and blood pressure were determined in the fasted resting state. Subjects included 15 untreated, hypocretin-deficient male narcoleptics and 15 male controls matched for age and body mass index. Spectral power analysis revealed greater heart rate and blood pressure variability in hypocretin-deficient male narcoleptic patients (heart rate: p = 0.01; systolic blood pressure: p = 0.02; diastolic: p < 0.01). The low to high frequency ratio of heart rate power did not differ between groups (p = 0.48), nor did resting metabolic rate (controls: 1767 +/- 226 kcal/24 h; patients: 1766 +/- 227 kcal/24h; p = 0.99). Resting metabolic rate was not reduced in hypocretin-deficient narcoleptic men and therefore does not explain obesity in this group. Whether the increased heart rate and blood pressure variability--suggesting reduced sympathetic tone--is involved in this regard remains to be elucidated.


Anatomy and relations of the infraspinatus and the teres minor muscles: a fresh cadaver dissection study.
Despite their functional importance, the infraspinatus (ISP) and teres minor (TM) muscles have been little investigated. This study aimed to describe the macroscopic morphology, innervation, and inter-relations of the ISP and TM muscles. Forty fresh cadaver dissections and histologic analysis were performed. Three groups of specimens were distinguished according to the rotator cuff tendon status: (1) intact rotator cuff; (2) supraspinatus tendon tears with intact ISP tendon; and (3) both supraspinatus and ISP tendons torn. Muscle fiber organization and muscle and tendon length were recorded. ISP and TM innervation and fiber structure were studied. ISP muscles were composed of three groups of fiber organized in two planes: two superficial groups, with mean pennation angles of, respectively, 27° ± 4° and 23° ± 3° with respect to the axis of the central tendon of the underlying group. TMs were thick fusiform muscles showing a parallel organization; 26 specimens (67 %) had aponeuroses isolating the TM, with a mean length of 5.2 ± 2.7 cm. Rotator cuff lesions were associated with relatively greater ISP tendon than muscle length. Innervation of the ISP muscle comprised 2-4 main branches from the suprascapular nerve and that of the TM 1 branch from the axillary nerve. ISP muscle body morphology derives from three groups of fibers in two planes. The TM has a parallel organization. Several nerve branches innervate the ISP muscle, whereas only one supplies the TM. The limits between the two muscles bodies consist of an aponeurotic fascia in two-thirds of cases.


Chryseobacterium carnipullorum sp. nov., isolated from raw chicken.
Three Gram-staining-negative, rod-shaped, non-spore-forming, non-motile, oxidase-positive, yellow pigmented and aerobic bacterial isolates designated 8_R23573, 9_R23581(T) and 10_R23577 were isolated from raw chicken at a broiler processing plant in Bloemfontein, South Africa. A polyphasic taxonomic approach was used to determine their exact taxonomic identities. Phylogenetic analysis of the 16S rRNA gene sequences showed that the three strains belonged to the genus Chryseobacterium, exhibiting the highest similarities to Chryseobacterium shigense DSM 17126(T) (98.6-99.2%) and Chryseobacterium luteum DSM 18605(T) (98.3-98.7%). The most abundant quinone was menaquinone MK-6 and the predominant cellular fatty acids were iso-15:0, iso-17:1ω9c, iso-17:0 3-OH and summed feature 3 (iso-16:1ω7c and/or iso-15:0 2-OH), which supported the affiliation of the strains to the genus Chryseobacterium. The DNA G+C contents of the strains were 36.9, 36.7 and 36.6 mol% respectively. The DNA-DNA hybridization results gave relatedness values ranging from 78.8 to 87.2% among the three strains and 23.4 to 56.1% to the two nearest phylogenetic neighbours C. shigense DSM 17126(T) and C. luteum LMG 23785(T). On the basis of the data from this polyphasic study, the three strains are concluded to represent a novel species of the genus Chryseobacterium for which the name Chryseobacterium carnipullorum sp. nov. is proposed. The type strain is 9_R23581(T) ( = LMG 26732(T) =DSM 25581(T)).


Synthesis and gastric antisecretory properties of 15-deoxy-16-hydroxyprostaglandin E analogues.
The preparation and gastric antisecretory activity of a series of 15-deoxy-16-hydroxyprostaglandin analogues are described. The compounds were tested intravenously in histamine-stimulated Heidenhain pouch dogs in relation to the reference standards PGE1 and PGE1 methyl ester (PGE1ME). The parent compound of this seris, (+/-)-15-deoxy-16alpha,beta-hydroxyprostaglandin E1 methyl ester (3), was found to be equipotent to the reference standard PGE1ME. Methylation at C-16 of 3 produced 8 which was found to be some 40 times more potent than PGE1. In sharp contrast, addition of two methyl groups to 3 at C15 or C17 markedly reduced the antisecretory action. The 16-ethyl analogue of 3 also showed reduced potency. Removal or epimerization of the C-11 hydroxy group of 8 reduced the activity. Likewise, hydrogenation or changing the stereochemistry of the 13,14 double bond from trans to cis decreased the activity. On the other hand, omega-homologation of 8 or the introduction of a cis-5,6 double bond did not affect the potency. From these studies, it appears that 8, 16, and 17 possess optimum gastric antisecretory effects in this series.


Tackling health determinants in rural India: the KHOJ initiative.
There have been significant public health achievements in recent years; not only do people live longer and healthier lives, but there has also been a decline in communicable diseases, like tuberculosis, and water-borne diseases, especially in developing countries like India. Although lifestylerelated problems are emerging globally, developing countries carry heavier burdens of poor health conditions, which is an issue of serious concern, in particular among marginalized populations. Reaching out to these groups is a global challenge, and particularly in India, where one-third of the population (between 250 and 300 million people) live in remote, difficult and vulnerable areas lacking basic amenities. In order to address the 'health for all' challenge, this Commentary advocates for the public, private and non-profit sectors to work together to implement innovative community-based approaches that address the various social determinants of health. The case of the Voluntary Health Association of India (VHAI), a national NGO, is presented as an example of successful coordinated community and policy actions to improve health determinants in remote rural areas of India.


Meningococcal group C and w135 immunological hyporesponsiveness in african toddlers.
A phase II clinical study was conducted in African toddlers (aged 12 to 23 months), with subjects receiving either investigational meningococcal group A conjugate (PsA-TT), meningococcal ACWY polysaccharide (PsACWY), or Haemophilus influenzae type b (Hib-TT) vaccine. Ten months following vaccination, the 3 study groups were further randomized to receive a dose of PsA-TT, a 1/5 dose of PsACWY, or a dose of Hib-TT vaccine. Group A serum bactericidal antibody (SBA) results have been reported previously, with PsA-TT demonstrating superior immunogenicity versus PsACWY vaccine. Immunogenicity for serogroups W135 and C was assessed by SBA assay to investigate the impact of multiple doses in this age group. Blood samples were taken prior to vaccination, 28 days and 40 weeks post-primary vaccination, and 7 and 28 days post-booster vaccination with a 1/5 dose of PsACWY. Subjects who had previously received a full dose of PsACWY had W135 SBA geometric mean titers (GMTs) of 26.1 and 4.4 at 7 and 28 days post-booster vaccination with a 1/5 PsACWY dose, respectively, whereas the W135 SBA GMTs of naïve subjects at these time points following vaccination with a 1/5 dose of PsACWY were 861.1 and 14.6, respectively. Similar differences were observed for serogroup C, with SBA GMTs of 99 and 5.9 at 7 and 28 days post-booster vaccination with a 1/5 dose of PsACWY, respectively, for naïve subjects, compared to 4.1 and 3.2 for previously vaccinated subjects. Immunologic hyporesponsiveness for groups C and W135 was observed following a full dose of PsACWY vaccine at 12 to 23 months of age and a 1/5 dose of PsACWY 10 months later compared to the case for PsACWY-naïve subjects receiving a 1/5 dose of PsACWY vaccine.


Antimicrobials commonly used for urinary tract infection: sulfonamides, trimethoprim-sulfamethoxazole, nitrofurantoin, nalidixic acid.
Sulfonamides, trimethoprim-sulfamethoxazole, nitrofurantoin, and nalidixic acid are excreted in the urine in high concentration and, with the exception of Pseudomonas aeruginosa and Serratia marcescens, are all active in vitro against usual aerobic gram-negative bacteria. They are useful for treatment of uncomplicated lower urinary tract infections in an outpatient setting but are probably not indicated for acute upper tract infections, especially in the hospitalized patient. Trimethoprim-sulfamethoxazole is a very effective combination agent in vitro, has appealing pharmacokinetic properties, and is usually well tolerated by patients. However, it is more expensive than the sulfonamides and is ordinarily not indicated for initial treatment. A sulfonamide is in our view still the agent of first choice, with either nitrofurantoin or nalidixic acid as an alternative if sulfonamides cannot be tolerated.


Self and cross-mode interactions in a weakly nonlinear two-dimensional structural-acoustic waveguide.
In this study, that is entirely semi-analytical, weakly nonlinear wave propagation in an infinite two-dimensional structural-acoustic waveguide is studied. The lower boundary of the waveguide is a rigid wall, while the top boundary is a flexible plate. Both in-plane and transverse displacements are included in the flexible plate model. The acoustic fluid and the plate are modeled using standard nonlinear equations. The waveguide is driven by an oscillating piston at the origin. The regular perturbation method is used to separate the equations at linear and nonlinear order. The self- and cross-mode interactions of the non-orthogonal propagating modes are solved for. It is found that in the self-mode interactions, resonances occur both in pressure and in the in-plane plate displacement at their own different frequencies. Whereas in the cross-mode interactions, there is no in-plane plate resonance and mostly beats (in space) occur except at some frequencies where resonance in pressure is seen. Also, boundary flexibility reduces the number of resonances drastically in comparison to the rigid waveguide. The relevant conditions and closed form solutions are derived for the resonance cases. It is also observed among the nonresonant solutions (or beats) that below the coincidence frequency, the bending mode dominates, and above the coincidence frequency, the acoustic mode dominates.


Clinical evaluation of the Cavitron Biotronics tonometer.
The Mackay-Marg tonometer has been shown to be an accurate tonometer for the measurement of intraocular pressure in eyes with both normal and diseased corneas. This tonometer is no longer manufactured and has been replaced by the Cavitron Biotronics tonometer that works on the same principle but utilizes a different recording display. The Cavitron Biotronics tonometer's accuracy was compared with that of the Goldmann applanation tonometer in 75 eyes. The Cavitron Biotronics tonometer is not as accurate as the original Mackay-Marg tonometer for individual readings. However, if four readings are taken, the value of the Cavitron Biotronics tonometer that correlated best with Goldmann applanation tonometry was the one reading of the four with the highest value. Using this one value, the Cavitron Biotronics instrument underestimates the true intraocular pressure below 27 mm Hg and overestimates it above this value.


Preliminary Validation of the Pain Burden Inventory in a Pediatric Chronic Pain Population.
To determine the preliminary reliability and validity of the Pain Burden Inventory-Youth (PBI-Y), a 7-item measure of the impact of chronic pain in adolescents with chronic pain that was, initially validated in youth with sickle cell disease. A retrospective chart review of 130 patients presenting to an interdisciplinary pain clinic were examined with 98 (mean age=14.49; 66% female) comprising the final sample. Demographic information as well as adolescent and parent self-reported measures were examined. Youth reported a variety of pains including abdominal pain, headaches, back pain, and amplified musculoskeletal pain. The PBI-Y demonstrated strong internal reliability (α=0.792) and strong cross-informant concordance (r=0.822; P=0.000). Good construct validity was seen where higher scores on the PBI-Y were correlated with higher scores of (1) functional disability (r=0.689; P=0.000), (2) pain catastrophizing (r=0.494; P=0.000), (3) pain frequency days (r=0.526; P=0.000), (4) usual pain intensity (r=0.467; P=0.000), and (5) the worst pain intensity (r=0.485; P=0.000). Similar results were seen with caregiver assessments. Neither caregiver nor youth reports differed based on the sex or age of the child. The results support the psychometric properties of a brief self-report measure of pain impact in a pediatric chronic pain population. This measure may have great utility for clinicians caring for youth with chronic pain.


Chest pain--indigestion or impending heart attack?
A high proportion (40%) of patients with definite myocardial ischaemia who were questioned on admission to a Cardiac Monitoring Unit had experienced preceding chest pain which had been misinterpreted by both the patients themselves and doctors as 'indigestion' and which had often been inappropriately treated. 'Indigestion' in the chest in previously non-dyspeptic subjects over 40 years of age should be regarded as myocardial ischaemia until proved otherwise.


THC and CBD produce divergent effects on perception and panic behaviours via distinct cortical molecular pathways.
Clinical and pre-clinical evidence demonstrates divergent psychotropic effects of THC vs. CBD. While THC can induce perceptual distortions and anxiogenic effects, CBD displays antipsychotic and anxiolytic properties. A key brain region responsible for regulation of cognition and affect, the medial prefrontal cortex (PFC), is strongly modulated by cannabinoids, suggesting that these dissociable THC/CBD-dependent effects may involve functional and molecular interplay within the PFC. The primary aim of this study was to investigate potential interactions and molecular substrates involved in PFC-mediated effects of THC and CBD on differential cognitive and affective behavioural processing. Male Sprague Dawley rats received intra-PFC microinfusions of THC, CBD or their combination, and tested in the latent inhibition paradigm, spontaneous oddity discrimination test, elevated T-maze and open field. To identify local, drug-induced molecular modulation in the PFC, PFC samples were collected and processed with Western Blotting. Intra-PFC THC induced strong panic-like responses that were counteracted with CBD. In contrast, CBD did not affect panic-like behaviours but blocked formation of associative fear memories and impaired latent inhibition and oddity discrimination performance. Interestingly, these CBD effects were dependent upon 5-HT1A receptor transmission but not influenced by THC co-administration. Moreover, THC induced robust phosphorylation of ERK1/2 that was prevented by CBD, while CBD decreased phosphorylation of p70S6K, independently of THC. These results suggest that intra-PFC infusion of THC promotes panic-like behaviour associated with increased ERK1/2 phosphorylation. In contrast, CBD impairs perceptive functions and latent inhibition via activation of 5-HT1A receptors and reduced phosphorylation of p70S6K.


Time as a variable with niacin extended-release/lovastatin vs. atorvastatin and simvastatin.
Time may be an important variable when evaluating the efficacy of lipid-altering drugs. In this analysis of the Advicor Versus Other Cholesterol-Modulating Agents Trial Evaluation, niacin extended-release/lovastatin 1000/40 mg was as effective as atorvastatin 10 mg and more effective than simvastatin (both 10 mg and 20 mg) in achieving low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals. The titration schedule for this study included the initiation of niacin-extended release/lovastatin 500/20 mg once a day for 4 weeks, titrated to the starting dose of 1000/40 mg after 4 weeks, and then titrated to the final dose of 2000/40 mg. The titration schedule for both atorvastatin and simvastatin was 10 mg per day for 8 weeks and then titrated to 40 mg per day. Using this schedule, 50% of niacin extended-release/lovastatin and atorvastatin patients reached low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals within approximately 7 weeks, compared with simvastatin, in which 50% reached both treatment goals in 13-14 weeks. These time differences may have potential clinical relevance in reducing coronary heart disease risk.


The occurrence of deep pectoral myopathy in roaster chickens.
A study was conducted to determine the incidence of deep pectoral myopathy (DPM) in male roaster chickens reared under intensive conditions, processed at different ages (from 47 to 65 d of age), and belonging to 2 commercial genotypes (Ross 508 and Cobb 500). The study was carried out in a major Italian processing plant on a total of 120,700 male roaster chickens chosen at random from 151 flocks during a 6-mo period. The evaluation of DPM was performed on pectoralis minor muscles and consisted of a visual assessment of the presence or absence of the myopathy as well as the scoring of muscle damage level as being in an "early" (hemorrhagic appearance) or "old" (gray or green discoloration) developing stage. The average incidence of carcasses affected by DPM was found to be 0.84% (0.62 and 0.22% in early and old stages, respectively). The range in the incidence of total DPM was fairly large and varied from 0 to 16.7%. Considerable variations were also observed for early (range: 0 to 12.0%) and old (range: 0 to 5.6%) developing stages. Considering the effect of genotype, Ross 508 exhibited a higher incidence of DPM in respect to Cobb 500 (1.27 vs. 0.35%; P < or = 0.01). This result was due to the higher incidence of carcasses affected by both early (0.94 vs. 0.26%; P < or = 0.01) and old (0.33 vs. 0.09%; P < or = 0.01) developing stages of DPM in Ross 508 birds.


Alzheimer's Disease Classification Based on Individual Hierarchical Networks Constructed With 3-D Texture Features.
Brain network plays an important role in representing abnormalities in Alzheimers disease (AD) and mild cognitive impairment (MCI), which includes MCIc (MCI converted to AD) and MCInc (MCI not converted to AD). In our previous study, we proposed an AD classification approach based on individual hierarchical networks constructed with 3D texture features of brain images. However, we only used edge features of the networks without node features of the networks. In this paper, we propose a framework of the combination of multiple kernels to combine edge features and node features for AD classification. An evaluation of the proposed approach has been conducted with MRI images of 710 subjects (230 health controls (HC), 280 MCI (including 120 MCIc and 160 MCInc), and 200 AD) from the Alzheimer's disease neuroimaging initiative database by using ten-fold cross validation. Experimental results show that the proposed method is not only superior to the existing AD classification methods, but also efficient and promising for clinical applications for the diagnosis of AD via MRI images. Furthermore, the results also indicate that 3D texture could detect the subtle texture differences between tissues in AD, MCI, and HC, and texture features of MRI images might be related to the severity of AD cognitive impairment. These results suggest that 3D texture is a useful aid in AD diagnosis.


Interactions of constipation, dysfunctional elimination syndrome, and vesicoureteral reflux.
Vesicoureteral reflux (VUR) is simply described as incompetence of the unidirectional valve at the ureterovesical junction (UVJ), leading to backflow of urine to the kidney. Today, it is clear that VUR is not only related to the UVJ function but also to a combination of processes including immunity, bladder and pelvic floor function, dysfunctional voiding, and constipation. Although our surgical aims directed towards improving the valve coaptation at the UVJ, we understand today the importance of the diagnosis and treatment of constipation and dysfunctional voiding adjunctively.


Contributions of Motivation, Early Numeracy Skills, and Executive Functioning to Mathematical Performance. A Longitudinal Study.
The main goal of this longitudinal study is to examine the power of different variables and its dynamic interactions in predicting mathematical performance. The model proposed in this study includes indicators of motivational constructs (learning motivation and attributions), executive functioning (inhibition and working memory), and early numeracy skills (logical operations, counting, and magnitude comparison abilities), assessed during kindergarten, and mathematical performance in the second year of Primary Education. The sample consisted of 180 subjects assessed in two moments (5-6 and 7-8 years old). The results showed an indirect effect of initial motivation on later mathematical performance. Executive functioning and early numeracy skills mediated the effect of motivation on later mathematic achievement. Practical implications of these findings for mathematics education are discussed.


Are Antioxidants a Potential Therapy for FSHD? A Review of the Literature.
Facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy affecting approximately 1 in 7500 individuals worldwide. It is a progressive disease characterised by skeletal muscle weakness and wasting. A genetic mutation on the 4q35 chromosome results in the expression of the double homeobox 4 gene (DUX4) which drives oxidative stress, inflammation, toxicity, and atrophy within the skeletal muscle. FSHD is characterised by oxidative stress, and there is currently no cure and a lack of therapies for the disease. Antioxidants have been researched for many years, with investigators aiming to use antioxidants therapeutically for oxidative stress-associated diseases. This has included both natural and synthetic antioxidants. The use of antioxidants in preclinical or clinical models has been largely successful with a plethora of research reporting positive results. However, when translated to clinical trials, the use of antioxidants as a therapeutic intervention for a variety of disease has been largely unsuccessful. Moreover, specifically focusing on FSHD, limited research has been conducted on the use of antioxidants as a therapy in either preclinical or clinical models. This review summarises the current state of antioxidant use in the treatment of FSHD and discusses their potential avenue for therapeutic use for FSHD patients.


Thermodynamic Driving Forces for Dye Molecule Position and Orientation in Nanoconfined Solvents.
The results of replica exchange molecular dynamics simulations of a coumarin 153 (C153) dye molecule dissolved in ethanol confined within a 2.4 nm hydrophilic amorphous silica pore are presented. The C153 dye position and orientation distributions provide insight into time-dependent fluorescence measurements in nanoconfined solvents as well as general features of chemistry in mesoporous materials. In addition to the distributions themselves, the free energy, internal energy, and entropic contributions have been calculated to explore the factors determining the distributions. The most likely location of C153 is found to be near the pore surface, but two possible hydrogen-bonding structures lead to differing orientations. Internal energy and entropy are found to be competing forces within the pore, with entropy playing a significant role with unexpected consequences. These results represent a crucial step in determining how the nanoconfining framework can affect measurements of solvation dynamics.


[Expressions of Tau protein during the differentiation process of mesenchymal stem cells into neural cells].
To observe expressions and changes of Tau protein, pSer202 and Tau protein's contents during the differentiation process of bone-marrow mesenchymal stem cells (MSCs) into neural cells, and discuss Tau's effects on it. EGF and bFGF were combined for the induction of 4th, 8th, and 12th-MSCs into neural cells. Expressions of Tau protein and pSer202 were tested by immunocytochemistry. ELISA assay was applied for testing Tau protein's contents during differentiation process. Positive rates of Tau protein in uninduced MSCs of 4th, 8th, and 12th-MSCs were under < 6%; After 14-day induction, the cellular morphologic characteristics in different passages were very similar to neurons, positive rates of Tau protein had no significant differences between passages (P > 0.05), but had differences with their uninduced groups (P < 0.05). There hadn't had expression of pSer202 in uninduced and induced groups of passages. ELISA assay indicated that there was an upward tendency in Tau protein's contents during the 14-day induction process, those in the 14th day had no significant differences between passages too (P > 0.05). The increase in Tau protein's expressions and its non-phosphorylated state may make for MSCs differentiating into normal neural cells and formation of neuronal processes.


Emerging anti-inflammatory therapies for atherosclerosis.
Atherosclerosis remains one of the main causes of cardiovascular disease, which is the leading cause of death worldwide. It is now accepted that atherosclerosis is an inflammatory, dynamic and complex disease involving multiple cell types, and many antiinflammatory strategies have recently emerged as potential therapeutic approaches for atherosclerotic disease. In this review, we discuss the most recent progress in the development of anti-inflammatory strategies. We highlight the beneficial effects of potent antiinflammatory drugs, including recently developed biologics, and we describe diverse emerging approaches that target inflammatory processes involved in atherosclerosis including tumor necrosis factor antagonists, anti-interleukins, viral-derived serpins, P-selectin inhibition and leukotriene synthesis inhibition.


Fluctuating Hearing Loss in the Only Hearing Ear: Cochlear Implantation in the Contralateral Deaf Side.
Objective To investigate the hearing performance of adult patients presenting unilateral deafness with contralateral fluctuating hearing loss who received a cochlear implant on the deaf side. Study Design Case series with chart review. Setting University tertiary referral center. Subjects and Methods Preoperatively and at 6 and 12 months postoperatively, 23 patients underwent pure tone audiometry and speech audiometry with disyllabic and monosyllabic words in a quiet environment and sentences in quiet and noisy (signal-to-noise ratio +10 dB SPL) environments under best-aided conditions. The Abbreviated Profile of Hearing Aid Benefit (APHAB) inventory was evaluated preoperatively and at 6 and 12 months postoperatively. Results No difference was found between pre- and postoperative tests for disyllabic and monosyllabic words. For sentences in quiet and noisy environments, a difference between pre- and postoperative performance was present at 1 year ( P = .002 and P = .02, respectively). In a noisy environment, a difference was present at 6 and 12 months postoperatively as compared with the preoperative value (mean ± SD: 6 months: 42% ± 7.1% vs 61% ± 6.5%, P = .016). A significant improvement in the APHAB score was found at 6 and 12 months postimplantation (Friedman's 2-way analysis of variance by ranks, P < .001). The number of years of hearing deprivation of the deaf ear was not correlated with performance. Conclusion When incapacitating fluctuating hearing loss occurs in patients presenting a contralateral deaf ear, a cochlear implant is indicated in the latter ear, significantly improving performance in noisy conditions and allowing a better quality of communication to be achieved.


Compressed matrix core tablet as a quick/slow dual-component delivery system containing ibuprofen.
The purpose of the present research was to produce a quick/slow biphasic delivery system for ibuprofen. A dual-component tablet made of a sustained release tableted core and an immediate release tableted coat was prepared by direct compression. Both the core and the coat contained a model drug (ibuprofen). The sustained release effect was achieved with a polymer (hydroxypropyl methylcellulose [HPMC] or ethylcellulose) to modulate the release of the drug. The in vitro drug release profile from these tablets showed the desired biphasic release behavior: the ibuprofen contained in the fast releasing component was dissolved within 2 minutes, whereas the drug in the core tablet was released at different times (approximately 16 or >24 hours), depending on the composition of the matrix tablet. Based on the release kinetic parameters calculated, it can be concluded that the HPMC core was suitable for providing a constant and controlled release (zero order) for a long period of time.


High-frequency changes in transcriptional activity in polyomavirus-transformed cell lines.
We applied the Luria and Delbruck fluctuation test to analyze high-frequency changes in the phenotype of rat cells transformed by a plasmid carrying the polyomavirus middle T (pmt) gene. All of the transformed cell lines analyzed were capable of switching to the normal state with rates ranging from 10(-3) to 10(-2) per cell per generation. Analysis of both middle T antigen and middle T transcripts indicated that the reversion occurred by a mechanism involving a transcriptional block of the pmt locus. Cell lines containing two separate loci reverted with a lower rate, suggesting that phenotypic switching in these cells involved two independent events affecting each locus. The flat revertants mutated to the transformed state with rates in the range of 10(-5) to 5 X 10(-5) per cell per generation. To determine whether changes in pmt expression would affect neighboring sequences, we transfected a hybrid plasmid carrying pmt linked to the neo marker and selected either for morphological transformants or for G418-resistant cells. Although their coordinate regulation was not absolute, both genes were usually subject to the same changes, reflected by loss and reacquisition of transcriptional activity.


Breast Cancer in Arab and Jewish Women in Northern Israel: A Retrospective Database Study.
In Israel, breast cancer prevalence is lower among Arab than Jewish women, but incidence is increasing among Arab women at a younger age. To explore differences between Arab and Jewish women with breast cancer with respect to age at diagnosis, associated risk factors, and use of hormonal medications. We conducted a retrospective database study comparing Arab and Jewish women with breast cancer focusing on age at diagnosis, smoking history, obesity, and previous hormonal medication usage, including oral combined contraceptive pills (OCCP), progestogens, hormonal medications for treatment of infertility, and hormone replacement therapy (HRT). The study included 2494 women who were diagnosed with breast cancer during 2004-2015. Age at diagnosis was lower among Arab women (50.7 ± 13.1 years vs. 55.4 ± 12.6 years, P < 0.0001). The rate of smoking was higher among Jewish women (16.0% vs. 4.3%, P < 0.0001). The rate of obesity was higher in Arab women older than 50 years at diagnosis (59.0% vs. 42.4%, P < 0.0001). Arab women demonstrated a lower overall chance of previous use of all types of hormonal medications (odds ratio [OR] 0.6, 95% confidence interval [95%CI] 0.6-0.8) compared to Jewish women. Arab women were more likely to have used progestogens (OR 1.7, 95%CI 1.4-2.2) and medications for treatment of infertility (OR 2.3, 95%CI 1.5-3.4) and less likely OCCP (OR 0.4, 95%CI 0.3-0.6) and HRT (OR 0.4, 95%CI 0.3-0.5). Previous use of hormonal medications may contribute to incidence of breast cancer in Arab women.


Using stepped anvils to make even insulation layers in laser-heated diamond-anvil cell samples.
We describe a method to make even insulation layers for high-pressure laser-heated diamond-anvil cell samples using stepped anvils. The method works for both single-sided and double-sided laser heating using solid or fluid insulation. The stepped anvils are used as matched pairs or paired with a flat culet anvil to make gasket insulation layers and not actually used at high pressures; thus, their longevity is ensured. We compare the radial temperature gradients and Soret diffusion of iron between self-insulating samples and samples produced with stepped anvils and find that less pronounced Soret diffusion occurs in samples with even insulation layers produced by stepped anvils.


Revised non-contact mapping of ventricular scar in a post-infarct ovine model with validation using contact mapping and histology.
Identification of arrhythmogenic scar using non-contact (NC) sinus rhythm (SR) mapping is limited. Dynamic substrate mapping (DSM) overcomes these limitations but is less accurate than plunge needle electrode mapping. We developed a revised method for calculating DSM which was validated using detailed histological analysis and compared with conventional mapping modalities. Mapping was performed in eight sheep, >9 weeks post-myocardial infarction. Twenty multielectrode needles were deployed at thoracotomy in the left ventricle within and surrounding scar, and located using Ensite. Simultaneous catheter, needle, and NC electrograms were recorded during SR and multisite pacing. Dynamic substrate mapping maps were calculated as the maximum local peak negative voltage (PNV). Absolute mean DSM (AMDSM) maps, based on peak-peak voltage (P-PV), were calculated to minimize local pacing effects and take into account anisotropic influence. Dynamic substrate mapping and AMDSM maps were normalized based on global maximum voltages attained. Histologically quantified scar and mapping criteria were compared using Spearman's correlation and receiver operator curves (area under the curve, AUC) using 50% scar cut-off. For unipolar mapping, needles had greatest sensitivity at identifying scar which was better for P-PV (AUC; needle = 0.90, catheter = 0.70, NC = 0.66) than for PNV (AUC; needle = 0.79, NC = 0.38). AMDSM (AUC = 0.75) had superior scar discrimination than either catheter (AUC; unipolar = 0.70, bipolar = 0.71) or DSM (AUC = 0.67). Absolute mean DSM accuracy was improved when valvular geometries were excluded (AUC = 0.77). Absolute mean DSM was comparably accurate in identifying scarred myocardium as PNV needle mapping but was superior to conventional catheter and NC mapping.


Noncollapsing solution below r(c) for a randomly forced particle.
We show that a noncollapsing solution below r(c) can be constructed for the dynamics of randomly forced particle interacting with a dissipating boundary. The scaling analysis predicts a divergent collision rate at the boundary for the noncollapsing solution. This prediction is tested numerically.


Application of mass spectrometry-based proteomics techniques for the detection of protein doping in sports.
Mass spectrometry-based proteomic approaches have been used to develop methodologies capable of detecting the abuse of protein therapeutics such as recombinant human erythropoietin and recombinant human growth hormone. Existing detection methods use antibody-based approaches that, although effective, suffer from long assay development times and specificity issues. The application of liquid chromatography with tandem mass spectrometry and selected reaction-monitoring-based analysis has demonstrated the ability to detect and quantify existing protein therapeutics in plasma. Furthermore, the multiplexing capability of selected reaction-monitoring analysis has also aided in the detection of multiple downstream biomarkers in a single analysis, requiring less sample than existing immunological techniques. The flexibility of mass spectrometric instrumentation has shown that the technique is capable of detecting the abuse of novel and existing protein therapeutics, and has a vital role in the fight to keep sports drug-free.


Bioengineering of Pulmonary Epithelium With Preservation of the Vascular Niche.
The shortage of transplantable donor organs directly affects patients with end-stage lung disease, for which transplantation remains the only definitive treatment. With the current acceptance rate of donor lungs of only 20%, rescuing even one half of the rejected donor lungs would increase the number of transplantable lungs threefold, to 60%. We review recent advances in lung bioengineering that have potential to repair the epithelial and vascular compartments of the lung. Our focus is on the long-term support and recovery of the lung ex vivo, and the replacement of defective epithelium with healthy therapeutic cells. To this end, we first review the roles of the lung epithelium and vasculature, with focus on the alveolar-capillary membrane, and then discuss the available and emerging technologies for ex vivo bioengineering of the lung by decellularization and recellularization. While there have been many meritorious advances in these technologies for recovering marginal quality lungs to the levels needed to meet the standards for transplantation - many challenges remain, motivating further studies of the extended ex vivo support and interventions in the lung. We propose that the repair of injured epithelium with preservation of quiescent vasculature will be critical for the immediate blood supply to the lung and the lung survival and function following transplantation.


Hemodynamic observations on pulmonary edema associated with a beta-mimetic agent. A report of two cases.
Pulmonary edema associated with the use of beta agonists in the treatment of preterm labor is a major risk of tocolytic therapy. The data obtained from echocardiographic and hemodynamic evaluation in one such case and echocardiography in another differ markedly from those in two previously published reports. Specifically, the pulmonary capillary wedge pressure became elevated, and both patients failed to improve with oxygen therapy and positional changes only. Left ventricular dysfunction was ruled out as the possible cause since the left ventricular structure and function were normal on echocardiography. The heart failure was probably the result of increased preload, giving rise to increased end diastolic pressure and hence pulmonary edema. Diuretic therapy is very important in this situation.


An unusual steroid-producing ovarian tumour: case report.
The rapid onset of virilization in a post-menopausal woman is usually the result of androgen secretion from a tumour of adrenal or ovarian origin. Androgen secreting neoplasms of the ovary are rare and usually show autonomous secretion. Rarely, these may be driven by the high levels of gonadotrophins seen in the post-menopausal state. We describe the case of a 67-year-old woman with high serum testosterone and estradiol in association with the high gonadotrophin levels usually associated with the post-menopausal state. All hormonal parameters showed a significant suppression over 12 h with administration of the GnRH antagonist, cetrorelix. This observation implies that excess hormone synthesis was of ovarian origin and was gonadotrophin driven. Localization of the tumour was not possible by conventional ultrasound or computerized tomography scanning, but was achieved by venous sampling. Complete cure was achieved by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with restoration of the endocrine profile to that expected for a post-menopausal woman. Rapidly acting GnRH antagonists, such as cetrorelix, offer a safe and useful diagnostic and therapeutic option in the management of ovarian steroid-secreting tumours, which show gonadotrophin dependency.


Prevalence and Risk Factors of Internet Gaming Disorder Among Female Secondary School Students in Al-Ahsa, Kingdom of Saudi Arabia.
This study measured the prevalence and potential risk factors of Internet gaming disorder (IGD) among female secondary school students in Al-Ahsa, Kingdom of Saudi Arabia. This cross-sectional study was conducted between January and February 2023. A total of 400 female secondary school students in Al-Ahsa were recruited through multistage stratified cluster sampling. Data were collected by distributing a self-administered questionnaire among students. A chi-squared test was performed to compare categorical variables. The associations between IGD, depression, and anxiety scores were determined using the Pearson correlation coefficient. Among the total sample, 282 were classified as "gamers" and included in our analysis. The prevalence of IGD was found to be 19%. We also found a statistically significant and moderately positive correlation between IGD and anxiety and depression scores. Spending more than four hours daily playing video games, starting to play video games at less than seven years of age, having depression, having anxiety, and playing an online game were found to be potential risk factors for IGD. IGD among female adolescent students in Al-Ahsa is a public health concern that requires attention from the concerned parties. Health education projects on IGD, its risk factors, and its consequences should be designed for adolescents and their families.


Physiologic benefits of exercise training in rehabilitation of patients with severe chronic obstructive pulmonary disease.
We determined the effect on exercise tolerance and physiological exercise responses of rigorous rehabilitative exercise training in chronic obstructive pulmonary disease (COPD). Fifteen men and 10 women (mean age, 68 +/- 6 yr; FEV1, 0.93 +/- 0.27 L) participated in a rehabilitation program with an exercise component of three per week 45-min sessions of cycle ergometer training for 6 wk with exercise intensity kept near maximal targets. Before and after rehabilitation, patients performed an incremental test and a constant work rate (CWR) test at 80% of the peak work rate in the preprogram incremental test. Ventilation (V(E)) and gas exchange were measured breath by breath; arterialized venous blood was analyzed for blood gas determinations and lactate. Rehabilitation yielded an average increase in peak work rate in the incremental test of 36% (p < 0.001), and in the duration of the CWR test of 77% (p < 0.001). In the CWR test, the kinetics of O2 uptake, CO2 output, V(E), and heart rate were markedly slower than those of healthy subjects. After training, mean response time decrease averaged 17, 22, 34, and 29%, respectively (p < 0.02), evidence of a physiologic training effect. Further, for identical CWR tasks, V(E) was 10% lower (p < 0.02) after training, attributable to altered breathing pattern: tidal volume increased by 8% and respiratory rate decreased by 19%, yielding lower V(D) /V(T) (0.46 versus 0.53 p < 0.005). Rigorous exercise training for patients with severe COPD yields more efficient exercise breathing pattern and lower V(E); this is associated with improved exercise tolerance.


Phenology-Based Management of Alternaria Fruit Rot in Pink Lady Apples.
Fruit body rot and calyx rot caused by Alternaria alternata f. sp. mali has recently become a severe disease of Pink Lady apple in Israel. Severe fruit rot caused by A. alternata f. sp. mali has not been reported elsewhere in the world, and control measures are not currently known. Our objective was to determine the peak periods of susceptibility and develop methods to manage the disease by timing fungicide applications according to fruit phenological stage. We determined the relationship between fruit phenological stage and rot susceptibility by (i) monitoring the appearance of first fruit symptoms in the orchard; (ii) inoculating detached and attached fruit in the laboratory and orchard, respectively, at various time intervals after petal fall; and (iii) starting fungicide applications at various time intervals after petal fall. Fruit of Pink Lady acquired susceptibility to the disease at about 115 days after petal fall (DAPF) when reaching a diameter of ≥55 mm. Based on these findings, a new spray strategy was adopted involving a limited number of 4 to 6 foliar sprays of azoxystrobin + difenoconazole or tebuconazole + captan, or their alternation, starting at 115 DAPF. This strategy provided excellent control of both body rot and calyx rot in Pink Lady apple fruit in Israel.


Subtle Dynamic Changes Accompany Hck Activation by HIV-1 Nef and are Reversed by an Antiretroviral Kinase Inhibitor.
The HIV-1 virulence factor Nef interacts with the macrophage Src-family kinase Hck, resulting in constitutive kinase activation that contributes to viral replication and immune escape. Previous chemical library screens identified the diphenylfuranopyrimdine kinase inhibitor DFP-4AB, which selectively inhibits Nef-dependent Hck activity in biochemical assays and potently blocks HIV replication in vitro. In the present study, hydrogen exchange mass spectrometry (HX MS) was used to study conformational changes in downregulated Hck that result from Nef binding, as well as the impact of DFP-4AB on these changes. Remarkably, interaction with Nef induced only subtle changes in deuterium uptake by Hck, with the most significant changes in the N-lobe of the kinase domain adjacent to the docking site for Nef on the SH3 domain. No changes in hydrogen exchange were observed in the Hck SH2 domain or C-terminal tail, indicating that this regulatory interaction is unaffected by Nef binding. When HX MS was performed in the presence of DFP-4AB, the effect of Nef on Hck N-lobe dynamics was completely reversed. These results show that constitutive activation of Hck by HIV-1 Nef requires only modest changes to the conformational dynamics of the overall kinase structure. DFP-4AB reverses these effects, consistent with its activity against this Nef-induced signaling event in HIV-infected cells.


Metastatic malignant ectomesenchymoma initially presenting as a pelvic mass: report of a case and review of literature.
Pediatric soft tissue sarcomas account for approximately 10% of all pediatric malignancies. Malignant ectomesenchymoma is rare biphasic sarcomas consisting of both mesenchymal and neuroectodermal elements. Approximately 64 cases have been reported in the literature and are believed to arise from pluripotent embryologic migratory neural crest cells. We report a 4-year-old boy who initially presented with a pelvic mass and inguinal lymphadenopathy at 6 months of age. Inguinal lymph node biopsy revealed a distinct biphasic tumor with microscopic and immunophenotypic characteristics diagnostic for both alveolar rhabdomyosarcoma and poorly differentiated neuroblastoma. The patient received national protocol chemotherapy against rhabdomyosarcoma with good response and presented with a cerebellar mass 21 months later. The metastatic tumor revealed sheets of primitive tumor cells and diagnostic areas of rhabdomyosarcoma and neuroblastoma were identified only by immunohistochemistry. Cytogenetic analysis of metastatic tumor demonstrated complex karyotype with multiple chromosomal deletions and duplications. The patient received national protocol chemotherapy against neuroblastoma and adjuvant radiotherapy after surgical resection of the cerebellar tumor with good response. He is currently off from any treatment for 18 months with no evidence of tumor recurrence or metastasis.


Effectiveness of weight loss interventions--is there a difference between men and women: a systematic review.
Effective strategies are required to reduce the prevalence of overweight and obesity; however, the effectiveness of current weight loss programmes is variable. One contributing factor may be the difference in weight loss success between men and women. A systematic review was conducted to determine whether the effectiveness of weight loss interventions differs between men and women. Randomized controlled trials published up until March 2014 were included. Effect sizes (Hedges' g) were used to examine the difference in weight outcomes between men and women. A total of 58 studies met the eligibility criteria with 49 studies of higher quality included in the final data synthesis. Eleven studies that directly compared weight loss in men and women reported a significant sex difference. Ten of these reported that men lost more weight than women; however, women also lost a significant amount of weight. Analysis of effect sizes found small differences in weight loss favouring men for both diet (g = 0.489) and diet plus exercise (g = 0.240) interventions. There is little evidence from this review to indicate that men and women should adopt different weight loss strategies. Current evidence supports moderate energy restriction in combination with exercise for weight loss in both men and women.


Endoscopic and symptoms analysis in Mexican patients with irritable Bowel syndrome, dyspepsia, and gastroesophageal reflux disease.
The aim of this study was to analyze the data of endoscopy and symptoms in 118 Mexican patients with irritable bowel syndrome (IBS), dyspepsia, non-erosive reflux disease (NERD) and erosive esophagitis (EE). IBS criteria were fulfilling for dyspepsia patients in 47%, for NERD in 48%, and for EE patients in 48% of cases. Esophagitis was present in 42% of patients with IBS and in 45% of patients with dyspepsia. A higher prevalence of hiatus hernia was found in EE vs. NERD. Heartburn and acid eructation were associated with the presence of esophagitis; acid eructation, regurgitation and nocturnal pain with duodenitis; and heartburn and regurgitation with hiatus hernia. Males more frequently reported: mucus in feces, abdominal distension, nausea and gastritis; and women more frequently reported esophagitis and duodenitis. Patients with NERD (OR 2.54, 95% CI 1.08 to 5.99, p=0.04), tenesmus and early satiety, and men had an increase risk for reporting hard or lumpy stools. In conclusion, nearly half of the Mexican patients with NERD, EE and dyspepsia fulfill criteria for IBS. A large number of symptoms were correlated with endoscopy, which can be used to improve the indication of the endoscopy and its implementation in clinical studies.


Factor-VII activity and ischaemic heart disease: fatal and non-fatal events.
The Northwick Park Heart Study suggested that factor VII activity might be more strongly related to fatal than non-fatal events of ischaemic heart disease. We used polychotomous logistic regression to model simultaneously the probabilities of fatal events, non-fatal myocardial infarction, dying of causes other than ischaemic heart disease and of events, non-fatal myocardial infarction, dying of causes other than ischaemic heart disease and of event-free survival. We followed 1459 white men aged 40-64 at recruitment for a mean period of 16.1 years. Of these, 92 died of ischaemic heart disease, 100 experienced non-fatal myocardial infarction, 173 died of other causes, and 1094 men were alive. Factor VII activity was strongly related to fatal events of ischaemic heart disease but not to non-fatal events (p = 0.008). A difference of 1 SD in factor VII activity was associated with a difference of nearly 50% in the probability of dying of ischaemic heart disease, but with no difference for non-fatal myocardial infarction. This contrast was not seen for smoking, cholesterol, blood pressure, fibrinogen or factor VIII activity. High levels of VII activity may influence outcome at the time of plaque rupture and tissue factor release by enhancing thrombin production and thus fibrin deposition and platelet aggregability. The apparently differential effect of factor VII activity on fatal and non-fatal ischaemic heart disease may have important screening and prophylactic implications.


Identifying modifiable features of home bowel cancer screening kits to facilitate use: consumer perspectives.
Despite the widely publicised health benefits of participation in bowel cancer screening, only 43.5% of recipients participate in the Australian National Bowel Cancer Screening Program (NBCSP). Through consultation with kit recipients, this study aimed to identify features of home bowel screening kits that could be modified to increase their use. Participants (n = 25) were presented with nine different bowel cancer screening kits and asked to identify features of each kit that might prevent or promote their use. Responses were coded using content analysis, and a narrative synthesis is presented summarising preferences relating to each element of the kit. Six modifiable elements were identified: collection tool, collection sheet, specimen container, instruction, packaging and processes. Participant preferences were for collection devices that limited the users' proximity to faecal matter, smaller packaging, simpler processes and step-by-step pictorial instructions. Responses regarding aesthetics, the amount of information included and receiving immediate results were mixed. Findings provide several consumer-driven recommendations, which are to be tested in future research aimed at improving the acceptability and usability of kits distributed in population bowel cancer screening programs.


[Inhibiting effect of ethanol extract from Achyranthes bidentata on A beta 42 aggregation].
To observe inhibiting effect of ethanol extract from Achyranthes bidentata (Nx-E) on A beta 42 on (beta-amyloid protein 42) aggregation and fibril formation. A beta 42 and Nx-E were incubated in 37 degrees C, 5%, CO2 incubator first, fibril formation was monitored by thioflavine-T fluorescence and was observed with transmission electron microscopy. At 7 days, 1 microgram.microL-1 A beta 42 fluorescence intensity was significantly increased, and much amyloid-like fibril was observed. A beta 42 co-incubated with 15 and 30 micrograms.microL-1 Nx-E for 7 days, their fluorescence intensities were remarkably reduced, few fibrils but an amorphous material were often observed. After 1 microgram.microL-1 A beta 42 was incubated alone up to 7 days, A beta 42 aggregated and amyloid-like fibril formed. 15 and 30 micrograms.microL-1 Nx-E can prevent A beta 42 from polymerizing to some extent.


Long-term results and current indications in femoropopliteal vascular reconstructions.
The current indications to and long-term results of the femoropopliteal by-passes are analysed. The absolute indication is critical ischaemia with rest pain or trophic change i.e. ulcers and gangrene. The most important factor influencing the long-term results is the nature of the graft per se. The indications, arteriographic run-off, site of anastomosis, earlier femoropopliteal operations all exert a major influence on the late results, particularly prosthetic grafts are used. The results indicate the need for more prospective studies with careful monitoring of different variants in order to better understand the role of the femoropopliteal by-pass in the palliation of infra-inguinal atherosclerotic occlusive disease.


Plasma concentration, mammary excretion and side-effects of phenylbutazone after repeated oral administration in healthy cows.
Seven clinically healthy dairy cows were each given 2.5 g phenylbutazone (approximately 5 mg/kg body weight) by oral administration twice daily for 8 days. The concentrations of phenylbutazone in plasma and milk and several blood parameters were studied. The minimum plasma concentration during steady state was 100.4 +/- 7.3 micrograms/ml. During the same period the milk concentration never exceeded 1% of the plasma concentration. The elimination half-life in plasma was 38.6 +/- 3.7 h. Five days after administration had been discontinued, the milk concentration was 0.05 +/- 0.01 microgram/ml. All seven cows were clinically healthy throughout the experiment. The most pronounced side-effect of the blood parameters studied was a decreased concentration of leucocytes to about two-thirds of the control value. This might have a pronounced influence on the effectiveness of the immune system. There was also a significant decrease in total bilirubin indicating a decrease in the breakdown of erythrocytes.


Two novel factor V null mutations associated with activated protein C resistance phenotype/genotype discrepancy.
Activated protein C (APC) resistance phenotype/genotype discrepancy is a very rare event. The objective of this study was to characterize the molecular mechanisms in two cases of APC phenotype/genotype discrepancy. An approach using direct sequencing of each exon and splicing junctions of the factor V gene showed that two novel factor V null mutations combined with heterozygous factor V Leiden mutation were responsible for this discrepancy. Our results suggest the necessity to use both phenotypic and genotypic analyses in some cases to determine an accurate diagnosis.


Which cervical sampler? A comparison of four methods.
Four cytology sampling methods were compared in 1063 patients referred for colposcopy with a recent abnormal smear. A dyskaryotic smear of any grade was considered a positive result, though comparisons were limited to cases with a subsequent biopsy confirming CINII or III. There were no differences between the abilities of any of the four methods to detect higher grades of CIN (chi (2)3 = 4.603, P > 0.20). The presence or absence of endocervical cells in a smear was not significantly associated with any variation in success rate (chi (2)1 = 0.959, P > 0.30). The joint analysis of the four methods and the presence/absence of endocervical cells also showed no significant effects (chi (2)7 = 12.768, 0.1 > P > 0.05). In the latter analysis the trend towards a conventional level of significance was accounted for by the Aylesbury spatula giving a relatively high success rate when endocervical cells were present. The suggestion of advantage for the Aylesbury spatula merits further investigation.


Incompetence of the internal jugular venous valve: spectrum of echo-Doppler appearances.
The echocardiographic literature contains very scant reference to incompetence of the valve in the internal jugular vein. However, we found frequent Doppler evidence of such incompetence, especially in patients with congestive failure. This incompetence manifests as a variety of color Doppler and pulsed Doppler patterns, illustrated here in 3 patients.


Structural details of Asp(B9) human insulin at low pH from two-dimensional NMR titration studies.
A titration study of the dimeric Asp(B9) mutant of human insulin was performed using two-dimensional NMR spectroscopy. Based on 10 NOESY spectra recorded in the pH range 1.73-3.93, the pKa values of the seven carboxyl groups in the mutant were determined, and the titration shifts of 46 pH-dependent protons in non-ionizable groups were investigated. Further, the pKa values of the two histidine imidazole rings were determined from a series of 1D spectra recorded in the pH range 6.65-10.0. The titration shifts of all pH-dependent protons were analyzed by a nonlinear least-squares fitting procedure, using an equation that describes a one-step titration. Also the pH dependence of the exchange rate of the amide proton of Phe(B24) was determined in the applied pH range. On the basis of the experimental results, it is concluded that the Asp(B9) residue forms an N-cap of the B-chain alpha-helix through an interaction between the side-chain carboxyl group of the residue and the dipole of the helix. Further, the titration data show that salt bridges are established between Glu(B13) and His(B10) and between Asn(A21) and Arg(B22) at pH values, where the interacting groups are ionized, and that a hydrogen bond exists between the amide proton of Val(A3) and the C-terminal carboxyl group of Thr(B30). Most surprisingly, the data analysis shows that the Asp(B9) insulin exists as a dimer throughout the investigated pH range, that is, also at pH values where there is a substantial negative charge repulsion in the monomer-monomer interface of the dimer.


[Serrated lesions of the large intestine: Prevalence analysis and clinical and morphologic characteristics].
to retrospectively estimate the prevalence of serrated lesions of the large intestine and to reveal the features of dis- tribution of serrated lesions in the previously diagnosed classical adenomas and hyperplastic polyps. A continuous sampling method was used to take biopsy specimens from the archive material of 440 polypoid lesions of the large intestine, which had entered in 2012-2013, and which were be morphologically reexamined by three experts. The mor- phological criteria for diagnosing different types of serrated lesions were taken according to the 2010 WHO classification of premalignant lesions of the large intestine and to the recommendations from an expert panel (Am J of Gastroenterology 2012). A group of serrated lesions included tubular (13.7%), tubulovillous adenomas (12.5%), and villous (50%) adenomas. The reexamination revealed 121 serrated lesions, including hyperplastic polyps (n = 55 (45.5%)), sessile serrated adenomas/ polyps (SSA/P) (n = 24 (19.8%)), out of which there were those with dysplasia (n=6 (5%)), traditional serrated adenomas (TSAs) (n = 20 (16.5%)), out of which there were those with dysplasia (n = 1 4 (11.6%)), and unclassified serrated polyps (n =22 (18.2%)). Most hyperplastic polyps (89%) and SSA/P (71%) were located distal to the splenic flexure of the colon; TSAs were equally distributed between the proximal and distal portions of the large intestine. The proportion of serrated lesions with dysplasia was 16.5%; that among SSA/P and TSAs was 25 and 70%, respectively. Serrated lesions with dysplasia were more often located proximally and were larger in size than those without dysplasia. Serrated lesions of the large intestine are its more common abnormalities than previously thought. The reexamination has revealed that serrated lesions occur in both the preexisting group of hyperplastic polyps and all groups of classical adenomas, suggesting the need for widespread introduction of the current classification intO everyday diagnostic practice.


Education and experience of pharmacy directors in large hospitals.
The education and experience of pharmacy directors in large hospitals are described. Questionnaires were sent in September 1981 to pharmacy directors of all hospitals in the United States having at least 300 beds. The questionnaire elicited background characteristics, postgraduate degrees, and administrative experience of the pharmacy director and descriptive information about the hospital. Of the 1483 questionnaires distributed, 609 (41%) were returned. Sixty percent of the respondents had an entry-level degree as their highest degree; 26%, 6%, and 7% of the respondents had M.S., M.B.A., and postgraduate Pharm .D. degrees, respectively. M.B.A. and postgraduate Pharm .D. degrees were more common for younger respondents. Only 6% of directors with entry-level degrees and 10% with M.B.A. degrees had completed an ASHP-accredited hospital pharmacy residency compared with 53% and 46% of directors with postgraduate Pharm .D. and M.S. degrees, respectively. Of directors with M.B.A. or postgraduate Pharm .D. degrees, 73% and 77%, respectively, had less than 11 years of administrative experience; just over 50% of directors with M.S. and entry-level degrees had less than 11 years of administrative experience; just over 50% of directors with M.S. and entry-level degrees had less than 11 years of experience. The majority of directors with postgraduate degrees had been in their current position for five years or less. Additional research is needed to evaluate the relationship of these variables more fully.


Correlations Between Working Memory Impairment and Neurometabolites of the Prefrontal Cortex in Drug-Naive Obsessive-Compulsive Disorder.
This study aimed to investigate the mechanism of working memory (WM) impairment in drug-naive obsessive-compulsive disorder (OCD) by using neuropsychological tests and proton magnetic resonance spectroscopy (1H-MRS). A total of 55 patients with drug-naive OCD and 55 healthy controls (HCs) were recruited for this study. The working memory (WM) was evaluated using the digit span test (DST), visual space memory test (VSMT), and the 2-back task and stroop color word test (SCWT). The bilateral metabolite levels of the prefrontal cortex (PFC) were evaluated by 1H-MRS, then determined the ratios of N-acetyl aspartate (NAA), choline-containing compounds (Cho), and myo-inositol (MI) to creatine (Cr). The independent sample t-test was used to analyse the differences in WM performance and neurometabolite ratios. Multivariate linear regression analysis was performed to screen the influential factors of WM, with an introduction level of 0.05 and a rejection level of 0.10. 1) Patients with OCD performed significantly worse on DST (score), VSMT (score), 2-back task (accuracy rate), SCWT (execution time) when compared with HCs. 2) NAA/Cr and Cho/Cr in the left PFC (lPFC) and MI/Cr ratios in the bilateral PFC of OCD patients were significantly lower when compared to HCs. 3) For OCD patients, the NAA/Cr ratio in the lPFC was negatively correlated with the score of DST (forwards), the Cho/Cr ratio in the lPFC was positively correlated with the accuracy rate of 2-back task, and the MI/Cr ratio in the right PFC (rPFC) was positively correlated with the score of DST (forwards) and the accuracy rate of VSMT. We also found that the compulsive symptoms showed a positive correlation with MI/Cr ratio of the rPFC. Drug-naive OCD patients have demonstrated WM impairments, including phonological loop, visual-spatial sketchpad and central executive system, and the WM impairments might be associated with hypometabolism in the PFC, especially the lPFC.


Direct medical cost of COVID-19 in children hospitalized at a tertiary referral healthcare center in Mexico City.
Despite the end of the COVID-19 pandemic being declared by the WHO, the economic consequences are far from over. One of these implications was the cost of inpatient care for health institutions. To date, some studies have examined the economic burden of COVID-19 in the adult population but only a few have focused on child populations. To estimate the direct medical costs of COVID-19, focusing on children in Mexico. Data about resources consumed during hospital stays were extracted from the medical records of patients hospitalized at a Mexican tertiary healthcare institution. Other sources of information were the unit prices of inputs and the salaries of health personnel. A micro-costing methodology was used to obtain cost results by age group over different hospital areas. Data analysis was performed with descriptive statistics and regression models to evaluate the predictors of total cost. One hundred and ten medical records were reviewed of which 57.3% corresponded to male patients and the mean age was 7.2 years old. The estimated average cost per patient was US$5,943 (95% CI: US$4,249-7,637). When the costs of the three clinical areas were summed, only the 5-10 years old group showed a maximum cost of US$14,000. The regression analysis revealed the following factors as significant: sex, age, staying at an emergency room, having a positive bacterial culture, and having comorbidities. The cost results were somewhat similar to those reported in children from the USA, but only regarding low severity COVID-19 cases. However, comparability between these types of studies should be done with caution due to the huge differences between the healthcare systems of countries. The study cost results may help public decision-makers in budget planning and as inputs for future cost-effectiveness studies about interventions regarding COVID-19.


UV-Triggered Surface-Initiated Polymerization from Colorless Green Tea Polyphenol-Coated Surfaces.
A facile and versatile approach to constructing colorless surface coatings based on green tea polyphenols is reported, which can further act as a photoinitiating layer to initiate radical polymerization. These colorless green tea polyphenol coatings are capable of successfully photografting polymer brushes, and the resulting polymer brush patterns show spatial shape adjustability by masked UV irradiation. Both surface modifications and photografted polymer brushes do not alter the original color of the substrates. This method could be promising for the development of surface modifications.


Resolvin D1 Attenuates Mpp+-Induced Parkinson Disease via Inhibiting Inflammation in PC12 Cells.
BACKGROUND We investigated the influence of Resolvin D1 (RvD1) on the inflammatory response in PC12 cells (a cell model of Parkinson disease, PD). MATERIAL AND METHODS 4 mmol/L 1-methyl-4-phenylpyridinium ion (Mpp+) was used in PC12 cells for an in vitro PD model. 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to explore PC12 cell viability. Western blot (WB) experiments were used to identify nuclear factor-κB (NF-κB), phosphorylated extracellular signal-regulated kinase (p-ERK)/p-Jun N-terminal kinase (JNK)/p-P38 mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 protein levels. Transcription levels of inflammatory factors, for instance, TNF-α and IL-6, were explored by real-time quantitative polymerase chain reaction (RT-QPCR). Lactic dehydrogenase (LDH) level was detected by enzyme-linked immunosorbent (ELISA). Cell apoptosis was assessed by Annexin-V Fluorescein (FITC) kit. RESULTS RvD1 dose-dependently inhibited MPP+ induced upregulation of PC12 cell apoptosis/cellular damage/TNF-α and p-P38/p-ERK/NF-κB as well as downregulation of PC12 cell viability. CONCLUSIONS We can draw the conclusion that RvD1 attenuates PD via inhibiting Mpp+-induced inflammation in PC12 cells.


Follow-up of children with brain tumors.
One hundred two patients were evaluated for late effects of brain tumor in childhood by a medical record review and follow-up questionnaire. The patients had survived brain tumor for 5 to 47 years (median, 18 years). Among 30 patients who had received brain irradiation, 3 were successfully treated for second neoplasms that developed within the radiotherapy field 11, 16, and 29, years later, respectively. Moderate or severe functional deficits were present in 24 patients (24%), more commonly among those treated before 2 years of age and among those with cerebral astrocytoma. The other 78 patients (76%) had mild or no gross deficits, and all but 1 of them were attending school or were employed. Twenty-one patients in the series reported a total of 41 offspring, none of whom had cancer or mental retardation. Although markedly diverse performance levels were found among the 102 long-term survivors of childhood brain tumors, the majority had an acceptable quality of life.


Development and validation of the primary care team dynamics survey.
To develop and validate a survey instrument designed to measure team dynamics in primary care. We studied 1,080 physician and nonphysician health care professionals working at 18 primary care practices participating in a learning collaborative aimed at improving team-based care. We developed a conceptual model and administered a cross-sectional survey addressing team dynamics, and we assessed reliability and discriminant validity of survey factors and the overall survey's goodness-of-fit using structural equation modeling. We administered the survey between September 2012 and March 2013. Overall response rate was 68 percent (732 respondents). Results support a seven-factor model of team dynamics, suggesting that conditions for team effectiveness, shared understanding, and three supportive processes are associated with acting and feeling like a team and, in turn, perceived team effectiveness. This model demonstrated adequate fit (goodness-of-fit index: 0.91), scale reliability (Cronbach's alphas: 0.71-0.91), and discriminant validity (average factor correlations: 0.49). It is possible to measure primary care team dynamics reliably using a 29-item survey. This survey may be used in ambulatory settings to study teamwork and explore the effect of efforts to improve team-based care. Future studies should demonstrate the importance of team dynamics for markers of team effectiveness (e.g., work satisfaction, care quality, clinical outcomes).


Immunostimulatory Effects Triggered by Self-Assembled Microspheres with Tandem Repeats of Polymerized RNA Strands.
Self-assembled RNA particles have been exploited widely to maximize the therapeutic potential of RNA. However, the immune response via RNA particles is not fully understood. In addition, the investigation of the immunogenicity from RNA-based particles is required owing to inherent immunostimulatory effects of RNA for clinical translation. To examine the immune stimulating potency, rationally designed microsized RNA particles, called RNA microspheres (RMSs), are generated with single or double strands via rolling circle transcription. The RMSs show an exceptional stability in the presence of serum, while they are selectively degraded under endolysosomal conditions. With precisely controlled size, both RMSs are successfully taken up by macrophages. Unlike the nature of RNA fragments, RMSs induce only basal-level expression of inflammatory cytokines as well as type I interferon from macrophages, suggesting that RMSs are immunocompatible in the therapeutic dose range. Taken together, this study could help accelerate clinical translation and broaden the applicability of the self-assembled RNA-based particles without being limited by their potential immunotoxicity, while a systematic controllability study observing the release of RNA fragments from RMSs would provide self-assembled RNA-based structures with a great potential for immunomodulation.


Prevalence of fibromyalgia: literature review update.
The present study aimed to update the literature review on the prevalence of fibromyalgia published in 2006. A bibliographical survey was carried out from 2005 to 2014 in the MEDLINE, Web of Science, Embase, LILACS and SciELO databases and 3274 records were identified. Five researchers selected the studies, following the inclusion criteria: studies that obtained the prevalence of fibromyalgia. Fibromyalgia studies in associated diseases were excluded. When screening by title and abstract, 2073 irrelevant articles were excluded. The full texts of 210 articles were evaluated for eligibility and this review included 39 studies, described in 41 articles. The selected studies were grouped into four categories: (A) prevalence of fibromyalgia in the general population; (B) prevalence of fibromyalgia in women; (C) prevalence of fibromyalgia in rural and urban areas; (D) prevalence of fibromyalgia in special populations. The literature shows values of fibromyalgia prevalence in the general population between 0.2 and 6.6%, in women between 2.4 and 6.8%, in urban areas between 0.7 and 11.4%, in rural areas between 0.1 and 5.2%, and in special populations values between 0.6 and 15%. This literature review update shows a significant increase in fibromyalgia prevalence studies in the world. The new 2010 American College of Rheumatology criteria have not been widely used yet and the COPCORD (Community-oriented program for control of Rheumatic Diseases) methodology has increased the quality of studies on the prevalence of rheumatic diseases in general.


2,2,4,4-Tetra-phenyl-1,3-bis-(3,3,5,5-tetra-methyl-1,1-diphenyl-5-vinyl-trisilox-an-1-yl)-cyclo-disilazane.
The title mol-ecule, C(60)H(70)N(2)O(4)Si(8), lies on an inversion center. In the asymmetric unit, one of the phenyl rings is disordered over two sets of sites with refined occupancies 0.58 (2) and 0.42 (2). In addition, in two substitution sites of the terminal dimeth-yl(vin-yl)silyl unit, a methyl group and the vinyl group are disordered over the same site with refined occupancies 0.523 (13) and 0.477 (13).


Investigating the impact of written emotion disclosure on the level of occupational stress among intensive care nurses.
The present study was conducted with the aim of determining the impact of rewriting pleasant events on the level of occupational stress in Intensive Care Unit (ICU) nurses. This is a quasi-experimental research conducted on nurses working in the intensive care units of Imam Khomeini and Golestan hospitals in Ahvaz, from July to November 2021. Seventy-six nurses were selected based on the inclusion criteria, and were then randomly assigned to the intervention and the control groups. The nurses' demographic information form and the Expanded Nursing Stress Scale (ENSS) were used to collect data. In the intervention group, the technique of rewriting pleasant events was used for 8 weeks, at least once a week. The data was analyzed with SPSS V20. No significant difference in the demographic characteristics was observed between the intervention and the control groups (p > 0.05). The pre-intervention occupational stress of the nurses in the intervention and the control groups were reported to be 173.86 ± 26.75 and 173.05 ± 24.47, respectively, showing no statistically significant difference (p = 0.89). After the intervention, the occupational stress scores were 134.21 ± 16.09 and 172.36 ± 24.33, respectively, showing a significant difference between the two groups (p < 0.001). Considering the impact of rewriting pleasant events on the level of occupational stress of ICU nurses, it is recommended that nursing managers and nurses plan training programs for nurses in this area, and encourage other nurses to do so, too. It is also suggested to implement this intervention on the nurses of other wards as well.


Residue-residue interactions regulating the Ca2+-induced EF-hand conformation changes in calmodulin.
Calmodulin (CaM) is a Ca2+-binding messenger protein having four Ca2+-binding motifs named 'EF-hand'; the EF-hand motifs undergo a conformation change induced by Ca2+-binding. In order to study how Ca2+-binding induces the conformation change of EF-hand motifs and which residues are involved in the reaction, two 1μ second long MD simulations were independently performed from the apo- and holo-CaM and their structures and interactions were compared. The Ca2+-binding weakens the helix-helix interaction in all EF-hand, however, the holo-CaM MD adopted the close-like form. The correlation coefficients obtained from the two MDs show the residues comprising interactions being involved in their close-open conformation changes; most of these residues are hydrophobic amino acids but some of them are hydrophilic (T34, H107, N111 and Q143). The hydrophilic residues are expected to lock the EF-hands by their side-chains and main-chain carbonyl oxygen of another hydrophobic residue. Furthermore, the interaction pattern of EF-hand3 and 4 are similar to each other. On the other hand, the interaction pattern of EF-hand2 is different from others; its polar residues are expected to play an important role in regulating the EF-hand2 conformation.


Bacterial protein azurin and derived peptides as potential anti-SARS-CoV-2 agents: insights from molecular docking and molecular dynamics simulations.
The current pandemic SARS-CoV-2 has wreaked havoc in the world, and neither drugs nor vaccine is available for the treatment of this disease. Thus, there is an immediate need for novel therapeutics that can combat this deadly infection. In this study, we report the therapeutic assessment of azurin and its peptides: p18 and p28 against the viral structural S-protein and non-structural 3CLpro and PLpro proteins. Among the analyzed complexes, azurin docked relatively well with the S2 domain of S-protein compared to the other viral proteins. The derived peptide p18 bound to the active site domain of the PLpro protein; however, in other complexes, lesser interactions were recorded. The second azurin derived peptide p28, fared the best among the docked proteins. p28 interacted with all the three viral proteins and the host ACE-2 receptor by forming several electrostatic and hydrogen bonds with the S-protein, 3CLpro, and PLpro. MD simulations indicated that p28 exhibited a strong affinity to S-protein and ACE-2 receptor, indicating a possibility of p28 as a protein-protein interaction inhibitor. Our data suggest that the p28 has potential as an anti-SARS-CoV-2 agent and can be further exploited to establish its validity in the treatment of current and future SARS-CoV crisis.Communicated by Ramaswamy H. Sarma.


A comparative study for selectivity of micronuclei in oral exfoliated epithelial cells.
Micronucleus (MN) represents small, additional nuclei formed by the exclusion of chromosome fragments or whole chromosomes lagging at mitosis. MN rates, therefore, indirectly reflect chromosome breakage or impairment of the mitotic apparatus. During the last few decades, micronuclei ("MNi") in oral exfoliated epithelial cells are widely used as biomarkers of chromosomal damage, genome instability and cancer risk in humans. However, until now only little attention has been given to the effect of different staining procedures on the results of these MN assays. To compare the MNi frequencies in oral exfoliated epithelial cells using three different stains, i.e.,Feulgen stain, Papanicolaou stain (Pap) and hemotoxylin and eosin stain (H and E). Oral exfoliated cells from 45 cases of potentially malignant disorders (15 oral submucous fibrosis, 15 lichen planus and 15 leukoplakia) and 15 controls with healthy mucosa, were taken and MNi frequencies (No. of MNi/1000 cells) were compared using three different stains. Mean MNi frequency in cases was found to be 3.8 with Feulgen stain, 16.8 with PAP and 25.9 with H and E. In controls, mean MNi frequency was 1.6 with Feulgen stain, 7.7 with PAP and 9.6 with H and E stain. Statistically significant value (P < 0.01) were observed when the three stains were compared together using Kruskal Walli's ANOVA test. Feulgen being a DNA-specific stain gave the least counts, although statistically significant results from the comparison of MNi frequency between cases and controls were obtained with all the three stains.


[Not Available].
Anatomical fugitive sheets are of great interest, as a typographical genre, not only for the history of printing and the history of medicine, but also, more generally, for the history of culture as a whole. They were published as folio woodcuts (more rarely engravings) in Germany, France, Italy, England and the Netherlands from the end of the XVth centkury to the mid XVIIIth century. These sheets contain a figure representing the human body (male and female) and a text describing in a concise and quite rough way the elements of the illustration. What is unusual about these sheets is that the trunk of the figures and some of the internal organs can be lifted up or peeled away, like some contemporary books for children. The figures and some internal parts are very often coloured. Judging from the number of editions (I have found 15 editions published between 1538 and 1540!), anatomical sheets met with a huge commercial success and a very wide circulation indeed. Students of the faculties of medicine and philosophy and barber-surgeons were the more obvious consumers. Students would use them as aids to memory to accompany non-illustrated medical books; barbers to grasp some basic notions of the human body, useful for the practice of phlebotomy. They could be purchased in bookshops, but they were more likely to have been sold in market places or around the University where many colporteurs displayed their cheap prints and booklets. I shall argue, however, that anatomical fugitive sheets have also been produced for and used by a non-professional public, literate but not highly educated, unable to read Latin and more used to learning from images rather than from the written word. A public that was eager to discover the inner secrets of the bodily self, the divine machine that we inhabit. From a scientific point of view anatomical fugitive sheets often reveal errors and differences compared to academic textual and iconographic material on the same subject. The discrepancy was evident from the very first editions, although a very limited number of sheets were published in corrected and updated editions to follow medical research in universities. In many ways, anatomical fugitive sheets are exceptional documents through which one can measure the gap between academic knowledge and popularization and identify the iconographic and textual strategies used in order to break the academic monopoly on scientific discourses. Through fugitive sheets, anatomical knowledge partially lost its strictly scientific connotations and was adapted to a multiplicity of often quite unexpected uses.